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https://www.readbyqxmd.com/read/28212541/analysis-of-variability-in-high-throughput-screening-data-applications-to-melanoma-cell-lines-and-drug-responses
#1
Kuan-Fu Ding, Darren Finlay, Hongwei Yin, William P D Hendricks, Chris Sereduk, Jeffrey Kiefer, Aleksandar Sekulic, Patricia M LoRusso, Kristiina Vuori, Jeffrey M Trent, Nicholas J Schork
High-throughput screening (HTS) strategies and protocols have undergone significant development in the last decade. It is now possible to screen hundreds of thousands of compounds, each exploring multiple biological phenotypes and parameters, against various cell lines or model systems in a single setting. However, given the vast amount of data such studies generate, the fact that they use multiple reagents, and are often technician-intensive, questions have been raised about the variability, reliability and reproducibility of HTS results...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212466/withdrawn-propranolol-for-migraine-prophylaxis
#2
REVIEW
Klaus Linde, Karin Rossnagel
BACKGROUND: Propranolol is one of the most commonly prescribed drugs for migraine prophylaxis. OBJECTIVES: We aimed to determine whether there is evidence that propranolol is more effective than placebo and as effective as other drugs for the interval (prophylactic) treatment of patients with migraine. SEARCH METHODS: Potentially eligible studies were identified by searching MEDLINE/PubMed (1966 to May 2003) and the Cochrane Central Register of Controlled Trials (Issue 2, 2003), and by screening bibliographies of reviews and identified articles...
February 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28212414/decline-in-infection-related-morbidities-following-drug-mediated-reductions-in-the-intensity-of-schistosoma-infection-a-systematic-review-and-meta-analysis
#3
Gisele Andrade, David J Bertsch, Andrea Gazzinelli, Charles H King
BACKGROUND: Since 1984, WHO has endorsed drug treatment to reduce Schistosoma infection and its consequent morbidity. Cross-sectional studies suggest pre-treatment correlation between infection intensity and risk for Schistosoma-related pathology. However, evidence also suggests that post-treatment reduction in intensity may not reverse morbidity because some morbidities occur at all levels of infection, and some reflect permanent tissue damage. The aim of this project was to systematically review evidence on drug-based control of schistosomiasis and to develop a quantitative estimate of the impact of post-treatment reductions in infection intensity on prevalence of infection-associated morbidity...
February 17, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28212377/optimality-principles-reveal-a-complex-interplay-of-intermediate-toxicity-and-kinetic-efficiency-in-the-regulation-of-prokaryotic-metabolism
#4
Jan Ewald, Martin Bartl, Thomas Dandekar, Christoph Kaleta
A precise and rapid adjustment of fluxes through metabolic pathways is crucial for organisms to prevail in changing environmental conditions. Based on this reasoning, many guiding principles that govern the evolution of metabolic networks and their regulation have been uncovered. To this end, methods from dynamic optimization are ideally suited since they allow to uncover optimality principles behind the regulation of metabolic networks. We used dynamic optimization to investigate the influence of toxic intermediates in connection with the efficiency of enzymes on the regulation of a linear metabolic pathway...
February 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28212219/drug-infusion-systems-technologies-performance-and-pitfalls
#5
Uoo R Kim, Robert A Peterfreund, Mark A Lovich
This review aims to broadly describe drug infusion technologies and raise subtle but important issues arising from infusion therapy that can potentially lead to patient instability and morbidity. Advantages and disadvantages of gravity-dependent drug infusion are described and compared with electromechanical approaches for precise control of medication infusion, including large-volume peristaltic and syringe pumps. This review discusses how drugs and inert carriers interact within infusion systems and outlines several complexities and potential sources of drug error...
February 16, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#6
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28212005/stimuli-responsive-polymersomes-for-biomedical-applications
#7
Xiuli Hu, Yuqi Zhang, Zhigang Xie, Xiabin Jing, Adriano Bellotti, Zhen Gu
Polymersomes, the structural analogues of liposomes, are hollow structures enclosed by a bilayer membrane made from amphiphilic copolymers. Polymersomes have been proposed to mimic the structure and properties of cellular membranes and viral capsids. Excellent robustness and stability, chemical versatility for tunable membrane properties and surface functionalization make polymersomes attractive candidates for drug delivery, diagnostic imaging, nanoreactor vessels, and artificial organelles. In further biomimetic strategies, stimuli-responsive polymersomes that can recognize various external physical or internal biological environmental stimuli and conduct "on demand" release in dose-, spatial-, and temporal-controlled fashions have been widely developed...
