DOCSLIB.ORG

Towards Understanding the Mechanism of Clioquinol Neurotoxicity

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Towards Understanding the Mechanism of Clioquinol Neurotoxicity Towards Understanding the Mechanism of Clioquinol Neurotoxicity by Jamuna Chhetri BPharm (Hons), Kathmandu University, Nepal MPharmSc, University of Tasmania, Australia Submitted in fulfilment of the requirements for the Doctor of Philosophy Division of Pharmacy, School of Medicine, Faculty of Health University of Tasmania, Hobart October 2016 Declaration of Originality This thesis contains no material which has been accepted for a degree or diploma by the University or any other institution, except by way of background information and duly acknowledged in the thesis, and to the best of my knowledge and belief no material previously published or written by another person except where due acknowledgement is made in the text of the thesis, nor does the thesis contain any material that infringes copyright. Jamuna Chhetri 4 October 2016 i Authority of Access This thesis is not to be made available for loan or copying for two years following the date this statement was signed. following that time, the thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. Jamuna Chhetri 4 October 2016 ii Statement of Ethical Conduct The research associated with this thesis abides by the international and Australian codes on human and animal experimentation, the guidelines by the Australian Government's Office of the Gene Technology Regulator and the rulings of the Safety, Ethics and Institutional Biosafety Committees of the University. All animal experiments were approved by the Animal Ethics Committee (AEC), University of Tasmania, Australia (Animal Ethics approval numbers: A12817 and A0015097). iii Statement Regarding Published Work Contained in Thesis The publishers of the papers comprising Chapters 1 and 2 hold the copyright for that content, and access to the material should be sought from the respective journals. The remaining non published content of the thesis may be made available for loan and limited copying and communication in accordance with the Copyright Act 1968. iv List of Publications and Statement of Co-authorship The following people and institutions contributed to the publication of the work undertaken as part of this thesis: Candidate: Jamuna Chhetri1 (JC) Author 1: Nuri Gueven1 (NG) Author 2: Glenn Jacobson1 (GJ) Author 3: Anna E. King2 (AEK) 1Pharmacy, School of Medicine, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia 2Wicking Dementia Research and Education Centre, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia Author details and their roles: Peer-reviewed journal publications Paper 1, Chhetri J, Jacobson G, Gueven N. Zebrafish-on the move towards ophthalmological research. Eye 2014;7(10):19. (IF: 2.213) Located in chapter 1 Candidate was the primary author and with NG and GJ contributed to the idea, its formalisation and refinement. NG and GJ assisted in editing the manuscript. v Paper 2, Chhetri J, Gueven N. Targeting mitochondrial function to protect against vision loss. Expert Opin Ther Targets 2016:1-16. (IF: 4.79) Located in chapter 1 Candidate was the primary author and with NG contributed to the idea and its formalisation and refinement. NG also assisted in evaluating and editing the manuscript. Paper 3, Alzheimer’s Disease and NQO1: Is there a Link? (Accepted for Publication: Current Alzheimer Research) (IF: 3.58) Located in chapter 1 and chapter 2 Candidate was the primary author and with NG and AEK contributed to the idea, its formalisation and refinement. NG and AEK also assisted in evaluating and editing the manuscript. Conference abstracts (Oral) (Presenting author is underlined) 1. Chhetri J, Gasperini R, Jacobson G, Foa L, Gueven N. Mechanism of Clioquinol Toxicity-relevance to neurodegenerative diseases. APSA-ASCEPT (29 Nov-2 Dec 2015), Hobart, Australia. Conference abstracts (Poster) (Presenting author is underlined) 1. Chhetri J, Jacobson G, Gueven N. Development of a zebrafish model to detect mitochondrial dysfunction-induced vision loss. University of Tasmania Graduate Research conference (Aug 2013, Hobart, Australia). 2. Chhetri J, Jacobson G, Gueven N. Detoxification of clioquinol by NQO1. University of Tasmania Higher Degree Research (HDR) conference (Jul 2014, Hobart, Australia). vi 3. Chhetri J, Dilek J, Jacobson G, Gasperini R, Foa L, Gueven N. Clioquinol induces mitochondrial dysfunction by inhibiting NQO1. AussieMit conference (Dec 1-3 2014, Perth, Western Australia). 