Show simple item record

Circulating microparticles and biomarkers of oxidative stress in patients with rheumatoid arthritis

dc.contributor.advisorAntović, Aleksandra
dc.contributor.otherVeselinović, Mirjana
dc.contributor.otherJakovljević, Vladimir
dc.contributor.otherAnđelković, Nebojša
dc.contributor.otherPetronijević, Milan
dc.creatorVranić, Aleksandra
dc.date.accessioned2020-01-27T14:06:14Z
dc.date.available2020-01-27T14:06:14Z
dc.date.available2020-07-03T15:20:33Z
dc.date.issued2019-11-28
dc.identifier.urihttp://eteze.kg.ac.rs/application/showtheses?thesesId=7058
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/11816
dc.identifier.urihttps://fedorakg.kg.ac.rs/fedora/get/o:1179/bdef:Content/download
dc.description.abstractUvod: Reumatoidni artritis (RA) je hronična, inflamatorna, autoimuna bolest koja uzrokuje sinovitis i destruktivni artritis, progresivno oštećenje hrskavice i zglobova, deformitete praćene van-zglobnim, sistemskim manifestacijama bolesti, snažan sistemski inflamatorni odgovor sa ubrzanim razvojem ateroskleroze, kao i invaliditet, skraćeni životni vek i povećan mortalitet. Cilj: Ispitati uticaj RA na koncentraciju mikropartikula, aktiviranje hemostaze, pojavu prokoagulabilnog stanja, fibrinsku mrežu i morfologiju vlakana fibrinskog ugruška, parametre oksidacionog stresa i antioksidacionog sistema zaštite, kao i uticaj reumatoidnog artritisa na biohemijske, hematološke i hemostatske parametre i sve analize uporediti sa zdravim ispitanicima. Materijal i metode: Kod 42 pacijenta sa RA i 48 zdravih kontrola, ispitivana je koncentracija mikropartikula protočnom citometrijom pri čemu su praćene mikropartikule koje potiču od trombocita, leukocita, monocita, endotelne mikropartikule, mikropartikule koje eksprimiraju P-selektin i E-selektin i tkivni faktor. Hemostaza i pojava prokoagulabilnog stanja praćena je globalnim metodama, endogenim trombin potencijalom i ukupnim hemostatski potencijalom. Elektronskom mikroskopijom ispitan je uticaj RA na fibrinsku mrežu i morfologiju vlakana fibrinskog ugruška. Redoks status je određivan spektrofotometrijski. Kompletne biohemijske, hematološke i hemostatske analize su urađene u Centralnoj laboratoriji Kliničkog centra Kragujevac. Rezultati: Ukupna koncentracija mikropartikula kao i koncentracija mikropartikula koje potiču od trombocita, monocita, leukocita i P-selektina bile su povišene kod pacijenata sa RA u odnosu na zdrave ispitanike. Globalne metode hemostaze ukazuju da je koagulacija snažno pogođena dugotrajnom inflamacijom kod pacijenata sa RA, i menopauzom kod zdravih žena. Elektronskom mikroskopijom pokazano je da pacijenti sa reumatoidnim artritisom kao i zdrave kontrole u menopauzi imaju gušću strukturu fibrinskog ugruška sa manjim porama, koji je manje osetljiv na fibrinolizu. Prooksidacioni i antioksidacioni parametri praćeni u studiji ukazuju na postojanje oksidacionog stresa i smanjenje aktivnosti antioksidacionog sistema zaštite kod pacijenata sa RA. I RA i menopauza dovode do značajnog smanjenja mineralne gustine kostiju. Svi nespecifični parametri inflamacije bili su povišeni kod pacijenata sa RA. Zaključak: Mikropartikule koje potiču od trombocita mogu biti potencijalni biomarker za trombocitnu reaktivnost u RA koja predstavlja prediktor za nastanak tromboze i povećanje kardiovaskularnog rizika. Parametri globalnih hemostatskih metoda mogu biti korisni u dijagnostikovanju i praćenju hiperkoagulacionog stanja kod pacijenata sa RA. Kod pacijenata sa reumatoidnim artritisom postoji potreba za suplementacijom antioksidansima.sr
