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G Protein-Coupled Receptors As Therapeutic Targets for Multiple Sclerosis
npg GPCRs as therapeutic targets for MS Cell Research (2012) 22:1108-1128. 1108 © 2012 IBCB, SIBS, CAS All rights reserved 1001-0602/12 $ 32.00 npg REVIEW www.nature.com/cr G protein-coupled receptors as therapeutic targets for multiple sclerosis Changsheng Du1, Xin Xie1, 2 1Laboratory of Receptor-Based BioMedicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sci- ences and Technology, Tongji University, Shanghai 200092, China; 2State Key Laboratory of Drug Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shou Jing Road, Pudong New District, Shanghai 201203, China G protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmit- ters and environmental stimulants. They are considered as the most successful therapeutic targets for a broad spec- trum of diseases. Multiple sclerosis (MS) is an inflammatory disease that is characterized by immune-mediated de- myelination and degeneration of the central nervous system (CNS). It is the leading cause of non-traumatic disability in young adults. Great progress has been made over the past few decades in understanding the pathogenesis of MS. Numerous data from animal and clinical studies indicate that many GPCRs are critically involved in various aspects of MS pathogenesis, including antigen presentation, cytokine production, T-cell differentiation, T-cell proliferation, T-cell invasion, etc. In this review, we summarize the recent findings regarding the expression or functional changes of GPCRs in MS patients or animal models, and the influences of GPCRs on disease severity upon genetic or phar- macological manipulations. -
A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies
Comparative Medicine Vol 69, No 6 Copyright 2019 December 2019 by the American Association for Laboratory Animal Science Pages 520–534 Overview A Review of the Effects of Pain and Analgesia on Immune System Function and Inflammation: Relevance for Preclinical Studies George J DeMarco1* and Elizabeth A Nunamaker2 One of the most significant challenges facing investigators, laboratory animal veterinarians, and IACUCs, is how to bal- ance appropriate analgesic use, animal welfare, and analgesic impact on experimental results. This is particularly true for in vivo studies on immune system function and inflammatory disease. Often times the effects of analgesic drugs on a particu- lar immune function or model are incomplete or don’t exist. Further complicating the picture is evidence of the very tight integration and bidirectional functionality between the immune system and branches of the nervous system involved in nociception and pain. These relationships have advanced the concept of understanding pain as a protective neuroimmune function and recognizing pathologic pain as a neuroimmune disease. This review strives to summarize extant literature on the effects of pain and analgesia on immune system function and inflammation in the context of preclinical in vivo studies. The authors hope this work will help to guide selection of analgesics for preclinical studies of inflammatory disease and immune system function. Abbreviations and acronyms: CB,Endocannabinoid receptor; CD,Crohn disease; CFA, Complete Freund adjuvant; CGRP,Calcitonin gene-related -
Purinergic P2 Receptors As Targets for Novel Analgesics
Pharmacology & Therapeutics 110 (2006) 433 – 454 www.elsevier.com/locate/pharmthera Purinergic P2 receptors as targets for novel analgesics Geoffrey Burnstock * Autonomic Neuroscience Centre, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK Abstract Following hints in the early literature about adenosine 5V-triphosphate (ATP) injections producing pain, an ion-channel nucleotide receptor was cloned in 1995, P2X3 subtype, which was shown to be localized predominantly on small nociceptive sensory nerves. Since then, there has been an increasing number of papers exploring the role of P2X3 homomultimer and P2X2/3 heteromultimer receptors on sensory nerves in a wide range of organs, including skin, tongue, tooth pulp, intestine, bladder, and ureter that mediate the initiation of pain. Purinergic mechanosensory transduction has been proposed for visceral pain, where ATP released from epithelial cells lining the bladder, ureter, and intestine during distension acts on P2X3 and P2X2/3, and possibly P2Y, receptors on subepithelial sensory nerve fibers to send messages to the pain centers in the brain as well as initiating local reflexes. P1, P2X, and P2Y receptors also appear to be involved in nociceptive neural pathways in the spinal cord. P2X4 receptors on spinal microglia have been implicated in allodynia. The involvement of purinergic signaling in long-term neuropathic pain and inflammation as well as acute pain is discussed as well as the development of P2 receptor antagonists as novel analgesics. D -
Pepper Spray: What Do We Have to Expect?
