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This thesis explores the concept of healing used by Canada’s Truth and Reconciliation Commission and survivors as a conceptual tool to address and redress the legacy of residential schools. Using public testimony and selected interviews, I explore how the TRC’s statement-gathering process is perceived and experienced by survivors. This thesis also documents the personal tensions and political limits encountered during the implementation of a globalized, institutional process of truth-telling applied to resolve diverse and localized ‘traumas’ experienced by students enrolled in dozens of residential schools. This approach illustrates the inherent shortcomings of a top-down approach to solving residential school issues, drawing on the public testimonies of survivors to identify tensions between a national process and survivor-led and community-based alternatives for healing. Despite its intention to create a forum that allows survivors to tell their story about residential schools, the TRC has also, often, been used as space of political activism and social critique. Survivors have used the public testimonial spaces offered by the TRC to both critique the Canadian government’s commitment to reconciliation and also to demand more effective forms of redress, which have subtly shaped and transformed the TRC during its mandate. Thus, while I draw attention to institutional practices, ideologies and power relations shaping the TRC, I also emphasize how people perceive, engage and transform the process as a result.

This work used <i>Pax6</i>^+/- mice as a model for Pax6-realted corneal diseases and assessed the roles of oxidative stress and epithelial injury in the aetiology of ARK. Histological investigation revealed epithelial lesions in <i>Pax</i>6^+/- corneas. Proteomic analysis demonstrated reduced levels of protective enzymes, transketolase, aldehyde dehydrogenase 3A1 and glutathione S-transferase α4, and cytoskeletal proteins. Keratin 5 and 12 in <i>Pax</i>6^+/- adult mouse corneas. These physical/structural and chemical defects imply that <i>Pax</i>6^+/- corneas may be in a chronic ‘stressed and wounded’ state. Using a DNPH/protein oxidation assay, <i>Pax</i>6^+/- corneal protein oxidation was found to be consistently higher than that in <i>wild-type</i> (WT), and to get worse with age, in parallel with the development of corneal opacity. H₂O₂ was used to induce oxidative stress in mouse corneas and this was found to activate the Ca²⁺ (protein kinase C/ phospholipase C) → p38/p42/p44 mitogen activated kinase signalling pathway. Oxidative stress-induced Pax6 exclusion form cell nucleus led to abnormal expression of non-corneal epithelial markers, indicating a metaplasia process that may cause normally transparent epithelial cells to become opaque. This report for the first time describes cytoskeleton architectures <i>in vivo</i> using flat-mount mouse corneal epithelial by fluorescent staining and confocal microscopy, which is potentially applicable to studies interested in cytoskeleton <i>in vivo</i>. Keratin, desmoplakin and actin cytoskeletal structures were found to be heterogeneous and defective in <i>Pax</i>6^+/- cells. Twenty-one hours after wounding WT corneal epithelia <i>in vivo</i>, healing cells developed desmoplakin and actin structural features, intercellular gaps, interdigitated filopodia-like processes and vesicles similar to the unscratched <i>Pax</i>6^+/- corneal epithelia. These data support the hypothesis of a ‘chronic wounded’ state in apparently uninjured <i>Pax</i>6^+/- corneal epithelia and reveal the cytoskeletal origins of poor adhesion and cellular structure.

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Philosophiae Doctor - PhD / Wound healing is a complex process that involves several overlapping and interacting biological pathways. The consequences of delayed or abnormal wound healing may result in tissue formation that has impaired function or structural abnormalities. As a result, clinicians have sought ways to enhance this process. Recently, the use of autologous platelet concentrates have become popular in the management of wound healing sites. However, controversy exists as to how these biomaterials should be prepared and applied. We therefore sought to investigate whether a biologically viable and clinically effective platelet concentrate could be prepared using standard laboratory equipment. The findings are presented in a series of articles that have been published in peer-reviewed journals. The results suggest that the experimental platelet concentrate produced, has a morphological structure that consists of a dense fibrin network intermingled with platelets, has the ability to accelerate cellular growth in-vitro, has no adverse effects on cells in-vitro, can concentrate and release a systemically ingested antibiotic over a period of 24 hours in-vitro, can be stored for at least 60 minutes without showing signs of deterioration, and has shown clinical evidence of accelerating wound healing in sinus augmentation and alveolar ridge preservation procedures. The reduced cost of producing such a biomaterial allows it to be available to resource poor settings and to wider range of healthcare providers as compared to standard platelet concentration techniques. Further studies are required to investigate the clinical potential of this promising biomaterial.

