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https://www.readbyqxmd.com/read/28742337/gallium-complexation-stability-and-bioconjugation-of-1-4-7-triazacyclononane-derived-chelators-with-azaheterocyclic-arms
#1
Alexander Schmidtke, Tilman Läppchen, Christian Weinmann, Lorenz Bier-Schorr, Manfred Keller, Yvonne Kiefer, Jason P Holland, Mark D Bartholomä
We have recently introduced a 1,4,7-triazacyclononane (TACN) based chelating system with additional five-membered azaheterocyclic substituents for complexation of radioactive Cu(2+) ions. In this work, we investigated the complexation properties of these novel chelators with Ga(3+). In labeling experiments, we could show that the penta- and hexadentate imidazole derivatives NODIA-Me 4 and NOTI-Me 1 can be labeled with (68)Ga in specific activities up to ∼30 MBq nmol(-1), while the corresponding thiazole derivative NOTThia 2 did not label satisfactorily under identical conditions...
July 25, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28742051/cooperative-tracking-of-networked-agents-with-a-high-dimensional-leader-qualitative-analysis-and-performance-evaluation
#2
Guanghui Wen, Tingwen Huang, Wenwu Yu, Yuanqing Xia, Zhi-Wei Liu
Cooperative consensus tracking and its L²-gain performance is investigated in this paper for a class of multiple agent systems (MASs) in the presence of a single high-dimensional leader. Compared with the traditional models for MASs, the inherent dynamics of the leader are allowed to be different with those of the followers in the present framework, which is thus much more favorable in various practical applications. A new kind of distributed controllers associated with a reduced-order state observer are designed for each follower to track the high-dimensional leader under directed switching topology...
July 21, 2017: IEEE Transactions on Cybernetics
https://www.readbyqxmd.com/read/28740614/new-class-of-antitrypanosomal-agents-based-on-imidazopyridines
#3
Daniel G Silva, J Robert Gillespie, Ranae M Ranade, Zackary M Herbst, Uyen T T Nguyen, Frederick S Buckner, Carlos A Montanari, Michael H Gelb
The present work describes the synthesis of 22 new imidazopyridine analogues arising from medicinal chemistry optimization at different sites on the molecule. Seven and 12 compounds exhibited an in vitro EC50 ≤ 1 μM against Trypanosoma cruzi (T. cruzi) and Trypanosoma brucei (T. brucei) parasites, respectively. Based on promising results of in vitro activity (EC50 < 100 nM), cytotoxicity, metabolic stability, protein binding, and pharmacokinetics (PK) properties, compound 20 was selected as a candidate for in vivo efficacy studies...
July 13, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28739410/1-3-5-triazine-2-4-6-tribenzaldehyde-derivative-as-a-new-crosslinking-agent-for-synthesis-of-ph-thermo-dual-responsive-chitosan-hydrogels-and-their-nanocomposites-swelling-properties-and-drug-release-behavior
#4
Ali Reza Karimi, Mahsa Tarighatjoo, Golara Nikravesh
In this work, 1,3,5-triazine-2,4,6-tribenzaldehyde was synthesized and chosen as the cross-linking agent for preparation of novel thermo- and pH-responsive hydrogels based on chitosan. The cross-linking proceeds through formation of imine bond by reaction of amino groups of chitosan with aldehyde groups of the cross-linker. The various amounts (6, 10, 14% w/w) of the cross-linker were used with respect to chitosan to produce three 1,3,5-triazine-2,4,6-tribenzaldehyde cross-linked chitosans. Then, their hydrogel nanocomposites were prepared by crosslinking of chitosan with 1,3,5-triazine-2,4,6-tribenzaldehyde in the presence of 0...
July 21, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28738861/the-risk-of-hiv-transmission-at-each-step-of-the-hiv-care-continuum-among-people-who-inject-drugs-a-modeling-study
#5
Daniel J Escudero, Mark N Lurie, Kenneth H Mayer, Maximilian King, Sandro Galea, Samuel R Friedman, Brandon D L Marshall
BACKGROUND: People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID. METHODS: We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012...
