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https://www.readbyqxmd.com/read/29351433/%C3%AE-nitrostyrene-derivatives-attenuate-lps-mediated-acute-lung-injury-via-the-inhibition-of-neutrophil-platelet-interactions-and-net-release
#1
Yao-Wen Chang, Ching-Ping Tseng, Chih-Hsun Lee, Tsong-Long Hwang, Yu-Li Chen, Mei-Tzu Su, Kowit-Yu Chong, Ying-Wei Lan, Chin-Chung Wu, Kung-Ju Chen, Fen-Hua Lu, Hsiang-Ruei Liao, Chuen Hsueh, Pei-Wen Hsieh
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) are high-mortality and life-threatening diseases that are associated with neutrophil activation and accumulation within lung tissue. Emerging evidence indicates that neutrophil-platelet aggregates (NPAs) at sites of injury increases acute inflammation and contributes to the development of ALI. Even though numerous studies have increased our understanding of the pathophysiology of ALI, there is still a lack of innovative and useful treatments that reduce mortality, emphasizing that there is an urgent need for novel treatment strategies...
January 11, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/29351204/mtor-cross-talk-in-cancer-and-potential-for-combination-therapy
#2
REVIEW
Fabiana Conciatori, Ludovica Ciuffreda, Chiara Bazzichetto, Italia Falcone, Sara Pilotto, Emilio Bria, Francesco Cognetti, Michele Milella
The mammalian Target of Rapamycin (mTOR) pathway plays an essential role in sensing and integrating a variety of exogenous cues to regulate cellular growth and metabolism, in both physiological and pathological conditions. mTOR functions through two functionally and structurally distinct multi-component complexes, mTORC1 and mTORC2, which interact with each other and with several elements of other signaling pathways. In the past few years, many new insights into mTOR function and regulation have been gained and extensive genetic and pharmacological studies in mice have enhanced our understanding of how mTOR dysfunction contributes to several diseases, including cancer...
January 19, 2018: Cancers
https://www.readbyqxmd.com/read/29350902/hierarchically-self-assembled-supramolecular-host-guest-delivery-system-for-delivery-of-chemotherapeutics-to-drug-resistant-cancer-tumours
#3
Hongwei Cheng, Xiaoshan Fan, Xiaoyuan Wang, Enyi Ye, Xian Jun Loh, Zibiao Li, Yun-Long Wu
In this report, a new star-like copolymer -CD-g-(PNIPAAm-b-POEGA)x consisting of a -CD core, grafted with temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and biocompatible poly(oligo(ethylene glycol) acrylate) (POEGA) in a block copolymer of the arms, was used to deliver chemotherapeutics to drug resistant cancer tumours. The first step of the self-assembly process involves the encapsulation of chemotherapeutics through host-guest inclusion complexation between the -cyclodextrin cavity and the anti-cancer drug...
January 19, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29350495/the-current-landscape-of-3d-in-vitro-tumor-models-what-cancer-hallmarks-are-accessible-for-drug-discovery
#4
REVIEW
Darren Rodenhizer, Teresa Dean, Elisa D'Arcangelo, Alison P McGuigan
Cancer prognosis remains a lottery dependent on cancer type, disease stage at diagnosis, and personal genetics. While investment in research is at an all-time high, new drugs are more likely to fail in clinical trials today than in the 1970s. In this review, a summary of current survival statistics in North America is provided, followed by an overview of the modern drug discovery process, classes of models used throughout different stages, and challenges associated with drug development efficiency are highlighted...
January 19, 2018: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/29350327/hypermutated-tumors-and-immune-checkpoint-inhibition
#5
Kristen K Ciombor, Richard M Goldberg
Microsatellite instability-high/DNA mismatch repair deficient tumors are found across the cancer spectrum and often harbor markedly increased numbers of mutations when compared to microsatellite stable/DNA mismatch repair proficient tumors. As a result of this high mutational load, tumor-infiltrating lymphocyte density is increased and more immunogenic neoepitopes are expressed, leading to upregulation of immune checkpoints in these tumors. Checkpoint inhibitors such as pembrolizumab and nivolumab, both immunoglobulin G4 (IgG4) monoclonal antibodies that block interactions between the programmed cell death receptor-1 and its ligands, have significant activity in this tumor class...