4. Chhetri J, Gasperini R, Jacobson G, Foa L, Gueven N. Mechanism of Clioquinol Toxicity-relevance to neurodegenerative diseases. APSA-ASCEPT (29 Nov-Dec 2015, Hobart, Australia). 5. Chhetri J, Farooq M, Dilek J, Jacobson G, Gasperini R, Foa L, Gueven N. NQO1- dependent toxicity of clioquinol. United Mitochondrial Disease Foundation, Mitochondrial Medicine (15-18th of June 2016, Seattle, WA, USA, presented by N Gueven). We the undersigned agree with the above stated “proportion of work undertaken” for each of the above published (or submitted) peer-reviewed manuscripts contributing to this thesis: Signed: A/Prof Nuri Gueven Prof Ben Canny Supervisor Head of School School of Medicine School of Medicine University of Tasmania University of Tasmania Date: 22/9/2016 vii Acknowledgements This PhD thesis would have never been possible if I was not given an opportunity in the first place. Therefore, first and foremost I would like to thank the University of Tasmania, in particular, Professor Gregory Peterson, Deputy Dean (Research), in believing my potential and providing me with an opportunity to pursue PhD study at the University of Tasmania. I am very much grateful to my primary supervisor, A/Professor Nuri Gueven who introduced me to research in a real sense and nurtured my enthusiasm for research. I appreciate his time, immense support and expert suggestions for my PhD study. He has always been a tremendous mentor who has always encouraged my research and allowed me to grow as an independent researcher. I am so much impressed with his immense knowledge of the subject matter, problem-solving skills, and networking skills. All in all, it has been a great honour to be his PhD student. I would also like to express my sincere gratitude to my co-supervisors A/Professor Lisa Foa, Dr Robert Gasperini and Dr Glenn Jacobson for their support and insightful comments on my research project. In addition, I am thankful to Lisa for letting me use the zebrafish facility at Medical Science Precinct (MSP) for the in-vivo experiments. My special thanks go to Dr Peter Traill, Anthony Whitty, Melissa Aubrey of Pharmacy and Dr David Steele, Sarah Kane of Medical Science Precinct (MSP) for the efficient management of logistics to facilitate the smooth running of my day-to-day research work. I could not stay without thanking Mr Steven Weston, Ms Narelle Phillips, Dr Ellen Bennett from MSP for so willingly sharing their histology expertise with me whenever I required them. I would also like viii to thank A/Professor Noel Davies, Central Science Laboratory, University of Tasmania, for his help with mass spectrometric analysis, Petr Smejkal and Aliaa Shallan for their help with 3D printing, Adrian Thompson for providing me with zebrafish eggs for the experiments, Jem Dilek for the initial drug screening and Mohammed Farooq for assisting me with some of the in-vitro studies. I would also like to express my sincere thanks to Emeritus Professor Stuart Mclean for providing me insightful feedback on my write-up, Dr Rosanne Guijt, Dr Rahul Patel and Dr Syed Tabish R. Zaidi for their support and suggestions on my research project and future career. I am thankful to my colleagues in Pharmacy for their companionship, emotional support and of course for the wonderful time we spent together. Last but not the least, I am very much indebted to my family, who has always been a source of inspiration to me and has always stood by me in all my pursuits. They are the reason why I am here today and I happily dedicate this thesis to them. ix List of Abbreviations Acronym Definition 8-HQ 8-hydroxyquinoline Acetyl-CoA acetyl-coenzyme A AD Alzheimer’s disease ADOA autosomal dominant optic atrophy ADP adenosine diphosphate AEC animal ethics committee AEG advance glycation end products ALDH4 aldehyde dehydrogenase 4 AMD age-related macular degeneration ANOVA analysis of variance ANT adenine nucleotide transporter APA acetaminophen APP amyloid precursor protein APS ammonium persulphate ARE antioxidant response element ATP adenosine triphosphate AVMA American Veterinary Medical Association Aβ amyloid beta BSA bovine albumin serum CAG cytosine adenine guanine Cat catalase CM-H2DCFDA chloromethyl 2',7'-dichlorodihydrofluorescein diacetate x CoQ coenzyme ubiquinone Cu Copper Cu/ZnSOD copper/zinc