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Experimental therapeutics

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https://www.readbyqxmd.com/read/28231499/surfactant-cobalt-iii-complexes-the-impact-of-hydrophobicity-on-interaction-with-hsa-and-dna-insights-from-experimental-and-theoretical-approach
#1
Selvakumar Veeralakshmi, Gopal Sabapathi, Selvan Nehru, Ponnambalam Venuvanalingam, Sankaralingam Arunachalam
To develop surfactant-based metallodrugs, it is very important to know about their hydrophobicity, micelle forming capacity, their interaction with biomacromolecules such as proteins and nucleic acids, and biological activities. Here, diethylenetriamine (dien) and tetradecylamine ligand (TA) based surfactant-cobalt(III) complexes with single chain domain, [Co(dien)(TA)Cl2]ClO4 (1) and double chain domain [Co(dien)(TA)2Cl](ClO4)2 (2) were chosen to study the effect of hydrophobicity on the interaction with human serum albumin and calf thymus DNA...
February 16, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28231035/biologically-relevant-heterogeneity-metrics-and-practical-insights
#2
Albert Gough, Andrew M Stern, John Maier, Timothy Lezon, Tong-Ying Shun, Chakra Chennubhotla, Mark E Schurdak, Steven A Haney, D Lansing Taylor
Heterogeneity is a fundamental property of biological systems at all scales that must be addressed in a wide range of biomedical applications, including basic biomedical research, drug discovery, diagnostics, and the implementation of precision medicine. There are a number of published approaches to characterizing heterogeneity in cells in vitro and in tissue sections. However, there are no generally accepted approaches for the detection and quantitation of heterogeneity that can be applied in a relatively high-throughput workflow...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230865/erbb4-signaling-stimulates-pro-inflammatory-macrophage-apoptosis-and-limits-colonic-inflammation
#3
Michael A Schumacher, Matija Hedl, Clara Abraham, Jessica K Bernard, Patricia R Lozano, Jonathan J Hsieh, Dana Almohazey, Edie B Bucar, Shivesh Punit, Peter J Dempsey, Mark R Frey
Efficient clearance of pro-inflammatory macrophages from tissues after resolution of a challenge is critical to prevent prolonged inflammation. Defects in clearance can contribute to conditions such as inflammatory bowel disease, and thus may be therapeutically targetable. However, the signaling pathways that induce termination of pro-inflammatory macrophages are incompletely defined. We tested whether the ErbB4 receptor tyrosine kinase, previously not known to have role in macrophage biology, is involved in this process...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230749/design-of-drug-delivery-systems-containing-artemisinin-and-its-derivatives
#4
REVIEW
Blessing Atim Aderibigbe
Artemisinin and its derivatives have been reported to be experimentally effective for the treatment of highly aggressive cancers without developing drug resistance, they are useful for the treatment of malaria, other protozoal infections and they exhibit antiviral activity. However, they are limited pharmacologically by their poor bioavailability, short half-life in vivo, poor water solubility and long term usage results in toxicity. They are also expensive for the treatment of malaria when compared to other antimalarials...
