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K+ Channel Modulators Product ID Product Name Description D3209 Diclofenac Sodium Salt NSAID; COX-1/2 Inhibitor, Potential K+ Channel Modulator
K+ Channel Modulators Product ID Product Name Description D3209 Diclofenac Sodium Salt NSAID; COX-1/2 inhibitor, potential K+ channel modulator. G4597 18β-Glycyrrhetinic Acid Triterpene glycoside found in Glycyrrhiza; 15-HPGDH inhibitor, hERG and KCNA3/Kv1.3 K+ channel blocker. A4440 Allicin Organosulfur found in garlic, binds DNA; inwardly rectifying K+ channel activator, L-type Ca2+ channel blocker. P6852 Propafenone Hydrochloride β-adrenergic antagonist, Kv1.4 and K2P2 K+ channel blocker. P2817 Phentolamine Hydrochloride ATP-sensitive K+ channel activator, α-adrenergic antagonist. P2818 Phentolamine Methanesulfonate ATP-sensitive K+ channel activator, α-adrenergic antagonist. T7056 Troglitazone Thiazolidinedione; PPARγ agonist, ATP-sensitive K+ channel blocker. G3556 Ginsenoside Rg3 Triterpene saponin found in species of Panax; γ2 GABA-A agonist, Kv7.1 K+ channel activator, α10 nAChR antagonist. P6958 Protopanaxatriol Triterpene sapogenin found in species of Panax; GABA-A/C antagonist, slow-activating delayed rectifier K+ channel blocker. V3355 Vindoline Semi-synthetic vinca alkaloid found in Catharanthus; Kv2.1 K+ channel blocker and H+/K+ ATPase inhibitor. A5037 Amiodarone Hydrochloride Voltage-gated Na+, Ca2+, K+ channel blocker, α/β-adrenergic antagonist, FIASMA. B8262 Bupivacaine Hydrochloride Monohydrate Amino amide; voltage-gated Na+, BK/SK, Kv1, Kv3, TASK-2 K+ channel inhibitor. C0270 Carbamazepine GABA potentiator, voltage-gated Na+ and ATP-sensitive K+ channel blocker. C9711 Cyclovirobuxine D Found in Buxus; hERG K+ channel inhibitor. D5649 Domperidone D2/3 antagonist, hERG K+ channel blocker. G4535 Glimepiride Sulfonylurea; ATP-sensitive K+ channel blocker. G4634 Glipizide Sulfonylurea; ATP-sensitive K+ channel blocker. I5034 Imiquimod Imidazoquinoline nucleoside analog; TLR-7/8 agonist, KCNA1/Kv1.1 and KCNA2/Kv1.2 K+ channel partial agonist, TREK-1/ K2P2 and TRAAK/K2P4 K+ channel blocker. -
Therapeutic Potential of RQ-00311651, a Novel T-Type Ca
Research Paper Therapeutic potential of RQ-00311651, a novel T-type Ca21 channel blocker, in distinct rodent models for neuropathic and visceral pain Fumiko Sekiguchia, Yuma Kawaraa, Maho Tsubotaa, Eri Kawakamia, Tomoka Ozakia, Yudai Kawaishia, Shiori Tomitaa, Daiki Kanaokaa, Shigeru Yoshidab, Tsuyako Ohkuboc, Atsufumi Kawabataa,* Abstract 21 T-type Ca channels (T channels), particularly Cav3.2 among the 3 isoforms, play a role in neuropathic and visceral pain. We thus characterized the effects of RQ-00311651 (RQ), a novel T-channel blocker, in HEK293 cells transfected with human Cav3.1 or 21 Cav3.2 by electrophysiological and fluorescent Ca signaling assays, and also evaluated the antiallodynic/antihyperalgesic activity of RQ in somatic, visceral, and neuropathic pain models in rodents. RQ-00311651 strongly suppressed T currents when tested at holding potentials of 265 ; 260 mV, but not 280 mV, in the Cav3.1- or Cav3.2-expressing cells. RQ-00311651 also inhibited high K1-induced Ca21 signaling in those cells. In mice, RQ, administered intraperitoneally (i.p.) at 5 to 20 mg/kg or orally at 20 to 40 mg/kg, significantly suppressed the somatic hyperalgesia and visceral pain-like nociceptive behavior/referred hyperalgesia caused by intraplantar and intracolonic administration of NaHS or Na2S, H2S donors, respectively, which involve the enhanced activity of Cav3.2 channels. RQ-00311651, given i.p. at 5 to 20 mg/kg, exhibited antiallodynic or antihyperalgesic activity in rats with spinal nerve injury–induced neuropathy or in rats and mice with paclitaxel-induced neuropathy. Oral and i.p. RQ at 10 to 20 mg/kg also suppressed the visceral nociceptive behavior and/or referred hyperalgesia accompanying cerulein-induced acute pancreatitis and cyclophosphamide-induced cystitis in mice. -
