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The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets

Thesis (MSc)--Stellenbosch University, 2019.

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Main Author: Nkosi, Nondumiso Belvia
Other Authors: Pretorius, Resia
Format: Thesis
Language:en_ZA
Published: Stellenbosch : Stellenbosch University 2019
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access_status_str Open Access
author Nkosi, Nondumiso Belvia
author2 Pretorius, Resia
author_browse Nkosi, Nondumiso Belvia
Pretorius, Resia
author_facet Pretorius, Resia
Nkosi, Nondumiso Belvia
author_sort Nkosi, Nondumiso Belvia
collection Thesis
dc_rights_str_mv Stellenbosch University
description Thesis (MSc)--Stellenbosch University, 2019.
format Thesis
id oai:scholar.sun.ac.za:10019.1/107322
institution Stellenbosch University (South Africa)
language en_ZA
last_indexed 2026-06-10T12:43:57.159Z
license_str Other — see source repository
provenance_str_mv Harvested via OAI-PMH from SUNScholar — Stellenbosch University Repository
publishDate 2019
publishDateRange 2019
publishDateSort 2019
publisher Stellenbosch : Stellenbosch University
publisherStr Stellenbosch : Stellenbosch University
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source_str SUNScholar — Stellenbosch University Repository
spelling oai:scholar.sun.ac.za:10019.1/107322 The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets Nkosi, Nondumiso Belvia Pretorius, Resia Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences. Blood -- Coagulation Hypercoagulation -- Fibrosis Erythrocytes -- Metabolism Confocal microscopy Microbial polysaccharides -- Biotechnology Endotoxins -- Analysis Amyloidosis -- Metabolism -- Disorders Inflammation -- Immunological aspects Fibrin Blood platelets -- Metabolism UCTD Thesis (MSc)--Stellenbosch University, 2019. ENGLISH ABSTRACT: Hypercoagulation and amyloidogenesis are commonly known as hallmarks for inflammation. Hypercoagulation and amyloidogenesis are linked to quite a few communicable and non-communicable ailments such as cancer, rheumatoid arthritis and several neuro-inflammatory conditions, like Parkinson’s and Alzheimer’s disease. Recently, it was discovered that adding low concentrations of bacterial components such as lipopolysaccharide (LPS) to platelet poor plasma (PPP) and whole blood (WB) brings about hypercoagulation and amyloidogenesis. The main protein that showed these structural changes, was soluble fibrinogen. Fibrinogen changes to insoluble fibrin, in the presence of thrombin during clot formation. Studies show that in the presence of specific plasma proteins and/or “mopping” agents, the presence hypercoagulation and amyloid might be removed or reduced. An example of such serum protein is the presence of LPS binding protein (LBP). In this thesis, the aim is to investigate the effects of bacterial component lipoteichoic acid (LTA) when directly added to healthy WB and fibrinogen and compare the clotting profiles and ultrastructure of these samples to that of Type two diabetes mellites (T2DM) PPP. Furthermore, this thesis aims to investigate the potential role of Apolipoprotein A-1 (ApoA1) as a mopping agent, by adding ApoA1 to healthy WB, fibrinogen and T2DM PPP. Here we suggest that ApoA1 may reduce hypercoagulation and amyloidogenesis in healthy WB and fibrinogen with added amyloid forming molecule, LTA and T2DM PPP. We hypothesis that by adding low concentrations of LTA (5ng/L) to healthy WB and fibrinogen, LTA will cause hyperactivation of platelets, eryptosis of red blood cells (RBC) and amyloidogenesis in fibrin(ogen) respectively. In addition to this, we hypothesis that by adding ApoA1 to WB and fibrinogen that has been spiked with LTA, ApoA1 will attenuate supposed hyperactivation, eryptosis and amyloidogenesis. Moreover, we hypothesise that by adding ApoA1 to T2DM PPP, it will decrease the coagulopathies and amyloid state typically associated with T2DM patients. Thromboelastography was used to assess clotting parameters of WB and Scanning electron microscopy (SEM) was used to view any ultrastructural changes on RBC and platelets before and after the addition of LTA and LTA with ApoA1 to healthy WB. Confocal microscopy was used to investigate whether amyloid protein formation occurred in fibrin(ogen) in the presence of LTA and if this amyloid was reduced when ApoA1 was added. For our T2DM control’s, SEM and Confocal were used to view the differences in the PPP clot formed before and after the addition of ApoA1. The results for WB from the healthy controls showed a trend towards hypercoagulation in the presence of LTA and a trend towards attenuation of hypercoagulation and amyloidogenesis in the presence of ApoA1. In the T2DM model, a significant change was observed between the naïve T2DM PPP and the ApoA1 treated T2DM PPP. These are significant findings because they provide an alternative novel approach to the formation of a hypercoagulable environment and amyloidogenesis and these findings can be advantageous in finding a potential treatment of chronic inflammatory conditions. Masters 2019-08-08T09:42:29Z 2019-12-11T06:59:07Z 2019-08-08T09:42:29Z 2019-12-11T06:59:07Z 2019-12 Thesis http://hdl.handle.net/10019.1/107322 en_ZA Stellenbosch University x, 111 pages : illustrations application/pdf Stellenbosch : Stellenbosch University
spellingShingle Blood -- Coagulation
Hypercoagulation -- Fibrosis
Erythrocytes -- Metabolism
Confocal microscopy
Microbial polysaccharides -- Biotechnology
Endotoxins -- Analysis
Amyloidosis -- Metabolism -- Disorders
Inflammation -- Immunological aspects
Fibrin
Blood platelets -- Metabolism
UCTD
Nkosi, Nondumiso Belvia
The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title_full The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title_fullStr The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title_full_unstemmed The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title_short The role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
title_sort role of lipoteichoic acid on amyloidogenesis and its effect on erythrocytes and platelets
topic Blood -- Coagulation
Hypercoagulation -- Fibrosis
Erythrocytes -- Metabolism
Confocal microscopy
Microbial polysaccharides -- Biotechnology
Endotoxins -- Analysis
Amyloidosis -- Metabolism -- Disorders
Inflammation -- Immunological aspects
Fibrin
Blood platelets -- Metabolism
UCTD
url http://hdl.handle.net/10019.1/107322
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