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visual pharmacology

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https://www.readbyqxmd.com/read/28102227/singular-location-and-signaling-profile-of-adenosine-a2a-cannabinoid-cb1-receptor-heteromers-in-the-dorsal-striatum
#1
Estefanía Moreno, Anna Chiarlone, Mireia Medrano, Mar Puigdellívol, Lucka Bibic, Lesley A Howell, Eva Resel, Nagore Puente, María J Casarejos, Juan Perucho, Joaquín Botta, Nuria Suelves, Francisco Ciruela, Silvia Ginés, Ismael Galve-Roperh, Vicent Casadó, Pedro Grandes, Beat Lutz, Krisztina Monory, Enric I Canela, Carmen Lluís, Peter J McCormick, Manuel Guzmán
The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A2A receptor (A2AR) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A2AR and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A2AR-CB1R heteromeric complexes...
January 19, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28100828/an-integrated-modelling-framework-for-neural-circuits-with-multiple-neuromodulators
#2
Alok Joshi, Vahab Youssofzadeh, Vinith Vemana, T M McGinnity, Girijesh Prasad, KongFatt Wong-Lin
Neuromodulators are endogenous neurochemicals that regulate biophysical and biochemical processes, which control brain function and behaviour, and are often the targets of neuropharmacological drugs. Neuromodulator effects are generally complex partly owing to the involvement of broad innervation, co-release of neuromodulators, complex intra- and extrasynaptic mechanism, existence of multiple receptor subtypes and high interconnectivity within the brain. In this work, we propose an efficient yet sufficiently realistic computational neural modelling framework to study some of these complex behaviours...
January 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28098729/vitrectomy-for-persistent-macular-holes-following-ocriplasmin-injection-a-comparative-multicenter-study
#3
Ricarda G Schumann, Armin Wolf, Hans Hoerauf, Albrecht Lommatzsch, Mathias Maier, Joachim Wachtlin, Michael J Koss, Thomas Kreutzer, Thomas Bertelmann, Sara Kazerounian, Stefan Mennel, Siegfried G Priglinger
PURPOSE: To determine functional and anatomical outcomes of pars plana vitrectomy for persistent full-thickness macular hole (MH) after intravitreal injection of ocriplasmin. METHODS: This is a multicenter retrospective interventional study of 37 eyes of 37 patients who underwent pars plana vitrectomy with internal limiting membrane peeling for persistent MH after ocriplasmin treatment between December 2013 and December 2015 and comparison with 35 eyes of 35 patients who were offered ocriplasmin injection but underwent pars plana vitrectomy alone without pharmacologic vitreolysis before surgery...
January 16, 2017: Retina
https://www.readbyqxmd.com/read/28095676/radiosynthesis-and-evaluation-of-11-c-3-hydroxycyclopent-1-enecarboxylic-acid-as-potential-pet-ligand-for-the-high-affinity-%C3%AE-hydroxybutyric-acid-binding-sites
#4
Claus H Jensen, Hanne D Hansen, Tina Bay, Stine B Vogensen, Szabolcs Lehel, Louise Thiesen, Christoffer Bundgaard, Rasmus P Clausen, Gitte M Knudsen, Matthias M Herth, Petrine Wellendorph, Bente Frølund
γ-Hydroxybutyric acid (GHB) is an endogenous neuroactive substance and proposed neurotransmitter with affinity for both low- and high-affinity binding sites. A radioligand with high and specific affinity toward the high-affinity GHB binding site would be a unique tool toward a more complete understanding of this population of binding sites. With its high specific affinity and monocarboxylate transporter (MCT1) mediated transport across the blood-brain barrier in pharmacological doses, 3-hydroxycyclopent-1-enecarboxylic acid (HOCPCA) seems like a suitable PET radiotracer candidate...
