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https://www.readbyqxmd.com/read/28214218/implication-of-downregulation-and-prospective-pathway-signaling-of-microrna-375-in-lung-squamous-cell-carcinoma
#1
Wen-Jie Chen, Ting-Qing Gan, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Zu-Yun Li, Lin-Jiang Pan, Gang Chen
BACKGROUND: Lung cancer is one of the most typical cancers in the world. Altered expression profiles of microRNA-375(miR-375) are linked to many diseases including lung cancer. However, the relationship between miR-375 and lung squamous cell carcinoma (LUSC) is controversial. METHODS: We first evaluated the 23 LUSCs and the paired normal lung tissues by qRT-PCR. Then we analyzed the LUSC samples with miR-375 expression based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO)...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28214069/-pharmacokinetic-drug-interaction-between-miconazole-mucoadhesive-tablet-and-tacrolimus-about-3%C3%A2-case-reports-in-transplant-patients
#2
Marion Lepelley, Sophie Logerot, Xavier Fonrose, Céline Villier
Loramyc(®) is a mucoadhesive tablet of miconazole, indicated for the treatment of oropharyngeal candidiasis in immunocompromised patients. Miconazole, as others azole antifungals, is known for its potent inhibitory properties of cytochromes P450 enzymes and P-glycoprotein (P-gp). Inhibition of cytochromes P450 enzymes and P-gp can produce pharmacokinetic drug interaction. Immunosuppressive agents, such as calcineurin inhibitors (tacrolimus, cyclosporine) are substrates of cytochromes P450 3A4 and P-gp. Nevertheless, the impact of systemic absorption of miconazole mucoadhesive tablet has not been investigated by the laboratory before regulatory approval...
January 12, 2017: Thérapie
https://www.readbyqxmd.com/read/28213330/drug-discovery-strategies-in-the-field-of-tumor-energy-metabolism-limitations-by-metabolic-flexibility-and-metabolic-resistance-to-chemotherapy
#3
REVIEW
N D Amoedo, E Obre, R Rossignol
The search for new drugs capable of blocking the metabolic vulnerabilities of human tumors has now entered the clinical evaluation stage, but several projects already failed in phase I or phase II. In particular, very promising in vitro studies could not be translated in vivo at preclinical stage and beyond. This was the case for most glycolysis inhibitors that demonstrated systemic toxicity. A more recent example is the inhibition of glutamine catabolism in lung adenocarcinoma that failed in vivo despite a strong addiction of several cancer cell lines to glutamine in vitro...
February 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28213276/engineering-approaches-in-sirna-delivery
#4
Anna Angela Barba, Sara Cascone, Diego Caccavo, Gaetano Lamberti, Gianluca Chiarappa, Michela Abrami, Gabriele Grassi, Mario Grassi, Giovanna Tomaiuolo, Stefano Guido, Valerio Brucato, Francesco Carfì Pavia, Giulio Ghersi, Vincenzo La Carrubba, Roberto Andrea Abbiati, Davide Manca
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes...
February 14, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28213177/tiered-analytics-for-purity-assessment-of-macrocyclic-peptides-in-drug-discovery-analytical-consideration-and-method-development
#5
Jingfang Jenny Qian Cutrone, Xiaohua Stella Huang, Edward S Kozlowski, Ye Bao, Yingzi Wang, Christopher S Poronsky, Dieter M Drexler, Adrienne A Tymiak
Synthetic macrocyclic peptides with natural and unnatural amino acids have gained considerable attention from a number of pharmaceutical/biopharmaceutical companies in recent years as a promising approach to drug discovery, particularly for targets involving protein-protein or protein-peptide interactions. Analytical scientists charged with characterizing these leads face multiple challenges including dealing with a class of complex molecules with the potential for multiple isomers and variable charge states and no established standards for acceptable analytical characterization of materials used in drug discovery...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28213174/evidence-of-the-presence-of-a-calmodulin-sensitive-plasma-membrane-ca-2-atpase-in-trypanosoma-equiperdum
#6
María Carolina Pérez-Gordones, José Rubén Ramírez-Iglesias, Vincenza Cervino, Graciela L Uzcanga, Gustavo Benaim, Marta Mendoza
Trypanosoma equiperdum belongs to the subgenus Trypanozoon, which has a significant socio-economic impact by limiting animal protein productivity worldwide. Proteins involved in the intracellular Ca(2+) regulation are prospective chemotherapeutic targets since several drugs used in experimental treatment against trypanosomatids exert their action through the disruption of the parasite intracellular Ca(2+) homeostasis. Therefore, the plasma membrane Ca(2+)-ATPase (PMCA) is considered as a potential drug target...
