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https://www.readbyqxmd.com/read/28934348/antimicrobial-resistance-in-clinical-escherichia-coli-isolates-from-poultry-and-livestock-china
#1
Afrah Kamal Yassin, Jiansen Gong, Patrick Kelly, Guangwu Lu, Luca Guardabassi, Lanjing Wei, Xiangan Han, Haixiang Qiu, Stuart Price, Darong Cheng, Chengming Wang
Poultry and livestock are the most important reservoirs for pathogenic Escherichia coli and use of antimicrobials in animal farming is considered the most important factor promoting the emergence, selection and dissemination of antimicrobial-resistant microorganisms. The aim of our study was to investigate antimicrobial resistance in E. coli isolated from food animals in Jiangsu, China. The disc diffusion method was used to determine susceptibility to 18 antimicrobial agents in 862 clinical isolates collected from chickens, ducks, pigs, and cows between 2004 and 2012...
2017: PloS One
https://www.readbyqxmd.com/read/28933302/smart-organic-inorganic-nanogels-for-activatable-theranostics
#2
Fangyuan Li, Zeyu Liang, Daishun Ling
Intelligent polymeric nanogels, with the rationally designed stimuli-responsive drug delivery and controlled drug release, have attracted considerable attention as an ideal nanoplatform for activatable therapy. On the other hand, functional inorganic nanomaterials are widely used as medical imaging agents due to their unique magnetic or optical properties. The construction of stimuli-responsive polymeric nanogels incorporating with functional inorganic nanomaterials inherits the excellent properties of both polymers and inorganic nanomaterials, consequently, the resulted organic-inorganic hybrid nanogels naturally exhibit stimuli-responsive multi-functionalities for both imaging and therapy...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28931578/lipid-topology-and-electrostatic-interactions-underpin-lytic-activity-of-linear-cationic-antimicrobial-peptides-in-membranes
#3
David J Paterson, Manlio Tassieri, Julien Reboud, Rab Wilson, Jonathan M Cooper
Linear cationic antimicrobial peptides are a diverse class of molecules that interact with a wide range of cell membranes. Many of these peptides disrupt cell integrity by forming membrane-spanning pores that ultimately lead to their death. Despite these peptides high potency and ability to evade acquired bacterial drug resistance, there is a lack of knowledge on their selectivity and activity mechanisms. Such an understanding would provide an informative framework for rational design and could lead to potential antimicrobial therapeutic targets...
September 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28930600/line-1-as-a-therapeutic-target-for-castration-resistant-prostate-cancer
#4
Nadine Houede, Pier Vincenzo Piazza, Philippe Pourquier
Prostate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28923870/associations-between-voriconazole-therapeutic-drug-monitoring-toxicity-and-outcome-in-liver-transplant-patients-an-observational-study
#5
Zahra Hashemizadeh, Parisa Badiee, Seyed Ali Malekhoseini, Hadi Raeisi Shahraki, Bita Geramizadeh, Hashem Montaseri
The aim of this study was to investigate the variability of voriconazole plasma level and its relationship with clinical outcomes and adverse events, among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included and voriconazole trough levels were quantified by the validated high-performance liquid chromatography method. Cytochrome P450 genotypes of CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured...
September 18, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28919737/bacterial-membrane-vesicles-as-novel-nanosystems-for-drug-delivery
#6
REVIEW
Sapna Jain, Jonathan Pillai
Bacterial membrane vesicles (BMVs) are closed spherical nanostructures that are shed naturally and ubiquitously by most bacterial species both in vivo and in vitro. Researchers have elucidated their roles in long-distance transport of a wide array of cargoes, such as proteins, toxins, antigens, virulence factors, microbicidal agents and antibiotics. Given that these natural carriers are important players in intercellular communication, it has been hypothesized that they are equally well attuned for transport and delivery of exogenous therapeutic cargoes...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28918483/effects-of-multidisciplinary-teams-and-an-integrated-follow-up-electronic-system-on-clinical-pharmacist-interventions-in-a-cancer-hospital
#7
Muhammad Tahir Aziz, Tofeeq Ur Rehman, Sadia Qureshi, Sidrah Andleeb
Background The aim of drug therapy is to attain distinct therapeutic effects that not only improve patient's quality of life but also reduce the inherent risks associated with the therapeutic use of drugs. Pharmacists play a key role in reducing these risks by developing appropriate interventions. Whether to accept or reject the intervention made by the pharmacist is a relevant consultant's decision. Objective To evaluate the impact of electronic prompts and follow-up of rejected pharmacy interventions by clinical pharmacists in an in-patient setting...
