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[{"key": "dc.contributor.author", "value": "Lempi\u00e4inen, Joanna", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2013-04-22T09:49:42Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2013-04-22T09:49:42Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2013", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1259271", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/41231", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Myeloperoksidaasi on neutrofiilien ja monosyyttien entsyymi, joka muuttaa vetyperoksidia bakterisidisiksi yhdisteiksi, kuten hypokloorihapokkeeksi. Myeloperoksidaasia on pidetty neutrofiilien bakterisidiselle toiminnalle elint\u00e4rke\u00e4n\u00e4, sill\u00e4 sen on ajateltu tehostavan neutrofiilien bakteeritappoa merkitt\u00e4v\u00e4sti. Viimeaikoina on kuitenkin saatu tutkimustuloksia, joiden mukaan veress\u00e4 vapaana oleva myeloperoksidaasi voisi toimia sairauden aiheuttajana pahentaen muun muassa ateroskleroosin ja nivelreuman oireita. Myeloperoksidaasin tuottamaa hypokloorihapokkeen m\u00e4\u00e4r\u00e4\u00e4 voidaan mitata ep\u00e4suorasti luminolivahvisteisella kemiluminesenssilla. Eristetyn myeloperoksidaasin ja neutrofiilien kyky\u00e4 tappaa bakteereja on mahdollista tutkia my\u00f6s suoraan k\u00e4ytt\u00e4m\u00e4ll\u00e4 bioluminesoivaa Escherichia coli bakteeria (E.coli -lux), joka sis\u00e4lt\u00e4\u00e4 Photorhabdus luminescens bakteerin lusiferaasigeenin. Reaktiosta emittoituva valo on t\u00e4ll\u00f6in suoraan verrannollinen reaktiossa olevien E.coli \u2013lux bakteerien m\u00e4\u00e4r\u00e4\u00e4n. Suosittu kipul\u00e4\u00e4ke, parasetamoli, inhiboi myeloperoksidaasin hypokloorihapokkeen tuottoa ja sen on havaittu inhiboivan my\u00f6s myeloperoksidaasin kemiluminesenssia. Parasetamolin vaikutuksia myeloperoksidaasin bakteeritappoon ei kuitenkaan ole aiemmin tutkittu, eik\u00e4 parasetamolin vaikutuksia myeloperoksidaasiin ole aiemmin tutkittu mittaamalla kemiluminesenssia yht\u00e4jaksoisesti.\n\nT\u00e4m\u00e4n tutkimuksen tarkoituksena oli selvitt\u00e4\u00e4, miten parasetamoli vaikuttaa myeloperoksidaasin kemiluminesenssiin ja bakteeritappoon. Kokeet tehtiin happamassa ja neutraalissa pH:ssa, sill\u00e4 myeloperoksidaasia on neutrofiilien happamien fagolysosomien lis\u00e4ksi solun ulkopuolella.\n\nKaikki mittaukset tehtiin luminometrilla. Myeloperoksidaasin tuottamaa hypokloorihapokkeen m\u00e4\u00e4r\u00e4\u00e4 mitattiin luminoliv\u00e4litteisen\u00e4 kemiluminesenssina eri parasetamolipitoisuuksilla. Bakteeritapon reaktioissa tarkkailtiin myeloperoksidaasin tappamien E. coli -lux bakteerien m\u00e4\u00e4r\u00e4\u00e4 mittaamalla reaktiosta emittoituvaa bakteerien bioluminesenssia eri parasetamolipitoisuuksilla.\n\nParasetamoli kasvatti myeloperoksidaasin kemiluminesenssivastetta jopa kymmenkertaisesti pienill\u00e4 pitoisuuksilla ensimm\u00e4isen 15 minuutin aikana, jonka j\u00e4lkeen sen vaikutus oli inhiboiva. T\u00e4m\u00e4 havaittiin sek\u00e4 happamassa ett\u00e4 neutraalissa pH:ssa. Aktivaatio ja sit\u00e4 seuraava inhibitio saavutettiin parasetamolin normaalilla k\u00e4yt\u00f6ll\u00e4 saavutettavilla pitoisuuksilla veress\u00e4, eli alle 22,5 \u03bcg/ml (150 \u03bcM) pitoisuuksilla. Aktivaatio ja inhibitio ei ollut yht\u00e4 voimakasta bakteeritapon reaktioissa, joissa happamassa pH:ssa parasetamolin vaikutus oli my\u00f6s heikompaa. Suurimmillaan parasetamolin aiheuttama aktivaatio johti vain noin 10 %:in lis\u00e4ykseen kuolleiden bakteerien m\u00e4\u00e4r\u00e4ss\u00e4. Tulosten perusteella parasetamoli vaikuttaa myeloperoksidaasin hypokloorihapokkeen muodostumiseen alle 22,5 \u03bcg/ml pitoisuuksilla merkitt\u00e4v\u00e4sti sek\u00e4 neutraalissa ett\u00e4 happamassa pH:ssa. Lis\u00e4ksi parasetamoli vaikuttaa myeloperoksidaasiin neutraalissa ja happamassa pH:ssa samalla tavalla sek\u00e4 yht\u00e4 voimakkaasti. Parasetamolipitoisuus 22,5 \u03bcg/ml on saavutettavissa, kun l\u00e4\u00e4keainetta k\u00e4ytet\u00e4\u00e4n l\u00e4\u00e4k\u00e4rin ohjeiden mukaisesti, joten olisi t\u00e4rke\u00e4\u00e4 selvitt\u00e4\u00e4, mik\u00e4 vaikutus myeloperoksidaasin inhibitiolla ja mahdollisella aktivaatiolla on ihmisen elimist\u00f6n toiminnalle.