Z944: an Oral T-Type Calcium Channel Modulator for the Treatment of Pain Margaret S
Z944: An oral T-type calcium channel modulator for the treatment of pain Margaret S. Lee, PhD Ion Channel Retreat 2014, June 25, 2014 T-type Calcium Channels: A Novel Target for Pain and Other CNS Disorders • T-type calcium channels are voltage gated and comprised of three subtypes: Cav3.1, Cav3.2 & Cav3.3 • Expressed in Central and Peripheral Nervous System, including primary afferent, dorsal horn neurons, thalamus and somatosensory cortex • Contribute to neuronal excitability, synaptic excitation, burst firing and action potential trains, and also lower threshold for action potentials Pain Signaling Thalamocortical Connectivity Source: Adapted from Zamponi, et al., Brain Res. Reviews. 2009 Source: Adapted from Park, et al., Frontiers Neural Circuits. 2013 • Rodent neuropathic and IBS pain models exhibit increased • Thalamocortical dysrythmia linked to CNS indications, e.g. T-type current density motor, neuropsychiatric and chronic pain syndromes • Gene knockout or antisense reduces pain in neuropathic, • Mutations in T-type channels are found in rodent and acute and visceral pain models human excitability disorders • T-type channel blockers attenuate neuropathic, • Approved anti-convulsants (e.g. ethosuximide, valproate) inflammatory, acute and visceral pain in animal models target T-type channels © Copyright Neuromed 2 Z944 is a Potent, Selective Blocker of T-type Calcium Channels IC50 (nM) Channel 30% Fold-Selectivity Closed Inactivated (30% Inactivated) CaV3.1(human, exogenous) 50 130 1 CaV3.2 (human, exogenous) 160 540 3.2 CaV3.3 (human, exogenous) 110 260 2.2 N-type (rat, exogenous) 11,000 150,000 220 L-type cardiac calcium (rat CaV1.2) 32,000 -- 640 Cardiac Sodium (human NaV1.5) 100,000 -- 2000 hERG channel (human) 7,800 -- 156 • Displays enhanced potency for the inactivated state across T-type channels • Z944 block of Cav3.2 is more pronounced during high-frequency firing • Z944 has >150-fold selectivity vs. -
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K. Bilby How the ýolder headsý talk: a Jamaican Maroon spirit possession language and its relationship to the creoles of Suriname and Sierra Leone In: New West Indian Guide/ Nieuwe West-Indische Gids 57 (1983), no: 1/2, Leiden, 37-88 This PDF-file was downloaded from http://www.kitlv-journals.nl Downloaded from Brill.com09/25/2021 11:19:53AM via free access 37 KENNETH M. BILBY HOW THE "OLDER HEADS" TALK: A JAMAICAN MAROON SPIRIT POSSESSION LANGUAGE AND ITS RELATIONSHIP TO THE CREOLES OF SURINAME AND SIERRA LEONE Introduction 37 The meaning of 'deep' language 39 Some distinctive characteristics of'deep' language 42 The question of preservation 56 Historical questions 59 Notes 62 Appendix A-C 70 References 86 In the interior of Jamaica exist four major Maroon communities, inhabited by the descendants of slaves who escaped from planta- tions during the seventeenth and eighteenth centuries, and gained their freedom by treaty in 1739. The present-day Maroon settle- ments — Moore Town, Charles Town, and Scott's Hall in the east, and Accompong in the west — are now nearly indistin- guishable, on the surface, from other rural Jamaican villages.1 Among the things which continue to set the Maroons apart from their non-Maroon neighbors are a number of linguistic features which appear to be found only in Maroon areas. The Maroon settlements have been described by two leading authorities as "centres of linguistic conservatism" (Cassidy & Le Page 1980: xli); but very little substantial documentation has yet appeared in print to back up this claim.2 While conducting an ethnographic study among the Jamaican Maroons in 1977-8,1 encountered a number of complex linguistic phenomena which were closely tied to the traditional ceremonial sphere in the various communities. -