January 19, 2018: Drugs
https://www.readbyqxmd.com/read/29350320/ethical-implications-in-vaccine-pharmacotherapy-for-treatment-and-prevention-of-drug-of-abuse-dependence
#6
Anna Carfora, Paola Cassandro, Alessandro Feola, Francesco La Sala, Raffaella Petrella, Renata Borriello
Different immunotherapeutic approaches are in the pipeline for the treatment of drug dependence. "Drug vaccines" aim to induce the immune system to produce antibodies that bind to drugs and prevent them from inducing rewarding effects in the brain. Drugs of abuse currently being tested using these new approaches are opioids, nicotine, cocaine, and methamphetamine. In human clinical trials, "cocaine and nicotine vaccines" have been shown to induce sufficient antibody levels while producing few side effects. Studies in humans, determining how these vaccines interact in combination with their target drug, are underway...
January 19, 2018: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/29350179/risks-in-clinical-applications-of-scopolamine-butylbromide-injection
#7
Lei Zheng, Jing Yang, Chao Song
OBJECTIVE: To investigate and analyze the clinical application of scopolamine butylbromide injection and promote the rational use of the drug. MATERIALS AND METHODS: We classified and analyzed 3,695 cases of scopolamine butylbromide injection (effective cases only) collected over the period of January 2016 to July 2017, including details on gender, age, course of treatment, high-risk patients with other medications, adverse drug reactions, and drug combinations...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29350178/use-of-rifabutin-to-treat-tuberculosis-in-a-cardiac-transplant-recipient-a-case-report%C3%A2
#8
Maya Takayoshi, Kyoichi Wada, Yuka Terada, Sachi Matsuda, Kazuki Nakagita, Akira Oita, Mitsutaka Takada, Aki Shionoiri, Haruki Sunami, Seiko Nakajima, Kensuke Kuroda, Takuma Sato, Osamu Seguchi, Masanobu Yanase, Norihide Fukushima
OBJECTIVE: Tuberculosis is an important concern following organ transplantation. Unfortunately, several antituberculosis drugs interact with immunosuppressants. This report describes our experience with rifabutin (RBT) in the treatment of acute tuberculosis in a cardiac transplant recipient. CASE: A 61-year-old cardiac transplant recipient developed tuberculosis meningitis during treatment of miliary tuberculosis. RBT was given for 27 days concomitantly with cyclosporine (CsA)...
January 19, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29350111/sustained-viral-suppression-with-co-administration-of-oxcarbazepine-and-dolutegravir
#9
Manar M Kandil, Melissa E Badowski, Christopher A Schriever
Co-administration of dolutegravir and oxcarbazepine has been reported to reduce levels of dolutegravir and therefore is contraindicated due to insufficient data to make dosing recommendations. We present eight cases in which patients with human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while concurrently receiving 50 mg of dolutegravir daily as part of their antiretroviral therapy. Upon further evaluation, lab results revealed that despite the risk of decreased levels of dolutegravir due to possible oxcarbazepine enzyme induction, patients maintained at or near virologic suppression (viral load <20 copies/ml)...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29349926/extracellular-vesicles-from-early-stage-p-falciparum-infected-red-blood-cells-contain-pfemp1-and-induce-transcriptional-changes-in-human-monocytes
#10
Natália G Sampaio, Samantha Emery, Alexandra Garnham, Qiao Y Tan, Xavier Sisquella, Matthew A Pimentel, Neta Regev-Rudzki, Louis Schofield, Emily M Eriksson
Pathogens can release extracellular vesicles (EVs) for cell-cell communication and host modulation. EVs from Plasmodium falciparum, the deadliest malaria parasite species, can transfer drug resistance genes between parasites. EVs from late-stage parasite-infected RBC (iRBC-EVs) are immunostimulatory and affect endothelial cell permeability, but little is known about EVs from early-stage iRBC. We detected the parasite virulence factor PfEMP1, which is responsible for iRBC adherence and a major contributor to disease severity, in EVs only up to 12 hours-post RBC invasion...
