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https://www.readbyqxmd.com/read/27921432/-composition-of-macronutrients-in-the-diabetic-diet
#1
Zdeněk Rušavý, Michal Žourek
The diabetic diet is one of the pillars of diabetes treatment. The rapid development of knowledge relating to the treatment of diabetes also includes diet. The paper focuses on the importance of a diet in the treatment of type 2 diabetes and prevention of atherosclerosis. Its main goal is to assess the impact of a composition of macronutrients on individuals with type 2 diabetes. The paper is divided into several parts, each of which ends with a conclusion. The first part examines weight reduction. The diet aimed at a weight loss is effective, it can effectively prevent diabetes, it leads to improvements in glucose control and reduction of the risk factors for atherosclerosis, however it will not impact on cardiovascular morbidity and mortality until after more than 20 years...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27920546/chronotherapy-with-low-dose-modified-release-prednisone-for-the-management-of-rheumatoid-arthritis-a-review
#2
REVIEW
Stefano Paolo Beltrametti, Aurora Ianniello, Clara Ricci
To date, rheumatoid arthritis (RA) remains a debilitating, life-threatening disease. One major concern is morning symptoms (MS), as they considerably impair the patients' quality of life and ability to work. MS change in a circadian fashion, resembling the fluctuations of inflammatory cytokines such as interleukin-6, whose levels are higher in RA patients compared to healthy donors. Conversely, serum levels of the potent anti-inflammatory glucocorticoid cortisol are similar to that of healthy subjects, suggesting an imbalance that sustains a pro-inflammatory state...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27918545/warfarin-traps-human-vitamin-k-epoxide-reductase-in-an-intermediate-state-during-electron-transfer
#3
Guomin Shen, Weidong Cui, Hao Zhang, Fengbo Zhou, Wei Huang, Qian Liu, Yihu Yang, Shuang Li, Gregory R Bowman, J Evan Sadler, Michael L Gross, Weikai Li
Although warfarin is the most widely used anticoagulant worldwide, the mechanism by which warfarin inhibits its target, human vitamin K epoxide reductase (hVKOR), remains unclear. Here we show that warfarin blocks a dynamic electron-transfer process in hVKOR. A major fraction of cellular hVKOR is in an intermediate redox state containing a Cys51-Cys132 disulfide, a characteristic accommodated by a four-transmembrane-helix structure of hVKOR. Warfarin selectively inhibits this major cellular form of hVKOR, whereas disruption of the Cys51-Cys132 disulfide impairs warfarin binding and causes warfarin resistance...
December 5, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27918198/ppar%C3%AE-dependent-increase-of-mouse-urine-output-by-gemfibrozil-and-fenofibrate
#4
Danjun Song, Min Luo, Manyun Dai, Shizhong Bu, Weihua Wang, Burong Zhang, Frank J Gonzalez, Aiming Liu
While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity...
September 6, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27917846/knowledge-and-attitudes-of-physicians-and-pharmacists-towards-the-use-of-generic-medicines-in-bosnia-and-herzegovina
#5
Tarik Čatić, Lejla Avdagić, Igor Martinović
Aim To investigate and assess knowledge and attitudes of pharmacists and physicians towards generic drugs prescription in order to evaluate current trends, obstacles to prescribe/dispense generics and suggest possible improvements of rational and economic prescribing having in mind scarce public budgets for drugs. Methods A cross-sectional survey among 450 primary care physicians (prescribers) and pharmacists in four major cities in Bosnia and Herzegovina (Sarajevo, Banja Luka, Tuzla and Mostar) during the period between January and March 2016 was conducted...
February 1, 2017: Medicinski Glasnik
https://www.readbyqxmd.com/read/27917684/the-long-term-effect-of-oral-isotretinoin-therapy-on-macula-ganglion-cell-complex-thickness
#6
Gülizar Demirok, Yasemin Topalak, Özge Gündüz, Dilsun Yıldırım, Mehmet Fatih Kocamaz, Ahmet Sengun
PURPOSE: To evaluate the long term effect of oral isotretinoin therapy on macula ganglion cell complex (GCC) thickness by spectral domain optical coherence tomography (SD-OCT). MATERIALS AND METHODS: Newly diagnosed cystic acne patients who received low dose for a long time systemic isotretinoin therapy were included to study. Thorough ophthalmic evaluation and GCC thickness analysis by using SD-OCT were performed at baseline, and at 1, 3, 6, and 12 months of treatment...
December 4, 2016: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/27915457/combined-use-of-the-rationalization-of-home-medication-by-an-adjusted-stopp-in-older-patients-rasp-list-and-a-pharmacist-led-medication-review-in-very-old-inpatients-impact-on-quality-of-prescribing-and-clinical-outcome
#7
Lorenz Van der Linden, Liesbeth Decoutere, Karolien Walgraeve, Koen Milisen, Johan Flamaing, Isabel Spriet, Jos Tournoy
BACKGROUND: Polypharmacy and potentially inappropriate drugs have been associated with negative outcomes in older adults which might be reduced by pharmacist interventions. OBJECTIVES: Our objective was to evaluate the effect of a pharmacist intervention, consisting of the application of the Rationalization of home medication by an Adjusted STOPP in older Patients (RASP) list and a pharmacist-led medication review on polypharmacy, the quality of prescribing, and clinical outcome in geriatric inpatients...