July 25, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28738091/the-second-window-icg-technique-demonstrates-a-broad-plateau-period-for-near-infrared-fluorescence-tumor-contrast-in-glioblastoma
#6
Ryan Zeh, Saad Sheikh, Leilei Xia, John Pierce, Andrew Newton, Jarrod Predina, Steve Cho, MacLean Nasrallah, Sunil Singhal, Jay Dorsey, John Y K Lee
INTRODUCTION: Fluorescence-guided surgery has emerged as a powerful tool to detect, localize and resect tumors in the operative setting. Our laboratory has pioneered a novel way to administer an FDA-approved near-infrared (NIR) contrast agent to help surgeons with this task. This technique, coined Second Window ICG, exploits the natural permeability of tumor vasculature and its poor clearance to deliver high doses of indocyanine green (ICG) to tumors. This technique differs substantially from established ICG video angiography techniques that visualize ICG within minutes of injection...
2017: PloS One
https://www.readbyqxmd.com/read/28737992/temporal-trends-in-use-of-biologic-dmards-for-rheumatoid-arthritis-in-the-united-states-a-cohort-study-of-publicly-and-privately-insured-patients
#7
Rishi J Desai, Daniel H Solomon, Yinzhu Jin, Jun Liu, Seoyoung C Kim
BACKGROUND: Ten biologic disease-modifying antirheumatic drugs (bDMARDs) are available as treatment for rheumatoid arthritis (RA), but relatively little is known about population-level time trends in the use of these agents. OBJECTIVE: To describe time trends in the use of bDMARDs in RA patients with private or public insurance in the United States. METHODS: Claims data from private (Optum Clinformatics, 2004-2015) and public (Medicaid Analytic eXtract [MAX], 2000-2010) insurance programs were used...
August 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28737788/a-multiscale-agent-based-framework-integrated-with-a-constraint-based-metabolic-network-model-of-cancer-for-simulating-avascular-tumor-growth
#8
Mehrdad Ghadiri, Mahshid Heidari, Sayed-Amir Marashi, Seyed Hasan Mousavi
In recent years, many efforts have been made in the field of computational modeling of cancerous tumors, in order to obtain a better understanding and predictions of their growth patterns. Furthermore, constraint-based modeling of metabolic networks has become increasingly popular, which is appropriate for the systems-level reconstruction of cell physiology. The goal of the current study is to integrate a multiscale agent-based modeling framework with a constraint-based metabolic network model of cancer cells in order to simulate the three dimensional early growth of avascular tumors...
July 24, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28737131/pharmacokinetics-of-flucloxacillin-and-its-metabolites-in-patients-with-renal-failure-impact-on-liver-toxicity%C3%A2
#9
Alexandra Maier-Salamon, Salwa Ahmed Elgendy, Brigitte Meyer, Matthias Vossen, Theresia Thalhammer, Florian Thalhammer, Walter Jäger
OBJECTIVE: The antimicrobial agent flucloxacillin is a potential cause of drug-induced liver disease, but the underlying mechanisms for toxicity have not been fully elucidated. As in-vitro and in-vivo findings suggest that biotransformation products contribute to hepatotoxicity, the purpose of this study was to characterize formation and accumulation of its metabolites in patients with renal failure. METHODS: Twelve intensive care patients undergoing continuous venovenous hemofiltration received 4...
July 24, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28736734/compliance-to-self-monitoring-of-blood-glucose-among-patients-with-type-2-diabetes-mellitus-and-its-influential-factors-a-real-world-cross-sectional-study-based-on-the-tencent-tdf-i-blood-glucose-monitoring-platform
#10
Zhi-De Hu, Kai-Ping Zhang, Ying Huang, Shu Zhu
BACKGROUND: To investigate the compliance to self-monitoring of blood glucose (SMBG) among patients with type 2 diabetes mellitus (T2DM) and its influential factors. METHODS: The real-world SMBG use over 90 days among 415 T2DM patients were recorded by using a blood glucose monitoring platform (TDF-I, Tencent, China). Clinical features including age, sex, duration of diabetes, insulin treatment or not, and use of oral antidiabetic drugs were collected. Poor compliance was defined as the average frequency of weekly SMBG use over 90 days was below the criteria established by the physicians, and otherwise the patients were regarded as with good compliance...
