Issn: 2455-7080

Total Page:16

File Type:pdf, Size:1020Kb

Issn: 2455-7080 ISSN: 2455-7080 Contents lists available at http://www.albertscience.com ASIO Journal of Experimental Pharmacology & Clinical Research (ASIO-JEPCR) Volume 1, Issue 1, 2016, 01-07 AN OVERVIEW OF TUBERCULOSIS MANAGEMENT: MECHANISM AND THERAPEUTIC APPLICATIONS Nidhi Singh Joint Replacement Surgery Research Unit, Fortis Escort Hospital, Jaipur, Rajasthan, India ARTICLE INFO ABSTRACT Tuberculosis infections have exceptional virulence factors compared to other Review Article History pathogens and they infect host cell and persist inside phagosomes. First Received: 29 October, 2015 symptoms of active pulmonary TB can include weight loss, night sweats, fever, Accepted: 05 January, 2016 and loss of appetite etc. The infection can either go into remission or become more serious with onset of chest pain and coughing up bloody sputum. The exact Corresponding Author: symptoms of extra-pulmonary TB vary according to the site of infection in the body. The Mantoux tuberculin skin test, also called as the PPD (purified protein Nidhi Singh derivative) test, is primarily used to identify TB infection. According to their clinical utility the anti-TB drugs can be divided into, two categories; one is first Joint Replacement Surgery line, these drugs have high anti-tubercular efficiency as well as low toxicity; are Research Unit, Fortis Escort used routinely, as for examples- Rifampin (R), Isoniazid (H), Streptomycin (S), Hospital, Jaipur, Rajasthan, India Pyrazinamide (Z), Ethambutol (E) and another is second line, these drugs have either low anti-tubercular efficacy or high toxicity or both; are used in special circumstances only. There are six classes of second-line drugs likes amino Email: [email protected] glycosides, fluoro quinolones, polypeptides, thioamides, cycloserine, p-amino salicylic acid. Another group of scientists found that a newly identified protein with carboxy-esterase activity is required for the virulence of Mycobacterium tuberculosis. Preliminary treatment for tuberculosis involved eats nourishing food and have plenty of fresh air. Keywords: TB, Mantoux, symptoms, anti-TB drugs, Mechanism of Actions. © www.albertscience.com, All Right Reserved. INTRODUCTION Tuberculosis is a chronic infectious disease caused by the source of nutrient, the utilization of glycerol by M. tubercle bacillus (Mycobacterium tuberculosis) and tuberculosis is inhibited. Therefore, it’s been shown that currently, the World Health Organization estimates that glutamate, and not glucose, is actually the main source of over 13 million people globally develop active TB and nutrient for initiating growth [4]. M. tuberculosis has about 1.7 million die each year from the disease. circular chromosomes of about 4,200,000 nucleotides long. Tuberculosis most commonly affects the lungs (pulmonary The genomes contain about 4000 genes. M. tuberculosis TB). Tb can also occur outside the lungs (extra has a tough cell wall that prevents passage of nutrients pulmonary), most commonly in the central nervous, into and excreted from the cell therefore giving it the lymphatic, or in the bones and joints [1-2]. characteristic of slow growth rate. Cell envelope contains Tuberculosis infections have unique virulence factors polypeptide layer, a peptidoglycan layer and there is also a compared to most pathogens and they infect host cell and complex structure of fatty acids such as mycolic acids, cell persist inside phagosomes where there are limited wall also contains lipid complexes such as acyl glycolipids nutrients [2-4]. Mycobacterium tuberculosis is an acid fast and beneath the cell wall there are layers of arabino- bacterium, which can form acid-stable complexes when galactan and peptidoglycan. certain aryl-methane is added [4]. All species of mycobacterium have rope like structures of peptidoglycan Classification- that are arranged in such a way to give them properties of Domain-Bacteria an acid fast bacterium [4]. Most commonly used strain of Phylum- Actinobacteria M. tuberculosis is the H37Rv strain. One way to study M. Class- Actinobacteria tuberculosis in culture is to collect samples of Order-Actinomycetales mononuclear cells in peripheral blood samples from a Family-Mycobacteriaceae healthy human donor and challenge macrophages with the Genus-Mycobacterium MTC. Their acid fast property is the strongest when there Species- M. africanmum, M. bovis, M. canettii, M. microti, 1 is glycerol around. However, when glucose is the main M. tuberulosis Page dids no.: 03.2016-35559215, dids Link: http://dids.info/didslink/03.2016-24581951/ Nidhi Singh / ASIO Journal of Experimental Pharmacology & Clinical Research (ASIO-JEPCR), 2016, 1(1): 01-07 Symptoms mammalian species as well as humans; M. bovis BCG, a Early symptoms of active pulmonary TB can include variant of M. bovis and M. canettii, a pathogen that infects weight loss, night sweats, fever, and loss of appetite [1]. human [8]. M. tuberculosis first infected humans 10,000- The infection can either go into remission or become more 15,000 years ago. It has been found in early hominids serious with onset of chest pain and coughing up bloody originating in East-Africa. Therefore, studying the sputum [5]. The exact symptoms of extra-pulmonary TB population structure of the species might provide insights vary according to the site of infection in the body. about Homo sapiens’ migratory and demographic history. Transmission In 1993, the World Health Organization declared TB a TB is spread through the air from one person to another. global public health emergency. A new dimension got Microscopic droplets that contain the bacteria may be added in the 1980s due to spread of HIV with high expelled when a person who has infectious TB coughs or prevalence of tuberculosis a Mycobacterium avium sneezes. They can remain suspended in the air for several complex (MAC) infection among these patients and India hours, depending on the environment. When a person has large load of HIV infected subjects and these patients breathes in M. tuberculosis, the bacteria can settle in the are especially vulnerable to serve forms of tubercular lungs and begin to grow. From there, they can move infection [9]. While lately the increase in TB case rate through the blood to other parts of the body. Tb in other associated with HIV infection has been halted in the USA, parts of the body, such as kidney or spine, is not infectious no such trend is apparent in India. Remarkable progress [1]. has been made in the last 60 years since the introduction Risk groups of Streptomycin in 1947 for the treatment of TB and its full Anyone can get TB. However, some groups are at higher therapeutic potential could be utilized only after 1952 risk to get active TB disease. when isoniazid was produced to accompany it [9]. The People at high risk include those [6]: discovery of ethambutol was in 1961, and rifampin was in With HIV infection. 1962. In close contact with those known to be infectious The sanatorium movement for treatment of with TB. Tuberculosis With medical conditions that make the body less able Until the discovery of tubercle bacillus, TB was treated in to protect itself from disease (for example: diabetes the home and doctors prescribed a variety of treatments or people undergoing treatment with drugs that can including snake oil and wearing a beard [3]. The suppress the immune system, such as long-term use sanatorium made its first appearance in the 1850s in of corticosteroids) Germany. The idea was developed by Herman Brehmer From countries with high TB rates after he was apparently cured by living in the Himalayan Who work in or are residents of long-term care climate [10-14]. Sanatoria treatment was reserved for the facilities (nursing homes, prisons, some hospitals) middle and upper class due to the costs associated with Who are malnourished? providing the 24 hours care, surgeries, and resort type Who are alcoholics or IV drug users? activities found at these institutions. Diagnosis The Prince Albert Sanatorium was the largest and most The Mantoux tuberculin skin test, also known as the PPD modern sanatorium in Saskatchewan, it opened in 1930 at (purified protein derivative) test, is used to detect TB Prince Albert, Saskatchewan. Part of idea behind Sanatoria infection. It is performed by injecting a small amount of was patient education and educational programs taught tuberculin, a complex of purified M. tuberculosis proteins, the infected what was known about the disease, new into the skin of the arm. A positive reaction for TB only health habits and how to live with and protect others [15]. reports that a person has been infected with TB bacteria. It After treatment was completed Sanatoria was offered does not tell whether or not the person has active disease rehabilitation to assist patients in achieving a satisfactory [7]. Other tests including a chest x-ray are often seen in the economic status. Rehabilitation involved slowly apical segments of the upper lobe or in the upper segments introducing occupational therapy into the treatment of the lower lobe. Chest x-rays may be used to rule out the regimen. Preliminary treatment for tuberculosis involved possibility of pulmonary TB in a person who has a positive following two rules [16]. reaction to the tuberculin skin test and no symptoms of Absolute and utter rest of mind and body, no bath, no disease. Person suspected of having pulmonary TB will movement except to toilet once a day, no sitting up have sputum specimens examined by acid-fast bacilli except propped by pillows and semi-reclining,