GABA Receptors
D Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews • BIOTREND Reviews Review No.7 / 1-2011 GABA receptors Wolfgang Froestl , CNS & Chemistry Expert, AC Immune SA, PSE Building B - EPFL, CH-1015 Lausanne, Phone: +41 21 693 91 43, FAX: +41 21 693 91 20, E-mail: [email protected] GABA Activation of the GABA A receptor leads to an influx of chloride GABA ( -aminobutyric acid; Figure 1) is the most important and ions and to a hyperpolarization of the membrane. 16 subunits with γ most abundant inhibitory neurotransmitter in the mammalian molecular weights between 50 and 65 kD have been identified brain 1,2 , where it was first discovered in 1950 3-5 . It is a small achiral so far, 6 subunits, 3 subunits, 3 subunits, and the , , α β γ δ ε θ molecule with molecular weight of 103 g/mol and high water solu - and subunits 8,9 . π bility. At 25°C one gram of water can dissolve 1.3 grams of GABA. 2 Such a hydrophilic molecule (log P = -2.13, PSA = 63.3 Å ) cannot In the meantime all GABA A receptor binding sites have been eluci - cross the blood brain barrier. It is produced in the brain by decarb- dated in great detail. The GABA site is located at the interface oxylation of L-glutamic acid by the enzyme glutamic acid decarb- between and subunits. Benzodiazepines interact with subunit α β oxylase (GAD, EC 4.1.1.15). It is a neutral amino acid with pK = combinations ( ) ( ) , which is the most abundant combi - 1 α1 2 β2 2 γ2 4.23 and pK = 10.43. -
FIC-Prop-65-Notice-Reporter.Pdf
FIC Proposition 65 Food Notice Reporter (Current as of 9/25/2021) A B C D E F G H Date Attorney Alleged Notice General Manufacturer Product of Amended/ Additional Chemical(s) 60 day Notice Link was Case /Company Concern Withdrawn Notice Detected 1 Filed Number Sprouts VeggIe RotInI; Sprouts FruIt & GraIn https://oag.ca.gov/system/fIl Sprouts Farmers Cereal Bars; Sprouts 9/24/21 2021-02369 Lead es/prop65/notIces/2021- Market, Inc. SpInach FettucIne; 02369.pdf Sprouts StraIght Cut 2 Sweet Potato FrIes Sprouts Pasta & VeggIe https://oag.ca.gov/system/fIl Sprouts Farmers 9/24/21 2021-02370 Sauce; Sprouts VeggIe Lead es/prop65/notIces/2021- Market, Inc. 3 Power Bowl 02370.pdf Dawn Anderson, LLC; https://oag.ca.gov/system/fIl 9/24/21 2021-02371 Sprouts Farmers OhI Wholesome Bars Lead es/prop65/notIces/2021- 4 Market, Inc. 02371.pdf Brad's Raw ChIps, LLC; https://oag.ca.gov/system/fIl 9/24/21 2021-02372 Sprouts Farmers Brad's Raw ChIps Lead es/prop65/notIces/2021- 5 Market, Inc. 02372.pdf Plant Snacks, LLC; Plant Snacks Vegan https://oag.ca.gov/system/fIl 9/24/21 2021-02373 Sprouts Farmers Cheddar Cassava Root Lead es/prop65/notIces/2021- 6 Market, Inc. ChIps 02373.pdf Nature's Earthly https://oag.ca.gov/system/fIl ChoIce; Global JuIces Nature's Earthly ChoIce 9/24/21 2021-02374 Lead es/prop65/notIces/2021- and FruIts, LLC; Great Day Beet Powder 02374.pdf 7 Walmart, Inc. Freeland Foods, LLC; Go Raw OrganIc https://oag.ca.gov/system/fIl 9/24/21 2021-02375 Ralphs Grocery Sprouted Sea Salt Lead es/prop65/notIces/2021- 8 Company Sunflower Seeds 02375.pdf The CarrIngton Tea https://oag.ca.gov/system/fIl CarrIngton Farms Beet 9/24/21 2021-02376 Company, LLC; Lead es/prop65/notIces/2021- Root Powder 9 Walmart, Inc. -
