This thesis is composed of two studies. The principal aim of the first study, the Sites of Atheroma Study, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and plasminogen activator inhibitor - type I) were related to the angiographic site and severity of atherosclerosis in the arteries of the lower limb. The principal aim of the second study, the Prognostic Study of Intermittent Claudication, was to determine whether plasma fibrinogen, fibrin D-dimer and other haemostatic factors (von Willebrand Factor and tissue plasminogen activator), were related to the future incidence of atherothrombotic events, and deterioration of peripheral arterial disease in subjects with intermittent claudication. The study samples in both studies consisted of men and women with ischaemic symptoms in the lower limb referred to the Peripheral Vascular Clinic, Royal Infirmary of Edinburgh. In the Sites of Atheroma Study, 192 patients referred for angiography were categorised by site and severity of peripheral atherosclerosis using the Bollinger angiographic scoring system. A clinical examination was conducted on each patient including the administration of a questionnaire and taking of a blood sample for the measurement of haemostatic factors. In the Prognostic Study, 607 patients with intermittent claudication who had had a comprehensive examination at baseline, including measurement of haemostatic factors, were followed up over six years to determine the incidence of fatal and non-fatal ischaemic heart disease and stroke and deterioration of peripheral arterial disease. Follow-up data were obtained from hospital records, general practitioners, self-administered questionnaires, the Information and Statistics division of the Common Services Agency and the Scottish National Health Service Central Registry. Results from the Sites of Atheroma Study indicated that 34 (17.7%) patients had predominantly aorto-iliac disease, 85 (44.3%) had femoro-popliteal disease and 73 (38.0%) had dual-site disease. There were no significant differences in the mean levels of the haemostatic factors between patients with disease affecting different sites. An independent relationship was found between nephelometric fibrinogen and between fibrin D-dimer and disease severity only in the femoro-popliteal arteries. On multiple regression, fibrinogen remained independently associated with disease severity in the femoro-popliteal arteries, when life-time smoking or current smoking were taken into account. There was no influence of current smoking on the association between fibrin D-dimer and disease severity but, on inclusion of life-time smoking, the association became non-significant. In the Prognostic Study of Intermittent Claudication, a total of 210 (34.6%) patients died during the six year follow-up period. Of these 90 (42.9%) died from ischaemic heart disease, 29 (13.8%) from stroke and 27 (12.9%) from other vascular causes, including cardiac arrhythmias and ruptured aneurysm. Ninety three (15.3%) patients had a non-fatal myocardial infarction and 79 (13.0%) had a fatal or non-fatal stroke. Forty five (7.4%) patients underwent investigations for peripheral arterial disease and 64 (10.5%) patients progressed to severe chronic leg ischaemia. A total of 203 (33.4%) patients did not have a vascular event or show any deterioration of limb ischaemia. Baseline median levels of plasma fibrinogen, fibrin D-dimer and von Willebrand Factor were significantly higher in patients who died from ischaemic heart disease compared to those who had no vascular events. Tissue plasminogen activator antigen levels were significantly elevated in patients who suffered a stroke. All the relationships between the haemostatic factors and vascular events became weaker and statistically non-significant in analysis adjusting for cardiovascular risk factors and baseline ischaemic heart disease. von Willebrand Factor levels were significantly raised in claudicants who developed severe chronic leg ischaemia (rest pain, ulceration and gangrene). In multivariate analyses adjusting for life-time smoking, fibrinogen became significantly associated with the risk of vascular intervention, and von Willebrand Factor was associated with the risk of severe chronic leg ischaemia. In conclusion, these results indicate that there may be a stronger relationship between chronic smoking and increased fibrin turnover than coagulation in symptomatic peripheral arterial disease. Increased coagulation and fibrinolytic activity may also contribute to thrombosis or progression of atherosclerosis in the coronary and cerebral arteries in claudicants. The effect that fibrinogen, fibrin D-dimer and other haemostatic factors may have on the progression of peripheral arterial disease was mostly independent of cigarette smoking.

No description available.

