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https://www.readbyqxmd.com/read/29134638/inhibition-of-acid-sensing-ion-channels-by-diminazene-and-apetx2-evoke-partial-and-highly-variable-antihyperalgesia-in-a-rat-model-of-inflammatory-pain
#1
Jia Yu Peppermint Lee, Natalie J Saez, Ben Cristofori-Armstrong, Raveendra Anangi, Glenn F King, Maree T Smith, Lachlan D Rash
BACKGROUND AND PURPOSE: Acid-sensing ion channels (ASICs) are primary acid sensors in mammals, with the ASIC1b and ASIC3 subtypes being involved in peripheral nociception. The antiprotozoal drug diminazene is a moderately potent ASIC inhibitor but its analgesic activity has not been assessed. EXPERIMENTAL APPROACH: We determined the ASIC subtype selectivity of diminazene and the mechanism by which it inhibits ASICs using voltage-clamp electrophysiology of Xenopus oocytes expressing ASICs 1-3...
November 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29130788/complex-action-of-tyramine-tryptamine-and-histamine-on-native-and-recombinant-asics
#2
Oleg I Barygin, Margarita S Komarova, Tatyana B Tikhonova, Anastasiia S Korosteleva, Maxim V Nikolaev, Lev G Magazanik, Denis B Tikhonov
Proton-gated channels of the ASIC family are widely distributed in the mammalian brain, and, according to the recent data, participate in synaptic transmission. However, ASIC-mediated currents are small, and special efforts are required to detect them. This prompts the search for endogenous ASIC ligands, which can activate or potentiate these channels. A recent finding of the potentiating action of histamine on recombinant homomeric ASIC1a has directed attention to amine-containing compounds. In the present study, we have analyzed the action of histamine, tyramine, and tryptamine on native and recombinant ASICs...
November 13, 2017: Channels
https://www.readbyqxmd.com/read/29128507/moderators-and-mediators-of-effects-of-unloading-shoes-on-knee-pain-in-people-with-knee-osteoarthritis-an-exploratory-analysis-of-the-shark-randomised-controlled-trial
#3
Kade L Paterson, Jessica Kasza, Kim L Bennell, Tim V Wrigley, Ben R Metcalf, Penny K Campbell, David J Hunter, Rana S Hinman
OBJECTIVE: To investigate moderators and biomechanical mediators of effects of unloading shoes on knee pain in people with knee osteoarthritis (OA). METHODS: Exploratory analysis from 164 participants in a clinical trial comparing unloading (ASICS GEL-Melbourne OA) to conventional walking shoes. The primary outcome was 6-month change in knee pain (11-point numerical rating scale). Moderators included baseline peak knee adduction moment (KAM), radiographic severity (Kellgren & Lawrence (KL) scale), body mass, foot posture, neuropathic pain and diffuse knee pain...
November 8, 2017: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29123030/the-nonproton-ligand-of-acid-sensing-ion-channel-3-activates-mollusk-specific-fanac-channels-via-a-mechanism-independent-of-native-fmrfamide-peptide
#4
Xiao-Na Yang, You-Ya Niu, Yan Liu, Yang Yang, Wang Jin, Xiao-Yang Cheng, Hong Liang, Heng-Shan Wang, You-Min Hu, Xiang-Yang Lu, Michael X Zhu, Tian-Le Xu, Yun Tian, Ye Yu
The degenerin/epithelial sodium channel (DEG/ENaC) superfamily of ion channels contains subfamilies with diverse functions that are fundamental to many physiological and pathological processes, ranging from synaptic transmission to epileptogenesis. The absence in mammals of some DEG/ENaCs subfamily orthologs such as FMRFamide peptide-activated sodium channels (FaNaCs), which have been identified only in mollusks, indicates that the various subfamilies diverged early in evolution. We recently reported that the nonproton agonist 2-guanidine-4-methylquinazoline (GMQ) activates acid-sensing ion channels (ASICs), a DEG/ENaC subfamily mainly in mammals, in the absence of acidosis...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29111855/neuroprotective-effects-of-inhibitors-of-acid-sensing-ion-channels-asics-in-optic-nerve-crush-model-in-rodents
#5
Dorota L Stankowska, Brett H Mueller, Hidehiro Oku, Tsunehiko Ikeda, Adnan Dibas
PURPOSE: The purpose of the current study was to assess the potential involvement of acid-sensing ion channel 1 (ASIC1) in retinal ganglion cell (RGC) death and investigate the neuroprotective effects of inhibitors of ASICs in promoting RGC survival following optic nerve crush (ONC). RESULTS: ASIC1 protein was significantly increased in optic nerve extracts at day 7 following ONC in rats. Activated calpain-1 increased at 2 and 7 days following ONC as evidenced by increased degradation of α-fodrin, known substrate of calpain...
