DOCSLIB.ORG

Determination of Lipid a and Endotoxin in Serum by Mass Spectroscopy (Ft-Hydroxymyristic Acid/Gas Chromatography-Mass Spectrometry/Gram-Negative Sepsis) SHYAMAL K

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Determination of Lipid a and Endotoxin in Serum by Mass Spectroscopy (Ft-Hydroxymyristic Acid/Gas Chromatography-Mass Spectrometry/Gram-Negative Sepsis) SHYAMAL K Proc. Nati. Acad. Sci. USA Vol. 75, No. 8, pp. 3993-3997, August 1978 Medical Sciences Determination of lipid A and endotoxin in serum by mass spectroscopy (ft-hydroxymyristic acid/gas chromatography-mass spectrometry/Gram-negative sepsis) SHYAMAL K. MAITRA*t, MICHAEL C. SCHOTZtf, THOMAS T. YOSHIKAWA*t, AND LUCIEN B. GUZE*tl * Research Service, Veterans Administration, Wadsworth Hospital Center, Los Angeles, California 90073; * Departments of Medicine, Harbor General Hospital, Torrance, California 90509; and t UCLA School of Medicine, Los Angeles, California 90024 Communicated by William N. Valentine, June 1, 1978 ABSTRACr A quantitative technique for determining lipid tography-mass spectrometry. Mass spectrometry has been used A content of endotoxin added to serum by combined gas chro- successfully in the past to detect various biological compounds matography-mass spectrometry is described. This technique uses (26). This procedure is highly specific and very sensitive. detection of the -hydroxymyristic acid content of Salmonella The minnesota R595 lipopolysaccharide by selected ion monitoring method described in this communication quantitates nanogram at atomic mass unit of 315.4 The fatty acids produced on hy- quantities of lipid A and endotoxin in serum. drolysis of serum containing lipopolysaccharide were extracted and the methyl esters were made. Silica gel chromatography was MATERIALS AND METHODS used to separate methyl esters of hydroxy fatty acids from other Serum Samples. New Zealand white rabbits weighing ap- fatty acid methyl esters. Trimethylsilyl ether derivatives of the proximately 2 kg, and not fed overnight, were used. Blood was hydroxy fatty acid methyl ester fraction were quantitated by this technique. As little as 200 fmol of fi-hydroxymyristic acid obtained by heart puncture under sterile conditions. Blood was could be detected. also obtained aseptically from human volunteers by veni- puncture. Serum was separated by centrifugation and stored Gram-negative bacillary sepsis continues to be an important in pyrogen-free tubes at -200. clinical entity with a high mortality rate (1-3). Based primarily Solvents. All solvents were either freshly distilled or were on animal studies (1, 3-6), it appears that many of the physio- liquid chromatography grade and purchased from Burdick and logical consequences of gram-negative bacteremia are causally Jackson Co. related to the presence of bacterial lipopolysaccharides, namely, Determination of #(OH) Myristic Acid Content of Lipid endotoxin. Endotoxin is a complex substance located in the cell A. Varying amounts of Salmonella minnesota R595-lipid A or wall of Gram-negative bacteria and is composed of o-specific Escherichia coli 0127:B8 endotoxin in 5 ml of pyrogen-free side chains, a core polysaccharide, and a lipid moiety called 0.85% wt/vol NaCl or in 3-5 ml of rabbit or human serum were lipid A (7-14). Extensive studies by several investigators (9, 10, hydrolyzed with 5 ml of 8 M HCI for 4.5 hr at 1100. The free 15) have suggested that the "toxic'' component of endotoxin fatty acids of the hydrolysate were extracted three times with resides in this lipid-A moiety. Lipid A has a molecular weight 10 ml of diethyl ether. The ether extracts were pooled, washed of approximately 1700, with its major constituents being with 5 ml of pyrogen-free water, and dried under nitrogen. The glucosamine (20-30%), phosphate (2%), and long-chain fatty extracted free fatty acids were methylated by the procedure acids (60-70%) (10, 11, 16). fl-Hydroxy [,B(OH)] fatty acids of Schlenk and Gellerman (27), dried under nitrogen, dissolved comprise the major fatty acids and are unique in