Pepper Spray: What Do We Have to Expect? Assoc. Prof. Mehmet Akif KARAMERCAN, MD Gazi University School of Medicine Department of Emergency Medicine Presentation Plan • History • Pepper Spray • Tear Gas • Symptoms • Medical Treatment • If you are the victim ??? History • PEPPER SPRAY ▫ OC (oleoresin of capsicum) (Most Commonly Used Compound) • TEAR GAS ▫ CN (chloroacetophenone) (German scientists 1870 World War I and II) ▫ CS (orthochlorobenzalmalononitrile) (US Army adopted in 1959) ▫ CR (dibenzoxazepine) (British Ministry of Defence 1950-1960) History of Pepper Spray • Red Chili Pepper was being used for self defense in ancient India - China - Japan (Ninjas). ▫ Throw it at the faces of their enemies, opponents, or intruders. • Japan Tukagawa Empire police used a weapon called the "metsubishi." • Accepted as a weapon ▫ incapacitate a person temporarily. • Pepper as a weapon 14th and 15th century for slavery rampant and became a popular method for torturing people (criminals, slaves). History of Pepper Spray • 1980's The USA Postal Workers started using pepper sprays against dogs, bears and other pets and became a legalized non-lethal weapon ▫ Pepper spray is also known as oleoresin of capsicum (OC) spray • The FBI in 1987 endorse it as an official chemical agent and it took 4 years it could be legally accepted by law enforcement agency. Pepper Spray • The active ingredient in pepper spray is capsaicin, which is a chemical derived from the fruit of plants of chilis. • Extraction of Oleoresin Capsicum from peppers ▫ capsicum to be finely ground, capsaicin is then extracted using an organic solvent (ethanol). The solvent is then evaporated, remaining waxlike resin is the Oleoresin Capsicum • Propylene Glycol is used to suspend the OC in water, pressurized to make it aerosol in Pepper Spray. -
Phytochem Referenzsubstanzen
High pure reference substances Phytochem Hochreine Standardsubstanzen for research and quality für Forschung und management Referenzsubstanzen Qualitätssicherung Nummer Name Synonym CAS FW Formel Literatur 01.286. ABIETIC ACID Sylvic acid [514-10-3] 302.46 C20H30O2 01.030. L-ABRINE N-a-Methyl-L-tryptophan [526-31-8] 218.26 C12H14N2O2 Merck Index 11,5 01.031. (+)-ABSCISIC ACID [21293-29-8] 264.33 C15H20O4 Merck Index 11,6 01.032. (+/-)-ABSCISIC ACID ABA; Dormin [14375-45-2] 264.33 C15H20O4 Merck Index 11,6 01.002. ABSINTHIN Absinthiin, Absynthin [1362-42-1] 496,64 C30H40O6 Merck Index 12,8 01.033. ACACETIN 5,7-Dihydroxy-4'-methoxyflavone; Linarigenin [480-44-4] 284.28 C16H12O5 Merck Index 11,9 01.287. ACACETIN Apigenin-4´methylester [480-44-4] 284.28 C16H12O5 01.034. ACACETIN-7-NEOHESPERIDOSIDE Fortunellin [20633-93-6] 610.60 C28H32O14 01.035. ACACETIN-7-RUTINOSIDE Linarin [480-36-4] 592.57 C28H32O14 Merck Index 11,5376 01.036. 2-ACETAMIDO-2-DEOXY-1,3,4,6-TETRA-O- a-D-Glucosamine pentaacetate 389.37 C16H23NO10 ACETYL-a-D-GLUCOPYRANOSE 01.037. 2-ACETAMIDO-2-DEOXY-1,3,4,6-TETRA-O- b-D-Glucosamine pentaacetate [7772-79-4] 389.37 C16H23NO10 ACETYL-b-D-GLUCOPYRANOSE> 01.038. 2-ACETAMIDO-2-DEOXY-3,4,6-TRI-O-ACETYL- Acetochloro-a-D-glucosamine [3068-34-6] 365.77 C14H20ClNO8 a-D-GLUCOPYRANOSYLCHLORIDE - 1 - High pure reference substances Phytochem Hochreine Standardsubstanzen for research and quality für Forschung und management Referenzsubstanzen Qualitätssicherung Nummer Name Synonym CAS FW Formel Literatur 01.039. -
Trpa1) Activity by Cdk5