Recommended publications
  • Chloroquine Stimulates Cl Secretion by Ca Activated Cl Channels in Rat
    Chloroquine Stimulates Cl2 Secretion by Ca2+ Activated Cl2 Channels in Rat Ileum Ning Yang1., Zhen Lei2., Xiaoyu Li1, Junhan Zhao1, Tianjian Liu1, Nannan Ning1, Ailin Xiao1, Linlin Xu1, Jingxin Li1* 1 Department of Physiology, Shandong University School of Medicine, Jinan, China, 2 Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, China Abstract Chloroquine (CQ), a bitter tasting drug widely used in treatment of malaria, is associated gastrointestinal side effects including nausea or diarrhea. In the present study, we investigated the effect of CQ on electrolyte transport in rat ileum using the Ussing chamber technique. The results showed that CQ evoked an increase in short circuit current (ISC) in rat ileum at lower concentration (#561024 M ) but induced a decrease at higher concentrations ($1023 M). These responses were not affected by tetrodotoxin (TTX). Other bitter compounds, such as denatoniumbenzoate and quinine, exhibited similar 24 + effects. CQ-evoked increase in ISC was partly reduced by amiloride(10 M), a blocker of epithelial Na channels. Furosemide 24 + + 2 2 (10 M), an inhibitor of Na -K -2Cl co-transporter, also inhibited the increased ISC response to CQ, whereas another Cl channel inhibitor, CFTR(inh)-172(1025M), had no effect. Intriguingly, CQ-evoked increases were almost completely abolished by niflumic acid (1024M), a relatively specific Ca2+-activated Cl2 channel (CaCC) inhibitor. Furthermore, other CaCC inhibitors, such as DIDS and NPPB, also exhibited similar effects. CQ-induced increases in ISC were also abolished by thapsigargin(1026M), a Ca2+ pump inhibitor and in the absence of either Cl2 or Ca2+ from bathing solutions. Further studies demonstrated that T2R and CaCC-TMEM16A were colocalized in small intestinal epithelial cells and the T2R agonist CQ evoked an increase of intracelluar Ca2+ in small intestinal epithelial cells.
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • VDAC1 Is Essential for Neurite Maintenance and the Inhibition Of
    www.nature.com/scientificreports OPEN VDAC1 is essential for neurite maintenance and the inhibition of its oligomerization protects Received: 4 July 2019 Accepted: 4 September 2019 spinal cord from demyelination Published: xx xx xxxx and facilitates locomotor function recovery after spinal cord injury Vera Paschon1, Beatriz Cintra Morena1, Felipe Fernandes Correia1, Giovanna Rossi Beltrame1, Gustavo Bispo dos Santos2, Alexandre Fogaça Cristante2 & Alexandre Hiroaki Kihara 1 During the progression of the neurodegenerative process, mitochondria participates in several intercellular signaling pathways. Voltage-dependent anion-selective channel 1 (VDAC1) is a mitochondrial porin involved in the cellular metabolism and apoptosis intrinsic pathway in many neuropathological processes. In spinal cord injury (SCI), after the primary cell death, a secondary response that comprises the release of pro-infammatory molecules triggers apoptosis, infammation, and demyelination, often leading to the loss of motor functions. Here, we investigated the functional role of VDAC1 in the neurodegeneration triggered by SCI. We frst determined that in vitro targeted ablation of VDAC1 by specifc morpholino antisense nucleotides (MOs) clearly promotes neurite retraction, whereas a pharmacological blocker of VDAC1 oligomerization (4, 4′-diisothiocyanatostilbene-2, 2′-disulfonic acid, DIDS), does not cause this efect. We next determined that, after SCI, VDAC1 undergoes conformational changes, including oligomerization and N-terminal exposition, which are important steps in the triggering of apoptotic signaling. Considering this, we investigated the efects of DIDS in vivo application after SCI. Interestingly, blockade of VDAC1 oligomerization decreases the number of apoptotic cells without interfering in the neuroinfammatory response. DIDS attenuates the massive oligodendrocyte cell death, subserving undisputable motor function recovery. Taken together, our results suggest that the prevention of VDAC1 oligomerization might be benefcial for the clinical treatment of SCI.