January 18, 2018: Cellular Microbiology
https://www.readbyqxmd.com/read/29349890/case-report-cytochrome-p450-implications-for-comorbid-adhd-and-ocd-pharmacotherapy
#11
Michaela K Hogan, Nikhil P Rao
TOPIC: This case report details the treatment of an early adolescent already receiving treatment for attention-deficit hyperactivity disorder who presents with recurrent obsessive-compulsive disorder. Potential atomoxetine (Strattera) and fluoxetine (Prozac) interactions via Cytochrome P450 (CYP450) pathways are examined and alternate therapies are recommended. PURPOSE: Provide a discussion of psychopharmacogenomics, especially in the case of combining medications, CYP450 enzymes, and clinical implications in the context of the burgeoning field of precision medicine...
January 19, 2018: Journal of Child and Adolescent Psychiatric Nursing
https://www.readbyqxmd.com/read/29349578/in-situ-tissue-labeling-of-cerebral-amyloid-using-hiv-related-tat-peptide
#12
E Maderna, L Colombo, A Cagnotto, G Di Fede, A Indaco, F Tagliavini, M Salmona, G Giaccone
Delivering peptide-based drugs to the brain is a major challenge because of the existence of the blood-brain barrier (BBB). To overcome this problem, cell-penetrating peptides derived from proteins that are able to cross biological membranes have been used as cell-permeable and brain-penetrant compounds. An example is the transactivator of transcription protein transduction domain (Tat) of the human immunodeficiency virus. The basic domain of Tat is formed of arginine and lysine amino acid residues. Tat has been used as brain-penetrant carrier also in therapies for Alzheimer disease (AD), the most common form of dementia characterized by extracellular cerebral deposits of amyloid made up of Aβ peptide...
January 19, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349513/3d-qsar-study-of-steroidal-and-azaheterocyclic-human-aromatase-inhibitors-using-quantitative-profile-of-protein-ligand-interactions
#13
Sehan Lee, Mace G Barron
Aromatase is a member of the cytochrome P450 superfamily responsible for a key step in the biosynthesis of estrogens. As estrogens are involved in the control of important reproduction-related processes, including sexual differentiation and maturation, aromatase is a potential target for endocrine disrupting chemicals as well as breast cancer therapy. In this work, 3D-QSAR combined with quantitative profile of protein-ligand interactions was employed in the identification and characterization of critical steric and electronic features of aromatase-inhibitor complexes and the estimation of their quantitative contribution to inhibition potency...
January 18, 2018: Journal of Cheminformatics
https://www.readbyqxmd.com/read/29348869/role-of-the-n-terminal-lid-in-regulating-the-interaction-of-phosphorylated-mdmx-with-p53
#14
Jane Vin Chan, Dawn Xin Ping Koh, Yun Liu, Thomas L Joseph, David P Lane, Chandra S Verma, Yaw Sing Tan
Murine double minute 4 protein (MDMX) is crucial for the regulation of the tumor suppressor protein p53. Phosphorylation of the N-terminal domain of MDMX is thought to affect its binding with the transactivation domain of p53, thus playing a role in p53 regulation. In this study, the effects of MDMX phosphorylation on the binding of p53 were investigated using molecular dynamics simulations. It is shown that in addition to the previously proposed mechanism in which phosphorylated Y99 of MDMX inhibits p53 binding through steric clash with P27 of p53, the N-terminal lid of MDMX also appears to play an important role in regulating the phosphorylation-dependent interactions between MDMX and p53...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348856/prognostic-value-of-diametrically-polarized-tumor-associated-macrophages-in-multiple-myeloma
#15
Xinyi Chen, Jin Chen, Wenyan Zhang, Ruixue Sun, Ting Liu, Yuhuan Zheng, Yu Wu
Tumor-associated macrophages (TAMs) are correlated with the prognosis of different types of solid tumors and lymphoma, according to many clinical studies. In vitro experiments have demonstrated the roles of these cells in myeloma cell survival, angiogenesis, immunomodulation, drug resistance, and the interaction between malignant myeloma cells and the microenvironment. Here, we investigated the prognostic significance of TAMs in patients with multiple myeloma (MM). We evaluated the polarized functional status of bone marrow infiltrated by TAMs by immunohistochemical staining of CD68, iNOS, and CD163 in 240 patients with MM from January 2009 to December 2014...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348830/inactivation-deficiency-of-dhodh-induces-cell-cycle-arrest-and-programed-cell-death-in-melanoma
