DOCSLIB.ORG

Contractile Response of Horse Deep Dorsal Penile Vein to Histamine

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Contractile Response of Horse Deep Dorsal Penile Vein to Histamine International Journal of Impotence Research (2002) 14, 85–92 ß 2002 Nature Publishing Group All rights reserved 0955-9930/02 $25.00 www.nature.com/ijir Contractile response of horse deep dorsal penile vein to histamine AC Martı´nez1, D Prieto1, M Herna´ndez1, A Garcı´a-Sacrista´n1 and S Benedito1* 1Seccio´n Departamental de Fisiologı´a, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain The present investigation was designed to evaluate the effect of histamine on isolated rings of horse deep dorsal penile vein. Under precontracted or basal conditions, histamine evoked an endothelium-independent contraction. Preincubation of the vein rings with the selective H1 receptor antagonist, mepyramine, shifted the concentration – response curve for histamine and to the H1 receptor agonist 2-pyridylethylamine to the right in a competitive manner. Pretreatment with cimetidine, a specific H2 receptor antagonist, did not modify the pEC50 and maximal contraction of the histamine response. Cimetidine and propranolol failed to induce a change in the relaxation caused by dimaprit, the H2 receptor agonist. Histamine contraction was unaffected by thioperamide, the specific H3 receptor antagonist. (R)-a-methylhistamine, the H3 receptor agonist, also induced contractions which persisted in the presence of either thioperamide or tetrodotoxin. These data indicate that horse deep dorsal penile vein shows an endothelium-independent contraction response to histamine, mainly mediated by H1 receptors. International Journal of Impotence Research (2002) 14, 85–92. DOI: 10.1038=sj=ijir=3900830 Keywords: deep dorsal penile vein; histamine; histamine receptors; H1 receptor; penile erection Introduction treatment of impotency,5,6 the role played by vasoactive factors such as cytokines, autacoids and=or neurotransmitters in maintaining normal The integrity of the vasculature of the penis is penile function is not yet fully understood. Post- essential for normal erectile function, with vascular junctional a-andb-adrenoceptors and prejunctional damage being one of the most common pathological a2-adrenoceptors have been identified in corpus 1 causes of erectile dysfunction. Under both normal cavernosum7 and in penile resistance (helicine) and pathological conditions, pressure buildup in the arteries, which control blood flow between the corpus cavernosum during erection depends mainly systemic arterial circulation and cavernous sinu- on the interaction between the arterial inflow system soids.8,9 In circumflex veins10 and in the deep dorsal and the venous draining system. It should be penile vein,11 a-adrenoceptor functions have also pointed out that venous draining vessels do not been demonstrated. Histamine has also been pro- fully collapse and flow through the penis continues posed as a possible mediator of penile erection on 2 throughout the erection period. The active con- the grounds that histamine-containing mastocytes tribution of penile veins to the reduction in venous have been identified in erectile tissue, coupled with outflow has not been fully established, but the the fact that the administration of this amine to the findings of several studies suggest that an active cavernous body is capable of evoking an erec- mechanism of venous occlusion adds to passive tion.12,13 Kirkeby et al,10 however, found that the compression of the outflow pathway resulting from histamine-induced relaxation of precontracted hu- 1,3 cavernous sinusoidal distension. Moreover, some man corpus cavernosum preparations and circum- authors claim that large veins including the deep flex veins was not significantly affected by blockage dorsal veins might be involved in the physiology of 14 of H1 and H2 receptors. In contrast, Kim et al, erection.4 reported that the histamine H1 receptor was the Though the discovery of the selective and potent main functional receptor subtype mediating smooth inhibitor of type V cyclic GMP phosphodiesterase, muscle contraction in the rabbit corpus cavernosum, sildenafil, has meant considerable advance in the yet other authors have shown the involvement of H2 receptors and no evidence of H1 receptor function in the histamine-induced relaxation of human caver- nosal strips.15 Moreover, our recent observations *Correspondence: S Benedito, Seccio´n Departamental de Fisiologı´a, Facultad de Farmacia, Universidad Complutense, indicate that the effect of histamine on dorsal penile 28040 Madrid, Spain. arteries is quite variable among different species E-mail: [email protected] (human, horse and rabbit).16 – 18 This amine has been Received 27 August 2001; accepted 21 November 2001 shown to elicit vasodilation, vasoconstriction, or a Contractile response of horse deep dorsal penile vein to histamine AC Martı´nez et al 86 combination of both these responses via stimulation (1074 M), was interpreted to indicate a non-func- of H1 receptors, H2 receptors or both. Taken tional endothelium. together, the results of these studies point to a role For experiments in which the effect of agonists on of this endogenous amine in the regulation of penile vein rings precontracted with noradrenaline function. (1076 M) (2.58 Æ 0.21 g; n ¼ 30) were examined, the This study was designed to determine the results are given as a percentage of the vascular response of the horse deep