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drugs testing and analysis

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https://www.readbyqxmd.com/read/28437613/evaluating-the-role-of-multidrug-resistance-protein-3-mdr3-inhibition-in-predicting-drug-induced-liver-injury-using-125-pharmaceuticals
#1
Michael D Aleo, Falgun Shah, Kan He, Paul D Bonin, A David Rodrigues
The role of bile salt export protein (BSEP) inhibition in drug-induced liver injury (DILI) has been investigated widely, while inhibition of the canalicular multidrug resistant protein 3 (MDR3) has received less attention. This transporter plays a pivotal role in secretion of phospholipids into bile and functions coordinately with BSEP to mediate the formation of bile acid-containing biliary micelles. Therefore, inhibition of MDR3 in human hepatocytes was examined across 125 drugs (70 of Most- and 55 of No-DILI-concern)...
April 24, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28437395/global-survey-of-the-immunomodulatory-potential-of-common-drugs
#2
Gregory I Vladimer, Berend Snijder, Nikolaus Krall, Johannes W Bigenzahn, Kilian V M Huber, Charles-Hugues Lardeau, Kumar Sanjiv, Anna Ringler, Ulrika Warpman Berglund, Monika Sabler, Oscar Lopez de la Fuente, Paul Knöbl, Stefan Kubicek, Thomas Helleday, Ulrich Jäger, Giulio Superti-Furga
Small-molecule drugs may complement antibody-based therapies in an immune-oncology setting, yet systematic methods for the identification and characterization of the immunomodulatory properties of these entities are lacking. We surveyed the immumomodulatory potential of 1,402 small chemical molecules, as defined by their ability to alter the cell-cell interactions among peripheral mononuclear leukocytes ex vivo, using automated microscopy and population-wide single-cell image analysis. Unexpectedly, ∼10% of the agents tested affected these cell-cell interactions differentially...
April 24, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28437091/speeding-up-early-drug-discovery-in-antiviral-research-a-fragment-based-in-silico-approach-for-the-design-of-virtual-anti-hepatitis-c-leads
#3
Alejandro Speck-Planche, M Natalia Dias Soeiro Cordeiro
Hepatitis C constitutes an unresolved global health problem. This infectious disease is caused by the hepatotropic hepatitis C virus (HCV), and it can lead to the occurrence of life-threatening medical conditions such as cirrhosis and liver cancer. Nowadays, major clinical concerns have arisen due to the appearance of multidrug resistance (MDR), and the side effects especially associated with long-term treatments. In this work, we report the first multitasking model for quantitative structure-biological effect relationships (mtk-QSBER), focused on the simultaneous exploration of anti-HCV activity and in vitro safety profiles related to the absorption, distribution, metabolism, elimination, and toxicity (ADMET)...
April 24, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/28434968/cardiac-contractility-correction-strategies-applied-to-telemetry-data-from-a-hesi-sponsored-consortium
#4
Emmanuel Boulay, Michael K Pugsley, Vincent Jacquemet, Alain Vinet, Michael V Accardi, Maxim Soloviev, Eric Troncy, Jennifer M Doyle, Jennifer Beck Pierson, Simon Authier
INTRODUCTION: QT has a long history of heart rate (HR) correction but limited investigations have been undertaken to assess the impact of cardiovascular parameters on left ventricular (LV) contractility in drug safety testing. Cardiac contractility is affected by preload (Cyon-Frank-Starling law), afterload (Anrep effect) and HR (Bowditch effect). We evaluated multi-parameter correction methods to help with dP/dtmax interpretation. METHODOLOGY: Modeling was undertaken using data from dogs in single or double 4×4 Latin square studies...
April 20, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28434654/compulsive-addiction-like-aggressive-behavior-in-mice
#5
Sam A Golden, Conor Heins, Marco Venniro, Daniele Caprioli, Michelle Zhang, David H Epstein, Yavin Shaham
BACKGROUND: Some people are highly motivated to seek aggressive encounters, and among those who have been incarcerated for such behavior, recidivism rates are high. These observations echo two core features of drug addiction: high motivation to seek addictive substances, despite adverse consequences, and high relapse rates. Here we used established rodent models of drug addiction to determine whether they would be sensitive to "addiction-like" features of aggression in CD-1 mice. METHODS: In experiments 1 and 2, we trained older CD-1 mice to lever press for opportunities to attack younger C57BL6/J mice...
