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https://www.readbyqxmd.com/read/27923186/influence-of-surface-passivation-of-2-methoxyestradiol-loaded-plga-nanoparticles-on-cellular-interactions-pharmacokinetics-and-tumour-accumulation
#1
Gopikrishna J Pillai, Bindhu Paul-Prasanth, Shantikumar V Nair, Deepthy Menon
In the present work, 2-Methoxyestradiol [2ME2] loaded PLGA nanoparticles [NPs] were stabilized with Casein or poly(ethylene glycol) [PEG] and evaluated for its cellular interactions, pharmacokinetics and tumour accumulation. Surface stabilized PLGA nanoparticles prepared through a modified emulsion route possessed similar size, surface charge, drug loading and release characteristics. Particle-cell interactions as well as the anti-angiogenesis activity were similar for both nanoformulations in vitro. However, in vivo pharmacokinetics and tumour accumulation of the drug were substantially improved for the PEGylated nanoformulation...
November 29, 2016: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/27923144/folic-acid-grafted-bovine-serum-albumin-decorated-graphene-oxide-an-efficient-drug-carrier-for-targeted-cancer-therapy
#2
Naxin Ma, Jing Liu, Wenxiu He, Zhonghao Li, Yuxia Luan, Yunmei Song, Sanjay Garg
Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent...
November 29, 2016: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/27922880/investigation-of-key-circuit-constituents-affecting-drug-sequestration-during-extracorporeal-membrane-oxygenation-treatment
#3
Jiheum Park, Dong Ah Shin, Saram Lee, Young-Jae Cho, Sanghoon Jheon, Jung Chan Lee, Hee Chan Kim
We quantified the influence of the elements of the extracorporeal oxygenation (ECMO) circuit on drug sequestration by focusing on the interactions between materials and drugs. Tubing of three different brands (Tygon/Maquet/Terumo) and oxygenators of two different brands (Maquet/Terumo) were used. Drugs included dexmedetomidine, meropenem, and heparin which were dissolved in deionized water. Tubing was cut into ~7 cm sections and allowed drug solutions enclosed inside by clamping both ends. The oxygenator housing, gas membrane, and heat exchanger were dissected into ~1 g pieces and submerged into drug solutions...
December 2, 2016: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/27922762/nonchemotherapy-drug-induced-agranulocytosis-in-children-detected-by-a-prospective-pharmacovigilance-program
#4
Nicolás Medrano-Casique, Hoi Y Tong, Alberto M Borobia, Antonio J Carcas, Jesús Frías, Elena Ramírez
OBJECTIVES: A prospective evaluation of nonchemotherapy drug-induced agranulocytosis (DIA) cases, which are infrequent in the pediatric population. We characterize agranulocytosis cases and assess lab test differences between drug- and nondrug-induced agranulocytosis. METHODS: Through our Prospective Pharmacovigilance Program from Laboratory Signals at Hospital we detected pediatric agranulocytosis cases from July 2007 to December 2010. This program estimates the incidence, drug causality, clinical features, outcomes of DIA pediatric cases, and assesses laboratory differences with respect to non-DIA...
December 6, 2016: Pediatric Hematology and Oncology
https://www.readbyqxmd.com/read/27921997/comparative-molecular-dynamics-study-of-dimeric-and-monomeric-forms-of-hiv-1-protease-in-ligand-bound-and-unbound-state
#5
Monikaben Padariya, Umesh Kalathiya
Human immunodeficiency virus type 1 protease is a viral-encoded enzyme and it is essential for replication and assembly of the virus. Inactivation of HIV-1 protease causes production of immature, noninfectious viral particles and thus HIV-1 protease is an attractive target in anti-AIDS drug design. In our current work, we performed molecular dynamics (MD) calculations (500 ns) for two different ligands (COM5 - designed in our previous study, and Darunavir) and made effort to understand dynamics behaviour of our designed compound COM5...
December 6, 2016: General Physiology and Biophysics
https://www.readbyqxmd.com/read/27921633/healthcare-resources-are-inadequate-to-address-the-burden-of-illness-among-hiv-infected-male-prisoners-in-malaysia
#6
Joseph Bick, Gabriel Culbert, Haider A Al-Darraji, Clayton Koh, Veena Pillai, Adeeba Kamarulzaman, Frederick Altice
Purpose Criminalization of drug use in Malaysia has concentrated people who inject drugs (PWID) and people living with HIV into prisons where health services are minimal and HIV-related mortality is high. Few studies have comprehensively assessed the complex health needs of this population. The paper aims to discuss these issues. Design/methodology/approach From October 2012 through March 2013, 221 sequentially selected HIV-infected male prisoners underwent a comprehensive health assessment that included a structured history, physical examination, and clinically indicated diagnostic studies...
