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https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#1
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29145151/vildagliptin-loaded-triangular-dna-nanospheres-coated-with-eudragit-for-oral-delivery-and-better-glycemic-control-in-type-2-diabetes-mellitus
#2
Mirza Muhammad Faran Ashraf Baig, Sara Khan, Muhammad Ahsan Naeem, Ghulam Jilany Khan, Muhammad Tayyab Ansari
Diabetes mellitus type 2 is a multidimensional disease associated with poor glycemic control through compromised sensitivity of pancreatic islet α and β cells against glucose and dwindled secretion of insulin which is linked with the quantity of incretin hormones that are abridged by dipeptidyl peptidase-4 (DPP-4) in diseased condition. Vildagliptin (VG) inhibits DPP-4 therefore regulates the incretins that conversely maintains glycemic control. The safe reach and absorption of VG from intestine was dubious...
November 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29145012/the-gut-brain-interaction-in-opioid-tolerance
#3
REVIEW
Hamid I Akbarali, William L Dewey
The prevailing opioid crisis has necessitated the need to understand mechanisms leading to addiction and tolerance, the major contributors to overdose and death and to develop strategies for developing drugs for pain treatment that lack abuse liability and side-effects. Opioids are commonly used for treatment of pain and symptoms of inflammatory bowel disease. The significant effect of opioids in the gut, both acute and chronic, includes persistent constipation and paradoxically may also worsen pain symptoms...
November 13, 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/29144726/physalis-mottle-virus-like-particles-as-nanocarriers-for-imaging-reagents-and-drugs
#4
Hema Masarapu, Bindi K Patel, Paul L Chariou, He Hu, Neetu M Gulati, Bradley L Carpenter, Reza A Ghiladi, Sourabh Shukla, Nicole F Steinmetz
Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively...
November 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29144123/the-sign-of-nmr-chemical-shift-difference-as-a-determinant-of-the-origin-of-binding-selectivity-elucidation-of-the-position-dependence-of-phosphorylation-in-ligands-binding-to-scribble-pdz1
#5
Gustav Sundell, Beat Vögeli, Ylva Ivarsson, Celestine Chi
The use of NMR chemical shift perturbation to monitor changes taking place around the binding site of a ligand-protein interaction is a routine and widely applied methodology in the field of protein biochemistry. Shifts are often acquired by titrating various concentrations of ligand to a fixed concentration of the receptor and may serve the purposes, amongst others, to determine affinity constants, locate binding surfaces, or differentiate between binding mechanisms. Shifts are quantified by the so-called combined chemical shift difference...
November 16, 2017: Biochemistry
https://www.readbyqxmd.com/read/29143966/drug-interaction-at-herg-channel-in-vitro-assessment-of-the-electrophysiological-consequences-of-drug-combinations-and-comparison-against-theoretical-models
#6
Barbara Wiśniowska, Bartosz Lisowski, Magdalena Kulig, Sebastian Polak
Drugs carry a proarrhythmic risk, which gets even greater when they are used in combination. In vitro assessment of the proarrhythmic potential of drugs is limited to one compound and thus neglects the potential of drug-drug interactions, including those involving active metabolites. Here we present the results of an in vitro study of potential drug-drug interactions at the level of the hERG channel for the combination of up to three compounds: loratadine, desloratadine and ketoconazole. Experiments were performed at room temperature on an automated patch-clamp device CytoPatch 2, with the use of heterogeneously, stably transfected HEK cells...
November 16, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29143948/label-free-nmr-based-dissociation-kinetics-determination
#7
Pablo Trigo-Mouriño, Christian Griesinger, Donghan Lee
Understanding the dissociation of molecules is the basis to modulate interactions of biomedical interest. Optimizing drugs for dissociation rates is found to be important for their efficacy, selectivity, and safety. Here, we show an application of the high-power relaxation dispersion (RD) method to the determination of the dissociation rates of weak binding ligands from receptors. The experiment probes proton RD on the ligand and, therefore, avoids the need for any isotopic labeling. The large ligand excess eases the detection significantly...
November 16, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/29143894/mechanism-of-resistance-in-gastrointestinal-stromal-tumors
#8
E Tamborini
Imatinib has revolutionized the treatment of GIST since this drug is able to inhibit tumoral growth by blocking the activity of receptor tyrosine kinases, KIT or PDGFRA, that in these tumors are constitutively activated because of the presence of mutations that alters their catalytic activity. However, despite this enormous improvement in the RFS and OS and in the quality of life of GIST patients, imatinib is not able to eradicate the disease: recurrences occur and acquired resistance is a common event which develops during targeted treatments...