dc.description.abstractIntroduction: Rheumatoid Arthritis (RA) is a chronic, inflammatory, autoimmune disease that causes synovitis and destructive arthritis, progressive cartilage and joints damage, deformities followed by outside of the articular manifestations, systemic disease manifestations, a strong systemic inflammatory response with rapid development of atherosclerosis, disabilities, shortened life expectancy and increased mortality. Aim: We aimed this study, therefore, to explore the effect of RA on the microparticles expression in peripheral blood, to assess hemostatic disturbances and the occurrence of procoagulable state, to identify fibrin clot properties and the morphology of fibrin clot fibers, to determine parameters of oxidative stress and the antioxidantative system as well as the impact of rheumatoid arthritis on biochemical, hematological and hemostatic parameters and to compare all the analyzes with healthy subjects. Material and methods: In 42 patients with RA and 48 healthy controls, the following parameters were examined using appropriate methods. The concentration of microparticles was determined by flow cytometry, whereby microparticles derived from platelets, leukocytes, monocytes, endothelial microparticles, microparticles expressing P-selectin, Eselectin and a tissue factor were determined. Parameters of hemostasis and the occurrence of a procoagulable condition were followed by global hemostatic methods, endogenous thrombin potential and overall hemostasis potential. Тhe effect of RA on the fibrin network and the morphology of fibrin clot fibers was analyzed by electron microscopy. Redox status was determined spectrophotometrically. Biochemical, haematological and hemostatic analyzes were done in the Central Laboratory of the Clinical Center Kragujevac. Results: The total concentration of microparticles, the concentration of platelet-, мonocyte-, leukocyte- and P-selectin-derived microparticles, were elevated in patients with RA compared to healthy subjects. Global hemostatic methods indicate that coagulation is strongly affected by long-term inflammation in patients with RA, and menopause in healthy women. Electron microscopy shown that patients with RA as well as healthy control had denser fibrin structures with smaller pores which are less prone to fibrinolysis. The prooxidative and antioxidantive parameters followed in the study indicate the existence of oxidative stress and decreased activity of the antioxidative system in patients with RA. Both RA and menopause lead to a significant decrease in bone mineral density. All non-specific inflammatory parameters were elevated in patients with RA. Conclusions: Platelet-derived microparticles could be a potential biomarker for platelet reactivity in RA, which is a predictor of thrombosis and increased cardiovascular risk. Global hemostatic methods can be useful in hypercoagulation diagnosing and monitoring in patients with RA. Futhermore, in patients with rheumatoid arthritis there is a need for supplements containing antioxidants.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Крагујевцу, Факултет медицинских наукаsr
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Крагујевцуsr
dc.subjectreumatoidni artritissr
dc.subjectrheumatoid arthritisen
dc.subjectmikropartikulesr
dc.subjectglobalne metode hemostazesr
dc.subjectelektronska mikroskopijasr
dc.subjectoksidacioni stressr
dc.subjectmicroparticlesen
dc.subjectglobal hemostatic methodsen
dc.subjectelectron microscopyen
dc.subjectoxidative stressen
dc.titleCirkulišuće mikropartikule i biomarkeri oksidacionog stresa kod pacijenata obolelih od reumatoidnog artritisasr
dc.title.alternativeCirculating microparticles and biomarkers of oxidative stress in patients with rheumatoid arthritisen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/50253/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/50254/Aleksandra_Vranic_Medicina.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/50253/Disertacija.pdf
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/50254/Aleksandra_Vranic_Medicina.pdf
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_11816


Files in this item

Thumbnail
Thumbnail

This item appears in the following Collection(s)

Show simple item record