Studying GABAA Receptors Using AII Amacrine Cells in the Rat Retina by Tuan Van Trinh
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(12) Patent Application Publication (10) Pub. No.: US 2017/0020892 A1 Thompson Et Al
US 20170020892A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2017/0020892 A1 Thompson et al. (43) Pub. Date: Jan. 26, 2017 (54) USE OF NEGATIVE MODULATORS OF Related U.S. Application Data GABA RECEPTORS CONTAINING ALPHAS SUBUNITS AS FAST ACTING (60) Provisional application No. 61/972,446, filed on Mar. ANTDEPRESSANTS 31, 2014. (71) Applicant: University of Maryland, Baltimore, Publication Classification Baltimore, MD (US) (51) Int. Cl. A 6LX 3/557 (2006.01) (72) Inventors: Scott Thompson, Baltimore, MD (US); A6II 3/53 (2006.01) Mark D. Kvarta, Ellicott City, MD A6II 45/06 (2006.01) (US); Adam Van Dyke, Baltimore, MD (52) U.S. Cl. (US) CPC ........... A61 K3I/55.17 (2013.01); A61K 45/06 (2013.01); A61 K3I/53 (2013.01) (73) Assignee: University of Maryland, Baltimore, Baltimore, MD (US) (57) ABSTRACT Embodiments of the disclosure include methods and com (21) Appl. No.: 15/300,984 positions related to treatment of one or more medical conditions with one or more negative modulators of GABA (22) PCT Filed: Mar. 31, 2015 receptors. In specific embodiments, depression and/or Sui cidability is treated or ameliorated or prevented with one or (86) PCT No.: PCT/US2O15/023667 more negative modulators of GABA receptors, such as a S 371 (c)(1), partial inverse agonist of a GABA receptor comprising an (2) Date: Sep. 30, 2016 alpha5 subunit. Patent Application Publication Jan. 26, 2017. Sheet 1 of 12 US 2017/002O892 A1 ×1/ /|\ Patent Application Publication Jan. 26, 2017. Sheet 3 of 12 US 2017/002O892 A1 & Patent Application Publication Jan. -
Picrotoxin-Like Channel Blockers of GABAA Receptors
COMMENTARY Picrotoxin-like channel blockers of GABAA receptors Richard W. Olsen* Department of Molecular and Medical Pharmacology, Geffen School of Medicine, University of California, Los Angeles, CA 90095-1735 icrotoxin (PTX) is the prototypic vous system. Instead of an acetylcholine antagonist of GABAA receptors (ACh) target, the cage convulsants are (GABARs), the primary media- noncompetitive GABAR antagonists act- tors of inhibitory neurotransmis- ing at the PTX site: they inhibit GABAR Psion (rapid and tonic) in the nervous currents and synapses in mammalian neu- system. Picrotoxinin (Fig. 1A), the active rons and inhibit [3H]dihydropicrotoxinin ingredient in this plant convulsant, struc- binding to GABAR sites in brain mem- turally does not resemble GABA, a sim- branes (7, 9). A potent example, t-butyl ple, small amino acid, but it is a polycylic bicyclophosphorothionate, is a major re- compound with no nitrogen atom. The search tool used to assay GABARs by compound somehow prevents ion flow radio-ligand binding (10). through the chloride channel activated by This drug target appears to be the site GABA in the GABAR, a member of the of action of the experimental convulsant cys-loop, ligand-gated ion channel super- pentylenetetrazol (1, 4) and numerous family. Unlike the competitive GABAR polychlorinated hydrocarbon insecticides, antagonist bicuculline, PTX is clearly a including dieldrin, lindane, and fipronil, noncompetitive antagonist (NCA), acting compounds that have been applied in not at the GABA recognition site but per- huge amounts to the environment with haps within the ion channel. Thus PTX major agricultural economic impact (2). ͞ appears to be an excellent example of al- Some of the other potent toxicants insec- losteric modulation, which is extremely ticides were also radiolabeled and used to important in protein function in general characterize receptor action, allowing and especially for GABAR (1). -
Current Awareness in Clinical Toxicology Editors: Damian Ballam Msc and Allister Vale MD