February 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28230065/in-vivo-evaluation-of-a-novel-format-of-a-bivalent-her3-targeting-and-albumin-binding-therapeutic-affibody-construct
#5
Tarek Z Bass, Maria Rosestedt, Bogdan Mitran, Fredrik Y Frejd, John Löfblom, Vladimir Tolmachev, Stefan Ståhl, Anna Orlova
Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229422/therapeutic-application-of-adult-stem-cells-in-the-heart
#6
Taylor A Johnson, Dinender K Singla
Cell therapies have been explored as a potential treatment avenue to treat heart diseases, such as myocardial infarction, doxorubicin-induced cardiomyopathy, and heart failure. Embryonic and adult stem cells (ASCs) have been examined in animal and clinical settings. Unlike embryonic and induced pluripotent stem cells, ASCs do not pose a threat to form teratomas, nor do they have immune system concerns, making them ideal for therapeutic use in humans. In this review, we will investigate different characteristics and sources of adult stem cells and progenitor cells, as well as determine their efficacy in cell transplantation in experimental and clinical trials...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28228926/antibody-h3-structure-prediction
#7
REVIEW
C Marks, C M Deane
Antibodies are proteins of the immune system that are able to bind to a huge variety of different substances, making them attractive candidates for therapeutic applications. Antibody structures have the potential to be useful during drug development, allowing the implementation of rational design procedures. The most challenging part of the antibody structure to experimentally determine or model is the H3 loop, which in addition is often the most important region in an antibody's binding site. This review summarises the approaches used so far in the pursuit of accurate computational H3 structure prediction...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28228000/c60-fullerene-as-promising-therapeutic-agent-for-the-prevention-and-correction-of-skeletal-muscle-functioning-at-ischemic-injury
#8
D M Nozdrenko, D O Zavodovskyi, T Yu Matvienko, S Yu Zay, K I Bogutska, Yu I Prylutskyy, U Ritter, P Scharff
The therapeutic effect of pristine C60 fullerene aqueous colloid solution (C60FAS) on the functioning of the rat soleus muscle at ischemic injury depending on the time of the general pathogenesis of muscular system and method of administration C60FAS in vivo was investigated. It was found that intravenous administration of C60FAS is the optimal for correction of speed macroparameters of contraction for ischemic muscle damage. At the same time, intramuscular administration of C60FAS shows pronounced protective effect in movements associated with the generation of maximum force responses or prolonged contractions, which increase the muscle fatigue level...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28227989/computational-models-of-non-invasive-brain-and-spinal-cord-stimulation
#9
Pedro C Miranda, Ricardo Salvador, Cornelia Wenger, Sofia R Fernandes, Pedro C Miranda, Ricardo Salvador, Cornelia Wenger, Sofia R Fernandes, Sofia R Fernandes, Pedro C Miranda, Cornelia Wenger, Ricardo Salvador
Non-invasive brain and spinal cord stimulation techniques are increasingly used for diagnostic and therapeutic purposes. Knowledge of the spatial distribution of the induced electric field is necessary to interpret experimental results and to optimize field delivery. Since the induced electric field cannot be measured in vivo in humans, computational models play a fundamental role in determining the characteristics of the electric field. We produced computational models of the head and trunk to calculate the electric field induced in the brain and spinal cord by transcranial magnetic stimulation, transcranial direct current stimulation and transcutaneous spinal cord direct current stimulation...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227638/simulation-of-fluid-environment-using-a-robotic-orthosis-on-human-lower-extremity-for-therapeutic-purposes
#10
Tayfun Efe Ertop, Tolga Yuksel, Erhan Ilhan Konukseven, Tayfun Efe Ertop, Tolga Yuksel, Erhan Ilhan Konukseven, Tolga Yuksel, Erhan Ilhan Konukseven, Tayfun Efe Ertop
Rehabilitation under water is a viable physical rehabilitation option, but it has some limitations in terms of adapting to needs of each patient. In addition, its facility requirements are relatively high. Simulating the fluid environment using a robotic system would enable therapists adjust various parameters so that the therapy is tailored to the patient's unique state. Also, using a robotic system instead might be less costly and easily reachable. In this study, human lower extremity movement in fluids is modeled...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28227077/optimal-control-of-inspired-perfluorocarbon-temperature-for-induction-of-hypothermia-by-total-liquid-ventilation-in-juvenile-lamb-model
