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https://www.readbyqxmd.com/read/29793215/in-silico-insight-into-voltage-gated-sodium-channel-1-7-inhibition-for-anti-pain-drug-discovery
#1
Mingxing Wang, Wei Li, Ying Wang, Yongbo Song, Jian Wang, Maosheng Cheng
Studies on human genetics have implicated the voltage-gated sodium channel Nav1.7 as an appealing target for the treatment of pain. In this study, we put forward a ligand-based pharmacophore for the first time, which was generated by a set of multiple chemical scaffolds including sulfonamide and non-sulfonamide derivatives and consisted of four chemical features: an aromatic ring, a hydrophobic group and two hydrogen acceptors. The active cavity was divided into three regions according to the properties of the amino acids surrounded and was used for the docking of 16 known active inhibitors...
May 18, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29793094/effects-of-chronic-antipsychotic-drug-exposure-on-the-expression-of-translocator-protein-and-inflammatory-markers-in-rat-adipose-tissue
#2
Anita Calevro, Marie-Caroline Cotel, Sridhar Natesan, Michel Modo, Anthony C Vernon, Valeria Mondelli
The precise effect of antipsychotic drugs on either central or peripheral inflammation remains unclear. An important issue in this debate is to what extent the known peripheral metabolic effects of antipsychotics, including increased adiposity, may contribute to increased inflammation. Adipose tissue is known to contribute to the development of systemic inflammation, which can eventually lead to insulin resistance and metabolic dysregulation. As a first step to address this question, we evaluated whether chronic exposure to clinically comparable doses of haloperidol or olanzapine resulted in the immune activation of rat adipose tissue...
May 16, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29793073/bubble-generating-polymersomes-loaded-with-both-indocyanine-green-and-doxorubicin-for-effective-chemotherapy-combined-with-photothermal-therapy
#3
Dunwan Zhu, Fan Fan, Chenlu Huang, Zhiming Zhang, Yu Qin, Li Lu, Hai Wang, Xu Jin, Hanxue Zhao, Hu Yang, Chao Zhang, Jun Yang, Zhipeng Liu, Hongfan Sun, Xigang Leng, Deling Kong, Linhua Zhang
The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000 -PEG8000 -PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure...
May 21, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29793051/promising-antileishmanial-activity-of-novel-imidazole-antifungal-drug-luliconazole-against-leishmania-major-in-vitro-and-in-silico-studies
#4
Azar Shokri, Mahdi Abastabar, Masoud Keighobadi, Saeed Emami, Mahdi Fakhar, Saeed Hosseini Teshnizi, Koichi Makimura, Ali Rezaei-Matehkolaei, Hassan Mirzaei
OBJECTIVES: Pentavalent antimonials have been used for the treatment of leishmaniasis for more than 70 years; however their toxicity limits their benefits. Unfortunately, the efficacy of the first line drugs has been decreased and resistance seems to be noticeable. Luliconazole is a new azole with unique effects on fungi which has not been tested on Leishmania parasites yet. METHODS: In the present study, we evaluated cytotoxicity and anti-leishmanial activities of Luliconazole on promastigotes and intracellular amastigotes of Leishmania major (L...
May 21, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29793038/therapeutic-drug-monitoring-and-safety-of-voriconazole-therapy-in-patients-with-child-pugh-class-b-and-c-cirrhosis-a-multicenter-study
#5
Taotao Wang, Miao Yan, Dan Tang, Ling Xue, Tao Zhang, Yuzhu Dong, Li Zhu, Xinggang Wang, Yalin Dong
OBJECTIVES: The purpose of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in patients with Child-Pugh class B and C cirrhosis. METHODS: Liver cirrhosis patients receiving recommended voriconazole maintenance dose (group A) and halved maintenance dose (group B) orally or intravenously were involved. Voriconazole-related adverse events (AEs) were defined according to Common Terminology Criteria for Adverse Events. RESULTS: A total of 110 voriconazole Cmin were monitored from 78 patients...
May 21, 2018: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/29793000/effect-of-a-bisphosphonate-and-selective-estrogen-receptor-modulator-on-bone-remodeling-in-streptozotocin-induced-diabetes-and-ovariectomized-rat-model
#6
Young-Seok Lee, Rishab Gupta, Jeong-Taik Kwon, Dae-Chul Cho, Ye Jin Seo, Sung Young Seu, Eui Kyun Park, Inbo Han, Chi-Heon Kim, Joo-Kyung Sung, Kyoung-Tae Kim
BACKGROUND CONTEXT: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes...
