Personal profiling is a dynamic learning process designed to enable individuals to identify their strengths, needs and aspirations in order to set strategic and behavioural goals. This single-site case study seeks to explore undergraduate occupational therapy students' attitudes and experiences of the process of personal profiling in the context of early professional development. The profiling system aims to support students through the process of integrating their University-based and practice-based learning experiences for personal and professional development. The investigation was carried out in two phases, a pilot study and main study, using an inclusive approach for inquiry. From the initial research question several sub-themes emerged during the pilot study which informed the overarching design of the main study. Students' attitudes towards the existing system were examined using a cohort study approach which employed a survey design of quantitative and qualitative data-gathering questionnaires. Attitudes and experiences of students were further explored through semi-structured interviews. A cross-sectional approach which included a sample of students from each year was adopted. In addition questionnaire data was collected from tutors and practice educators who play a significant role in students' professional education. Findings indicate students generally appear to have a positive attitude to personal profiling. The value is experienced at varying psychological levels, depending on students' willingness, motivation to engage with the process and psychological preparedness. A model of levels of engagement in profiling is proposed. Students' report the process of profiling was a challenging, psychologically messy and uncertain process yet worthwhile in the overall pursuit of professional development. Tutors perceived it as an enabling process in the students' learning. The conclusion drawn is that students have the intellectual capability and potential to benefit from personal profiling. Students appear to self-consciously recognise, articulate and acknowledge the value of personal profiling in facilitating early professional development.

Poly(lactide-co-glycolide) (PLG) biodegradable microparticles were evaluated as an oral delivery system for immunisation against equine influenza virus. Model particulates (fluorescent polystyrene and gold labelled polystyrene) were used to characterise the route and mechanism of intestinal uptake. Peyer's patches were found to be the site of particulate intestinal absorption characterised by phagocytosis at the M cell surface. Microparticles were found within intercellular compartments indicating a paracellular route for the transit of microparticles from lumen to lymph. A quantitative method of counting the number of microparticles passing into the lymph in both the superior mesenteric and thoracic lymph ducts indicated levels of intestinal uptake high enough to deliver vaccines via this route. PLG microparticles encapsulating equine influenza virus were prepared by the process of solvent evaporation. The immune responses were evaluated in mice after either systemic or oral immunisation of Balb\c mice using formalin treated equine influenza (Prague 56 H7N7) either encapsulated in PLG biodegradable microparticles or free in solution. Using the single-radial- immunodiffusion test, the haemagglutinin integrity of the microencapsulated influenza was found to be preserved during the microencapsulation process. When administered systemically the microencapsulated virus induced raised levels of anti-influenza IgG antibody in serum that were comparable with those obtained with the virus in solution. Oral administration of the microencapsulated virus induced raised levels of anti-influenza IgA antibody in saliva as well as levels of anti-influenza IgG comparable to those obtained after parenteral injection. Raised levels (compared to preimmune levels) of anti-influenza antibodies in both the systemic circulation and mucosal secretions indicates that orally administered microencapsulalated equine influenza virus represents a practical method of immunisation against influenza.

The ultimate aim of the work described in this thesis was to (1) utilise PAMAM dendrimers as a tool to achieve differential transport across the intestinal mucosa and the blood brain barrier, where these dendrimers can be used to achieve oral bioavailability but avoid BBB penetration and CNS access and (2) to create cannabinoid-dendrimer conjugates that are active in their own right and whose penetration to the brain is prevented but whose intestinal activity is afforded for the treatment of IBD. Overall, the work described in this thesis has promoted a strategy whereby an active polymer (dendrimer)-drug conjugate could be formed that is active in its own right and where the polymer can serve to provide differential biological barrier transport which with regard to cannabinoid pharmacology obviates adverse CNS effects. The work in this thesis describes the design and synthesis of novel and active cannabinoid structures that should have commercial interest. These novel compounds served to further elucidate SAR in amino alkyl indole cannabinoids. SAR findings have revealed a site on these cannabinoids that can be functionally altered without loss of pharmacological activity. Additionally, studies in this thesis have led to the development of a novel radiolabelling strategy for anionic polymers that offers a number of distinct advantages over other approaches. Ultimately, a novel stable Dendrimer-cannabinoid conjugate has been synthesised but to date has not shown biological activity in the models utilised in this work.