#11
Mathieu Nadeau, Michael Sage, Jean-Paul Praud, Renaud Tissier, Herve Walti, Philippe Micheau, Mathieu Nadeau, Michael Sage, Jean-Paul Praud, Renaud Tissier, Herve Walti, Philippe Micheau, Michael Sage, Philippe Micheau, Jean-Paul Praud, Mathieu Nadeau, Herve Walti, Renaud Tissier
Mild hypothermia is well known for its therapeutic value in cardio- and neuroprotection. Many recent experimental studies have shown that the swiftness of the cooling offered by total liquid ventilation (TLV) holds great promise in achieving maximal therapeutic effect. TLV is an emerging ventilation technique in which the lungs are filled with breathable liquids, namely perfluorocarbons (PFCs). A liquid ventilator ensures subject ventilation by periodically renewing a volume of oxygenated, CO2-free and temperature-controlled breathable PFC...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226660/identifying-stereotypic-evolving-micro-scale-seizures-sems-in-the-hypoxic-ischemic-eeg-of-the-pre-term-fetal-sheep-with-a-wavelet-type-ii-fuzzy-classifier
#12
Hamid Abbasi, Laura Bennet, Alistair J Gunn, Charles P Unsworth, Hamid Abbasi, Laura Bennet, Alistair J Gunn, Charles P Unsworth, Charles P Unsworth, Laura Bennet, Hamid Abbasi, Alistair J Gunn
Perinatal hypoxic-ischemic encephalopathy (HIE) around the time of birth due to lack of oxygen can lead to debilitating neurological conditions such as epilepsy and cerebral palsy. Experimental data have shown that brain injury evolves over time, but during the first 6-8 hours after HIE the brain has recovered oxidative metabolism in a latent phase, and brain injury is reversible. Treatments such as therapeutic cerebral hypothermia (brain cooling) are effective when started during the latent phase, and continued for several days...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28226224/different-electrophysiological-effects-of-the-levo-and-dextrorotatory-isomers-of-mexiletine-in-isolated-rabbit-cardiac-muscle
#13
Zsolt Gurabi, Bence Patocskai, Balázs Györe, László Virág, Péter Mátyus, Julius Gy Papp, András Varró, Istvan Koncz
Racemic mexiletine is a widely used antiarrhythmic agent which blocks sodium channels. The effects of R-(-) and S-(+) mexiletine stereoisomers on maximum rate of depolarization (Vmax), conduction time and repolarization have not yet been investigated in isolated cardiac preparations. We studied the effect of the R-(-) and S-(+) mexiletine on rabbit cardiac action potential parameters by using the conventional microelectrode technique. Both enantiomers at 20 µM of therapeutically and experimentally relevant concentration, significantly depressed the Vmax at fast heart rates (BCLs 300 - 700 ms)...
February 22, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28225161/treatment-of-experimental-status-epilepticus-with-synergistic-drug-combinations
#14
Jerome Niquet, Roger Baldwin, Lucie Suchomelova, Lucille Lumley, Roland Eavey, Claude G Wasterlain
During status epilepticus (SE), synaptic γ-aminobutyric acid A receptors (GABAA Rs) become internalized and inactive, whereas spare N-methyl-d-aspartate receptors (NMDARs) assemble, move to the membrane, and become synaptically active. When treatment of SE is delayed, the number of synaptic GABAA Rs is drastically reduced, and a GABAA agonist cannot fully restore inhibition. We used a combination of low-dose diazepam (to stimulate the remaining GABAA Rs), ketamine (to mitigate the effect of the NMDAR increase), and valproate (to enhance inhibition at a nonbenzodiazepine site) to treat seizures in a model of severe cholinergic SE...
February 22, 2017: Epilepsia
https://www.readbyqxmd.com/read/28224995/genetics-of-eosinophilic-esophagitis
#15
REVIEW
L C Kottyan, M E Rothenberg
Eosinophilic esophagitis (EoE) is a chronic, allergic disease associated with marked mucosal eosinophil accumulation. EoE disease risk is multifactorial and includes environmental and genetic factors. This review will focus on the contribution of genetic variation to EoE risk, as well as the experimental tools and statistical methodology used to identify EoE risk loci. Specific disease-risk loci that are shared between EoE and other allergic diseases (TSLP, LRRC32) or unique to EoE (CAPN14), as well as Mendellian Disorders associated with EoE, will be reviewed in the context of the insight that they provide into the molecular pathoetiology of EoE...
