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Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin

Nonclinical evaluation of novel cationically modified ...

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dc.contributor.author Kałaska, Bartłomiej pl
dc.contributor.author Kamiński, Kamil [SAP14003414] pl
dc.contributor.author Sokolowska, Emilia pl
dc.contributor.author Czaplicki, Dominik [SAP12019892] pl
dc.contributor.author Kujdowicz, Monika [USOS94712] pl
dc.contributor.author Stalińska, Krystyna [SAP12013193] pl
dc.contributor.author Bereta, Joanna [SAP11012315] pl
dc.contributor.author Szczubiałka, Krzysztof [SAP11014318] pl
dc.contributor.author Pawlak, Dariusz pl
dc.contributor.author Nowakowska, Maria [SAP11005597] pl
dc.contributor.author Mogielnicki, Andrzej pl
dc.date.accessioned 2015-05-25T08:01:31Z
dc.date.available 2015-05-25T08:01:31Z
dc.date.issued 2015 pl
dc.identifier.uri http://ruj.uj.edu.pl/xmlui/handle/item/7884
dc.language eng pl
dc.rights Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa *
dc.rights.uri http://creativecommons.org/licenses/by/4.0/pl/legalcode *
dc.title Nonclinical evaluation of novel cationically modified polysaccharide antidotes for unfractionated heparin pl
dc.type JournalArticle pl
dc.identifier.weblink https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0119486&type=printable pl
dc.abstract.en Protamine, the only registered antidote of unfractionated heparin (UFH), may produce a number of adverse effects, such as anaphylactic shock or serious hypotension. We aimed to develop an alternative UFH antidote as efficient as protamine, but safer and easier to produce. As a starting material, we have chosen generally non-toxic, biocompatible, widely available, inexpensive, and easy to functionalize polysaccharides. Our approach was to synthesize, purify and characterize cationic derivatives of dextran, hydroxypropylcellulose, pullulan and γ-cyclodextrin, then to screen them for potential heparin-reversal activity using an in vitro assay and finally examine efficacy and safety of the most active polymers in Wistar rat and BALB/c mouse models of experimentally induced arterial and venous thrombosis. Efficacy studies included the measurement of thrombus formation, activated partial thromboplastin time, bleeding time, and anti-factor Xa activity; safety studies included the measurement of hemodynamic, hematologic and immunologic parameters. Linear, high molecular weight dextran substituted with glycidyltrimethylammonium chloride groups at a ratio of 0.65 per glucose unit (Dex40-GTMAC3) is the most potent and the safest UFH inhibitor showing activity comparable to that of protamine while possessing lower immunogenicity. Cationic polysaccharides of various structures neutralize UFH. Dex40-GTMAC3 is a promising and potentially better UFH antidote than protamine. pl
dc.description.volume 10 pl
dc.description.number 3 pl
dc.identifier.doi 10.1371/journal.pone.0119486 pl
dc.identifier.eissn 1932-6203 pl
dc.title.journal PLoS ONE pl
dc.language.container eng pl
dc.date.accession 2019-02-18 pl
dc.affiliation Wydział Chemii : Zakład Chemii Fizycznej i Elektrochemii pl
dc.affiliation Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biochemii Komórki pl
dc.subtype Article pl
dc.identifier.articleid e0119486 pl
dc.rights.original CC-BY; otwarte czasopismo; ostateczna wersja wydawcy; w momencie opublikowania; 0; pl
dc.identifier.project ROD UJ / P pl
dc.pbn.affiliation USOS94712:UJ.WCh; pl
.pointsMNiSW [2015 A]: 40


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Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa Except where otherwise noted, this item's license is described as Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa