Janette Bester

University of Pretoria | UP · Department of Physiology

Factor XIII, a transglutaminase that plays a crucial role in clot formation, consists of subunits A and B. Single nucleotide polymorphisms in Factor XIII-A have been linked to thrombotic risk. In Type 2 Diabetes mellitus (T2DM), a hypercoagulable state is thought to contribute to the high mortality rate associated with thrombotic diseases. Due to t...

Higher thrombotic burden in the acute phase of COVID-19 relies on a complex interplay between pro-inflammatory cytokine/chemokine release, increased endothelial dysfunction/damage, and potential sepsis-induced coagulopathy development in severe cases, all promoting coagulation activation. Plasma levels of cytokines and chemokines are known to be in...

Background: Increased risk of thromboembolic events is associated with prostate cancer, specifically linked to activation of tissue factor. Vitamin D has potential anticoagulant effects by the downregulation of tissue factor expression. Objectives: To evaluate the effects on clot formation, the morphological and viscoelastic profiles of prostate...

IntroductionMetabolome variations have long been associated with normal hormonal fluctuations, and similar effects, related to the use of early generation synthetic hormones as a means of contraception, have also been identified.Objective We investigated the serum amino acid and acylcarnitine profiles induced by the use of combined oral contracepti...

Breast cancer (BC) is one of the most prevalent forms of cancer in women worldwide. Clinical research indicates that BC patients are at an increased risk for thrombotic events, drastically decreasing their quality-of-life and treatment outcomes. There is ample evidence of this in the literature, but it is mainly focused on metastatic BC. Therefore,...

Combined oral contraceptives (COCs) are commonly prescribed and increase the risk of venous thromboembolism (VTE). We have previously found that two COCs, both containing drospirenone (DRSP) and ethinyl estradiol (EE), cause spontaneous fibrin formation in whole blood. The aim of this study was, therefore, to use platelet-poor plasma (PPP) from the...

The association between hypercoagulability and use of drospirenone (DRSP) and ethinylestradiol (EE) containing combined oral contraceptives (COCs) is an important clinical concern. We have previously reported that the two formulations of DRSP combined with EE (namely, DRSP/20EE and DRSP/30EE) bring about a prothrombotic state in hemostatic traits o...

Introduction: Migraine is a debilitating primary headache disorder with a poorly understood aetiology. An extensive body of literature supports the theory of migraine as a systemic vascular inflammatory disorder characterised by endothelial dysfunction. It is also well-known that chronic inflammation results in an excessive burden of oxidative stre...

Venous thrombosis is associated with combined oral contraceptive (COC) use. We investigated the impact of two ethinyl estradiol (EE) and drospirenone (DRSP) containing COCs (3 mg DRSP/20 µ g EE and 3 µ g DRSP/30 µ g EE) on the viscoelasticity of whole blood clots along with the biophysical and biochemical characteristics of erythrocytes. Thromboela...

There are several possible mechanisms by which combined oral contraceptives (COC) use increase venous thromboembolism (VTE) risk. Melodene® is a monophasic COC containing the third‐generation progestin Gestodene (GSD), which is associated with increased risk of VTE. Therefore, the aim of this study was to investigate the possible alterations in vis...

Many studies indicate that there is a (mainly dormant) microbial component in the progressive development of Alzheimer-type dementias (ADs); and that in the case of Gram-negative organisms, a chief culprit might be the shedding of the highly inflammagenic lipopolysaccharide (LPS) from their cell walls. We have recently shown that a highly sensitive...

Background: Haemochromatosis is an iron-storage disease with different genetic mutations, characterized by an increased intestinal absorption of iron, resulting in a deposition of excessive amounts of iron in parenchymal cells. When the iron is released in the blood, it is left in an unliganded form, where it can participate in Haber-Weiss and Fen...

Circulating cytokines, and particularly the interleukin (IL)-family are known to play an important role in inflammation. These molecules circulate in the blood and therefore have a direct effect on the plasma molecules and the formed elements like the erythrocytes and platelets. Aberrant coagulation (hypercoagulation or blood clots that form too ea...

Tissue necrosis factor-α (TNF-α) and complement component 3 (C3) are two well-known pro-inflammatory molecules. When TNF-α is upregulated, it contributes to changes in coagulation and causes C3 induction. They both interact with receptors on platelets and erythrocytes (RBCs). Here, we look at the individual effects of C3 and TNF-α, by adding low le...

Background/aims: Heavy metal pollution is increasing in the environment, contaminating water, food and air supplies. This can be linked to many anthropogenic activities. Heavy metals are absorbed through the skin, inhalation and/or orally. Irrespective of the manner of heavy metal entry in the body, the blood circulatory system is potentially the...

Background: Clotting parameters are informative of overall haematological healthiness of an individual. Particularly, clotting parameters can be used as a measure of the degree of pathology of the coagulation system. Thromboelastography (TEG) is a well-known technique that is an important point-of-care method, as well as research method. Scanning...

The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...

Introduction: Type 2 diabetes mellitus is a pandemic associated with disturbance in haemostasis that could contribute to the development of diabetic vascular disease and accelerated atherosclerosis. In this population, hypercoagulation is prevalent, as well as pathological changes to erythrocytes. This is mainly due to upregulated circulating infl...

The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...

A significant burden of illness is caused globally by snakebites particularly by the puff adder, Bitis arietans. Presently there is no reliable and rapid method to confirm envenomation on blood chemistry; although coagulation parameters like prothrombin time, partial thromboplastin time, international normalized ratio and also serum electrolytes ar...