Current Awareness in Clinical Toxicology Editors: Damian Ballam MSc and Allister Vale MD August 2016 CONTENTS General Toxicology 6 Metals 30 Management 14 Pesticides 31 Drugs 16 Chemical Warfare 33 Chemical Incidents & 24 Plants 34 Pollution Chemicals 25 Animals 34 CURRENT AWARENESS PAPERS OF THE MONTH Toxicity evaluation of α-pyrrolidinovalerophenone (α-PVP): results from intoxication cases within the STRIDA project Beck O, Franzén L, Bäckberg M, Signell P, Helander A. Clin Toxicol 2016; 54: 568-75. Context An increasing number of new psychoactive substances (NPS) of different chemical classes have become available through marketing and sale over the Internet. This report from the Swedish STRIDA project presents the prevalence, laboratory results, and clinical features in a series of intoxications involving the stimulant NPS -pyrrolidinovalerophenone (-PVP), a potent dopamine re-uptake inhibitor, over a 4-year period. Study design Observational case series of consecutive patients with admitted or suspected intake of NPS presenting to hospitals in Sweden from 2012 to 2015. Patients and methods In the STRIDA project, blood and urine samples are collected from intoxicated patients with admitted or suspected intake of NPS or unknown drugs presenting to hospitals over the country. Analysis of NPS is performed by mass spectrometry multicomponent methods. Clinical data are collected when caregivers consult the Swedish Poisons Information Centre Current Awareness in Clinical Toxicology is produced monthly for the American Academy of Clinical Toxicology by the Birmingham Unit of the UK National Poisons Information Service, with contributions from the Cardiff, Edinburgh, and Newcastle Units. The NPIS is commissioned by Public Health England 2 (PIC), and retrieved from medical records. -
(12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig. -
XXXV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 26–29 May 2015, St Julian's, Malta
Clinical Toxicology ISSN: 1556-3650 (Print) 1556-9519 (Online) Journal homepage: http://www.tandfonline.com/loi/ictx20 XXXV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 26–29 May 2015, St Julian's, Malta To cite this article: (2015) XXXV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 26–29 May 2015, St Julian's, Malta, Clinical Toxicology, 53:4, 233-403, DOI: 10.3109/15563650.2015.1024953 To link to this article: http://dx.doi.org/10.3109/15563650.2015.1024953 Published online: 26 Mar 2015. Submit your article to this journal Article views: 3422 View related articles View Crossmark data Citing articles: 2 View citing articles Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ictx20 Download by: [UPSTATE Medical University Health Sciences Library] Date: 28 December 2016, At: 10:31 Clinical Toxicology (2015), 53, 233–403 Copyright © 2015 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2015.1024953 ABSTRACTS XXXV International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 26–29 May 2015, St Julian ’ s, Malta 1. Modelling dose-concentration-response Introduction: The American Association of Poison Control Cen- ters (AAPCC) published its fi rst annual report in 1983. Call data Ursula Gundert-Remy from sixteen US poison centers was chronicled in that report. Seven submitted data for the entire year. By July 2000, 63 centers Institute for Clinical Pharmacology and Toxicology, Charit é were part of the national poison center system, but only 59 submit- Medical School, Berlin, Germany ted data for the full year. -
(12) United States Patent (10) Patent No.: US 9.204,630 B2 Shirley Et Al