that they have in 0.5 ml of pentane, and applied to a dry silica gel column not been reported in significant amounts in normal human 60-200 mesh (0.5 X 3 cm). The column was eluted with 3% serum (17). The most commonly occurring ,B(OH) fatty acid ether in pentane to remove saturated and unsaturated methyl in Gram-negative bacteria is fl-hydroxymyristic acid, which esters of fatty acids (28). The remaining polar fatty acids, in- is present in lipid A or endotoxin (14). Thus, this unique com- cluding hydroxy fatty acid methyl esters, were eluted quanti- pound could be useful as a "marker" for the presence of lipid tatively with 20% ether in pentane and dried under nitrogen. A or endotoxin (18). After addition of 0.25 ml of trimethylsilyl reagent (MesSi im- Previous attempts at determining endotoxin activity have idazole, Applied Science), the samples were shaken on a Vortex been dependent on biological assay systems. These include the mixer. After 2 min, 1 ml of water was added. The Me3Si ethers pyrogen test (19), fever index (20), animal lethality (21), epi- of hydroxy fatty acid methyl esters were extracted three times nephrine skin test (22), and synovial inflammatory response with 1 ml of pentane. The pentane extracts were pooled and (23). Also, the Limulus lysate gelation test has been developed dried carefully under a nitrogen stream at 300. The dried Me3Si as a means for detecting circulating endotoxin (24). Disap- ethers were dissolved in 0.1 ml of acetonitrile, mixed on a pointingly, the clinical correlation with this last assay has been Vortex, and filtered through pasteur pipettes plugged with si- unsatisfactory because of the significant incidence of false- lanized glass wool. positive and false-negative results (25). Moreover, like the other Two to five microliters of the acetonitrile solution were in- bioassay systems, the Limulus lysate test fails to measure en- jected into a gas chromatograph-mass spectrometer (model dotoxin directly but rather attempts to quantitate some bio- 5992 A, Hewlett-Packard, Palo Alto) equipped with a mem- logical effect. On the basis of the chemical structure of lipid A, brane separator. The relative abundance at 315.4 atomic mass we have developed a method to detect endotoxin in serum by unit was determined by using a selected ion monitoring pro- quantitating f3(OH) myristic acid by means of gas chroma- gram in conjunction with a six-ion data acquisition program available from Hewlett-Packard. The glass column (2 mm inner The costs of publication of this article were defrayed in part by the diameter X 1.8 m) was packed with 3% Silar-lOC on 100/120 payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate Abbreviations: #(OH), fl-hydroxy; Me3Si, trimethylsilyl; Me3Si-Me- this fact. fl(OH)C14, trimethylsilyl ether of ,B(OH) methyl myristate. 3993 Downloaded by guest on September 27, 2021 3994 Medical Sciences: Maitra et al. Proc. Natl. Acad. Sci. USA 75 (1978) gas chrom Q (Applied Science Laboratories). The column and at concentrations below 1000 fmol was less than 1% and was not injection port temperatures were 180' and 2400, respectively). significant at higher concentrations. When an equimolar Zero helium (Liquid Carbonic) was used as a carrier gas at a mixture of both derivatives was diluted from 1:10,000 to 1: flow rate of 30 ml/min. The electron multiplier voltage setting 1,000,000, the observed ratio (1.415) of nondeuterated to was 2800. pentadeuterated derivative remained unchanged. Fragmentation Pattern of Me3Si Ether of #(OH) Methyl Internal Standard. A pentadeuterated (3(OH) myristic acid Ester of Myristic Acid [Me3Si-Me-i(OH)C14J and Its Penta- was used as our internal standard. The five deuterium atoms deuterated Derivative. A Hewlett-Packard 5992A gas chro- are located on carbons 2, 3, and 4. Initially, the internal stnard matograph-mass spectrometer with a peak finding program was added prior to hydrolysis of serum. However, our experi- was used. MeSi-Me-#(OH)CA4 showed mass fragmentation of mental data showed that this deuterated standard was