dorsal penile vein to contraction induced by this preconstrictor. These histamine, to characterise the functionally active noradrenaline concentrations yielded a stable level histamine receptors and to examine the dependence of contraction of sufficient duration to permit the of the histamine-induced response on the presence analysis of the agonist response. Effects observed in of the endothelial layer. preparations at basal tone were expressed as a percentage of the contractile response to K-PSS shown by each vessel (4.30 Æ 0.33 g; n ¼ 30). Materials and methods Since consecutive cumulative concentration – response curves to histamine indicated a desensiti- sation effect that modified the agonist response; only Vascular preparations and measurement of tension one concentration – response curve per vein ring was obtained under precontracted and basal condi- tions. Thus, it was necessary to use consecutive The penile tracts of young horses were obtained segments from the same animal in parallel experi- from a local slaughterhouse shortly after they were ments, with one ring acting as the control for the killed. The entire penis was transported to the other. Cumulative concentration – response curves laboratory in ice-cold physiological saline solution for histamine and various histaminergic agonists (PSS) to minimise tissue metabolism. were obtained by increasing the organ bath concen- The deep dorsal vein was identified and dissected tration in half-log-unit steps. free from surrounding connective tissue with the aid In order to examine the activity of each individual of a stereomicroscope (Nikon SMZ 2B). Vessel rings histamine receptor subtype, a given receptor agonist approximately 3 mm in length were transferred to was tested after pretreatment with a specific antago- organ baths containing PSS at 37C and aerated with nist to the other two receptor subtypes. a mixture of 95% O2 and 5% CO2 to maintain the pH at 7.4. The rings were mounted between two parallel L-shaped stainless steel wires (150 mm diameter). Analysis of results The endothelium of some rings was mechanically removed by gentle rubbing of the intimal surface with a stainless steel wire. Special care was taken to The agonist concentration required to give a half- avoid damage to the endothelium. One wire was maximal response (EC50) was determined for each fixed to a displacement unit allowing fine adjust- concentration – response curve by computerised ment of tension while the other was attached to a iteration. Responses and logarithmic concentrations force transducer (Grass FT03C). Isometric tension were fitted to the Hill equation using the GraphPAD was recorded on a polygraph (Houston D-5236-5). InPlot, non-linear curve fitting programme for The preparations were allowed to equilibrate for personal computers (GraphPAD Software, San Die- about 30 min in PSS and washed with fresh (37C) go, CA, USA). Sensitivities to the agonists are given PSS at 15 min intervals. After this equilibration in terms of pEC50 values, defined as the negative period, each ring was stretched in a stepwise logarithm of the EC50 for the agonists used. fashion to the optimal point of its length-tension Antagonist potency was assessed by calculating ratio ( 1 g). the pA2 value determined from the Schild plot analysis.19 In this method, the log concentration ratio (CR)-1 of the agonist is plotted against the log Experimental procedure concentration of the antagonists and these plots are then subjected to linear regression analysis. The concentration ratio denotes the ratio of the EC50 In all the experiments, the vein rings were exposed value obtained in the presence and absence of a to a twice depolarising potassium solution (119 mM, given concentration of antagonist. The slope of the K-PSS) at intervals of about 30 min. Schild plot is an indication of the nature of the The integrity of the vascular endothelium was antagonism. The slope should ideally be 1 if the confirmed by immediate relaxation (80 – 100%) response involves simple competitive antagonism at induced by acetylcholine (1076 M) in vessels pre- one receptor subtype only. Provided the regression contracted by noradrenaline. A lack of relaxation of the Schild plot is linear and the slope is not
Load more

Recommended publications
  • SYNTHESIS and STRUCTURE ACTIVITY STUDIES of NOVEL H3-RECEPTOR HISTAMINE ANTAGONISTS. a Thesis Presented in Partial Fulfilment Of
    1 SYNTHESIS AND STRUCTURE ACTIVITY STUDIES OF NOVEL H3-RECEPTOR HISTAMINE ANTAGONISTS. A thesis presented in partial fulfilment of the requirements for the Doctor of Philosophy Degree of the University of London SEYED KIUMARS HOSSEINI Department of Chemistry University College London September 1991 Attention is drawn to the fact that copyright of this thesis rests with its author. This copy of the thesis has been supplied on condition that anyone who consults it is understood to recognise that the copyright rests with its author and that no quotation from the thesis and no information derived from it may be published without prior consent of the author. Signature: Date..^*^^~ ProQuest Number: 10609847 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 10609847 Published by ProQuest LLC(2017). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 2 Acknowledgements I would like to express my gratitude for the guidance and generous support of Prof. C. R. Ganellin and for the financial support of Bioproject in association with Centre Paul Broca de rinserm, Paris. Thanks to Prof.
