Inflammation-Induced Airway Hypersensitivity: From Ion Channels to Patients
|
|
- Charles Goodwin
- 6 years ago
- Views:
Transcription
1 Inflammation-Induced Airway Hypersensitivity: From Ion Channels to Patients Lu-Yuan Lee, Ph.D. Airway Sensory Neurobiology Laboratory Department of Physiology University of Kentucky Medical Center BACKGROUND AND HYPOTHESES My research interest focuses on the neurogenic mechanisms involved in the bronchial hyperreactivity, and ongoing projects are currently conducted in the Airway Sensory Neurobiology Laboratory at the University of Kentucky to study this in animal models and in human subjects. Airway hypersensitivity is a characteristic feature of airway inflammatory diseases such as asthma. When airway hypersensitivity develops during airway mucosal inflammation, the excitability of chemosensitive nerve endings innervating the airways is drastically enhanced. In healthy lungs, these tachykinin-containing sensory terminals located superficially in the airway mucosa (Fig. 1) play an important role in protecting the airways against inhaled irritants. Stimulation of these sensory endings elicits extensive cardiopulmonary reflex responses such as cough, bronchospasm, hypersecretion of mucus, etc. However, when these nerve endings become hypersensitive as a result of inflammation or injury of airway mucosa, a given level of stimulus will then evoke more sustained and intense stimulation. Thus, greater intensities of the reflex reactions as well as the neurogenic inflammation mediated through local release of tachykinins can lead to the development of bronchial hyperreactivity. Function of TRPV1-expressing sensory nerves and their interaction with other cell types in airway mucosa. EO, eosinophil; LO, lipooxygenase; PGE 2, prostaglandin E 2 ; BK, bradykinin; NGF, nerve growth factor; MBP, eosinophil major basic proteins; TKs, tachykinins; CGRP, calcitonin gene-related peptide. (From: Lee & Gu, 2009)
2 LONG-TERM OBJECTIVES Our long-term objectives are to answer the following questions: What are the physiological and pharmacological properties of the chemosensitive nerve endings in the lung? What are the roles of these sensory nerves in regulating cardiopulmonary functions under normal and various pathophysiological conditions of the airways? What are the endogenous and exogenous chemical substances that can alter the sensitivity of these sensory endings? What are the cellular mechanisms underlying the hypersensitivity of these sensory nerves caused by inflammation of airway mucosa, such as during airway injury or allergic reaction? What is the role of the transient receptor potential vanilloid type 1 (TRPV) ion channels in the airway hypersensitivity (exaggerated cough and bronchoconstrictive responses to inhaled irritants) developed during airway inflammatory reaction? ONGOING PROJECTS Several projects are currently conducted in our lab aimed specifically to: Uncover the mechanism of hypersensitivity of bronchopulmonary C neurons caused by cationic proteins, that are released from inflammatory cells (e.g., eosinophil, neutrophil, etc.) during airway anaphylaxis or injury. Identify the specific ion channels and the intracellular signal transduction pathways involved in the hypersensitivity of pulmonary sensory neurons induced by certain endogenous chemical mediators (e.g., prostaglandin E 2, adenosine, hydrogen ions, etc.) and pro-inflammatory cytokines (e.g., tumor necrosis factor-α) Determine the temperature-sensitive properties of bronchopulmonary C neurons, and investigate their roles in regulating the cardiopulmonary functions in responses to an acute increase in airway temperature (e.g., during airway inflammation, exercise, etc.) Understand the underlying mechanisms of airway hypersensitivity in patients with mild asthma, allergic rhinitis, laryngopharyngeal reflux, and post-viral infection Investigate the possible involvement of the TRPV1 channel in the manifestation of bronchoconstriction, cough and dyspneic sensation in these patients. REPRESENTATIVE RECENT STUDIES Sensitization of Vagal Pulmonary Sensory Neurons by Human Eosinophil-Derived Cationic Proteins Rationale and Hypothesis: During airway inflammatory reaction (e.g., in asthma), a number of low molecular weight, highly cationic proteins, such as major basic protein (MBP) and eosinophil cationic protein, are secreted by eosinophils that infiltrate into the airways. It is well documented that the release of these proteins can induce mucosal injury and airway hyperresponsiveness. However, the mechanism underlying both the initial stimulatory and the sustained sensitizing effects of cationic proteins on pulmonary sensory nerves is poorly understood.
3 Fig. 1 Fig. 3 Fig. 2 Fig. 1. MBP potentiates the capsaicin-evoked whole-cell inward current in isolated rat vagal pulmonary sensory neurons. Fig. 2. MBP enhances the action potential firing in response to electrical stimulation in rat vagal pulmonary sensory neurons. Fig. 3. MBP inhibits both sustained delayed-rectifier voltage-gated K + current (IK dr ) and A-type, fast-inactivating K+ current (IK a ) in rat vagal pulmonary sensory neurons. Summary of Results: Our studies have established the first evidence demonstrating an intense and sustained effect of eosinophil granule-derived proteins on vagal bronchopulmonary C-fiber endings, which is dependent on their cationic charge. Our results also demonstrate that MBP potentiates the capsaicin-evoked inward current in isolated pulmonary sensory neurons and up-regulates the excitability of these neurons to electrical stimulation. Our data further demonstrate that MBP significantly inhibits both IK dr and IK a in these neurons. Our studies therefore suggest that the direct and long-lasting sensitizing effect of these cationic proteins on pulmonary sensory nerves may play an important part in the manifestation of airway hyperresponsiveness associated with eosinophil infiltration in the airways. Hypersensitivity of TRPV1 Induced by Activation of Protease-activated Receptor-2 Rationale and Hypothesis: Protease-activated Receptor-2 (PAR 2 ) belongs to a family of G-protein-coupled, seven-transmembrane-domain receptors named PARs that are uniquely activated by proteolysis. Compelling evidence indicates that PAR 2 plays a critical role in the pathogenesis of airway inflammation and airway hyperresponsiveness. The primary objective of this study is to uncover the mechanism involved in the interaction between PAR 2 and C-fiber sensory nerves in the lung/airways.