USOO920463OB2 (12) United States Patent (10) Patent No.: US 9.204,630 B2 Shirley et al. (45) Date of Patent: Dec. 8, 2015 (54) CAPSULE FORMULATION (58) Field of Classification Search CPC ... A01N 2300/00: A01N 43/90: A01N 47/02: (75) Inventors: Ian Malcolm Shirley, Bracknell (GB); A01N 25/22: A01N 25/28 Tanya Wright, Basel (CH); Robert See application file for complete search history. Michael Perrin, Bracknell (GB); Patrick Mulqueen, Bracknell (GB); Anne Waller, Bracknell (GB); Andy (56) References Cited Pierce, Bracknell (GB) U.S. PATENT DOCUMENTS (73) Assignee: Syngenta Participations AG, Basel 4,440,756 A * 4/1984 Herve et al. ................... 514,521 (CH) 6,395,776 B1* 5/2002 Losel et al. ................... 514,531 2002/003730.6 A1* 3/2002 Van Koppenhagen et al. ............................. 424/408 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 2004/O198704 A1* 10, 2004 Shuster et al. ... 514/151 U.S.C. 154(b) by 1634 days. 2004/0235898 A1* 11/2004 Klein et al. ................... 514,318 (21) Appl. No.: 11/817,068 FOREIGN PATENT DOCUMENTS CN 1386419 A 12/2002 (22) PCT Filed: Feb. 23, 2006 CN 149 1552 A 4/2004 DE 4009 141 A1 9, 1990 (86). PCT No.: PCT/EP2006/OO1657 DE 19503157 A1 8, 1995 EP O761096 A 3, 1997 S371 (c)(1), WO 89,04170 A 5, 1989 (2), (4) Date: Aug. 19, 2008 WO OO/O5951. A 2, 2000 (87) PCT Pub. No.: WO2006/089747 OTHER PUBLICATIONS PCT Pub. Date: Aug. 31, 2006 Anonymous, “Pyrethrinoids Stabilized by Non-azo—dyes'. -
(12) Patent Application Publication (10) Pub. No.: US 2011/00284.18 A1 Parker Et Al
US 2011 002841 8A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/00284.18 A1 Parker et al. (43) Pub. Date: Feb. 3, 2011 (54) USE OF GABBA RECEPTOR ANTAGONISTS Publication Classification FOR THE TREATMENT OF EXCESSIVE SLEEPINESS AND DISORDERS ASSOCATED (51) Int. Cl. WITH EXCESSIVE SLEEPINESS A63L/7028 (2006.01) A 6LX 3/557 (2006.01) (75) Inventors: Kathy P. Parker, Rochester, NY A63L/335 (2006.01) (US); David B. Rye, Dunwoody, A63L/4355 (2006.01) GA (US); Andrew Jenkins, A63L/047 (2006.01) Decatur, GA (US) A6IP 25/00 (2006.01) Correspondence Address: (52) U.S. Cl. ........... 514/29: 514/220; 514/450, 514/291; FISH & RICHARDSON P.C. (AT) 5147738 P.O BOX 1022 Minneapolis, MN 55440-1022 (US) (57) ABSTRACT (73) Assignee: Emory University, Atlanta, GA GABA receptor mediated hypersomnia can be treated by (US) administering a GABA receptor antagonist (e.g., flumazenil; clarithromycin; picrotoxin; bicuculline; cicutoxin; and (21) Appl. No.: 12/922,044 oenanthotoxin). In some embodiments, the GABA receptor antagonist is flumazenil or clarithromycin. The GABA (22) PCT Filed: Mar. 12, 2009 receptor mediated hypersomnia includes shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, narco (86). PCT No.: PCT/USO9/37034 lepsy, excessive sleepiness, hypersomnia (e.g., idiopathic hypersomnia; recurrent hyperSonmia; endozepine related S371 (c)(1), recurrent stupor; and amphetamine resistant hyperSonmia), (2), (4) Date: Sep. 10, 2010 and excessive sleepiness associated with shift work sleep disorder, obstructive sleep apnea/hypopnea syndrome, and Related U.S. Application Data hypersomnia (e.g., idiopathic hypersomnia; recurrent hyper (60) Provisional application No. -
Environmental Science Water Research & Technology
Environmental Science Water Research & Technology View Article Online CRITICAL REVIEW View Journal | View Issue Hydrophilic trace organic contaminants in urban Cite this: Environ. Sci.: Water Res. stormwater: occurrence, toxicological relevance, Technol., 2020, 6,15 and the need to enhance green stormwater infrastructure Stephanie Spahr, †*ab Marc Teixidó, bc David L. Sedlak bc and Richard G. Luthy *ab Hydrophilic trace organic contaminants (hyphil-TrOCs) are polar, often ionizable organic compounds of anthropogenic origin that have various applications in the urban environment e.g., as pesticides, plasticizers, and flame retardants. Hyphil-TrOCs can be washed off in storm events and enter surface waters via untreated urban stormwater discharges or combined sewer overflows. Though trace concentrations of these chemicals may pose a risk to ecosystem and human health, information on their Creative Commons Attribution 3.0 Unported Licence. presence in urban stormwater remains elusive. Monitoring and source apportionment of hyphil-TrOCs in urban stormwater is complicated by the vast number and sources of organic contaminants and the high variability in aqueous concentration over time and space. Here, we present the current state of knowledge on the occurrence and toxicological relevance of hyphil-TrOCs in urban stormwater. To mitigate negative impacts of contaminated surface runoff to receiving water bodies and to prevent sanitary or combined sewer overflows, many cities implement sustainable green stormwater infrastructure, also called best -
