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https://www.readbyqxmd.com/read/28934216/genetic-polymorphisms-of-cytochrome-p450-1a2-cyp1a2-among-emiratis
#1
Mohammad M Al-Ahmad, Naheed Amir, Subramanian Dhanasekaran, Anne John, Yousef M Abdulrazzaq, Bassam R Ali, Salim M A Bastaki
Cytochrome P450 1A2 (CYP1A2) is one of the CYP450 mixed-function oxidase system that is of clinical importance due to the large number of drug interactions associated with its induction and inhibition. In addition, significant inter-individual differences in the elimination of drugs metabolized by CYP1A2 enzyme have been observed which are largely due to the highly polymorphic nature of CYP1A2 gene. However, there are limited studies on CYP1A2 phenotypes and CYP1A2 genotypes among Emiratis and thus this study was carried out to fill this gap...
2017: PloS One
https://www.readbyqxmd.com/read/28934153/inhibitory-effect-of-selaginellins-from-selaginella-tamariscina-beauv-spring-against-cytochrome-p450-and-uridine-5-diphosphoglucuronosyltransferase-isoforms-on-human-liver-microsomes
#2
Jae-Kyung Heo, Phi-Hung Nguyen, Won Cheol Kim, Nguyen Minh Phuc, Kwang-Hyeon Liu
Selaginella tamariscina (Beauv.) has been used for traditional herbal medicine for treatment of cancer, hepatitis, and diabetes in the Orient. Numerous bioactive compounds including alkaloids, flavonoids, lignans, and selaginellins have been identified in this medicinal plant. Among them, selaginellins having a quinone methide unit and an alkylphenol moiety have been known to possess anticancer, antidiabetic, and neuroprotective activity. Although there have been studies on the biological activities of selaginellins, their modulatory potential of cytochrome P450 (P450) and uridine 5'-diphosphoglucuronosyltransferase (UGT) activities have not been previously evaluated...
September 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28933938/development-of-a-statewide-publicly-accessible-drug-overdose-surveillance-and-information-system
#3
Brandon D L Marshall, Jesse L Yedinak, Jonathan Goyer, Traci C Green, Jennifer A Koziol, Nicole Alexander-Scott
In response to Rhode Island's overdose epidemic, we developed a collaborative, statewide online "dashboard" to provide the public with timely overdose surveillance data. The Web site- www.PreventOverdoseRI.org (PORI)-offers user-friendly data visualizations, plain language education, and interactive resource maps. Development of the site has improved overdose data sharing and transparency in Rhode Island. Preliminary results suggest a successful site launch. Future research will evaluate the effectiveness of PORI in terms of informing strategic initiatives to reduce overdoses in affected communities...
September 21, 2017: American Journal of Public Health
https://www.readbyqxmd.com/read/28933851/design-and-structure-guided-development-of-novel-inhibitors-of-the-xeroderma-pigmentosum-group-a-xpa-protein-dna-interaction
#4
Navnath S Gavande, Pamela VanderVere-Carozza, Akaash K Mishra, Tyler L Vernon, Katherine S Pawelczak, John J Turchi
XPA is a unique and essential protein required for the nucleotide excision DNA repair pathway and represents a therapeutic target in oncology. Herein, we are the first to develop novel inhibitors of the XPA-DNA interaction through structure-guided drug design efforts. Ester derivatives of the compounds 1 (X80), 22, and 24 displayed excellent inhibitory activity (IC50 of 0.82 ± 0.18 μM and 1.3 ± 0.22 μM, respectively) but poor solubility. We have synthesized novel amide derivatives that retain potency and have much improved solubility...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28933729/structure-and-catalysis-of-fe-iii-and-cu-ii-microperoxidase-11-interacting-with-the-positively-charged-interfaces-of-lipids
#5
Tatiana Prieto, Vinicius Santana, Adrianne M M Britto, Juliana C Araujo-Chaves, Otaciro R Nascimento, Iseli L Nantes-Cardoso
Numerous applications have been described for microperoxidases (MPs) such as in photoreceptors, sensing, drugs, and hydrogen evolution. The last application was obtained by replacing Fe(III), the native central metal, by cobalt ion and inspired part of the present study. Here, the Fe(III) of MP-11 was replaced by Cu(II) that is also a stable redox state in aerated medium, and the structure and activity of both MPs were modulated by the interaction with the positively charged interfaces of lipids. Comparative spectroscopic characterization of Fe(III) and Cu(II)MP-11 in the studied media demonstrated the presence of high and low spin species with axial distortion...