The Myth Behind Alcohol Happiness Author: Dr
The Myth Behind Alcohol Happiness Author: Dr. Chencho Dorji Abstract By drawing on the socio-cultural, religious and traditional practices that encourage the use of alcohol in Bhutan, the author will examine the causes and factors that induce and maintain drinking habits among Bhutanese. Next, the impact of heavy drinking on Gross National Happiness will be examined. As an outcome of this study, some relevant strategies to minimize harm related to alcohol in Bhutan will be presented. Author’s background Dr. Chencho Dorji is a consultant psychiatrist and technical advisor to the National Mental Health Programme – Bhutan. He has written several articles on mental health in Bhutan including the article “Achieving Gross National Happiness (GNH) through Community-based Mental Health Services in Bhutan”, which he presented during the first seminar on GNH in Thimphu 2004. Contact address: J D W National Referral Hospital, Thimphu, Bhutan Email address: [email protected] Telephone: +975 2 325201 (residence) +975 2 322496/7 (office) Fax: +975 2 325384 INTRODUCTION In the pursuit of happiness, human beings will do anything. Some opt for the long haul, while others prefer a shortcut. A common shortcut is alcohol, known to produce happiness or euphoria, even if momentarily. For this reasons, millions of people worldwide drink it repeatedly everyday. Scientific research has proved that alcohol releases dopamine in the brain, which is responsible for the pleasure sensation. Humankind has used alcohol in one form or another as early as the Stone Age. History is beset with anecdotes of heavy drinking: from Europe to Asia, the Americas to Africa, alcohol has played a significant role in shaping history, politics and religion. -
Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review
Current Pain and Headache Reports (2019) 23: 37 https://doi.org/10.1007/s11916-019-0774-0 OTHER PAIN (A KAYE AND N VADIVELU, SECTION EDITORS) Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review Omar Viswanath1,2,3 & Ivan Urits4 & Mark R. Jones4 & Jacqueline M. Peck5 & Justin Kochanski6 & Morgan Hasegawa6 & Best Anyama7 & Alan D. Kaye7 Published online: 1 May 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review Neuropathic pain is often debilitating, severely limiting the daily lives of patients who are affected. Typically, neuropathic pain is difficult to manage and, as a result, leads to progression into a chronic condition that is, in many instances, refractory to medical management. Recent Findings Gabapentinoids, belonging to the calcium channel blocking class of drugs, have shown good efficacy in the management of chronic pain and are thus commonly utilized as first-line therapy. Various sodium channel blocking drugs, belonging to the categories of anticonvulsants and local anesthetics, have demonstrated varying degrees of efficacy in the in the treatment of neurogenic pain. Summary Though there is limited medical literature as to efficacy of any one drug, individualized multimodal therapy can provide significant analgesia to patients with chronic neuropathic pain. Keywords Neuropathic pain . Chronic pain . Ion Channel blockers . Anticonvulsants . Membrane stabilizers Introduction Neuropathic pain, which is a result of nervous system injury or lives of patients who are affected. Frequently, it is difficult to dysfunction, is often debilitating, severely limiting the daily manage and as a result leads to the progression of a chronic condition that is, in many instances, refractory to medical This article is part of the Topical Collection on Other Pain management. -
