Browsing by Author "Dube, Kopano Rebaona"

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    The availability, utilisation and relevance of therapeutic apparatuses in South African occupational therapy clinical practice
    (The Occupational Therapy Association of South Africa, 2019-12) Duvenage, Catharina Maria Elizabeth; Dube, Kopano Rebaona; Rodrigues, Anne Maria; Swart, Alicia; Slater, Kelly
    The World Federation of Occupational Therapists (WFOT) steers the development, use and practice of occupational therapy internationally through numerous operations including policy and research in an effort to homogenise and advance occupational therapy training globally. The Federation has compiled and published the Minimum Standards for the Education of Occupational Therapists that serves as a blueprint to both set the minimum standard for educational programmes in occupational therapy and to foster continuous quality assurance and professional development. In South Africa, the Professional Board for Occupational Therapy, Medical Orthotics and Prosthetics and Arts Therapy has incorporated these standards into the national policies and guidelines for occupational therapy training2,3. Consistent with international standards, one of the key outcomes highlighted in the national policies and guidelines is the graduate’s knowledge of occupation.
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    The Significance of Mitophagy in Myocardial Ischaemia/ Reperfusion: the effect of melatonin
    (Stellenbosch : Stellenbosch University, 2018-03) Dube, Kopano Rebaona; Lochner, Amanda; Salie, Ruduwaan; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Medical Physiology.
    Introduction: Myocardial ischaemia and concomitant cell damage are caused by a reduction in the blood supply to the heart. To date, the most effective strategy to salvage the myocardium is timely reperfusion which is unfortunately associated with further tissue damage. This phenomenon, termed ischaemia reperfusion injury, is associated with mitochondrial structural damage which could lead to death of cells previously damaged by ischaemia. Damaged and dysfunctional mitochondria play a key role in mediating tissue damage in this setting, thus the swift yet selective removal of these damaged organelles by mitochondrial autophagy – mitophagy could be of importance in cell survival and therefore is a potential therapeutic target. Studies have shown that upregulation of autophagy during ischaemia/reperfusion is cardioprotective, however, very little is known about the role of mitophagy in this setting. Subsequently, the aims of this study were to (i) characterise the effect of ischaemia/reperfusion on functional recovery during reperfusion and to correlate this with mitochondrial oxidative phosphorylation capacity, infarct size and mitophagy in the working heart model using male Wistar rats; (ii) evaluate the effect of mitophagy manipulation on cardioprotection using the parameters listed above. To achieve this, used was made of melatonin, the pineal hormone, which is well-known for its cardioprotective effects. Methods: Male Wistar rat hearts were perfused ex vivo in the working mode using Krebs-Henseleit buffer and glucose (10mM) as substrate. After a stabilization period of 30 min, hearts were subjected to 20min global ischaemia followed by 30min reperfusion during which time functional recovery was monitored. Mitochondria were isolated from hearts at different times during the perfusion protocol: after stabilization for 30min, after 20min global ischaemia and after 30min of reperfusion. The mitochondrial pellets were used for measurement of mitochondrial oxidative phosphorylation using an Oxygraph as well as for western blotting to evaluate a number of indicators of mitophagy. In addition, hearts were subjected to the perfusion protocol as described above and freeze-clamped at the same time intervals for subsequent Western blotting for mitophagy markers in the cytosolic fraction. In a separate series melatonin (0.3, 50M) was added to the perfusate for 10min before and 10 min after ischaemia and the same parameters evaluated as above. For evaluation of infarct size by the tetrazolium method, hearts were stabilized for 30min, followed by 35min of regional ischaemia and 60min reperfusion. Results: Exposure of hearts to either 35min regional ischaemia/ 60min reperfusion or 20min global ischaemia/ 30min reperfusion was associated with impaired recovery of myocardial function during reperfusion, characterized by significant reduction in several haemodynamic endpoints including coronary flow, aortic output and total work performed. Exposure to 20min global ischaemia per se had no effect on mitochondrial oxidative phosphorylation function, but a significant reduction in QO2 States 3 and 4 was observed after reperfusion, with glutamate/malate as substrates. Contrary to expectations, ischaemia/reperfusion did not upregulate mitophagy, as indicated by the reduced expression of PINK1, Parkin and TOM70 as well as markers of the alternative pathway (ULK1, DRP-1 and Rab9). Melatonin at both concentrations studied, significantly reduced the myocardial infarct size (p<0.0001), but did not improve mechanical recovery during reperfusion. In the global ischaemia model, melatonin increased mitochondrial oxphos during reperfusion only. While not having marked effects on the conventional PINK1/Parkin pathway, melatonin caused significant increases in the expression and phosphorylation of ULK1 and DRP-1, suggesting upregulation of the alternative pathway of mitophagy. Conclusion: In this experimental model ischaemia/ reperfusion reduced (i) contractile function and (ii) oxidative phosphorylation during reperfusion. It also subdued both the (iii) conventional and alternative mitophagy pathways suggesting that mitochondrial fission, which is a prerequisite for mitophagy, may be impaired under these conditions. These changes may contribute to the impaired functional recovery during reperfusion. Melatonin’s cardioprotective effects were associated with upregulation of a novel mitophagy signalling pathway, the significance of which in its cardioprotective actions needs to be further elucidated.