January 18, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28092651/long-lasting-antinociceptive-effects-of-green-light-in-acute-and-chronic-pain-in-rats
#5
Mohab M Ibrahim, Amol Patwardhan, Kerry B Gilbraith, Aubin Moutal, Xiaofang Yang, Lindsey A Chew, Tally Largent-Milnes, T Philip Malan, Todd W Vanderah, Frank Porreca, Rajesh Khanna
Treatments for chronic pain are inadequate, and new options are needed. Nonpharmaceutical approaches are especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains to be explored for modulation of pain. We investigated the effects of light-emitting diodes (LEDs), in the visible spectrum, on acute sensory thresholds in naive rats as well as in experimental neuropathic pain...
February 2017: Pain
https://www.readbyqxmd.com/read/28088231/efficacy-of-gabapentin-for-prevention-of-postherpetic-neuralgia-study-protocol-for-a-randomized-controlled-clinical-trial
#6
Manuel Rullán, Oana Bulilete, Alfonso Leiva, Aina Soler, Antonia Roca, María José González-Bals, Patricia Lorente, Joan Llobera
BACKGROUND: Postherpetic neuralgia (PHN) is a chronic neuropathic pain that results from alterations of the peripheral nervous system in areas affected by the herpes zoster virus. The symptoms include pain, paresthesia, dysesthesia, hyperalgesia, and allodynia. Despite the availability of pharmacological treatments to control these symptoms, no treatments are available to control the underlying pathophysiology responsible for this disabling condition. METHODS/DESIGN: Patients with herpes zoster who are at least 50 years old and have a pain score of 4 or higher on a visual analogue scale (VAS) will be recruited...
January 14, 2017: Trials
https://www.readbyqxmd.com/read/28087236/determination-of-the-feasibility-of-a-multicomponent-intervention-program-to-prevent-delirium-in-the-intensive-care-unit-a-modified-rand-delphi-study
#7
Annelies Wassenaar, Mark van den Boogaard, Underpin-Icu Study Group, Lisette Schoonhoven, Peter Pickkers
BACKGROUND: Delirium is common in Intensive Care Unit (ICU) patients and associated with poor outcome. In non-ICU patients a multicomponent intervention program with non-pharmacological interventions has shown to reduce delirium. Currently, there is insufficient evidence regarding the effects of such a program in ICU patients. We developed a draft program based on a review. As most studies were conducted in non-ICU patients, the feasibility of the program in ICU patients needs to be assessed before investigating its effectiveness...
January 10, 2017: Australian Critical Care: Official Journal of the Confederation of Australian Critical Care Nurses
https://www.readbyqxmd.com/read/28078356/-marketability-of-food-supplements-criteria-for-the-legal-assessment
#8
Evelyn Breitweg-Lehmann
To be placed on the market legally, food supplements have to meet national and European food law regulations. This is true for all substances used as well as for the labeling on the packaging of and the advertising for food supplements. The food business operator is responsible for its compliance with all regulations. Therefore, in this article, a concise step-by-step assessment is presented, covering all necessary legal requirements to market food supplements. Additionally, all steps are visualized in a flow chart...
January 11, 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28073700/the-yeast-ste2p-g-protein-coupled-receptor-dimerizes-on-the-cell-plasma-membrane
#9
Orkun Cevheroğlu, Gözde Kumaş, Melinda Hauser, Jeffrey M Becker, Çağdaş D Son
Dimerization of G protein-coupled receptors (GPCR) may play an important role in maturation, internalization, signaling and/or pharmacology of these receptors. However, the location where dimerization occurs is still under debate. In our study, variants of Ste2p, a yeast mating pheromone GPCR, were tagged with split EGFP (enhanced green fluorescent protein) fragments inserted between transmembrane domain seven and the C-terminus or appended to the C-terminus. Bimolecular Fluorescence Complementation (BiFC) assay was used to determine where receptor dimerization occurred during protein trafficking by monitoring generation of EGFP fluorescence, which occurred upon GPCR dimerization...
