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Novel approaches to study the haematological system during inflammation
Thesis (PhD)--Stellenbosch University, 2021.
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| Format: | Thesis |
| Language: | en_ZA |
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Stellenbosch : Stellenbosch University
2021
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| _version_ | 1867614078402297856 |
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| access_status_str | Open Access |
| author | Page, Martin Justin |
| author2 | Pretorius, Etheresia |
| author_browse | Page, Martin Justin Pretorius, Etheresia |
| author_facet | Pretorius, Etheresia Page, Martin Justin |
| author_sort | Page, Martin Justin |
| collection | Thesis |
| dc_rights_str_mv | Stellenbosch University |
| description | Thesis (PhD)--Stellenbosch University, 2021. |
| format | Thesis |
| id | oai:scholar.sun.ac.za:10019.1/110266 |
| institution | Stellenbosch University (South Africa) |
| language | en_ZA |
| last_indexed | 2026-06-10T12:46:18.613Z |
| license_str | Other — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | Stellenbosch : Stellenbosch University |
| publisherStr | Stellenbosch : Stellenbosch University |
| record_format | dspace |
| source_str | SUNScholar — Stellenbosch University Repository |
| spelling | oai:scholar.sun.ac.za:10019.1/110266 Novel approaches to study the haematological system during inflammation Page, Martin Justin Pretorius, Etheresia Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Inflammation -- Mediators Blood -- Clotting Blood -- Coagulation Haematology Blood platelets -- Receptors Erythrocytes -- Transfusion Chronic diseases -- Pathogenesis Microbiome UCTD Thesis (PhD)--Stellenbosch University, 2021. ENGLISH ABSTRACT: Chronic diseases (think diabetes, Alzheimer’s disease, Parkinson’s disease, cancer, and the like) are a scourge and an insidious pandemic. These conditions are biologically complex and heterogeneous, and this makes tackling them tremendously challenging. However, integrative and systems-based analyses reveal common factors and processes operating across the seemingly disparate classes of chronic diseases. A predominant role of inflammation along with stimulation from pathogen-derived inflammatory components offer a framework for investigating general contributions to the development and progression of chronic diseases. However, these factors and processes do not contribute only to the hallmark pathology that defines a specific disease, but also provoke attendant pathology – a serious concomitant being coagulopathy. Pathological coagulation is the focus of this dissertation. This dissertation explores the involvement and consequence for pathology of pathogen-derived components on inflammatory signalling and on the haemostatic and inflammatory activity of blood platelets. This dissertation investigates the effects of host and external inflammatory molecules on the coagulation system. Using various methodologies, which include measurements of clot mechanics (by thromboelastography and rheometry) and structure (by confocal microscopy and scanning electron microscopy), the procoagulant profiles caused by these inflammatory molecules are characterised. Furthermore, the underlying processes that might give rise to the observation of anomalous fibrin clot networks and their ability to discriminate between healthy and patient clots were also investigated. Ultimately, this dissertation emphasises the profound effects that disease-specific inflammatory mediators and pathogen-derived products that define the inflammatory milieu of chronic disease can exert on the components of blood and its ability to clot. A consequence of this is that the state of the blood can reflect the broader state of pathophysiology and blood is therefore positioned as an appealing and propitious source of biomarkers for the diagnosis and tracking of chronic diseases and their pathologies, a number of which are set out in this dissertation. AFRIKAANSE OPSOMMING: Chroniese siektes (dink aan diabetes, Alzheimer se siekte, Parkinson se siekte, kanker, ensovoorts) is 'n kwelling en 'n groeiendepandemie. Omdat die siektes so geweldig ingewikkeld is, met ‘n verskeidenheid faktore wat 'n rol mag speel, is dit uiters uitdagend om hierdie toestande aan te pak. Wanneer hierdie chroniese siektes egter met holistiese en stelsel-gebaseerde metodes ondersoek word, word daar soortgelyke faktore en fisiologiese prosesse geidentifiseer regoor die oënskynlik verskillende klas toestande. 'n Oorheersende rol van inflammasie, tesame met die stimulasie van inflammatoriese komponente afkomstig vanaf patogene, bied 'n raamwerk om algemene bydraes tot die ontwikkeling en progressie van chroniese siektes te ondersoek. Hierdie faktore en prosesse dra egter nie net by tot die kenmerkende patologie wat 'n spesifieke siekte definieër nie, maar dit vererger ook gepaardgaande abnormaliteite. Abnormale bloedstolling verteenwoordig hier 'n ernstige komorbiditeit. Patologiese bloedstolling is die fokus van hierdie proefskrif. Die patologiese effek van patogeen-afgeleide komponente op inflammatoriese seine, asook die hemostatiese en inflammatoriese werking van bloedplaatjies, word hier ondersoek. Hierdie proefskrif analiseer die effekte wat interne en eksterne inflammatoriese molekules op die bloedstollingsisteem het. Deur gebruik te maak van ‘n verskeidenheid metodes, wat die meting van klontmeganika en -struktuur insluit, word die profiele van hiperkoagulasie, wat veroorsaak word deur hierdie inflammatoriese molekules, beskryf. Die onderliggende prosesse wat mag aanleiding gee tot die waarneming van abnormale fibrienklontnetwerke, en die vermoë daarvan om te kan onderskei tussen klonte van gesonde individue en dié van siek pasiënte, word ook ondersoek. Die proefskrif beklemtoon uiteindelik die diepgaande uitwerkings wat siekte-spesifieke inflammatoriese molekules en patogeen-afgeleide produkte (wat die inflammatoriese omgewing van chroniese siektes definieër) op die bloedkomponente en bloedstollingsvermoë kan hê. 'n Gevolg hiervan is dat die toestand van die bloed die wyer toestand van patofisiologie kan weerspieël. Bloed is dus 'n aanloklike en belowende bron van biomerkers vir die diagnose en monitering van chroniese siektes en hul verwante patologieë, waarvan daar 'n aantal in hierdie proefskrif uiteengesit word. Doctoral 2021-02-17T13:18:38Z 2021-04-22T10:11:42Z 2022-02-01T03:00:10Z 2021-04 Thesis http://hdl.handle.net/10019.1/110266 en_ZA Stellenbosch University 333 pages : illustrations (some color) application/pdf Stellenbosch : Stellenbosch University |
| spellingShingle | Inflammation -- Mediators Blood -- Clotting Blood -- Coagulation Haematology Blood platelets -- Receptors Erythrocytes -- Transfusion Chronic diseases -- Pathogenesis Microbiome UCTD Page, Martin Justin Novel approaches to study the haematological system during inflammation |
| title | Novel approaches to study the haematological system during inflammation |
| title_full | Novel approaches to study the haematological system during inflammation |
| title_fullStr | Novel approaches to study the haematological system during inflammation |
| title_full_unstemmed | Novel approaches to study the haematological system during inflammation |
| title_short | Novel approaches to study the haematological system during inflammation |
| title_sort | novel approaches to study the haematological system during inflammation |
| topic | Inflammation -- Mediators Blood -- Clotting Blood -- Coagulation Haematology Blood platelets -- Receptors Erythrocytes -- Transfusion Chronic diseases -- Pathogenesis Microbiome UCTD |
| url | http://hdl.handle.net/10019.1/110266 |
| work_keys_str_mv | AT pagemartinjustin novelapproachestostudythehaematologicalsystemduringinflammation |