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https://www.readbyqxmd.com/read/29351570/joint-adolescent-adult-early-phase-clinical-trials-to-improve-access-to-new-drugs-for-adolescents-with-cancer-proposals-from-the-multi-stakeholder-platform-accelerate
#1
N Gaspar, L V Marshall, D Binner, R Herold, R Rousseau, P Blanc, R Capdeville, J Carleer, C Copland, Y Kerloeguen, K Norga, L Pacaud, M-A Sevaux, C Spadoni, J Sterba, F Ligas, T Taube, M Uttenreuther-Fischer, S Chioato, M A O'Connell, B Geoerger, J-Y Blay, J C Soria, S Kaye, B Wulff, L Brugières, G Vassal, A D J Pearson
The impressive progress recently observed in adult cancers through the introduction of new drugs has not yet been translated to adolescents between 12 and 17 years of age. Currently adolescents are grouped with children, so their access to new, effective drugs already available for adults is delayed because paediatric drug development starts late relative to adult programmes. Moreover, specific early phase trials designed exclusively for adolescents in rare diseases recruit poorly, even if conducted internationally...
January 16, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29351374/fast-dynamic-docking-guided-by-adaptive-electrostatic-bias-the-md-binding-approach
#2
Andrea Spitaleri, Sergio Decherchi, Andrea Cavalli, Walter Rocchia
Engineering chemical entities to modify how pharmaceutical targets function, as it is done in drug design, requires a good understanding of molecular recognition and binding. In this context, the limitations of statically describing bimolecular recognition, as done in docking/scoring, call for insightful and efficient dynamical investigations. On the experimental side, the characterization of dynamical binding processes is still in its infancy. Thus, computer simulations, particularly molecular dynamics (MD), are compelled to play a prominent role, allowing a deeper comprehension of the binding process and its causes and thus a more informed compound selection, making more significant the computational contribution to drug discovery1...
January 19, 2018: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/29351214/synthesis-and-evaluation-of-the-antioxidant-activity-of-lipophilic-phenethyl-trifluoroacetate-esters-by-in-vitro-abts-dpph-and-in-cell-culture-dcf-assays
#3
Roberta Bernini, Maurizio Barontini, Valentina Cis, Isabella Carastro, Daniela Tofani, Rosa Anna Chiodo, Paolo Lupattelli, Sandra Incerpi
Polyphenols are natural compounds showing a variety of health-promoting effects. Unfortunately, due to low lipid solubility, their applications in the pharmaceutical, food, and cosmetic industries are limited. With the aim of obtaining novel lipophilic derivatives, the present study reports the synthesis of a series of phenethyl trifluoroacetate esters containing up to two hydroxyl groups in the aromatic ring. Experimental logP values confirmed a greater lipophilicity of the novel compounds compared to the parent compounds...
January 19, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29350995/a-review-of-analytical-methods-for-the-determination-of-clopidogrel-in-pharmaceuticals-and-biological-matrices
#4
Kavitha J, K S Kokilambigai, R Seetharaman, Harini R R, A A Kaaviya, Sowndaravel P, Lakshmi K S
P2Y12 belongs to a group of G protein - coupled (GPCR) purinergic receptors and is a receptor for adenosine diphosphate (ADP). The P2Y12 receptor is involved in platelet aggregation and acts as a biological target for treating thromboembolisms and other clotting disorders. The use of Clopidogrel (CLO) has improved the morbidity and mortality endpoints including cardiovascular death, recurrent myocardial infarction (MI) and stroke at 30 days after percutaneous coronary intervention (PCI). CLO is one such drug that specifically and irreversibly inhibits the P2Y12 subtype of ADP receptor...
January 19, 2018: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/29350758/obesity-and-pediatric-drug-development
#5
Janelle D Vaughns, Laurie S Conklin, Ying Long, Panli Zheng, Fahim Faruque, Dionna J Green, John N van den Anker, Gilbert J Burckart
There is a lack of dosing guidelines for use in obese children. Moreover, the impact of obesity on drug safety and clinical outcomes is poorly defined. The paucity of information needed for the safe and effective use of drugs in obese patients remains a problem, even after drug approval. To assess the current incorporation of obesity as a covariate in pediatric drug development, the pediatric medical and clinical pharmacology reviews under the Food and Drug Administration (FDA) Amendments Act of 2007 and the FDA Safety and Innovation Act (FDASIA) of 2012 were reviewed for obesity studies...
January 19, 2018: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29350257/a-new-approach-for-the-extraction-of-tetracyclines-from-soil-matrices-application-of-the-microwave-extraction-technique
#6
Paulina Łukaszewicz, Anna Białk-Bielińska, Joanna Dołżonek, Jolanta Kumirska, Magda Caban, Piotr Stepnowski
The widespread use of tetracyclines (TCs) in animal husbandry is associated with their constant penetration into the environment and the threat they might pose to living organisms. While the literature data on the analysis of these substances in such matrices as food, tissues, or wastewater are quite extensive, there are still only a few methods presented for the determination of these compounds in soil samples. Moreover, among the literature methods for the extraction of TCs from soil samples, microwave-assisted solvent extraction (MAE) was used only once and in combination with liquid chromatography with spectrophotometric detection (LC-UV)...