The History of the Introduction and Adoption of Important Food Crops in Bhutan
The history of the introduction and adoption of important food crops in Bhutan Rice, maize, potato and chili Dedicated to the Fourth Druk Gyalpo Jigme Singye Wangchuck National Biodiversity Centre Ministry of Agriculture and Forests Serbithang, Thimphu, Bhutan 2nd June 2015 Working team members 1. Dr. Tashi Y. Dorji, Program Director, National Biodiversity Centre, MoAF 2. Asta M. Tamang, Principal Biodiversity Officer, National Biodiversity Centre, MoAF 3. Dr. Ronnie Vernoy, Policy Expert, Bioversity International, Rome CONTENTS FOREWORD ............................................................................ 6 ACRONYMS .............................................................................. 6 LIST OF FIGURES ................................................................... 7 1. INTRODUCTION .............................................................. 8 2. OBJECTIVES OF THE STUDY .......................................... 9 3. METHODS .......................................................................... 10 3.1. Initial compilation of literature .......................................... 10 3.2. Selection of crops ............................................................... 10 3.3. Compilation of country-specific information ..................... 10 3.4. Literature review ................................................................ 11 3.5. Documentation ................................................................. 11 4. RICE ................................................................................... -
Flufenamic Acid Prevents Behavioral Manifestations of Salicylate-Induced Tinnitus in the Rat
Experimental research Flufenamic acid prevents behavioral manifestations of salicylate-induced tinnitus in the rat Ramazan Bal1, Yasemin Ustundag2, Funda Bulut3, Caner Feyzi Demir4, Ali Bal5 1Department of Physiology, Faculty of Medicine, Gaziantep University, Gaziantep, Corresponding author: Turkey Prof. Dr. Ramazan Bal 2Department of Anatomy, Faculty of Veterinary, Firat University, Elazig, Turkey Department of Physiology 3Department of Medical Biology, Faculty of Medicine, Kirikkale University, Kirikkale, Faculty of Medicine Turkey Gaziantep University 4Department of Neurology, Faculty of Medicine, Firat University, Elazig, Turkey 27310 Gaziantep, Turkey 5Department of Plastic-Reconstructive and Esthetic Surgery, Faculty of Medicine, Phone: +90 342 Firat University, Elazig, Turkey 3606060/77732 Fax: +90 342 360 16 17 Submitted: 7 March 2014 E-mail: [email protected], Accepted: 21 May 2014 [email protected] Arch Med Sci 2016; 12, 1: 208–215 DOI: 10.5114/aoms.2016.57597 Copyright © 2016 Termedia & Banach Abstract Introduction: Tinnitus is defined as a phantom auditory sensation, the per- ception of sound in the absence of external acoustic stimulation. Given that flufenamic acid (FFA) blocks TRPM2 cation channels, resulting in reduced neuronal excitability, we aimed to investigate whether FFA suppresses the behavioral manifestation of sodium salicylate (SSA)-induced tinnitus in rats. Material and methods: Tinnitus was evaluated using a conditioned lick sup- pression model of behavioral testing. Thirty-one Wistar rats, randomly di- vided into four treatment groups, were trained and tested in the behavioral experiment: (1) control group: DMSO + saline (n = 6), (2) SSA group: DMSO + SSA (n = 6), (3) FFA group: FFA (66 mg/kg bw) + saline (n = 9), (4) FFA + SSA group: FFA (66 mg/kg bw) + SSA (400 mg/kg bw) (n = 10). -
