Chemistry of novel fluorinated alkenes

The work described in this thesis is concerned with three areas relating to nueleophilic reactions of novel-polyfluorinated alkenes-. a) Very highly strained fluorinated epoxides have been synthesised from bicyclic internal alkenes using Ca(OCl)(_2). These molecules display an almost unprecedented therira.1 and chemical stability. b) Aromatic bifunctional nucleophiles have been reacted with a variety of perfluorinated alkenes and cycloalkenes to give high yielding heterocyclic compounds. These are discussed within a mechanistic framework which my rationalise the product structures. c) Additions of fluoride ion from CsF and TAS-F to fluorinated alkenes in a suitable solvent are shown to yield long-lived fluorocarbanions. N.m.r. observations indicate the systems are whollyin the form of the respective anions and are essentially static on then.m.r. timescale. Competition experiments for a deficiency of CsF are available and can render useful infornmtion on F(^-) affinities. The (^13) and (^19)F n.m.r. spectra of the anions display unusual chemical shift and coupling constant phenomena. The n.m.r. spectra are unchanged over a wide temperature range but at a distinct threshold temperature line broadening occurs. This is indicative of the onset of F exchange on the n.m.r. timescale, is specific to the M(^+)C(^-) system and. therefore, is a guide to the carbanion stabilities. High yielding trapping reactions with simple electrophiles are described but, in some cases F(^-) donation from the carbanion is preferred. This competing reaction is found for particular electrophiles and above the threshold exchange temperature as determined by n.m.r

Plantar pressure: comparing two Poron insoles

Plantar pressure management in the neuropathic diabetic foot is an important element of ulcer prevention. The authors investigated two types of insole for their relative ability to redistribute plantar pressures in an older population with diabetes. No significant difference between the two insoles was found, but wearing either insole resulted in significantly improved plantar pressure distribtuion in comparison with wearing no insol

Effects of Human RelA Transgene on Murine Macrophage Inflammatory Responses

The NFκB transcription factors are major regulators of innate immune responses, and NFκB signal pathway dysregulation is linked to inflammatory disease. Here, we utilised bone marrow-derived macrophages from the p65-DsRedxp/IκBα-eGFP transgenic strain to study the functional implication of xenogeneic (human) RelA(p65) protein introduced into the mouse genome. Confocal imaging showed that human RelA is expressed in the cells and can translocate to the nucleus following activation of Toll-like receptor 4. RNA sequencing of lipid A-stimulated macrophages, revealed that human RelA impacts on murine gene transcription, affecting both non-NFκB and NFκB target genes, including immediate-early and late response genes, e.g., Fos and Cxcl10. Validation experiments on NFκB targets revealed markedly reduced mRNA levels, but similar kinetic profiles in transgenic cells compared to wild-type. Enrichment pathway analysis of differentially expressed genes revealed interferon and cytokine signaling were affected. These immune response pathways were also affected in macrophages treated with tumor necrosis factor. Data suggests that the presence of xenogeneic RelA protein likely has inhibitory activity, altering specific transcriptional profiles of key molecules involved in immune responses. It is therefore essential that this information be taken into consideration when designing and interpreting future experiments using this transgenic strain

Adult Asthma Consensus Guidelines Update 2003

BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines

Adult Asthma Consensus Guidelines Update 2003

BACKGROUND: Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines.OBJECTIVES: To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management.METHODS: Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed.RESULTS: The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta2-agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education.CONCLUSION: The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.Peer Reviewe