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https://www.readbyqxmd.com/read/29138838/effects-of-scn9a-gene-modification-on-na-channel-and-the-expression-of-nerve-growth-factor-in-a-rat-model-of-diarrhea%C3%A2-predominant-irritable-bowel-syndrome
#1
Yong-Yan Cai, Chen Li, Zhi-Xin Yan, Na Ma, Fang-Fang Li
The aim of the present study was to identify whether the sodium voltage-gated channel alpha subunit 9 (SCN9A) gene modification is a potential treatment for diarrhea‑predominant irritable bowel syndrome (D‑IBS), via regulating the Na+ channel and the expression of nerve growth factor (NGF). The recombinant adenovirus vector of the SCN9A gene was established, and rat colon cells were isolated for SCN9A gene modification. All subjects were divided into four groups: i) The SCN9A‑modified (D‑IBS rat model implanted with SCN9A‑modified colon cells), ii) negative control (NC; D‑IBS rat model implanted with colon cells without SCN9A gene modification), iii) blank (D‑IBS rat model without any treatment) and iv) normal (normal rats without any treatment)...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29134472/real-time-wireless-tumor-tracking-during-breast-conserving-surgery
#2
Natasja Janssen, Roeland Eppenga, Marie-Jeanne Vrancken Peeters, Frederieke van Duijnhoven, Hester Oldenburg, Jos van der Hage, Emiel Rutgers, Jan-Jakob Sonke, Koert Kuhlmann, Theo Ruers, Jasper Nijkamp
PURPOSE: To evaluate a novel surgical navigation system for breast conserving surgery (BCS), based on real-time tumor tracking using the Calypso[Formula: see text] 4D Localization System (Varian Medical Systems Inc., USA). Navigation-guided breast conserving surgery (Nav-BCS) was compared to conventional iodine seed-guided BCS ([Formula: see text]I-BCS). METHODS: Two breast phantom types were produced, containing spherical and complex tumors in which wireless transponders (Nav-BCS) or a iodine seed ([Formula: see text]I-BCS) were implanted...
November 13, 2017: International Journal of Computer Assisted Radiology and Surgery
https://www.readbyqxmd.com/read/29118920/combination-therapy-with-extracorporeal-shock-wave-and-melatonin-markedly-attenuated-neuropathic-pain-in-rat
#3
Kuan-Hung Chen, Chien-Hui Yang, Christopher Glenn Wallace, Chung-Ren Lin, Chia-Kai Liu, Tsung-Cheng Yin, Tien-Hung Huang, Yi-Ling Chen, Cheuk-Kwan Sun, Hon-Kan Yip
This study tested the hypothesis that combination therapy using extracorporeal shock wave (ECSW)-melatonin (Mel) was superior to either alone at ameliorating neuropathic pain (NP). NP was induced by chronic constriction injury (CCI) to the left sciatic nerve in rats. Animals were categorized into sham control (group 1), CCI only (group 2), CCI-ECSW (group 3), CCI-Mel (group 4) and CCI-ECSW-Mel (group 5). By days 2 and 8 after CCI, the mechanical paw withdrawal threshold (MPWT)/thermal paw withdrawal latency (TPWL) were highest in group 2, lowest in group 1, significantly lower in group 5 than in groups 3 and 4 (all p<0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28917704/accuracy-of-pedicle-screw-insertion-among-three-image-guided-navigation-systems-a-systematic-review-and-meta-analysis
#4
REVIEW
Jin Peng Du, Yong Fan, Qi Ning Wu, Dai Hua Wang, Jing Zhang, Ding Jun Hao
BACKGROUND: Many retrospective studies of pedicle screw placement have revealed that intraoperative navigation systems provide higher accuracy rates and safety than do free-hand techniques. The accuracy of various image-guided navigation systems has been studied; however, differences have not been well defined due to the lack of adequate evidence-based comparative studies. OBJECTIVE: A meta-analysis was conducted to focus on the variation in pedicle screw insertion among three navigation systems: a three-dimensional fluoroscopy-based navigation system (3D FluoroNav), a two-dimensional fluoroscopy-based navigation system (2D FluoroNav) and a conventional computed tomography navigation system (CT Nav)...