July 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28933670/on-enrichment-strategies-for-biomarker-stratified-clinical-trials
#6
Xiaofei Wang, Jingzhu Zhou, Ting Wang, Stephen L George
In the era of precision medicine, drugs are increasingly developed to target subgroups of patients with certain biomarkers. In large all-comer trials using a biomarker stratified design (BSD), the cost of treating and following patients for clinical outcomes may be prohibitive. With a fixed number of randomized patients, the efficiency of testing certain treatments parameters, including the treatment effect among biomarker positive patients and the interaction between treatment and biomarker, can be improved by increasing the proportion of biomarker positives on study, especially when the prevalence rate of biomarker positives is low in the underlying patient population...
September 21, 2017: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/28933629/ezetimibe-ameliorates-steatohepatitis-via-amp-activated-protein-kinase-tfeb-mediated-activation-of-autophagy-and-nlrp3-inflammasome-inhibition
#7
Soo Hyun Kim, Gyuri Kim, Dai Hoon Han, Milim Lee, Irene Kim, Bohkyung Kim, Kook Hwan Kim, Young-Mi Song, Jeong Eun Yoo, Hye Jin Wang, Soo Han Bae, Yong-Ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Myung-Shik Lee
Impairment in macroautophagy/autophagy flux and inflammasome activation are common characteristics of nonalcoholic steatohepatitis (NASH). Considering the lack of approved agents for treating NASH, drugs that can enhance autophagy and modulate inflammasome pathways may be beneficial. Here, we investigated the novel mechanism of ezetimibe, a widely prescribed drug for hypercholesterolemia, as a therapeutic option for ameliorating NASH. Human liver samples with steatosis and NASH were analyzed. For in vitro studies of autophagy and inflammasomes, primary mouse hepatocytes, human hepatoma cells, mouse embryonic fibroblasts with Ampk or Tsc2 knockout, and human or primary mouse macrophages were treated with ezetimibe and palmitate...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28933616/are-newly-launched-pharmacotherapies-efficacious-in-treating-idiopathic-pulmonary-fibrosis-or-is-there-still-more-work-to-be-done
#8
Riccardo Inchingolo, Carola Condoluci, Andrea Smargiassi, Annelisa Mastrobattista, Cristina Boccabella, Alessia Comes, Nicoletta Golfi, Luca Richeldi
Idiopathic pulmonary fibrosis (IPF) is a challenging and multifactorial disease that has been thought for some time to lack effective treatments. The approval of two drugs, nintedanib and pirfenidone, has heralded a new era in its management. Areas covered: Currently, there is a growing interest on therapeutic strategies. Many studies have been designed and performed, although few of them turned out to be successful. Nowadays, nintedanib and pirfenidone are considered disease modifying drugs, recommended treatments by current evidence-based guidelines...
September 21, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28933567/vitamin-k-and-cancer
#9
Sofia Dahlberg, Jacob Ede, Ulf Schött
Subclinical vitamin K deficits refer to carboxylation defects of different types of vitamin K-dependent hepatic and extrahepatic so-called Gla proteins without prolongation of the prothrombin time. This condition has been reported in different clinical situations due to insufficient supply or malabsorption of vitamin K as well as drug interactions. This review discusses the effects of different vitamin K subspecies on tumour growth and the possible anti-tumour effects of increased vitamin K intake. Blocking carboxylation of vitamin K-dependent proteins with warfarin anticoagulation - what are the risks/benefits for carcinogenesis? Previous studies on both heparin and low molecular weight heparin blocking of the vitamin K-dependent factors X and II have shown tumour suppressive effects...