February 17, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28211962/smoking-prevalence-among-lesbian-bisexual-and-queer-women-in-sydney-remains-high-analysis-of-trends-and-correlates
#8
Rachel M Deacon, Julie Mooney-Somers
INTRODUCTION AND AIMS: To investigate smoking prevalence trends and correlates among lesbian, bisexual and queer-identifying (LBQ) women in Sydney, Australia. DESIGN AND METHODS: Data from 5007 respondents to a repeated cross-sectional community survey were used to examine smoking trends between 2004 and 2014. Multinomial logistic regression was used to examine smoking correlates. RESULTS: Thirty percent of respondents were current smokers, including 48% of 16 to 24-year-olds...
February 17, 2017: Drug and Alcohol Review
https://www.readbyqxmd.com/read/28211604/delays-in-treatment-intensification-with-oral-antidiabetic-drugs-and-risk-of-microvascular-and-macrovascular-events-in-patients-with-poor-glycemic-control-an-individual-patient-simulation-study
#9
Henry J Folse, Jayanti Mukherjee, John J Sheehan, Alexandra J Ward, Ryan L Pelkey, Tuan A Dinh, Lei Qin, Jennifer Kim
AIMS: Despite guideline recommendations, many patients with type 2 diabetes on oral antidiabetic drugs (OADs) whose HbA1c results remain above target do not experience timely treatment intensification. This study uses the Archimedes Model® to estimate the consequences of delays in OAD treatment intensification on glycemic control and long-term outcomes at 5 and 20 years. MATERIALS AND METHODS: Using real world data, we modeled a cohort of hypothetical patients with HbA1c ≥8%, on metformin, with no history of insulin use...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211343/immediate-reactions-to-more-than-1-nsaid-must-not-be-considered-cross-hypersensitivity-unless-tolerance-to-asa-is-verified
#10
D Pérez-Alzate, J A Cornejo-García, N Pérez-Sánchez, I Andreu, A García-Moral, J A Agúndez, J Bartra, I Doña, M J Torres, M Blanca, N Blanca-López, G Canto
BACKGROUND AND OBJECTIVES: Individuals who develop drug hypersensitivity reactions (DHRs) to chemically unrelated nonsteroidal anti-inflammatory drugs (NSAIDs) are considered cross-hypersensitive. The hallmark for this classification is that the patient presents a reaction after intake of or challenge with acetylsalicylic acid (ASA). Whether patients react to 2 or more NSAIDs while tolerating ASA remains to be studied (selective reactions, SRs). Objective: To identify patients with SRs to 2 or more NSAIDs including strong COX-1 inhibitors...
2017: Journal of Investigational Allergology & Clinical Immunology
https://www.readbyqxmd.com/read/28210989/net-clinical-benefit-of-dabigatran-vs-warfarin-in-venous-thromboembolism-analyses-from-re-cover-%C3%A2-re-cover%C3%A2-ii-and-re-medy%C3%A2
#11
Martin Feuring, Sam Schulman, Henry Eriksson, Ajay J Kakkar, Sebastian Schellong, Stefan Hantel, Elke Schueler, Jörg Kreuzer, Samuel Z Goldhaber
The direct oral anticoagulants, e.g., dabigatran etexilate (DE), are effective and well tolerated treatments for venous thromboembolism (VTE). Net clinical benefit (NCB) is a useful concept in weighing potential benefits against potential harm of comparator drugs. The NCB of DE vs. warfarin in VTE treatment was compared. Post-hoc analyses were performed on pooled data from the 6-month RE-COVER® and RE-COVER™ II trials, and data from the RE-MEDY™ trial (up to 36 months), to compare the NCB of DE (150 mg twice daily) and warfarin [target international normalized ratio (INR) 2...