September 13, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28880874/discovery-and-mode-of-action-of-a-novel-analgesic-%C3%AE-toxin-from-the-african-spider-ceratogyrus-darlingi
#5
Silmara R Sousa, Joshua S Wingerd, Andreas Brust, Christopher Bladen, Lotten Ragnarsson, Volker Herzig, Jennifer R Deuis, Sebastien Dutertre, Irina Vetter, Gerald W Zamponi, Glenn F King, Paul F Alewood, Richard J Lewis
Spider venoms are rich sources of peptidic ion channel modulators with important therapeutical potential. We screened a panel of 60 spider venoms to find modulators of ion channels involved in pain transmission. We isolated, synthesized and pharmacologically characterized Cd1a, a novel peptide from the venom of the spider Ceratogyrus darlingi. Cd1a reversibly paralysed sheep blowflies (PD50 of 1318 pmol/g) and inhibited human Cav2.2 (IC50 2.6 μM) but not Cav1.3 or Cav3.1 (IC50 > 30 μM) in fluorimetric assays...
2017: PloS One
https://www.readbyqxmd.com/read/28734032/characterization-of-the-axon-initial-segment-of-mice-substantia-nigra-dopaminergic-neurons
#6
Cristian González-Cabrera, Rodrigo Meza, Lorena Ulloa, Paulina Merino-Sepúlveda, Valentina Luco, Ana Sanhueza, Alejandro Oñate-Ponce, J Paul Bolam, Pablo Henny
The axon initial segment (AIS) is the site of initiation of action potentials and influences action potential waveform, firing pattern, and rate. In view of the fundamental aspects of motor function and behavior that depend on the firing of substantia nigra pars compacta (SNc) dopaminergic neurons, we identified and characterized their AIS in the mouse. Immunostaining for tyrosine hydroxylase (TH), sodium channels (Nav ) and ankyrin-G (Ank-G) was used to visualize the AIS of dopaminergic neurons. Reconstructions of sampled AIS of dopaminergic neurons revealed variable lengths (12-60 μm) and diameters (0...
July 22, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28723274/identifying-voxels-at-risk-for-progression-in-glioblastoma-based-on-dosimetry-physiologic-and-metabolic-mri
#7
Mekhail Anwar, Annette M Molinaro, Olivier Morin, Susan M Chang, Daphne A Haas-Kogan, Sarah J Nelson, Janine M Lupo
Despite the longstanding role of radiation in cancer treatment and the presence of advanced, high-resolution imaging techniques, delineation of voxels at-risk for progression remains purely a geometric expansion of anatomic images, missing subclinical disease at risk for recurrence while treating potentially uninvolved tissue and increasing toxicity. This remains despite the modern ability to precisely shape radiation fields. A striking example of this is the treatment of glioblastoma, a highly infiltrative tumor that may benefit from accurate identification of subclinical disease...
September 2017: Radiation Research
https://www.readbyqxmd.com/read/28522215/blocking-voltage-gated-sodium-channels-as-a-strategy-to-suppress-pathological-cough
#8
REVIEW
Hui Sun, Marian Kollarik, Bradley J Undem
Pathological cough is thought to be secondary to inappropriate activation of vagal sensory nerves. Sensory nerves can be activated by a large number of disparate stimuli. The most relevant stimuli to block for effective anti-tussive therapy likely depend on the specific underlying pathology that is leading to the coughing. Blocking voltage-gated sodium channels (NaV) will prevent action potential initiation and conduction and therefore prevent sensory communication between the airways and brainstem. In so doing, they would be expected to inhibit evoked cough independently of the nature of the stimulus and underlying pathology...