November 7, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29099043/involvement-of-opioid-system-trpm8-and-asic-receptors-in-antinociceptive-effect-of-arrabidaea-brachypoda-dc-bureau
#6
Vinícius Peixoto Rodrigues, Cláudia Quintino da Rocha, Larissa Lucena Périco, Raquel de Cássia Dos Santos, Rie Ohara, Catarine Massucato Nishijima, Emerson Ferreira Queiroz, Jean-Luc Wolfender, Lúcia Regina Machado da Rocha, Adair Roberto Soares Santos, Wagner Vilegas, Clélia Akiko Hiruma-Lima
Arrabidaea brachypoda (DC) Bureau is a medicinal plant found in Brazil. Known as "cipó-una", it is popularly used as a natural therapeutic agent against pain and inflammation. This study evaluated the chemical composition and antinociceptive activity of the dichloromethane fraction from the roots of A. brachypoda (DEAB) and its mechanism of action. The chemical composition was characterized by high-performance liquid chromatography, and this fraction is composed only of dimeric flavonoids. The antinociceptive effect was evaluated in formalin and hot plate tests after oral administration (10-100 mg/kg) in male Swiss mice...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29059850/rodent-wearable-ultrasound-system-for-wireless-neural-recording
#7
David K Piech, Joshua E Kay, Bernhard E Boser, Michel M Maharbiz
Advances in minimally-invasive, distributed biological interface nodes enable possibilities for networks of sensors and actuators to connect the brain with external devices. The recent development of the neural dust sensor mote has shown that utilizing ultrasound backscatter communication enables untethered sub-mm neural recording devices. These implanted sensor motes require a wearable external ultrasound interrogation device to enable in-vivo, freely-behaving neural interface experiments. However, minimizing the complexity and size of the implanted sensors shifts the power and processing burden to the external interrogator...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29059849/an-integrated-multichannel-neural-recording-analog-front-end-asic-with-area-efficient-driven-right-leg-circuit
#8
Tao Tang, Wang Ling Goh, Lei Yao, Jia Hao Cheong, Yuan Gao
This paper describes an integrated multichannel neural recording analog front end (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the system common mode rejection ratio (CMRR). The proposed AFE consists of an AC-coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a 10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less DRL design achieves 90% chip area reduction with enhanced CMRR performance, making it ideal for multichannel biomedical recording applications...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29058095/potentiation-and-block-of-asic1a-by-memantine
#9
Vasiliy Y Shteinikov, Tatiana B Tikhonova, Vyacheslav S Korkosh, Denis B Tikhonov
Acid-sensing ion channels (ASICs) are modulated by various classes of ligands, including the recently described hydrophobic monoamines, which inhibit and potentiate ASICs in a subunit-specific manner. In particular, memantine inhibits ASIC1a and potentiates ASIC2a homomers. The aim of the present work was to characterize action mechanism of memantine on recombinant ASIC1a expressed in CHO (Chinese hamster ovary) cells. We have demonstrated that effect of memantine on ASIC1a strongly depends on membrane voltage, conditioning pH value and application protocol...