September 21, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28933316/photo-activatable-akt-probe-a-new-tool-to-study-the-akt-dependent-physiopathology-of-cancer-cells
#10
Sanae Haga, Takeaki Ozawa, Naoki Morita, Mami Asano, Shigeki Jin, Michitaka Ozakia
Akt is commonly overexpressed and activated in cancer cells, and plays a pivotal role in cell survival, protection andchemo-resistance. Therefore, Akt is one of the target molecules in understanding characters of cancer cells and developing anti-cancer drugs. Here, we examined whether a newly developed photo-activatable Akt (PA-Akt) probe, based on a light-inducible protein interaction module of plant cryptochrome2 (CRY2) and cryptochrome-interacting basic-helix-loop-helix (CIB1), can regulate Akt-associated cell functions...
August 30, 2017: Oncology Research
https://www.readbyqxmd.com/read/28933312/characterization-of-imatinib-resistant-cml-leukemic-stem-initiating-cells-and-their-sensitivity-to-cbp-catenin-antagonists
#11
Yi Zhao, Kaijin Wu, Yongfeng Wu, Elizabeth Melendez, Goar Smbatyan, David Massiello, Michael Kahn
The development of the tyrosine kinase inhibitor Imatinib (IM) represents a milestone breakthrough in CML (Chronic Myeloid Leukemia) treatment. However, it is not curative and patients develop IM resistance. IM resistance has been previously correlated with the emergence of drug-resistant LIC/LSC (Leukemia Initiating Cell/Leukemia Stem Cell) and increased nuclear catenin levels and enhanced Wnt signaling. It has been demonstrated previously that drug resistant CML LIC/LSC can be safely eliminated both in vitro and in vivo via disruption of the CBP/catenin interaction, utilizing the highly biochemically selective small molecule CBP/catenin antagonist ICG-001...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28933310/socialization-alleviates-burden-of-oxidative-stress-in-hippocampus-and-prefrontal-cortex-in-morphine-addiction-period-in-male-rats
#12
Hamidreza Famitafreshi, Morteza Karimian
INTRODUCTION: Addiction is a compulsive drug-seeking and drug-taking behavior. Reduction of high-risk behaviors can reduce the burden of addiction in society and can improve the overall prognosis of drug addiction. The aim of this study is to show that reduction of oxidative stress with socialization will reduce occurrence of high-risk behavior during addiction period. METHODS AND MATERIALS: Fifty-four male Sprague-Dawley rats were randomly divided into four groups: socialized, isolated, addicted socialized and addicted isolated...
September 19, 2017: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/28933287/modulation-of-abc-transporters-by-nuclear-receptors-physiological-pathological-and-pharmacological-aspects
#13
Juan Pablo Rigalli, Guillermo Nicolás Tocchetti, Johanna Weiss
ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28933205/mass-spectrometry-methods-to-study-protein-metabolite-interactions
#14
Hongbo Guo, Hui Peng, Andrew Emili
To ​​​​understand and manipulate biochemical processes and signaling pathways, the knowledge of endogenous protein-metabolite interactions would be extremely helpful. Recent developments in precision mass spectrometry, high-throughput proteomics and sensitive metabolomic profiling are beginning to converge on a possible solution, heralding a new era of global metabolome-proteome 'interactome' studies that promise to change biomedical research and drug discovery. Areas covered: Here, we review innovative mass spectrometry-based methods and recent pioneering studies aimed at elucidating the physical associations of small molecule ligands with cellular proteins...