November 17, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/29143777/margination-of-fluorescent-polylactic-acid-polyaspartamide-based-nanoparticles-in-microcapillaries-in-vitro-the-effect-of-hematocrit-and-pressure
#9
Emanuela Fabiola Craparo, Rosa D'Apolito, Gaetano Giammona, Gennara Cavallaro, Giovanna Tomaiuolo
The last decade has seen the emergence of vascular-targeted drug delivery systems as a promising approach for the treatment of many diseases, such as cardiovascular diseases and cancer. In this field, one of the major challenges is carrier margination propensity (i.e., particle migration from blood flow to vessel walls); indeed, binding of these particles to targeted cells and tissues is only possible if there is direct carrier-wall interaction. Here, a microfluidic system mimicking the hydrodynamic conditions of human microcirculation in vitro is used to investigate the effect of red blood cells (RBCs) on a carrier margination in relation to RBC concentration (hematocrit) and pressure drop...
October 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29143479/encapsulation-of-rifampin-in-a-polymeric-layer-by-layer-structure-for-drug-delivery
#10
Akbar Esmaeili, Meissam Khodaei
Rifampin (RIF) is a bactericidal antibiotic drug and potent inducer of hepatic and intestinal cytochrome P-450 (CYP-450) enzyme systems. Given by mouth or intravenously, it can cause numerous clinical drug interactions; thus, alternative systems of drug delivery that bypass some or all of its toxic effects are well worth investigating. In this study, a controlled layer-by-layer (LBL) process of encapsulating RIF in biocompatible alginate and chitosan polymers loaded onto Fe3 O4 nanoparticles was developed. Fe3 O4 nanoparticles were synthesized from FeCl3 ·6H2 O using a hydrothermal procedure...
November 16, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29143454/high-prevalence-of-drug-drug-interactions-in-primary-health-care-is-caused-by-prescriptions-from-other-health-care-units
#11
Marine L Andersson, Ylva Böttiger, Henrik Kockum, Birgit Eiermann
Drug-drug interactions are increasingly common, as patients are getting older and the number of drugs per patient is increasing. In this study, we investigated to which extent potential drug-drug interactions originated from single or multiple prescribers. All patients attending any of 20 primary health care centres were included in a retrospective observational cohort study. Data on all prescriptions to these patients, irrespectively of the prescriber, were collected for two 4-month periods. Potential drug interactions were identified using the drug-drug interaction database SFINX...
November 15, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29143219/glutamatergic-gabaergic-and-endocannabinoid-neurotransmissions-within-the-dorsal-hippocampus-modulate-the-cardiac-baroreflex-function-in-rats
#12
Nilson Carlos Ferreira-Junior, Davi Campos Lagatta, Leonardo Barbosa Moraes Resstel
The dorsal hippocampus (DH) is involved in the modulation of the cardiac baroreflex function. There is a wide expression of the NMDA and AMPA/Kainate receptors within the DH. Glutamate administration into the DH triggers both tachycardia and pressor responses. Moreover, GABAergic interneurons and endocannabinoid system play an important role in modulation of the activity of glutamatergic neurons within the DH. Therefore, the present work aimed to evaluate the involvement of the glutamatergic, GABAergic, and endocannabinoid neurotransmissions within the DH in cardiac baroreflex function in rats...
November 15, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29143053/recent-advances-in-microfluidic-technologies-for-cell-to-cell-interaction-studies
#13
REVIEW
Mario Rothbauer, Helene Zirath, Peter Ertl
Microfluidic cell cultures are ideally positioned to become the next generation of in vitro diagnostic tools for biomedical research, where key biological processes such as cell signalling and dynamic cell-to-cell interactions can be reliably analysed under reproducible physiological cell culture conditions. In the last decade, a large number of microfluidic cell analysis systems have been developed for a variety of applications including drug target optimization, drug screening and toxicological testing. More recently, advanced in vitro microfluidic cell culture systems have emerged that are capable of replicating the complex three-dimensional architectures of tissues and organs and thus represent valid biological models for investigating the mechanism and function of human tissue structures, as well as studying the onset and progression of diseases such as cancer...
