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https://www.readbyqxmd.com/read/28823018/prevalence-and-nature-of-potential-drug-drug-interactions-among-kidney-transplant-patients-in-a-german-intensive-care-unit
#1
Julia Amkreutz, Alexander Koch, Lukas Buendgens, Anja Muehlfeld, Christian Trautwein, Albrecht Eisert
Background Complex polypharmacotherapy makes kidney transplant patients vulnerable to drug-drug interactions (DDIs). Objective To study prevalence and nature of potential DDIs (pDDIs) in kidney transplant patients. Setting Internal medicine ICU, University Hospital RWTH Aachen. Method In this retrospective observational study, pDDIs were identified in the first week after transplant from 1999 to 2010. Patients aged at least 18 years with prescription of at least two drugs were included. Patients with incomplete data were excluded...
August 19, 2017: International Journal of Clinical Pharmacy
https://www.readbyqxmd.com/read/28822783/the-expression-induction-and-pharmacological-activity-of-cyp1a2-are-post-transcriptionally-regulated-by-microrna-hsa-mir-132-5p
#2
Yinting Chen, Linjuan Zeng, Yong Wang, William H Tolleson, Bridgett Knox, Si Chen, Zhen Ren, Lei Guo, Nan Mei, Feng Qian, Kaihong Huang, David Liu, Weida Tong, Dianke Yu, Baitang Ning
Cytochrome P450 1A2 (CYP1A2) is one of the most abundant and important drug metabolizing enzymes in human liver. However, little is known about the post-transcriptional regulation of CYP1A2, especially the mechanisms involving microRNAs (miRNAs). This study applied a systematic approach to investigate the post-transcriptional regulation of CYP1A2 by miRNAs. Candidate miRNAs targeting the 3'-untranslated region (3'-UTR) of CYP1A2 were screened in silico, resulting in the selection of sixty-two potential miRNAs for further analysis...
August 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28822348/risk-factors-for-potential-drug-drug-interactions-in-intensive-care-unit-patients
#3
Slobodan M Janković, Ana V Pejčić, Miloš N Milosavljević, Valentina D Opančina, Nikola V Pešić, Tamara T Nedeljković, Goran M Babić
PURPOSE: To determine risk factors for each severity-based category of potential drug-drug interactions (DDIs) encountered at intensive care unit (ICU) patients. METHODS: This was a retrospective cohort analysis of patients treated at the ICU of the Clinical Center Kragujevac, a public tertiary care hospital in Kragujevac, Serbia. Three interaction checkers were used to reveal drug-drug interactions: Medscape, Epocrates and Micromedex. RESULTS: The study included 201 patients, 66...
August 14, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28822346/comparative-study-of-single-combination-use-of-huang-lian-jie-du-decoction-and-berberine-on-their-protection-on-sepsis-induced-acute-liver-injury-by-nmr-metabolic-profiling
#4
Yan Lv, Junsong Wang, Dingqiao Xu, Shanting Liao, Pei Li, Qian Zhang, Minghua Yang, Lingyi Kong
Sepsis is a serious clinical disease with a high mortality rate all around the world. Liver organ dysfunction is an important sign for the severity and outcome of sepsis in patients. In this study, (1)H NMR-based metabolomics approach and biochemical assays were applied to investigate the metabolic profiling for cecal ligation and puncture (CLP) induced acute liver injury, the therapeutical effect of single/combination use of Huang-Lian-Jie-Du decoction (HLJDD) and berberine, and the interaction of them. Metabolomics analysis revealed significant perturbations in livers of septic rats, which could be ameliorated by HLJDD, berberine and their combination treatment...
August 1, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28822273/ligand-binding-characterization-of-simulated-%C3%AE-adrenergic-like-octopamine-receptor-in-schistocerca-gregaria-via-progressive-structure-simulation
#5
Hui-Meng Lu, Xiao-Li Lu, Jia-Hui Zhai, Ren-Bin Zhou, Yan-Li Qin, Jing-Di Li, Chen-Yan Zhang, Jian-Yu Shi
It is important to design insecticides having both low drug resistance and less undesirable toxicity for desert locust control. Specific GPCRs of Schistocerca gregaria, especially β-adrenergic-like octopamine receptor (SgOctβR), can be considered as its potential effective insecticide targets. However, either the unavailability of SgOctβR's structure or the inadequate capability of its sequence lead the development of insecticide for Schistocerca gregaria meets its plateau. To relax this difficulty, this paper develops a promising progressive structure simulation from SgOctβR's sequence, to its predicted structure of SgOctβR in vacuum, to its conformation as well as its complex with endogenous ligand octopamine in a solvent-membrane system...
