published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Chinese Medicine / Master / Master of Philosophy

The advance of nanotechnology has made it possible that pure silver can be engineered into nano scale level with less than 100 nm in size. So far many studies have confirmed anti-bacterial and anti-inflammatory efficacy of silver nanoparticles (AgNPs). In our previous study we have revealed that AgNPs could promote wound healing through modulation of cytokines in a burn wound model in mice. Nonetheless, the exact effects mediated by AgNPs on various cell types in skin, including keratinocytes and fibroblasts, during wound healing still remain unknown. Therefore, in the present study we targeted a full-thickness excisional wound model in mice to explore the action and potential toxicity of AgNPs on keratinocytes and fibroblasts. Immunohistochemistry staining and molecular assay were conducted to explore AgNPs-induced re-epithelization and cell differentiation in both in vivo and in vitro studies. We next targeted the healed skin after AgNPs-mediated wound healing using tensile test to compare their mechanical function. Meanwhile, immunohistochemistry staining and quantitative assay were utilized to further investigate and compare collagen deposition, and scanning electron microscopy (SEM) was used to observe the morphology and distribution of collagen fibrils in healed skin. Moreover, AgNPs of different sizes and doses were studied to investigate the potential toxicity, their influence on cell migration, and extracellular matrix (ECM) production. Key results: 1. AgNPs could accelerate excisional wound healing in mouse skin when compared with other formats of silver. 2. AgNPs mediated differential cellular response in skin cells. They promoted proliferation and migration of keratinocytes in epidermal layer, through which the re-epithelization process during wound healing was enhanced; while proliferation of fibroblasts in dermal layer was inhibited and they were driven into the differentiation of myofibroblasts, through which wound contraction process was strengthened. 3. AgNPs could suppress the proliferation of human keloid fibroblasts and ECM production including collagen, fibronectin and heat shock protein, which would suggest that AgNPs had anti-fibrosis effect. 4. The AgNPs could stimulate the proliferation of epidermal progenitors and their differentiation into keratinocytes during wound healing. This biological event further contributed to the re-epithelization process. 5. AgNPs-mediated healed skin possessed comparable mechanical function, collagen deposition and fibril alignment to normal skin, which suggested AgNPs could modulate collagen production during skin wound healing. 6. The inhibitory effect on fibroblasts and cytotoxicity mediated by AgNPs showed a dose-dependent and size-dependent manner. In conclusion, AgNPs not only contribute to healing of infected skin wounds through antibacterial activity, but can also accelerate wound healing through mediating differential cellular responses in different skin cell types and modulate collagen production during wound healing. Furthermore, there should be an optimal concentration and size to exert maximal biological action with minimal toxicity for each specific cell type. Present studies further extended our knowledge of AgNPs and have implications for treatment of wounds in clinical setting. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

Thesis (MTech. degree in Pharmaceutical Sciences)--Tshwane University of Technology, 2008. / The aim of the study is to investigate whether the chemical composition and antimicrobial activity of orally administered medicinal plants are affected by in vitro dissolution and gastrointestinal absorption processes. Few in vitro screening assays for biological activities of plant extracts consider the effect of the gastrointestinal system. This is an important factor for the bioavailability of plant extracts intended to be administered via the oral route. In this study, crude water and methanol extracts of selected plants (green tea, 'buchu', thyme, sage and wild camphor) were prepared and exposed to simulated gastric fluid and simulated intestinal fluid during dissolution studies. The crude extracts and resulting simulated gastric fluid and simulated intestinal fluid products were screened for antimicrobial activity.

published_or_final_version / abstract / toc / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Zoology / Master / Master of Philosophy

published_or_final_version / Medicine / Master / Master of Philosophy

The metaphor of weaving and the methodology of phenomenology are used to expose eight ordinary people’s lived experience of receiving client-centred occupational therapy at home. This qualitative study reveals the themes of Thread, Weave and Texture interlocking to create the phenomenological structure of the lived experience. The two threads of being acknowledged and being respected are used with the five weaves of listening, taking time, demonstrating, having knowledge, and projecting a positive attitude, building four simple textures. The four textures -- having opportunity for choice, receiving support, getting information, and being cared about -- blended to form the participants’ lived experience. Their stories have inspired me to weave a tapestry of words, something that in its beauty celebrates the delivery of client-centred occupational therapy but also teaches these principles. / ix, 111 leaves ; 29 cm.

The emergence of multidrug resistant tumours during the course of chemotherapeutic treatment of cancer patients is a major obstacle in cancer chemotherapy. Although several mechanisms may contribute to the appearance of multidrug resistance phenotype (MDR) in tumour cells, reduced drug accumulation and the ability of cells to undergo apoptosis are thought to be very important in expression of MDR. The work in this thesis focuses on the mechanism responsible for the reduced drug accumulation in tumour cells, mainly the multidrug resistance protein (MRP1). / The molecular mechanism underlying the binding and efflux of drugs by the MRP1 is currently not well understood. Several studies have now demonstrated that the cysteinyl leukotriene C$ sb4$ (LTC$ sb4$) and other glutathione (GSH) S-conjugated anions are substrates for the MRP. To learn more about MRP-drug interactions, we characterized the binding of MRP to a non-glutathione photoactive quinoline compound (abbreviated, ASA-AQ) (Chapter II). Since MRP mediated multi-drug resistance can be modulated by the anionic quinoline LTD$ sb4$ cysteinyl leukotriene receptor antagonist (MK571), we speculated that other quinoline-based compounds are likely to interact with MRP. In Chapter III, we show that MDR cells that express MRP1 are more resistant to the antimalarial drug, chloroquine. We also show that. chloroquine is a substrate for MRP1 drug efflux. / Taken together, the results of this thesis describe the interactions of MRP1 with a quinoline-based photoactive drug and the antimalarial drug chloroquine.

Treatment delivery verification is an essential step of radiotherapy. The purpose of this thesis is to develop new methods to improve the verification of photon and electron beam radiotherapy treatments. This is achieved through developing and testing (1) a way to acquire portal images during electron beam treatments, (2) a method to reconstruct the dose delivered to patients during photon beam treatments and (3) a technique to improve image quality in kilovoltage (kV) cone beam computed tomography (CBCT) by correcting for scattered radiation. The portal images were acquired using the Varian CL21EX linac and the Varian aS500 electronic portal imaging device (EPID). The EGSnrc code was used to model fully the CL21EX, the aS500 and the kV CBCT system. / We demonstrate that portal images of electron beam treatments with adequate contrast and resolution can be produced using the bremsstrahlung photons portion of the electron beam. Monte Carlo (MC) calculations were used to characterize the bremsstrahlung photons and to obtain predicted images of various phantoms. The technique was applied on a head and neck patient. / An algorithm to reconstruct the dose given to patients during photon beam radiotherapy was developed and validated. The algorithm uses portal images and MC simulations. The primary fluence at the detector is back-projected through the patient. CT geometry to obtain a reconstructed phase space file. The reconstructed phase space file is used to calculate the reconstructed dose to the patient using MC simulations. The reconstruction method was validated in homogeneous and heterogeneous phantoms for conventional and IMRT fields. / The scattered radiation present in kV CBCT images was evaluated using MC simulations. Simulated predictions of the scatter distribution were subtracted from CBCT projection images prior to the reconstruction to improve the reconstructed image quality. Reducing the scattered radiation was found to improve contrast and reduce shading artifacts. / MC simulations, in combination with experimental techniques, have been shown to be valuable tools in the development of treatment verification methods. The three novel methods presented in this thesis contribute to the improvement of radiotherapy treatment verification. They can potentially improve treatment outcome by ensuring a better target coverage.