May 15, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28473457/pharmacologic-characterization-of-amg8379-a-potent-and-selective-small-molecule-sulfonamide-antagonist-of-the-voltage-gated-sodium-channel-nav1-7
#9
Thomas J Kornecook, Ruoyuan Yin, Stephen Altmann, Xuhai Be, Virginia Berry, Christopher P Ilch, Michael Jarosh, Danielle Johnson, Josie H Lee, Sonya G Lehto, Joseph Ligutti, Dong Liu, Jason Luther, David Matson, Danny Ortuno, John Roberts, Kristin Taborn, Jinti Wang, Matthew M Weiss, Violeta Yu, Dawn X D Zhu, Robert T Fremeau, Bryan D Moyer
Potent and selective antagonists of the voltage-gated sodium channel NaV1.7 represent a promising avenue for the development of new chronic pain therapies. We generated a small molecule atropisomer quinolone sulfonamide antagonist AMG8379 and a less active enantiomer AMG8380. Here we show that AMG8379 potently blocks human NaV1.7 channels with an IC50 of 8.5 nM and endogenous tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglion (DRG) neurons with an IC50 of 3.1 nM in whole-cell patch clamp electrophysiology assays using a voltage protocol that interrogates channels in a partially inactivated state...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28450535/sodium-channel-nav1-8-underlies-ttx-resistant-axonal-action-potential-conduction-in-somatosensory-c-fibers-of-distal-cutaneous-nerves
#10
Amanda H Klein, Alina Vyshnevska, Timothy V Hartke, Roberto De Col, Joseph L Mankowski, Brian Turnquist, Frank Bosmans, Peter W Reeh, Martin Schmelz, Richard W Carr, Matthias Ringkamp
Voltage-gated sodium (NaV) channels are responsible for the initiation and conduction of action potentials within primary afferents. The nine NaV channel isoforms recognized in mammals are often functionally divided into tetrodotoxin (TTX)-sensitive (TTX-s) channels (NaV1.1-NaV1.4, NaV1.6-NaV1.7) that are blocked by nanomolar concentrations and TTX-resistant (TTX-r) channels (NaV1.8 and NaV1.9) inhibited by millimolar concentrations, with NaV1.5 having an intermediate toxin sensitivity. For small-diameter primary afferent neurons, it is unclear to what extent different NaV channel isoforms are distributed along the peripheral and central branches of their bifurcated axons...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28425222/class-iii-antiarrhythmic-drugs-amiodarone-and-dronedarone-impair-kir-2-1-backward-trafficking
#11
Yuan Ji, Hiroki Takanari, Muge Qile, Lukas Nalos, Marien J C Houtman, Fee L Romunde, Raimond Heukers, Paul M P van Bergen En Henegouwen, Marc A Vos, Marcel A G van der Heyden
Drug-induced ion channel trafficking disturbance can cause cardiac arrhythmias. The subcellular level at which drugs interfere in trafficking pathways is largely unknown. KIR 2.1 inward rectifier channels, largely responsible for the cardiac inward rectifier current (IK1 ), are degraded in lysosomes. Amiodarone and dronedarone are class III antiarrhythmics. Chronic use of amiodarone, and to a lesser extent dronedarone, causes serious adverse effects to several organs and tissue types, including the heart. Both drugs have been described to interfere in the late-endosome/lysosome system...
October 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28424991/expression-and-role-of-voltage-gated-sodium-channels-in-human-dorsal-root-ganglion-neurons-with-special-focus-on-nav1-7-species-differences-and-regulation-by-paclitaxel
#12
Wonseok Chang, Temugin Berta, Yong Ho Kim, Sanghoon Lee, Seok-Yong Lee, Ru-Rong Ji
Voltage-gated sodium channels (Navs) play an important role in human pain sensation. However, the expression and role of Nav subtypes in native human sensory neurons are unclear. To address this issue, we obtained human dorsal root ganglion (hDRG) tissues from healthy donors. PCR analysis of seven DRG-expressed Nav subtypes revealed that the hDRG has higher expression of Nav1.7 (~50% of total Nav expression) and lower expression of Nav1.8 (~12%), whereas the mouse DRG has higher expression of Nav1.8 (~45%) and lower expression of Nav1...
April 19, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28418213/pain-thresholds-supra-threshold-pain-and-lidocaine-sensitivity-in-patients-with-erythromelalgia-including-the-i848tmutation-in-nav-1-7
#13
T Helås, D Sagafos, I P Kleggetveit, H Quiding, B Jönsson, M Segerdahl, Z Zhang, H Salter, M Schmelz, E Jørum
OBJECTIVES: Nociceptive thresholds and supra-threshold pain ratings as well as their reduction upon local injection with lidocaine were compared between healthy subjects and patients with erythromelalgia (EM). METHODS: Lidocaine (0.25, 0.50, 1.0 or 10 mg/mL) or placebo (saline) was injected intradermally in non-painful areas of the lower arm, in a randomized, double-blind manner, to test the effect on dynamic and static mechanical sensitivity, mechanical pain sensitivity, thermal thresholds and supra-threshold heat pain sensitivity...
April 18, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28380690/chemogenetic-inhibition-of-pain-neurons-in-a-mouse-model-of-osteoarthritis
#14
Rachel E Miller, Shingo Ishihara, Bula Bhattacharyya, Ada Delaney, Daniela M Menichella, Richard J Miller, Anne-Marie Malfait
OBJECTIVE: To determine the ability of drugs that activate inhibitory G protein-coupled receptors (GPCRs) expressed in peripheral voltage-gated sodium channel 1.8 (NaV 1.8)-positive sensory neurons to control osteoarthritis (OA)-associated pain. METHODS: We used designer receptors exclusively activated by a designer drug (DREADD) technology, which employs engineered GPCRs to activate or inhibit neurons upon binding the synthetic ligand clozapine N-oxide (CNO). NaV 1...
