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Nav 1.8

Yao Li, Feng Cao, Tat Thang Vo Doan, Hirotaka Sato
The mechanisms and principles of insect flight have long been investigated by researchers working on micro and nano air vehicles (MAVs/NAVs). However, studies of insect flight maneuvers require high speed filming and high spatial resolution in a small experimental space, or the tethering of the insect to a fixed place. Under such artificial conditions, the insects may deviate its flying behavior from that of regular flight. In this study, we mounted a tiny wireless system, or 'backpack', on live beetles (Mecynorrhina torquata; length 62 ± 8 mm; mass 7...
2016: Bioinspiration & Biomimetics
Anatoly Uzdensky, Svetlana Demyanenko, Grigory Fedorenko, Tayana Lapteva, Alexej Fedorenko
After ischemic stroke, cell damage propagates from infarct core to surrounding tissues (penumbra). To reveal proteins involved in neurodegeneration and neuroprotection in penumbra, we studied protein expression changes in 2-mm ring around the core of photothrombotic infarct induced in the rat brain cortex by local laser irradiation after administration of Bengal Rose. The ultrastructural study showed edema and degeneration of neurons, glia, and capillaries. Morphological changes gradually decreased across the penumbra...
June 21, 2016: Molecular Neurobiology
Liyong Zhang, Feng Zhou, Lei Huang, Qiuping Wu, Jinxiang Zheng, Yeda Wu, Kun Yin, Jianding Cheng
Sudden unexplained nocturnal death syndrome (SUNDS) remains an autopsy negative entity with unknown etiology to both forensic pathologists and physicians. The electrocardiogram (ECG) characteristics and clinical phenotype of SUNDS survivors strongly suggest that SUNDS shares some similarities with Brugada syndrome (BrS). Recently, the variants of sodium channel Nav 1.8 coding gene SCN10A were identified to be associated with BrS. Here, we investigated the association of SCN10A gene variants with 105 sporadic SUNDS victims and 22 BrS cases in the Chinese Han population...
June 7, 2016: International Journal of Legal Medicine
Parashar Thapa, Chino C Cabalteja, Edwin E Philips, Michael J Espiritu, Steve Peigneur, Bea G Mille, Jan Tytgat, Theodore R Cummins, Jon-Paul Bingham
Tert-butyloxycarbonyl (t-Boc)-based native chemical ligation (NCL) techniques commonly employ hydrogen fluoride (HF) to create the thioester fragment required for the ligation process. Our research aimed to assess the replacement of HF with Trifluoromethanesulfonic acid (TFMSA). Here we examined a 33 amino acid test peptide, Huwentoxin-I (HwTx-I) as a novel candidate for our TFMSA cleavage protocol. Structurally HwTx-I has an X-Cys(16) -Cys(17) -X sequence mid-region, which makes it an ideal candidate for NCL...
September 2016: Biopolymers
Avantika Banerjee, Karan Sarode, Atif Mohammad, Emmanouil S Brilakis, Subhash Banerjee, Gail A Shammas, Nicolas W Shammas
BACKGROUND: The risk of distal embolization (DE) during infrainguinal peripheral artery interventions (PAI) is often mitigated by the use of embolic protection devices. There are limited data on the use of filters with the Jetstream (JS) atherectomy device, a rotational cutter with aspiration capacity. The Nav-6 filter is uniquely suited for use with the JS due to its wire compatibility and detachment from the filter; however, data on the off-label use of this combination have not been reported...
August 2016: Journal of Invasive Cardiology
Carsten Stoetzer, Bastian Papenberg, Thorben Doll, Marc Völker, Joerg Heineke, Marcus Stoetzer, Florian Wegner, Andreas Leffler
Duloxetine and venlafaxine are selective serotonin-norepinephrine-reuptake-inhibitors used as antidepressants and co-analgesics. While venlafaxine rather than duloxetine induce cardiovascular side-effects, neither of the substances are regarded cardiotoxic. Inhibition of cardiac Na(+)-channels can be associated with cardiotoxicity, and duloxetine was demonstrated to block neuronal Na(+)-channels. The aim of this study was to investigate if the non-life threatening cardiotoxicities of duloxetine and venlafaxine correlate with a weak inhibition of cardiac Na(+)-channels...
July 15, 2016: European Journal of Pharmacology
Tal Hoffmann, Katrin Kistner, Mohammed Nassar, Peter W Reeh, Christian Weidner
KEY POINTS: This study examines conduction in peripheral nerves and its use dependence in tetrodotoxin-resistant (TTXr) sodium channel (Nav 1.8, Nav 1.9) knockout and wildtype animals. We observed use-dependent decreases of single fibre and compound action potential amplitude in peripheral mouse C-fibres (wildtype). This matches the previously published hypothesis that increased Na/K-pump activity is not the underlying mechanism for use-dependent changes of neural conduction. Knocking out TTXr sodium channels influences use-dependent changes of conductive properties (action potential amplitude, latency, conduction safety) in the order Nav 1...