February 14, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28213005/is-clarithromycin-a-potential-treatment-for-cachexia-in-people-with-lung-cancer-a-feasibility-study
#7
Sarah Awan, Vincent Crosby, Vanessa Potter, Ivo Hennig, David Baldwin, Mehluli Ndlovu, Sharon Paradine, Andrew Wilcock
Clarithromycin may improve cachexia and survival in non-small cell lung cancer (NSCLC), but adequately controlled data are lacking. This study was undertaken primarily to inform the feasibility and scale of a phase III trial. Eligible consenting patients with stage IV NSCLC and cachexia were to be randomized to receive either clarithromycin 250mg twice daily or placebo for eight weeks. Aspects of trial feasibility recorded included numbers eligible, approached and recruited, together with adherence and completion of treatment and assessments...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212930/molecular-recognition-between-pancreatic-lipase-and-natural-and-synthetic-inhibitors
#8
Martiniano Bello, Basilio-Antonio Lucia, Fragoso-Vázquez Jonathan, Avalos-Soriano Anaguiven, Correa-Basurto José
Pancreatic lipase (PL) is a primary lipase critical for triacylglyceride digestion in humans and is considered as a promising target for the treatment of obesity. Although the current synthetic drugs available for treating obesity have been demonstrated to be effective in inhibiting PL, their prolonged usage results in severe side effects. Based on this argument, in this study, we evaluated the structural and energetic features linked to molecular recognition between two well-known PL inhibitors, orlistat (ORL, synthetic inhibitor) and (-)-epigallocatechin gallate (EGCG, natural inhibitor) and PL through molecular dynamics simulations and free energy calculations of ORL and EGCG at the PL binding site when it is isolated (PL) from the heterodimer complex, forming the heterodimer complex with colipase (PLCL) and lacking structural calcium...
February 14, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28212731/hamlet-a-protein-lipid-complex-with-broad-tumoricidal-activity
#9
REVIEW
James C S Ho, Aftab Nadeem, Catharina Svanborg
HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a tumoricidal protein-lipid complex with broad effects against cancer cells of different origin. The therapeutic potential is emphasized by a high degree of specificity for tumor tissue. Here we review early studies of HAMLET, in collaboration with the Orrenius laboratory, and some key features of the subsequent development of the HAMLET project. The early studies focused on the apoptotic response that accompanies death in HAMLET treated tumor cells and the role of mitochondria in this process...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28212602/happi-2-a-comprehensive-and-high-quality-map-of-human-annotated-and-predicted-protein-interactions
#10
Jake Y Chen, Ragini Pandey, Thanh M Nguyen
BACKGROUND: Human protein-protein interaction (PPI) data is essential to network and systems biology studies. PPI data can help biochemists hypothesize how proteins form complexes by binding to each other, how extracellular signals propagate through post-translational modification of de-activated signaling molecules, and how chemical reactions are coupled by enzymes involved in a complex biological process. Our capability to develop good public database resources for human PPI data has a direct impact on the quality of future research on genome biology and medicine...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28212537/itraconazole-exerts-its-anti-melanoma-effect-by-suppressing-hedgehog-wnt-and-pi3k-mtor-signaling-pathways
#11
Guanzhao Liang, Musang Liu, Qiong Wang, Yongnian Shen, Huan Mei, Dongmei Li, Weida Liu
Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown. However, the goal of this study is to investigate the effect of itraconazole on melanoma and to reveal some details of its underlying mechanism. In the in vivo xenograft mouse model, we find that itraconazole can inhibit melanoma growth and extend the survival of melanoma xenograft mice, compared to non-itraconazole-treated mice...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212220/hcv-antiviral-therapy-in-liver-transplant-candidates-and-recipients-with-renal-insufficiency
#12
Elizabeth C Verna, Robert S Brown
Hepatitis C virus (HCV) remains the leading indication for liver transplant in much of the world, and has traditionally been associated with diminished posttransplant survival due to recurrent HCV-related liver disease. This field has been dramatically changed by the advent of safe and effective directly active antiviral (DAA) therapy, such that most patients can be cured in the pre or posttransplant setting. In addition, there are now DAA regimens specifically approved for use in patients with severe renal insufficiency...
February 16, 2017: Transplantation
https://www.readbyqxmd.com/read/28212219/drug-infusion-systems-technologies-performance-and-pitfalls
#13
Uoo R Kim, Robert A Peterfreund, Mark A Lovich
This review aims to broadly describe drug infusion technologies and raise subtle but important issues arising from infusion therapy that can potentially lead to patient instability and morbidity. Advantages and disadvantages of gravity-dependent drug infusion are described and compared with electromechanical approaches for precise control of medication infusion, including large-volume peristaltic and syringe pumps. This review discusses how drugs and inert carriers interact within infusion systems and outlines several complexities and potential sources of drug error...
February 16, 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28211640/complexation-of-oxethazaine-with-2-hydroxypropyl-%C3%AE-cyclodextrin-increased-drug-solubility-decreased-cytotoxicity-and-analgesia-at-inflamed-tissues
#14
Andressa R Prado, Fabiano Yokaichiya, Margareth Kazuyo Kobayashi Dias Franco, Camila Morais Gonçalves da Silva, Laura Oliveira-Nascimento, Michelle Franz-Montan, Maria C Volpato, Luís F Cabeça, Eneida de Paula
OBJECTIVES: Oxethazaine (OXZ) is one of the few local anaesthetics that provides analgesia at low pH, but presents poor solubility, cytotoxicity and no parenteral formulations. To address these issues, we aimed to prepare OXZ host-guest inclusion complex with hydroxypropyl-beta-cyclodextrin (HP-β-CD). METHODS: The inclusion complex was formed by co-solubilization, followed by a job plot analysis to determine stoichiometry of complexation and dialysis equilibrium analysis (based on UV/VIS absorption and fluorescence profiles of OXZ)...