February 16, 2017: Journal of Thrombosis and Thrombolysis
https://www.readbyqxmd.com/read/28210980/molecular-mechanisms-of-ire1%C3%AE-ask1-pathway-reactions-to-unfolded-protein-response-in-drn-neurons-of-post-traumatic-stress-disorder-rats
#12
Fanzhen Kong, Fang Han, Yanhao Xu, Yuxiu Shi
The goal of this study was to further elucidate the molecular mechanisms of post-traumatic stress disorder (PTSD) pathogenesis and to provide experimental evidence for new drug targets for effective PTSD treatment. Expression changes of IRE1α, ASK1, and other downstream molecules of the IRE1α-ASK1 endoplasmic reticulum stress (ERS) signaling pathway were investigated. JNK, P38, CHOP, Bcl-2, and Bax were analyzed at both protein and mRNA levels of dorsal raphe nucleus (DRN) neurons of PTSD rats. The rat PTSD model was established via the single-prolonged stress (SPS) method...
February 16, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28210927/efficacy-and-safety-of-daclatasvir-plus-pegylated-interferon-alfa-2a-and-ribavirin-in-previously-untreated-hcv-subjects-coinfected-with-hiv-and-hcv-genotype-1-a-phase-iii-open-label-study
#13
Mark S Sulkowski, Walford J Fessel, Adriano Lazzarin, Juan Berenguer, Natalia Zakharova, Hugo Cheinquer, Pierre Côté, Douglas Dieterich, Adrian Gadano, Gail Matthews, Jean-Michel Molina, Christophe Moreno, Juan Antonio Pineda, Federico Pulido, Antonio Rivero, Jurgen Rockstroh, Dennis Hernandez, Fiona McPhee, Timothy Eley, Zhaohui Liu, Patricia Mendez, Eric Hughes, Stephanie Noviello, Peter Ackerman
BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks...
February 16, 2017: Hepatology International
https://www.readbyqxmd.com/read/28210505/nanotechnology-based-approach-in-tuberculosis-treatment
#14
REVIEW
Mohammad Nasiruddin, Md Kausar Neyaz, Shilpi Das
Tuberculosis, commonly known as TB, is the second most fatal infectious disease after AIDS, caused by bacterium called Mycobacterium tuberculosis. Prolonged treatment, high pill burden, low compliance, and stiff administration schedules are factors that are responsible for emergence of MDR and XDR cases of tuberculosis. Till date, only BCG vaccine is available which is ineffective against adult pulmonary TB, which is the most common form of disease. Various unique antibodies have been developed to overcome drug resistance, reduce the treatment regimen, and elevate the compliance to treatment...
2017: Tuberculosis Research and Treatment
https://www.readbyqxmd.com/read/28210500/drug-release-characteristics-and-tissue-distribution-of-rifapentine-polylactic-acid-sustained-release-microspheres-in-rabbits-after-paravertebral-implantation
#15
Zheng Zhang, Linbo Wu, Haijian Li, Zhicheng Long, Xinghua Song
BACKGROUND: Rates of drug-resistant tuberculosis (TB) and TB associated with human immunodeficiency virus (HIV) infection have increased dramatically, intensifying challenges in TB control. New formulations of TB treatment drugs that control drug release and increase local drug concentrations will have a significant impact on mitigating the toxic side effects and increasing the clinical efficacy of anti-TB drugs. OBJECTIVES: The aim was to observe the sustained release characteristics of rifapentine polylactic acid sustained-release microspheres in vivo and the accumulation of rifapentine in other tissues following paravertebral implantation...
November 2016: Iranian Red Crescent Medical Journal
https://www.readbyqxmd.com/read/28210462/accuracy-of-a-new-rapid-antigen-detection-test-for-pulmonary-tuberculosis
#16
Rasoul Aliannejad, Ahmadreza Bahrmand, Hamidreza Abtahi, Mahnaz Seifi, Enayat Safavi, Farid Abdolrahimi, Shahriyar Shahriaran
BACKGROUND AND OBJECTIVES: Tuberculosis (TB) is a major problem in the world. Treatment and control of TB needs detection of the Mycobacterium tuberculosis (MT) in the proper samples. While smear doesn't have enough sensitivity, culture and PCR are expensive, time consuming and unavailable in many centers. Recent development of a rapid TB antigen detection test (PrTBK) at Pasteur Institute of Iran could give a simple way for diagnosis of TB in about two hours. In this test the antigen-antibody complex will change color when gold conjugated mouse anti-rabbit antibody detects specific MT cell wall antigen in suspected samples...