2017: MHealth
https://www.readbyqxmd.com/read/28736536/mind-reading-and-behavior-reading-against-agents-with-and-without-anthropomorphic-features-in-a-competitive-situation
#11
Kazunori Terada, Seiji Yamada
Humans use two distinct cognitive strategies separately to understand and predict other humans' behavior. One is mind-reading, in which an internal state such as an intention or an emotional state is assumed to be a source of a variety of behaviors. The other is behavior-reading, in which an actor's behavior is modeled based on stimulus-response associations without assuming internal states behind the behavior. We hypothesize that anthropomorphic features are key for an observer switching between these two cognitive strategies in a competitive situation...
2017: Frontiers in Psychology
https://www.readbyqxmd.com/read/28736522/gliotoxin-targets-nuclear-notch2-in-human-solid-tumor-derived-cell-lines-in-vitro-and-inhibits-melanoma-growth-in-xenograft-mouse-model
#12
Rainer Hubmann, Wolfgang Sieghart, Susanne Schnabl, Mohammad Araghi, Martin Hilgarth, Marlies Reiter, Dita Demirtas, Peter Valent, Christoph Zielinski, Ulrich Jäger, Medhat Shehata
Deregulation of NOTCH2 signaling is implicated in a wide variety of human neoplasias. The current concept of targeting NOTCH is based on using gamma secretase inhibitors (GSI) to regulate the release of the active NOTCH intracellular domain. However, the clinical outcome of GSI remains unsatisfactory. Therefore we analyzed human solid tumor derived cell lines for their nuclear NOTCH activity and evaluated the therapeutic potential of the NOTCH2 transactivation inhibitor gliotoxin in comparison to the representative GSI DAPT...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28736294/enhanced-neuroprotection-of-anthocyanin-loaded-peg-gold-nanoparticles-against-a%C3%AE-1-42-induced-neuroinflammation-and-neurodegeneration-via-the-nf-kb-jnk-gsk3%C3%AE-signaling-pathway
#13
Min Ju Kim, Shafiq Ur Rehman, Faiz Ul Amin, Myeong Ok Kim
Amyloid-beta (Aβ1-42) plaques and neurofibrillary tangles (NFTs) are the main hallmarks considered to be associated with neuroinflammation in Alzheimer's disease (AD). Recently, nanoparticle-based targeted drug delivery approaches have been found to be a useful tool in the neurotherapeutics field. Therefore, we examined and compared the neuroprotective effect of anthocyanins alone and anthocyanin-loaded poly (ethylene glycol)-gold nanoparticles (PEG-AuNPs) in Aβ1-42-injected mouse and in vitro models of AD...
July 20, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28735214/indazole-based-ligands-for-estrogen-related-receptor-%C3%AE-as-potential-anti-diabetic-agents
#14
Raymond J Patch, Hui Huang, Sharmila Patel, Wing Cheung, Guozhang Xu, Bao-Ping Zhao, Derek A Beauchamp, Dionisios Rentzeperis, John G Geisler, Hossein B Askari, Jianying Liu, Jyotsna Kasturi, Meghan Towers, Micheal D Gaul, Mark R Player
Estrogen-related receptor α (ERRα) is an orphan nuclear receptor that has been functionally implicated in the regulation of energy homeostasis. Herein is described the development of indazole-based N-alkylthiazolidenediones, which function in biochemical assays as selective inverse agonists against this receptor. Series optimization provided several potent analogues that inhibited the recruitment of a co-activator peptide fragment in vitro (IC50s < 50 nM) and reduced fasted circulating insulin and triglyceride levels in a sub-chronic pre-diabetic rat model when administered orally (10 mg/kg)...
July 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28735040/co-encapsulation-of-paclitaxel-and-c6-ceramide-in-tributyrin-containing-nanocarriers-improve-co-localization-in-the-skin-and-potentiate-cytotoxic-effects-in-2d-and-3d-models
#15
Vanessa F M Carvalho, Amanda Migotto, Daniela V Giacone, Débora P de Lemos, Thalita B Zanoni, Silvya S Maria-Engler, Leticia V Costa-Lotufo, Luciana B Lopes
Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0.50%) in micro and nanoemulsions containing tributyrin (a butyric acid pro-drug included for potentiation of cytotoxicity), and compared their ability to co-localize the drugs in viable skin layers. The nanoemulsion delivered 2- and 2.4-fold more paclitaxel into viable skin layers of porcine skin in vitro at 4 and 8h post-application than the microemulsion, and 1...