March 17, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28434413/drug-evaluation-and-decision-making-in-catalonia-development-and-validation-of-a-methodological-framework-based-on-multi-criteria-decision-analysis-mcda-for-orphan-drugs
#6
Antoni Gilabert-Perramon, Josep Torrent-Farnell, Arancha Catalan, Alba Prat, Manel Fontanet, Ruth Puig-Peiró, Sandra Merino-Montero, Hanane Khoury, Mireille M Goetghebeur, Xavier Badia
OBJECTIVES: The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). METHODS: The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members...
April 24, 2017: International Journal of Technology Assessment in Health Care
https://www.readbyqxmd.com/read/28433839/the-diagnostic-accuracy-of-evoked-potential-monitoring-techniques-during-intracranial-aneurysm-surgery-for-predicting-postoperative-ischaemic-damage-a-systematic-review-and-meta-analysis
#7
REVIEW
Benjamin Thomas, Dongsheng Guo
OBJECTIVE: To investigate the diagnostic accuracy of various evoked potential monitoring techniques in predicting postoperative neurological deficit in intracranial aneurysm surgery. METHODS: A literature search of the MEDLINE, Embase and Cochrane databases was conducted for English language papers published between 31 March 1983 and 31 March 2016. Original studies that reported the use of evoked potential monitoring during intracranial aneurysm surgery in predicting postoperative neurological damage were selected, and their relevant reference lists were hand searched...
April 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28432528/conventional-acupuncture-for-cardiac-arrhythmia-a-systematic-review-of-randomized-controlled-trials
#8
Jing Liu, Si-Nai Li, Lu Liu, Kun Zhou, Yan Li, Xiao-Yun Cui, Jie Wan, Jin-Jin Lu, Yan-Chao Huang, Xu-Sheng Wang, Qian Lin
OBJECTIVE: To exam the effect and safety of conventional acupuncture (CA) on cardiac arrhythmia. METHODS: Nine medical databases were searched until February 2016 for randomized controlled trials. Heterogeneity was measured by Cochran Q test. Meta-analysis was conducted if I(2) was less than 85% and the characteristics of included trials were similar. RESULTS: Nine qualified studies involving 638 patients were included. Only 1 study had definitely low risk of bias, while 7 trials were rated as unclear and 1 as high...
April 22, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28431942/chitosan-based-nanocomplexes-for-simultaneous-loading-burst-reduction-and-controlled-release-of-doxorubicin-and-5-fluorouracil
#9
Antonio Di Martino, Pavel Kucharczyk, Zdenka Capakova, Petr Humpolicek, Vladimir Sedlarik
In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method...
April 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28431642/pcr-based-detection-methods-for-single-nucleotide-polymorphism-or-mutation-real-time-pcr-and-its-substantial-contribution-toward-technological-refinement
#10
Kazuyuki Matsuda
Single-nucleotide polymorphisms (SNPs) and single-nucleotide mutations result from the substitution of only a single base. The SNP or mutation can be relevant to disease susceptibility, pathogenesis of disease, and efficacy of specific drugs. It is important to detect SNPs or mutations clinically. Methods to distinguish/detect SNPs or mutations should be highly specific and sensitive. In this regard, polymerase chain reaction (PCR) has provided the necessary analytical performance for many molecular analyses...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28431640/rapid-assessment-of-drugs-of-abuse
#11
Joesph R Wiencek, Jennifer M Colby, James H Nichols
Laboratory testing for drugs of abuse has become standard practice in many settings both forensic and clinical. Urine is the predominant specimen, but other specimens are possible including hair, nails, sweat, and oral fluid. Point-of-care test kits provide for rapid analysis at the site where specimens are collected allowing for immediate action on the results. POCT is based on immunochromatography where the drug in the patient's sample competes with drug and antibody conjugates in the test to develop or block the development of a colored line...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28431628/clinical-and-quantitative-analysis-of-patients-with-crowned-dens-syndrome
#12
Teruyuki Takahashi, Masato Tamura, Toshiaki Takasu, Satoshi Kamei
BACKGROUND: Crowned dens syndrome (CDS) is a radioclinical entity defined by calcium deposition on the transverse ligament of atlas (TLA). In this study, the novel semi-quantitative diagnostic criteria for CDS to evaluate the degree of calcification on TLA by cervical CT are proposed. METHOD: From January 2010 to September 2014, 35 patients who were diagnosed with CDS by cervical CT were adopted as subjects in this study. Based on novel criteria, calcium deposition on TLA was classified into "Stage" and "Grade", to make a score, which was evaluated semi-quantitatively...