superoxide dismutase Cul 3 cullin 3 Cys cysteine Cytc cytochrome c DAB 3, 3’-diaminobenzidine DCPIP dicholorophenolindophenol DCs double cones Dic dicoumarol DLG dorsal lateral geniculate nucleus DMD digital micromirror device DMEM dulbecco’s modified eagle’s medium DMSO dimethylsulfoxide DNA deoxyribonucleic acid DR diabetic retinopathy DTT dithiothreitol E2 ubiquitin-conjugation enzyme ECL enhanced chemiluminescence EDTA ethylenediaminetetraacetic acid EGTA ethylene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid EMA European Medicines Agency ER escape response ETC electron transport chain FADH2 flavin adenine dinucleotide reduced xi Fe iron Fe-S iron-sulphur centres FMN flavin mononucleotide GAPDH glyceraldehyde-3-phosphate dehydrogenase GLS-2 glutaminase 2 GPT glutamate
Load more

Recommended publications
  • National Center for Toxicological Research
    National Center for Toxicological Research Annual Report Research Accomplishments and Plans FY 2015 – FY 2016 Page 0 of 193 Table of Contents Preface – William Slikker, Jr., Ph.D. ................................................................................... 3 NCTR Vision ......................................................................................................................... 7 NCTR Mission ...................................................................................................................... 7 NCTR Strategic Plan ............................................................................................................ 7 NCTR Organizational Structure .......................................................................................... 8 NCTR Location and Facilities .............................................................................................. 9 NCTR Advances Research Through Outreach and Collaboration ................................... 10 NCTR Global Outreach and Training Activities ............................................................... 12 Global Summit on Regulatory Science .................................................................................................12 Training Activities .................................................................................................................................14 NCTR Scientists – Leaders in the Research Community .................................................. 15 Science Advisory Board ...................................................................................................
    [Show full text]
  • Eosin Y Catalysed Photoredox Synthesis: a Review
    RSC Advances REVIEW View Article Online View Journal | View Issue Eosin Y catalysed photoredox synthesis: a review a b Cite this: RSC Adv.,2017,7,31377 Vishal Srivastava and Praveen P. Singh * In recent years, photoredox catalysis using eosin Y has come to the fore front in organic chemistry as a powerful strategy for the activation of small molecules. In a general sense, these approaches rely on the ability of organic dyes to convert visible light into chemical energy by engaging in single-electron Received 14th May 2017 transfer with organic substrates, thereby generating reactive intermediates. In this perspective, we Accepted 13th June 2017 highlight the unique ability of photoredox catalysis to expedite the development of completely new DOI: 10.1039/c7ra05444k reaction mechanisms, with particular emphasis placed on multicatalytic strategies that enable the rsc.li/rsc-advances construction of challenging carbon–carbon and carbon–heteroatom bonds. 1. Introduction However, the transition metal based photocatalysts disadvantageously exhibit high cost, low sustainability and Visible light photoredox catalysis has recently received much potential toxicity. Recently, a superior alternative to transition Creative Commons Attribution 3.0 Unported Licence. attention in organic synthesis owing to ready availability, metal photoredox catalysts, especially metal-free organic dyes sustainability, non-toxicity and ease of handling of visible particularly eosin Y has been used as economically and 1–13 light but the general interest in the eld started much ecologically superior surrogates for Ru(II)andIr(II)complexes earlier.14 Unlike thermal reactions, photoredox processes occur in visible-light promoted organic transformations involving 18–21 under mild conditions and do not require radical initiators or SET (single electron transfer).