4 Fig. 4 Fig. 5 Fig. 4. Activation of PAR 2 potentiates the capsaicin-evoked whole-cell inward current in isolated rat vagal pulmonary sensory neurons. Fig. 5. PAR 2 -AP potentiates single-channel activity of TRPV1 in cell-attached patches from rat pulmonary sensory neurons. Summary of Results: In anesthetized spontaneously breathing rats, airway exposure to trypsin, an endogenous agonist of PAR 2, significantly amplifies the capsaicin-induced pulmonary chemoreflex responses. In isolated rat vagal pulmonary sensory neurons, pretreatment with trypsin potentiated the capsaicin-induced whole-cell inward current; the effect is mimicked by PAR 2 -activating peptide (PAR 2 -AP) in a concentration-dependent manner. Activation of PAR 2 up-regulates single-channel activities of TRPV1 and the effect is mediated through the protein kinase C-dependent transduction pathway. An increase in capsaicin sensitivity and TRPV1 expression of pulmonary myelinated afferents in ovalbumin-sensitized rats Rationale and Hypothesis: Increasing evidence indicates that the TRPV1 receptor selectively expressed in vagal bronchopulmonary C-fibers plays a pivotal role in the manifestation of airway hypersensitivity, a prominent pathophysiological feature of airway inflammatory diseases. This study was carried out to investigate whether the sensitivity vagal afferents and expression of TRPV1 in these nerves are altered when chronic airway inflammation is induced by ovalbumin (Ova) sensitization in an animal model of asthma. Fig. 6 Fig. 6. Effect of Ova sensitization on TRPV1 expression in NF-positive and NF-negative neurons with DiI-labelling in nodose ganglion. Arrows, colocalization of NF staining, DiI labelling and TRPV1 staining in the same neurons. Asterisks, co-localization of NF staining and DiI labeling, but without TRPV1 staining. Scale bar, 50 μm.
5 Summary of Results: This study showed that allergen sensitization markedly elevates the baseline activity and excitability of pulmonary C-fibers. Interestingly, vagal bronchopulmonary myelinated afferents also exhibited capsaicin sensitivity in sensitized rats. Furthermore, the immunohistochemistry experiments showed that there was a significant increase in the proportion of TRPV1-expressing pulmonary neurons in nodose ganglia of sensitized rats, particularly in neurofilament-positive (myelinated) neurons. Hyperthermia Increases Sensitivity of Pulmonary C-fiber Neurons: Role of TRPV channels Rationale and Hypothesis: When body temperature increases during strenuous exercise or fever, the lung tissues including the sensory endings residing within the lung structures are subjected to hyperthermia. The TRPV channels expressed in the sensory terminals of bronchopulmonary C fibers are known to function as thermal transducers, with a different activation temperature threshold in each subtype of the TRPV channels. This study was, therefore, carried out to answer the following specific questions: 1) Are vagal pulmonary C- fibers sensitive to an increase in the temperature within the normal physiological range, and if so, can hyperthermia also directly activate isolated vagal pulmonary sensory neurons? 2) Is the response of these neurons to increase in temperature mediated through activation of TRPV channels? Fig. 7 Fig. 7. Effect of increasing temperature on vagal pulmonary sensory neurons in voltage-clamp (A) and current-clamp mode (B). C: the temperature-current relationships obtained from the two hyperthermia challenges in the same neuron (data taken from A). Fig. 8 Fig. 8. Blocking effects of capsazepine (CPZ, 10 µm) and ruthenium red (RR, 3 µm) on the hyperthermia-induced current in rat vagal pulmonary sensory neurons. C: group data (n=11) showing the effects of different treatments on cell response to hyperthermia.
6 Fig. 9 Fig. 9. Effect of increasing temperature on the response of vagal pulmonary sensory neurons to capsaicin (Cap). V m, membrane potential; BT, body temperature; HT, hyperthermic temperature; I, inward current evoked by Cap. Summary of Results: Isolated vagal pulmonary sensory neurons can be activated by an increase in temperature within the physiological range, and the thermal sensitivity of these neurons is mediated primarily through the activation of TRPV1. Increasing temperature also exerts a pronounced potentiating effect on the responses to TRPV1 activators in these neurons. This sensitizing effect results from a positive interaction between hyperthermia and these chemical activators at the TRPV1 channel. Hyperthermia-induced bronchoconstriction and cough in patients with mild asthma: a translational study Rationale and Hypothesis: Our recent studies have demonstrated that an activation of TRPV1 is primarily responsible for the stimulatory effect of hyperthermia on vagal bronchopulmonary C-fibers. We reasoned that a stimulation of these afferents will elicit bronchoconstriction via cholinergic reflex mechanism. Further, we hypothesized that the temperature threshold for activating these afferents will be reduced in patients with mild asthma. Hence, breathing warm, humid air can activate TRPV1 and elicit reflex bronchoconstriction and other airway dysfunction (e.g., cough, dyspnea, etc.).
7 Fig.10 Fig.11 Fig.12 Fig. 10. Effect of pretreatment with ipratropium aerosol or placebo on the response of airway resistance to warm humid air inhalation challenge air in six asthmatic patients. Fig. 11. Bronchomotor and cough responses were measured in asthmatic patients (UK Pulmonary Function Testing Laboratory and Clinical Research Development & Operations Center) Fig. 12. Experimental records illustrating a comparison of the flow-volume curves between baseline (blue) and that after termination of hyperventilation with humidified air (red) at room (RA; panel A) or high temperature (HA; panels B,C & D) on four different days in a patient with mild asthma. Summary of Results: This pilot study showed that breathing warm humidified air triggered cough and acute bronchoconstriction in mild asthmatic patients; the latter could be prevented by a pretreatment with ipratropium (atropine). These preliminary results indicated the involvement of airway sensory nerves and cholinergic mechanisms in the manifestation of various symptoms evoked by airway hyperthermia in these patients, which further suggests the potential involvement of TRPV1 over-expression in asthmatic airways as a possible contributing factor.