July 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28296957/computer-assisted-electromagnetic-navigation-improves-accuracy-in-computed-tomography-guided-interventions-a-prospective-randomized-clinical-trial
#15
RANDOMIZED CONTROLLED TRIAL
Pierre Durand, Alexandre Moreau-Gaudry, Anne-Sophie Silvent, Julien Frandon, Emilie Chipon, Maud Médici, Ivan Bricault
PURPOSE: To assess the accuracy and usability of an electromagnetic navigation system designed to assist Computed Tomography (CT) guided interventions. MATERIALS AND METHODS: 120 patients requiring a percutaneous CT intervention (drainage, biopsy, tumor ablation, infiltration, sympathicolysis) were included in this prospective randomized trial. Nineteen radiologists participated. Conventional procedures (CT group) were compared with procedures assisted by a navigation system prototype using an electromagnetic localizer to track the position and orientation of a needle holder (NAV group)...
2017: PloS One
https://www.readbyqxmd.com/read/28225079/multiple-sodium-channel-isoforms-mediate-the-pathological-effects-of-pacific-ciguatoxin-1
#16
Marco C Inserra, Mathilde R Israel, Ashlee Caldwell, Joel Castro, Jennifer R Deuis, Andrea M Harrington, Angelo Keramidas, Sonia Garcia-Caraballo, Jessica Maddern, Andelain Erickson, Luke Grundy, Grigori Y Rychkov, Katharina Zimmermann, Richard J Lewis, Stuart M Brierley, Irina Vetter
Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216001/loperamide-inhibits-sodium-channels-to-alleviate-inflammatory-hyperalgesia
#17
Ying Wu, Beiyan Zou, Lingli Liang, Min Li, Yuan-Xiang Tao, Haibo Yu, Xiaoliang Wang, Min Li
Previous studies demonstrated that Loperamide, originally known as an anti-diarrheal drug, is a promising analgesic agent primarily targeting mu-opioid receptors. However some evidences suggested that non-opioid mechanisms may be contributing to its analgesic effect. In the present study, Loperamide was identified as a Nav1.7 blocker in a pilot screen. In HEK293 cells expressing Nav1.7 sodium channels, Loperamide blocked the resting state of Nav1.7 channels (IC50 = 1.86 ± 0.11 μM) dose-dependently and reversibly...
February 16, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28166971/functional-and-molecular-characterization-of-voltage-gated-sodium-channel-nav-1-8-in-bull-spermatozoa
#18
Dharmendra Singh Chauhan, Dilip Kumar Swain, Nadeem Shah, Hanuman Prasad Yadav, Udayraj P Nakade, Vijay Kumar Singh, Rajesh Nigam, Sarvajeet Yadav, Satish Kumar Garg
The aim of our study was to characterize the voltage gated sodium channel Nav 1.8 in bull spermatozoa. Forty ejaculates were collected from four Hariana bulls and semen samples were pooled in view of the nonsignificant variations between different ejaculates. Functional characterization was undertaken using A-803467, a selective blocker of Nav1.8, and veratridine as an opener of the voltage gated sodium channels while molecular characterization was done using western blotting and indirect immunofluorescence assays...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28105664/visceral-and-somatic-pain-modalities-reveal-nav-1-7-independent-visceral-nociceptive-pathways
#19
James R F Hockley, Rafael González-Cano, Sheridan McMurray, Miguel A Tejada-Giraldez, Cian McGuire, Antonio Torres, Anna L Wilbrey, Vincent Cibert-Goton, Francisco R Nieto, Thomas Pitcher, Charles H Knowles, José Manuel Baeyens, John N Wood, Wendy J Winchester, David C Bulmer, Cruz Miguel Cendán, Gordon McMurray
KEY POINTS: Voltage-gated sodium channels play a fundamental role in determining neuronal excitability. Specifically, voltage-gated sodium channel subtype NaV 1.7 is required for sensing acute and inflammatory somatic pain in mice and humans but its significance in pain originating from the viscera is unknown. Using comparative behavioural models evoking somatic and visceral pain pathways, we identify the requirement for NaV 1.7 in regulating somatic (noxious heat pain threshold) but not in visceral pain signalling...
April 15, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/27903401/-impact-of-neuronal-sodium-channel-nav-1-8-on-cardiac-function-and-cardiovascular-diseases
#20
(no author information available yet)
No abstract text is available yet for this article.
November 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
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