partially high abundance at atomic mass units of 315.4 and 175 (Fig. 1). destroyed during hydrolysis. The kinetics of this reaction will We have obtained a pentadeuterated (3(OH) myristic acid from need further study to minimize the loss. In the present study Merck, Sharp & Dohme, Canada Ltd. Montreal, Canada. The the internal standard was added after hydrolysis. Thus, the mass fragmentation pattern of this derivative is also shown in values obtained are minimum values for #(OH) myristic acid Fig. 1. The pattern is essentially identical to the nondeuterated content of serum. derivative except the major mass peak is at 320.4 rather than Extraction and Separation of Serum Lipids. Three milli- at 315.4 and the second major peak is seen at 178. liters of serum were extracted with chloroform/methanol/ Standard Curve and Cross Talk. Known concentrations of water 8:4:3 vol/vol (29). The aqueous extract was removed and both the nondeuterated and pentadeuterated Me3Si-Me- washed with chloroform. The organic phase was removed and fl(OH)CA4 were prepared and the relative abundance at 315.4 dried under nitrogen. The lipids were separated by silica gel for the nondeuterated and at 320.4 for the pentadeuterated column chromatography (0.5 X 6 cm), with chloroform, ace- derivative were measured. These standard curves were linear tone, and methanol as eluting solvents. The eluted lipids and when plotted on double logarithmic graph paper for both de- the remaining silica gel were dried and used for further anal- rivatives. The range covered in these experiments was 200 ysis. fmol-1000 pmol (Fig. 1). At the lower limit, 200 fmol produced Liquid Chromatography. Fatty acid methyl esters were a relative abundance of about 350 at m/e 315.4. The back- separated with a liquid chromatograph (model ALC/GLC 200, ground under these conditions was less than 50. Cross talk Waters Associates). This instrument was equipped with a model (overlap of 315.4 from 320.4 or vice versa) for both derivatives 6000 solvent delivery system, a model U6K Universal Injector, and a Micro-Bondapak C18 column (30 cm X 4 mm), all ob- tained from Waters Associates.
Load more

Recommended publications
  • Pathological and Therapeutic Approach to Endotoxin-Secreting Bacteria Involved in Periodontal Disease
    toxins Review Pathological and Therapeutic Approach to Endotoxin-Secreting Bacteria Involved in Periodontal Disease Rosalia Marcano 1, M. Ángeles Rojo 2 , Damián Cordoba-Diaz 3 and Manuel Garrosa 1,* 1 Department of Cell Biology, Histology and Pharmacology, Faculty of Medicine and INCYL, University of Valladolid, 47005 Valladolid, Spain; [email protected] 2 Area of Experimental Sciences, Miguel de Cervantes European University, 47012 Valladolid, Spain; [email protected] 3 Area of Pharmaceutics and Food Technology, Faculty of Pharmacy, and IUFI, Complutense University of Madrid, 28040 Madrid, Spain; [email protected] * Correspondence: [email protected] Abstract: It is widely recognized that periodontal disease is an inflammatory entity of infectious origin, in which the immune activation of the host leads to the destruction of the supporting tissues of the tooth. Periodontal pathogenic bacteria like Porphyromonas gingivalis, that belongs to the complex net of oral microflora, exhibits a toxicogenic potential by releasing endotoxins, which are the lipopolysaccharide component (LPS) available in the outer cell wall of Gram-negative bacteria. Endotoxins are released into the tissues causing damage after the cell is lysed. There are three well-defined regions in the LPS: one of them, the lipid A, has a lipidic nature, and the other two, the Core and the O-antigen, have a glycosidic nature, all of them with independent and synergistic functions. Lipid A is the “bioactive center” of LPS, responsible for its toxicity, and shows great variability along bacteria. In general, endotoxins have specific receptors at the cells, causing a wide immunoinflammatory response by inducing the release of pro-inflammatory cytokines and the production of matrix metalloproteinases.