    [Show full text]
  • Discovery, Characterization, and Development of Small
    DISCOVERY, CHARACTERIZATION, AND DEVELOPMENT OF SMALL MOLECULE INHIBITORS OF GLYCOGEN SYNTHASE Buyun Tang Submitted to the faculty of the University Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Department of Biochemistry and Molecular Biology, Indiana University June 2020 Accepted by the Graduate Faculty of Indiana University, in partial fulfillment of the requirements for the degree of Doctor of Philosophy. Doctoral Committee ______________________________________ Thomas D. Hurley, Ph.D., Chair ______________________________________ Peter J. Roach, Ph.D. April 30, 2020 ______________________________________ Millie M. Georgiadis, Ph.D. ______________________________________ Steven M. Johnson, Ph.D. ______________________________________ Jeffrey S. Elmendorf, Ph.D. ii © 2020 Buyun Tang iii Dedication I dedicate this work to my beloved family, my grandparents, my parents, and my brother. iv Acknowledgement First and foremost, I would like to express my deepest gratitude to my thesis advisor, Dr. Thomas D. Hurley. I am grateful to have him as my research mentor over the past four years. He has continuously guided, supported, and inspired me during my study at IUSM. His passion for science and devotion of mentorship offered me the best training experience I could ever receive in graduate school. His easygoing personality reminded me of all the wonderful times inside and outside of the lab. I remember him instructing me handling crystal instrument hand by hand, flying with me to San Diego for a conference, and driving me to a farm restaurant at Illinois. Dr. Hurley is not only an outstanding research mentor, but also a trustful friend. I deeply thank him for all his time, patience, and encouragement along my graduate training.
    [Show full text]
  • A Voltage-Dependent Chloride Channel Fine-Tunes Photosynthesis in Plants
    ARTICLE Received 19 Nov 2015 | Accepted 16 Apr 2016 | Published 24 May 2016 DOI: 10.1038/ncomms11654 OPEN A voltage-dependent chloride channel fine-tunes photosynthesis in plants Andrei Herdean1, Enrico Teardo2, Anders K. Nilsson1, Bernard E. Pfeil1, Oskar N. Johansson1, Rena´ta U¨nnep3,4, Gergely Nagy3,4, Otto´ Zsiros5, Somnath Dana1, Katalin Solymosi6,Gyoz+ o+ Garab5, Ildiko´ Szabo´2,7, Cornelia Spetea1 & Bjo¨rn Lundin1 In natural habitats, plants frequently experience rapid changes in the intensity of sunlight. To cope with these changes and maximize growth, plants adjust photosynthetic light utilization in electron transport and photoprotective mechanisms. This involves a proton motive force (PMF) across the thylakoid membrane, postulated to be affected by unknown anion (Cl À ) channels. Here we report that a bestrophin-like protein from Arabidopsis thaliana functions as a voltage-dependent Cl À channel in electrophysiological experiments. AtVCCN1 localizes to the thylakoid membrane, and fine-tunes PMF by anion influx into the lumen during illumination, adjusting electron transport and the photoprotective mechanisms. The activity of AtVCCN1 accelerates the activation of photoprotective mechanisms on sudden shifts to high light. Our results reveal that AtVCCN1, a member of a conserved anion channel family, acts as an early component in the rapid adjustment of photosynthesis in variable light environments. 1 Department of Biological and Environmental Sciences, University of Gothenburg, Gothenburg 40530, Sweden. 2 Department of Biology, University of Padova, Padova 35121, Italy. 3 Laboratory for Neutron Scattering and Imaging, Paul Scherrer Institute, Villigen 5232, Switzerland. 4 Institute for Solid State Physics and Optics, Wigner Research Centre for Physics, Hungarian Academy of Sciences, Budapest 1121, Hungary.