July 27, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28822272/b24n24-fullerene-as-a-carrier-for-5-fluorouracil-anti-cancer-drug-delivery-dft-studies
#6
Mehrnoosh Khodam Hazrati, Zahra Javanshir, Zargham Bagheri
It has been previously indicated that BN nanostructures may be nontoxic and biocompatible. Here the potential application of a B24N24 is explored as a drug delivery system for anti-cancer 5-fluorouracil based on the density functional theory. This drug prefers to attach via its oxygen atoms to the B atoms of the cluster with adsorption energy about -11.90kcalmol(-1) based on the dispersion corrected B3LYP level of theory. To make the cluster more appropriate for drug delivery, we replaced a B atom by Si or Al atom to improve the interaction strength...
August 9, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28822103/current-progress-in-innovative-engineered-antibodies
#7
REVIEW
William R Strohl
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year...
August 18, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28822076/studies-of-the-benzopyran-class-of-selective-cox-2-inhibitors-using-3d-qsar-and-molecular-docking
#8
Dharmendra K Yadav, Saloni, Praveen Sharma, Sanjeev Misra, Harpreet Singh, Ricardo L Mancera, Kang Kim, Cheongyun Jang, Mi-Hyun Kim, Horacio Pérez-Sánchez, Eun Ha Choi, Surendra Kumar
The Gaussian-based 3D-QSAR studies for 58 selective COX-2 (cyclooxygenase-2) inhibitors belonging to benzopyran chemical class were performed. Partial least squares analysis produced statistically significant model with (R training(2)  = 0.866) and predictability (Q training(2)  = 0.66, Q test(2)  = 0.846). The 3D-QSAR model includes steric, electrostatic, hydrophobic, and hydrogen bond acceptor field indicators, whereas the potential field contributions indicate that the steric and hydrophobic features of the molecules play an important role in governing their biological activity...
August 18, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28822069/characterization-of-ofloxacin-interaction-with-mutated-a91v-quinolone-resistance-determining-region-of-dna-gyrase-in-mycobacterium-leprae-through-computational-simulation
#9
J Nisha, V Shanthi
Mycobacterium leprae, the causal agent of leprosy is non-cultivable in vitro. Thus, the assessment of antibiotic activity against Mycobacterium leprae depends primarily upon the time-consuming mouse footpad system. The GyrA protein of Mycobacterium leprae is the target of the antimycobacterial drug, Ofloxacin. In recent times, the GyrA mutation (A91V) has been found to be resistant to Ofloxacin. This phenomenon has necessitated the development of new, long-acting antimycobacterial compounds. The underlying mechanism of drug resistance is not completely known...
August 18, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28821882/identification-of-a-short-sequence-in-the-hcmv-terminase-pul56-essential-for-interaction-with-pul89-subunit
#10
G Ligat, C Jacquet, S Chou, A Couvreux, S Alain, S Hantz
The human cytomegalovirus (HCMV) terminase complex consists of several components acting together to cleave viral DNA into unit length genomes and translocate them into capsids, a critical process in the production of infectious virions subsequent to DNA replication. Previous studies suggest that the carboxyl-terminal portion of the pUL56 subunit interacts with the pUL89 subunit. However, the specific interacting residues of pUL56 remain unknown. We identified a conserved sequence in the C-terminal moiety of pUL56 (671WMVVKYMGFF680)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821810/extracting-intercellular-signaling-network-of-cancer-tissues-using-ligand-receptor-expression-patterns-from-whole-tumor-and-single-cell-transcriptomes
#11
Joseph X Zhou, Roberto Taramelli, Edoardo Pedrini, Theo Knijnenburg, Sui Huang
Many behaviors of cancer, such as progression, metastasis and drug resistance etc., cannot be fully understood by genetic mutations or intracellular signaling alone. Instead, they are emergent properties of the cell community which forms a tumor. Studies of tumor heterogeneity reveal that many cancer behaviors critically depend on intercellular communication between cancer cells themselves and between cancer-stromal cells by secreted signaling molecules (ligands) and their cognate receptors. We analyzed public cancer transcriptome database for changes in cell-cell interactions as the characteristic of malignancy...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821762/multi-tissue-interactions-in-an-integrated-three-tissue-organ-on-a-chip-platform