January 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28070619/theory-of-visual-attention-tva-applied-to-mice-in-the-5-choice-serial-reaction-time-task
#10
C M Fitzpatrick, M Caballero-Puntiverio, U Gether, T Habekost, C Bundesen, S Vangkilde, D P D Woldbye, J T Andreasen, A Petersen
RATIONALE: The 5-choice serial reaction time task (5-CSRTT) is widely used to measure rodent attentional functions. In humans, many attention studies in healthy and clinical populations have used testing based on Bundesen's Theory of Visual Attention (TVA) to estimate visual processing speeds and other parameters of attentional capacity. OBJECTIVES: We aimed to bridge these research fields by modifying the 5-CSRTT's design and by mathematically modelling data to derive attentional parameters analogous to human TVA-based measures...
January 9, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28069540/multi-modal-analysis-of-functional-connectivity-and-cerebral-blood-flow-reveals-shared-and-unique-effects-of-propofol-in-large-scale-brain-networks
#11
Maolin Qiu, Dustin Scheinost, Ramachandran Ramani, R Todd Constable
Anesthesia-induced changes in functional connectivity and cerebral blow flow (CBF) in large-scale brain networks have emerged as key markers of reduced consciousness. However, studies of functional connectivity disagree on which large-scale networks are altered or preserved during anesthesia, making it difficult to find a consensus amount studies. Additionally, pharmacological alterations in CBF could amplify or occlude changes in connectivity due to the shared variance between CBF and connectivity. Here, we used data-driven connectivity methods and multi-modal imaging to investigate shared and unique neural correlates of reduced consciousness for connectivity in large-scale brain networks...
January 6, 2017: NeuroImage
https://www.readbyqxmd.com/read/28061688/aptamers-as-therapeutics
#12
Shahid M Nimjee, Rebekah R White, Richard C Becker, Bruce A Sullenger
Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development...
January 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/28060586/evidence-based-treatment-of-diabetic-macular-edema
#13
Rasha Barham, Hala El Rami, Jennifer K Sun, Paolo S Silva
Diabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy...
2017: Seminars in Ophthalmology
https://www.readbyqxmd.com/read/28060303/an-in-vitro-model-of-the-blood-brain-barrier-using-impedance-spectroscopy-a-focus-on-t-cell-endothelial-cell-interaction
#14
Ivan Kuzmanov, Alexander M Herrmann, Hans-Joachim Galla, Sven G Meuth, Heinz Wiendl, Luisa Klotz
Breakdown of the blood-brain barrier (BBB) is a critical step in the development of autoimmune diseases such as multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). This process is characterized by the transmigration of activated T cells across brain endothelial cells (ECs), the main constituents of the BBB. However, the consequences on brain EC function upon interaction with such T cells are largely unknown. Here we describe an assay that allows for the evaluation of primary mouse brain microvascular EC (MBMEC) function and barrier integrity during the interaction with T cells over time...
December 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28053025/activity-dependent-dynamics-of-the-transcription-factor-of-camp-response-element-binding-protein-in-cortical-neurons-revealed-by-single-molecule-imaging
#15
Hironobu Kitagawa, Noriyuki Sugo, Masatoshi Morimatsu, Yoshiyuki Arai, Toshio Yanagida, Nobuhiko Yamamoto
: Transcriptional regulation is crucial for neuronal activity-dependent processes that govern neuronal circuit formation and synaptic plasticity. An intriguing question is how neuronal activity influences the spatiotemporal interactions between transcription factors and their target sites. Here, using a single-molecule imaging technique, we investigated the activity dependence of DNA binding and dissociation events of cAMP-response element binding protein (CREB), a principal factor in activity-dependent transcription, in mouse cortical neurons...
January 4, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28049203/the-involvement-of-protein-kinase-d-in-t-cell-induced-mast-cell-activation
#16
Pazit Salamon, Irit Shefler, Alon Y Hershko, Yoseph A Mekori
BACKGROUND: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation. METHODS: Human MC were stimulated by activated T cell membranes (T*m). Phosphorylation of kinases was assessed by Western blotting...