August 2016: Iranian Journal of Microbiology
https://www.readbyqxmd.com/read/28209992/from-basic-apoptosis-discoveries-to-advanced-selective-bcl-2-family-inhibitors
#17
REVIEW
Avi Ashkenazi, Wayne J Fairbrother, Joel D Leverson, Andrew J Souers
Members of the B cell lymphoma 2 (BCL-2) gene family have a central role in regulating programmed cell death by controlling pro-apoptotic and anti-apoptotic intracellular signals. In cancer, apoptosis evasion through dysregulation of specific BCL-2 family genes is a recurring event; accordingly, selective inhibition of specific anti-apoptotic BCL-2 family proteins represents an exciting therapeutic opportunity. A combination of nuclear magnetic resonance (NMR)-based screening and structure-based drug design has yielded the first bona fide BCL-2 homology 3 (BH3) mimetics, including the BCL-2 and BCL-XL dual antagonist navitoclax, which is the first BCL-2 family inhibitor to show efficacy in patients with cancer...
February 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28209738/optogenetic-low-frequency-stimulation-of-specific-neuronal-populations-abates-ictogenesis
#18
Zahra Shiri, Maxime Lévesque, Guillaume Etter, Frédéric Manseau, Sylvain Williams, Massimo Avoli
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one third of mesial temporal lobe epilepsy patients. Here, we established the efficacy of cell type-specific low-frequency stimulation (LFS) in controlling ictogenesis in the mouse entorhinal cortex (EC) in an in vitro brain slice preparation. Specifically, we used 1 Hz optogenetic stimulation of Ca(2+)/calmodulin-dependent protein kinase II-positive principal cells as well as of parvalbumin- or somatostatin-positive interneurons to study the effects of such repetitive activation on epileptiform discharges induced by 4-aminopyridine...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209540/in-vitro-characterization-of-ph-sensitive-azithromycin-loaded-methoxy-poly-ethylene-glycol-block-poly-aspartic-acid-graft-imidazole-micelles
#19
Fangfang Teng, Peizong Deng, Zhimei Song, Feilong Zhou, Runliang Feng, Na Liu
In order to improve azithromycin's antibacterial activity in acidic medium, monomethoxy poly (ethylene glycol)-block-poly (aspartic acid-graft-imidazole) copolymer was synthesized through allylation, free radical addition, ring-opening polymerization and amidation reactions with methoxy poly (ethylene glycol) as raw material. Drug loading capacity and encapsulation efficiency of azithromycin-loaded micelles prepared via thin film hydration method were 11.58±0.86% and 96.06±1.93%, respectively. The drug-loaded micelles showed pH-dependent property in the respects of particle size, zeta potential at the range of pH 5...
February 9, 2017: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/28209443/continued-benefit-to-rectal-separation-for-prostate-radiation-therapy-final-results-of%C3%A2-a%C3%A2-phase-iii-trial
#20
Daniel A Hamstra, Neil Mariados, John Sylvester, Dhiren Shah, Lawrence Karsh, Richard Hudes, David Beyer, Steven Kurtzman, Jeffrey Bogart, R Alex Hsi, Michael Kos, Rodney Ellis, Mark Logsdon, Shawn Zimberg, Kevin Forsythe, Hong Zhang, Edward Soffen, Patrick Francke, Constantine Mantz, Peter Rossi, Theodore DeWeese, Stephanie Daignault-Newton, Benjamin W Fischer-Valuck, Anupama Chundury, Hiram Gay, Walter Bosch, Jeff Michalski
PURPOSE: SpaceOAR, a Food and Drug Administration-approved hydrogel intended to create a rectal-prostate space, was evaluated in a single-blind phase III trial of image guided intensity modulated radiation therapy. A total of 222 men were randomized 2:1 to the spacer or control group and received 79.2 Gy in 1.8-Gy fractions to the prostate with or without the seminal vesicles. The present study reports the final results with a median follow-up period of 3 years. METHODS AND MATERIALS: Cumulative (Common Terminology Criteria for Adverse Events, version 4...
December 23, 2016: International Journal of Radiation Oncology, Biology, Physics
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