December 3, 2016: Drugs & Aging
https://www.readbyqxmd.com/read/27915387/the-translational-potential-of-human%C3%A2-induced-pluripotent-stem-cells-for-clinical-neurology-the-translational-potential-of-hipscs-in-neurology
#8
REVIEW
Helen Devine, Rickie Patani
The induced pluripotent state represents a decade-old Nobel prize-winning discovery. Human-induced pluripotent stem cells (hiPSCs) are generated by the nuclear reprogramming of any somatic cell using a variety of established but evolving methods. This approach offers medical science unparalleled experimental opportunity to model an individual patient's disease "in a dish." HiPSCs permit developmentally rationalized directed differentiation into any cell type, which express donor cell mutation(s) at pathophysiological levels and thus hold considerable potential for disease modeling, drug discovery, and potentially cell-based therapies...
December 3, 2016: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/27911825/elucidating-the-druggable-interface-of-protein-protein-interactions-using-fragment-docking-and-coevolutionary-analysis
#9
Fang Bai, Faruck Morcos, Ryan R Cheng, Hualiang Jiang, José N Onuchic
Protein-protein interactions play a central role in cellular function. Improving the understanding of complex formation has many practical applications, including the rational design of new therapeutic agents and the mechanisms governing signal transduction networks. The generally large, flat, and relatively featureless binding sites of protein complexes pose many challenges for drug design. Fragment docking and direct coupling analysis are used in an integrated computational method to estimate druggable protein-protein interfaces...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27908829/exploring-the-binding-mechanism-of-heteroaryldihydropyrimidines-and-hepatitis-b-virus-capsid-combined-3d-qsar-and-molecular-dynamics
#10
Jing Tu, Jiao Jiao Li, Zhi Jie Shan, Hong Lin Zhai
The non-nucleoside drugs have been developed to treat HBV infection owing to their increased efficacy and lesser side effects, in which heteroaryldihydropyrimidines (HAPs) have been identified as effective inhibitors of HBV capsid. In this paper, the binding mechanism of HAPs targeting on HBV capsid protein was explored through three-dimensional quantitative structure-activity relationship, molecular dynamics and binding free energy decompositions. The obtained models of comparative molecular field analysis and comparative molecular similarity indices analysis enable the sufficient interpretation of structure-activity relationship of HAPs-HBV...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27906178/a-mechanism-for-overcoming-p-glycoprotein-mediated-drug-resistance-novel-combination-therapy-that-releases-stored-doxorubicin-from-lysosomes-via-lysosomal-permeabilization-using-dp44mt-or-dpc
#11
Nicole A Seebacher, Des R Richardson, Patric J Jansson
The intracellular distribution of a drug can cause significant variability in both activity and selectivity. Herein, we investigate the mechanism by which the anti-cancer agents, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and the clinically trialed, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), re-instate the efficacy of doxorubicin (DOX), in drug-resistant P-glycoprotein (Pgp)-expressing cells. Both Dp44mT and DpC potently target and kill Pgp-expressing tumors, while DOX effectively kills non-Pgp-expressing cancers...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27903217/rational-drug-discovery-of-hcv-helicase-inhibitor-improved-docking-accuracy-with-multiple-seedings-of-autodock-vina-and-in-situ-minimization
#12
SeeKhai Lim, Rozana Othman, Rohana Yusof, ChoonHan Heh
BACKGROUND: Hepatitis C is a significant cause for end-stage liver diseases and liver transplantation which affects approximate 3% of the global populations. Despite the present of several direct antiviral agents in the treatment of hepatitis C, the standard treatment for HCV is accompanied by several drawbacks such as adverse side effects, high pricing of medications and the rapid emerging rate of resistant HCV variants. OBJECTIVES: To discover potential inhibitors for HCV helicase through an optimized in silico approach...
November 30, 2016: Current Computer-aided Drug Design
https://www.readbyqxmd.com/read/27900374/spatially-resolved-microfluidic-stimulation-of-lymphoid-tissue-ex-vivo
#13
Ashley E Ross, Maura C Belanger, Jacob F Woodroof, Rebecca R Pompano
The lymph node is a structurally complex organ of the immune system, whose dynamic cellular arrangements are thought to control much of human health. Currently, no methods exist to precisely stimulate substructures within the lymph node or analyze local stimulus-response behaviors, making it difficult to rationally design therapies for inflammatory disease. Here we describe a novel integration of live lymph node slices with a microfluidic system for local stimulation. Slices maintained the cellular organization of the lymph node while making its core experimentally accessible...