This study identified striking increase in plasma of plasminogen activator inhibitor 1(PAI-I), a major inhibitor of fibrinolysis levels in septic patients who are non-neutropenic. Neutropenic patients show less striking changes. Where shock occurs both groups of patients show very high levels of PAI-1. These observations suggest a role for leucocytes in PAI production. In the second section neutrophils are identified as containing PAI-1 in normal subjects, the levels rising significantly in sepsis. Monocytes contain no PAI-1 but do contain Plasminogen activator inhibitor 2(PAI-2) levels of which inhibitor also rise in sepsis. Normal neutrophils contained no PAI-2 but neutrophils from septic patients contained significant quantities of this inhibitor. In the third section mononuclear cells from septic patients are identified as enhancing PAI-1 production in cultured endothelial cell (EC). Septic neutrophils have a more complex effect on EC. Mononuclear cells and neutrophils therefore, both contribute to the fibrinolytic inhibition of septic disorders but by different mechanisms. Each cell type contains one of the major inhibitor of plasminogen activator and levels of these rise in sepsis. Both cell types from septic patients promote greater release of PAI-1 from endothelial cells than do cells from normal individuals. Inhibition of fibrinolysis by leucocytes may contribute to fibrin persistence in sepsis. This may be useful in localizing infection. If generalized, it may contribute to vascular occlusive complications of sepsis such as shock lung, acute renal failure or digital gangrene. Absence of leucocytes may account for the apparent reduction of vascular occlusive complications in leucopenic septic patients.

O presente trabalho teve como objetivo caracterizar o desenvolvimento da semente de Araucaria angustifolia através da proteômica comparativa, buscando compreender as alterações fisiológicas e metabólicas que ocorrem durante esse processo. Inicialmente, foram avaliados três diferentes metodologias de extração de proteínas. A metodologia composta por solução de extração contendo 7 M de uréia, 2 M de tiouréia, 1% de ditiotreitol, 2% de Triton-100, 1 mM de fluoreto de fenilmetilsulfonil e 5 µM de pepstatina, seguido de precipitação em 20% de ácido tricloroacético apresentou géis de maior resolução e reprodutibilidade, tendo sido escolhida como metodologia de extração protéica para o estudo das alterações no proteoma da semente de A. angustifolia. Uma dificuldade associada ao estudo do proteoma de espécies não sequenciadas é a baixa representatividade nos bancos de dados protéicos, resultando em identificações baseadas em homologia. Estratégias proteômicas baseadas em fracionamento em gel resultam em grandes contaminações por fragmentos de queratina. Sendo assim, foi desenvolvido um programa de remoção de espectros de baixa qualidade para utilização em proteômica baseada em homologia. As análises mostraram que o programa reduz o tempo de busca, melhora a qualidade dos alinhamentos e não resulta em perda de identificações positivas. Finalmente, utilizando as metodologias descritas, foram estudadas as alterações no proteoma durante o desenvolvimento da semente de A. angustifolia. Noventa e seis proteínas foram identificadas e agrupadas de acordo com sua função biológica e padrão de detecção. Os resultados obtidos permitiram o estabelecimento de marcadores protéicos no início e final do desenvolvimento embrionário. A análise das proteínas abundantes no início da embriogênese indica um maior controle no metabolismo oxidativo em relação aos estádios finais. Contrariamente, o final da embriogênese é caracterizado por um alto metabolismo de assimilação de carbono e acúmulo de proteínas de reserva. As implicações dos resultados obtidos no controle e melhoramento de sistemas de embriogênese somática na espécie também foram discutidas / The aim of the present work was to characterize the seed development of Araucaria angustifolia through proteomics in order to understand the physiological and biochemical changes during this process. For that, initially, three different protein extraction methods were evaluated. The extraction based on protein solubilization in 7 M urea, 2 M thiourea, 1% dithiothreitol, 2% Triton-100, 1 mM phenylmethylsulphonyl fluoride, 5 µM pepstatin, followed by 20% trichloroacetic acid precipitation showed the highest gel resolution and reprodutivity and, thus, was chosen to be used in the analysis of the proteome of A. angustifolia seeds. One aspect that hampers the proteome study of unsequenced species is the low protein representativity in databases. So, protein identification is usually carried out through homology. Strategies based on 2-DE result in high keratin contamination. In the present work a spectra filtering software was developed and evaluated for use in homology driven proteomics. The software reduced the time of search, improved alignment quality and did not result in lost of positive identifications. Finally, using the described strategies, the changes in the proteome of A. angustifolia seeds were studied. Ninety six proteins were identified and classified according to their biological functions and expression profiles during seed development. The identified proteins may be used as protein markers of early and late embryogenesis. Proteins involved in the control of oxidative metabolism were highly expressed during the early stages of seed development; while, carbon metabolism and storage proteins were highly expressed in late stages. Considerations on the improvement and control of somatic embryogenesis through medium manipulation and protein markers screening using data generated are also discussed.