    [Show full text]
  • Characterization of L-Glutamic Acid Transport by Glioma Cells in Culture: Evidence for Sodium- Independent, Chloride-Dependent High Affinity Influx1
    0270.6474/84/0409-2237$02.00/O The Journal of Neuroscience Copyright 0 Society for Neuroscience Vol. 4, No. 9, pp. 2237-2246 Printed in U.S.A. September 1984 CHARACTERIZATION OF L-GLUTAMIC ACID TRANSPORT BY GLIOMA CELLS IN CULTURE: EVIDENCE FOR SODIUM- INDEPENDENT, CHLORIDE-DEPENDENT HIGH AFFINITY INFLUX1 ROBERT A. WANIEWSKI* AND DAVID L. MARTIN Center for Laboratories and Research, New York State Department of Health, Albany, New York 12201 Received January 23, 1984; Revised March 8, 1984; Accepted March 12, 1984 Abstract The transport of radiolabeled L-glutamic acid by LRM55 glioma cells in culture was examined. Time course studies indicated that L-[3H]glutamic acid is rapidly accumulated, and then 3H is lost from the cell, presumably in the form of glutamate metabolites. Kinetic analysis of L-glutamate uptake provided evidence for two components of transport. A low affinity component was found to persist at 0 to 4°C and was not saturable, influx being proportional to the substrate concentration. A high affinity component, resolved by subtraction of the influx at 0 to 4”C, followed Michaelis-Menten kinetics having a K, of 123 pM and a V,,, of 2.99 nmol/ min/mg of protein. The transport system was highly substrate-specific: At least 27-fold larger concentrations of the most potent analogues-cysteic acid, cysteine sulfinic acid, and L-aspartic acid-were required to compete effectively with glutamate. Second, the system was not severely affected by exposure to inhibitors of oxidative phosphorylation or y-glutamyltranspeptidase. Third, only 65% of the high affinity uptake was dependent upon the presence of sodium, the other 35% being dependent upon chloride.
    [Show full text]
  • 7Th International Congress on Amino Acids and Proteins Vienna, Austria
    Amino Acids (2001) 21: 1–90 7th International Congress on Amino Acids and Proteins Vienna, Austria August 6–10, 2001 Abstracts Co-Presidents: Steve Schaffer, Mobilel, AL, U.S.A. Michael Fountoulakis, Basel, Switzerland Gert Lubec, Vienna, Austria Contents Analysis................................................................................ 3 Biology ................................................................................ 10 Proteomics . 14 Medicine . 22 Metabolism/Nutrition . 25 Neurobiology . 35 Neuroscience . 45 Plant Amino Acids . 56 Physiology/Exercise and Sport . 59 Polyamines . 63 Synthesis . 68 Taurine ................................................................................ 74 Amino Acids Transport . 79 Addendum . 86 3 Analysis Fully automated HPLC based analysis of cysteine and related used for calculation of the degree of substitution in case of compounds in plasma using on line microdialysis as sample peptide-conjugates. The results of amino acid analysis were preparation verified by the data of ES mass spectrometry method. [This study was supported by grants from Hungarian E. Bald Research Fund (OTKA) T 030838, T025834, T032425, F034886 Department of Environmental Chemistry, University of ´Lodz´, and from the Ministry of Education (FKFP/0153/2001).] Poland Low molecular weight thiols play important roles in metabolism and homeostasis. While plasma thiols, including Free and bound cysteine in homocystinuria: assessment of metabolically related cysteine, glutathione, and homocysteine, cysteine and glutathione status are being investigated as potential indicators of health status A. Briddon1, I. P. Hargreaves1, and P. J. Lee2 and disease risk, trace levels, poor stability, and the lack of 1 structural properties necessary for the production of signals Department of Clinical Biochemistry, and compatible with common detection methods have hampered 2 Metabolic Unit, The National Hospital for Neurology and their accurate assessment. The facile oxidation of sulfhydryl Neurosurgery, London, U.K.