8 REPRESENTATIVE RECENT PUBLICATIONS ( ): Burki, N.K., M. Sheatt, and L.-Y. Lee. Effects of airway anesthesia on dyspnea and ventilatory response to intravenous injection of adenosine in healthy human subjects. Pulm Pharmacol Ther. 21: , Gu, Q., M.E. Wiggers, G.I. Gleich, and L.-Y. Lee. Sensitization of isolated rat vagal pulmonary sensory neurons by human eosinophil granule-derived cationic proteins. Am. J. Physiol.: Lung Cell. Mol. Physiol. 294: L544-52, Ni, D., and L.-Y. Lee. Effect of hyperthermia on excitability of isolated rat vagal pulmonary sensory neurons: role of TRPV1 receptor. Am. J. Physiol.: Lung Cell. Mol. Physiol. 294: L563-71, Zhang, G.,R.-L. Lin, M. Wiggers, D.M. Snow, and L.-Y. Lee. Altered expression of TRPV1 and sensitivity to capsaicin in pulmonary myelinated afferents following chronic airway inflammation in the rat. J. Physiol. (Lond) 586: , Lee, L.-Y. Respiratory Sensations Evoked by Activation of Bronchopulmonary C-fibers. In: Dyspnea (Special Issue), ed. by D.E. O Connell and J.T. Fisher. Respir. Physiol. Neurobiol. 167: 26-35, 2009 (Invited review). Lin, R.-L., D. Hayes, and L.-Y. Lee, Bronchoconstriction induced by hyperventilation with humidified hot air: role of TRPV1-expressing airway afferents. J. Apply. Physiol. 106: , Lee, L.-Y., and Q. Gu. Nicotine membrane receptors on cough sensors. In: Pharmacology and Therapeutics of Cough, ed by K.F. Chung and J.G. Widdicombe. Handbook of Experimental Pharmacology 187: 77-98, 2009 (Invited review). Lee, L.-Y., and Q. Gu. Role of TRPV1 receptor in inflammation-induced airway hypersensitivity. Current Opinion in Pharmacol. 9: , 2009 (Invited review). Hu, Y, Q. Gu, R.-L. Lin, R. Kryscio, and L.-Y. Lee. Calcium transient evoked by TRPV1 activators is enhanced by tumor necrosis factor alpha in rat pulmonary sensory neurons. Am. J. Physiol. Lung Cell. Mol. Physiol. 299: L483-92, Gu, Q., and L.-Y. Lee. Regulation of acid signaling in rat pulmonary sensory neurons by protease-activated receptor-2. Am. J. Physiol. Lung Cell. Mol. Physiol. 298: L454-61, Burki, N.K., and L.-Y. Lee. Mechanisms of dyspnea. Chest 138: , 2010 (Invited review). Lee, L.-Y., D. Ni, D. Hayes, and R.-L. Lin. TRPV1 as a cough sensor and its temperature-sensitive properties. Pulm. Pharmacol. Therap. 24: 280-5, 2011 (Invited review). Gu, Q. and L.-Y. Lee. Airway irritation and cough evoked by acid: from human to ion channel. Current Opinion in Pharmacol. 11: , 2011 (Invited review). Hayes, D., P.B. Collins, M. Khosravi, and L.-Y. Lee. Bronchoconstriction triggered by breathing hot humid air in asthmatics: role of TRPV1 receptor. Am. J. Resp. Crit Care Med. 185: , Hsu, C.C., Y.S. Lin, R.-L. Lin and L.-Y. Lee. Bronchoconstriction induced by increasing airway temperature in ovalbumin-sensitized rats: role of tachykinins. J. Appl. Physiol. 115: , Hsu, C.C., R.-L. Lin, L.-Y. Lee and Y.S. Lin. Hydrogen sulfide induces hypersensitivity of rat lung vagal neurons: role of TRPA1 receptors. Am. J. Physiol. : Reg. Int. Comp. Physiol. 305: R769-79, Lin, R.-L., Y.J. Lin, M.J. Geer, R. Kryscio and L.-Y. Lee. Pulmonary chemoreflex responses are potentiated by tumor necrosis factor-alpha in mice. J Appl Physiol. 114: , Lee, L.-Y., Q. Gu, F. Xu, J.L. Hong. Acid-sensing by airway afferent nerves. Pulm Pharmacol Ther. 26: 491-7, Lee, L.-Y., J. Yu. Sensory nerves in lung and airways. Comprehensive Physiology (American Physiological Society). 4: , 2014 (Invited review). doi: /cphy.