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 De Juan Et Al
    US 200601 10428A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110428A1 de Juan et al. (43) Pub. Date: May 25, 2006 (54) METHODS AND DEVICES FOR THE Publication Classification TREATMENT OF OCULAR CONDITIONS (51) Int. Cl. (76) Inventors: Eugene de Juan, LaCanada, CA (US); A6F 2/00 (2006.01) Signe E. Varner, Los Angeles, CA (52) U.S. Cl. .............................................................. 424/427 (US); Laurie R. Lawin, New Brighton, MN (US) (57) ABSTRACT Correspondence Address: Featured is a method for instilling one or more bioactive SCOTT PRIBNOW agents into ocular tissue within an eye of a patient for the Kagan Binder, PLLC treatment of an ocular condition, the method comprising Suite 200 concurrently using at least two of the following bioactive 221 Main Street North agent delivery methods (A)-(C): Stillwater, MN 55082 (US) (A) implanting a Sustained release delivery device com (21) Appl. No.: 11/175,850 prising one or more bioactive agents in a posterior region of the eye so that it delivers the one or more (22) Filed: Jul. 5, 2005 bioactive agents into the vitreous humor of the eye; (B) instilling (e.g., injecting or implanting) one or more Related U.S. Application Data bioactive agents Subretinally; and (60) Provisional application No. 60/585,236, filed on Jul. (C) instilling (e.g., injecting or delivering by ocular ion 2, 2004. Provisional application No. 60/669,701, filed tophoresis) one or more bioactive agents into the Vit on Apr. 8, 2005. reous humor of the eye. Patent Application Publication May 25, 2006 Sheet 1 of 22 US 2006/0110428A1 R 2 2 C.6 Fig.
    [Show full text]
  • Hematoxylin and Eosin Stain (H&E)
    Hematoxylin and Eosin Stain (H&E) TECHNIQUE: Formalin fixed, paraffin tissue sections REAGENTS: Mayer’s Hematoxylin (Source Medical, catalog# 9235360) 0.5% Acid Alcohol 70% Ethanol ----------------------------------------------------------------------995ml Hydrochloric Acid, (36.5% - 38%) ------------------------------------------- 5ml 1X PBS (pH 7.2-7.3) Alcoholic-Eosin 1.0% Eosin Y Eosin Y (CAS# 17372-87-1) -------------------------------------------------- 1.0 g Distilled water ------------------------------------------------------------------ 100 ml 1.0% Phloxine B Phloxine B (CAS# 18472-87-2) ---------------------------------------------- 0.5 g Distilled water ------------------------------------------------------------------ 50.0 ml Working Alcoholic-Eosin Solution 1.0% Eosin Y ------------------------------------------------------------------- 50.0 ml 1.0% Phloxine B --------------------------------------------------------------- 5.0 ml 95% Ethanol -------------------------------------------------------------------- 390.0 ml Acetic acid, glacial ------------------------------------------------------------- 4.0 ml 11/2018 Hematoxylin and Eosin Stain (H&E) 5 micron Paraffin Sections PROCEDURE: 1. Deparaffinize and rehydrate slides to distilled water 2. Stain in Mayers Hematoxylin for 1 minute 3. Wash with 4-5 changes of Tap water or until blue stops coming off slides 4. Blue nuclei in 1X PBS for 1 minute 5. Wash with 3 changes of distilled water 6. Counterstain in Alcoholic-Eosin for 1 minute (DO NOT RINSE) 7. Dehydrate through 3
    [Show full text]
  • Outcomes of Conservative Treatment of Giant Omphaloceles with Dissodic 2% Aqueous Eosin: 15 Years' Experience
    Access this article online Website: Original Article www.afrjpaedsurg.org DOI: 10.4103/0189-6725.132825 PMID: *** Outcomes of conservative treatment of giant Quick Response Code: omphaloceles with dissodic 2% aqueous eosin: 15 years’ experience B. D. Kouame, T. H. Odehouri Koudou, J. B. Yaokreh, M. Sounkere, S. Tembely, K. G. S. Yapo, R. Boka, M. Koffi, A. G. Dieth, O. Ouattara, A. da Silva, R. Dick INTRODUCTION ABSTRACT Background: The surgical management of giant Surgical treatment of the giant omphaloceles leads to omphalocele is a surgical challenge with high several haemodynamic and respiratory complications mortality and morbidity in our country due to the which increase their mortality. To reduce the morbidity absence of neonatal resuscitation. This study evaluates conservative management of giant and the mortality of the surgical management of the giant omphalocele with dissodic 2% aqueous eosin. omphalocele, conservative’s treatments with antiseptic Materials and Methods: In the period from January solutions were carried out.[1-3] Povidone iodine and 1997 to December 2012, giant omphaloceles were merbromin have been used during several years due to their treated with dissodic 2% aqueous eosin. The capacity to promote escharification and epithelialization procedure consisted of twice a day application of of the omphalocele sac. However due to complications dissodic 2% aqueous eosin (sterile solution for topical application) on the omphalocele sac. The such as transient hypothyroidism with povidone iodine or procedure was taught to the mother to continue mercury poising with merbromin, there was the cessation at home with an outpatient follow-up to assess of their use for conservative treatment.[1-4] epithelialization.