December 19, 2016: International Journal of Prisoner Health
https://www.readbyqxmd.com/read/27921393/the-role-of-the-microvascular-network-structure-on-diffusion-and-consumption-of-anti-cancer-drugs
#7
P Mascheroni, R Penta
We investigate the impact of microvascular geometry on the transport of drugs in solid tumors, focusing on the diffusion and consumption phenomena. We embrace recent advances in the asymptotic homogenization literature starting from a double Darcy, double advection-diffusion-reaction system of partial differential equations that is obtained exploiting the sharp length separation between the intercapillary distance and the average tumor size. The geometric information on the microvascular network is encoded into effective hydraulic conductivities and diffusivities, which are numerically computed by solving periodic cell problems on appropriate microscale representative cells...
December 6, 2016: International Journal for Numerical Methods in Biomedical Engineering
https://www.readbyqxmd.com/read/27921334/synacton-and-individual-activity-of-synthetic-and-natural-corticotropins
#8
T V Vyunova, L A Andreeva, K V Shevchenko, N F Myasoedov
Short endogenous peptides represent one of the most important constituents of the mammalian body's general regulatory system. Some synthesized analogs and modified natural peptides (eg, corticotropins) also show high biological activity. Nevertheless, the mechanism of action of regulatory peptides remains unclear. To explain the effects of peptides of intermolecular processes, the hypothesis that a synactonal mechanism underlies the action of regulatory peptides, exemplified by the heptapeptide Semax, has been proposed...
December 6, 2016: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/27920755/finding-potential-therapeutic-targets-against-shigella-flexneri-through-proteome-exploration
#9
Mohammad Uzzal Hossain, Md Arif Khan, Abu Hashem, Md Monirul Islam, Mohammad Neaz Morshed, Chaman Ara Keya, Md Salimullah
Background:Shigella flexneri is a gram negative bacteria that causes the infectious disease "shigellosis." S. flexneri is responsible for developing diarrhea, fever, and stomach cramps in human. Antibiotics are mostly given to patients infected with shigella. Resistance to antibiotics can hinder its treatment significantly. Upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis. Methods: The study was designed for the identification and qualitative characterization for potential drug targets from S...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27920544/pharmaceutical-interventions-in-the-management-of-tuberculosis-in-a-pneumophtisiology-department-ivory-coast
#10
Danho Pascal Abrogoua, Boua Alexis Thierry Kamenan, Brou Jean Marcel Ahui, Elisée Doffou
OBJECTIVES: This study aims to analyze the profile and relevance of pharmaceutical interventions (PIs) in the management of tuberculosis (TB) at inpatient settings. PATIENTS AND METHODS: Cross-sectional descriptive study conducted from March to December 2014 within the inpatient unit of pneumophtisiology department, Ivory Coast. Information collected was based on the classification of drug-related problems (DRPs) and PIs outlined by the French Society of Clinical Pharmacy...
2016: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#11
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27919897/genetic-evidence-for-cytochrome-b-qi-site-inhibition-by-4-1h-quinolone-3-diarylethers-and-antimycin-in-toxoplasma-gondii
#12
P Holland Alday, Igor Bruzual, Aaron Nilsen, Sovitj Pou, Rolf Winter, Choukri Ben Mamoun, Michael K Riscoe, J Stone Doggett
Toxoplasma gondii is an apicomplexan parasite that causes fatal and debilitating brain and eye disease. Endochin-like-quinolones (ELQs) are preclinical compounds that are efficacious against apicomplexan-caused diseases including toxoplasmosis, malaria and babesiosis. Of the ELQs, ELQ-316 has demonstrated the greatest efficacy against acute and chronic experimental toxoplasmosis. Although genetic analyses in other organisms have highlighted the importance of the cytochrome bc1 complex Qi site for ELQ sensitivity, the mechanism of action of ELQs against T...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919891/structure-activity-relationships-of-a-series-of-echinocandins-and-the-discovery-of-cd101-a-highly-stable-and-soluble-echinocandin-with-distinctive-pharmacokinetic-properties
#13
Kenneth D James, Christopher P Laudeman, Navdeep B Malkar, Radha Krishnan, Karen Polowy
Echinocandins are first-line therapy for candidemia and invasive candidiasis. They are generally safe with few drug interactions, but the stability and pharmacokinetic properties of currently approved echinocandins are such that each was developed for daily intravenous infusion. We sought to discover a novel echinocandin with properties that would enable more flexible dosing regimens, alternate routes of delivery, and expanded utility. Derivatives of known echinocandin scaffolds were generated, and an iterative process of design and screening led to the discovery of CD101, a novel echinocandin that has since demonstrated improved chemical stability and pharmacokinetics...