May 21, 2018: Spine Journal: Official Journal of the North American Spine Society
https://www.readbyqxmd.com/read/29792945/cross-linking-by-epichlorohydrin-and-diepoxybutane-correlates-with-cytotoxicity-and-leads-to-apoptosis-in-human-leukemia-hl-60-cells
#7
Phuong M Le, Vanesa L Silvestri, Samuel C Redstone, Jordanne B Dunn, Julie T Millard
The bifunctional alkylating agents epichlorohydrin (ECH) and diepoxybutane (DEB) have been linked to increased cancer risks in industrial workers. These compounds react with DNA and proteins, leading to genotoxic effects. We used the comet assay to monitor formation of cross-links in HL-60 cells treated with ECH, DEB, and the structurally related anti-cancer drug mechlorethamine (HN2). We report a time- and dose-dependent cytotoxicity that correlated with cross-linking activity, following the order HN2 > DEB > ECH...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792929/recent-advances-in-intra-articular-drug-delivery-systems-for-osteoarthritis-therapy
#8
REVIEW
Pierre Maudens, Olivier Jordan, Eric Allémann
Osteoarthritis (OA) is the most common degenerative disease of the joint. Despite many reports and numerous clinical trials, OA is not entirely understood, and there is no effective treatment available for this disease. To satisfy this unmet medical need, drug delivery systems (DDSs) containing disease-modifying OA drugs (DMOADs) for intra-articular (IA) administration are required to improve the health of OA patients. DDSs should provide controlled and/or sustained drug release, enabling long-term treatment with a reduced number of injections...
May 21, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29792920/inner-ear-drug-delivery-recent-advances-challenges-and-perspective
#9
Jinsong Hao, S Kevin Li
Effective and safe treatment of auditory and vestibular diseases has become increasingly dependent on inner ear drug delivery systems. This review highlights recent advances in inner ear drug delivery research and technologies. The focus is on strategies to overcome delivery barriers and to improve drug residence and targeting, with special attention to in vivo animal and human studies. The research in gene and stem cell delivery to the inner ear is briefly reviewed. Newly developed research tools to address experimental challenges and safety issues are discussed...
May 21, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29792889/ros-triggered-degradable-iron-chelating-nanogels-safely-improving-iron-elimination-in-vivo
#10
Zhi Liu, Jing Qiao, Tamas Nagy, May P Xiong
Iron-mediated generation of highly toxic Reactive Oxygen Species (ROS) plays a major role in the process leading to iron overload-related diseases. The long-term subcutaneous administration of Deferoxamine (DFO) is currently clinically-approved to improve patient symptoms and survival. However, non-specific toxicity and short circulation times of the drug in humans often leads to poor patient compliance. Herein, thioketal-based ROS-responsive polymeric nanogels containing DFO moieties (rNG-DFO) were designed to chelate iron and to degrade under oxidative stimuli into fragments <10 nm to enhance excretion of iron-bound chelates...
May 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29792888/oral-vitamin-a-coupled-valsartan-nanomedicine-high-hepatic-stellate-cell-receptors-accessibility-and-prolonged-enterohepatic-residence
#11
Nesrine S El-Mezayen, Wessam F El-Hadidy, Wessam M El-Refaie, Thanaa I Shalaby, Mahmoud M Khattab, Aiman S El-Khatib
So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA ) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor-gamma (PPAR-γ), respectively, in activated HSCs...
May 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29792865/aspirin-restores-abt-737-mediated-apoptosis-in-human-renal-carcinoma-cells
#12
Yen-Chuan Ou, Jian-Ri Li, Jiaan-Der Wang, Wen-Ying Chen, Yu-Hsiang Kuan, Ching-Ping Yang, Su-Lan Liao, Hsi-Chi Lu, Chun-Jung Chen
Aspirin is a novel chemopreventive agent against malignancy. However, outcomes of aspirin monotherapy of renal cell carcinoma (RCC) are inconsistent across studies. ABT-737, an BH3 mimetic inhibitor, is also a promising antitumor drug. Cancer cells including those from RCC, that have high levels of Mcl-1, are refractory to ABT-737-induced apoptosis. We here investigated how aspirin treatment modulates the ABT-737-induced apoptosis. Using the in vitro model of human 786-O cells, we showed that aspirin had sensitized cells to ABT-737 induced apoptosis...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792857/tgf-%C3%AE-plays-a-vital-role-in-triple-negative-breast-cancer-tnbc-drug-resistance-through-regulating-stemness-emt-and-apoptosis
#13
Xiaodan Xu, Lu Zhang, Xiaogang He, Ping Zhang, Caihong Sun, Xiaojun Xu, Yaojuan Lu, Feifei Li
Triple negative breast cancer (TNBC) is the most malignant subtype of breast cancer in which the cell surface lacks usual targets for drug to exhibit its effects. Epirubicin (Epi) is widely used for TNBC, but a substantial number of patients develop Epi resistance that is usually associated with poor prognosis. Transforming growth factor (TGF-β) is a multifunctional cytokine. In recent study, it appears that TGF-β influences the cancer stem cell population, thus, the drug resistance of cancer may also be affected...