October 20, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/29057936/glioblastoma-cancer-stem-cell-lines-express-functional-acid-sensing-ion-channels-asic1a-and-asic3
#10
Yuemin Tian, Pia Bresenitz, Anna Reska, Laila El Moussaoui, Christoph Patrick Beier, Stefan Gründer
Acidic microenvironment is commonly observed in tumour tissues, including glioblastoma (GBM), the most aggressive and lethal brain tumour in adults. Acid sensing ion channels (ASICs) are neuronal voltage-insensitive sodium channels, which are sensors of extracellular protons. Here we studied and functionally characterized ASICs in two primary glioblastoma stem cell lines as cell culture models. We detected transcripts of the ACCN2 and ACCN3 genes, coding for ASIC1 and ASIC3, respectively, but not transcripts of ACCN1 (coding for ASIC2)...
October 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29056828/acid-sensing-ion-channels-as-potential-therapeutic-targets-in-neurodegeneration-and-neuroinflammation
#11
REVIEW
Audrey Ortega-Ramírez, Rosario Vega, Enrique Soto
Acid-sensing ion channels (ASICs) are a family of proton-sensing channels that are voltage insensitive, cation selective (mostly permeable to Na(+)), and nonspecifically blocked by amiloride. Derived from 5 genes (ACCN1-5), 7 subunits have been identified, 1a, 1b, 2a, 2b, 3, 4, and 5, that are widely expressed in the peripheral and central nervous system as well as other tissues. Over the years, different studies have shown that activation of these channels is linked to various physiological and pathological processes, such as memory, learning, fear, anxiety, ischemia, and multiple sclerosis to name a few, so their potential as therapeutic targets is increasing...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29054733/disrupted-ionic-homeostasis-in-ischemic-stroke-and-new-therapeutic-targets
#12
REVIEW
Hui-Jie Hu, Mingke Song
BACKGROUND: Stroke is a leading cause of long-term disability. All neuroprotectants targeting excitotoxicity have failed to become stroke medications. In order to explore and identify new therapeutic targets for stroke, we here reviewed present studies of ionic transporters and channels that are involved in ischemic brain damage. METHOD: We surveyed recent literature from animal experiments and clinical reports in the databases of PubMed and Elsevier ScienceDirect to analyze ionic mechanisms underlying ischemic cell damage and suggest promising ideas for stroke therapy...
October 17, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/29044528/endomorphins-potentiate-asic-currents-and-enhance-the-lactic-acid-mediated-increase-in-arterial-blood-pressure-effects-amplified-in-hindlimb-ischemia
#13
Mohamed Farrag, Julie K Drobish, Henry L Puhl, Joyce S Kim, Paul B Herold, Marc P Kaufman, Victor Ruiz-Velasco
Chronic muscle ischemia leads to accumulation of lactic acid and other inflammatory mediators with a subsequent drop in interstitial pH. Acid-sensing ion channels (ASICs), expressed in thin muscle afferents, sense the decrease in pH and evoke a pressor reflex known to increase mean arterial pressure. The naturally occurring endomorphins are also released by primary afferents under ischemic conditions. We examined whether high affinity mu opioid receptor (MOR) agonists, endomorphin-1 (E-1) and -2 (E-2), modulate ASIC currents and the lactic acid-mediated pressor reflex...
October 16, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/29039242/computational-elucidation-mutational-and-hot-spot-based-designing-of-potential-inhibitors-against-human-acid-sensing-ion-channels-hasic-1a-to-treatment-of-various-physiological-conditions
#14
Anurag Singh Chauhan, Md Yousuf Ansari, Rani Mansuri, Manas Ranjan Dikhit, Vahab Ali, Ganesh Chandra Sahoo, Pradeep Das
Acid-sensing ion channels (ASICs) are ligand/proton-gated ion channels belonging to the family of the degenerin/epithelial Na(+) channel (DEG/ENaC). They function as a sodium-selective pore for Ca(2+) entry into neuronal cells during pathological conditions. The blocking of this channel has therapeutic importance, because at basal physiological pH (7.2), it is in a closed state and under a more acidic condition, and the ASIC1a ion channel is activated. To investigate the different states of the hASIC1a channel based on mutational analysis, structure based virtual screening and molecular dynamics simulation studies...