An investigation into the pH stability of the BCNAs was also carried out and the parent analogue bearing a pentyphenyl side chain was found to be stable at a range of pHs. Finally, with the X-ray crystal structure of VZV thymidine kinase published we began a preliminary investigation into the possible interaction the BCNAs with this enzyme using molecular modelling

Muscle injuries are one of the most common sports related injuries. An audit published by The Football Association (FA) in 2004, suggested that 12% of all injuries were hamstring injuries, which are 2.5 times more common than quadriceps injuries (Woods et al., 2004). Recent figures published by Ekstrand et al suggested that, in a professional male football team of 25 players, about 5 hamstring injuries occur each season, equivalent to more than 80 lost football days (Ekstrand et al., 2011). In terms of professional elite athletes, shortened recovery time could mean continuing with training, increased game play and benefit to the team and club. Therefore, further research is needed to analyse the new techniques in treating muscle injuries. In 2008, an article in the British Journal of Sports Medicine titled "The early management of muscle strains in the elite athlete: Best practice in the world with a limited evidence", summarised that currently almost all our socalled knowledge has a basis of level 4 or level 5 (Orchard et al., 2008a). The panel of experts continued to highlight the importance of Dr. Mueller- Wohlfahrt's injection treatment regimen for treating muscle injuries. In brief, the treatment protocol involves multiple local injections and associated back injections with a mixture of a homeopathic and pharmacological cocktail (Wohlfahrt, 2008). Therefore, the biochemical property, pharmacodynamics and pharmacokinetics of each drug are altered and unpredictable. The only potential “active” substance in Dr. Mueller-Wohlfahrt’s cocktail could be a drug called “Actovegin” which is a licenced clinically used drug with a track record of over 60 years. Therefore in this PhD thesis, in order to avoid the unpredictable nature of poly-pharmacy as discussed above, only Actovegin will be investigated. In order to investigate the potential therapeutic effect or efficacy of Actovegin on muscle injury, basic muscle structures, histology and pathophysiology of the healing process were discussed. The biochemical 10 events following skeletal muscle injuries and repair are driven by cytokines, monocytes and leukocytes. The speed and quality of muscle healing are dependent on the inflammatory process. In order to alter the speed or quality of muscle repair, Actovegin must be able to modulate the inflammatory process. The in-vitro study in this PhD thesis was the first study to investigate the role of Actovegin in the inflammatory process and demonstrated significant results. It confirmed that Actovegin could modulate the inflammatory process by influencing the CD68+ and CD163+ macrophages and CD163+ THP-1 cells, which could influence the muscle healing process. Based on the findings from the in vitro studies and data from previous literature, a stand-alone single drug intramuscular Actovegin injection therapy regimen was developed to treat acute muscle injuries. The first clinical study using this stand-alone Actovegin treatment regimen was conducted in this PhD in professional footballer players and translated the in vitro findings to clinical practice, which confirmed that Actovegin could influence clinical outcome in treating acute muscle injuries. This thesis summarises the current evidence on Actovegin. Compared with conventional conservative RICE and NSAID therapy, Actovegin proposes an exciting and legal alternative for high performance athletes. From the studies, Actovegin injection therapy seems safe and well tolerated. Overall, this PhD has suggested that Actovegin has an active role in the treatment of muscle strain injuries biochemically and clinically.

P-glycoprotein (P-gp – MDR-1), a 170 kDa glycosylated membrane bound protein, is a member of the ATP-binding cassette transporter family. The potential for P-gp to reduce drug absorption across lung epithelia is of significant interest; this is particularly so, given P-gp’s broad substrate specificity mediating efflux transport of a range of structurally unrelated substrates. Within lung, Pgp expression is evident in bronchial and alveolar epithelia with functional characterisation of P-gp transport capacity within lung epithelial cells currently restricted to respective in-vitro cell culture models. The aims of this project were to establish the relative mRNA expression of several ATP Binding Cassette (ABC), Solute Carrier (SLC) and Solute Carrier Organic Anion (SLCO) drug transporters within rat lung samples through use of RT-PCR; expression suggesting the potential to serve as targets for pulmonary drug delivery. Further, validation of an Isolated Perfused Rat Lung preparation for use in assessment of drug transport across the lung was conducted. In order to assess the functional significance of the ABC drug transporter, P-glycoprotein, on drugs instilled intra-tracheally to the IPRL set-up, use of the P-gp substrates; Rhodamine 123 (Rh123), digoxin, and flunisolide and the P-gp inhibitor, GF120918 was employed. Further, use of kinetic modelling was employed to establish pharmacokinetic parameters involved. Using the IPRL, the P-gp dependent pulmonary absorption of the P-gp substrate, Rh123, was demonstrated. Dose-dependent absorption, consistent with a saturable component in the molecule’s pulmonary absorption, was demonstrated. Further, the absorption of low dose Rh123 was promoted by the presence of the highly selective P-gp inhibitor GF120918, consistent with a functional role of P-gp mediated efflux within an intact lung; an efflux process which may limit the pulmonary absorption of a lung administered molecule. Further studies using this system and extending the range of molecules studied will provide greater understanding of the quantitative significance of P-gp in limiting pulmonary absorption across lung epithelium.