MODULATION OF TRANSIENT RECEPTOR POTENTIAL CATION CHANNEL, SUBFAMILY A, MEMBER 1 (TRPA1) ACTIVITY BY CDK5 A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Michael A. Sulak December 2011 Dissertation written by Michael A. Sulak B.S., Cleveland State University, 2002 Ph.D., Kent State University, 2011 Approved by _________________, Chair, Doctoral Dissertation Committee Dr. Derek S. Damron _________________, Member, Doctoral Dissertation Committee Dr. Robert V. Dorman _________________, Member, Doctoral Dissertation Committee Dr. Ernest J. Freeman _________________, Member, Doctoral Dissertation Committee Dr. Ian N. Bratz _________________, Graduate Faculty Representative Dr. Bansidhar Datta Accepted by _________________, Director, School of Biomedical Sciences Dr. Robert V. Dorman _________________, Dean, College of Arts and Sciences Dr. John R. D. Stalvey ii TABLE OF CONTENTS LIST OF FIGURES ............................................................................................... iv LIST OF TABLES ............................................................................................... vi DEDICATION ...................................................................................................... vii ACKNOWLEDGEMENTS .................................................................................. viii CHAPTER 1: Introduction .................................................................................. 1 Hypothesis and Project Rationale -
A Rapid Capsaicin-Activated Current in Rat Trigeminal Ganglion Neurons (Pain/Taste/Nociceptive Fibers/Ph/Capsazepine) L
Proc. Natl. Acad. Sci. USA Vol. 91, pp. 738-741, January 1994 Neurobiology A rapid capsaicin-activated current in rat trigeminal ganglion neurons (pain/taste/nociceptive fibers/pH/capsazepine) L. LIu* AND S. A. SIMONt Departments of *Neurobiology and tAnesthesiology, Duke University Medical Center, Durham, NC 27710 Communicated by Irving T. Diamond, October 15, 1993 ABSTRACT A subpopulation of pain fibers are activated Na2HPO4, 5.6 mM D-glucose, and 10 mM Hepes. They were by capsaicin, the ingredient in red peppers that produces a then incubated for 40 min at 37°C in HBSS containing 1 mg burning sensation when eaten or placed on skin. Previous of collagenase per ml (type XI-S), triturated with a flamed studies on dorsal root ganglion neurons indicated thatcapsaicin Pasteur pipette, and finally incubated at 37°C for 6 min with activates sensory nerves via a single slowly activating and 0.1 mg of DNase I per ml (type IV). Then they were inactivating inward current. In rat trigeminal neurons, we retriturated and washed/centrifuged three times in HBSS. identified a second capsaicin-activated inward current. This They were then resuspended in F-14 medium (GIBCO) current can be distinguished from the slow one in that it rapidly containing 10%o fetal calf serum in a Petri dish. The cultures activates and inactivates, requires Ca2+ for activation, and is were maintained in an incubator at 37°C equilibrated with 5% insensitive to the potent capsaicin agonist resiniferatoxin. The CO2. Most patch clamp experiments were done on cells rapid current, like the slower one, is inhibited by ruthenium cultured for 12-24 hr. -
Toxic Materials to Cornea INTRODUCTION
International Journal of Veterinary and Animal Research Uluslararası Veteriner ve Hayvan Araştırmaları Dergisi E-ISSN: 2651-3609 2(1): 06-10, 2019 Toxic Materials to Cornea Eren Ekici1, Ender Yarsan2* 1Ankara Ulucanlar Eye Training and Research Hospital, Department of Ophtalmology, Ankara, Turkey 2Ankara University Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Ankara, Turkey *Corresponding Author Received: February 12, 2019 E-mail:[email protected] Accepted: March 6, 2019 Abstract Every day; many chemical agents, materials or medicines whether in the pharmaceutical industry or daily life are offered for consuming for human beings. At this point, it has great importance that if the substances threaten heath or not. Because the toxicity of materials can lead to many target organ damage. The eye, together with many anatomical layers that make it up is among the target organs exposed to toxicity. In this review, we handled the classification, effects and treatment methods of toxic materials on the corneal layer of the eye. Keywords: Cornea, toxic materials, chemicals, eye INTRODUCTION and materials known to be toxic in high-risk situations (ie Toxic material is a chemical substance