    [Show full text]
  • Instability of Toxin a Subunit of AB5 Toxins in the Bacterial Periplasm Caused by Deficiency of Their Cognate B Subunits
    Biochimica et Biophysica Acta 1808 (2011) 2359–2365 Contents lists available at ScienceDirect Biochimica et Biophysica Acta journal homepage: www.elsevier.com/locate/bbamem Instability of toxin A subunit of AB5 toxins in the bacterial periplasm caused by deficiency of their cognate B subunits Sang-Hyun Kim a, Su Hyang Ryu a, Sang-Ho Lee a, Yong-Hoon Lee a, Sang-Rae Lee a, Jae-Won Huh a, Sun-Uk Kim a, Ekyune Kim d, Sunghyun Kim b, Sangyong Jon b, Russell E. Bishop c,⁎, Kyu-Tae Chang a,⁎⁎ a The National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang, Cheongwon, Chungbuk 363–883, Republic of Korea b School of Life Science, Gwangju Institute of Science and Technology (GIST), 1 Oryong-dong, Gwangju 500–712, Republic of Korea c Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada L8N 3Z5 d College of Pharmacy, Catholic University of Daegu, Hayang-eup, Gyeongsan, Gyeongbuk 712-702, Republic of Korea article info abstract Article history: Shiga toxin (STx) belongs to the AB5 toxin family and is transiently localized in the periplasm before secretion Received 26 April 2011 into the extracellular milieu. While producing outer membrane vesicles (OMVs) containing only A subunit of Received in revised form 3 June 2011 the toxin (STxA), we created specific STx1B- and STx2B-deficient mutants of E. coli O157:H7. Surprisingly, Accepted 23 June 2011 STxA subunit was absent in the OMVs and periplasm of the STxB-deficient mutants. In parallel, the A subunit Available online 5 July 2011 of heat-labile toxin (LT) of enterotoxigenic E.
    [Show full text]
  • Mycotoxin Analysis in Infant Formula Using Captiva EMR-Lipid
    Application Note Food Testing & Agriculture Mycotoxin Analysis in Infant Formula Using Captiva EMR—Lipid Cleanup and LC/MS/MS Author Abstract Derick Lucas Agilent Technologies, Inc. Several countries regulate the levels of mycotoxins in foods. However, the complexity of certain foodstuffs in terms of protein and lipid content can prove challenging in the accurate quantitation of low-level mycotoxins in these matrices. This Application Note describes the determination of 13 multiclass mycotoxins in solid and liquid infant formulations using a Quick Easy Cheap Effective Rugged Safe (QuEChERS) workflow followed by Agilent Captiva EMR—Lipid cartridge cleanup. Due to the high selectivity of the Captiva EMR—Lipid sorbent, excellent recoveries (70.4 to 106.8 %) and precision (<18 %) were achieved for all mycotoxins. This simple and robust methodology requires minimal equipment and expertise, which promotes easy implementation in food laboratories. Introduction Experimental Mycotoxins are produced as secondary metabolites by fungal Sample preparation species that grow on various crops such as grain, corn, and • Captiva EMR—Lipid 3-mL tubes (p/n 5190-1003) nuts. When cows ingest contaminated feed, mycotoxins and their metabolites can be excreted into the animal’s milk1. • Captiva EMR—Lipid 6-mL tubes (p/n 5190-1004) Aflatoxin M1 is the most commonly found mycotoxin in milk, • QuEChERS original extraction salts (p/n 5982-5550) and is monitored and regulated in many countries, including • VacElut SPS 24 vacuum manifold (p/n 12234022) the United States and European countries2,3. Despite a lack of regulations for other mycotoxins in milk, there is a growing LC configuration and parameters interest to monitor additional mycotoxins such as fumonisins and ochratoxins.