Cannabinoids show potential as new treatments for inflammatory bowel disease (IBD),exerting several favourable effects in the gut, including anti-inflammatory and antimotilityeffects. The main difficulty with cannabinoids is their psychotropic side effects,but access to the brain may be prevented by conjugating the cannabinoid to a bulkygroup such as a dendrimer. The aims of this thesis were to investigate the mechanism by which cannabinoids reduce gut motility and to investigate whether cannabinoids protect the intestine from inflammatory-damage. A further aim was to determine whether cannabinoids remain pharmacologically active when conjugated to a dendrimer. All cannabinoids used (apart from arachidonoylcyclopropylamide and (-)WIN 55,212-2) caused a concentration-dependent reduction in the size of electrically-stimulated contractions in the guinea-pig ileum. The responses were not blocked by CB1, CB2, CBe(putative endothelial cannabinoid receptor) or GPR55 antagonists, suggesting that none of these receptors were involved in mediating cannabinoid responses. PSN 375963 reduced carbachol-induced contraction, suggesting that the GPR119 may be present on ileum smooth muscle. (+)WIN 55,212-2 was shown to protect the guinea-pig ileum from hydrogen peroxide-induced damage but this protection was not blocked by CB1, CB2, CBe or GPR55 antagonists, suggesting that the protective effects were not mediated through these receptors. Conjugation of JWH007 to a spacer (GA003) abolished activity in the guinea-pig ileum and the conjugation of JWH007 to a spacer and dendrimer (GA006) was found to be toxic in the macrophage assay. These studies show that cannabinoid-mediated inhibition of guinea-pig ileum contractions is not mediated through the CB1, CB2, CBe or GPR55 receptor. These receptors were not involved in the (+)WIN 55,212-2 mediated protection against hydrogen peroxide-induced damage in the ileum. The approach of attaching a dendrimer to JWH007 to prevent central nervous system (CNS) penetration does not appear to be a feasible approach because the cannabinoid-dendrimer was unexpectedly cytotoxic.

Neuronal death is induced by a series of pathogeneses in different neurodegenerative diseases, and one of them, which has been widely accepted previously, is the overload of intracellular calcium (Ca2+) in neurones. This study has investigated ryanodine receptor (RyR) on the endoplasmic reticulum (ER) and several potassium (K+) channels which might be neuroprotective, such as the large conductance Ca2+-activated K+ channel (BK) and adenosine-5’-triphosphate (ATP)-sensitive K+ channel, in both neuronal and astrocytoma cell lines. The reverse transcription (RT)-polymerase chain react (PCR) results in this Thesis show that the messages of RyR, BK channel and ATP-sensitive K+ channel (KATP) exist at the messenger ribonucleic acid (RNA) level in those cell lines. And, the expression of RyRIII message was found being increased in SH-SY5Y cells but decreased in NTERA-2 cells after differentiation. The BK channel was confirmed as functional in SH-SY5Y cells with patch clamp recording. Cell insults which increase intracellular Ca2+ ([Ca2+]i), such as cobalt (II) chloride (CoCl2), hydrogen peroxide (H2O2), beta-amyloid (Aβ1-42) and glutamate, were found to reduce cell number in those cell lines in cell proliferation MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assays, and the cells with higher expression of RyRIII message were more sensitive to CoCl2 and H2O2 insults. In cell proliferation assays testing RyR or K+ channel modulators in the presence of insults, it has been found that generic blockade of RyR or K+ channel might be neuroprotective, and the activation of RyR or BK channel and the blockade of KATP channel may aggravate the insults. Selective blockade of RyRI and RyRII cannot protect the cells, which probably indicates that RyRIII is the key target in neuroprotection. Activators of the KATP channel cannot protect the cells at a low dose of CoCl2 but might be protective at a high dose, although cromakalim was an exception. Hence, blockade of RyRIII and the BK channel, and activation of the KATP channel, could be possible neuroprotective strategies. Future study should measure [Ca2+]i and cell apoptosis through Ca2+ imaging and fluorescence-activated cell sorting (FACS) respectively, and design selective a RyRIII blocker.

Final submission of a dissertation in partial compliance with the requirements for a Master's Degree in Technology: Chiropractic, Technikon Natal, 2002. / The purpose of this randomised, placebo-controlled clinical trial was to investigate the efficacy of foot and ankle manipulation and mobilization as opposed to a placebo treatment (de-tuned ultrasound), in terms of objective and subjective findings in the treatment of Morton's neuroma. This clinical trial consisted of two groups, each with twenty patients. Patients who were diagnosed by the researcher as suffering from Morton's neuroma were included in the study. The patients were randomly allocated into the respective groups. The ages of the patients ranged from 23 to 79 years old. Group A received the de-tuned ultrasound as the placebo treatment and Group B received foot and ankle manipulation and mobilization as well as the de-tuned ultrasound to eliminate any massage effect that may have been incurred. It was hypothesised that foot and ankle manipulation and mobilization would be effective in the treatment of Morton's neuroma. The treatment protocol consisted of a course of six treatments over a treatment period of three weeks. Subjective and objective measurements were taken at the initial, third and final consultations. Subjective data was obtained via the use of the Numerical Rating Scale 101, the Short-form McGill Pain Questionnaire and the Foot Function Index. Objective data was obtained by means of digital algometer measurements / M

M.Tech.