1-Iodo-1-Pentyne
MIAMI UNIVERSITY-THE GRADUATE SCHOOL CERTIFICATE FOR APPROVING THE DISSERTATION We hereby approve the Dissertation of Lizhi Zhu Candidate for the Degree: Doctor of Philosophy ________________________________ Robert E. Minto, Director ________________________________ John R. Grunwell, Reader ________________________________ John F. Sebastian, Reader ________________________________ Ann E. Hagerman, Reader ________________________________ Richard E. Lee, Graduate School Representative ABSTRACT INVESTIGATING THE BIOSYNTHESIS OF POLYACETYLENES: SYNTHESIS OF DEUTERATED LINOLEIC ACIDS & MECHANISM STUDIES OF DMDS ADDITION TO 1,4-ENYNES By Lizhi Zhu A wide range of polyacetylenic natural products possess antimicrobial, antitumor, and insecticidal properties. The biosyntheses of these natural products are widely distributed among fungi, algae, marine sponges, and higher plants. As details of the biosyntheses of these intriguing compounds remains scarce, it remains important to develop molecular probes and analytical methods to study polyacetylene secondary metabolism. An effective pathway to prepare selectively deuterium-labeled linoleic acids was developed. By this Pd-catalyzed method, deuterium can be easily introduced into the vinyl position providing deuterolinoleates with very high isotopic purity. This method also provides a general route for the construction of 1,4-diene derivatives with different chain lengths and 1,4-diene locations. Linoleic acid derivatives (12-d, 13-d and 16,16,17,17,18,18,18-d7) were synthesized according to this method. A stereoselective synthesis of methyl (14Z)- and (14E)-dehydrocrepenynate was achieved in five to six steps that employed Pd-catalyzed cross-coupling reactions to construct the double bonds between C14 and C15. Compared with earlier methods, the improved syntheses are more convenient (no spinning band distillations or GLC separation of diastereomers were necessary) and higher Z/E ratios were obtained. -
Fall TNP Herbals.Pptx
8/18/14 Introduc?on to Objecves Herbal Medicine ● Discuss history and role of psychedelic herbs Part II: Psychedelics, in medicine and illness. Legal Highs, and ● List herbs used as emerging legal and illicit Herbal Poisons drugs of abuse. ● Associate main plant and fungal families with Jason Schoneman RN, MS, AGCNS-BC representave poisonous compounds. The University of Texas at Aus?n ● Discuss clinical management of main toxic Schultes et al., 1992 compounds. Psychedelics Sacraments: spiritual tools or sacred medicine by non-Western cultures vs. Dangerous drugs of abuse vs. Research and clinical tools for mental and physical http://waynesword.palomar.edu/ww0703.htm disorders History History ● Shamanic divinaon ○ S;mulus for spirituality/religion http://orderofthesacredspiral.blogspot.com/2012/06/t- mckenna-on-psilocybin.html http://www.cosmicelk.net/Chukchidirections.htm 1 8/18/14 History History http://www.10zenmonkeys.com/2007/01/10/hallucinogenic- weapons-the-other-chemical-warfare/ http://rebloggy.com/post/love-music-hippie-psychedelic- woodstock http://fineartamerica.com/featured/misterio-profundo-pablo- amaringo.html History ● Psychotherapy ○ 20th century: un;l 1971 ● Recreaonal ○ S;mulus of U.S. cultural revolu;on http://qsciences.digi-info-broker.com http://www.uspharmacist.com/content/d/feature/c/38031/ http://en.wikipedia.org/nervous_system 2 8/18/14 Main Groups Main Groups Tryptamines LSD, Psilocybin, DMT, Ibogaine Other Ayahuasca, Fly agaric Phenethylamines MDMA, Mescaline, Myristicin Pseudo-hallucinogen Cannabis Dissociative -
Is Palatability of a Root-Hemiparasitic Plant Influenced by Its Host Species?