    [Show full text]
  • Impact of Bacterial Toxins in the Lungs
    toxins Review Impact of Bacterial Toxins in the Lungs 1,2,3, , 4,5, 3 2 Rudolf Lucas * y, Yalda Hadizamani y, Joyce Gonzales , Boris Gorshkov , Thomas Bodmer 6, Yves Berthiaume 7, Ueli Moehrlen 8, Hartmut Lode 9, Hanno Huwer 10, Martina Hudel 11, Mobarak Abu Mraheil 11, Haroldo Alfredo Flores Toque 1,2, 11 4,5,12,13, , Trinad Chakraborty and Jürg Hamacher * y 1 Pharmacology and Toxicology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA; hfl[email protected] 2 Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA; [email protected] 3 Department of Medicine and Division of Pulmonary Critical Care Medicine, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA; [email protected] 4 Lungen-und Atmungsstiftung, Bern, 3012 Bern, Switzerland; [email protected] 5 Pneumology, Clinic for General Internal Medicine, Lindenhofspital Bern, 3012 Bern, Switzerland 6 Labormedizinisches Zentrum Dr. Risch, Waldeggstr. 37 CH-3097 Liebefeld, Switzerland; [email protected] 7 Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, QC H3T 1J4, Canada; [email protected] 8 Pediatric Surgery, University Children’s Hospital, Zürich, Steinwiesstrasse 75, CH-8032 Zürch, Switzerland; [email protected] 9 Insitut für klinische Pharmakologie, Charité, Universitätsklinikum Berlin, Reichsstrasse 2, D-14052 Berlin, Germany; [email protected] 10 Department of Cardiothoracic Surgery, Voelklingen Heart Center, 66333
    [Show full text]
  • Host-Based Lipid Inflammation Drives Pathogenesis in Francisella Infection
    Host-based lipid inflammation drives pathogenesis in Francisella infection Alison J. Scotta, Julia Maria Postb, Raissa Lernerb, Shane R. Ellisc, Joshua Liebermand, Kari Ann Shireye, Ron M. A. Heerenc, Laura Bindilab, and Robert K. Ernsta,1 aDepartment of Microbial Pathogenesis, School of Dentistry, University of Maryland, Baltimore, MD 21201; bLaboratory for Eicosanoids and Endocannabinoids, Johannes Gutenberg University Mainz, 55099 Mainz, Germany; cMaastricht MultiModal Molecular Imaging Institute, Maastricht University, 6229 ER Maastricht, The Netherlands; dDepartment of Pathology, University of Washington Medical Center, Seattle, WA 98118; and eDepartment of Microbiology and Immunology, School of Medicine, University of Maryland, Baltimore, MD 21201 Edited by Roy Curtiss III, University of Florida, Gainesville, FL, and approved October 16, 2017 (received for review July 19, 2017) Mass spectrometry imaging (MSI) was used to elucidate host lipids MSI (18), although other ionization methods [such as desorption involved in the inflammatory signaling pathway generated at the electrospray ionization (DESI) and liquid extraction surface host–pathogen interface during a septic bacterial infection. Using analysis (LESA), and others] are also employed. MSI has been Francisella novicida as a model organism, a bacterial lipid virulence used in a wide array of applications ranging from fingerprint factor (endotoxin) was imaged and identified along with host phos- analysis to mapping drug distribution in tissue. MSI studies of pholipids involved in the splenic response in murine tissues. Here, cancer biology for biomarker discovery, therapeutic target iden- we demonstrate detection and distribution of endotoxin in a lethal tification, and fundamental pathology hold particular promise. In murine F. novicida infection model, in addition to determining the contrast, comparatively few systematic studies have leveraged MSI – temporally and spatially resolved innate lipid inflammatory response to describe the host microbe relationship (19, 20).
