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Ursodeoxycholic acid

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https://www.readbyqxmd.com/read/29032305/physicochemical-pharmacokinetics-as-an-optimization-tool-for-generic-development-a-case-study
#1
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 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29031874/an-update-on-the-physiopathology-and-therapeutic-management-of-cholestatic-pruritus-in-children
#2
A Thébaut, D Debray, E Gonzales
Pruritus is a disabling symptom accompanying chronic cholestasis. In extreme cases, the refractory nature of pruritus can result in a need for invasive therapies including liver transplantation. The pathogenesis of pruritus in cholestatic disease is poorly understood. It may involve a specific neural pathway (similar to that associated with pain) regulated by several pruritogenic substances such as bile acids, opioids, serotonin, and the more recently identified lysophosphatidic acid. While the therapeutic management of cholestatic pruritus is well established in adults, there is no consensus in children, in light of the difficulty of conducting controlled clinical studies...
October 11, 2017: Clinics and Research in Hepatology and Gastroenterology
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
#3
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/29016567/effects-of-bezafibrate-on-outcome-and-pruritus-in-primary-biliary-cholangitis-with-suboptimal-ursodeoxycholic-acid-response
#4
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
#5
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...
October 10, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28993258/twenty-year-comparative-analysis-of-patients-with-autoimmune-liver-diseases-on-transplant-waitlists
#6
G J Webb, A Rana, J Hodson, M Z Akhtar, J W Ferguson, J M Neuberger, J M Vierling, G M Hirschfield
BACKGROUND & AIMS: The rarity of autoimmune liver disease poses challenges to epidemiology studies. However, waitlists for liver transplantation can be used to study patients with end-stage liver diseases. We used these waitlists to assess trends in numbers and demographics patients awaiting liver transplant for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH). METHODS: We collected data from United Kingdom (UK) and United States (US) national registries for all adults on liver transplant waitlists, from January 1, 1995 through December 31, 2014...
October 6, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28987258/an-update-on-the-treatment-and-follow-up-of-patients-with-primary-biliary-cholangitis
#7
REVIEW
Blaire E Burman, Manan A Jhaveri, Kris V Kowdley
Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by chronic granulomatous lymphocytic cholangitis of the small bile ducts. PBC was a leading indication for liver transplant in the United States; with early diagnosis and treatment, the majority of patients with PBC have a normal life expectancy. Pathogenesis involves inflammatory damage of bile duct epithelium secondary to innate and adaptive immune responses, and toxicity from accumulated bile acids. Cholestasis and disease progression can lead to cirrhosis...
November 2017: Clinics in Liver Disease
https://www.readbyqxmd.com/read/28981097/activation-of-mir-34a-impairs-autophagic-flux-and-promotes-cochlear-cell-death-via-repressing-atg9a-implications-for-age-related-hearing-loss
#8
Jiaqi Pang, Hao Xiong, Peiliang Lin, Lan Lai, Haidi Yang, Yimin Liu, Qiuhong Huang, Suijun Chen, Yongyi Ye, Yingfeng Sun, Yiqing Zheng
Age-related hearing loss is a major unresolved public health problem. We have previously elucidated that the activation of cochlear miR-34a is correlated with age-related hearing loss in C57BL/6 mice. A growing body of evidence points that aberrant autophagy promotes cell death during the development of multiple age-related diseases. The aim of this study was to investigate the role of miR-34a-involved disorder of autophagy in the pathogenesis of age-related hearing loss. Our results showed that miR-34a expression was markedly upregulated in the aging cochlea accompanied with impairment of autophagic flux...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28978875/agaro-oligosaccharides-regulate-gut-microbiota-and-adipose-tissue-accumulation-in-mice
#9
Yasuki Higashimura, Yasunori Baba, Ryo Inoue, Tomohisa Takagi, Katsura Mizushima, Hiromu Ohnogi, Akira Honda, Yasushi Matsuzaki, Yuji Naito
Gut microbiota are deeply associated with the prevalence of obesity. Agarose is hydrolyzed easily to yield oligosaccharides, designated as agaro-oligosaccharides (AGO). This study evaluated the effects of AGO on obese phenotype and gut microbial composition in mice. Mice were administered AGO in drinking water (AGO-receiving mice). 16S rRNA gene sequencing analyses revealed their fecal microbiota profiles. Serum bile acids were ascertained using a LC-MS/MS system. Compared to the control group, AGO administration significantly reduced epididymal adipose tissue weights and serum non-esterified fatty acid concentrations, but the cecal content weights were increased...
2017: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/28962898/role-of-the-bicarbonate-responsive-soluble-adenylyl-cyclase-in-cholangiocyte-apoptosis-in-primary-biliary-cholangitis-a-new-hypothesis
#10
REVIEW
Jung-Chin Chang, Simei Go, Arthur J Verhoeven, Ulrich Beuers, Ronald P J Oude Elferink
Primary biliary cholangitis (PBC) is a chronic fibrosing cholangiopathy characterized by an autoimmune stereotype and defective biliary bicarbonate secretion due to down-regulation of anion exchanger 2 (AE2). Despite the autoimmune features, immunosuppressants are ineffective while two bile acid-based therapies (ursodeoxycholic acid and obeticholic acid) have been shown to improve biochemical and histological features of cholestasis and long-term prognosis. However, the etiology and pathogenesis of PBC is largely unknown...