#12
Aleksander Skardal, Sean V Murphy, Mahesh Devarasetty, Ivy Mead, Hyun-Wook Kang, Young-Joon Seol, Yu Shrike Zhang, Su-Ryon Shin, Liang Zhao, Julio Aleman, Adam R Hall, Thomas D Shupe, Andre Kleensang, Mehmet R Dokmeci, Sang Jin Lee, John D Jackson, James J Yoo, Thomas Hartung, Ali Khademhosseini, Shay Soker, Colin E Bishop, Anthony Atala
Many drugs have progressed through preclinical and clinical trials and have been available - for years in some cases - before being recalled by the FDA for unanticipated toxicity in humans. One reason for such poor translation from drug candidate to successful use is a lack of model systems that accurately recapitulate normal tissue function of human organs and their response to drug compounds. Moreover, tissues in the body do not exist in isolation, but reside in a highly integrated and dynamically interactive environment, in which actions in one tissue can affect other downstream tissues...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821686/effect-of-simvastatin-on-csf-alzheimer-disease-biomarkers-in-cognitively-normal-adults
#13
Ge Li, Cynthia L Mayer, Daniel Morelli, Steven P Millard, Wendy H Raskind, Eric C Petrie, Monique Cherrier, Anne M Fagan, Murray A Raskind, Elaine R Peskind
OBJECTIVE: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. METHODS: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group)...
August 18, 2017: Neurology
https://www.readbyqxmd.com/read/28821652/calpain-grip-signaling-in-nucleus-accumbens-core-mediates-the-reconsolidation-of-drug-reward-memory
#14
Jie Liang, Jia-Li Li, Ying Han, Yi-Xiao Luo, Yan-Xue Xue, Yàn Zhang, Yán Zhang, Li-Bo Zhang, Man-Li Chen, Lin Lu, Jie Shi
Exposure to drug-paired cues causes drug memories to be in a destabilized state, and interfering with memory reconsolidation can inhibit relapse. Calpain, a calcium-dependent neutral cysteine protease, is involved in synaptic plasticity and the formation of long-term fear memory. However, the role of calpain in the reconsolidation of drug reward memory is still unknown. In the present study, using conditioned place preference (CPP) model, we found that exposure to drug-paired contextual stimuli induced the activation of calpain and decreased the expression of glutamate receptor interacting protein 1 (GRIP1) in the nucleus accumbens (NAc) core but not shell of male rats...
August 14, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821631/6-methoxyethylamino-numonafide-inhibits-hepatocellular-carcinoma-xenograft-growth-as-a-single-agent-and-in-combination-with-sorafenib
#15
Yanning Liu, Guohua Lou, John T Norton, Chen Wang, Irawati Kandela, Shuai Tang, Nathaniel I Shank, Pankaj Gupta, Min Huang, Michael J Avram, Richard Green, Andrew Mazar, Daniel Appella, Zhi Chen, Sui Huang
Hepatocellular carcinoma (HCC) is the third leading form of cancer worldwide, and its incidence is increasing rapidly in the United States, tripling over the past 3 decades. The current chemotherapeutic strategies against localized and metastatic HCC are ineffective. Here we report that 6-methoxyethylamino-numonafide (MEAN) is a potent growth inhibitor of murine xenografts of 2 human HCC cell lines. At the same dose and with the same treatment strategies, MEAN was more efficacious in inhibiting tumor growth in mice than sorafenib, the only approved drug for HCC...
August 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28821485/simple-evaluation-method-for-cyp3a4-induction-from-human-hepatocytes-the-relative-factor-approach-with-an-induction-detection-limit-concentration-based-on-the-emax-model
#16
Shino Kuramoto, Motohiro Kato, Hidetoshi Shindoh, Akihisa Kaneko, Masaki Ishigai, Seiji Miyauchi
We investigated the robustness and utility of the relative factor (RF) approach based on the Emax model, which was reported by Kaneko, using mRNA induction data of 10 typical CYP3A4 inducers in cryopreserved human hepatocytes. The RF value is designated as the ratio of the induction detection limit concentration (IDLC) for a standard inducer, such as rifampicin (RIF) or phenobarbital (PB), to that for the compound (RFRIF is IDLCRIF/IDLCcpd; RFPB is IDLCPB/IDLCcpd). An important feature of the RF approach is that the profiles of the induction response curves on the logarithmic scale remain unchanged irrespective of inducers but are shifted parallel depending on the EC50 values...
