Faculty of Health Sciences
School of Medicine
Department of Physiology
Selected Highlights from Research Findings
The Department of Physiology is actively involved in research relating to the pathogenesis of osteoporosis and cardiovascular disease, with special reference to cardiomyopathy. The physiological effects of stress, in particular autonomic dysfunction, the in vitro effects of polyunsaturated fatty acids on bone biology and the modulation of insulin sensitivity in visceral fat tissue important in the treatment of Type 2 diabetes mellitus are also being investigated. Various aspects of sport physiology and neuroscience, as well as the in silico design, synthesis and analysis of estradiol analogues for tubulin-, kinesin motor protein and carbonic anhydrase isoforms with potential anticancer activity in vitro, are being researched.
Contact person: Prof DH van Papendorp.
The focus of research is on variants of papillary muscles and the various electrocardiographical effects of these variants, and the possibility that it may be an underrecognised cause of sudden cardiac death. Furthermore, a new variant of hypertrophic cardiomyopathy, which is caused by subaortic muscular tendons, has been described and published. This was seen due to the focus on alterations of endoventricular structures. Ultimately, the work focuses on the possibility of a new cause of sudden death that may be due to dysrhythmias caused by papillary muscle anomalies and other endoventricular structural alterations. Left ventricular false tendons are a common echocardiographic finding and consist of thin fibrous or fibromuscular structures traversing the left ventricular cavity. They have no connection to any valvular cusps and may be single or multiple. Histologic examination has shown that they can be composed of any combination of cardiac muscle, fibrous tissue, blood vessels and Purkinje cells. At present, the clinical significance of these false tendons is uncertain, with some studies showing a possible causal role for ventricular arrhythmias. These tendons have been divided into five categories, based on the site of implantation. In this study, a sixth category of left ventricular false tendon is identified, with implantation into the ventricular septum in a subaortic position. These subaortic false tendons are associated with localised subaortic hypertrophy and it is suggested that they play a causal role in the genesis of localised subaortic hypertrophy with a possible new variant of hypertrophic cardiomyopathy – false tendon induced subaortic hypertrophy.
Contact person: Prof J Ker.
Osteoblasts in culture can differentiate into mature mineralising osteoblasts when stimulated with osteogenic agents. Clinical trials and in vivo animal studies suggest that specific polyunsaturated fatty acids (PUFAs) may benefit bone health. The aim of this study was to investigate whether arachidonic acid (AA) and docosahexaenoic acid (DHA) affect osteogenesis in osteoblasts and the transdifferentiation into adipocytes. Results from this study show that long-term exposure to AA inhibited alkaline phosphatase (ALP) activity in these cells, which might be prostaglandin E2 (PGE2)-mediated. DHA exposure also inhibited ALP activity, which was evident after both short- and long-term exposure. The mechanism whereby DHA inhibits ALP activity is not clear and needs to be investigated. Although long-term exposure to PUFAs inhibited ALP activity, the mineralising properties of these cells were not compromised. Furthermore, PUFA exposure did not induce adipocyte-like features in these cells as evidenced by the lack of cytoplasmic triacylglycerol accummulation.
Pro-inflammatory cytokines such as IL-1, IL-6 and TNF-? are known to be active in the pathogenesis of osteoporosis. Results from clinical trials and in vivo animal studies suggest that specific long chain polyunsaturated fatty acids (LC-PUFAs), especially those of the n-3 PUFA family, might be beneficial for bone health. In order to elucidate possible cellular mechanisms, the effects of some LC-PUFAs, representative of the n-3 and n-6 families were investigated on osteoblastic secretion of various inflammatory cytokines.
Contact person: Dr M Coetzee.
Organisational wellness is about assisting employees and their families to make voluntary behavioural changes that reduce their health risks and enhance their individual productivity and well-being. To have an effect on health outcomes at the worksite, wellness strategies need to enable healthy lifestyles for all, including the whole range of staff members – those at risk of chronic disease (such as heart disease, cancer and diabetes), as well as those with a lower risk for chronic disease and those who are already convinced that they need to make healthy lifestyle choices. Wellness programmes should be a part of the overall company strategy for a healthy workplace. The most effective workplace wellness promotion is comprehensive and aims to improve all of the elements involved.
Contact person: Dr PJ du Toit.
The modulation of insulin sensitivity in visceral fat tissue could be important in the treatment of Type 2 diabetes mellitus. Selected fatty acids may impact on insulin-stimulated and basal glucose uptake in adipocytes, thus isolated rat epididymal adipocytes or murine 3T3-L1 adipocyte cultures were exposed to 100 µM oleic, arachidonic (AA), eicosapentaenoic (EPA), docosahexaenoic or stearic acids and insulin (15 nM) or vehicle for 30 minutes. Glucose uptake was quantified by measuring uptake of 3H-deoxyglucose/mg adipocyte protein/min. All fatty acids tested, except for stearic acid, depressed insulin-stimulated glucose uptake by an average of 33 ± 4.2%. In cultures, however, AA and EPA stimulated insulin-dependent glucose uptake with 58 and 47%, respectively. On the other hand, all fatty acids tested, except stearic and arachidonic acids, stimulated basal glucose uptake with an average of 34 ± 8.1%. In cultures, EPA, but not AA could stimulate basal glucose uptake. Inhibitor studies in fresh adipocytes showed the involvement of prostaglandins, lipoxins, protein kinase C and tyrosine kinase in these processes. The results gained from 3T3-l1 cultures suggest a positive role for polyunsaturated fatty acids in the treatment of Type II diabetes mellitus.
Contact person: Prof M Haag.
The department has embarked on developing a protocol that examines the physiological effects of stress, in particular autonomic dysfunction. A pilot study will be conducted on final-year medical students using a fenometer to measure baroreceptor sensitivity and heart rate variability as markers. Subsequently, autonomic dysfunction in patients with psychiatric diseases will be addressed. The involvement of the department in the Neuroscience Research Group will lead to multidisciplinary projects. The possibility of new treatment modalities in ADHD is envisaged.
Contact person: Dr P Soma.
Since several anticancer drugs of clinical importance specifically target tubulin and thereby interfere with microtubule dynamics, the microtubule cytoskeleton represents one of the most highly validated cancer targets identified to date. Thus, the in silico design, synthesis and investigation of estradiol analogues as potential anticancer agents are being investigated in vitro. Novel estradiol analogues for tubulin-, kinesin motor protein and carbonic anhydrase (CA) (CA II, IX, XII) binding affinity were designed by means of in silico analysis and subsequently synthesised. In vitro cellular and molecular studies are currently being conducted to elucidate each compound’s signal transduction mechanism and to verify their potential anticancer activity to contribute to the design/improvement of compounds with therapeutic potential.
Contact person: Prof AM Joubert.
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