September 21, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28933008/importance-of-publishing-adverse-drug-reaction-case-reports-promoting-public-health-and-advancing-pharmacology-and-therapeutics
#15
Rashmi R Shah
This article, which encourages physicians to publish case reports of adverse drug reactions (ADRs), is a review of how well-documented published case reports have contributed to promoting public safety and health and thus served to advance basic pharmacology. The origin of a number of regulatory guidelines can ultimately be traced to safety concerns triggered by such reports. It illustrates how case reports of ADRs, when coupled with simultaneous monitoring of drug pharmacokinetics, have also led to further investigations resulting in major advances in pharmacology, especially pharmacogenetics, mechanisms of drug-drug interactions and modulation of drug metabolism during inflammatory co-morbidities...
September 20, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/28932966/regorafenib-in-advanced-hepatocellular-carcinoma-hcc-considerations-for-treatment
#16
Kyung Kim, Reena Jha, Petra A Prins, Hongkun Wang, Monica Chacha, Marion L Hartley, Aiwu Ruth He
PURPOSE: We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation. METHODS: Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria)...
September 20, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28932938/assessment-of-oral-anticoagulation-control-at-two-pharmacist-managed-clinics-in-brazil
#17
Rogério Guimarães de Lima Silva, Caryne Margotto Bertollo, Isadora Gonçalves Ferreira, Luisa Caldeira Brant, Maria Auxiliadora Parreiras Martins
Background Warfarin remains widely used by patients with cardiovascular diseases. When using warfarin, the quality of oral anticoagulation control is a critical determinant to minimize the risk of bleeding and thromboembolic events. Pharmacist engagement in patient care is relevant towards improving the quality of warfarin therapy. Objective To assess the quality of oral anticoagulation control measured by time in therapeutic range (TTR) at two pharmacist-managed anticoagulation clinics (AC). Method This study included adults with indication of continuous warfarin use...
September 20, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28932851/modulation-in-the-acidity-constant-of-acridine-dye-with-cucurbiturils-stimuli-responsive-pka-tuning-and-dye-relocation-into-live-cells
#18
R Khurana, N Barooah, A C Bhasikuttan, J Mohanty
The noncovalent host-guest interactions of the cationic (AcH(+)) and neutral (Ac) forms of an acridine dye with macrocyclic hosts such as cucurbit[7]uril (CB7) and cucurbit[8]uril (CB8) have been investigated to evaluate the effect of cavity size on the photophysical properties and the protolytic equilibrium of the acridine dye. The cationic form undergoes significant complexation with CB7 (Keq = 10(6) M(-1)), causing a sharp decrease in the fluorescence intensity, whereas the neutral Ac form of the dye undergoes weak complexation with CB7 (Keq = 10(3) M(-1)) and the binding constant is lowered by three orders of magnitude compared to that of the CB7-AcH(+) system...
September 21, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28932813/14-3-3-regulates-actin-filament-formation-in-the-deep-branching-eukaryote-giardia-lamblia
#19
Jana Krtková, Jennifer Xu, Marco Lalle, Melissa Steele-Ogus, Germain C M Alas, David Sept, Alexander R Paredez
The phosphoserine/phosphothreonine-binding protein 14-3-3 is known to regulate actin; this function has been previously attributed to sequestration of phosphorylated cofilin. 14-3-3 was identified as an actin-associated protein in the deep-branching eukaryote Giardia lamblia; however, Giardia lacks cofilin and all other canonical actin-binding proteins (ABPs). Thus, the role of G. lamblia 14-3-3 (Gl-14-3-3) in actin regulation was unknown. Gl-14-3-3 depletion resulted in an overall disruption of actin organization characterized by ectopically distributed short actin filaments...
September 2017: MSphere
https://www.readbyqxmd.com/read/28932079/nano-albumin-bound-paclitaxel-in-pancreatic-cancer-current-evidences-and-future-directions
#20
REVIEW
Guido Giordano, Massimo Pancione, Nunzio Olivieri, Pietro Parcesepe, Marianna Velocci, Tania Di Raimo, Luigi Coppola, Giuseppe Toffoli, Mario Rosario D'Andrea
Pancreatic cancer (PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor...
August 28, 2017: World Journal of Gastroenterology: WJG
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