September 16, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28916961/practical-computational-toolkits-for-dendrimers-and-dendrons-structure-design
#8
Nuno Martinho, Liana C Silva, Helena F Florindo, Steve Brocchini, Teresa Barata, Mire Zloh
Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures...
September 15, 2017: Journal of Computer-aided Molecular Design
https://www.readbyqxmd.com/read/28912448/a-general-reaction-mechanism-for-carbapenem-hydrolysis-by-mononuclear-and-binuclear-metallo-%C3%AE-lactamases
#9
María-Natalia Lisa, Antonela R Palacios, Mahesh Aitha, Mariano M González, Diego M Moreno, Michael W Crowder, Robert A Bonomo, James Spencer, David L Tierney, Leticia I Llarrull, Alejandro J Vila
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28911309/formulation-quality-control-and-safety-issues-of-nanocarriers-used-for-cancer-treatment
#10
Ismael D Bianco, Marcelo R Ceballos, Cristian Casado, Viviana G Dabbene, Carolina Rizzi, R Kiyomi Mizutamari
Cancer is becoming a leading cause of death in the last years. Although we have seen great advances, most human cancers remain incurable because many patients either do not respond or relapse to treatment. Several lines of research are disclosing new therapeutic targets which lead to new active drugs. However, there are still unsolved problems related to stabilization of the pharmaceutical ingredient in aqueous and biological media, pharmacokinetic and pharmacodynamic profiles and cellular uptake to name just a few...
June 7, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28911299/in-silico-models-for-nanomedicine-recent-developments
#11
Pietro Mascheroni, Bernhard Aribo Schrefler
Nanomedicine is a recent promising setting for the advancement of current medical therapies, in particular for cancer. Nanoparticle-mediated therapies are aimed to tackle extremely complex phenomena, involving different biochemical, mechanical and biophysical factors. Computational models can contribute to medical research by helping the understanding of biological mechanisms and by providing quantitative analyses. In this work, we report on computational models that address four main issues related to the use of nanoparticles in anti-cancer therapies, namely the delivery of nanoparticles, their uptake by cells, the release of drugs from nano-platforms and nanoparticle-based therapeutics...
April 17, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28911247/metabolic-pathways-and-pharmacokinetics-of-natural-medicines-with-low-permeability
#12
Mei Zeng, Lan Yang, Dan He, Yao Li, Mingxin Shi, Jingqing Zhang
Drug metabolism plays an important role in the drug disposal process. Differences in pharmacokinetics among individuals are the basis for personalized medicine. Natural medicines, formed by long-term evolution of nature, prioritize the action of a target protein with a drug. Natural medicines are valued for structural diversity, low toxicity, low cost, and definite biological activities. Metabolic pathway and pharmacokinetic research of natural medicines is highly beneficial for clinical dose adjustment and the development of personalized medicine...
September 14, 2017: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/28905963/coarse-grained-molecular-dynamics-studies-of-the-structure-and-stability-of-peptide-based-drug-amphiphile-filaments
#13
Myungshim Kang, Honggang Cui, Sharon M Loverde
Peptide-based supramolecular filaments, in particular filaments self-assembled by drug amphiphiles (DAs), possess great potential in the field of drug delivery. These filaments possess one hundred percent drug loading, with a release mechanism that can be tuned based on the dissociation of the supramolecular filaments and the degradation of the DAs [Cheetham et al., J. Am. Chem. Soc., 2013, 135(8), 2907]. Recently, much attention has been drawn to the competing intermolecular interactions that drive the self-assembly of peptide-based amphiphiles into supramolecular filaments...
September 14, 2017: Soft Matter
https://www.readbyqxmd.com/read/28904942/a-simple-but-accurate-method-for-evaluating-drug-resistance-in-infectious-hcvcc-system
#14
Jian-Rui Li, Wen-Jing Li, Jun-Jun Cheng, Meng-Hao Huang, Zhou-Yi Wu, Chen-Chen Jiang, Hu Li, Jin-Hua Chen, Xiao-Qin Lv, Biao Dong, Jian-Dong Jiang, Zong-Gen Peng
Use of direct-acting antivirals sometimes causes viral drug resistance, resulting in inefficiency in treated patients in real-world practice. Therefore, how to rapidly and accurately evaluate drug resistance is an urgent problem to be solved for rational use and development of antivirals in the future. Here, we aim to develop a new method by which we can evaluate easily but effectively whether a drug will still be efficient in the future treatment in infectious hepatitis C virus cell culture system. HCV-infected Huh7...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28904920/antimicrobial-susceptibility-pattern-of-extended-spectrum-beta-lactamases-producing-organisms-isolated-in-a-tertiary-care-hospital-bangladesh
#15
Mohammad Jobayer, Zeenat Afroz, Sultana Shazeda Nahar, Ayesha Begum, Shahin Ara Begum, S M Shamsuzzaman
CONTEXT: Infection caused by extended-spectrum beta-lactamases (ESBL) producing organism is a major problem regarding antibiotic resistance. AIMS: The aim of this study was to find out the antibiogram of ESBL producing organisms isolated from various samples. SETTINGS AND DESIGN: This cross-sectional study was carried out in the Department of Microbiology of a Tertiary Care Hospital, Dhaka, Bangladesh from January to June 2014. SUBJECTS AND METHODS: One Hundred and seventy-nine ESBL producing Gram-negative organisms detected phenotypically by double-disc synergy test were enrolled in this study...