October 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/29025967/diminazene-is-a-slow-pore-blocker-of-acid-sensing-ion-channel-1a-asic1a
#15
Axel Schmidt, Giulia Rossetti, Sylvia Joussen, Stefan Grunder
Acid-sensing ion channels (ASICs) are neuronal receptors for extracellular protons. They contribute to the excitatory postsynaptic current and to the detection of painful acidosis. Moreover, they are activated during peripheral inflammation and acidosis associated with various neuronal disorders such as stroke and neuro-inflammation, rendering them interesting drug targets. Diminazene aceturate is a small molecule inhibitor of ASICs with a reported apparent affinity in the low micromolar range, making it an interesting lead compound...
October 12, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28970722/pharmacological-evaluation-of-nsaid-induced-gastropathy-as-a-translatable-model-of-referred-visceral-hypersensitivity
#16
Michele Hummel, Terri Knappenberger, Meghan Reilly, Garth T Whiteside
AIM: To evaluate whether non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastropathy is a clinically predictive model of referred visceral hypersensitivity. METHODS: Gastric ulcer pain was induced by the oral administration of indomethacin to male, CD1 mice (n = 10/group) and then assessed by measuring referred abdominal hypersensitivity to tactile application. A diverse range of pharmacological mechanisms contributing to the pain were subsequently investigated...
September 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28964169/note-a-10-gbps-real-time-post-processing-free-physical-random-number-generator-chip
#17
Yi Qian, Futian Liang, Xinzhe Wang, Feng Li, Lian Chen, Ge Jin
A random number generator with high data rate, small size, and low power consumption is essential for a certain quantum key distribution (QKD) system. We designed a 10 Gbps random number generator ASIC, TRNG2016, for the QKD system. With a 6 mm × 6 mm QFN48 package, TRNG2016 has 10 independent physical random number generation channels, and each channel can work at a fixed frequency up to 1 Gbps. The random number generated by TRNG2016 can pass the NIST statistical tests without any post-processing. With 3...
September 2017: Review of Scientific Instruments
https://www.readbyqxmd.com/read/28956859/an-efficient-hardware-circuit-for-spike-sorting-based-on-competitive-learning-networks
#18
Huan-Yuan Chen, Chih-Chang Chen, Wen-Jyi Hwang
This study aims to present an effective VLSI circuit for multi-channel spike sorting. The circuit supports the spike detection, feature extraction and classification operations. The detection circuit is implemented in accordance with the nonlinear energy operator algorithm. Both the peak detection and area computation operations are adopted for the realization of the hardware architecture for feature extraction. The resulting feature vectors are classified by a circuit for competitive learning (CL) neural networks...
September 28, 2017: Sensors
https://www.readbyqxmd.com/read/28956226/evolutionary-and-neural-computing-based-decision-support-system-for-disease-diagnosis-from-clinical-data-sets-in-medical-practice
#19
M Sudha
As a recent trend, various computational intelligence and machine learning approaches have been used for mining inferences hidden in the large clinical databases to assist the clinician in strategic decision making. In any target data the irrelevant information may be detrimental, causing confusion for the mining algorithm and degrades the prediction outcome. To address this issue, this study attempts to identify an intelligent approach to assist disease diagnostic procedure using an optimal set of attributes instead of all attributes present in the clinical data set...
September 27, 2017: Journal of Medical Systems
https://www.readbyqxmd.com/read/28955199/endogenous-isoquinoline-alkaloids-agonists-of-acid-sensing-ion-channel-type-3
#20
Dmitry I Osmakov, Sergey G Koshelev, Yaroslav A Andreev, Sergey A Kozlov
Acid-sensing ion channels (ASICs) ASIC3 expressed mainly in peripheral sensory neurons play an important role in pain perception and inflammation development. In response to acidic stimuli, they can generate a unique biphasic current. At physiological pH 7.4, human ASIC3 isoform (hASIC3) is desensitized and able to generate only a sustained current. We found endogenous isoquinoline alkaloids (EIAs), which restore hASIC3 from desensitization and recover the transient component of the current. Similarly, rat ASIC3 isoform (rASIC3) can also be restored from desensitization (at pH < 7...
2017: Frontiers in Molecular Neuroscience
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