#16
Lichao Liu, Zhen Dong, Qian Lei, Jie Yang, Huanrong Hu, Qian Li, Yacong Ji, Leiyang Guo, Yanli Zhang, Yaling Liu, Hongjuan Cui
Malignant melanoma (MM) is one of the most malignant tumors and has a very poor prognosis. However, there are no effective drugs to treat this disease. As a kind of iron flavin dependent enzyme, dihydroorotate dehydrogenase (DHODH, EC 1.3.3.1) is the fourth and a key enzyme in the de novo biosynthesis of pyrimidines. Herein, we found that DHODH inactivation/deficiency inhibited melanoma cell proliferation, induced cell cycle arrest at S phase and lead to autophagy in human melanoma cells. Meanwhile, leflunomide treatment induced cell apoptosis and deficiency of DHODH sensitized cells to drug-induced apoptosis in BCL-2 deficient melanoma cells, while not in BCL-2 abundant melanoma cells...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29348631/dynamic-all-optical-drug-screening-on-cardiac-voltage-gated-ion-channels
#17
Jonas Streit, Sonja Kleinlogel
Voltage-gated ion channels (VGCs) are prime targets for the pharmaceutical industry, but drug profiling on VGCs is challenging, since drug interactions are confined to specific conformational channel states mediated by changes in transmembrane potential. Here we combined various optogenetic tools to develop dynamic, high-throughput drug profiling assays with defined light-step protocols to interrogate VGC states on a millisecond timescale. We show that such light-induced electrophysiology (LiEp) yields high-quality pharmacological data with exceptional screening windows for drugs acting on the major cardiac VGCs, including hNav1...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348627/chikungunya-virus-nsp1-interacts-directly-with-nsp2-and-modulates-its-atpase-activity
#18
Sameer Kumar, Abhishek Kumar, Prabhudutta Mamidi, Atul Tiwari, Sriram Kumar, Animamalar Mayavannan, Sagarika Mudulli, Ajit Kumar Singh, Bharat Bhusan Subudhi, Soma Chattopadhyay
Chikungunya virus (CHIKV) is a mosquito-borne virus, which has created an alarming threat in the world due to unavailability of vaccine and antiviral compounds. The CHIKV nsP2 contains ATPase, RTPase, helicase and protease activities, whereas, nsP1 is a viral capping enzyme. In alphaviruses, the four non-structural proteins form the replication complex in the cytoplasm and this study characterizes the interaction between CHIKV nsP1 and nsP2. It was observed that, both the proteins co-localize in the cytoplasm and interact in the CHIKV infected cells by confocal microscopy and immunoprecipitation assay...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348621/dynamic-cellular-maps-of-molecular-species-application-to-drug-target-interactions
#19
Carolina García, Alejandro Losada, Miguel A Sacristán, Juan Fernando Martínez-Leal, Carlos M Galmarini, M Pilar Lillo
The design of living cell studies aimed at deciphering the mechanism of action of drugs targeting proteins with multiple functions, expressed in a wide range of concentrations and cellular locations, is a real challenge. We recently showed that the antitumor drug plitidepsin (APL) localizes sufficiently close to the elongation factor eEF1A2 so as to suggest the formation of drug-protein complexes in living cells. Here we present an extension of our previous micro-spectroscopy study, that combines Generalized Polarization (GP) images, with the phasor approach and fluorescence lifetime imaging microscopy (FLIM), using a 7-aminocoumarin drug analog (APL*) as fluorescence tracer...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29348092/prescribing-pattern-of-angiotensin-receptor-blocker-a-study-of-errors-and-drug-drug-interactions
#20
Shagufta Nesar, Muhammad Harris Shoaib, Kiran Rafiq, Najia Rahim, Iyad Naeem Muhammad, Wajiha Iffat
Prescriptions comprising multi-drug therapy mostly illustrate the prescribing error. The phenomenon of error is bonded with human inaccuracy. The erroneous practice is observed in under developed countries like Pakistan, Bangladesh and also in developed ones. Consequently drug-drug interaction is one of the most common error associated with potentially serious adverse response even death. Accordingly the present study was conducted to assess the prevalence of prescribing errors and drug-drug interactions in out-patients receiving angiotensin receptor blockers...
January 2018: Pakistan Journal of Pharmaceutical Sciences
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