    [Show full text]
  • In Vitro Pharmacology of Clinically Used Central Nervous System-Active Drugs As Inverse H1 Receptor Agonists
    0022-3565/07/3221-172–179$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 322, No. 1 Copyright © 2007 by The American Society for Pharmacology and Experimental Therapeutics 118869/3215703 JPET 322:172–179, 2007 Printed in U.S.A. In Vitro Pharmacology of Clinically Used Central Nervous System-Active Drugs as Inverse H1 Receptor Agonists R. A. Bakker,1 M. W. Nicholas,2 T. T. Smith, E. S. Burstein, U. Hacksell, H. Timmerman, R. Leurs, M. R. Brann, and D. M. Weiner Department of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands (R.A.B., H.T., R.L.); ACADIA Pharmaceuticals Inc., San Diego, California (R.A.B., M.W.N., T.T.S., E.S.B., U.H., M.R.B., D.M.W.); and Departments of Pharmacology (M.R.B.), Neurosciences (D.M.W.), and Psychiatry (D.M.W.), University of California, San Diego, California Received January 2, 2007; accepted March 30, 2007 Downloaded from ABSTRACT The human histamine H1 receptor (H1R) is a prototypical G on this screen, we have reported on the identification of 8R- protein-coupled receptor and an important, well characterized lisuride as a potent stereospecific partial H1R agonist (Mol target for the development of antagonists to treat allergic con- Pharmacol 65:538–549, 2004). In contrast, herein we report on jpet.aspetjournals.org ditions. Many neuropsychiatric drugs are also known to po- a large number of varied clinical and chemical classes of drugs tently antagonize this receptor, underlying aspects of their side that are active in the central nervous system that display potent effect profiles.
    [Show full text]
  • G Protein-Coupled Receptors
    S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: G protein-coupled receptors Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4, Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5, Jamie A Davies5 and CGTP Collaborators 1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK, 2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK, 3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK, 4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK, 5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/ 10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading.
    [Show full text]
  • International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors
    1521-0081/67/3/601–655$25.00 http://dx.doi.org/10.1124/pr.114.010249 PHARMACOLOGICAL REVIEWS Pharmacol Rev 67:601–655, July 2015 Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics ASSOCIATE EDITOR: ELIOT H. OHLSTEIN International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors Pertti Panula, Paul L. Chazot, Marlon Cowart, Ralf Gutzmer, Rob Leurs, Wai L. S. Liu, Holger Stark, Robin L. Thurmond, and Helmut L. Haas Department of Anatomy, and Neuroscience Center, University of Helsinki, Finland (P.P.); School of Biological and Biomedical Sciences, University of Durham, United Kingdom (P.L.C.); AbbVie, Inc. North Chicago, Illinois (M.C.); Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany (R.G.); Department of Medicinal Chemistry, Amsterdam Institute of Molecules, Medicines and Systems, VU University Amsterdam, The Netherlands (R.L.); Ziarco Pharma Limited, Canterbury, United Kingdom (W.L.S.L.); Institute of Pharmaceutical and Medical Chemistry (H.S.) and Institute of Neurophysiology, Medical Faculty (H.L.H.), Heinrich-Heine-University Duesseldorf, Germany; and Janssen Research & Development, LLC, San Diego, California (R.L.T.) Abstract ....................................................................................602 Downloaded from I. Introduction and Historical Perspective .....................................................602 II. Histamine H1 Receptor . ..................................................................604 A. Receptor Structure
    [Show full text]
  • Supplementary Material a Gene Expression Signature Associated
