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https://www.readbyqxmd.com/read/29668114/-%C3%AE-2-adrenoceptors-inhibit-neutrophil-extracellular-traps-in-human-polymorphonuclear-leukocytes
#1
Franca Marino, Angela Scanzano, Laura Pulze, Monica Pinoli, Emanuela Rasini, Alessandra Luini, Raffaella Bombelli, Massimiliano Legnaro, Magda de Eguileor, Marco Cosentino
This study tests the hypothesis that in isolated human polymorphonuclear leukocytes (PMN) adrenergic ligands can affect neutrophil extracellular trap (NET) formation. We have previously shown that, in PMN, adrenaline (A), through the activation of adrenergic receptors (AR), reduces stimulus-dependent cell activation; we have, therefore, planned to investigate if AR are involved in NET production. PMN were obtained from venous blood of healthy subject. The ability of adrenergic ligands to affect reactive oxygen species (ROS) production, NET production, and cell migration was investigated in cells cultured under resting conditions or after activation with N-formyl-methionyl-leucyl-phenylalanine (fMLP), LPS, or IL-8...
April 18, 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29667756/pharmacokinetic-profiling-of-anticancer-phytocompounds-using-computational-approach
#2
Ashish Sharma, Shilpa Sharma, Mansi Gupta, Shehnaz Fatima, Ravi Saini, Subhash Mohan Agarwal
INTRODUCTION: Natural products exhibit diverse scaffolds and are considered as suitable candidates for development of leads. However, poor pharmacokinetics often acts as a hindrance during the drug discovery process. OBJECTIVE: With a view of exploring the absorption, distribution, metabolism, excretion and toxicity (ADMET) profile of plant-based anticancer compounds, open-access databases (NPACT, CancerHSP and TaxKB) were analysed to identify molecules having properties favourable for drug ability...
April 18, 2018: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/29667660/a-new-functional-membrane-protein-microarray-based-on-tethered-phospholipid-bilayers
#3
Meriem Chadli, Ofelia Maniti, Christophe Marquette, Bruno Tillier, Sandra Cortès, Agnès Girard-Egrot
A new prototype of a membrane protein biochip is presented in this article. This biochip was created by the combination of novel technologies of peptide-tethered bilayer lipid membrane (pep-tBLM) formation and solid support micropatterning. Pep-tBLMs integrating a membrane protein were obtained in the form of microarrays on a gold chip. The formation of the microspots was visualized in real-time by surface plasmon resonance imaging (SPRi) and the functionality of a GPCR (CXCR4), reinserted locally into microwells, was assessed by ligand binding studies...
April 18, 2018: Analyst
https://www.readbyqxmd.com/read/29667586/drug-drug-interactions-with-aprepitant-in-antiemetic-prophylaxis-for-chemotherapy
#4
R Schoffelen, A G Lankheet, C M L van Herpen, J J M van der Hoeven, I M E Desar, C Kramers
In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly emetogenic chemotherapy, aprepitant, an NK1-receptor antagonist, is combined with ondansetron and dexamethasone. Aprepitant can influence the pharmacokinetics of other drugs, as it is an inhibitor and inducer of CYP3A4. Some anticancer drugs and other co-medication frequently used in cancer patients are CYP3A4 or CYP29C substrates. We give an overview of the metabolism and current data on clinically relevant drug-drug interactions with aprepitant during chemotherapy...
April 2018: Netherlands Journal of Medicine
https://www.readbyqxmd.com/read/29667556/ultrasound-promoted-green-synthesis-docking-study-of-indole-spliced-thiadiazole-%C3%AE-amino-phosphonates-as-anticancer-agents-and-anti-tyrosinase-agents
#5
Anna Pratima G Nikalje, Pramod Gawhane, Shailee Tiwari, Jaiprakash Sangshetti, Manoj Damale
In this work, a new series of diethyl ((1H-indole-3-yl)((5-phenyl-1,3,4-thiadiazole-2- yl)amino)methyl)phosphonate derivatives 6(a-j) were designed and synthesized in Ultrasound by green protocol using Kabachnik-Fields reaction. The structures of the synthesized compounds were confirmed by spectral analysis such as elemental analyses, IR, 1H NMR, 13C NMR, 31P NMR and mass spectra. The synthesized compounds 6(a-j) were appraised for their in vitro anticancer activity against human cancer cell lines such as SK-MEL-2 (melanoma), IMR-32 (Neuroblastoma), HT-29(Colon) and also on normal murine embryonic fibroblast NIH/3T3 by Sulforhodamine B (SRB) assay, using Adriamycin as a standard drug...
April 17, 2018: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29667549/dentification-and-quantification-of-quercetin-a-major-consitituent-of-artocarpus-altilis-by-targeting-related-genes-of-apoptosis-and-cell-cycle-in-vitro-cytotoxic-activity-against-human-lung-carcinoma-cell-lines-a549
#6
Silvana Russo, Walter Filgueira De Azevedo
BACKGROUND: Cannabinoid Receptor 1 (CB1) is a membrane protein prevalent in the central nervous system, whose crystallographic structure has recently been solved. Studies will be needed to investigate CB1 complexes with its ligands and its role in the development of new drugs. OBJECTIVE: Our goal here is to review the studies on CB1, starting with general aspects and focusing on the recent structural studies, with emphasis on the inverse agonists bound structures...
April 17, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29667438/the-tolerability-and-safety-profile-of-patiromer-a-novel-polymer-based-potassium-binder-for-the-treatment-of-hyperkalemia
#7
Bertram Pitt, Dahlia Garza
Hyperkalemia (HK) occurs often among patients with chronic kidney disease (CKD) and heart failure (HF) and those treated with renin-angiotensin-aldosterone system inhibitors (RAASI). Even small deviations from normal potassium levels carry increased risk of mortality. Patiromer is approved for treatment of HK and has been shown in clinical trials to reduce serum potassium among patients with HK and comorbid conditions. Areas covered: We review pooled data from two clinical trials of patiromer in patients with CKD and HK, safety of patiromer in special populations, drug-drug interaction (DDI) studies, and other studies in healthy volunteers...
April 18, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29667225/activation-of-central-gaba-b-receptors-offsets-the-cyclosporine-counteraction-of-endotoxic-cardiovascular-outcomes-in-conscious-rats
#8
Marwa Y Sallam, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas
We have previously shown that cyclosporine (CSA) counteracts cardiovascular manifestations induced by endotoxemia (lipopolysaccharide, LPS) such as hypotension and cardiac autonomic dysfunction in conscious rats. In this study we investigated whether the facilitation of central γ-amino butyric acid (GABA) neurotransmission blunts these favorable influences of CSA. The LPS-CSA interaction was determined in the absence and presence of drugs that activate GABAA or GABAB receptors or elevate synaptic GABA levels in the central nervous system...
April 18, 2018: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/29667069/the-versatile-role-of-exosomes-in-cancer-progression-diagnostic-and-therapeutic-implications
#9
REVIEW
Vignesh Sundararajan, Fazlul H Sarkar, Thamil Selvee Ramasamy
BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming...
April 17, 2018: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/29667047/investigation-of-the-mechanism-of-therapeutic-protein-drug-interaction-between-methotrexate-and-golimumab-an-anti-tnf%C3%AE-monoclonal-antibody
#10
Weirong Wang, Jocelyn Leu, Rebecca Watson, Zhenhua Xu, Honghui Zhou
A prominent example of human therapeutic protein-drug interaction (TP-DI) is between methotrexate (MTX) and anti-TNFα mAbs. One plausible mechanism for this TP-DI is through the pharmacodynamic effect of MTX on immunogenicity. However, there is no definitive evidence to substantiate this mechanism, and other competing hypotheses, such as MTX suppressing FcγRI expression thereby affecting mAb PK, have also been proposed. In order to understand this mechanism, a cynomolgus monkey study was conducted using golimumab as a model compound...
April 17, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29667038/complex-drug-drug-gene-disease-interactions-involving-cytochromes-p450-systematic-review-of-published-case-reports-and-clinical-perspectives
#11
REVIEW
Flavia Storelli, Caroline Samer, Jean-Luc Reny, Jules Desmeules, Youssef Daali
Drug pharmacokinetics (PK) is influenced by multiple intrinsic and extrinsic factors, among which concomitant medications are responsible for drug-drug interactions (DDIs) that may have a clinical relevance, resulting in adverse drug reactions or reduced efficacy. The addition of intrinsic factors affecting cytochromes P450 (CYPs) activity and/or expression, such as genetic polymorphisms and diseases, may potentiate the impact and clinical relevance of DDIs. In addition, greater variability in drug levels and exposures has been observed when such intrinsic factors are present in addition to concomitant medications perpetrating DDIs...
April 17, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29666860/fluorescence-imaging-of-antibiotic-clofazimine-encapsulated-within-mesoporous-silica-particle-carriers-relevance-to-drug-delivery-and-the-effect-on-its-release-kinetics
#12
Lorenzo Angiolini, Sabrina Valetti, Boiko Cohen, Adam Feiler, Abderrazzak Douhal
We report on the encapsulation of the antibiotic clofazimine (CLZ) within the pores of mesoporous silica particles having hydrophilic (CBET value of 137) and more hydrophobic (CBET value of 94 after calcination at 600 °C) surfaces. We studied the effect of pH on the released amount of CLZ in aqueous solutions and observed a maximum at pH 4.1 in correlation with the solubility of the drug. Less release of the drug was observed from the more hydrophobic particles which was attributed to a difference in the affinity of the drug to the carrier particles...
April 18, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29666821/probiotics-for-the-control-of-helminth-zoonosis
#13
REVIEW
Abadi Amare Reda
This paper is a comprehensive, concise, and an up to date review about probiotics effect and mechanisms against helminth infections of zoonotic importance. Zoonoses are diseases that can be transmitted from animals to humans in a reversible way. Despite zoonotic helminth diseases being still a challenge to the public health and the agriculture industries globally, they were still neglected in both human and veterinary medicine. Moreover, the increasing emergence of anthelmintic drug resistance constitutes failures of most disease control strategies, alarming for a quest to new alternative control approaches...