    [Show full text]
  • Deletion of the Na/HCO3 Transporter Nbcn1 Protects Hippocampal Neurons from NMDA- Induced Seizures and Neurotoxicity in Mice Hae Jeong Park1, Carlos E
    www.nature.com/scientificreports OPEN Deletion of the Na/HCO3 Transporter NBCn1 Protects Hippocampal Neurons from NMDA- induced Seizures and Neurotoxicity in Mice Hae Jeong Park1, Carlos E. Gonzalez-Islas 2,3, Yunhee Kang4, Jun Ming Li3 & Inyeong Choi3* The Na/HCO3 cotransporter NBCn1/SLC4A7 can afect glutamate neurotoxicity in primary cultures of rat hippocampal neurons. Here, we examined NMDA-induced neurotoxicity in NBCn1 knockout mice to determine whether a similar efect also occurs in the mouse brain. In primary cultures of hippocampal neurons from knockouts, NMDA had no neurotoxic efects, determined by lactate dehydrogenase release and nitric oxide synthase (NOS)-dependent cGMP production. Male knockouts and wildtypes (6–8 weeks old) were then injected with NMDA (75 mg/kg; ip) and hippocampal neuronal damages were assessed. Wildtypes developed severe tonic-clonic seizures, whereas knockouts had mild seizure activity (motionless). In knockouts, the NOS activity, caspase-3 expression/activity and the number of TUNEL-positive cells were signifcantly low. Immunochemical analysis revealed decreased expression levels of the NMDA receptor subunit GluN1 and the postsynaptic density protein PSD- 95 in knockouts. Extracellular recording from hippocampal slices showed no Mg2+/NMDA-mediated epileptiform events in knockouts. In conclusion, these results show a decrease in NMDA neurotoxicity by NBCn1 deletion. Given that acid extrusion has been known to prevent pH decrease and protect neurons from acid-induced damage, our study presents novel evidence that acid extrusion by NBCn1 stimulates neurotoxicity. Te pH in the brain extracellular space and cerebrospinal fuid is normally maintained at pH 7.3, but it can be substantially low under some pathological conditions1–4.
    [Show full text]
  • Methods and Protocols M ETHODS in M OLECULAR B IOLOGY
    Methods in Molecular Biology 1694 Rubén Alcázar Antonio F. Tiburcio Editors Polyamines Methods and Protocols M ETHODS IN M OLECULAR B IOLOGY Series Editor John M. Walker School of Life and Medical Sciences University of Hertfordshire Hatfield, Hertfordshire, AL10 9AB, UK For further volumes: http://www.springer.com/series/7651 Polyamines Methods and Protocols Edited by Rubén Alcázar and Antonio F. Tiburcio Department of Biology, Healthcare and Environment, Faculty of Pharmacy and Food Sciences, Section of Plant Physiology, University of Barcelona, Spain Editors Rube´n Alca´zar Antonio F. Tiburcio Department of Biology, Department of Biology, Healthcare and Environment, Healthcare and Environment, Faculty of Pharmacy and Food Sciences, Faculty of Pharmacy and Food Sciences, Section of Plant Physiology Section of Plant Physiology University of Barcelona University of Barcelona Spain Spain ISSN 1064-3745 ISSN 1940-6029 (electronic) Methods in Molecular Biology ISBN 978-1-4939-7397-2 ISBN 978-1-4939-7398-9 (eBook) DOI 10.1007/978-1-4939-7398-9 Library of Congress Control Number: 2017956111 © Springer Science+Business Media LLC 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
    [Show full text]
  • Receptors for Purines and Pyrimidines
    0031-6997/98/5003-0413$03.00/0 PHARMACOLOGICAL REVIEWS Vol. 50, No. 3 Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics Printed in U.S.A. Receptors for Purines and Pyrimidines VERA RALEVICa AND GEOFFREY BURNSTOCK School of Biomedical Sciences (V.R.), Queen’s Medical Centre, University of Nottingham, Nottingham, England; Autonomic Neuroscience Institute (G.B.), Royal Free Hospital School of Medicine, London, England This paper is available online at http://www.pharmrev.org I. Introduction........................................................................... 415 A. Overview ....................................................................... 415 B. Historical perspective ............................................................ 416 II. Adenosine/P1 Receptors ................................................................ 418 A. Introduction..................................................................... 418 B. Structure ....................................................................... 419 C. Agonists ........................................................................ 420 D. Antagonists ..................................................................... 421 III. A1 receptor............................................................................ 421 A. Cloned A1 receptors.............................................................. 422 B. Signal transduction mechanisms .................................................. 422 C. Desensitization .................................................................