9 Airway Sensory Neurobiology Laboratory Lu-Yuan Lee You-Shuei (Emy) Lin
TITLE: Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves
Award Number: W81XWH-10-2-0189 TITLE: Pulmonary Stress Induced by Hyperthermia: Role of Airway Sensory Nerves PRINCIPAL INVESTIGATOR: Lu-Yuan Lee, Ph.D. CONTRACTING ORGANIZATION: University of Kentucky
More informationRole of TRPV Receptors in Respiratory Diseases
Role of TRPV Receptors in Respiratory Diseases Yanlin Jia, Lu-Yuan Lee To cite this version: Yanlin Jia, Lu-Yuan Lee. Role of TRPV Receptors in Respiratory Diseases. Biochimica et Biophysica Acta - Molecular
More informationTHERMAL SENSITIVITY OF VAGAL PULMONARY SENSORY NEURONS: ROLE OF TRANSIENT RECEPTOR POTENTIAL VANILLOID CHANNELS
University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2008 THERMAL SENSITIVITY OF VAGAL PULMONARY SENSORY NEURONS: ROLE OF TRANSIENT RECEPTOR POTENTIAL VANILLOID
More informationChapter 7. Anticholinergic (Parasympatholytic) Bronchodilators. Mosby items and derived items 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
Chapter 7 Anticholinergic (Parasympatholytic) Bronchodilators Clinical Indications for Use Indication for anticholinergic bronchodilator COPD maintenance Indication for combined anticholinergic and β-agonist
More informationSystems Pharmacology Respiratory Pharmacology. Lecture series : General outline
Systems Pharmacology 3320 2017 Respiratory Pharmacology Associate Professor Peter Henry (Rm 1.34) Peter.Henry@uwa.edu.au Division of Pharmacology, School of Biomedical Sciences Lecture series : General
More informationRespiratory Pharmacology. Manuel Otero Lopez Department of Anaesthetics and Intensive Care Hôpital Européen Georges Pompidou, Paris, France
Respiratory Pharmacology Manuel Otero Lopez Department of Anaesthetics and Intensive Care Hôpital Européen Georges Pompidou, Paris, France Programme Bronchomotor tone Drugs and factors influencing airway
More informationAsthma Management for the Athlete
Asthma Management for the Athlete Khanh Lai, MD Assistant Professor Division of Pediatric Pulmonary and Sleep Medicine University of Utah School of Medicine 2 nd Annual Sports Medicine Symposium: The Pediatric
More informationLearning Outcomes. Systems Pharmacology PHAR3320. Nerves of the Respiratory Tract. Dr Fernandes
Systems Pharmacology PHAR3320 Nerves of the Respiratory Tract Dr Fernandes Learning Outcomes By the end of this lecture, students should be able to describe nerve pathways that innervate the airways discuss
More informationRole of the Brain-Lung Axis in Fatigue
Role of the Brain-Lung Axis in Fatigue Y.S. Prakash, M.D., Ph.D. Professor of Anesthesiology and Physiology Chair, Department of Physiology & BME Mayo Clinic Rochester, Minnesota, USA Fatigue in Chronic
More informationEFFECT OF CHRONIC AIRWAY INFLAMMATION INDUCED BY ALLERGEN SENSITIZATION ON VAGAL BRONCHOPULMONARY SENSORY NERVES IN RATS
University of Kentucky UKnowledge University of Kentucky Doctoral Dissertations Graduate School 2008 EFFECT OF CHRONIC AIRWAY INFLAMMATION INDUCED BY ALLERGEN SENSITIZATION ON VAGAL BRONCHOPULMONARY SENSORY
More informationPathophysiology of Pain
Pathophysiology of Pain Wound Inflammatory response Chemical mediators Activity in Pain Path PAIN http://neuroscience.uth.tmc.edu/s2/chapter08.html Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci University
More informationRESPIRATORY BLOCK. Bronchial Asthma. Dr. Maha Arafah Department of Pathology KSU
RESPIRATORY BLOCK Bronchial Asthma Dr. Maha Arafah Department of Pathology KSU marafah@ksu.edu.sa Jan 2018 Objectives Define asthma (BA) Know the two types of asthma 1. Extrinsic or atopic allergic 2.
More informationImpact of Asthma in the U.S. per Year. Asthma Epidemiology and Pathophysiology. Risk Factors for Asthma. Childhood Asthma Costs of Asthma
American Association for Respiratory Care Asthma Educator Certification Prep Course Asthma Epidemiology and Pathophysiology Robert C. Cohn, MD, FAARC MetroHealth Medical Center Cleveland, OH Impact of
More informationIndex. Note: Page numbers of article titles are in boldface type.
Note: Page numbers of article titles are in boldface type. A Afferent nerves, interactions of, in cough, 20 21 Airway, eosinophilic inflammation of, 124 narrowing of, in asthma, 126 protection of, terms
More informationFunction of the Respiratory System. Exchange CO2 (on expiration) for O2 (on inspiration)
Function of the Respiratory System Exchange CO2 (on expiration) for O2 (on inspiration) Upper Respiratory Tract Includes: Nose Mouth Pharynx Larynx Function: Warms and humidifies the inspired air Filters
More informationImmunology of Asthma. Kenneth J. Goodrum,Ph. Ph.D. Ohio University College of Osteopathic Medicine
Immunology of Asthma Kenneth J. Goodrum,Ph Ph.D. Ohio University College of Osteopathic Medicine Outline! Consensus characteristics! Allergens:role in asthma! Immune/inflammatory basis! Genetic basis!
More informationDr Rodney Itaki Lecturer Division of Pathology Anatomical Pathology Discipline
Pathology of Asthma Dr Rodney Itaki Lecturer Division of Pathology Anatomical Pathology Discipline Bronchial Asthma Definition: chronic, relapsing inflammatory lung disorder characterised by reversible
More informationPharmacology of Pain Transmission and Modulation
Pharmacology of Pain Transmission and Modulation 2 Jürg Schliessbach and Konrad Maurer Nociceptive Nerve Fibers Pain is transmitted to the central nervous system via thinly myelinated Aδ and unmyelinated
More informationChronic Cough. Abhishek Kumar, MD, MPH Pulmonary and Critical Care Mercy Medical Center, Cedar Rapids, IA
Chronic Cough Abhishek Kumar, MD, MPH Pulmonary and Critical Care Mercy Medical Center, Cedar Rapids, IA What we shall discuss? Cough anatomy and pathophysiology Common etiologies Work-up Role of spirometry/pulmonary
More informationThe Pain Pathway. dorsal root ganglion. primary afferent nociceptor. TRP: Transient Receptor Potential
Presented by Issel Anne L. Lim 1 st Year PhD Candidate Biomedical Engineering Johns Hopkins University 580.427/580.633 Ca Signals in Biological Systems Outline The Pain Pathway TRP: Transient Receptor
More informationSystems Pharmacology Respiratory Pharmacology. Lecture series : General outline
Systems Pharmacology 3320 2017 Respiratory Pharmacology Associate Professor Peter Henry (Rm 1.34) Peter.Henry@uwa.edu.au Division of Pharmacology, School of Biomedical Sciences Lecture series : General
More informationWhat is on the Horizon in Drug Therapy for OAB?