Oecologia (2005) 146: 227–233 DOI 10.1007/s00442-005-0192-3 PLANTANIMALINTERACTIONS Martin Scha¨dler Æ Mareike Roeder Æ Roland Brandl Diethart Matthies Is palatability of a root-hemiparasitic plant influenced by its host species? Received: 16 November 2004 / Accepted: 21 June 2005 / Published online: 19 July 2005 Ó Springer-Verlag 2005 Abstract Palatability of parasitic plants may be influ- Introduction enced by their host species, because the parasites take up nutrients and secondary compounds from the hosts. If Parasitic plants attack shoots or roots of other plants and parasitic plants acquired the full spectrum of secondary take up water, nutrients and solutes from the hosts by compounds from their host, one would expect a corre- means of specialized contact organs (haustoria, Kuijt lation between host and parasite palatability. We 1969). About 1% of all plants are parasitic and parasitic examined the palatability of leaves of the root-hemi- plants are common components of many plant commu- parasite Melampyrum arvense grown with different host nities (Molau 1995). The majority of parasitic plants are plants and the palatability of these host plants for two actually hemiparasites that have green leaves and are generalist herbivores, the caterpillar of Spodoptera lit- able to photosynthesize (Kuijt 1969). Parasitic plants can toralis and the slug Arion lusitanicus. We used 19 species drastically reduce the growth of their host plants and of host plants from 11 families that are known to con- some are important agricultural pests (Parker and Riches tain a wide spectrum of anti-herbivore compounds. 1993; Pennings and Callaway 2002). Because parasitic Growth of M. -
Developmental Deltamethrin: Effects on Cognition, Neurotransmitter Systems, Inflammatory Cytokines and Cell Death
Developmental deltamethrin: Effects on cognition, neurotransmitter systems, inflammatory cytokines and cell death A dissertation submitted to the Graduate School of the University of Cincinnati In partial fulfillment of the requirements for the degree of Doctor of Philosophy In the Neuroscience Graduate Program of the College of Medicine By Emily Pitzer B.S. Westminster College April 2020 Dissertation Committee: Steve Danzer, Ph.D. Mary Beth Genter, Ph.D. Gary Gudelsky, Ph.D. Kimberly Yolton, Ph.D. Charles Vorhees, Ph.D. (Advisor) Michael Williams, Ph.D. (Chair) ABSTRACT Deltamethrin (DLM) is a Type II pyrethroid pesticide and is more widely used with the elimination of organophosphate pesticides. Epidemiological studies have linked elevated levels of pyrethroid metabolites in urine during development with neurological disorders, raising concern for the safety of children exposed to these agents. Few animal studies have explored the effects or mechanisms of DLM-induced deficits in behavior and cognition after developmental exposure. The aim of the present work is to examine the long-term effects of developmental (postnatal day (P) 3-20) DLM exposure in Sprague-Dawley rats on behavior, cognition, and cellular outcomes. First, the developmental effects of early DLM exposure on allocentric and egocentric learning and memory, locomotor activity, startle, conditioned freezing, and anxiety-like behaviors were assessed. The developmental effects of DLM on long-term potentiation (LTP) at P25-35, on adult dopamine (DA) release, monoamine levels, and mRNA levels of receptors/transporters/channels were then determined. In follow-up experiments, adult LTP, hippocampal glutamate release, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining for cell death, as well as DA and glutamate receptors, proinflammatory cytokines, and caspase-3 for protein expression were assessed.