that breaks down aminoglycosides, some glaucoma medications, antivirals, normal physiological and biochemical mechanisms when chronic disease, dry eyes and patients on multiple topical it enters the living organism (human and warm-blooded therapies) is effective to protect from toxicity (Dart, 2003). animals) through mouth, respiration, skin, and infection, or Table 1: Classification by route of exposure and time course. causes the death of the creature in an excess amount. For Local action, immediate corneal toxicity; there are many methods of classification Examples effects based on the disease, route of exposure and duration or agent Caustic chemicals Acids and alkalis (Grant, 1986). -
Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis
The Open Dentistry Journal, 2011, 5, 1-6 1 Open Access Systemic Chemical Desensitization of Peptidergic Sensory Neurons with Resiniferatoxin Inhibits Experimental Periodontitis Torbjørn Breivik1,2,*, Yngvar Gundersen2, Per Gjermo1, Inge Fristad3 and Per Kristian Opstad2 1Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway 2Norwegian Defence Research Establishment, Division for Protection, Kjeller, Norway 3Department of Clinical Dentistry - Endodontics, University of Bergen, Bergen, Norway Abstract: Background and objective: The immune system is an important player in the pathophysiology of periodontitis. The brain controls immune responses via neural and hormonal pathways, and brain-neuro-endocrine dysregulation may be a central determinant for pathogenesis. Our current knowledge also emphasizes the central role of sensory nerves. In line with this, we wanted to investigate how desensitization of peptidergic sensory neurons influences the progression of ligature- induced periodontitis, and, furthermore, how selected cytokine and stress hormone responses to Gram-negative bacterial lipopolysaccharide (LPS) stimulation are affected. Material and methods: Resiniferatoxin (RTX; 50 μg/kg) or vehicle was injected subcutaneously on days 1, 2, and 3 in stress high responding and periodontitis-susceptible Fischer 344 rats. Periodontitis was induced 2 days thereafter. Progres- sion of the disease was assessed after the ligatures had been in place for 20 days. Two h before decapitation all rats re- ceived LPS (150 μg/kg i.p.) to induce a robust immune and stress response. Results: Desensitization with RTX significantly reduced bone loss as measured by digital X-rays. LPS provoked a signifi- cantly higher increase in serum levels of the pro-inflammatory cytokine tumour necrosis factor (TNF)-, but lower serum levels of the anti-inflammatory cytokine interleukin (IL)-10 and the stress hormone corticosterone. -
Weaponizing Tear Gas: Bahrain’S Unprecedented Use of Toxic Chemical Agents Against Civilians
Physicians for Human Rights Weaponizing Tear Gas: Bahrain’s Unprecedented Use of Toxic Chemical Agents Against Civilians August 2012 physiciansforhumanrights.org About Physicians for Human Rights Physicians for Human Rights (PHR) uses medicine and science to investigate and expose human rights violations. We work to prevent rights abuses by seeking justice and holding offenders accountable. Since 1986, PHR has conducted investigations in more than 40 countries, including on: 1987 — Use of toxic chemical agents in South Korea 1988 — Iraq’s use of chemical weapons against Kurds 1988 — Use of toxic chemical agents in West Bank and the Gaza Strip 1989 — Use of chemical warfare agents in Soviet Georgia 1996 — Exhumation of mass graves in the Balkans 1996 — Critical forensic evidence of genocide in Rwanda 1999 — Drafting the UN-endorsed guidelines for documentation of torture 2004 — Documentation of the genocide in Darfur 2008 — US complicity of torture in Iraq, Afghanistan, and Guantánamo Bay 2010 — Human experimentation by CIA medical personnel on prisoners in violation of the Nuremberg Code 2011 — Violations of medical neutrality in times of armed conflict and civil unrest during the Arab Spring ... 2 Arrow Street | Suite 301 1156 15th Street, NW | Suite 1001 Cambridge, MA 02138 USA Washington, DC 20005 USA +1 617 301 4200 +1 202 728 5335 physiciansforhumanrights.org ©2012, Physicians for Human Rights. All rights reserved. ISBN: 1-879707-68-3 Library of Congress Control Number: 2012945532 Cover photo: Bahraini anti-riot police fire tear gas grenades at peaceful and unarmed civilians protesters, including a Shi’a cleric, in June 2012. http://www.youtube.com/watch?v=QxauI5hdjqk. -