July 2017: International Journal of Applied and Basic Medical Research
https://www.readbyqxmd.com/read/28902808/-anticoagulant-therapy-of-venous-thromboembolic-complications-balancing-between-risks
#16
K V Lobastov, S V Sapelkin
This article is a review of the literature, related to the problem of recurrence of venous thromboembolic complications and the possibilities of their secondary prevention. The problems of determining the rational duration of anticoagulant therapy on the basis of an individual assessment of its benefit and risk are considered. The information on modern prognostic models allowing quantitative assessment of the probability of hemorrhagic and thrombotic events occurrence is presented (Vienna prediction model, DASH, HAS-BLED, stratification according to ACCP 2016)...
2017: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/28902204/rational-design-and-structure-activity-relationship-studies-of-quercetin-amino-acid-hybrids-targeting-the-anti-apoptotic-protein-bcl-xl
#17
Tahsin F Kellici, Maria V Chatziathanasiadou, Min-Sung Lee, Nisar Sayyad, Elena G Geromichalou, Eirinaios I Vrettos, Antonis D Tsiailanis, Seung-Wook Chi, George D Geromichalos, Thomas Mavromoustakos, Andreas G Tzakos
Anti-apoptotic proteins, like the Bcl-2 family proteins, present an important therapeutic cancer drug target. Their activity is orchestrated through neutralization upon interaction of pro-apoptotic protein counterparts that leads to immortality of cancer cells. Therefore, generating compounds targeting these proteins is of immense therapeutic importance. Herein, Induced Fit Docking (IFD) and Molecular Dynamics (MD) simulations were performed to rationally design quercetin analogues that bind in the BH3 site of the Bcl-xL protein...
September 13, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28900315/efficacy-and-safety-of-deferasirox-in-pediatric-patients-of-thalassemia-at-a-tertiary-care-teaching-hospital
#18
Dhaval R Thakor, Chetna K Desai, Jigar D Kapadia, Ram K Dikshit, K M Mehariya
OBJECTIVE: To evaluate efficacy, safety and utilization pattern of deferasirox in paediatric patients of transfusion dependant β Thalassemia Major at a tertiary care teaching hospital in Gujarat. MATERIALS AND METHODS: This observational, prospective-retrospective, single centre, continuous study was conducted in a tertiary care teaching hospital among paediatric patients of transfusion dependent β Thalassemia Major. Patients treated with deferasirox for not more than 12 weeks were enrolled...
April 2017: Indian Journal of Medical and Paediatric Oncology
https://www.readbyqxmd.com/read/28900175/dynamic-and-kinetic-elements-of-%C3%A2%C2%B5-opioid-receptor-functional-selectivity
#19
Abhijeet Kapoor, Gerard Martinez-Rosell, Davide Provasi, Gianni de Fabritiis, Marta Filizola
While the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899971/matrix-screen-identifies-synergistic-combination-of-parp-inhibitors-and-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-in-ewing-sarcoma
#20
Christine M Heske, Mindy I Davis, Joshua T Baumgart, Kelli M Wilson, Michael V Gormally, Lu Chen, Xiaohu Zhang, Michele Ceribelli, Damien Duveau, Rajarshi Guha, Marc Ferrer, Fernanda I Arnaldez, Jiuping Jay Ji, Huong-Lan Tran, Yiping Zhang, Arnulfo Mendoza, Lee J Helman, Craig J Thomas
PURPOSE: While many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored the in vitro response of Ewing sarcoma cell lines against a large collection of investigational and approved drugs to identify candidate combinations. EXPERIMENTAL DESIGN: Drugs displaying activity as single agents were evaluated in combinatorial (matrix) format to identify highly active, synergistic drug combinations, and combinations were subsequently validated in multiple cell lines using various agents from each class...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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