2018: Journal of Veterinary Medicine
https://www.readbyqxmd.com/read/29666812/tumor-progression-the-neuronal-input
#14
REVIEW
Marco Arese, Federico Bussolino, Margherita Pergolizzi, Laura Bizzozero, Davide Pascal
One of the challenges of cancer is its heterogeneity and rapid capacity to adapt. Notwithstanding significant progress in the last decades in genomics and precision medicine, new molecular targets and therapies appear highly necessary. One way to approach this complex problem is to consider cancer in the context of its cellular and molecular microenvironment, which includes nerves. The peripheral nerves, the topic of this review, modulate the biological behavior of the cancer cells and influence tumor progression, including the events related to the metastatic spread of the disease...
March 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29666792/steady-state-linear-and-non-linear-optical-spectroscopy-of-organic-chromophores-and-bio-macromolecules
#15
REVIEW
Marco Marazzi, Hugo Gattuso, Antonio Monari, Xavier Assfeld
Bio-macromolecules as DNA, lipid membranes and (poly)peptides are essential compounds at the core of biological systems. The development of techniques and methodologies for their characterization is therefore necessary and of utmost interest, even though difficulties can be experienced due to their intrinsic complex nature. Among these methods, spectroscopies, relying on optical properties are especially important to determine their macromolecular structures and behaviors, as well as the possible interactions and reactivity with external dyes-often drugs or pollutants-that can (photo)sensitize the bio-macromolecule leading to eventual chemical modifications, thus damages...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29666374/hatric-based-identification-of-receptors-for-orphan-ligands
#16
Nadine Sobotzki, Michael A Schafroth, Alina Rudnicka, Anika Koetemann, Florian Marty, Sandra Goetze, Yohei Yamauchi, Erick M Carreira, Bernd Wollscheid
Cellular responses depend on the interactions of extracellular ligands, such as nutrients, growth factors, or drugs, with specific cell-surface receptors. The sensitivity of these interactions to non-physiological conditions, however, makes them challenging to study using in vitro assays. Here we present HATRIC-based ligand receptor capture (HATRIC-LRC), a chemoproteomic technology that successfully identifies target receptors for orphan ligands on living cells ranging from small molecules to intact viruses...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29666371/integration-of-human-adipocyte-chromosomal-interactions-with-adipose-gene-expression-prioritizes-obesity-related-genes-from-gwas
#17
David Z Pan, Kristina M Garske, Marcus Alvarez, Yash V Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K Raulerson, Rita M Cantor, Mete Civelek, Craig A Glastonbury, Kerrin S Small, Michael Boehnke, Aldons J Lusis, Janet S Sinsheimer, Karen L Mohlke, Markku Laakso, Päivi Pajukanta, Arthur Ko
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29666300/a-pan-cancer-landscape-of-interactions-between-solid-tumors-and-infiltrating-immune-cell-populations
#18
David Tamborero, Carlota Rubio-Perez, Ferran Muiños, Radhakrishnan Sabarinathan, Josep Maria Piulats, Aura Muntasell, Rodrigo Dienstmann, Nuria Lopez-Bigas, Abel Gonzalez-Perez
PURPOSE: Throughout their development tumors are challenged by the immune system and they acquire features to evade its surveillance. A systematic view of these traits which sheds light on how tumors respond to immunotherapies is still lacking. EXPERIMENTAL DESIGN: Here, we computed the relative abundance of an array of immune cell populations to measure the immune infiltration pattern of 9,174 tumors of 29 solid cancers. We then clustered tumors with similar infiltration pattern to define immune-phenotypes...
April 17, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29666228/deep-learning-improves-prediction-of-drug-drug-and-drug-food-interactions
#19
Jae Yong Ryu, Hyun Uk Kim, Sang Yup Lee
Drug interactions, including drug-drug interactions (DDIs) and drug-food constituent interactions (DFIs), can trigger unexpected pharmacological effects, including adverse drug events (ADEs), with causal mechanisms often unknown. Several computational methods have been developed to better understand drug interactions, especially for DDIs. However, these methods do not provide sufficient details beyond the chance of DDI occurrence, or require detailed drug information often unavailable for DDI prediction. Here, we report development of a computational framework DeepDDI that uses names of drug-drug or drug-food constituent pairs and their structural information as inputs to accurately generate 86 important DDI types as outputs of human-readable sentences...
April 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29666187/a-putative-g-quadruplex-structure-in-the-proximal-promoter-of-vegfr-2-has-implications-for-drug-design-to-inhibit-tumor-angiogenesis
#20
Yaping Liu, Wenxian Lan, Chunxi Wang, Chunyang Cao
Tumor angiogenesis is mainly regulated by vascular endothelial growth factor (VEGF), produced by cancer cells. It is active on the endothelium via VEGF receptor 2 (VEGFR-2). G-quadruplexes are DNA secondary structures formed by guanine-rich sequences, for example, within gene promoters where they may contribute to transcriptional activity. The proximal promoter of vegfr-2 contains a G-quadruplex, which has been suggested to interact with small molecules that inhibit VEGFR-2 expression and thereby tumor angiogenesis...
April 17, 2018: Journal of Biological Chemistry
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