    [Show full text]
  • LIPID MEDIATORS in HEALTH and DISEASE II: from the Cutting Edge–A Tribute to Edward Dennis and 7TH INTERNATIONAL CONFERENCE on PHOSPHOLIPASE A2 and LIPID MEDIATORS
    LIPID MEDIATORS IN HEALTH AND DISEASE II: From The Cutting Edge–A Tribute to Edward Dennis And 7TH INTERNATIONAL CONFERENCE ON PHOSPHOLIPASE A2 and LIPID MEDIATORS: From Bench To Translational Medicine Honorary Chair: Nobel Laureate Bengt Samuelsson La Jolla, California May 19-20, 2016 http://www.medschool.lsuhsc.edu/neuroscience/LipidMediatorsPLA2-2016/ Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis 2+ Steered molecular dynamics simulation of Group VIA Ca - independent phospholipase A2 (PLA2) embedded in a bilayer membrane composed mainly of 1-palmitoyl, 2-oleoyl phosphatidycholine (POPC) extracting and pulling a 1-palmitoyl, 2-archidonyl phosphatidylcholine (PAPC) into its binding pocket in the active site. [For movies of this simulation, see Mouchlis VD, Bucher, D, McCammon, JA, Dennia EA (2015) Membranes serve as allosteric activators of phospholipase A2 enabling it to extract, bind, and hydrolyze phospholipid substrates, Proc Natl Acad Sci U S A, 112, E516-25.] Lipid Mediators in Health and Disease II: From The Cutting Edge • A Tribute to Edward Dennis WELCOME I would like to welcome all of the participants of the Lipid Mediators in Health and Disease II: From The Cutting Edge, A Tribute to Edward Dennis, and the 7th International Conference on Phospholipase A2 and Lipid Mediators: From Bench To Translational Medicine. This conference follows upon the very successful meeting led by Professor Jesper Z. Haeggström at the Karolinska Institutet, Nobel Forum, Stockholm, Sweden, on August 27-29, 2014, where Nobel Laureate Professor Bengt Samuelsson was honored. Lipids serve a myriad of essential functions in cell signaling, cell organization, energy metabolism, and overall homeostasis.
    [Show full text]
  • Clostridium Perfringens
    INFECTION AND IMMUNITY, Aug. 1997, p. 3485–3488 Vol. 65, No. 8 0019-9567/97/$04.0010 Copyright © 1997, American Society for Microbiology Clostridium perfringens Enterotoxin Lacks Superantigenic Activity but Induces an Interleukin-6 Response from Human Peripheral Blood Mononuclear Cells TERESA KRAKAUER,1 BERNHARD FLEISCHER,2 DENNIS L. STEVENS,3,4 5 1 BRUCE A. MCCLANE, AND BRADLEY G. STILES * Department of Immunology and Molecular Biology, U.S. Army Medical Research Institute of Infectious Diseases, Frederick, Maryland1; Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany2; Infectious Diseases Section, Veterans Administration Medical Center, Boise, Idaho3; University of Washington School of Medicine, Seattle, Washington4; and Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania5 Received 20 February 1997/Returned for modification 3 April 1997/Accepted 22 May 1997 We investigated the potential superantigenic properties of Clostridium perfringens enterotoxin (CPE) on human peripheral blood mononuclear cells (PBMC). In contrast to the findings of a previous report (P. Bowness, P. A. H. Moss, H. Tranter, J. I. Bell, and A. J. McMichael, J. Exp. Med. 176:893–896, 1992), two different, biologically active preparations of CPE had no mitogenic effects on PBMC. Furthermore, PBMC incubated with various concentrations of CPE did not elicit interleukin-1, interleukin-2, gamma interferon, or tumor necrosis factor alpha or beta, which are cytokines commonly associated with superantigenic stimulation. However, CPE did cause a dose-related release of interleukin-6 from PBMC cultures. Clostridium perfringens enterotoxin (CPE) is traditionally Additionally, the full-length recombinant CPE species used in recognized as a virulence factor responsible for the diarrheal this study has recently been characterized in detail (10) and and cramping symptoms associated with C.
    [Show full text]
  • Scientific Program
    Scientific Program 1 he Annual Meeting of the Brazilian Biophysics Society, one of the largest T and most traditional gathering of Biophysicists in Latin America, occurs during the second semester of each year. Now in its 43rd edition, the 2018 meeting will be held again at the Mendes Plaza Hotel, in the city of Santos (SP), from September 27th to 30th. A rich program of 16 symposia, 4 plenary talks, and 2 poster sessions covering a broad range of topics in Biophysics will guarantee the appropriate environment for productive discussions about developments regarding Biophysics and its interfaces with Biochemistry, Medicine, Pharmacy, among other disciplines. World leaders in several areas of Biophysics, from at least 12 different countries have already confirmed participation in our meeting this year! We will host researchers from Argentina, Belgium, Canada, Denmark, England, France, Germany, Israel, Portugal, United States, Uruguay and, of course, from Brazil, which will be represented by colleagues from 10 different states. This shows our broad representation in both national and international scenarios. We believe our meeting is the perfect opportunity for researchers interested in Biophysics and related fields to present their latest results to a very distinguished audience. Therefore, we invite you to participate and to submit an abstract for the poster sessions. Looking forward to seeing you in Santos! Antonio Costa-Filho President of SBBf 2 3 Index Iseli L. Nantes Cardoso ................................................ 56 Tayana Mazin Tsubone ................................................. 83 Juliana S Yoneda ........................................................ 57 Yan M. H. Gonçalves ................................................... 84 Organizing Committee ............................................7 Katia Regina Perez ....................................................... 33 Lucas Rodrigues de Mello............................................ 57 Yeny Y. P. Valencia ....................................................