What is on the Horizon in Drug Therapy for OAB? K-E Andersson, MD, PhD Wake Forest Institute for Regenerative Medicine Wake Forest University School of Medicine Winston Salem, North Carolina Disclosures
More informationIntroduction to some interesting research questions: Molecular biology of the primary afferent nociceptor
Introduction to some interesting research questions: Molecular biology of the primary afferent nociceptor NOCICEPTORS ARE NOT IDENTICAL PEPTIDE SubP/CGRP Trk A NON-PEPTIDE IB4 P2X 3 c-ret Snider and McMahon
More informationIntracellular signalling cascades associated with TRP channels
Gerald Thiel Intracellular signalling cascades associated with TRP channels Current state of investigations and potential applications Saarland University, Germany Campus Saarbrücken Department of Medical
More informationChapter 2 Electrophysiologically Identified Airway Receptors: Main Characteristics
Chapter 2 Electrophysiologically Identified Airway Receptors: Main Characteristics The most generally accepted classification discriminates mechanosensory slowly adapting (stretch) receptors (SARs), rapidly
More informationTMC9 as a novel mechanosensitive ion channel
TMC9 as a novel mechanosensitive ion channel Mechanical forces play numerous roles in physiology. When an object contacts our skin, it exerts a force that is encoded as touch or pain depending on its intensity.
More information211MDS Pain theories
211MDS Pain theories Definition In 1986, the International Association for the Study of Pain (IASP) defined pain as a sensory and emotional experience associated with real or potential injuries, or described
More informationExercise-Induced Bronchoconstriction EIB
Exercise-Induced Bronchoconstriction EIB Case 1 14 yo boy, freshman in high school Complains of shortness of breath 2 minutes into a mile-run in his first gym class Same complains in his 2 nd gym class
More informationChapter 6 Communication, Integration, and Homeostasis
Chapter 6 Communication, Integration, and Homeostasis About This Chapter Cell-to-cell communication Signal pathways Novel signal molecules Modulation of signal pathways Homeostatic reflex pathways Cell-to-Cell
More informationHistory & Development
RSPT 2317 Anticholinergic Bronchodilators () History & Development Prototypical parasympatholytic agent is atropine an alkaloid found naturally in the plants Atropa belladona (nightshade) and Datura species
More informationProstaglandin E 2 Enhances Chemical and Mechanical Sensitivities of Pulmonary C Fibers in the Rat
Prostaglandin E 2 Enhances Chemical and Mechanical Sensitivities of Pulmonary C Fibers in the Rat CHING-YIN HO, QIHAI GU, JU-LUN HONG, and LU-YUAN LEE Department of Physiology, University of Kentucky,
More informationAnalgesic Drugs PHL-358-PHARMACOLOGY AND THERAPEUTICS-I. Mr.D.Raju,M.pharm, Lecturer
Analgesic Drugs PHL-358-PHARMACOLOGY AND THERAPEUTICS-I Mr.D.Raju,M.pharm, Lecturer Mechanisms of Pain and Nociception Nociception is the mechanism whereby noxious peripheral stimuli are transmitted to
More informationRisk Factors That Predispose Patients to Orofacial Pain
Risk Factors That Predispose Patients to Orofacial Pain Paul Durham, PhD Distinguished Professor of Cell Biology Director Center for Biomedical & Life Sciences Missouri State University Cluster Headache
More informationPathophysiology of Pain. Ramon Go MD Assistant Professor Anesthesiology and Pain medicine NYP-CUMC
Pathophysiology of Pain Ramon Go MD Assistant Professor Anesthesiology and Pain medicine NYP-CUMC Learning Objectives Anatomic pathway of nociception Discuss the multiple target sites of pharmacological
More informationBasic mechanisms disturbing lung function and gas exchange
Basic mechanisms disturbing lung function and gas exchange Blagoi Marinov, MD, PhD Pathophysiology Department, Medical University of Plovdiv Respiratory system 1 Control of breathing Structure of the lungs
More informationHYPERSENSITIVITY REACTIONS D R S H O AI B R AZ A
HYPERSENSITIVITY REACTIONS D R S H O AI B R AZ A HYPERSENSITIVITY REACTIONS Are exaggerated immune response upon antigenic stimulation Individuals who have been previously exposed to an antigen are said
More informationNeuro-immune interactions in allergic diseases: novel targets for therapeutics
International Immunology, Vol. 29, No. 6, pp. 247 261 doi:10.1093/intimm/dxx040 Advance Access publication 13 July 2017 The Japanese Society for Immunology. 2017. All rights reserved. For permissions,
More informationTitle proteinase-activated receptor 2 ago. Published by Elsevier Ireland Ltd.
NAOSITE: Nagasaki University's Ac Title Author(s) Olopatadine hydrochloride inhibits proteinase-activated receptor 2 ago Yoshizaki, Ayumi; Sato, Shinichi Citation Journal of dermatological science, Issue
More informationRespiratory Pharmacology PCTH 400 Asthma and β-agonists
Respiratory Pharmacology PCTH 400 Asthma and β-agonists Dr. Tillie-Louise Hackett Department of Anesthesiology, Pharmacology and Therapeutics University of British Columbia Associate Director, Centre of
More informationLocal Anesthetics. Xiaoping Du Room E417 MSB Department of Pharmacology Phone (312) ;
Local Anesthetics Xiaoping Du Room E417 MSB Department of Pharmacology Phone (312)355 0237; Email: xdu@uic.edu Summary: Local anesthetics are drugs used to prevent or relieve pain in the specific regions
More informationASTHMA. Epidemiology. Pathophysiology. Diagnosis. IAP UG Teaching slides
BRONCHIAL ASTHMA ASTHMA Epidemiology Pathophysiology Diagnosis 2 CHILDHOOD ASTHMA Childhood bronchial asthma is characterized by Airway obstruction which is reversible Airway inflammation Airway hyper
More informationPotent and Selective CRTh2 Antagonists are Efficacious in Models of Asthma, Allergic Rhinitis and Atopic Dermatitis
Potent and Selective CRTh2 Antagonists are Efficacious in Models of Asthma, Allergic Rhinitis and Atopic Dermatitis Laura L. Carter, Yoshi Shiraishi, Yooseob Shin, Laurence Burgess, Christine Eberhardt,
More informationAsthma. - A chronic inflammatory disorder which causes recurrent episodes of wheezing, breathlessness, cough and chest tightness.