Patent Application Publication ( 10 ) Pub . No . : US 2019 / 0192440 A1
US 20190192440A1 (19 ) United States (12 ) Patent Application Publication ( 10) Pub . No. : US 2019 /0192440 A1 LI (43 ) Pub . Date : Jun . 27 , 2019 ( 54 ) ORAL DRUG DOSAGE FORM COMPRISING Publication Classification DRUG IN THE FORM OF NANOPARTICLES (51 ) Int . CI. A61K 9 / 20 (2006 .01 ) ( 71 ) Applicant: Triastek , Inc. , Nanjing ( CN ) A61K 9 /00 ( 2006 . 01) A61K 31/ 192 ( 2006 .01 ) (72 ) Inventor : Xiaoling LI , Dublin , CA (US ) A61K 9 / 24 ( 2006 .01 ) ( 52 ) U . S . CI. ( 21 ) Appl. No. : 16 /289 ,499 CPC . .. .. A61K 9 /2031 (2013 . 01 ) ; A61K 9 /0065 ( 22 ) Filed : Feb . 28 , 2019 (2013 .01 ) ; A61K 9 / 209 ( 2013 .01 ) ; A61K 9 /2027 ( 2013 .01 ) ; A61K 31/ 192 ( 2013. 01 ) ; Related U . S . Application Data A61K 9 /2072 ( 2013 .01 ) (63 ) Continuation of application No. 16 /028 ,305 , filed on Jul. 5 , 2018 , now Pat . No . 10 , 258 ,575 , which is a (57 ) ABSTRACT continuation of application No . 15 / 173 ,596 , filed on The present disclosure provides a stable solid pharmaceuti Jun . 3 , 2016 . cal dosage form for oral administration . The dosage form (60 ) Provisional application No . 62 /313 ,092 , filed on Mar. includes a substrate that forms at least one compartment and 24 , 2016 , provisional application No . 62 / 296 , 087 , a drug content loaded into the compartment. The dosage filed on Feb . 17 , 2016 , provisional application No . form is so designed that the active pharmaceutical ingredient 62 / 170, 645 , filed on Jun . 3 , 2015 . of the drug content is released in a controlled manner. Patent Application Publication Jun . 27 , 2019 Sheet 1 of 20 US 2019 /0192440 A1 FIG . -
Lantern Parade & Magical Evening
Greater New Lodge Community Magazine December 2014 Ashton Centre, 5 Churchill Street, Belfast BT15 2BP Tel: (028) 90742255 email: [email protected] Thousands Attend Lantern Parade & Magical Evening Section of the crowd who took part in the Lantern Parade The North Belfast Lantern Parade and Magical Festival for the parade. took place this year on Wednesday 29th & Thursday 30th The parade itself left Crumlin Road Gaol, went along October in the Waterworks Park. During the day there was Cliftonpark Avenue, down Cliftonville Road and up the Antrim a range of activities involving street theatre performances, Road into the Waterworks Park. There were approximately storytelling, drumming, music by Cool FM’s Ryan A and visual 850 children and adults taking part in this fabulous carnival art workshops. The weather was lovely which made being parade along with performers from Fire Poise, Streetwise outdoors all the more enjoyable. Circus, and Arts Ekta. Motorway Site Continued on Page 3 - Page 4 for Photos The North Belfast Lantern Parade is part of the North Belfast Community Pride Programme which is funded through OFMDFM’s Good Relations Programme and led by Ashton Inside Highlights Community Trust. This programme is delivered by New Page 3 - Christmas Party Lodge Arts and supported by a steering group of various Page 5 - Ashton Community Bursaries North Belfast based youth and community organisations. Page 6 - Tar Isteach Face Funding Crisis Other funders for this project include Belfast City Council, Page 7 - Misuse of Prescription Drugs Community Foundation Northern Ireland and Department of Page 8 - BOH Peace Building Lessons In Berlin Foreign Affairs.