CPP-Ts: a New Intracellular Calcium Channel Modulator and a Promising
www.nature.com/scientificreports OPEN CPP-Ts: a new intracellular calcium channel modulator and a promising tool for drug delivery in cancer cells Received: 16 May 2018 Bárbara Bruna Ribeiro de Oliveira-Mendes1, Carolina Campolina Rebello Horta2, Accepted: 21 September 2018 Anderson Oliveira do Carmo 1, Gabriela Lago Biscoto1, Douglas Ferreira Sales- Published: xx xx xxxx Medina1, Hortênsia Gomes Leal1, Pedro Ferreira Pinto Brandão-Dias1, Sued Eustáquio Mendes Miranda3, Carla Jeane Aguiar4, Valbert Nascimento Cardoso3, André Luis Branco de Barros 3, Carlos Chávez-Olortégui5, M. Fátima Leite4 & Evanguedes Kalapothakis 1 Scorpion sting envenoming impacts millions of people worldwide, with cardiac efects being one of the main causes of death on victims. Here we describe the frst Ca2+ channel toxin present in Tityus serrulatus (Ts) venom, a cell penetrating peptide (CPP) named CPP-Ts. We show that CPP-Ts increases intracellular Ca2+ release through the activation of nuclear InsP3R of cardiomyocytes, thereby causing an increase in the contraction frequency of these cells. Besides proposing a novel subfamily of Ca2+ active toxins, we investigated its potential use as a drug delivery system targeting cancer cell nucleus using CPP-Ts’s nuclear-targeting property. To this end, we prepared a synthetic CPP-Ts sub peptide14–39 lacking pharmacological activity which was directed to the nucleus of specifc cancer cell lines. This research identifes a novel subfamily of Ca2+ active toxins and provides new insights into biotechnological applications of animal venoms. Scorpion sting envenoming has been ofcially established as a neglected public health issue by the World Health Organization1. Over 1.5 million of scorpion stings and more than 2,600 deaths occur annually worldwide2. -
Calabasas Enterprise
Volume 37, NumberArt 25of Whiskey MoreServing Appeals Warner Filed Center on Promenade Since 1982 2035 Scenes from August 15, 2019 Pours Out Page 15 the Park... ***WhenAugust stripping 23 in - take out date line below Valley Vantage - we’re getting doubleDancers, lines!!! Dogs and More See Page 4 See Page 7 L A S V I R G E N E S A N D CALABASAS ENTERPRISE VolumeValley 49,Volume Number 35, Issue 2425 Serving A CompendiousVantage Calabasas Source of Since Information 1963 August August 15, 2019 15, 2019 News in Brief CalJohn Trans Lee to WinsClose CouncilFreeway District Lanes Aug12 Seat 15-22 InCal the Trans runoff will election be working for theon theCity 101 CouncilFreeway Districtfor the 12next seat week, vacated specifically by Mitch in Englander,the areas of who Calabasas left public and officeAgoura. for the private sector mid-term,On Thursday, council August aide 15, Johnthe northbound Lee is the offramps apparent at winner.Mulholland/Valley Lee faced scientistCircle, LorraineParkway Lundquist.Calabasas, 100%Las ExposésOfficers on “Crimebusters”Entangled in Exposé Lead ofVirgenes, precincts Lost reported, Hills, Liberty and thoughCanyon notand allChesebro ballots had John Lee been willcounted, be closed Lee from was 7 on-ramps at Chesebro Road. aheadpm to 6by am. more than 1,300 districtOn August has 21 andtraditionally 22 all lanes to Investigationon Crimbusters of LAPD SLO’s votes,From 16,724 Monday, to 15,395,August votedof the Republican.southbound Lee101 iswill a be closed from 9 pm to 5 am. at19 tolast Thursday,count. DistrictAugust registered Republican. He Several online magazines, and often illegal suggestions Other officers, including Vehicles will be detoured off 1222, Calincludes Trans willWest close Hills, all has seven months in the including L.A.