December 5, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27919806/are-placebo-and-drug-specific-effects-additive-questioning-basic-assumptions-of-double-blinded-randomized-clinical-trials-and-presenting-novel-study-designs
#14
REVIEW
Tobias Kube, Winfried Rief
Double-blinded randomized clinical trials (RCTs) assume that pharmacological interventions have drug-specific and unspecific components. Traditional RCTs postulate an additivity of these two components. In this review, we provide evidence from both clinical trials and experimental studies that questions this 'additive model'. Given that the evaluation of drug treatments in RCTs is based on the assumption of additivity, its violation has far-reaching consequences. Therefore, we discuss an interactive model that, in contrast to the additive model, considers interactions between placebo and drug-specific effects...
December 2, 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/27919795/current-and-novel-insights-into-the-neurophysiology-of-migraine-and-its-implications-for-therapeutics
#15
REVIEW
Simon Akerman, Marcela Romero-Reyes, Philip R Holland
Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27919729/noradrenergic-modulation-of-evoked-dopamine-release-and-ph-shift-in-the-mouse-dorsal-hippocampus-and-ventral-striatum
#16
Adam Z Weitemier, Thomas J McHugh
Rapid monoamine release in the dorsal hippocampus is not well characterized, despite its postulated role in modulating fast hippocampal circuit dynamics. We measured monoamine release in the dorsal hippocampus upon stimulation of the ventral tegmental area (VTA) with fast-scan cyclic voltammetry in anesthetized norepinephrine-depleted and non-depleted mice. Within the hippocampus, norepinephrine depletion altered the ability of α2 adrenergic compounds and transporter blockers to modulate the small, evoked monoamine signal...
December 2, 2016: Brain Research
https://www.readbyqxmd.com/read/27919396/think-time-a-novel-approach-to-analysis-of-clinicians-behavior-after-reduction-of-drug-drug-interaction-alerts
#17
Richard Schreiber, Julia A Gregoire, Jacob E Shaha, Steven H Shaha
OBJECTIVES: Pharmacologic interaction alerting offers the potential for safer medication prescribing, but research reveals persistent concerns regarding alert fatigue. Research studies have tried various strategies to resolve this problem, with low overall success. We examined the effects of targeted alert reduction on clinician behavior in a resource constrained hospital. METHODS: A physician and a pharmacy informaticist reduced alert levels of several drug-drug interactions (DDI) that clinicians almost always overrode with approval from and knowledge of the medical staff...
January 2017: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/27919368/clinical-reasoning-in-the-context-of-active-decision-support-during-medication-prescribing
#18
Jan Horsky, Jos Aarts, Leonie Verheul, Diane L Seger, Heleen van der Sijs, David W Bates
OBJECTIVE: Describe and analyze reasoning patterns of clinicians responding to drug-drug interaction alerts in order to understand the role of patient-specific information in the decision-making process about the risks and benefits of medication therapy. Insights could be used to inform the design of decision-support interventions. METHODS: Thirty-two clinicians working with five EHRs in two countries completed sets of six medication orders each and responded to high- and low-severity drug-drug interaction alerts while verbalizing their thoughts in a standard think-aloud protocol...
January 2017: International Journal of Medical Informatics
https://www.readbyqxmd.com/read/27919216/topoisomerase-ii-inhibitors-and-poisons-and-the-influence-of-cell-cycle-checkpoints
#19
Nicholas D Arcy, Brian Gabrielli
Interactions between the decatenation checkpoint and Topoisomerase II (TopoII) are vital for maintaining integrity of the genome. Agents that target this enzyme have been in clinical use in cancer therapy for over 30 years with great success. The types of compounds that have been developed to target TopoII are broadly divided into poisons and catalytic inhibitors. The TopoII poisons are in clinical use as anti-cancer therapies, although in common to most chemotherapeutic agents, they display considerable normal tissue toxicity...
December 5, 2016: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/27919190/investigation-of-the-influence-of-glycyrrhizin-on-the-pharmacokinetics-of-celastrol-in-rats-using-lc-ms-and-its-potential-mechanism
#20
Guangkui Yan, Hanhua Zhang, Wei Wang, Yuan Li, Chenghuang Mao, Mingqiao Fang, Xianhong Yi, Jingdong Zhang
1. The aim of this study was to investigate the effects of glycyrrhizin on the pharmacokinetics of celastrol in rats. 2. Twelve male Sprague-Dawley rats were randomly assigned to two groups: control group and test group. Test group was pretreated with glycyrrhizin at a dose of 100 mg/kg/day for 10 days, and then the two groups were orally administered with celastrol at a dose of 1 mg/kg. The concentration of celastrol was determined using a sensitive and reliable LC-MS method. 3. The results showed that glycyrrhizin could significantly decrease the plasma concentration (from 64...
December 5, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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