2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/28046203/visualizing-changes-in-neuronal-dendritic-morphology-in-response-to-stress-and-pharmacological-challenge
#17
Cara L Wellman
This unit outlines a protocol for Golgi staining, which has been used extensively to reliably and quantitatively assess alterations in dendritic arborization and spine density as a result of a variety of factors, including chronic administration of glucocorticoids, chronic stress, and pharmacological manipulations. The method stains neurons in their entirety, allowing for sophisticated analyses of branch lengths and numbers as well as patterns of dendritic branching. Advantages of the technique include its usefulness in multisite collaborations and its utility in visualizing neurons in multiple regions within the same brain...
January 3, 2017: Current Protocols in Neuroscience
https://www.readbyqxmd.com/read/28038673/feature-visualization-and-classification-for-the-discrimination-between-individuals-with-parkinson-s-disease-under-levodopa-and-dbs-treatments
#18
Alessandro R P Machado, Hudson Capanema Zaidan, Ana Paula Souza Paixão, Guilherme Lopes Cavalheiro, Fábio Henrique Monteiro Oliveira, João Areis Ferreira Barbosa Júnior, Kheline Naves, Adriano Alves Pereira, Janser Moura Pereira, Nader Pouratian, Xiaoyi Zhuo, Andrew O'Keeffe, Justin Sharim, Yvette Bordelon, Laurice Yang, Marcus Fraga Vieira, Adriano O Andrade
BACKGROUND: Over the years, a number of distinct treatments have been adopted for the management of the motor symptoms of Parkinson's disease (PD), including pharmacologic therapies and deep brain stimulation (DBS). Efficacy is most often evaluated by subjective assessments, which are prone to error and dependent on the experience of the examiner. Our goal was to identify an objective means of assessing response to therapy. METHODS: In this study, we employed objective analyses in order to visualize and identify differences between three groups: healthy control (N = 10), subjects with PD treated with DBS (N = 12), and subjects with PD treated with levodopa (N = 16)...
December 30, 2016: Biomedical Engineering Online
https://www.readbyqxmd.com/read/28036021/monitoring-the-response-of-hyperbilirubinemia-in-the-mouse-brain-by-in-vivo-bioluminescence-imaging
#19
Isabella Manni, Giuliana Di Rocco, Salvatore Fusco, Lucia Leone, Saviana Antonella Barbati, Carmine Maria Carapella, Claudio Grassi, Giulia Piaggio, Gabriele Toietta
Increased levels of unconjugated bilirubin are neurotoxic, but the mechanism leading to neurological damage has not been completely elucidated. Innovative strategies of investigation are needed to more precisely define this pathological process. By longitudinal in vivo bioluminescence imaging, we noninvasively visualized the brain response to hyperbilirubinemia in the MITO-Luc mouse, in which light emission is restricted to the regions of active cell proliferation. We assessed that acute hyperbilirubinemia promotes bioluminescence in the brain region, indicating an increment in the cell proliferation rate...
December 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28034352/development-of-a-novel-carbon-11-labeled-pet-radioligand-for-melanin-concentrating-hormone-receptor-1
#20
Hideyuki Igawa, Vladimir Stepanov, Lenke Tari, Shoki Okuda, Syunsuke Yamamoto, Shizuo Kasai, Yasutaka Nagisa, Jenny Häggkvist, Marie Svedberg, Miklós Tóth, Akihiro Takano, Christer Halldin
Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents and many drug discovery programs have been dedicated to identify small-molecule antagonists of melanin-concentrating hormone receptor 1 (MCHR1). The aim of this study was to develop a positron emission tomography (PET) tracer for MCHR1 for translation of preclinical pharmacology to clinic to enhance success rate of drug discovery programs. We identified 4-(cyclopropylmethoxy)-N-[8-methyl-3-({[(1-methyl-1H-pyrrol-2-yl)methyl]amino}ethyl)quinolin-7-yl]benzamide (Compound II) from Takeda MCHR1 antagonist library by utilizing binding affinity, log D value, physicochemical parameters ideal for a central nerve system agent, and synthetic feasibility of corresponding carbon-11 labeled radioligands as selection parameters for tracer candidates...
December 30, 2016: Current Radiopharmaceuticals
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