February 17, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28211608/preclinical-characterisation-of-55p0251-a-novel-compound-that-amplifies-glucose-stimulated-insulin-secretion-and-counteracts-hyperglycaemia-in-rodents
#15
Karin Stadlbauer, Barbara Brunmair, Zsuzsanna Lehner, Immanuel Adorjan, Thomas Scherer, Anton Luger, Leonhardt Bauer, Clemens Fürnsinn
AIMS: 55P0251 is a novel compound with blood glucose lowering activity in mice, which has been developed from a molecular backbone structure found in herbal remedies. We here report its basic pharmacological attributes and initial progress in unmasking the mode of action. MATERIALS AND METHODS: Pharmacokinetic properties of 55P0251 were portrayed in several species. First efforts to elucidate the glucose lowering mechanism in rodents included numerous experimental protocols dealing with glucose tolerance, insulin secretion from isolated pancreatic islets, and comparison to established drugs...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211099/sedation-with-orally-administered-midazolam-in-elderly-dental-patients-with-major-neurocognitive-disorder
#16
Lena Rignell, Mona Mikati, Madeleine Wertsén, Catharina Hägglin
OBJECTIVE: The aim of this study was to evaluate acceptance of treatment after oral sedation with midazolam in dental patients with major neurocognitive disorder. BACKGROUND: Midazolam is commonly used as premedication in paediatric dentistry, oral surgery and people suffering from dental fear. Little is known about its use in other patient groups. METHODS: Dental and sedation records of 61 patients (64% women) sedated with midazolam were examined retrospectively...
February 17, 2017: Gerodontology
https://www.readbyqxmd.com/read/28210973/renal-drug-transporters-and-drug-interactions
#17
REVIEW
Anton Ivanyuk, Françoise Livio, Jérôme Biollaz, Thierry Buclin
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side...
February 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28210927/efficacy-and-safety-of-daclatasvir-plus-pegylated-interferon-alfa-2a-and-ribavirin-in-previously-untreated-hcv-subjects-coinfected-with-hiv-and-hcv-genotype-1-a-phase-iii-open-label-study
#18
Mark S Sulkowski, Walford J Fessel, Adriano Lazzarin, Juan Berenguer, Natalia Zakharova, Hugo Cheinquer, Pierre Côté, Douglas Dieterich, Adrian Gadano, Gail Matthews, Jean-Michel Molina, Christophe Moreno, Juan Antonio Pineda, Federico Pulido, Antonio Rivero, Jurgen Rockstroh, Dennis Hernandez, Fiona McPhee, Timothy Eley, Zhaohui Liu, Patricia Mendez, Eric Hughes, Stephanie Noviello, Peter Ackerman
BACKGROUND: Daclatasvir (DCV) is a potent, pangenotypic, hepatitis C virus (HCV) non-structural protein 5A inhibitor with low potential for drug interactions with antiretroviral therapy (ART). We evaluated the safety and efficacy of DCV plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in HIV-1/HCV genotype-1-coinfected patients. METHODS: AI444043 (NCT01471574), an open-label, Phase III, single-arm, response-guided treatment (RGT) study included 301 patients. They received DCV doses of 30, 60 or 90 mg once daily (depending on concomitant ART), plus weight-based RBV (<75 kg, 1000 mg/day; or ≥75 kg, 1200 mg/day), and once-weekly PegIFN 180 μg, for 24 weeks...
February 16, 2017: Hepatology International
https://www.readbyqxmd.com/read/28210864/pharmacy-benefit-management-companies-do-they-create-value-in-the-us-healthcare-system
#19
Alan Lyles
Pharmacy benefit management companies (PBMs) perform functions in the US market-based healthcare system that may be performed by public agencies or quasi-public institutions in other nations. By aggregating lives covered under their many individual contracts with payers, PBMs have formidable negotiating power. They influence pharmaceutical insurance coverage, design the terms of coverage in a plan's drug benefit, and create competition among providers for inclusion in a plan's network. PBMs have, through intermediation, the potential to secure lower drug prices and to improve rational prescribing...
February 16, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28210454/managing-patients-taking-edoxaban-in-dentistry
#20
REVIEW
Adrian Curto, Daniel Curto, Jorge Sanchez
BACKGROUND: Anticoagulation therapy is used in several conditions to prevent or treat thromboembolism. A new group of oral anticoagulants with clear advantages over classic dicoumarin oral anticoagulants (warfarin and acenocoumarol) has been developed in recent years. The Food and Drug Administration has approved edoxaban, dabigatran, rivaroxaban and apixaban. Their advantages include: predictable pharmacokinetics, drug interactions and limited food, rapid onset of action and short half-life...
February 2017: Journal of Clinical and Experimental Dentistry
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