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https://www.readbyqxmd.com/read/29452365/indigenous-medicine-and-biomedical-health-care-in-fragile-settings-insights-from-burundi
#1
Jean-Benoît Falisse, Serena Masino, Raymond Ngenzebuhoro
This study contributes to the health policy debate on medical systems integration by describing and analysing the interactions between health-care users, indigenous healers, and the biomedical public health system, in the so far rarely documented case of post-conflict Burundi. We adopt a mixed-methods approach combining (1) data from an existing survey on access to health-care, with 6,690 individuals, and (2) original interviews and focus groups conducted in 2014 with 121 respondents, including indigenous healers, biomedical staff, and health-care users...
February 14, 2018: Health Policy and Planning
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#2
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29452182/mussel-inspired-fabrication-of-konjac-glucomannan-microcrystalline-cellulose-intelligent-hydrogel-with-ph-responsive-sustained-release-behavior
#3
Lin Wang, Yu Du, Yi Yuan, Ruo-Jun Mu, Jingni Gong, Yongsheng Ni, Jie Pang, Chunhua Wu
Intelligent hydrogels are attractive biomaterials for various applications, however, fabricating a hydrogel with both adequate self-healing ability and mechanical properties remains a challenge. Herein, a series of novel intelligent konjac glucomannan (KGM)/microcrystalline cellulose (MCC) hydrogels were prepared vis the mussel-inspired chemistry. MCC was firstly functionalized by the oxidative polymerization of dopamine, and the intelligent hydrogels were obtained by mixing aqueous solutions of KGM and functionalized MCC (PDMCC)...
February 13, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29452093/autophagy-inhibition-enhances-anticancer-efficacy-of-artepillin-c-a-cinnamic-acid-derivative-in-brazilian-green-propolis
#4
Satoshi Endo, Manami Hoshi, Toshiyuki Matsunaga, Takahiro Inoue, Kenji Ichihara, Akira Ikari
Propolis, a resinous substance produced by honeybees, possesses various biological actions including anticancer activity towards tumor cells. Recently, the ethanol extract of Brazilian green propolis has been shown to induce autophagy, which is known to be induced in treatment of cancer cells with anticancer drugs, leading to cancer cell survival and decreased sensitivity to anticancer agents. In this study, we aimed to identify autophagy-inducing components of the propolis and elucidated the reciprocal relationship between anticancer cytotoxicity and protective autophagy in prostate cancer CWR22Rv1 cells...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29451980/tri-layer-polymeric-shells-containing-magnetite-nanocarrier-mediated-lcs-1-delivery-for-synthetic-lethal-therapy-of-blm-defective-colorectal-cancer-cells
#5
Anuradha Gupta, Anas Ahmad, Hardeep Singh, Sharanjeet Kaur, Neethu K M, Md Meraj Ansari, Govindasamy Jayamurugan, Rehan Khan
Synthetic lethality is a molecular targeted therapy for selective killing of cancer cells. We exploited a lethal interaction between Superoxide dismutase1 inhibition and Bloom syndrome gene product (BLM) defect for the treatment of colorectal cancer (CRC) cells (HCT 116) with lung cancer screen-1 (LCS-1) loaded customized nanocarrier. LCS-1 has poor aqueous solubility. To overcome its limitations, customized nanocarrier (NC), composed of magnetite core coated with three polymeric shells namely, aminocellulose, branched poly(amidoamine) and paraben-PEG, was developed for encapsulating LCS-1...
February 16, 2018: Biomacromolecules
https://www.readbyqxmd.com/read/29451962/nucleopeptide-assemblies-selectively-sequester-atp-in-cells
#6
Huaimin Wang, Zhaoqianqi Feng, Yanan Qin, Jiaqing Wang, Bing Xu
Here we report that assemblies of nucleopeptides selectively sequestrate ATP in complex conditions (e.g., serum and cytosol). We develop assemblies of nucleopeptides that selectively sequester ATP over ADP. Counteracting enzymes interconvert ATP and ADP to modulate the nanostructures formed by the nucleopeptides and the nucleotides. The nucleopeptides, sequestering ATP effectively in cells, slow down efflux pumps in multidrug resistance cancer cells, thus boosting the efficacy of an anticancer drug. Examining additional 11 nucleopeptides (including D- and L-enantiomers) yields five more nucleopeptides that differentiate ATP and ADP via either precipitation or gelation...
February 16, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29451870/long-term-efficacy-and-safety-of-rilpivirine-plus-abacavir-and-lamivudine-in-hiv-1-infected-patients-with-undetectable-viral-load
#7
Nadia Galizzi, Laura Galli, Andrea Poli, Nicola Gianotti, Elisabetta Carini, Alba Bigoloni, Giuseppe Tambussi, Silvia Nozza, Adriano Lazzarin, Antonella Castagna, Daniela Mancusi, Roberta Termini
INTRODUCTION: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. METHODS: Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015...