November 16, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/29142737/cloning-expression-and-identification-of-ktx-sp4-a-selective-kv1-3-peptidic-blocker-from-scorpiops-pococki
#14
Yan Zou, Feng Zhang, Yaxian Li, Yuanfang Wang, Yi Li, Zhengtao Long, Shujuan Shi, Li Shuai, Jiukai Liu, Zhiyong Di, Shijin Yin
Background: Specific and selective peptidic blockers of Kv1.3 channels can serve as a valuable drug lead for treating T cell-mediated autoimmune diseases, and scorpion venom is an important source of kv1.3 channel inhibitors. Through conducting transcriptomic sequencing for the venom gland of Scorpiops pococki from Xizang province of China, this research aims to discover a novel functional gene encoding peptidic blocker of Kv1.3, and identify its function. Results: We screened out a new peptide toxin KTX-Sp4 which had 43 amino acids including six cysteine residues...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29142438/molecular-simulation-based-combinatorial-modeling-and-antioxidant-activities-of-zingiberaceae-family-rhizomes
#15
Talambedu Usha, Sushen Pradhan, Arvind Kumar Goyal, Shanmugarajan Dhivya, H P Prashanth Kumar, Manoj Kumar Singh, Neelu Joshi, Bharat Chandra Basistha, K R Siddalinga Murthy, Saravanakumar Selvaraj, Sushil Kumar Middha
Objective: The main aim of this scientific report was to investigate a series of phytochemicals in silico and the pharmacology of four plants found at higher altitude in the ginger family, Zingiberaceae (incl. Costaceae) from North-East India, particularly Sikkim. First, the goal was to determine the biological activities of the four herbs (used under Zingiberaceae family) using antioxidant assays to identify the best species. Second, previously reported compounds in litero were subsequently screened for their anticancerous activities using in silico methods...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29142404/chalepin-a-compound-from-ruta-angustifolia-l-pers-exhibits-cell-cycle-arrest-at-s-phase-suppresses-nuclear-factor-kappa-b-nf-%C3%AE%C2%BAb-pathway-signal-transducer-and-activation-of-transcription-3-stat3-phosphorylation-and-extrinsic-apoptotic-pathway-in-non-small-cell
#16
Jaime Stella Moses Richardson, Norhaniza Aminudin, Sri Nurestri Abd Malek
Background: Plants have been a major source of inspiration in developing novel drug compounds in the treatment of various diseases that afflict human beings worldwide. Ruta angustifolia L. Pers known locally as Garuda has been conventionally used for various medicinal purposes such as in the treatment of cancer. Objective: A dihydrofuranocoumarin named chalepin, which was isolated from the chloroform extract of the plant, was tested on its ability to inhibit molecular pathways of human lung carcinoma (A549) cells...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29141569/isatin-new-hope-against-convulsion
#17
Rameshwar S Cheke, Sandip D Firke, Ravindra R Patil, Sanjay B Bari
Epilepsy is one of the most significant chronic neurological disorders with high occurrence worldwide. Many epileptic patients are not completely treated with currently available marketed drugs as well as so many drugs have shown unfavorable side effect and drug interaction. Therefore, there are continuing interests to find new anticonvulsant drugs. Recently, there has been wide interest in compounds containing the isatin moiety with diverse biological effects. In view of the previous continuation of an ongoing program aiming at finding new structure leads to potential anticonvulsant activities, we are trying to compile recent efforts which have been made in the design and development of isatin derived anticonvulsant agents...
November 13, 2017: Central Nervous System Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141210/pfclpc-is-an-essential-clp-chaperone-required-for-plastid-integrity-and-clp-protease-stability-in-plasmodium-falciparum
#18
Anat Florentin, David W Cobb, Jillian D Fishburn, Michael J Cipriano, Paul S Kim, Manuel A Fierro, Boris Striepen, Vasant Muralidharan
The deadly malaria parasite Plasmodium falciparum contains a nonphotosynthetic plastid, known as the apicoplast, that functions to produce essential metabolites, and drugs that target the apicoplast are clinically effective. Several prokaryotic caseinolytic protease (Clp) genes have been identified in the Plasmodium genome. Using phylogenetic analysis, we focused on the Clp members that may form a regulated proteolytic complex in the apicoplast. We genetically targeted members of this complex and generated conditional mutants of the apicoplast-localized PfClpC chaperone and PfClpP protease...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29141068/new-insight-into-the-pathophysiology-of-hair-loss-trigger-a-paradigm-shift-in-the-treatment-approach
#19
Neil S Sadick, Valerie D Callender, Leon H Kircik, Sophia Kogan
<p>Hair loss affects millions of men and women of all ages and ethnicities, impacting appearance, social interactions, and psycho-emotional well-being. Although a number of options are available, they are limited, carry a potential risk of side effects, and none have proven to be comprehensive for treatment of hair loss. Across the spectrum of hair loss disorders, there has long been a segmentation into distinct mechanisms, driving the main trend in current therapeutics to focus on targeting single molecules or pathways...
November 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/29141065/use-of-isoquercetin-in-the-treatment-of-prurigo-nodularis
#20
Christine M Pennesi, John Neely, Ames G Marks, S Alison Basak
<p>Atopic dermatitis and prurigo nodularis result from complex interactions between the skin, the immune system, and the external environment. The pruritus associated with these conditions greatly impacts patients' quality of life and lacks uniformly effective treatment. A 57-year-old patient presented with severe atopic dermatitis and subsequent prurigo nodularis refractory to numerous standard therapies. The supplement isoquercetin was initiated and he noted significant, sustained reduction in his pruritus after only four weeks...
November 1, 2017: Journal of Drugs in Dermatology: JDD
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