O presente trabalho teve como objetivo caracterizar o desenvolvimento da semente de Araucaria angustifolia através da proteômica comparativa, buscando compreender as alterações fisiológicas e metabólicas que ocorrem durante esse processo. Inicialmente, foram avaliados três diferentes metodologias de extração de proteínas. A metodologia composta por solução de extração contendo 7 M de uréia, 2 M de tiouréia, 1% de ditiotreitol, 2% de Triton-100, 1 mM de fluoreto de fenilmetilsulfonil e 5 µM de pepstatina, seguido de precipitação em 20% de ácido tricloroacético apresentou géis de maior resolução e reprodutibilidade, tendo sido escolhida como metodologia de extração protéica para o estudo das alterações no proteoma da semente de A. angustifolia. Uma dificuldade associada ao estudo do proteoma de espécies não sequenciadas é a baixa representatividade nos bancos de dados protéicos, resultando em identificações baseadas em homologia. Estratégias proteômicas baseadas em fracionamento em gel resultam em grandes contaminações por fragmentos de queratina. Sendo assim, foi desenvolvido um programa de remoção de espectros de baixa qualidade para utilização em proteômica baseada em homologia. As análises mostraram que o programa reduz o tempo de busca, melhora a qualidade dos alinhamentos e não resulta em perda de identificações positivas. Finalmente, utilizando as metodologias descritas, foram estudadas as alterações no proteoma durante o desenvolvimento da semente de A. angustifolia. Noventa e seis proteínas foram identificadas e agrupadas de acordo com sua função biológica e padrão de detecção. Os resultados obtidos permitiram o estabelecimento de marcadores protéicos no início e final do desenvolvimento embrionário. A análise das proteínas abundantes no início da embriogênese indica um maior controle no metabolismo oxidativo em relação aos estádios finais. Contrariamente, o final da embriogênese é caracterizado por um alto metabolismo de assimilação de carbono e acúmulo de proteínas de reserva. As implicações dos resultados obtidos no controle e melhoramento de sistemas de embriogênese somática na espécie também foram discutidas / The aim of the present work was to characterize the seed development of Araucaria angustifolia through proteomics in order to understand the physiological and biochemical changes during this process. For that, initially, three different protein extraction methods were evaluated. The extraction based on protein solubilization in 7 M urea, 2 M thiourea, 1% dithiothreitol, 2% Triton-100, 1 mM phenylmethylsulphonyl fluoride, 5 µM pepstatin, followed by 20% trichloroacetic acid precipitation showed the highest gel resolution and reprodutivity and, thus, was chosen to be used in the analysis of the proteome of A. angustifolia seeds. One aspect that hampers the proteome study of unsequenced species is the low protein representativity in databases. So, protein identification is usually carried out through homology. Strategies based on 2-DE result in high keratin contamination. In the present work a spectra filtering software was developed and evaluated for use in homology driven proteomics. The software reduced the time of search, improved alignment quality and did not result in lost of positive identifications. Finally, using the described strategies, the changes in the proteome of A. angustifolia seeds were studied. Ninety six proteins were identified and classified according to their biological functions and expression profiles during seed development. The identified proteins may be used as protein markers of early and late embryogenesis. Proteins involved in the control of oxidative metabolism were highly expressed during the early stages of seed development; while, carbon metabolism and storage proteins were highly expressed in late stages. Considerations on the improvement and control of somatic embryogenesis through medium manipulation and protein markers screening using data generated are also discussed.