    Supplementary Material A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy Jean-Pierre Gillet, Jesper B. Andersen, James P. Madigan, Sudhir Varma, Rachel K. Bagni, Katie Powell, William E. Burgan, Chung-Pu Wu, Anna Maria Calcagno, Suresh V. Ambudkar, Snorri S. Thorgeirsson, Michael M. Gottesman Journal: Molecular Pharmacology Table S1: Compounds highlighted through the Connectivity Map tool Rank for Name of drug on Connectivity Map score - Number of Connectivity Map Probability of getting Proportion of other drugs Drug signature is drug, rated Connectivity Map similarity between the experiments used score normalized an enrichment this that share this same significant for what according to gene expression signature to compute mean using scores from high if there is no signature (smaller values percent of the "n" p-value of drug and the signature similarity random selections of connection between mean that the signature is experiments? used as input genes drug signature and very specific to this input signature particular drug) Rank C-map name Mean n Enrichment p Specificity Percent non-null 1 8-azaguanine 0.916 4 0.975 0 0 100 2 adiphenine -0.765 5 -0.909 0 0.0242 100 3 trichostatin A 0.485 182 0.306 0 0.7204 73 4 tanespimycin 0.474 62 0.297 0 0.3834 72 5 apigenin 0.851 4 0.937 0.00002 0.0234 100 6 0175029-0000 0.797 6 0.86 0.00002 0.0177 100 7 thiamphenicol -0.711 5 -0.903 0.00004 0 100 8 thioguanosine 0.821 4 0.902 0.0001 0.0177 100 9 viomycin -0.723
    [Show full text]
  • 2 12/ 35 74Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 22 March 2012 (22.03.2012) 2 12/ 35 74 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 9/16 (2006.01) A61K 9/51 (2006.01) kind of national protection available): AE, AG, AL, AM, A61K 9/14 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/EP201 1/065959 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 14 September 201 1 (14.09.201 1) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, QA, RO, RS, RU, (25) Filing Language: English RW, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, (26) Publication Language: English TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 61/382,653 14 September 2010 (14.09.2010) US (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, NANOLOGICA AB [SE/SE]; P.O Box 8182, S-104 20 ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, Stockholm (SE).
    [Show full text]
  • Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release
    Neuropsychopharmacology (2004) 29, 705–717 & 2004 Nature Publishing Group All rights reserved 0893-133X/04 $25.00 www.neuropsychopharmacology.org Histamine H3 Receptor Antagonists Potentiate Methamphetamine Self-Administration and Methamphetamine-Induced Accumbal Dopamine Release 1,3,4 2,4 1,4 ,1 Patrik Munzar , Gianluigi Tanda , Zuzana Justinova and Steven R Goldberg* 1Preclinical Pharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Department of Health 2 and Human Services, Baltimore, MD, USA; Psychobiology Section, Medications Discovery Research Branch, Intramural Research Program, NIDA, NIH, Department of Health and Human Services, Baltimore, MD, USA Methamphetamine administration increases brain levels of histamine and neuronal histamine attenuates several of methamphetamine’s behavioral effects. The role of different subtypes of histamine receptors in this negative feedback, however, remains unclear. There is some evidence on possible involvement of histamine H3 receptors in these actions of methamphetamine. The aim of the present study was to evaluate the effects of two histamine H3 receptor antagonists, clobenpropit and thioperamide, on rewarding and neurochemical effects of methamphetamine utilizing three in vivo methodologies, drug self-administration, drug discrimination, and microdialysis in Sprague–Dawley rats. In rats self-administering methamphetamine intravenously under a fixed-ratio schedule, presession treatment with thioperamide (1.0–3.0 mg/kg, subcutaneous, s.c.) or clobenpropit (1.0–3.0 mg/kg, s.c.) potentiated the reinforcing effects of methamphetamine, as indicated by a dose-dependent increase in responding for a low 0.03 mg/kg dose of methamphetamine, that by itself failed to maintain responding above saline substitution levels, and a decrease in responding for a higher 0.06 mg/kg training dose of methamphetamine.