ABSTRACT The burning of selected indigenous plants and the inhalation of the smoke liberated from them has been a widely accepted and practised form of administration in traditional healing therapy dating back to as far as the Koi and San, and is a method still widely practised in South Africa today. Inhalation has various advantages as a method of administration in both allopathic and traditional practices. Not only is inhalation a highly effective mode of administration because of its direct and local effect on the lungs for the treatment of respiratory ailments, but also because of its ability to deliver drugs effectively systemically. This study elucidated the rationale behind this widely practised treatment by examining chromatographic and antimicrobial data. Five plants that are commonly administered traditionally through inhalation were chosen: Heteropyxis natalensis, Myrothamnus flabellifolius, Artemisia afra, Pellaea calomelanos, and Tarchonanthus camphoratus. An apparatus was designed and constructed and the burning process that occurs in the traditional setting was simulated with the selected plants. The induced volatile fraction (smoke) was captured for analysis. Control solvent extracts were made for each plant using conventional extraction solvents, methanol, acetone, water, and the essential oil of the aromatic plants was also investigated. Antimicrobial assays revealed that the extracts (smoke) obtained after burning had lower minimum inhibitory concentration (MIC) values than the corresponding solvent extracts in most cases. For Klebsiella pneumoniae all five inhalation samples were far more active than the conventional extracts. When tested against the pathogen B. cereus, M. flabellifolius and P. calomelanos inhalation samples proved to exhibit superior antimicrobial activity compared to the respective solvent extracts. Pellaea calomelanos inhalation extract had the lowest MIC values compared to the solvent extracts for all pathogens (P. calomelanos inhalation extract MIC values: 0.53; 1.00; 0.53; 0.53 mg/ml for S. aureus, B. cereus, K. pneumoniae and C. neoformans respectively). Inhalation extracts exhibited different chemical profiles from the solvent extracts of the same plant. For example, A. afra inhalation extract had an abundance of peaks at various retention times from 3.2 to 5.4 minutes, which were not present in the chromatograms of the acetone and methanol extracts of the same plant. These results, albeit preliminary, suggest that the chemistry and antimicrobial activity of plants are influenced by the combustion process which is often used in traditional healing rites.

The increasing occurrence of diabetes in the general population as a result of over nutrition and increasingly inactive lifestyle has led to an obesity epidemic which is set to grow over time. With an ever increasing obese population type 2 diabetes and cardiovascular complications are set to become the major causes of human mortality. Chronic non healing wounds are a major cause of mortality and morbidity in patients with type 2 diabetes. They are predominantly caused by macrophage dysfunction and a lack of migration of fibroblasts into the wound. This study aimed to investigate diabetic wound healing through development of an artificial scratch assay. An in vitro scratch assay developed in WS1 cells. The effect of heat shock treatments from 39°C to 45° was tested to determine if cell migration increased; however, no significant difference was seen. Mitomycin C was used to determine if wound closure occurred as a result of cell proliferation and migration or migration alone. 10μg/ml of mitomycin C inhibited cell division by 79.9% without exhibiting cytotoxicity over a 12h period. The effect of hyperglycaemia and heat shock was also tested and showed no significant difference when compared to control conditions, suggesting that fibroblast migration in vivo is hindered through other factors such as debridement or macrophage dysfunction in the wound. GLUT4 is present in insulin sensitive organs (liver, adipose and muscle) and is the major glucose transporter responsible for the clearance of glucose from the blood after a meal, thus playing a central role in glucose homeostasis. Monocytes are precursors to macrophages and can easily be isolated from whole blood. They have also been shown to express GLUT4 in response to insulin and could be used as model to assess inflammation in diabetes. A glucose uptake assay was developed in U937 cells using a fluorescent glucose analogue, 2NBDG. 2NBDG fluorescence was shown to be competitively inhibited by increasing concentrations of glucose suggesting that 2NBDG enters the cell through glucose transporters. 2NBDG uptake was also assessed at different pH and in presence of membrane fluidizers (DMSO, benzyl alcohol and phenethyl alcohol). Extremes of pH significantly reduced cell viability and only at pH 4 was 2NBDG fluorescence significantly reduced. Treatment with DMSO showed that at high concentrations (≤ 1.56%) cell viability was reduced with a concurrent reduction in 2NBDG fluorescence. The effect of benzyl alcohol and phenethyl alcohol was foundto be insignificant at the concentrations and time points tested. The presence of GLUT4 was also determined by flow cytometry and Western blotting and found to be situated in the cytoplasmic region of the cell. This study indicates that monocytes and macrophages could be a potential therapeutic target to improve diabetic wound healing as they are a source of growth factors and cytokines that can bring about resolution of inflammation and it is their dysfunction in diabetic wounds that causes poor clinical outcomes.