    [Show full text]
  • Eosin Staining
    Science of H & E Andrew Lisowski, M.S., HTL (A.S.C.P.) 1 Hematoxylin and Eosin Staining “The desired end result of a tissue stained with hematoxylin and eosin is based upon what seems to be almost infinite factors. Pathologists have individual preferences for section thickness, intensities, and shades. The choice of which reagents to use must take into consideration: cost, method of staining, option of purchasing commercially-prepared or technician-prepared reagents, safety, administration policies, convenience, availability, quality, technical limitations, as well as personal preference.” Guidelines for Hematoxylin and Eosin Staining National Society for Histotechnology 2 Why Do We Stain? In order to deliver a medical diagnosis, tissues must be examined under a microscope. Once a tissue specimen has been processed by a histology lab and transferred onto a glass slide, it needs to be appropriately stained for microscopic evaluation. This is because unstained tissue lacks contrast: when viewed under the microscope, everything appears in uniform dull grey color. Unstained tissue H&E stained tissue 3 What Does "Staining" Do? . Contrasts different cells . Highlights particular features of interest . Illustrates different cell structures . Detects infiltrations or deposits in the tissue . Detect pathogens Superbly contrasted GI cells Placenta’s large blood H&E stain showing extensive vessels iron deposits There are different staining techniques to reveal different structures of the cell 4 What is H&E Staining? As its name suggests, H&E stain makes use of a combination of two dyes – hematoxylin and eosin. It is often termed as “routine staining” as it is the most common way of coloring otherwise transparent tissue specimen.
    [Show full text]
  • A Screening-Based Approach to Circumvent Tumor Microenvironment
    JBXXXX10.1177/1087057113501081Journal of Biomolecular ScreeningSingh et al. 501081research-article2013 Original Research Journal of Biomolecular Screening 2014, Vol 19(1) 158 –167 A Screening-Based Approach to © 2013 Society for Laboratory Automation and Screening DOI: 10.1177/1087057113501081 Circumvent Tumor Microenvironment- jbx.sagepub.com Driven Intrinsic Resistance to BCR-ABL+ Inhibitors in Ph+ Acute Lymphoblastic Leukemia Harpreet Singh1,2, Anang A. Shelat3, Amandeep Singh4, Nidal Boulos1, Richard T. Williams1,2*, and R. Kiplin Guy2,3 Abstract Signaling by the BCR-ABL fusion kinase drives Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Despite their clinical activity in many patients with CML, the BCR-ABL kinase inhibitors (BCR-ABL-KIs) imatinib, dasatinib, and nilotinib provide only transient leukemia reduction in patients with Ph+ ALL. While host-derived growth factors in the leukemia microenvironment have been invoked to explain this drug resistance, their relative contribution remains uncertain. Using genetically defined murine Ph+ ALL cells, we identified interleukin 7 (IL-7) as the dominant host factor that attenuates response to BCR-ABL-KIs. To identify potential combination drugs that could overcome this IL-7–dependent BCR-ABL-KI–resistant phenotype, we screened a small-molecule library including Food and Drug Administration–approved drugs. Among the validated hits, the well-tolerated antimalarial drug dihydroartemisinin (DHA) displayed potent activity in vitro and modest in vivo monotherapy activity against engineered murine BCR-ABL-KI–resistant Ph+ ALL. Strikingly, cotreatment with DHA and dasatinib in vivo strongly reduced primary leukemia burden and improved long-term survival in a murine model that faithfully captures the BCR-ABL-KI–resistant phenotype of human Ph+ ALL.