September 26, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28951510/increased-cholestatic-enzymes-in-two-patients-with-long-term-history-of-ulcerative-colitis-consider-primary-biliary-cholangitis-not-always-primary-sclerosing-cholangitis
#11
Erietta Polychronopoulou, Vasiliki Lygoura, Nikolaos K Gatselis, George N Dalekos
Several hepatobiliary disorders have been reported in ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) being the most specific. Primary biliary cholangitis (PBC), previously known as primary biliary cirrhosis, rarely occurs in UC. We present two PBC cases of 67 and 71 years who suffered from long-standing UC. Both patients were asymptomatic but they had increased cholestatic enzymes and high titres of antimitochondrial antibodies (AMA)-the laboratory hallmark of PBC. After careful exclusion of other causes of cholestasis by MRI/magnetic resonance cholangiopancreatography (MRCP), virological and microbiological investigations, a diagnosis of PBC associated with UC was established...
September 25, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28947328/outcomes-of-biliary-atresia-in-the-nordic-countries-a-multicenter-study-of-158-patients-during-2005-2016
#12
Mikko P Pakarinen, Lars Søndergaard Johansen, Jan F Svensson, Kristin Bjørnland, Vladimir Gatzinsky, Pernilla Stenström, Antti Koivusalo, Nina Kvist, Markus Almström, Ragnhild Emblem, Sigurdur Björnsson, Torbjörn Backman, Runar Almaas, Hannu Jalanko, Björn Fischler, Jørgen Thorup
BACKGROUND/PURPOSE: Biliary atresia is the most common reason for newborn cholestasis and pediatric liver transplantation. Even after normalization of serum bilirubin after portoenterostomy, most patients require liver transplantation by adulthood due to expanding fibrosis. We addressed contemporary outcomes of biliary atresia in the Nordic countries. METHODS: Data on center and patients characteristics, diagnostic practices, surgical treatment, adjuvant medical therapy after portoenterostomy, follow-up and outcomes were collected from all the Nordic centers involved with biliary atresia care during 2005-2016...
September 5, 2017: Journal of Pediatric Surgery
https://www.readbyqxmd.com/read/28940004/adjuvant-therapy-in-biliary-atresia-hopelessly-optimistic-or-potential-for-change
#13
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...
September 22, 2017: Pediatric Surgery International
https://www.readbyqxmd.com/read/28938442/angiotensin-ii-causes-%C3%AE-cell-dysfunction-through-an-er-stress-induced-proinflammatory-response
#14
Stanley M H Chan, Yeh-Siang Lau, Alyson A Miller, Jacqueline M Ku, Simon Potocnik, Ji-Ming Ye, Owen L Woodman, Terence P Herbert
The metabolic syndrome is associated with an increase in the activation of the renin angiotensin system, whose inhibition reduces the incidence of new-onset diabetes. Importantly, angiotensin II (AngII), independently of its vasoconstrictor action, causes β-cell inflammation and dysfunction, which may be an early step in the development of type 2 diabetes. The aim of this study was to determine how AngII causes β-cell dysfunction. Islets of Langerhans were isolated from C57BL/6J mice that had been infused with AngII in the presence or absence of taurine-conjugated ursodeoxycholic acid (TUDCA) and effects on endoplasmic reticulum (ER) stress, inflammation, and β-cell function determined...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28934223/ursodeoxycholic-acid-prevents-ventricular-conduction-slowing-and-arrhythmia-by-restoring-t-type-calcium-current-in-fetuses-during-cholestasis
#15
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
#16
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/28925077/network-wide-screen-identifies-variation-of-novel-precise-on-module-targets-using-conformational-modudaoism
#17
Bing Li, Jun Liu, Yanan Yu, Pengqian Wang, Yingying Zhang, Xumin Ni, Qiong Liu, Xiaoxu Zhang, Zhong Wang, Yongyan Wang
Modular targeting is promising in drug research at network level, but it's challenging to quantificationally identify the precise On-modules. Based on a proposed Modudaoism (MD), we defined conserved MD (MDc) and varied MD (MDv) to quantitatively evaluate the conformational and energy variations of modules, and thereby identify the conserved and discrepant allosteric modules. Compared with the Zsummary , MDc/MDv got an optimized result of module preserved ratio and modular structure. In mice anti-ischemic networks, 3, 5, and 1 conserved allosteric modules as well as 4, 1, and 3 On-modules of baicalin (BA), jasminoidin (JA), and ursodeoxycholic acid (UA) were identified by MDc and MDv, 5 unique allosteric modules and their characteristic actions were revealed...
September 19, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28915943/derivatization-enhanced-separation-and-sensitivity-of-long-chain-free-fatty-acids-application-to-asthma-using-targeted-and-non-targeted-liquid-chromatography-mass-spectrometry-approach
#18
Xiqing Bian, Baoqing Sun, Peiyan Zheng, Na Li, Jian-Lin Wu
Long chain-free fatty acids (LCFFAs) play pivotal roles in various physiological functions, like inflammation, insulin resistance, hypertension, immune cell behavior and other biological activities. However, the detection is obstructed by the low contents, structural diversity, high structural similarity, and matrix interference. Herein, a fast cholamine-derivatization, within 1 min at room temperature, coupled with liquid chromatography-mass spectrometry (LC-MS) approach was developed to determine LCFFAs in complex samples...
October 9, 2017: Analytica Chimica Acta
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 14, 2017: Hepatology International
https://www.readbyqxmd.com/read/28891588/ursodeoxycholic-acid-for-cystic-fibrosis-related-liver-disease
#20
REVIEW
Katharine Cheng, Deborah Ashby, Rosalind L Smyth
BACKGROUND: Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid...
September 11, 2017: Cochrane Database of Systematic Reviews
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