2018: PloS One
https://www.readbyqxmd.com/read/29451739/stacking-interactions-of-heterocyclic-drug-fragments-with-protein-amide-backbones
#8
Andrea N Bootsma, Steven Edge Wheeler
Stacking interactions can be important enthalpic contributors to drug binding. Among the less well-studied stacking interactions are those occurring between an arene and the π-face of an amide group. Given the ubiquity of heterocycles in drugs, combined with the abundance of amides in the protein backbone, optimizing these non-covalent interactions can provide a potential route to enhanced drug binding. Previously, Diederich et al. (ChemMedChem 2013, 8, 397-404) studied stacked dimers of a model amide with a set of 18 heterocycles, showing that computed interaction energies correlate with the dipole moments of the heterocycles and providing guidelines for the optimization of these interactions...
February 16, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29451681/verification-of-a-physiologically-based-pharmacokinetic-model-of-ritonavir-to-estimate-drug-drug-interaction-potential-of-cyp3a4-substrates
#9
Ken-Ichi Umehara, Felix Huth, Christina S Won, Tycho Heimbach, Handan He
Ritonavir is one of several ketoconazole alternatives used to evaluate strong CYP3A4 inhibition potential in clinical drug-drug interaction (DDI) studies. In this study, four physiologically-based pharmacokinetic (PBPK) models of ritonavir as an in vivo time-dependent inhibitor of CYP3A4 were created and verified for the oral doses of 20, 50, 100 and 200 mg using fraction absorbed (Fa) and oral clearance (CLoral) values reported in the literature, as transporter and CYP enzyme reaction phenotyping data were not available...
February 16, 2018: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/29451568/upconversion-in-photodynamic-therapy-plumbing-the-depths
#10
Michael R Hamblin
Photodynamic therapy (PDT) involves the combination of non-toxic dyes called photosensitizers (PS) and harmless visible light that interact with ambient oxygen to give reactive oxygen species (ROS) that can damage biomolecules and kill cells. PDT has mostly been developed as a cancer therapy but can also be used as an antimicrobial approach against localized infections. However even the longest wavelength used for exciting PS (in the 700 nm region) has relatively poor tissue penetration, and many PS are much better excited by blue and green light...
February 16, 2018: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/29451470/use-of-integrated-clinical-trial-protocols-a-survey-in-early-medicines-development
#11
Katharina Erb-Zohar, Hildegard Sourgens, Kerstin Breithaupt-Groegler
PURPOSE: To collect information on the use of integrated protocols in early clinical medicines development. MATERIALS AND METHODS: The questionnaire was mailed in fall 2014 to members of human pharmacology societies in Europe for anonymous responses via the online tool SurveyMonkey®. RESULTS: 97 respondents reported on 164 integrated protocols overall. In general, integrated protocols comprised 2 or 3 trial elements. One third of integrated protocols involved patients...
February 16, 2018: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29451400/designing-selective-modulators-for-the-nicotinic-receptor-subtypes-challenges-and-opportunities
#12
Dina Manetti, Cristina Bellucci, Niccolò Chiaramonte, Silvia Dei, Elisabetta Teodori, Maria Novella Romanelli
Nicotinic receptors are membrane proteins involved in several physiological processes. They are considered suitable drug targets for various CNS disorders or conditions, as shown by the large number of compounds which have entered clinical trials. In recent years, nonconventional agonists have been discovered: positive allosteric modulators, allosteric agonists, site-specific agonists and silent desensitizers are compounds able to modulate the receptor interacting at sites different from the orthodox one, or to desensitize the receptor without prior opening...
February 16, 2018: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/29451287/computational-identification-of-the-binding-mechanism-of-a-triple-reuptake-inhibitor-amitifadine-for-the-treatment-of-major-depressive-disorder
#13
Weiwei Xue, Panpan Wang, Gao Tu, Fengyuan Yang, Guoxun Zheng, Xiaofeng Li, Xiaoxu Li, Yuzong Chen, Xiaojun Yao, Feng Zhu
Amitifadine, the only drug ever clinically tested in Phase 3 for treating depression, is a triple reuptake inhibitor (TRI) that simultaneously interacts with human monoamine transporters (MATs) including hSERT, hNET and hDAT. This novel multi-target strategy improves drug efficacy and reduces the toxic side effects of drugs. However, the binding modes accounting for amitifadine's polypharmacological mode of action are still elusive, and extensive exploration of the amitifadine-target interactions between amitifadine and MATs is urgently needed...