May 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28431584/monitoring-quality-and-coverage-of-harm-reduction-services-for-people-who-use-drugs-a-consensus-study
#13
Lucas Wiessing, Marica Ferri, Vendula Běláčková, Patrizia Carrieri, Samuel R Friedman, Cinta Folch, Kate Dolan, Brian Galvin, Peter Vickerman, Jeffrey V Lazarus, Viktor Mravčík, Mirjam Kretzschmar, Vana Sypsa, Ana Sarasa-Renedo, Anneli Uusküla, Dimitrios Paraskevis, Luis Mendão, Diana Rossi, Nadine van Gelder, Luke Mitcheson, Letizia Paoli, Cristina Diaz Gomez, Maitena Milhet, Nicoleta Dascalu, Jonathan Knight, Gordon Hay, Eleni Kalamara, Roland Simon, Catherine Comiskey, Carla Rossi, Paul Griffiths
BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels...
April 22, 2017: Harm Reduction Journal
https://www.readbyqxmd.com/read/28431492/anti-drug-antibodies-in-colombian-patients-with-rheumatoid-arthritis-treated-with-enbrel-vs-etanar-preliminary-report
#14
Benjamín Reyes-Beltrán, Gabriela Delgado
The present study was undertaken to detect antibodies against etanercept (ETN) in a group of Colombian patients with rheumatoid arthritis (RA) and being treated with Enbrel(®) vs. Etanar(®). From these patients with RA, clinical and laboratory data were collected and serum taken for anti-drug antibody (ADAb) analysis. Samples from 32 patients (16 who had been treated with Enbrel(®) and 16 with Etanar(®)) were analyzed. Positive sera for ADAb were found in six of the 32 subjects (18.7%); five (31.2%) in the Enbrel(®) group and one (6...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28431485/efficacy-of-golimumab-in-belgian-patients-with-active-rheumatoid-arthritis-despite-treatment-with-non-biologic-disease-modifying-anti-rheumatic-drugs-sub-analysis-of-the-go-more-study
#15
Patrick Durez, Marie Vanthuyne, Muhammad S Soyfoo, Ilse Hoffman, Michel Malaise, Piet Geusens
OBJECTIVES: The GO-MORE trial (NCT00975130) was a phase 3 study in 40 countries evaluating the efficacy and safety of golimumab as add-on therapy in biologic-naïve adults with active rheumatoid arthritis despite stable treatment with disease-modifying anti-rheumatic drugs. To inform local practice in Belgium and examine the role of baseline disease activity in treatment response, we compared the efficacy of golimumab in the Belgian subpopulation and the rest of the world. METHODS: Baseline disease activity and six-month efficacy rates in the GO-MORE trial were compared for the Belgian subpopulation and the rest of the world by t-tests and chi-squared tests...
April 21, 2017: Acta Clinica Belgica
https://www.readbyqxmd.com/read/28431392/characterization-of-aurora-a-and-its-impact-on-the-effect-of-cisplatin-based-chemotherapy-in-patients-with-non-small-cell-lung-cancer
#16
Peng Kuang, Zuhua Chen, JiaYuan Wang, Zhentao Liu, Jingyuan Wang, Jing Gao, Lin Shen
BACKGROUND AND OBJECTIVE: Aurora A, as a member of serine/threonine kinase family and a common characteristic of epithelial cancers, plays a critical role in cell mitosis. However, the clinical significance of Aurora A in non-small cell lung cancer (NSCLC) remains undetermined. METHODS: The expression of Aurora A in NSCLC and paired normal adjacent lung tissues was determined by immunohistochemistry, Western blot, and reverse transcriptase polymerase chain reaction...