February 22, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28223983/b-cell-homeostasis-and-functional-properties-are-altered-in-an-hypochlorous-acid-induced-murine-model-of-systemic-sclerosis
#16
Sébastien Sanges, Manel Jendoubi, Niloufar Kavian, Carine Hauspie, Silvia Speca, Jean-Charles Crave, Thomas Guerrier, Guillaume Lefèvre, Vincent Sobanski, Ariel Savina, Eric Hachulla, Pierre-Yves Hatron, Myriam Labalette, Frédéric Batteux, Sylvain Dubucquoi, David Launay
INTRODUCTION: During systemic sclerosis (SSc), peripheral B cells display alterations in subset homeostasis and functional properties and are a promising therapeutic target. However, there is only few data regarding whether these anomalies are accurately reproduced in animal models of SSc. OBJECTIVE: In this work, we assessed the B cell homeostasis modifications in an experimental model of SSc [hypochlorous acid (HOCl)-induced mouse], both at a phenotypic and functional level, during the course of the disease...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28223818/an-evidence-based-review-on-urate-lowering-treatments-implications-for-optimal-treatment-of-chronic-hyperuricemia
#17
REVIEW
Marilisa Bove, Arrigo Francesco Giuseppe Cicero, Maddalena Veronesi, Claudio Borghi
Several studies suggest that chronic hyperuricemia, the main precursor of gout, is involved in the pathogenesis of different systemic disorders that affect cardiovascular and renal systems, such as hypertension, obesity, hypercholesterolemia, atherosclerosis, metabolic syndrome, chronic heart failure, and chronic kidney disease. Recent epidemiological evidence has shown an increasing trend in the prevalence of hyperuricemia and gout in the Western world: a number of population-based studies estimate a prevalence of up to 21% for hyperuricemia and 1%-4% for gout...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28223550/nadh-autofluorescence-a-new-metabolic-biomarker-for-cancer-stem-cells-identification-of-vitamin-c-and-cape-as-natural-products-targeting-stemness
#18
Gloria Bonuccelli, Ernestina Marianna De Francesco, Rianne de Boer, Herbert B Tanowitz, Michael P Lisanti
Here, we assembled a broad molecular "tool-kit" to interrogate the role of metabolic heterogeneity in the propagation of cancer stem-like cells (CSCs). First, we subjected MCF7 cells to "metabolic fractionation" by flow cytometry, using fluorescent mitochondrial probes to detect PCG1α activity, as well ROS and hydrogen-peroxide (H2O2) production; NADH levels were also monitored by auto-fluorescence. Then, the various cell populations were functionally assessed for "stem cell activity", using the mammosphere assay (3D-spheroids)...
February 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28223235/interleukin-32-inflammation-and-cancer
#19
REVIEW
Jin Tae Hong, Dong Ju Son, Chong Kil Lee, Do-Young Yoon, Dong Hun Lee, Mi Hee Park
Interleukin-32 (IL-32) is a novel cytokine involved in inflammation and cancer development. IL-32 gene consists of eight small exons, and IL-32 mRNA has nine alternative spliced isoforms, and was thought to be secreted because it contains an internal signal sequence and lacks a transmembrane region. IL-32 is initially expressed selectively in activated T cells by mitogen and activated NK cells and their expression is strongly augmented by microbes, mitogens, and other cytokines. The IL-32 is induced mainly by pathogens and pro-inflammatory cytokines, but IL-32 is more prominent in immune cells than in non-immune tissues...
February 13, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28223165/heterogeneous-intratumoral-distribution-of-gadolinium-nanoparticles-within-u87-human-glioblastoma-xenografts-unveiled-by-micro-pixe-imaging
#20
Asuncion Carmona, Stéphane Roudeau, Baptiste L'Homel, Frédéric Pouzoulet, Sarah Bonnet-Boissinot, Yolanda Prezado, Richard Ortega
Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging...
February 18, 2017: Analytical Biochemistry
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