October 1, 2016: Journal of Physiology
C Stoetzer, T Doll, T Stueber, C Herzog, F Echtermeyer, F Greulich, C Rudat, A Kispert, F Wegner, A Leffler
The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine...
June 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Sayono Sayono, Anggie Puspa Nur Hidayati, Sukmal Fahri, Didik Sumanto, Edi Dharmana, Suharyo Hadisaputro, Puji Budi Setia Asih, Din Syafruddin
The emergence of insecticide resistant Aedes aegypti mosquitoes has hampered dengue control efforts. WHO susceptibility tests, using several pyrethroid compounds, were conducted on Ae. aegypti larvae that were collected and raised to adulthood from Semarang, Surakarta, Kudus and Jepara in Java. The AaNaV gene fragment encompassing kdr polymorphic sites from both susceptible and resistant mosquitoes was amplified, and polymorphisms were associated with the resistant phenotype. The insecticide susceptibility tests demonstrated Ae, aegypti resistance to the pyrethroids, with mortality rates ranging from 1...
2016: PloS One
Kung-Wen Lu, Chao-Kuei Hsu, Ching-Liang Hsieh, Jun Yang, Yi-Wen Lin
Transient receptor potential vanilloid 1 (TRPV1) and associated signaling pathways have been reported to be increased in inflammatory pain signaling. There are accumulating evidences surrounding the therapeutic effect of electroacupuncture (EA). EA can reliably attenuate the increase of TRPV1 in mouse inflammatory pain models with unclear signaling mechanisms. Moreover, the difference in the clinical therapeutic effects between using the contralateral and ipsilateral acupoints has been rarely studied. We found that inflammatory pain, which was induced by injecting the complete Freund's adjuvant (CFA), (2...
2016: Scientific Reports
A Laux-Biehlmann, J Boyken, H Dahllöf, N Schmidt, T M Zollner, J Nagel
BACKGROUND: Chronic pelvic pain (CPP) is a high burden for patients and society. It affects 15-24% of women in reproductive age and is an area of high unmet medical need. CPP can be caused by a wide range of visceral diseases such as abdominal infections, gastrointestinal or gynaecological diseases like endometriosis. Despite the high medical need for this condition, pharmacological approaches are hampered by the limited number of available methods for the behavioural evaluation of pain in inflammation-driven animal models of pelvic pain...
May 2016: European Journal of Pain: EJP
K-U Kern, T Weiser
BACKGROUND: Neuropathic pain is difficult to treat and available options are frequently not sufficient. The expectorant ambroxol also works as a strong local anesthetic and blocks sodium channels about 40 times more potently than lidocaine. Ambroxol preferentially inhibits the channel subtype Nav 1.8, which is expressed particularly in nociceptive C fibers. Due to the low toxicity, topical ambroxol seemed to represent a reasonable therapeutic attempt for treatment of neuropathic pain resistant to other standard options...
December 2015: Der Schmerz
Céline M Bourdin, Nathalie C Guérineau, Laurence Murillo, Sophie Quinchard, Ke Dong, Christian Legros
In Drosophila melanogaster, the functions of voltage-gated sodium (Nav) channels are modulated by TipE and its orthologs. Here, we describe a novel TipE homolog of the American cockroach, Periplaneta americana, called PaTipE. Like DmTipE, PaTipE mRNAs are ubiquitously expressed. Surprisingly, PaTipE mRNA was undetectable in neurosecretory cells identified as dorsal unpaired median neurons. Phylogenetic analysis placed this new sequence in TipE clade, indicating an independent evolution from a common ancestor...
November 2015: Insect Biochemistry and Molecular Biology
Kuang-I Cheng, Hung-Chen Wang, Yi-Chia Wu, Kuang-Yi Tseng, Yi-Ta Chuang, Chao-Wen Chou, Ping-Luen Chen, Lin-Li Chang, Chung-Sheng Lai
OBJECTIVE: Peripheral nerve block guidance with a nerve stimulator or echo may not prevent intrafascicular injury. This study investigated whether intrafascicular lidocaine induces peripheral neuropathic pain and whether this pain can be alleviated by minocycline administration. METHODS: A total of 168 male Sprague-Dawley rats were included. In experiment 1, 2% lidocaine (0.1 mL) was injected into the left sciatic nerve. Hindpaw responses to thermal and mechanical stimuli, and sodium channel and activating transcription factor (ATF-3) expression in dorsal root ganglion (DRG) and glial cells in the spinal dorsal horn (SDH), were measured on days 4, 7, 14, 21, and 28...