January 19, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29350255/nuclear-magnetic-resonance-and-high-performance-liquid-chromatography-techniques-for-the-characterization-of-bioactive-compounds-from-humulus-lupulus-l-hop
#7
Davide Bertelli, Virginia Brighenti, Lucia Marchetti, Anna Reik, Federica Pellati
Humulus lupulus L. (hop) represents one of the most cultivated crops, it being a key ingredient in the brewing process. Many health-related properties have been described for hop extracts, making this plant gain more interest in the field of pharmaceutical and nutraceutical research. Among the analytical tools available for the phytochemical characterization of plant extracts, quantitative nuclear magnetic resonance (qNMR) represents a new and powerful technique. In this ambit, the present study was aimed at the development of a new, simple, and efficient qNMR method for the metabolite fingerprinting of bioactive compounds in hop cones, taking advantage of the novel ERETIC 2 tool...
January 19, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29350184/chirality-in-molecular-collision-dynamics
#8
Andrea Lombardi, Federico Palazzetti
Chirality is a phenomenon that permeates the natural world, with implications for atomic and molecular physics, for fundamental forces and for the mechanisms at the origin of the early evolution of life and biomolecular homochirality. The manifestations of chirality in chemistry and biochemistry are numerous, the striking ones being chiral recognition and asymmetric synthesis with important applications in molecular sciences and in industrial and pharmaceutical chemistry. Chiral discrimination phenomena, due to the existence of two enantiomeric forms, very well known in the case of interaction with light, but still nearly disregarded in molecular collision studies...
January 19, 2018: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/29350177/antidepressant-medication-in-a-german-cohort-of-patients-with-alzheimer-s-disease%C3%A2
#9
Philipp Hessmann, Richard Dodel, Erika Baum, Matthias J Müller, Greta Paschke, Bernhard Kis, Jan Zeidler, Mike Klora, Jens-Peter Reese, Monika Balzer-Geldsetzer
OBJECTIVE: The use of antidepressant drugs in dementia patients is associated with the risk of adverse events, and the evidence for relevant effects is scarce. We aimed to determine the associations between the prescription of antidepressants and patients' sociodemographic (e.g., age, gender, living situation) and clinical characteristics (e.g., disease severity, neuropsychiatric symptoms). MATERIALS AND METHODS: We included 395 institutionalized and community-dwelling patients with Alzheimer's disease (AD) across all severity stages of dementia in a cross-sectional study design...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29350129/new-medications-for-treatment-resistant-depression-a-brief-review-of-recent-developments
#10
Michael E Thase
There is a great unmet need for new medications with novel mechanisms of action that can effectively treat patients who do not benefit from standard antidepressant therapies. After a period in which it seemed as if the pharmaceutical pipeline for new antidepressants was going dry, the past decade has witnessed renewed interest, beginning with discovery of the antidepressant effects of ketamine. This article briefly highlights more recent research on ketamine and other investigational antidepressants.
December 2017: CNS Spectrums
https://www.readbyqxmd.com/read/29350120/-continued-development-of-drugs-the-path-of-thioguanine
#11
M Simsek, K H N de Boer, C J J Mulder
Continued development of existing drugs ('drug rediscovery') may offer new therapeutic options and be cost-effective. Rediscovered drugs are commonly prescribed off-label, although licensing can be important to allow safe and controlled prescription of the drugs to patients. Licensing of a new indication for a generic drug, however, is a complicated process since there is no blueprint for this and there is little interest from the pharmaceutical industry due to an unattractive cost-recovery model. In this article, we illustrate the successful license-extension for thioguanine - initially developed in 1950 for leukaemia - as a new treatment for patients with inflammatory bowel disease...
2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29350069/new-and-developing-pharmacotherapy-for-osteoporosis-in-men
#12
Luigi Gennari, John P Bilezikian
Osteoporosis represents a major health and societal burden in men, as well as in women. However, only a minority of men are screened and treated for osteoporosis and fracture prevention, even after first fracture. Areas covered: This article provides a comprehensive summary of the currently available drugs for osteoporosis in men as well as insights into new and developing pharmacotherapy. Expert opinion: To date, therapeutic approaches to osteoporosis in men remain not as well defined as in women, since antifracture efficacy data are lacking for most approved pharmaceuticals...
January 19, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29349875/preclinical-qsp-modeling-in-the-pharmaceutical-industry-an-iq-consortium-survey-examining-the-current-landscape
#13
REVIEW
Marjoleen J M A Nijsen, Fan Wu, Loveleena Bansal, Erica Bradshaw-Pierce, Jason R Chan, Bianca M Liederer, Jerome T Mettetal, Patricia Schroeder, Edgar Schuck, Alice Tsai, Christine Xu, Anjaneya Chimalakonda, Kha Le, Mark Penney, Brian Topp, Akihiro Yamada, Mary E Spilker
No abstract text is available yet for this article.