    [Show full text]
  • Photophysical and Antibacterial Activity of Light- Activated Quaternary Eosin Y
    Open Chem., 2019; 17: 1244–1251 Research Article Desislava Staneva, Stanislava Yordanova*, Evgenia Vasileva-Tonkova, Stanimir Stoyanov, Ivo Grabchev Photophysical and antibacterial activity of light- activated quaternary eosin Y https://doi.org/10.1515/chem-2019-0135 received December 3, 2018; accepted May 9, 2019. Keywords: eosin Y, photophysics, antimicrobial activity, antibacterial textile Abstract: The functional characteristics of a new eosin dye with biocidal quaternary ammonium group (E) were studied in aqueous solution and in organic solvents of 1 Introduction different polarity. The spectral properties depend on the nature and polarity of the respective solvents. The Fluorescent compounds are often used in medicine, antimicrobial activity of compound E has been tested in pharmacy, biology and environmental protection [1,2]. vitro against Gram-negative bacteria (Escherichia coli, Among the known fluorophore structures used in these Acinetobacter johnsoni and Pseudomonas aeruginosa), fields, the eosin Y and its derivatives are very important. Gram-positive bacteria (Sarcina lutea and Bacillus cereus) They belong to the group of xanthene fluorescent dyes and the antifungal activity was tested against the yeasts with a wide range of photophysical and biological Candida lipolytica in solution and after treated on cotton applications, due to their low toxicity in vivo, and high fabric. Broth dilution test has been used for quantitative water solubility [3]. The utility of eosin derivatives is evaluation of the antimicrobial activity of compound E associated to their good spectral characteristics and the against the model strains. The ability of compound E to possibility to interact with different type of biomolecules inhibit the growth of model Gram-negative P.
    [Show full text]
  • Avant-Propos Le Format De Présentation De Cette Thèse Correspond À Une Recommandation À La Spécialité
    Avant-propos Le format de présentation de cette thèse correspond à une recommandation à la spécialité Maladies infectieuses, à l’intérieur du Master des Sciences de la Vie et de la Santé qui dépend de l’Ecole Doctorale des Sciences de la Vie de Marseille. Le candidat est amené à respecter les règles qui lui sont imposées et qui comportent un format de thèse utilisé dans le Nord de l’Europe et qui permet un meilleur rangement que les thèses traditionnelles. Par ailleurs, la partie introduction et bibliographie est remplacée par une revue envoyée dans un journal afin de permettre une évaluation extérieure de la qualité de la revue et de permettre à l’étudiant de commencer le plus tôt possible une bibliographie sur le domaine de cette thèse. Par ailleurs, la thèse est présentée sur article publié, accepté, ou soumis associé d’un bref commentaire donnant le sens général du travail. Cette forme de présentation a paru plus en adéquation avec les exigences de la compétition internationale et permet de se concentrer sur des travaux qui bénéficieront d’une diffusion internationale. Professeur Didier RAOULT 2 Remerciements J’adresse mes remerciements aux personnes qui ont contribué à la réalisation de ce travail. En premier lieu, au Professeur Didier RALOUT, qui m’a accueillie au sein de l’IHU Méditerranée Infection. Au Professeur Serge MORAND, au Docteur Marie KEMPF et au Professeur Philippe COLSON de m’avoir honorée en acceptant d’être rapporteurs et examinateurs de cette thèse. Je souhaite particulièrement remercier : Le Professeur Jean-Marc ROLAIN, de m’avoir accueillie dans son équipe et m’avoir orientée et soutenue tout au long de ces trois années de thèse.