Obstructive diseases Asthma - A chronic inflammatory disorder which causes recurrent episodes of wheezing, breathlessness, cough and chest tightness. - Characterized by Intermittent and reversible (the
More informationRESPIRATORY PHARMACOLOGY - ASTHMA. Primary Exam Teaching - Westmead ED
RESPIRATORY PHARMACOLOGY - ASTHMA Primary Exam Teaching - Westmead ED Sympathomimetic agents MOA: relax airway smooth muscle and inhibit broncho constricting mediators from mast cells May also inhibit
More informationCHAPTER 10 THE SOMATOSENSORY SYSTEM
CHAPTER 10 THE SOMATOSENSORY SYSTEM 10.1. SOMATOSENSORY MODALITIES "Somatosensory" is really a catch-all term to designate senses other than vision, hearing, balance, taste and smell. Receptors that could
More informationThe mammalian cochlea possesses two classes of afferent neurons and two classes of efferent neurons.
1 2 The mammalian cochlea possesses two classes of afferent neurons and two classes of efferent neurons. Type I afferents contact single inner hair cells to provide acoustic analysis as we know it. Type
More informationAnatomy and Neurophysiology of Cough CHEST Guideline and Expert Panel Report
[ Evidence-Based Medicine ] Anatomy and Neurophysiology of Cough CHEST Guideline and Expert Panel Report Brendan J. Canning, PhD ; Anne B. Chang, MBBS, PhD, MPH ; Donald C. Bolser, PhD ; Jaclyn A. Smith,
More informationRole of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary sensory neurons
J Appl Physiol 118: 1533 1543, 2015. First published April 9, 2015; doi:10.1152/japplphysiol.00043.2015. Role of calcium ions in the positive interaction between TRPA1 and TRPV1 channels in bronchopulmonary
More informationDefining Asthma: Clinical Criteria. Defining Asthma: Bronchial Hyperresponsiveness
Defining Asthma: Clinical Criteria Atopy 34% Recent wheeze 20% Asthma 11% AHR 19% n = 807 From: Woolcock, AJ. Asthma in Textbook of Respiratory Medicine, 2nd ed. Murray, Nadel, eds.(saunders:philadelphia)
More informationComplexity in asthma, fluctuations in airway function and avalanches; beyond single measurements of lung function.
Complexity in asthma, fluctuations in airway function and avalanches; beyond single measurements of lung function. Urs Frey, MD PhD Dept of Paediatric Respiratory Medicine, University Children s Hospital
More informationSynaptic Integration
Synaptic Integration 3 rd January, 2017 Touqeer Ahmed PhD Atta-ur-Rahman School of Applied Biosciences National University of Sciences and Technology Excitatory Synaptic Actions Excitatory Synaptic Action
More informationSupplementary Figure 1 NMR spectra of hydroxy α and β-sanshool isomers. (Top) Hydroxy-α-sanshool (2E,6Z,8E,10E)-2'-
Supplementary Figure 1 NMR spectra of hydroxy α and β-sanshool isomers. (Top) Hydroxy-α-sanshool (2E,6Z,8E,10E)-2'- hydroxyl-n-isobutyl-2,6,8,10-dodeca-tetraenamide) and (bottom) hydroxy-β-sanshool (2E,6E,8E,10E)-2'-hydroxyl-N-isobutyl-
More informationRespiratory Health L O O K, F E E L A N D L I V E B E T T E R
LOOK, FEEL AND LIVE BET TER Respiratory health: hay-fever and asthma Airway obstruction and symptoms in asthma and hay-fever alike are the result of inappropriate responses of the body s immune system
More informationSafety, PK and PD of ARRY-502, a CRTh2 Antagonist, in Healthy Subjects with a History of Seasonal Allergies
Safety, PK and PD of ARRY502, a CRTh2 Antagonist, in Healthy Subjects with a History of Seasonal Allergies L. Burgess*, L. Anderson, C. Nugent, N. Klopfenstein, C. Eberhardt, L. Carter, C. Kass, S. RojasCaro,
More informationBronchial asthma. MUDr. Mojmír Račanský Odd. Alergologie a klinické imunologie FNOL Ústav Imunologie LF UPOL
Bronchial asthma MUDr. Mojmír Račanský Odd. Alergologie a klinické imunologie FNOL Ústav Imunologie LF UPOL DEFINITION ASTHMA BRONCHIALE = Asthma is a chronic inflammatory disorder of the airways in which
More informationPain Pathways. Dr Sameer Gupta Consultant in Anaesthesia and Pain Management, NGH
Pain Pathways Dr Sameer Gupta Consultant in Anaesthesia and Pain Management, NGH Objective To give you a simplistic and basic concepts of pain pathways to help understand the complex issue of pain Pain
More informationSTRUCTURAL ELEMENTS OF THE NERVOUS SYSTEM
STRUCTURAL ELEMENTS OF THE NERVOUS SYSTEM STRUCTURE AND MAINTENANCE OF NEURONS (a) (b) Dendrites Cell body Initial segment collateral terminals (a) Diagrammatic representation of a neuron. The break in
More informationIntegrated Cardiopulmonary Pharmacology Third Edition
Integrated Cardiopulmonary Pharmacology Third Edition Chapter 13 Pharmacologic Management of Asthma, Chronic Bronchitis, and Emphysema Multimedia Directory Slide 7 Slide 12 Slide 60 COPD Video Passive
More informationAnatomy and Neurophysiology of the Cough Reflex. ACCP Evidence-Based Clinical Practice Guidelines
Anatomy and Neurophysiology of the Cough Reflex ACCP Evidence-Based Clinical Practice Guidelines Brendan J. Canning, PhD Objectives: To describe the anatomy and neurophysiology of the cough reflex. Methods:
More informationAir Flow Limitation. In most serious respiratory disease, a key feature causing morbidity and functional disruption is air flow imitation.