February 16, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29451063/epithelial-tumors-growing-from-within
#14
Mariana Muzzopappa, Marco Milán
The growth of epithelial tumors is often governed by cell interactions with the surrounding stroma. Drosophila has been instrumental in identifying the relevant molecular elements mediating these interactions. Of note is the role of the TNF ligand Eiger, released from recruited blood cells, in activating the JNK tumor-promoting pathway in epithelial tumors. JNK drives the transcriptional induction of mitogenic molecules, matrix metalloproteases and systemic signals that lead to tumor growth, tissue invasiveness and malignancy...
February 16, 2018: Fly
https://www.readbyqxmd.com/read/29450984/computational-studies-on-horseshoe-shape-pocket-of-human-orexin-receptor-type-2-and-boat-conformation-of-suvorexant-by-molecular-dynamics-simulations
#15
Qifeng Bai, Horacio Pérez-Sánchez, Zhuoyu Shi, Lanlan Li, Danfeng Shi, Huanxiang Liu, Xiaojun Yao
The FDA approved drug suvorexant binds to the horseshoe shape pocket of OX 2 R with the boat conformation. The horseshoe shape pocket plays an important role on the biological activity of OX 2 R in the cell membrane. To study the binding mechanism between the horseshoe shape pocket of OX 2 R and boat conformation of suvorexant, the crystal structures of wild type and N324A mutant of OX 2 R in complex with antagonist suvorexant are chosen to perform molecular dynamics (MD) simulations, QM/MM and MMGBSA calculations...
February 16, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29450683/common-adverse-effects-of-novel-therapies-for-multiple-myeloma-mm-and-their-management-strategies
#16
REVIEW
Kristen B McCullough, Miriam A Hobbs, Jithma P Abeykoon, Prashant Kapoor
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class...
February 15, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29450412/clinically-approved-liposomal-nanomedicines-lessons-learned-from-the-biomolecular-corona
#17
Giulio Caracciolo
Nowadays, liposomes are the most successful drug delivery systems with a dozen drug products available in the clinic. Grafting poly-(ethylene glycol) (PEG) onto the liposome surface prevents protein binding thus prolonging blood circulation, while synthetic modification of the terminal PEG molecule with ligands (e.g. monoclonal antibodies and peptides) should promote selective accumulation in the tumor region with respect to healthy tissues. However, despite big efforts, advances have not outgrown the development stage and just a few targeted liposomal drugs are commercially available...
February 16, 2018: Nanoscale
https://www.readbyqxmd.com/read/29450239/alcohol-related-mental-imagery-the-effects-of-a-priming-dose-in-at-risk-drinkers
#18
Michael Yates, Sunjeev K Kamboj
Objectives: Drug related mental imagery is proposed to play a central role in addictive behaviour. However, little is known about such cognition or how it is pharmacologically modulated. Here, we test theoretical predictions of the 'elaborated intrusion' theory by comparing neutral with alcohol related mental imagery, and examine the effects of low dose alcohol on phenomenological aspects of this imagery. Methods: Alcohol related and neutral imagery was assessed after at risk drinkers (n = 40) consumed alcohol (0...
December 2017: Addictive Behaviors Reports
https://www.readbyqxmd.com/read/29449830/screening-for-ppar-non-agonist-ligands-followed-by-characterization-of-a-hit-am-879-with-additional-no-adipogenic-and-cdk5-mediated-phosphorylation-inhibition-properties
#19
Helder Veras Ribeiro Filho, Natália Bernardi Videira, Aline Villanova Bridi, Thais Helena Tittanegro, Fernanda Aparecida Helena Batista, José Geraldo de Carvalho Pereira, Paulo Sérgio Lopes de Oliveira, Marcio Chaim Bajgelman, Albane Le Maire, Ana Carolina Migliorini Figueira
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of a nuclear receptor superfamily and acts as a ligand-dependent transcription factor, playing key roles in maintenance of adipose tissue and in regulation of glucose and lipid homeostasis. This receptor is the target of thiazolidinediones, a class of antidiabetic drugs, which improve insulin sensitization and regulate glycemia in type 2 diabetes. Despite the beneficial effects of drugs, such as rosiglitazone and pioglitazone, their use is associated with several side effects, including weight gain, heart failure, and liver disease, since these drugs induce full activation of the receptor...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29449809/digging-into-lipid-membrane-permeation-for-cardiac-ion-channel-blocker-d-sotalol-with-all-atom-simulations
#20
Kevin R DeMarco, Slava Bekker, Colleen E Clancy, Sergei Y Noskov, Igor Vorobyov
Interactions of drug molecules with lipid membranes play crucial role in their accessibility of cellular targets and can be an important predictor of their therapeutic and safety profiles. Very little is known about spatial localization of various drugs in the lipid bilayers, their active form (ionization state) or translocation rates and therefore potency to bind to different sites in membrane proteins. All-atom molecular simulations may help to map drug partitioning kinetics and thermodynamics, thus providing in-depth assessment of drug lipophilicity...
2018: Frontiers in Pharmacology
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