May 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29792845/current-frontline-endocrine-treatment-options-for-women-with-hormone-receptor-positive-human-epidermal-growth-factor-receptor-2-her2-negative-advanced-stage-breast-cancer
#14
REVIEW
Hikmat N Abdel-Razeq
Despite the recent advances in breast cancer early detection and awareness, a significant portion of patients present with an advanced-stage disease and more patients will progress to stage IV despite adequate treatment of their initial early-stage disease. Hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor-2 (HER2)-negative subtype is the commonest among all breast cancer subtypes. The management of the advanced-stage disease of this subtype has evolved significantly over the past few years...
May 19, 2018: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/29792762/genetic-profiling-in-acute-myeloid-leukemia-a-path-to-predicting-treatment-outcome
#15
Giuseppe Visani, Federica Loscocco, Alessandro Isidori, Pier Paolo Piccaluga
Despite substantial progresses in acute myeloid leukemia (AML) diagnosis and treatment, at least half of patient will eventually die for the disease. In the last decades, the use of genetic and genomic approaches allowed the identification of patients with higher risk of recurrence after and/or resistance to CHT. However, though many novel drugs have been proposed and tested, only little clinical improvements have been made concerning the treatment of the so called 'high risk' patients. Areas covered: In this article, the authors, based on their own experience and the most updated literature, review the basic knowledge of AML prognostication and treatment prediction developed throughout genetic and genomic profiling, and focus on the use of gene expression profiling as a promising predictive tool...
May 24, 2018: Expert Review of Hematology
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#16
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29792562/combined-effects-and-cross-interactions-of-different-antibiotics-and-polypeptides-in-salmonella-bredeney
#17
Xiangyu Ju, Mengjiao Zhu, Jinzhi Han, Zhaoxin Lu, Haizhen Zhao, Xiaomei Bie
Salmonella spp. are health-threatening foodborne pathogens. The increasingly common spread of antibiotic-resistant Salmonella spp. is a major public healthcare issue worldwide. In this study, we wished to explore (1) antibiotic or polypeptide combinations to inhibit multidrug-resistant Salmonella bredeney and (2) the regulation of cross-resistance and collateral sensitivity of antibiotics and polypeptides. We undertook a study to select antibiotic combinations. Then, we promoted drug-resistant strains of S...
May 24, 2018: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/29792544/synergistic-phytochemicals-fail-to-protect-against-ovariectomy-induced-bone-loss-in-rats
#18
Suresh Ambati, Colette N Miller, Erica F Bass, Natalie M Hohos, Diane L Hartzell, Emily W Kelso, Emily R Trunnell, Jeong-Yeh Yang, Mary Anne Della-Fera, Clifton A Baile, Srujana Rayalam
Menopause induces a loss of bone as a result of estrogen deficiency. Despite pharmaceutical options for the treatment of osteopenia and osteoporosis, many aging women use dietary supplements with estrogenic activity to prevent bone loss and other menopausal-related symptoms. Such supplements are yet to be tested for efficacy against a Food and Drug Administration (FDA) approved medication for menopausal bone loss such as zoledronic acid (ZA). The postmenopausal rat model was used to investigate the efficacy of various synergistic phytochemical blends mixed into the diet for 16 weeks...
May 24, 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/29792524/managing-comorbid-cardiovascular-disease-and-sleep-apnea-with-pharmacotherapy
#19
Jacek Wolf, Krzysztof Narkiewicz
Highly prevalent sleep disordered breathing (SDB) has been recognized as an independent cardiovascular disease (CVD) risk factor. Although these two entities often coexist, there is a shortage of sufficiently-powered studies testing the interplay between the course of sleep apnea and CVD pharmacotherapy. The mutual relationship between treated/untreated obstructive sleep apnea (OSA) with ongoing cardiovascular pharmacotherapies is an evident gap in clinical expertise. Areas covered: In this article, the authors review the available evidence and outline future research directions concerning the reciprocal relationship between the pharmacological treatment of CVD and SDB...
May 24, 2018: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29792435/measuring-drug-induced-changes-in-metabolite-populations-of-live-bacteria-real-time-analysis-by-raman-spectroscopy
#20
Paul R Carey, Grant R Whitmer, Michael J Yoon, Michael N Lombardo, Marianne Pusztai-Carey, Hossein Heidari-Torkabadi, Tao Che
Raman difference spectroscopy is shown to provide a wealth of molecular detail on changes within bacterial cells caused by infusion of antibiotics or hydrogen peroxide. E. coli strains paired with chloramphenicol, DHFR propargyl-based inhibitors, meropenem, or hydrogen peroxide provide details of the depletion of protein and nucleic acid populations in real time. Additionally, other reproducible Raman features appear and are attributed to changes in cell metabolite populations. An initial candidate for one of the metabolites involves population increases of citrate, an intermediate within the TCA cycle...
May 24, 2018: Journal of Physical Chemistry. B
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