January 19, 2018: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/29349812/drug-promotion-practices-a-review
#14
Nilan T Jacob
Over the years, the pharmaceutical industry has been at the forefront of research and innovation in drug discovery and development. The process of drug discovery extending from pre-clinical studies to multi-centric clinical trials and post-marketing phase is a costly affair running into billions of dollars. On the flip side, not all investigational molecules clear the trial phases and get approved; which puts pressure on the manufacturers to maximise the profit from approved drugs. It is in this key area, the practice of drug promotion plays its role...
January 18, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29349647/behaviour-of-freshwater-snails-radix-balthica-exposed-to-the-pharmaceutical-sertraline-under-simulated-predation-risk
#15
Melanie Lea Hedgespeth, Tomasz Karasek, Johan Ahlgren, Olof Berglund, Christer Brönmark
Due to their potential for affecting the modulation of behaviour, effects of selective serotonin reuptake inhibitors (SSRIs) in the environment are particularly interesting regarding interspecies interactions and non-consumptive effects (NCEs) induced by predator cues in prey organisms. We evaluated the effects of sertraline (0.4, 40 ng/L, 40 µg/L) over 8 days on activity and habitat choice in the freshwater snail Radix balthica, on snails' boldness in response to mechanical stimulation (simulating predator attack), and their activity/habitat choice in response to chemical cues from predatory fish...
January 18, 2018: Ecotoxicology
https://www.readbyqxmd.com/read/29349521/recent-developments-in-the-synthesis-and-applications-of-dihydropyrimidin-2-1h-ones-and-thiones
#16
REVIEW
Behzad Mohammadi, Farahnaz K Behbahani
Dihydropyrimidin-2(1H)-ones/thiones (DHPMs) are important heterocyclic compounds owing to their excellent biological activities and have been widely utilized in pharmaceutical applications. Recently, numerous DHPM derivatives have been prepared. This review covers the synthesis of DHPMs and improved procedures for the preparation of DHPMs from 1995 to 2016.
January 18, 2018: Molecular Diversity
https://www.readbyqxmd.com/read/29349359/resensitization-of-methicillin-resistant-staphylococcus-aureus-by-amoxapine-an-fda-approved-antidepressant
#17
Tyler J Wilson, Meghan S Blackledge, Patrick A Vigueira
The rapid increase in bacterial resistance to antibiotics is a global healthcare crisis. Non-antibiotic pharmaceuticals that have attained approval by the United States Food and Drug Administration have the potential to be repurposed as bacterial resistance-modifying agents and therefore could become valuable resources in our battle against antibiotic-resistant microbes. Amoxapine is a tetracyclic antidepressant used in the treatment of major depressive disorder. Here we demonstrate the ability of amoxapine to resensitize methicillin-resistant Staphylococcus aureus strain ATCC 43300 to oxacillin in both agar diffusion and broth microdilution assays...
January 2018: Heliyon
https://www.readbyqxmd.com/read/29349271/becoming-a-pharmaceutical-person-medication-use-trajectories-from-age-26-to-38-in-a-representative-birth-cohort-from-dunedin-new-zealand
#18
Peri J Ballantyne, Pauline Norris, Venkata Praveen Parachuru, W Murray Thomson
Despite the abundance of medications available for human consumption, and frequent concerns about increasing medicalization or pharmaceuticalization of everyday life, there is little research investigating medicines-use in young and middle-aged populations and discussing the implications of young people using increasing numbers of medicines and becoming pharmaceutical users over time. We use data from a New Zealand longitudinal study to examine changes in self-reported medication use by a complete birth cohort of young adults...
April 2018: SSM—Population Health
https://www.readbyqxmd.com/read/29348631/dynamic-all-optical-drug-screening-on-cardiac-voltage-gated-ion-channels
#19
Jonas Streit, Sonja Kleinlogel
Voltage-gated ion channels (VGCs) are prime targets for the pharmaceutical industry, but drug profiling on VGCs is challenging, since drug interactions are confined to specific conformational channel states mediated by changes in transmembrane potential. Here we combined various optogenetic tools to develop dynamic, high-throughput drug profiling assays with defined light-step protocols to interrogate VGC states on a millisecond timescale. We show that such light-induced electrophysiology (LiEp) yields high-quality pharmacological data with exceptional screening windows for drugs acting on the major cardiac VGCs, including hNav1...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348235/digitization-of-multistep-organic-synthesis-in-reactionware-for-on-demand-pharmaceuticals
#20
Philip J Kitson, Guillaume Marie, Jean-Patrick Francoia, Sergey S Zalesskiy, Ralph C Sigerson, Jennifer S Mathieson, Leroy Cronin
Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations...
January 19, 2018: Science
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