The thiazolidinedione Rosiglitazone can protect pancreatic beta cells from the detrimental effects of free fatty acids. The aim of this study was to determine the differential effects of saturated fatty acids on beta cells and to identify the mechanisms through which Rosiglitazone can protect beta cell viability. Utilising the mouse beta cell line MIN6, transmission electron microscopy (TEM) was used to determine the effects of palmitate and Rosiglitazone on lipid uptake and cell ultra-structure. H/PI staining and MTT assays were used to determine cell viability.

Cytapheresis is an extracorporeal separation technique widely used in medicine for elimination of specific classes of blood cells from circulating blood. It has been shown recently to have clinical efficacy in various disease states, such as leukaemia, autoimmune disorders, rheumatoid arthritis, renal allograft rejection and sickle–cell anaemia. There are two major methods of extracorporeal leukocyte removal therapy in use in the clinical field, these are the centrifugal method, and the adsorptive method with fibre or beads. Leukocytapheresis using the leukocyte filter Cellsorba and granulocytapheresis using an Adacolumn has been proven to reduce leukocyte load in patients with rheumatoid arthritis and inflammatory bowel disease, but still has major limitations of specificity and selectivity. An ideal extracorporeal technique with non-thrombogenic materials and selective adsorption matrix is still in demand. Extracorporeal separation techniques can be improved by a combination of properties, such as mechanical properties of the column, an appropriate porosity of the matrix, biocompatibility of the polymer and chemical modification of the surface by immobilization of a ligand with an affinity towards target molecules or cells.

Pathways of care are available for people with cerebral palsy (CP) including various conservative and surgical interventions. A common aim of these interventions is to improve functional ability and prevent or reduce the prevalence of pain. There is currently no research evidence that demonstrates whether a surgical approach is more effective in achieving these aims than conservative treatment. Moreover, there is also no available research that explores the experiences of young people and their satisfaction with life in relation to the clinical management of their CP. The aim of this research was, retrospectively, to establish whether young people with CP who had experienced surgery as children to their lower extremities had better long term functional outcomes, less pain and a greater satisfaction of life than young people who had not experienced surgery as children. It also aimed to gain an understanding about their lives with CP and about experiences of the pathways of care that they had received.

This thesis examines the challenges for professional practice, socialisation, and identity in Physiotherapy. The government‘s modernisation agenda and society‘s increasing expectations of healthcare require physiotherapists to update their role, location, and identity. Physiotherapy has viewed identity as a fixed entity emphasizing coherence, continuity and distinctiveness. Socialisation has required the acquisition of a professional identity as one among several necessary assets‘ for novices. Yet how do physiotherapists come to be the physiotherapists they are?

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Accumulating evidence suggests that Positive Affect (PA) is beneficial in determining health-outcomes. Defined as ‘feelings that reflect a level of pleasurable engagement with the environment, such as happiness, joy and excitement’, PA has been associated with social and physiological factors as well as health practices. The work undertaken in this thesis aimed to investigate the relationship between PA and health-outcomes in people living with and without diabetes mellitus, independent of negative affect (NA).

A number of pathological conditions are associated with the build up of toxic substances within the systemic circulation. For example, renal and hepatic failure can lead to the accumulation of metabolites which are usually processed by these organs. There has been much interest over a number of years in techniques such as haemoperfusion that could help clear these toxins from the body and improve patient outcome. Haemoperfusion is an extracorporeal blood purification technique in which a patient’s blood is passed over a column containing a material designed to adsorb a board spectrum of biological toxic molecules. Direct blood contact with the adsorbent requires a material that is able to display good haemocompatibility whilst maintaining adsorption efficiency. Activated carbons (AC) have great adsorption capacity and have previously been used as haemoadsorbents. However the haemocompatibility of carbons has been questioned and they are often coated with biocompatible polymers that increase their haemocompatibility but also act as a barrier to the removal of larger toxins and middle molecules.

Patients with differentiated thyroid cancer (DTC) are usually managed with total thyroidectomy and subsequent radioiodine ablation of the remnant thyroid tissue. Since these patients become athyrotic, L-throxine (L-T4) therapy is required for life, in order to replace the thyroid hormones and also to suppress the endogenous thyroid stimulating hormone (TSH) which may have a growth-promoting effect on any residual thyroid cancer cells. The approximate dose required to achieve this suppression is about 2 g/kg. However, there is wide variation between patients in their L-T4 requirement. Although factors such as the timing of the dose, compliance, weight and age play important roles, genetic factors are also thought to be important in this dose variability. Therefore, the aims of this study are to identify and evaluate the association of polymorphisms in six genes [(iodothyronine deiodinases (DIO) 1, 2 and 3, paired box gene 8 (PAX8), thyroid stimulating hormone subunit β (TSHβ), and sodium iodide symporter (NIS)], involved in thyroid hormone metabolic and functional pathways with DTC risk and L-T4 dose requirement.

The successful regeneration of damaged or injured tissues is strictly dependent upon the ability to control angiogenesis. The formation of new blood vessels from pre-existing ones is mainly regulated by the vascular endothelial growth factor (VEGF), a mitogen specific for endothelial cells. A number of therapeutic approaches are being pursued to control this process in pathological conditions, including the use of synthetic peptides which have shown their capacity to either promote or inhibit angiogenesis. However, their lack of stability and short half-lives have strictly limited their clinical applications. To address these limitations, here, both anti- and pro- angiogenic peptide sequences (WHLPFKC and YIGSR) were synthesised at the uppermost branching generation of poly-ɛ-lysine dendrons.

Severe back pain caused by intervertebral disc degeneration (IVDD) and disc herniation effects up to 35% of people within their lifetime, of which 10% of cases lead to sufferers being chronically disabled. The impact of these conditions has been estimated in terms of social-economic cost, to be in excess of €12 billion per year in the UK alone. While, the biological processes that cause IVDD are not currently fully understood, IVDD can be characterised as progressive degeneration of the nucleus pulposus tissue, driven by a combination of inflammatory immune processes, enzymatic degradation of extracellular matrix components and changes in cellular phenotype and expression. While there is currently no suitable long-term treatment for IVDD, there has been a new drive of research in the field of tissue engineering and regenerative medicine in an attempt to find a potential treatment for this condition. The aim of this study is to develop a novel bio-active self-assembly hydrogel capable of in situ formation as a potentially injectable treatment for IVDD. The design and intended formulation of this hydrogel was based on both the previous work of (Reches and Gazit, 2003) on the self-assembly peptide, Fmoc-F2, and the design of a novel peptide from the active site of human insulin like growth factor-1.