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Myeloperoxidase is an enzyme found from neutrophils and monocytes. It converts hydrogen peroxide to hypochlorous acid and other bactericidal compounds. Myeloperoxidase has been considered a crucial enzyme for neutrophil bactericidal function, because it is thought to enhance the bacterial killing of neutrophils significantly. However, recent studies have also proven that extracellular myeloperoxidase can have adverse effects in several diseases, like atherosclerosis and arthritis. Hypochlorous acid production by isolated myeloperoxidase and neutrophils can be measured non-specifically with luminol-dependent chemiluminescence. Bactericidal function of isolated myeloperoxidase and neutrophils can be monitored on a real-time basis by using bioluminescent Escherichia coli bacteria (E.coli -lux) which contain a luciferase gene from the Photorhabdus luminescens bacterium. Light emitted from the reaction is directly proportional to the amount of living E.coli -lux bacteria. Paracetamol, a popular analgesic, inhibits hypochlorous acid production by myeloperoxidase with therapeutically achievable concentrations and has been found to inhibit the chemiluminescence response of isolated myeloperoxidase and neutrophils. The effect of paracetamol on myeloperoxidase bacterial killing has not been studied before, and chemiluminescence experiments with paracetamol have not been done on a real-time basis before.\n\nAim of this study was to investigate the effects of paracetamol on myeloperoxidase chemiluminescence and bacterial killing. Experiments were done in acid and neutral pH, because myeloperoxidase can be intracellular and reside in the acid phagolysosomes of neutrophils or it can be extracellular and function in neutral pH.\n\nAll measurements were done with a luminometer. Luminol-dependent chemiluminescence was used to measure the amount of hypochlorous acid produced by myeloperoxidase in the presence of paracetamol. In killing experiments, the amount of E. coli-lux bacteria was measured on a real-time basis in the presence of myeloperoxidase and paracetamol.\n\nLow concentrations of paracetamol activated the myeloperoxidase chemiluminescence up to tenth fold in the first 15 minutes, after which the effect was inhibitory. This observation was made in acid and neutral pH. As expected, activation and inhibition was acquired with concentrations less than 22,5 \u03bcg/ml (150 \u03bcM), which is the therapeutically achievable concentration in plasma. Activation and inhibition in the killing experiments were not as strong as in the chemiluminescence experiments. The activation only caused a 10 % increase in the killing of bacteria by myeloperoxidase. According to the results of this study, paracetamol affects the hypochlorous acid production of myeloperoxidase at therapeutically achievable concentrations in neutral and acid pH. In addition, paracetamol seems to affect myeloperoxidase in a similar manner and with the same magnitude in both neutral and acid pH. Paracetamol concentration of 22,5 \u03bcg/ml in plasma can be achieved when the drug is used according to doctors recommendations. Thus, in the future, it would be important to study the effects of myeloperoxidase inhibition and possible activation on the human body.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Joanna Lempi\u00e4inen (jokalemp) on 2013-04-22 09:49:41.802721. Form: Pro gradu -lomake (1 tekij\u00e4) (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake-1-tekijae). 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No. of bitstreams: 2\nURN:NBN:fi:jyu-201304221476.pdf: 1209539 bytes, checksum: dc8064d2b2776081b9a1156ca9e0d8f0 (MD5)\nlicense.html: 107 bytes, checksum: a7d86e598caa500b1b433bbb9dc8ef1c (MD5)\n Previous issue date: 2013", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "45 sivua", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "myeloperoksidaasi", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.subject.other", "value": "kemiluminesenssi", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Parasetamolin vaikutus myeloperoksidaasin toimintaan", "language": null, "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201304221476", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.date.updated", "value": "2013-04-22T09:49:42Z", "language": null, "element": "date", "qualifier": "updated", "schema": "dc"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": null, "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "parasetamoli", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "bioluminesenssi", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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