    [Show full text]
  • Step-By-Step Guide to Better Laboratory Management Practices
    Step-by-Step Guide to Better Laboratory Management Practices Prepared by The Washington State Department of Ecology Hazardous Waste and Toxics Reduction Program Publication No. 97- 431 Revised January 2003 Printed on recycled paper For additional copies of this document, contact: Department of Ecology Publications Distribution Center PO Box 47600 Olympia, WA 98504-7600 (360) 407-7472 or 1 (800) 633-7585 or contact your regional office: Department of Ecology’s Regional Offices (425) 649-7000 (509) 575-2490 (509) 329-3400 (360) 407-6300 The Department of Ecology is an equal opportunity agency and does not discriminate on the basis of race, creed, color, disability, age, religion, national origin, sex, marital status, disabled veteran’s status, Vietnam Era veteran’s status or sexual orientation. If you have special accommodation needs, or require this document in an alternate format, contact the Hazardous Waste and Toxics Reduction Program at (360)407-6700 (voice) or 711 or (800) 833-6388 (TTY). Table of Contents Introduction ....................................................................................................................................iii Section 1 Laboratory Hazardous Waste Management ...........................................................1 Designating Dangerous Waste................................................................................................1 Counting Wastes .......................................................................................................................8 Treatment by Generator...........................................................................................................12
    [Show full text]
  • Chlorhexidine Bathing in a Tertiary Care Neonatal Intensive Care Unit
    Chlorhexidine Bathing in a Tertiary Care Neonatal Intensive Care Unit: Impact on Central Line–Associated Bloodstream Infections Author(s): Caroline Quach, MD, MSc; Aaron M. Milstone, MD, MHS; Chantal Perpête, RN, LSH, LSHH; Mario Bonenfant, RN; Dorothy L. Moore, MD, PhD; Therese Perreault, MD Source: Infection Control and Hospital Epidemiology, Vol. 35, No. 2 (February 2014), pp. 158- 163 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/674862 . Accessed: 24/01/2014 14:25 Your use of the JSTOR archive indicates your acceptance of the Terms & Conditions of Use, available at . http://www.jstor.org/page/info/about/policies/terms.jsp . JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact [email protected]. The University of Chicago Press and The Society for Healthcare Epidemiology of America are collaborating with JSTOR to digitize, preserve and extend access to Infection Control and Hospital Epidemiology. http://www.jstor.org This content downloaded from 209.172.182.131 on Fri, 24 Jan 2014 14:25:10 PM All use subject to JSTOR Terms and Conditions infection control and hospital epidemiology february 2014, vol. 35, no. 2 original article Chlorhexidine Bathing in a Tertiary Care Neonatal Intensive Care Unit: Impact on Central Line–Associated Bloodstream Infections Caroline Quach, MD, MSc;1,2,3 Aaron M.
    [Show full text]
  • Basics of Hematology and Patho-Histology
    Basics of Hematology and Patho-histology Practical Course in Molecular Pathology Winter Term 2015 Ernst Müllner MFPL (Max F Perutz Laboratories) Department of Medical Biochemistry Medical University of Vienna [email protected] www.mfpl.ac.at/mfpl-group/group/muellner.html (Müllner homepage / research) E. coli + macrophages medicalschool.tumblr.com/post/43914024728/sem-image-of-e-coli-bacteria-and-macrophages medicalschool.tumblr.com/post/18256087351/r ed-blood-cells-erythrocytes-trapped-by-fibrin Overview on main white blood cell (WBC) types – (Wikipedia) Mature white blood cell types I White Blood cells (WBCs) are frequently also referred to as peripheral blood mononuclear cells (PBMCs). Granulocytes in general are part of the innate immune system. Names derive from staining with hematoxylin and eosin. Whereas basophils stain dark blue and eosinophils are bright red, neutrophils stain neutral to pink. Basophil granulocytes Eosinophil granulocytes Neutrophil granulocytes Least common granulocyte type About 1-6% of WBCs; component Most abundant WBC type (40- (0.01- 0.3% of WBCs. Large of innate immune system to com- 75%) and essential part of the cytoplasmic granules obscure the bat parasites and certain infec- innate immune system. A patho- nucleus under the microscope. tions; also associated with allergy gen is likely to first encounter a When unstained, the nucleus is and asthma. Following activation, neutrophil. Normally contain a nu- visible and usually has 2 lobes. eosinophils effector functions in- cleus of 2-5 lobes. Neutrophils Basophils appear in inflammatory clude production and release (de- quickly congregate at a infection reactions, particularly those granulation) of cytotoxic substan- site, attracted by cytokines from causing allergies, mainly via the ces (granule proteins, reactive activated endothelium, mast cells, vasodilator histamine (antihistami- oxygen species …) and production or macrophages.
    [Show full text]