Aspartame is a dipeptide sweetener that can be found in most of the sugar-free products available on the market today. The FDA approved the use of aspartame, but ever since the safety of the consumption of aspartame has been questioned. Thus the aim of this thesis was to determine the effects of aspartame ingestion on the blood coagulation system and the blood filtering organs (liver and kidneys) of the rabbit. The protocol for obtaining blood from a rabbit as well as successful administration of aspartame was perfected. The rabbit was proven as best experimental model, when compared to a mouse, for studying the effects of aspartame on coagulation and haemostasis. The effects of aspartame were determined by: 1.) measuring the factors from the different coagulation pathways, namely the common pathway (factors II, V, X and fibrinogen); factors in the intrinsic pathway (factors VIII, IX), as well as factor VII, found in the extrinsic pathway. The prothrombin time (PT; measures how long blood takes to form a clot) and activated partial thromboplastin time (aPTT; measures recalcification time of plasma) was also measured; 2.) The ultrastructure of the fibrin networks, platelet morphology and endothelial lining were studied; 3.) The histological morphology of the leukocytes, liver and kidney were examined. Results obtained indicated that F VII, X and VIII were decreased with a prolonged prothrombin time. The concentration of circulating fibrinogen increased significantly, which corroborated with results obtained for the ultrastructure of the fibrin networks. The degree of fibrin fibre formation increased the higher the concentration of aspartame and the degree of platelet aggregation occurring, decreased with the increase of aspartame concentration. It is hypothesized that the amount of circulating serotonin decreased. The endothelial lining of the rabbits were damaged with the nuclei appearing apoptotic. The endothelial lining and their tight junctions play an integral part in the functioning of the BBB, in synchronization with cAMP (complexity of tight junctions, decreased due to decreased amount of serotonin), thus it appeared as though the BBB was compromised. The morphology of the leukocytes were altered, specifically that of the eosinophils and heterophils. The granules inside the eosinophils of the aspartame treated rabbit appeared to have increased and were more clearly visible, while the granules in the heterophils appeared to have decreased. The total number of leukocytes also decreased. Thenormal histological morphology of both the liver and kidney were affected by aspartame. Damage to the hepatocytes and their subsequent arrangement were noted. The visceral layer of the capsule of Bowman appeared thickened and the cuboidal epithelium lining the proximal convoluted tubule was also damaged The final judgment and conclusion of the results obtained in this thesis regarding the consumption of abuse doses of aspartame, was that aspartame could lead to bleeding disorders (especially in genetically predisposed individuals), suppressed immunity and a compromised BBB. Trouble can occur with formation of the glomerular filtrate and absorption of fluid from the proximal convoluted tubule, which could result in high blood pressure and an increased probability of dehydration respectively. / Thesis (PhD (Anatomy))--University of Pretoria, 2008. / Anatomy / PhD / unrestricted

Introdução: Estudos iniciais sugeriram que o risco para tromboembolismo venoso (TV) era atribuído ao componente estrogênico dos contraceptivos de forma dose-dependente. Estudos epidemiológicos têm sugerido que o risco para TV é maior com contraceptivos combinados que contêm progestagênios de terceira geração (gestodeno, desogestrel) comparados com aqueles com progestagênios de segunda geração (levonorgestrel). Esses achados inesperados têm sido alvo de muitos debates sem uma explicação definitiva. Assim, a questão das diferenças nas propriedades de cada progestagênio sobre a hemostasia tem sido levantada. Apesar dos progestagênios não serem associados a alterações marcantes nos parâmetros hemostáticos, existem poucos estudos sobre os efeitos dessas drogas, especialmente os progestagênios de terceira geração, no sistema hemostático. Objetivo: Avaliar o efeito do implante subdérmico de etonogestrel sobre a agregação plaquetária de mulheres hígidas, em seis meses de tratamento. Casuística e Métodos: Vinte e quatro mulheres saudáveis e voluntárias foram selecionadas neste estudo longitudinal e prospectivo, para usar um implante contraceptivo subdérmico de etonogestrel (metabólito biologicamente ativo do desogestrel). A agregação plaquetária foi avaliada em todas as mulheres, exceto uma, no período pré-inserção e após um, três e seis meses da inserção do implante. A agregação plaquetária foi induzida com adrenalina 50 µM, colágeno 10 µg/ml, colágeno 5 µg/ml, ADP 35 µM e ADP 17,5 µM. A análise estatística foi feita com o teste de Wilcoxon para comparar a diferença entre cada período de tratamento com os valores pré-tratamento. Resultados: Houve uma redução transitória, estatisticamente significativa, na mediana do percentual máximo de agregação plaquetária de 27%, 14% e 11%, respectivamente, com colágeno 5 µg/ml, adrenalina 50 µM e colágeno 10 µg/ml, observada um mês após a inserção do implante comparado ao valor pré-inserção (p< 0,05). A agregação plaquetária com esses agonistas retornou ao seu valor basal, após seis meses da inserção. Com outros agonistas, como o ADP 35 µM e ADP 17,5 µM, não se observou o mesmo fenômeno. Conclusão: Os resultados deste estudo mostram, pela primeira vez, que o uso do implante de etonogestrel está associado à redução transitória, mas significativa, da agregação plaquetária, observada em um mês de uso do contraceptivo, a qual retorna a seus valores normais em seis meses da inserção do implante. / Introduction: Several studies have suggested that the risk of venous thromboembolism (VTE) is attributable to the estrogen component of a contraceptive in a dose-dependent manner. Recent epidemiological studies have suggested that the risk of VTE was higher with contraceptives containing third-generation progestagens (desogestrel, gestodene) when compared with second-generation progestagens (levonorgestrel). These unexpected findings have been the subject of many debates with no definitive explanation and the question of differences in hemostatic properties of each progestagen has been raised. Although progestagens are not associated with marked changes in hemostatic variables, there are few studies on the effects of these drugs, especially third-generation progestagens, on the hemostatic system. Objective: To evaluate the acute effect of a long-term contraceptive implant of etonogestrel on platelet aggregation in healthy women. Material and Methods: Twenty-four healthy volunteer women were enrolled in this prospective longitudinal study, to use a subdermal contraceptive implant of etonogestrel (the biologically active metabolite of desogestrel). Platelet aggregation was measured in all users, except one, at baseline and after 1, 3 and 6 months of treatment. Platelet aggregation was induced with 50 µM adrenalin, 10 µg/ml collagen, 5µg/ml collagen, 35 µM ADP and 17,5 µM ADP. Statistical analysis included the Wilcoxon test to compare differences between each period of treatment from baseline. Results: Statistically significant 27%, 14% and 11% reductions of platelet aggregation with 5 µg/ml collagen, 50 µM adrenalin e 10 µg/ml collagen, respectively, were observed at 1 month of treatment (p < 0,05). Platelet aggregation returned to baseline values at 6 months of treatment with these reagents. Platelet aggregation did not show any statistic difference with ADP. Conclusions: The result of this study shows for the first time that an etonogestrel implant is associated with a transitory, but significant, reduction in platelet aggregation after the first month of treatment, which returns to normal values by 6 months of therapy.

[Truncated abstract] Cardiac surgery involving cardiopulmonary bypass is a complex procedure that results in significant changes to blood coagulation, fibrinolytic biochemistry, platelet number and function, and the vasculature. These are due to pharmacological agents which are administered, haemodilution and contact of the blood with artificial surfaces. Consequently there are significant risks of thrombosis and haemorrhage associated with this procedure. The research presented in this thesis utilises in vitro, in vivo, and a novel ex vivo model to investigate the nature of the haemostatic defect induced by cardiopulmonary bypass. The components studied include the drugs heparin, protamine sulphate, and aprotinin, different types of bypass circuitry (including heparin bonded circuits) and procedures such as acute normovolaemic haemodilution. Patient variables, such as Factor V Leiden, are also studied. Each of these components is assessed for the effects on a number of laboratory measures of haemostasis including activated partial thromboplastin time, prothrombin time, activated protein C ratio, antithrombin concentration, heparin concentration, thrombin-antithrombin complex formation, prothrombin fragment 1+2 formation, markers of platelet surface activation and secretion, activated clotting time, haemoglobin concentration and coagulation factor assays.

Motivation: Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in South Africa and worldwide. Dyslipidaemia and an increased coagulation state contribute to the development of CVD. The quality of fibrin network structure (FNS) may also contribute to the risk for CVD and thrombosis. Changes in fibrinogen concentration directly affect FNS. Management of these risk factors is important and dietary intervention forms an essential part of this management program. An increased intake of vitamin C can lead to a decreased susceptibility to infection and subsequently to decreased levels of haemostatic factors (that give rise to an anti-thrombotic state) and thus reduction in CVD and mortality. Furthermore, vitamin C may prove to be beneficial by increasing the pro-fibrinolytx activities of FNS (formation of thick fibrin fibers and more lysable clots) that could result in a reduction in atherosclerosis and subsequent CVD. Obiective: To investigate the effects of FoodState Vitamin C complex supplementation on haemostatic factors, FNS, serum lipids and lipoprotein (a) (Lp(a)) in hyperlipideamic adults. Methods: Thirty free-living hiperlipidaemic volunteers from the Lipid Clinic, Potchefstroom University for Christian Higher Education (CHE), participated in this randomised placebo controlled double blind crossover study. The subjects were randomly divided into two groups (A or B). After a run-in period of 4 weeks during which the subjects excluded all vitamin supplements, Group A received 2 tablets/day of FoodState Vitamin C complex (500mg vitamin C, 600mg magnesium food complex, 900mg vitamin B complex and 160mg bioflavonoids) and Group B received 2 tablets/day of placebo, for at least 8 weeks. A washout period of 8 weeks followed after which the treatments were crossed-over for a further 8 weeks. Fasting blood samples were drawn 8 times (two samples, one week apart at the beginning and end of each treatment). Results: FoodState Vitamin C complex supplementation did not significantly influence the levels of plasma fibrinogen, plasminogen activator inhibitor 1 activity (PAI-I act), tissue plasminogen activator antigen (tPA ag) or d-dimer. Serum lipids and Lp(a) were also not affected. Median plasmin-antiplasmin complex (PAP) and thrombin-antithrombin complex (TAT) levels, which are markers of plasmin (initiate fibrinolysis) and thrombin (initiate coagulation) generation respectively, were both significantly decreased compared to placebo (PAP: 4.05[-23.39, -0.231% vs 1.81[-8.95, 8.091%; TAT: -5.81[-18,47, 0.391% vs 0.12[-8.03, 13.51%). FoodState Vitamin C complex beneficially affected FNS by significantly increasing compaction (49.95[47.55,53.70]% to 51.85[48.55,56.65]%). Conclusion: The decreases in TAT and PAP are possibly an indication that the FoodState Vitamin C complex decreased the initiation of haemostasis, which in turn led to a compensatory reduction in fibrinolysis. FoodState Vitamin C complex may, therefore be protective of cardiovascular disease by causing a new reduced steady state of hemostatic balance and more lysable clots (increased compaction). / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.

Motivation: Cardiovascular disease (CVD) is one of the leading causes of mortality and morbidity in South Africa and worldwide. Dyslipidaemia and an increased coagulation state contribute to the development of CVD. The quality of fibrin network structure (FNS) may also contribute to the risk for CVD and thrombosis. Changes in fibrinogen concentration directly affect FNS. Management of these risk factors is important and dietary intervention forms an essential part of this management program. An increased intake of vitamin C can lead to a decreased susceptibility to infection and subsequently to decreased levels of haemostatic factors (that give rise to an anti-thrombotic state) and thus reduction in CVD and mortality. Furthermore, vitamin C may prove to be beneficial by increasing the pro-fibrinolytx activities of FNS (formation of thick fibrin fibers and more lysable clots) that could result in a reduction in atherosclerosis and subsequent CVD. Obiective: To investigate the effects of FoodState Vitamin C complex supplementation on haemostatic factors, FNS, serum lipids and lipoprotein (a) (Lp(a)) in hyperlipideamic adults. Methods: Thirty free-living hiperlipidaemic volunteers from the Lipid Clinic, Potchefstroom University for Christian Higher Education (CHE), participated in this randomised placebo controlled double blind crossover study. The subjects were randomly divided into two groups (A or B). After a run-in period of 4 weeks during which the subjects excluded all vitamin supplements, Group A received 2 tablets/day of FoodState Vitamin C complex (500mg vitamin C, 600mg magnesium food complex, 900mg vitamin B complex and 160mg bioflavonoids) and Group B received 2 tablets/day of placebo, for at least 8 weeks. A washout period of 8 weeks followed after which the treatments were crossed-over for a further 8 weeks. Fasting blood samples were drawn 8 times (two samples, one week apart at the beginning and end of each treatment). Results: FoodState Vitamin C complex supplementation did not significantly influence the levels of plasma fibrinogen, plasminogen activator inhibitor 1 activity (PAI-I act), tissue plasminogen activator antigen (tPA ag) or d-dimer. Serum lipids and Lp(a) were also not affected. Median plasmin-antiplasmin complex (PAP) and thrombin-antithrombin complex (TAT) levels, which are markers of plasmin (initiate fibrinolysis) and thrombin (initiate coagulation) generation respectively, were both significantly decreased compared to placebo (PAP: 4.05[-23.39, -0.231% vs 1.81[-8.95, 8.091%; TAT: -5.81[-18,47, 0.391% vs 0.12[-8.03, 13.51%). FoodState Vitamin C complex beneficially affected FNS by significantly increasing compaction (49.95[47.55,53.70]% to 51.85[48.55,56.65]%). Conclusion: The decreases in TAT and PAP are possibly an indication that the FoodState Vitamin C complex decreased the initiation of haemostasis, which in turn led to a compensatory reduction in fibrinolysis. FoodState Vitamin C complex may, therefore be protective of cardiovascular disease by causing a new reduced steady state of hemostatic balance and more lysable clots (increased compaction). / Thesis (M.Sc. (Nutrition))--North-West University, Potchefstroom Campus, 2004.