Asthma Air Flow Limitation In most serious respiratory disease, a key feature causing morbidity and functional disruption is air flow imitation. True whether reversible, asthma and exercise-induced bronchospasm,
More informationChapter 3 subtitles Action potentials
CELLULAR NEUROPHYSIOLOGY CONSTANCE HAMMOND Chapter 3 subtitles Action potentials Introduction (3:15) This third chapter explains the calcium current triggered by the arrival of the action potential in
More informationIntroduction to Neurobiology
Biology 240 General Zoology Introduction to Neurobiology Nervous System functions: communication of information via nerve signals integration and processing of information control of physiological and
More informationCorporate Medical Policy
Corporate Medical Policy Intravenous Anesthetics for the Treatment of Chronic Pain File Name: Origination: Last CAP Review: Next CAP Review: Last Review: intravenous_anesthetics_for_the_treatment_of_chronic_pain
More informationThe action potential travels down both branches because each branch is a typical axon with voltage dependent Na + and K+ channels.
BIO 360 - MIDTERM FALL 2018 This is an open book, open notes exam. PLEASE WRITE YOUR NAME ON EACH SHEET. Read each question carefully and answer as well as you can. Point values are shown at the beginning
More informationRESPIRATORY PHARMACOLOGY
Yerevan State Medical University Department of Anaesthesiology and Intensive Care Yerevan, Armenia RESPIRATORY PHARMACOLOGY Dr. Armen VAROSYAN Associate Professor, DEAA, PhD Lecture Outline Drugs stimulating
More informationAsthma Description. Asthma is a disease that affects the lungs defined as a chronic inflammatory disorder of the airways.
Asthma Asthma Description Asthma is a disease that affects the lungs defined as a chronic inflammatory disorder of the airways. Symptoms of asthma In susceptible individuals, this inflammation causes recurrent
More informationLecture Notes. Chapter 3: Asthma
Lecture Notes Chapter 3: Asthma Objectives Define asthma and status asthmaticus List the potential causes of asthma attacks Describe the effect of asthma attacks on lung function List the clinical features
More informationCough induction by high-frequency chest percussion in healthy volunteers and patients with common cold
Respiratory Medicine (2004) 98, 771 776 Cough induction by high-frequency chest percussion in healthy volunteers and patients with common cold P.C.L. Lee, R. Eccles* Common Cold Centre, Cardiff School
More informationMOLECULAR AND CELLULAR NEUROSCIENCE
MOLECULAR AND CELLULAR NEUROSCIENCE BMP-218 November 4, 2014 DIVISIONS OF THE NERVOUS SYSTEM The nervous system is composed of two primary divisions: 1. CNS - Central Nervous System (Brain + Spinal Cord)
More informationCOPD. Breathing Made Easier
COPD Breathing Made Easier Catherine E. Cooke, PharmD, BCPS, PAHM Independent Consultant, PosiHleath Clinical Associate Professor, University of Maryland School of Pharmacy This program has been brought
More informationImmunology of Asthma. Kenneth J. Goodrum,Ph. Ph.D. Ohio University College of Osteopathic Medicine
Immunology of Asthma Kenneth J. Goodrum,Ph Ph.D. Ohio University College of Osteopathic Medicine Outline Consensus characteristics/incidence data Immune/inflammatory basis Etiology/Genetic basis Hygiene
More informationSensory coding and somatosensory system
Sensory coding and somatosensory system Sensation and perception Perception is the internal construction of sensation. Perception depends on the individual experience. Three common steps in all senses
More informationan inflammation of the bronchial tubes
BRONCHITIS DEFINITION Bronchitis is an inflammation of the bronchial tubes (or bronchi), which are the air passages that extend from the trachea into the small airways and alveoli. Triggers may be infectious
More informationCancer-induced bone pain
Cancer-induced bone pain Common Prevalent in particular cancers: breast (73%), prostate (68%), thyroid (42%), lung (36%), renal (35%), colon (5%) Correlates with an increased morbidity Reduced performance
More informationAmanda Hess, MMS, PA-C President-Elect, AAPA-AAI Arizona Asthma and Allergy Institute Scottsdale, AZ
Amanda Hess, MMS, PA-C President-Elect, AAPA-AAI Arizona Asthma and Allergy Institute Scottsdale, AZ Financial Disclosures Advanced Practiced Advisory Board for Circassia Learning Objectives 1. Briefly
More informationBronchial hyperresponsiveness in type Ia (simple bronchoconstriction) asthma Relationship to patient age and the proportions of bronchoalveolar cells
28 Bronchial hyperresponsiveness in type I Bronchial hyperresponsiveness in type Ia (simple bronchoconstriction) Relationship to patient age and the proportions of bronchoalveolar cells Kouzou Ashida,
More informationThe role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness,
Eur Respir J 1997; 10: 1892 1906 DOI: 10.1183/09031936.97.10081892 Printed in UK - all rights reserved Copyright ERS Journals Ltd 1997 European Respiratory Journal ISS 0903-1936 PHARMACOLOGICAL REVIEW
More informationIncreased Expression of Transient Receptor Potential Vanilloid-1 in Airway Nerves of Chronic Cough
Increased Expression of Transient Receptor Potential Vanilloid-1 in Airway Nerves of Chronic Cough David A. Groneberg, Akio Niimi, Q. Thai Dinh, Borja Cosio, Mark Hew, Axel Fischer, and K. Fan Chung Division
More informationEE 791 Lecture 2 Jan 19, 2015
EE 791 Lecture 2 Jan 19, 2015 Action Potential Conduction And Neural Organization EE 791-Lecture 2 1 Core-conductor model: In the core-conductor model we approximate an axon or a segment of a dendrite
More informationSpecial Issue on Pain and Itch
Special Issue on Pain and Itch Title: Recent Progress in Understanding the Mechanisms of Pain and Itch Guest Editor of the Special Issue: Ru-Rong Ji, PhD Chronic pain is a major health problem world-wide.