November 30, 2016: Analyst
https://www.readbyqxmd.com/read/27899832/development-and-application-of-a-stepwise-assessment-process-for-rational-redesign-of-sequential-skills-based-courses
#14
Casey E Gallimore, Andrea L Porter, Susanne G Barnett
Objective. To develop and apply a stepwise process to assess achievement of course learning objectives related to advanced pharmacy practice experiences (APPEs) preparedness and inform redesign of sequential skills-based courses. Design. Four steps comprised the assessment and redesign process: (1) identify skills critical for APPE preparedness; (2) utilize focus groups and course evaluations to determine student competence in skill performance; (3) apply course mapping to identify course deficits contributing to suboptimal skill performance; and (4) initiate course redesign to target exposed deficits...
October 25, 2016: American Journal of Pharmaceutical Education
https://www.readbyqxmd.com/read/27899145/bibliometric-analysis-of-publications-on-campylobacter-2000-2015
#15
Waleed M Sweileh, Samah W Al-Jabi, Ansam F Sawalha, Adham S AbuTaha, Sa'ed H Zyoud
BACKGROUND: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis...
November 29, 2016: Journal of Health, Population, and Nutrition
https://www.readbyqxmd.com/read/27897366/active-site-crowding-of-p450-3a4-as-a-strategy-to-alter-its-selectivity
#16
Paolo Schiavini, Kin J Cheong, Nicolas Moitessier, Karine Auclair
Substrate promiscuous enzymes are a promising starting point for the development of versatile biocatalysts. In this study, human cytochrome P450 3A4, known for its ability to metabolize hundreds of drugs, was engineered to alter its regio- and stereoselectivity. Rational mutagenesis was used to specifically introduce steric hindrance in the large active site of P450 3A4 and favour oxidation at a more sterically accessible position on the substrate. Hydroxylation of a synthetic precursor of (R)-lisofylline, a compound under investigation for its anti-inflammatory properties, was chosen as a first proof-of-principle application of our protein engineering strategy...
November 29, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27897114/ureas-applications-in-drug-design-and-development
#17
Ajit Dhananjay Jagtap, Nagendra Bharatrao Kondekar, Amit A Sadani, Ji-Wang Chern
The unique hydrogen binding capabilities of ureas make them an important functional group to make drug-target interactions and thus incorporated in small molecules displaying broad range of bioactivities. The related research and numerous excellent achievements of ureas applicability in drug design for the modulation of selectivity, stability, toxicity and pharmacokinetic profile of lead molecules have become active topic. This review aims to provide insights in to the significance of urea in drug design by summarizing successful studies of various urea derivatives as modulators biological targets (viz...
November 29, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27892723/optimization-and-stratification-of-multiple-sclerosis-treatment-in-fast-developing-economic-countries-a-perspective-from-qatar
#18
Dirk Deleu, Boulenouar Mesraoua, Hisham El Khider, Beatriz Canibano, Gayane Melikyan, Hassan Al Hail, Noha Mhjob, Anjushri Bhagat, Faiza Ibrahim, Yolande Hanssens
OBJECTIVE: The introduction of disease-modifying therapies (DMTs) - with varying degrees of efficacy for reducing annual relapse rate and disability progression - has considerably transformed the therapeutic landscape of relapsing-remitting multiple sclerosis (RRMS). We aim to develop rational evidence-based treatment recommendations and algorithms for the management of clinically isolated syndrome (CIS) and RRMS conform to the healthcare system in a fast-developing economic country such as Qatar...
November 28, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27891677/staurosporine-scaffold-based-rational-discovery-of-the-wild-type-sparing-reversible-inhibitors-of-egfr-t790m-gatekeeper-mutant-in-lung-cancer-with-analog-sensitive-kinase-technology
#19
Xiaoyun Song, Xingcai Liu, Xi Ding
The human epidermal growth factor receptor (EGFR) has been established as an attractive target for lung cancer therapy. However, an acquired EGFR T790M gatekeeper mutation is frequently observed in patients treated with first-line anticancer agents such as gefitinib and erlotinib to cause drug resistance, largely limiting the application of small-molecule kinase inhibitors in EGFR-targeted chemotherapy. Previously, the reversible pan-kinase inhibitor staurosporine and its several analogs such as Gö6976 and K252a have been reported to selectively inhibit the EGFR T790M mutant (EGFR(T790M) ) over wild-type kinase (EGFR(WT) ), suggesting that the staurosporine scaffold is potentially to develop the wild-type sparing reversible inhibitors of EGFR(T790M) ...
November 28, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27890784/identifying-residues-that-determine-scf-molecular-level-interactions-through-a-combination-of-experimental-and-in-silico-analyses
#20
Eitan Rabinovich, Michael Heyne, Anna Bakhman, Mickey Kosloff, Julia M Shifman, Niv Papo
The stem cell factor (SCF)/c-Kit receptor tyrosine kinase complex - with its significant roles in hematopoiesis and angiogenesis - is an attractive target for rational drug design. There is thus a need to map, in detail, the SCF/c-Kit interaction sites and the mechanisms that modulate this interaction. While most residues in the direct SCF/c-Kit binding interface can be identified from the existing crystal structure of the complex, other residues that affect binding through protein unfolding, intermolecular interactions, or allosteric or long-distance electrostatic effects cannot be directly inferred...
November 24, 2016: Journal of Molecular Biology
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