Search results for "Bile"
showing 10 items of 2148 documents
Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci
2012
Background & Aims: A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on,a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). Methods: We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. Results: Seventeen SNPs representing 1…
Ion Pairing with Bile Salts Modulates Intestinal Permeability and Contributes to Food–Drug Interaction of BCS Class III Compound Trospium Chloride
2013
In the current study the involvement of ion pair formation between bile salts and trospium chloride (TC), a positively charged Biopharmaceutical Classification System (BCS) class III substance, showing a decrease in bioavailability upon coadministration with food (negative food effect) was investigated. Isothermal titration calorimetry provided evidence of a reaction between TC and bile acids. An effect of ion pair formation on the apparent partition coefficient (APC) was examined using (3)H-trospium. The addition of bovine bile and bile extract porcine led to a significant increase of the APC. In vitro permeability studies of trospium were performed across Caco-2-monolayers and excised seg…
Can't simply roll it out: Evaluating a real-world virtual reality intervention to reduce driving under the influence.
2020
Driving under the influence (DUI) increases the risk of crashes. Emerging technologies, such as virtual reality (VR), represent potentially powerful and attractive tools for the prevention of risky behaviours, such as DUI. Therefore, they are embraced in prevention efforts with VR interventions primed to grow in popularity in near future. However, little is known about the actual effectiveness of such DUI-targeting VR interventions. To help fill the knowledge gap, this study explored the effects of one VR intervention as delivered in the real world. Using pre and post test design, including an intervention group (n = 98) and a control group (n = 39), the intervention evaluation examined you…
Brief Acceptance and Commitment Therapy for Fibromyalgia: Feasibility and Effectiveness of a Replicated Single-Case Design
2020
Objective. Overall, the literature on the effectiveness of psychological treatments in general and those for fibromyalgia in particular has been dominated by research designs that focus on large groups and explore changes on average, so the treatment impact at the individual level remains unclear. In this quasi-experimental, replicated single-case design, we will test the feasibility and effectiveness of a brief acceptance and committed therapy intervention using ecological momentary assessment supported by technology. Methods. ,e sample comprised 7 patients (3 in the individual condition and 4 in the group condition) who received a brief, 5-week psychological treatment. Patient evolution w…
Mitochondrial biogenesis fails in secondary biliary cirrhosis in rats leading to mitochondrial DNA depletion and deletions
2011
Chronic cholestasis is characterizedby mitochondrial dysfunction, associated with loss of mitochondrialmembrane potential, decreased activities of respiratory chaincomplexes, and ATP production. Our aim was to determine themolecular mechanisms that link long-term cholestasis to mitochondrialdysfunction. We studied a model of chronic cholestasis inducedby bile duct ligation in rats. Key sensors and regulators of theenergetic state and mitochondrial biogenesis, mitochondrial DNA(mtDNA)-to-nuclear DNA (nDNA) ratio (mtDNA/nDNA) relativecopy number, mtDNA deletions, and indexes of apoptosis (BAX,BCL-2, and cleaved caspase 3) and cell proliferation (PCNA) wereevaluated. Our results show that long…
Δ5-Cholenoyl-amino acids as selective and orally available antagonists of the Epheephrin system
2015
The Eph receptor-ephrin system is an emerging target for the development of novel anti-angiogenic therapies. Research programs aimed at developing small-molecule antagonists of the Eph receptors are still in their initial stage as available compounds suffer from pharmacological drawbacks, limiting their application in vitro and in vivo. In the present work, we report the design, synthesis and evaluation of structure-activity relationships of a class of Δ(5)-cholenoyl-amino acid conjugates as Eph-ephrin antagonists. As a major achievement of our exploration, we identified N-(3β-hydroxy-Δ(5)-cholen-24-oyl)-L-tryptophan (UniPR1331) as the first small molecule antagonist of the Eph-ephrin syste…
The anti-inflammatory drugs diclofenac, naproxen and ibuprofen are found in the bile of wild fish caught downstream of a wastewater treatment plant.
2012
Pharmaceutical residues are ubiquitous in rivers, lakes, and at coastal waters affected by discharges from municipal wastewater treatment plants. In this study, the presence of 17 different pharmaceuticals and six different phase I metabolites was determined in the bile of two wild fish species, bream (Abramis brama) and roach (Rutilus rutilus). The fish were caught from a lake that receives treated municipal wastewater via a small river. Prior to analyses, the bile content was enzymatically hydrolyzed to convert the glucuronide metabolites into the original pharmaceuticals or phase I metabolites. The solid phase extracts of hydrolyzates were analyzed by liquid chromatography-tandem mass sp…
Can Brief, Daily Training Using a Mobile App Help Change Maladaptive Beliefs? Crossover Randomized Controlled Trial
2019
BackgroundObsessive-compulsive disorder (OCD) is a disabling condition with a wide variety of clinical presentations including contamination fears, fear of harm, and relationship-related obsessions. Cognitive behavioral models of OCD suggest that OC symptoms result from catastrophic misinterpretations of commonly occurring intrusive experiences and associated dysfunctional strategies used to manage them. OCD-related maladaptive beliefs including inflated responsibility, importance and control of thoughts, perfectionism, and intolerance for uncertainty increase the likelihood of such misinterpretations. ObjectiveConsidering accumulating evidence suggesting that mobile health (mHealth) apps b…
Gemcitabine and oxaliplatin combination chemotherapy in advanced biliary tract cancers
2006
Background Biliary tract cancers are uncommon tumors with a poor prognosis and most patients present with invasive and inoperable disease at diagnosis. Chemotherapy represents a palliative treatment, with poor response rates and a median survival of less than 6 months. Oxaliplatin and gemcitabine have shown an interesting activity as single agents in this group of patients. Patients and methods We carried out a multicenter phase II study to evaluate the efficacy and safety of combined oxaliplatin and gemcitabine in locally advanced and metastatic biliary tract carcinoma. The schedule of chemotherapy included oxaliplatin 100 mg/m2 on day 1 and gemcitabine 1000 mg/m2 on days 1 and 8, every 21…
A Model‐Based Workflow to Benchmark the Clinical Cholestasis Risk of Drugs
2021
We present a generic workflow combining physiology-based computational modeling and in vitro data to assess the clinical cholestatic risk of different drugs systematically. Changes in expression levels of genes involved in the enterohepatic circulation of bile acids were obtained from an in vitro assay mimicking 14 days of repeated drug administration for 10 marketed drugs. These changes in gene expression over time were contextualized in a physiology-based bile acid model of glycochenodeoxycholic acid. The simulated drug-induced response in bile acid concentrations was then scaled with the applied drug doses to calculate the cholestatic potential for each compound. A ranking of the cholest…