April 18, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28431329/stealth-recombinant-human-serum-albumin-nanoparticles-conjugating-5-fluorouracil-augmented-drug-delivery-and-cytotoxicity-in-human-colon-cancer-ht-29-cells
#17
Ankita Sharma, Amanpreet Kaur, Upendra Kumar Jain, Ramesh Chandra, Jitender Madan
BACKGROUND AND OBJECTIVE: 5-Fluorouracil (5-FU) is a first-line chemotherapeutic drug in colorectal cancer. However, intravenous administration of 5-FU at the dose of 7-12mg/kg exhibits curbs like short half-life (20min) and toxic side-effects on bone marrow cells. Therefore, in present investigation, 5-FU was conjugated to poly (ethylene glycol) anchored recombinant human serum albumin nanoparticles (5-FU-rHSA-PEG-NPs) to improve the pharmacokinetic and therapeutic profiles. METHODS AND RESULTS: The mean particle size of 5-FU-rHSA-NPs was measured to be 44...
April 12, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28431115/spatial-distribution-of-falciparum-malaria-infections-in-zanzibar-implications-for-focal-drug-administration-strategies-targeting-asymptomatic-parasite-carriers
#18
Anders Björkman, Jackie Cook, Hugh Sturrock, Mwinyi Msellem, Abdullah Ali, Weiping Xu, Fabrizio Molteni, Roly Gosling, Chris Drakeley, Andreas Mårtensson
Background.: Optimal use of mass/targeted screen-and-treat or mass or focal drug administration as malaria elimination strategies remains unclear. We therefore studied spatial distribution of Plasmodium falciparum infections to compare simulated effects of these strategies on reducing the parasite reservoir in a pre-elimination setting. Methods.: P. falciparum rapid diagnostic tests (RDTs) and molecular (polymerase chain reaction [PCR]) and serological (enzyme-linked immunosorbent assay) analyses were performed on finger-prick blood samples from a population-based survey in 3 adjacent communities...
May 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28430808/quantification-of-hypoxia-related-gene-expression-as-a-potential-approach-for-clinical-outcome-prediction-in-breast-cancer
#19
Abderrahim El Guerrab, Anne Cayre, Fabrice Kwiatkowski, Maud Privat, Jean-Marc Rossignol, Fabrice Rossignol, Frédérique Penault-Llorca, Yves-Jean Bignon
Breast cancers are solid tumors frequently characterized by regions with low oxygen concentrations. Cellular adaptations to hypoxia are mainly determined by "hypoxia inducible factors" that mediate transcriptional modifications involved in drug resistance and tumor progression leading to metastasis and relapse occurrence. In this study, we investigated the prognostic value of hypoxia-related gene expression in breast cancer. A systematic review was conducted to select a set of 45 genes involved in hypoxia signaling pathways and breast tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28430700/prescriber-compliance-with-liver-monitoring-guidelines-for-pazopanib-in-the-postapproval-setting-results-from-a-distributed-research-network
#20
Sumitra Shantakumar, Beth L Nordstrom, Susan A Hall, Luc Djousse, Myrthe P P van Herk-Sukel, Kathy H Fraeman, David R Gagnon, Karen Chagin, Jeanenne J Nelson
OBJECTIVES: Pazopanib received US Food and Drug Administration approval in 2009 for advanced renal cell carcinoma. During clinical development, liver chemistry abnormalities and adverse hepatic events were observed, leading to a boxed warning for hepatotoxicity and detailed label prescriber guidelines for liver monitoring. As part of postapproval regulatory commitments, a cohort study was conducted to assess prescriber compliance with liver monitoring guidelines. METHODS: Over a 4-year period, a distributed network approach was used across 3 databases: US Veterans Affairs Healthcare System, a US outpatient oncology community practice database, and the Dutch PHARMO Database Network...
April 20, 2017: Journal of Patient Safety
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