{"?xml":{"@version":"1.0"},"edm:RDF":{"@xmlns:dc":"http://purl.org/dc/elements/1.1/","@xmlns:edm":"http://www.europeana.eu/schemas/edm/","@xmlns:wgs84_pos":"http://www.w3.org/2003/01/geo/wgs84_pos","@xmlns:foaf":"http://xmlns.com/foaf/0.1/","@xmlns:rdaGr2":"http://rdvocab.info/ElementsGr2","@xmlns:oai":"http://www.openarchives.org/OAI/2.0/","@xmlns:owl":"http://www.w3.org/2002/07/owl#","@xmlns:rdf":"http://www.w3.org/1999/02/22-rdf-syntax-ns#","@xmlns:ore":"http://www.openarchives.org/ore/terms/","@xmlns:skos":"http://www.w3.org/2004/02/skos/core#","@xmlns:dcterms":"http://purl.org/dc/terms/","edm:WebResource":[{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-LM7WE4FS/e15ba18a-9dbc-4966-88fb-5b2a91a6b62e/PDF","dcterms:extent":"223 KB"},{"@rdf:about":"http://www.dlib.si/stream/URN:NBN:SI:doc-LM7WE4FS/efca6aec-d382-45fa-9ca2-b19067a9ccf2/TEXT","dcterms:extent":"32 KB"}],"edm:TimeSpan":{"@rdf:about":"2005-2025","edm:begin":{"@xml:lang":"en","#text":"2005"},"edm:end":{"@xml:lang":"en","#text":"2025"}},"edm:ProvidedCHO":{"@rdf:about":"URN:NBN:SI:doc-LM7WE4FS","dcterms:isPartOf":[{"@rdf:resource":"https://www.dlib.si/details/URN:NBN:SI:spr-8ER5ZBJN"},{"@xml:lang":"sl","#text":"Farmacevtski vestnik"}],"dcterms:issued":"2019","dc:creator":["Mlinarič-Raščan, Irena","Šmid, Alenka","Urbančič, Dunja"],"dc:format":[{"@xml:lang":"sl","#text":"številka:3"},{"@xml:lang":"sl","#text":"letnik:70"},{"@xml:lang":"sl","#text":"str. 220-227"}],"dc:identifier":["ISSN:0014-8229","COBISSID_HOST:4766065","URN:URN:NBN:SI:doc-LM7WE4FS"],"dc:language":"sl","dc:publisher":{"@xml:lang":"sl","#text":"Slovensko farmacevtsko društvo"},"dc:subject":[{"@xml:lang":"sl","#text":"farmakogenomika"},{"@xml:lang":"sl","#text":"genetski polimorfizmi"},{"@xml:lang":"sl","#text":"S-adenozilmetionin"},{"@xml:lang":"sl","#text":"tiopurin S-metiltransferaza"},{"@xml:lang":"sl","#text":"tiopurini"}],"dcterms:temporal":{"@rdf:resource":"2005-2025"},"dc:title":{"@xml:lang":"sl","#text":"Farmakogenomsko vrednotenje tiopurinov| Pharmacogenomic evaluation of thiopurines|"},"dc:description":[{"@xml:lang":"sl","#text":"Thiopurines represent an important therapeutic pillar in the therapy of acute lymphoblastic leukaemia, autoimmune disorders and in preventing transplant rejections. Their major route of deactivation is directed via thiopurine S-methyltransferase (TPmT). With the discovery of trimodal population distribution of its enzymatic activity, resulting from genetic polymorphisms present in its gene, the determination of TPmT status became one of the most successful implementations of pharmacogenomics into clinical practice. In patients treated with standard dose of thiopurines, decreased TPmT activity triggers severe side effects, due to poorer deactivation of these drugs. Guidelines from European and American consortia for implementation of pharmacogenetics advocate determination of most common genetic polymorphisms or activity of TPmT prior to initiating thiopurine therapy. In patients heterozygous for TPMT 30%70% of target dose is recommended and substantially reduced doses or use of alternative treatment is advised in homozygous patients with deficient TPmT activity"},{"@xml:lang":"sl","#text":"Tiopurini so predzdravila, ki jih uporabljamo pri zdravljenju akutne limfoblastne levkemije, avtoimunskih bolezni in pri preprečevanju zavrnitvenih reakcij po transplantaciji organov. Eden najpomembnejših encimov v deaktivacijski poti njihovega metabolizma je tiopurin S-metiltransferaza (TPmT). Odkritje populacijske raznolikosti v aktivnosti tega encima zaradi prisotnih genetskih polimorfizmov v njegovem genu je botrovalo vključitvi določanja le-teh v klinično prakso in še danes predstavlja enega najboljših farmakogenomskih primerov. Pacienti z genetskimi polimorfizmi ob standardnem zdravljenju s tiopurini namreč bolj verjetno razvijejo neželene učinke, saj v manjšem obsegu deaktivirajo te zdravilne učinkovine. Smernice evropskih in ameriških združenj za implementacijo farmakogenomike zato priporočajo določanje prisotnosti najpogostejših genetskih polimorfizmov TPMT ali aktivnosti encima pred začetkom zdravljenja. Hkrati svetujejo 30%70-odstotno znižanje standardnega odmerka tiopurinov ob prisotnem enem variantnem alelu ter zamenjavo terapije ali 90-odstotno znižanje standardnega odmerka tiopurinov v primeru dveh prisotnih variantnih alelov TPMT"}],"edm:type":"TEXT","dc:type":[{"@xml:lang":"sl","#text":"znanstveno časopisje"},{"@xml:lang":"en","#text":"journals"},{"@rdf:resource":"http://www.wikidata.org/entity/Q361785"}]},"ore:Aggregation":{"@rdf:about":"http://www.dlib.si/?URN=URN:NBN:SI:doc-LM7WE4FS","edm:aggregatedCHO":{"@rdf:resource":"URN:NBN:SI:doc-LM7WE4FS"},"edm:isShownBy":{"@rdf:resource":"http://www.dlib.si/stream/URN:NBN:SI:doc-LM7WE4FS/e15ba18a-9dbc-4966-88fb-5b2a91a6b62e/PDF"},"edm:rights":{"@rdf:resource":"http://rightsstatements.org/vocab/InC/1.0/"},"edm:provider":"Slovenian National E-content Aggregator","edm:intermediateProvider":{"@xml:lang":"en","#text":"National and University Library of Slovenia"},"edm:dataProvider":{"@xml:lang":"sl","#text":"Slovensko farmacevtsko društvo"},"edm:object":{"@rdf:resource":"http://www.dlib.si/streamdb/URN:NBN:SI:doc-LM7WE4FS/maxi/edm"},"edm:isShownAt":{"@rdf:resource":"http://www.dlib.si/details/URN:NBN:SI:doc-LM7WE4FS"}}}}