The investigation of metabolic profiling of human synovial fluid to provide joint disease analysis and the association with implant material wear

The goal of this thesis was to establish a biobank of human synovial fluid (HSF) samples. Furthermore, the methodology, conditions, fit-for-purpose criteria were needed to ensure validity and robustness. Once those conditions were met, the relationship between HSF and the behaviour of the joint implant material was to be evaluated. The current literature relating to the metabolism of osteoarthritis, synovial fluid, its storage and analysis was systematically reviewed. A biobank of HSF samples was collected. Metabolite identification of HSF was achieved using a combination of published NMR studies, the Human Metabolite Database (HMDB), 1D and 2D NMR spectra and STOCSY analysis. The stability of samples to handling, collection and long-term -80oC storage was investigated. All metabolite concentrations affected by storage were reported. This work has validated the systems and methodology to metabolically profile HSF. A variety of protein precipitation steps to maximise the metabolic information from the samples were evaluated. An acetonitrile liquid/liquid extraction performed well with additional recovery of unknown metabolites, albeit with increased variation and diminished lipid detection. To understand which metabolic components are important for mechanical wear, the metabolic profile of HSF and its wear model, BCS, were analysed for components of both fluids which correlate to measured wear in a bench-top testing rig. Wear analysis demonstrated variation in the HSF mechanical properties. This correlated to the presence of glycosaminoglycan (GAG) and proteoglycan molecules with binding to citrate and glucose. Furthermore, specific amino acids: lysine, glutamine, glycine, threonine, asparagine, proline, histidine and tyrosine, correlated with measured wear.The reported unstable metabolites must be considered for any HSF study. The acetonitrile liquid/liquid extraction method is recommended to maximise metabolite detection. The small molecule components of HSF contributing to the wear properties of implant materials has not been reported previously, is unique and opens a new field of study in implant survival.Open Acces

Ischemic preconditioning does not enhance repeated sprint ability in team sport athletes

This study tested the hypothesis that ischemic preconditioning (IPC) would enhance the physiological processes associated with repeated sprint ability (RSA) and improve performance by reducing fatigue. In a randomised, single-blind, cross over study 10 active team sport playing participants (mean ± SD; age 23.3 ± 3.4 years, stature 1.76 ± 0.89 m, mass 72.5 ± 11.6 kg) completed six 40m (20 + 20 m) shuttle sprints following four 5 minute periods of unilateral limb occlusion with cuff pressure set at 55 mgHg over resting systolic blood pressure (IPC) and 20 mmHg (placebo). No significant differences were evident through all experimental measures; sprint time, blood lactate, jump height, heart rate and rate of perceived exertion when comparing IPC and placebo interventions. The results of this study suggest future application of IPC should not be considered to aid RSA within team sport athletes

The Great Reform Act and the Modernization of British Politics: The Impact of Conservative Associations, 1835–1841

Original article can be found at: http://www.journals.uchicago.edu/loi/JBS/ Copyright University of Chicago Press. DOI: 10.1086/587723Peer reviewe