    [Show full text]
  • PROGRAM/ABSTRACTS International Honorary Local Organizing Advisory Board President Committee
    PROGRAM/ABSTRACTS International Honorary Local Organizing Advisory Board President Committee Y. Agid (Paris) G.L. Gessa (Cagliari) M. Diana (Coordinator) F.E. Bloom (La Jolla) V. Bassareo (Cagliari) A. Bjorklund (Lund) C. Cadoni (Cagliari) A. Carlsson (Goteborg) Organizers A. Carta (Cagliari) M. Caron (Durham) E. Carboni (Cagliari) G.U. Corsini (Pisa) M. Diana (Sassari) M.A. De Luca (Cagliari) S.B. Dunnett (Cardiff) G. Di Chiara (Cagliari) P. Enrico (Sassari) G.L. Gessa (Cagliari) P.F. Spano (Brescia) S. Fenu (Cagliari) A.M. Graybiel (Boston) M. Melis (Cagliari) P. Greengard (New York) C. Missale (Brescia) T. Hökfelt (Stockholm) M. Morelli (Cagliari) G.F. Koob (La Jolla) A.T. Peana (Sassari) J. Mallet (Paris) G. Piras (Cagliari) T.W. Robbins (Cambridge) U. Spampinato (Bordeaux) W. Schultz (Cambridge) S. Spiga (Cagliari) T. Svensson (Stockholm) V. Valentini (Cagliari) N.D. Volkow (Bethesda) M. Zigmond (Pittsburgh) ORGANIZED UNDER THE AUSPICES OF Provincia di Sassari Università di Sassari Camera di Commercio Nord Sardegna ADDITIONAL SPONSOR EXHIBITORS ORGANIZING SECRETARIAT Address: Via Del Pozzetto 13 - 09126 Cagliari, Sardinia (Italy) Ph.: +39 070 383373 - Fax: +39 070 3837102 e-mail: [email protected] - web address: www.corsiecongressi.com PROGRAM/ABSTRACTS Dopamine 2013 Friday, MAY 24th 8:00 – 8:30 REGISTRATION 8:30 – 10:30 SESSION 1 Topic: DOPAMINE AND REWARD Room: SAYÀL ENDOCANNABINOID/DOPAMINE INTERACTIONS AND THE PURSUIT OF REWARD Chair: E.L. Gardner (USA) - Co-Chair: J.F. Cheer (USA) Organizer: J. F. Cheer (USA) -M. Melis (Italy) Enhanced 2-arachidonoylglycerol signaling in dopamine neurons as a possible marker of heightened predisposition to addiction -C. Lupica (USA) Cocaine inhibition of synaptic GABA inputs to VTA DA neurons: Roles for serotonin and endocannabinoids -L.
    [Show full text]
  • Histamine Antagonists to Temper the Cytokine Overproduction in Gastrointestinal Cells Infected by SARS-Cov-2
    Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 30 April 2020 doi:10.20944/preprints202004.0542.v1 Histamine antagonists to temper the cytokine overproduction in gastrointestinal cells infected by SARS-CoV-2 A data / text minig study guided by biochemical knowledge Han Geurdes1 and Ivoyl Koutsaroff2 1 Abstract 2 The premise regarding COVID-19 disease is that it is a spectrum which begins with 3 infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The 4 individual response to it depends on many factors including co-morbid conditions. An 5 important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops 6 after the infection. The immuno-chemical chaos created in this cytokine storm is to the 7 benefit of the virus. In this meta analysis the authors explore ways to let the cytokine 8 storm die down by looking into the role of histamine. Histamine is a metabolic product 9 of the essential aminoacid histidine. Histamine has 4 known receptors: H1, H2, H3 and 10 H4. 11 The immunoglobulines IgE and IgM are indicative for a COVID-19 infection. This 12 immune response is related to inflammation. Inflammation, in turn, runs mainly via 13 histamine after e.g. virus inoculation. The goal of the meta-study is to gather evi- 14 dence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the 15 cytokine overproduction in the ≈ 30% of the patients suffering from gastrointestinal 16 problems caused by SARS-CoV-2. 17 Our concept is as follows. If we can strike a careful balance between hampering the 18 gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine 19 storm, then the natural immunity can later on come on line again and attack the virus 20 without being led astray by cytokine chaos.