    [Show full text]
  • Universidade De São Paulo Escola De Comunicações E Artes Departamento De Informação E Cultura
    UNIVERSIDADE DE SÃO PAULO ESCOLA DE COMUNICAÇÕES E ARTES DEPARTAMENTO DE INFORMAÇÃO E CULTURA Bruna Acylina Gallo Indicadores de Produção Científica: o caso do Instituto Butantan São Paulo 2019 Bruna Acylina Gallo Indicadores de Produção Científica: o caso do Instituto Butantan Relatório Final de Iniciação Científica submetido ao Departamento de Informação e Cultura da Escola de Comunicações e Artes da Universidade de São Paulo. Orientador: Profª. Drª. Nair Yumiko Kobashi São Paulo 2019 AGRADECIMENTOS Gostaria de agradecer à minha orientadora, professora Nair Yumiko Kobashi por orientar este trabalho e por tantos aprendizados. E à Mariana Crivelente por me auxiliar nessa caminhada, pela paciência e colaboração, pois o trabalho analisou parte dos dados do projeto de sua dissertação “Métodos e técnicas bibliométricas de análise de produção científica: um estudo crítico”, do Programa de Pós- Graduação em Ciência da Informação da Escola de Comunicações e Artes. RESUMO Análise de produção científica do Instituto Butantan, do período 2007-2016, recuperados na Plataforma Lattes. O objetivo da pesquisa foi compreender os conceitos e métodos da Bibliometria e realizar um estudo de caso para aplicá-los. O trabalho seguiu os seguintes procedimentos: revisão de literatura; recuperação de artigos de pesquisadores do Instituto Butantan registrados na Plataforma Lattes; limpeza e normalização dos dados; tratamento bibliométrico dos dados; comparação dos resultados com os indicadores de produção científica publicados nos relatórios anuais do Instituto Butantan. Os resultados referem-se aos seguintes aspectos: indicadores de produção científica e de outras atividades de pesquisa e discussão dos problemas encontrados na produção de indicadores. O processo de pesquisa foi importante para conhecer os conceitos e métodos da Bibliometria e trazer à luz os diversos problemas enfrentados em estudos bibliométricos.
    [Show full text]
  • Perspectives
    PERSPECTIVES not undergone decomposition failed to have TIMELINE such effects. In attempts to isolate and charac- terize the poisonous material, Peter L. Panum (1820–1885) could be considered a pioneer. Innate immune sensing and its roots: He showed that putrid fluids contained a water-soluble, but alcohol-insoluble, heat- the story of endotoxin resistant, non-volatile substance, which was lethal to dogs3. Also, Ernst von Bergmann (1836–1906) believed that a chemically Bruce Beutler and Ernst Th. Rietschel defined substance was responsible for putrid intoxication, which he termed sepsin4. How does the host sense pathogens? formed the conceptual framework within Of course, the contagionists could not Our present concepts grew directly which early workers sought to identify it. explain how a single contact with putrid flu- from longstanding efforts to understand Impressed by the malodorous exhalations ids or a sick patient could transmit so much infectious disease: how microbes harm of patients suffering from plague and their poison that not only the affected person, but the host, what molecules are sensed and, similarity to the foul vapours emanating from also thousands of other people, would die. It ultimately, the nature of the receptors that marshes, physicians came to believe that the was, therefore, an intellectual breakthrough the host uses. The discovery of the host putative poison was generated by putrefac- to postulate that the putrid venom commu- sensors — the Toll-like receptors — was tion (from the Greek for sepsis) of organic nicated by miasma or contagion could rooted in chemical, biological and genetic matter present in sick people or in locations reproduce in the affected individual, thereby analyses that centred on a bacterial poison, such as swamps.