    [Show full text]
  • Molecular Basis of Potassium Channels in Pancreatic Duct Epithelial Cells
    Molecular basis of potassium channels in pancreatic duct epithelial cells Hayashi, M.; Novak, Ivana Published in: Channels (Austin) DOI: 10.4161/chan.26100 Publication date: 2013 Document version Publisher's PDF, also known as Version of record Citation for published version (APA): Hayashi, M., & Novak, I. (2013). Molecular basis of potassium channels in pancreatic duct epithelial cells. Channels (Austin), 7(6), 432-441. https://doi.org/10.4161/chan.26100 Download date: 27. sep.. 2021 PAPER TYPE Channels 7:6, 432–441; November/December 2013; © 2013 Landes Bioscience Molecular basis of potassium channels in pancreatic duct epithelial cells Mikio Hayashi†,* and Ivana Novak* Department of Biology; University of Copenhagen; Copenhagen, Denmark; †Current affiliation: Department of Physiology; Kansai Medical University; Hirakata, Japan Keywords: cancer, EAG2, epithelia, HERG, pancreas, SK4, Slack, Slick, Slo1, TASK-2 Abbreviations: AKAP, A-kinase anchoring protein; BK, voltage – and Ca2+-dependent maxi-K+; BxPC3, human pancreas adenocarcinoma cell line; Capan-1, human pancreas adenocarcinoma cell line; CFPAC-1, human cystic fibrosis pancreatic adenocarcinoma cell line; CFTR, cystic fibrosis transmembrane conductance regulator; DC-EBIO, 5,6-dichloro-1-ethyl-1,3- dihydro-2H-benzimidazole-2-one; DHS-I, dehydrosoyasaponin I; DIDS, 4,4’-diisothiocyanatostilbene-2,2’-disulfonic acid; E-4031, N-[4-[1-[2-(6-methylpyridin-2-yl)ethyl]piperidine-4-carbonyl]phenyl] methanesulfonamide; EAG, ether-à-go-go gene; 1-EBIO, 1-ethyl-2-benzimidazolinone; HERG,
    [Show full text]
  • Lysophosphatidic Acid Receptor Agonism: Discovery of Potent Nonlipid Benzofuran Ethanolamine Structures S
    Supplemental material to this article can be found at: http://jpet.aspetjournals.org/content/suppl/2020/05/14/jpet.120.265454.DC1 1521-0103/374/2/283–294$35.00 https://doi.org/10.1124/jpet.120.265454 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS J Pharmacol Exp Ther 374:283–294, August 2020 Copyright ª 2020 by The American Society for Pharmacology and Experimental Therapeutics Lysophosphatidic Acid Receptor Agonism: Discovery of Potent Nonlipid Benzofuran Ethanolamine Structures s Etienne Guillot, Jean-Christophe Le Bail, Pascal Paul, Valérie Fourgous, Pascale Briand, Michel Partiseti, Bruno Cornet, Philip Janiak, and Christophe Philippo Diabetes and Cardiovascular Unit, Sanofi R&D, Chilly-Mazarin, France (E.G., J.C.L.B., P.B., P.J.); Global Research Portfolio and Project Management, Sanofi R&D, Chilly-Mazarin, France (C.P.); Translational Science Unit, Sanofi R&D, Chilly-Mazarin, France (P.P., V.F.); In-silico design, Chilly-Mazarin, France (B.C.); and Integrated Drug Discovery, Sanofi R&D, Vitry-Sur-Seine, France (M.P.) Received January 30, 2020; accepted May 11, 2020 Downloaded from ABSTRACT Lysophosphatidic acid (LPA) is the natural ligand for two potent agonist, CpY, doubled intraurethral pressure in anesthetized phylogenetically distinct families of receptors (LPA1–3, LPA4–6) female rats at 3 mg/kg i.v. Alternatively, CpX was shown to inhibit whose pathways control a variety of physiologic and patho- human preadipocyte differentiation, a process totally reversed by physiological responses. Identifying the benefit of balanced KI16425. Together with original molecular docking data, these jpet.aspetjournals.org activation/repression of LPA receptors has always been a challenge findings clearly established these molecules as potent agonists of because of the high lability of LPA and the limited availability of LPA1–3 and consolidated the pivotal role of LPA1 in urethra/prostate selective and/or stable agonists.
    [Show full text]