July 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28734903/the-olfactory-bulbectomized-rat-model-is-not-an-appropriate-model-for-studying-depression-based-on-morphological-stereological-studies-of-the-hippocampus
#16
Canan Yurttas, Christoph Schmitz, Mehmet Turgut, Tatyana Strekalova, Harry W M Steinbusch
Bilateral olfactory bulbectomy (OBX) has been used as an animal model for major depression that results in behavioral, neurochemical, and neuroendocrinological changes were reversed by chronic treatment with antidepressants, including fluoxetine. However, both etiological and construct validities are lacking in OBX for rats. In the present study, we investigated the morphological changes in the hippocampi of rats undergoing OBX that were treated with fluoxetine (10mg/kg, p.o. once daily for 4 and 12 weeks) using stereological techniques...
July 19, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28733439/implementation-of-a-model-based-design-in-a-phase-1b-study-of-combined-targeted-agents
#17
Nolan A Wages, Craig A Portell, Michael E Williams, Mark R Conaway, Gina R Petroni
In recent years, investigators have recognized the rigidity of single agent, safety only, traditional designs, rendering them ineffective for conducting contemporary early-phase clinical trials, such as those involving combinations and /or biological agents.  Novel approaches are required to address these research questions, such as those posed in trials involving targeted therapies. We describe the implementation of a model-based design for identifying an optimal treatment combination, defined by low toxicity and high efficacy, in an early-phase trial evaluating a combination of two oral targeted inhibitors in relapsed / refractory mantle cell lymphoma...
July 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28732770/pharmacologic-modeling-of-primary-mitochondrial-respiratory-chain-dysfunction-in-zebrafish
#18
James Byrnes, Rebecca Ganetzky, Richard Lightfoot, Michael Tzeng, Eiko Nakamaru-Ogiso, Christoph Seiler, Marni J Falk
Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects on function as well as mitochondrial biochemistry and physiology...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28730643/differences-in-gadolinium-retention-after-repeated-injections-of-macrocyclic-mr-contrast-agents-to-rats
#19
Simona Bussi, Alessandra Coppo, Catherine Botteron, Valérie Fraimbault, Antonello Fanizzi, Elisa De Laurentiis, Sonia Colombo Serra, Miles A Kirchin, Fabio Tedoldi, Federico Maisano
PURPOSE: To compare the levels of gadolinium in the blood, cerebrum, cerebellum, liver, femur, kidneys, and skin after multiple exposure of rats to the macrocyclic gadolinium-based contrast agents (GBCAs) gadoterate, gadobutrol, and gadoteridol. MATERIALS AND METHODS: Fifty male Wistar Han rats were randomized to three exposure groups (n = 15 per group) and one control group (n = 5). Animals in the exposure groups received a total of 20 GBCA administrations (four administrations per week for 5 consecutive weeks) at a dose of 0...
July 21, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28730230/magnetic-nanoparticles-based-therapy-for-malignant-mesothelioma
#20
Ion Mîndrilă, Sandra Alice Buteică, Dan Eduard Mihaiescu, Florin Burada, Bogdan Mîndrilă, Maria Cristina Predoi, Ionica Pirici, Adrian Fudulu, Octavian Croitoru
This work was aimed to analyze the versatility of the chick embryo chorioallantoic membrane (CAM) as in vivo model for the study of the malignant pleural mesothelioma (MPM) and the therapeutic potential of Fe3O4÷salicylic acid magnetic nanoparticles (SaMNPs) on MPM cells. The antitumor effects of SaMNPs were studied by in vitro and in vivo tests on CARM-L12 TG3 rat malignant mesothelioma cells and human MPM xenografts implanted on CAMs. In order to assess the human MPM xenograft growth characteristics, calretinin, HBME-1 (Hector Battifora mesothelial epitope-1), and cytokeratins immunohistochemical stainings were performed...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
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