Erythrocytes (RBCs) are extremely sensitive cells, and although they do not have nuclei and mitochondria, are important health indicators. This is particularly true because, during inflammation, whether it is systemic or chronic, the haematological system is constantly exposed to circulating inflammatory mediators. RBCs have a highly specialized an...

Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot fo...

It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide (LPS) in this hypercoagulability, but it seems never to have been te...

Complex interactions exist between cytokines, and the interleukin family plays a fundamental role in inflammation. Particularly circulating IL-1β, IL-6 and IL-8 are unregulated in systemic and chronic inflammatory conditions. Hypercoagulability is an important hallmark of inflammation, and these cytokines are critically involved in abnormal clot fo...

Objectives Type 2 diabetes patients (T2D) have a considerably higher cardiovascularrisk, which is closely associated with systemic inflammation, and an accompanying pathologic coagulation system. Due to the complexity of the diabetic profile, we suggest that we need to look at each patient individually and particularly at his or her clotting profil...

The progression of Alzheimer's disease (AD) is accompanied by a great many observable changes, both molecular and physiological. These include oxidative stress, neuroinflammation, and (more proximal to cognitive decline) the death of neuronal and other cells. A systems biology approach seeks to organize these observed variables into pathways that d...

It is well known that a variety of inflammatory diseases are accompanied by hypercoagulability, and a number of more-or-less longer-term signalling pathways have been shown to be involved. In recent work, we have suggested a direct and primary role for bacterial lipopolysaccharide in this hypercoagulability, but it seems never to have been tested d...

Central to the pathogenesis of ischaemic stroke are the normally protective processes of platelet adhesion and activation. Experimental evidence has shown that the ligand-receptor interactions in ischaemic stroke represent a thrombo-inflammatory cascade, which presents research opportunities into new treatment. However, as anti-platelet drugs have...

Transient ischemic attack (TIA) is an important predictor of future ischemic events, including stroke. Due to the typically brief period of neurologic dysfunction, patients often overlook the importance of reporting a TIA. We have recently shown that platelet activation plays an important role in TIA pathology. In a similar vein, smoking is associa...

We have noted in previous work, in a variety of inflammatory diseases, where iron dysregulation occurs, a strong tendency for erythrocytes to lose their normal discoid shape and to adopt a skewed morphology (as judged by their axial ratios in the light microscope and by their ultrastructure in the SEM). Similarly, the polymerization of fibrinogen,...

Alzheimer-type dementia (AD) is a neurodegenerative disorder and the most common form of dementia. Patients typically present with neuro- and systemic inflammation and iron dysregulation, associated with oxidative damage that reflects in hypercoagulability. Hypercoagulability is closely associated with increased fibrin(ogen) and in AD patients fibr...

Blood in healthy organisms is seen as a 'sterile' environment: it lacks proliferating microbes. Dormant or not-immediately-culturable forms are not absent, however, as intracellular dormancy is well established. We highlight here that a great many pathogens can survive in blood and inside erythrocytes. 'Non-culturability', reflected by discrepancie...

Alzheimer's disease (AD) is a significant source of morbidity and mortality for millions of people worldwide, and multiple potential etiologies have been postulated to contribute to AD. Among these, spontaneous cerebral emboli and increased cerebral and circulating heme oxygenase (Hmox) activity in AD patients are of particular interest, as two of...

A 76-year-old man with an extremely high serum ferritin concentration (33 790 μg/L) was referred to the National Reference Laboratory for further laboratory testing to determine the cause. Genetic analysis showed that he was a carrier of a haemo chromatosis-associated allele (H63D/hetero zygous). Pathology con fi rmed renal insuffi ciency and liver...

It is well-known that individuals with increased iron levels are more prone to thrombotic diseases, mainly due to the presence of unliganded iron, and thereby the increased production of hydroxyl radicals. It is also known that erythrocytes (RBCs) may play an important role during thrombotic events. Therefore the purpose of the current study was to...

Introduction: Unliganded iron both contributes to the pathology of Alzheimer's disease (AD) and also changes the morphology of erythrocytes (RBCs). We tested the hypothesis that these two facts might be linked, i.e., that the RBCs of AD individuals have a variant morphology, that might have diagnostic or prognostic value. Methods: We included a lit...

Abstract Prothrombin mutation G20210A, anti-phospholipid syndrome as well as iron overload has previously been shown to cause thrombotic events. The main reason for this is the involvement of these anomalies in causing hypercoagulability of the coagulation system, which frequently leads to venous and arterial thrombotic events. We report the case o...

Abstract Serum albumin is an essential plasma protein that serves an important function in maintaining osmotic pressure. Low levels of this protein are associated with the kidney failure and hemodialysis that are often seen in diabetic patients who are at high risk of thrombotic events. In diabetes, fibrin fiber nets are changed to form dense matte...

Fibrinogen is key to the maintenance of hemostasis and is an acute phase protein that is part of the coagulation cascade of proteins. It plays a fundamental role in inflammation, particularly as indicator for a proinflammatory state and is a prominent marker for developing vascular inflammatory diseases. The ultrastructure of fibrin nets can be stu...

Aims: Inflammatory diseases associated with iron overload are characterized by a changed coagulation profile, where there is a persistent presence of fibrin-like material of dense-matted deposits (DMDs). It is believed that one source of such material is a result of the activation of blood coagulation without the generation of thrombin, causing cl...

Blood coagulation under physiological conditions is activated by thrombin, which converts soluble plasma fibrinogen (FBG) into an insoluble clot. The structure of the enzymatically-generated clot is very characteristic being composed of thick fibrin fibers susceptible to the fibrinolytic degradation. However, in chronic degenerative diseases, such...