June 2016: Clinical Journal of Pain
Audrey J Stone, Steven W Copp, Marc P Kaufman
Voltage-gated sodium channels (NaV) 1.7 are highly expressed on the axons of somatic afferent neurons and are thought to play an important role in the signaling of inflammatory pain. NaV 1.7 channels are classified as tetrodotoxin (TTX)-sensitive, meaning that they are blocked by TTX concentrations of less than 300 nM. These findings prompted us to determine in decerebrated, unanesthetized rats, the role played by NaV 1.7 channels in the transmission of muscle afferent input evoking the exercise pressor reflex...
November 15, 2015: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Albert G Remacle, Sonu Kumar, Khatereh Motamedchaboki, Piotr Cieplak, Swathi Hullugundi, Jennifer Dolkas, Veronica I Shubayev, Alex Y Strongin
Congenital insensitivity to pain (CIP) or congenital analgesia is a rare monogenic hereditary condition. This disorder is characterized by the inability to perceive any form of pain. Nonsense mutations in Nav.1.7, the main pain signaling voltage-gated sodium channel, lead to its truncations and, consequently, to the inactivation of the channel functionality. However, a non-truncating homozygously inherited missense mutation in a Bedouin family with CIP (Nav1.7-R907Q) has also been reported. Based on our currently acquired in-depth knowledge of matrix metalloproteinase (MMP) cleavage preferences, we developed the specialized software that predicts the presence of the MMP cleavage sites in the peptide sequences...
September 18, 2015: Journal of Biological Chemistry
Leida Calegário de Oliveira, Fabiana V Campos, Suely Gomes Figueiredo, Marta N Cordeiro, Beatriz R Adaime, Michael Richardson, Adriano M C Pimenta, Marie-France Martin-Eauclaire, Paulo S L Beirão, Maria Elena De Lima
A potent insecticidal toxin, β/δ-PrIT1, molecular mass of 5598.86 [M+H](+), was characterized from Phoneutria reidyi spider venom. Its partial amino acid sequence showed high similarity with insecticidal spider toxins from the genus Phoneutria. β/δ-PrIT1 was very toxic (LD50 = 4 nmol/g) to flies (Musca domestica), but not to mice (Mus musculus). Kinetic studies showed that (125)I-β/δ-PrIT1 binds to two distinct sites in insect sodium channels, with close affinity (Kd1 = 34.7 pM and Kd2 = 35.1 pM). Its association is rather fast (t1/2(1) = 1...
September 15, 2015: Toxicon: Official Journal of the International Society on Toxinology
Benjamin Berte, Jatin Relan, Frederic Sacher, Xavier Pillois, Anthony Appetiti, Seigo Yamashita, Saagar Mahida, Frederic Casassus, Darren Hooks, Jean-Marc Sellal, Sana Amraoui, Arnaud Denis, Nicolas Derval, Hubert Cochet, Mélèze Hocini, Michel Haïssaguerre, Rukshen Weerasooriya, Pierre Jaïs
BACKGROUND: Substrate-based VT ablation is mostly based on maps acquired with ablation catheters. We hypothesized that multipolar mapping catheters are more effective for identification of scar and local abnormal ventricular activity (LAVA). METHODS AND RESULTS: Phase1: In a sheep infarction model (2 months post-infarction), substrate mapping and LAVA tagging (CARTO(®) 3) was performed, using a Navistar (NAV) vs. a PentaRay (PR) catheter (Biosense Webster). Phase2: Consecutive VT ablation patients from a single center underwent NAV vs...
July 22, 2015: Journal of Cardiovascular Electrophysiology
Richard C Oude Voshaar, Date C van der Veen, Isabelle Hunt, Nav Kapur
OBJECTIVE: Comorbid anxiety in depression increases the risk of suicidal ideation and behavior, although data on death by suicide are scarce. We compared characteristics of depressed elderly patients with and without anxiety disorders who died by suicide. METHODS: From a 16-year clinical survey of all suicides in the UK (n = 25,128), we identified 1909 cases aged ≥60 years with a primary diagnosis of depression and no comorbidity other than anxiety disorders...
February 2016: International Journal of Geriatric Psychiatry
Thalita S Camargos, Frank Bosmans, Solange C Rego, Caroline B F Mourão, Elisabeth F Schwartz
We identified Tf2, the first β-scorpion toxin from the venom of the Brazilian scorpion Tityus fasciolatus. Tf2 is identical to Tb2-II found in Tityus bahiensis. We found that Tf2 selectively activates human (h)Nav1.3, a neuronal voltage-gated sodium (Nav) subtype implicated in epilepsy and nociception. Tf2 shifts hNav1.3 activation voltage to more negative values, thereby opening the channel at resting membrane potentials. Seven other tested mammalian Nav channels (Nav1.1-1.2; Nav1.4-1.8) expressed in Xenopus oocytes are insensitive upon application of 1 μM Tf2...
2015: PloS One
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