    [Show full text]
  • Molecular Aspects of Endotoxic Reactions A
    BACTERIOLCGICAL REVIEWS, Mar. 1969, p. 72-98 Vol. 33, No. I Copyright © 1969 American Society for Microbiology Printed in U.S.A. Molecular Aspects of Endotoxic Reactions A. NOWOTNY Department of Microbiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19122 INTRODUCTION............................................................ 72 CHEMICAL PROPERTIES AND CONSTITUENTS ............................ 73 BIOLOGICAL PROPERTIES ................................................. 73 Characteristic Endotoxic Reactions ............................................ 73 Sensitization and Desensitization Against Endotoxic Effects ....................... 75 Relationships Among Endotoxic Reactions ...................................... 76 Fate of Injected Endotoxins ................................................... 77 RELATION OF STRUCTURAL PARTS TO BIOLOGICAL FUNCTIONS ........ 78 Role of Polysaccharides ..................................................... 78 Role of Polypeptides ........................................................ 78 Lipid Moiety ........................................................... 78 Polysaccharide-free Endotoxic Glycolipids ....... ............................... 80 SEARCH FOR THE TOXIC PRINCIPLE ..................................... 80 Role of Hypersensitivity ..................................................... 80 Relation of Particle Size to Endotoxicity ....................................... 81 Toxic Constituents or Toxic Conformation? ..................................... 82 DETOXIFICATION AS
    [Show full text]
  • Antibacterial and Hemolytic Activity of Crotalus Triseriatus and Crotalus Ravus Venom
    animals Article Antibacterial and Hemolytic Activity of Crotalus triseriatus and Crotalus ravus Venom Adrian Zaragoza-Bastida 1 , Saudy Consepcion Flores-Aguilar 2, Liliana Mireya Aguilar-Castro 2, Ana Lizet Morales-Ubaldo 1 , Benjamín Valladares-Carranza 3, Lenin Rangel-López 1, Agustín Olmedo-Juárez 4 , Carla E. Rosenfeld-Miranda 5 and Nallely Rivero-Pérez 1,* 1 Universidad Autónoma del Estado de Hidalgo, Área Académica de Medicina Veterinaria y Zootecnia, Instituto de Ciencias Agropecuarias, Rancho Universitario Av. Universidad km 1, EX-Hda de Aquetzalpa, Tulancingo, Hidalgo 43600, Mexico; [email protected] (A.Z.-B.); [email protected] (A.L.M.-U.); [email protected] (L.R.-L.) 2 Universidad Autónoma del Estado de Hidalgo, Área Académica de Biología, Instituto de Ciencias Básicas e Ingeniería. Carretera Pachuca-Tulancingo S/N Int. 22 Colonia Carboneras, Mineral de la Reforma, Hidalgo 42180, Mexico; [email protected] (S.C.F.-A.); [email protected] (L.M.A.-C.) 3 Facultad de Medicina Veterinaria y Zootecnia Universidad Autónoma del Estado de México, El Cerrillo Piedras Blancas, Toluca 50295, Mexico; [email protected] 4 Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad (CENID SAI-INIFAP), Carretera Federal Cuernavaca-Cuautla No. 8534 / Col. Progreso, Jiutepec 62550, Morelos, Mexico; [email protected] 5 Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Isla Teja s/n, Casilla 567, Valdivia, Chile; [email protected] * Correspondence: [email protected]; Tel.: +52-771-717-2000 Received: 14 January 2020; Accepted: 7 February 2020; Published: 11 February 2020 Simple Summary: Rattlesnakes (Crotalus ravus and Crotalus triseriatus) have some compounds that resemble polypeptides and proteins in their venoms which can be used in therapeutic treatment as antibacterial compounds.
    [Show full text]