    [Show full text]
  • Conviction on Itch
    Journal of Preventive Medicine and Holistic Health 2020;6(2):88–94 Content available at: https://www.ipinnovative.com/open-access-journals Journal of Preventive Medicine and Holistic Health Journal homepage: https://www.ipinnovative.com/journals/JPMHH Short Communication Conviction on itch Sunil Chaudhry1,* 1Bioclinitech Technologies Pvt. Ltd, Mumbai, Maharashtra, India ARTICLEINFO ABSTRACT Article history: Pruritus or itch is defined as an unpleasant sensation of the skin that provokes the urge to scratch. Received 25-12-2020 Histamine is one of the most important mediators of itch, although other chemical substances have also been Accepted 30-12-2020 implicated. In 10–50% of adults with persistent pruritus, it can be an important dermatologic clue for the Available online 02-02-2021 presence of a significant underlying systemic disease such as renal insufficiency, cholestasis, hematologic disorder, or malignancy. Antihistamines are used in the management of allergic conditions. They are useful for treating the itching that results from the release of histamine. Desloratadine and fexofenadine are Keywords: registered for use in infants six months and older, while loratadine and cetirizine can be used from 12 Pruritis months of age. A new era of antipruritic drugs targeting specific neural receptors, itchy cytokines, and small Chronic eczema molecules is swiftly approaching. Ultraviolet B, broad band or narrow band, Acupuncture, Transcutaneous Antihistamines electrical stimulation are supportive methods. Steroids © This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    [Show full text]
  • ( 12 ) United States Patent
    US010493080B2 (12 ) United States Patent (10 ) Patent No.: US 10,493,080 B2 Schultz et al. (45 ) Date of Patent : Dec. 3 , 2019 ( 54 ) DIRECTED DIFFERENTIATION OF (56 ) References Cited OLIGODENDROCYTE PRECURSOR CELLS TO A MYELINATING CELL FATE U.S. PATENT DOCUMENTS 7,301,071 B2 11/2007 Zheng (71 ) Applicants : The Scripps Research Institute , La 7,304,071 B2 12/2007 Cochran et al. Jolla , CA (US ) ; Novartis AG , Basel 9,592,288 B2 3/2017 Schultz et al. 2003/0225072 A1 12/2003 Welsh et al. ( CH ) 2006/0258735 Al 11/2006 Meng et al. 2009/0155207 Al 6/2009 Hariri et al . (72 ) Inventors : Peter Schultz , La Jolla , CA (US ) ; Luke 2010/0189698 A1 7/2010 Willis Lairson , San Diego , CA (US ) ; Vishal 2012/0264719 Al 10/2012 Boulton Deshmukh , La Jolla , CA (US ) ; Costas 2016/0166687 Al 6/2016 Schultz et al. Lyssiotis , Boston , MA (US ) FOREIGN PATENT DOCUMENTS (73 ) Assignees : The Scripps Research Institute , La JP 10-218867 8/1998 Jolla , CA (US ) ; Novartis AG , Basel JP 2008-518896 5/2008 (CH ) JP 2010-533656 A 10/2010 WO 2008/143913 A1 11/2008 WO 2009/068668 Al 6/2009 ( * ) Notice : Subject to any disclaimer , the term of this WO 2009/153291 A1 12/2009 patent is extended or adjusted under 35 WO 2010/075239 Al 7/2010 U.S.C. 154 ( b ) by 0 days . (21 ) Appl. No .: 15 /418,572 OTHER PUBLICATIONS Molin - Holgado et al . “ Regulation of muscarinic receptor function in ( 22 ) Filed : Jan. 27 , 2017 developing oligodendrocytes by agonist exposure ” British Journal of Pharmacology, 2003 , 138 , pp .
    [Show full text]
  • Histamine Antagonists to Temper the Cytokine Overproduction in Gastrointestinal Cells Infected by SARS-Cov-2
    & My gy co lo lo ro g i y V ISSN: 2161-0517 Virology & Mycology Perspective Histamine Antagonists to Temper the Cytokine Overproduction in Gastrointestinal Cells Infected by SARS-CoV-2 Geurdes H* Biochemistry Data Analyst, GDS Applied Mathematics BV, Den Haag, Netherlands ABSTRACT The premise regarding COVID-19 disease is that it is a spectrum which begins with infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The individual response to it depends on many factors including co- morbid conditions. An important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops after the infection. The immunochemical chaos created in this cytokine storm is to the benefit of the virus. In this meta- analysis the authors explore ways to let the cytokine storm die down by looking into the role of histamine. Histamine is a metabolic product of the essential amino acid histidine. Histamine has 4 known receptors: H1, H2, H3 and H4. The immuno globulines IgG and IgM are indicative for a COVID-19 infection. This immune response is related to inflammation. Inflammation, in turn, runs mainly via histamine after e.g. virus inoculation. The goal of the meta- study is to gather evidence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the cytokine overproduction in the problems caused by SARS-CoV-2. Our concept is as follows. If we can strike a careful balance between hampering the gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine storm, then the natural immunity can later on come on line again and attack the virus without being led astray by cytokine chaos.
    [Show full text]