August 18, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28821463/lymphatic-transport-and-lymph-node-targeting-of-methotrexate-conjugated-pegylated-dendrimers-is-enhanced-by-reducing-the-length-of-the-drug-linker-or-masking-interactions-with-the-injection-site
#17
Gemma M Ryan, Victoria M McLeod, Dharmini Mehta, Brian D Kelly, Pauline C Stanislawski, David J Owen, Lisa M Kaminskas, Christopher J H Porter
Drug conjugation to dendrimer-based delivery systems has been shown to enhance delivery to the lymphatic system after subcutaneous administration. Dendrimer interaction with components of the interstitium at the injection site, however, may prevent drainage from the injection site. The current study sought to vary the length of a linker employed to conjugate methotrexate (MTX) to a PEGylated dendrimer, in an attempt to reduce MTX interaction with interstitial binding sites and enhance lymphatic drainage. Dendrimers with shorter linkers resulted in higher lymphatic drainage, presumably via shielding of interaction sites by the PEG mantle, but were not retained in lymph nodes...
August 15, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28821452/pinocembrin-a-novel-histidine-decarboxylase-inhibitor-with-anti-allergic-potential-in-in-vitro
#18
Hamza Hanieh, Villianur Ibrahim Hairul Islam, Subramanian Saravanan, Muthiah Chellappandian, Kessavane Ragul, Arumugam Durga, Kaliyamoorthy Venugopal, Venugopal Senthilkumar, Palanisamy Senthilkumar, Krishnaraj Thirugnanasambantham
Pinocembrin (5, 7- dihydroxy flavanone) is the most abundant chiral flavonoid found in propolis, exhibiting antioxidant, antimicrobial and anti-inflammatory properties. However, the effect of Pinocembrin on allergic response is unexplored. Thus, current study aimed at investigating the effects of Pinocembrin on IgE-mediated allergic response in vitro. A special emphasis was directed toward histidine decarboxylase (HDC) and other pro-allergic and pro-inflammatory mediators. Preliminary studies, using a microbiological model of Klebsiella pneumoniae, provided first evidences that suggest Pinocembrin as a potential thermal stable inhibitor for HDC...
August 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28821392/schisandra-chinensis-extract-decreases-chloroacetaldehyde-production-in-rats-and-attenuates-cyclophosphamide-toxicity-in-liver-kidney-and-brain
#19
Jianxiu Zhai, Feng Zhang, Shouhong Gao, Li Chen, Ge Feng, Jun Yin, Wansheng Chen
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (S. chinensis) has been used for thousands years in China, and is usually applied in treatment of urinary tract disorders and liver injury. S. chinensis extract (SCE) has board protective effects on liver, kidney and nervous system. Schisandra lignans are generally considered as the bioactive components of SCE. AIM OF THE STUDY: To investigate the pharmacokinetic herb-drug interactions (HDIs) between SCE and cyclophosphamide (CTX)...
August 15, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28821154/design-and-characterization-of-a-biocompatible-physical-hydrogel-based-on-scleroglucan-for-topical-drug-delivery
#20
Patrizia Paolicelli, Gabriele Varani, Settimio Pacelli, Elisa Ogliani, Martina Nardoni, Stefania Petralito, Alessandra Adrover, Maria Antonietta Casadei
Physical hydrogels of a high-carboxymethylated derivative of scleroglucan (Scl-CM300) were investigated as potential systems for topical drug delivery using three different therapeutic molecules (fluconazole, diclofenac and betamethasone). Rheological tests were carried out on drug-loaded hydrogels along with in-vitro release studies in a vertical Franz cell, in order to investigate if and how different drugs may influence the rheological and release properties of Scl-CM300 hydrogels. Experimental results and theoretical modeling highlighted that, in the absence of drug/polymer interactions (as for fluconazole and betamethasone) Scl-CM300 matrices offer negligible resistance to drug diffusion and a Fickian transport model can be adopted to estimate the effective diffusion coefficient in the swollen hydrogel...
October 15, 2017: Carbohydrate Polymers
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