More informationPATHOPHYSIOLOGICAL PROCESS TEMPLATE
1 PATHOPHYSIOLOGICAL PROCESS TEMPLATE DISEASE: Chronic obstructive pulmonary disease (COPD) DEFINITION: COPD can be defined as a disease in which there is a significant damage to the lungs thus reducing
More informationConflicts of Interest
Exercise and Asthma: What patients and doctors can do to improve outcomes Timothy Craig, DO Professor of Medicine and Pediatrics Distinguished Educator Program Director Penn State University Hershey, PA,
More informationPain Mechanisms. Prof Michael G Irwin MD, FRCA, FANZCA FHKAM Head Department of Anaesthesiology University of Hong Kong. The Somatosensory System
ain Mechanisms rof Michael G Irwin MD, FRCA, FANZCA FHKAM Head Department of Anaesthesiology University of Hong Kong The Somatosensory System Frontal cortex Descending pathway eriaqueductal gray matter
More informationNEURONS Chapter Neurons: specialized cells of the nervous system 2. Nerves: bundles of neuron axons 3. Nervous systems
NEURONS Chapter 12 Figure 12.1 Neuronal and hormonal signaling both convey information over long distances 1. Nervous system A. nervous tissue B. conducts electrical impulses C. rapid communication 2.
More informationReceptors and Drug Action. Dr. Subasini Pharmacology Department Ishik University, Erbil
Receptors and Drug Action Dr. Subasini Pharmacology Department Ishik University, Erbil Receptors and Drug Action Receptor Receptor is defined as a macromolecule or binding site located on the surface or
More informationWhat are the Human Health Effects of Air Pollution?
What are the Human Health Effects of Air Pollution? Dr. Judy Guernsey Department of Community Health and Epidemiology Dalhousie University Nova Scotia Department of Environment and Labour Outdoor Air Quality
More informationJoint Session ACOFP and AOASM: Exercise Induced Asthma. Bruce Dubin, DO, JD, FCLM, FACOI
Joint Session ACOFP and AOASM: Exercise Induced Asthma Bruce Dubin, DO, JD, FCLM, FACOI ACOFP FULL DISCLOSURE FOR CME ACTIVITIES Please check where applicable and sign below. Provide additional pages as
More informationAbstract. IgE. IgE Th2. x x IL-4 IL-5 IgE CD4 +
D. o ƒf 6,''!" # + % %$ '& ' '' & " k n k x k k k k k x k IgE k x IgE Ò1Ó k Ò2Ó v k x IgE Th2 x } x x IL-4 IL-5 IgE IgE j IFN-γ IgG j j CD4 + { k d «d j B7 w k k x IgE k 1 k Abstract Parental immunization
More informationPhysiological processes in the GI tract:
Gastrointestinal physiology for medical students General principal of gastrointestinal function Motility, nervous control and blood circulation Physiological processes in the GI tract: Motility Secretion
More informationNeurotransmitter Systems II Receptors. Reading: BCP Chapter 6
Neurotransmitter Systems II Receptors Reading: BCP Chapter 6 Neurotransmitter Systems Normal function of the human brain requires an orderly set of chemical reactions. Some of the most important chemical
More informationMedicine Dr. Kawa Lecture 1 Asthma Obstructive & Restrictive Pulmonary Diseases Obstructive Pulmonary Disease Indicate obstruction to flow of air
Medicine Dr. Kawa Lecture 1 Asthma Obstructive & Restrictive Pulmonary Diseases Obstructive Pulmonary Disease Indicate obstruction to flow of air through the airways. As asthma, COPD ( chronic bronchitis
More informationulcer healing role 118 Bicarbonate, prostaglandins in duodenal cytoprotection 235, 236
Subject Index Actin cellular forms 48, 49 epidermal growth factor, cytoskeletal change induction in mucosal repair 22, 23 wound repair 64, 65 polyamine effects on cytoskeleton 49 51 S-Adenosylmethionine
More informationClinical Implications of Asthma Phenotypes. Michael Schatz, MD, MS Department of Allergy
Clinical Implications of Asthma Phenotypes Michael Schatz, MD, MS Department of Allergy Definition of Phenotype The observable properties of an organism that are produced by the interaction of the genotype
More informationAllergic diseases and treatment. Feng Qian ( 钱峰 )
Allergic diseases and treatment Feng Qian ( 钱峰 ) fengqian@sjtu.edu.cn Hypersensitivity Antigen Host Adaptive responses protective to the host harmful to the host The deleterious consequences of the adaptive
More informationChapter 5 subtitles GABAergic synaptic transmission
CELLULAR NEUROPHYSIOLOGY CONSTANCE HAMMOND Chapter 5 subtitles GABAergic synaptic transmission INTRODUCTION (2:57) In this fifth chapter, you will learn how the binding of the GABA neurotransmitter to
More informationCOPD and Asthma: Similarities and differences Prof. Peter Barnes
and Asthma: Similarities and Differences and Asthma: 1 Imperial College Peter Barnes FRS, FMedSci, National Heart & Lung Institute Imperial College, London, UK p.j.barnes@imperial.ac.uk Royal Brompton
More informationModulation of TRP channels by resolvins in mouse and human
July 9, 2015, Ion Channel Retreat, Vancouver Ion Channel and Pain Targets Modulation of TRP channels by resolvins in mouse and human Ru-Rong Ji, PhD Pain Research Division Department of Anesthesiology
More informationWorld Health Organisation Initiative. Allergic rhinitis and its impact on asthma. (ARIA). Bousquet J, van Cauwenberge P. Geneva: WHO;2000.
Glenis Scadding Infectious Viral Bacterial Other infective agents Allergic Intermittent Persistent Occupational (allergic/non-allergic) Intermittent Persistent Drug-induced Aspirin Other medications Hormonal
More informationCough in Allergic Rhinitis
6 Cough in Allergic Rhinitis Renata Pecova and Milos Tatar Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin Slovakia 1. Introduction The diseases of the nose and paranasal sinuses
More informationRespiratory Pharmacology
Allergy Targets of allergies Type I Histamine Leukotrienes Prostaglandins Bradykinin Hypersensitivity reactions Asthma Characterised by Triggered by Intrinsic Extrinsic (allergic) Mediators Result Early
More information