Plasmids confer genes encoding clinically relevant antibiotic resistance. It was hypothesised that the AcrAB-TolC multidrug resistance efflux pump was required for clinically relevant levels of carbapenem resistance. However, carbapenemase-producing \(Salmonella\) TolC mutants w…
This thesis reports a study into aspects of the discourse concerning the measles, mumps and rubella (MMR) triple vaccine. The aim of the thesis is to contribute to knowledge about the ways in which debates about science are enacted in the public sphere. The study uses a corpus-a…
Background: Cardiovascular disease (CVD) is one of the major causes of morbidity and mortality worldwide. Clinical guidelines, based on the results of randomised controlled trials, state that effective secondary prevention therapies should be prescribed following a diagnosis of …
Women develop pulmonary arterial hypertension (PAH) more frequently than men suggesting that female sex and/or female sex hormones i.e. estrogens play a role in disease pathogenesis. Building evidence also implicates a role for microRNAs (miRNAs) in PAH. Little is known surround…
Adenoviruses are the most commonly used vectors for clinical gene therapy applications, accounting for 24% of all clinical trials to date, the majority of which are based on Ad serotype 5 (Ad5). However, the high prevalence of neutralising antibodies and a range of “off target” …
The traditional paradigm relying on drug discovery to treat and heal the body is changing. Medicine for the 21st century is moving towards using the body’s internal language of DNA and RNA to cure disease and repair injuries to the body. We now appreciate the complexity of signa…
The experiments presented in this thesis describe the roles of the post-junctional α1, α2-adrenoceptors (AR) and P2X purinoceptors in response to sympathetic nerve stimulation in mouse mesenteric and tail arteries. Such roles were determined by combining wire myography technique…
Most drugs have a considerably low solubility in the environmentally friendly hydrofluoroalkane propellants (HFAs) currently used in pressurized metered dose inhalers (pMDIs). As a consequence, instability can occur from crystal growth and Ostwald ripening of the system altering…
Epilepsy is a chronic neurological disorder which can arise following an initial insult that over time, progresses into a condition characterised by recurrent spontaneous seizures. During a latent period between the initial insult and the epilepsy condition proper, major changes…
This developmental research study concerned how trainers, drawn mainly from the commercial (pharmaceutical) sector of the field of clinical research, shared understandings of practice in a professionally localised community, as part of their continuing professional development. …
Fenofibrate is a PPARα agonist, used to treat dyslipidemia. Unpublished work that has been previously carried out in our group has identified that fenofibrate also displays affinity for the cannabinoid receptors, CB1 and CB2. A dual receptor ligand, with the PPARα agonist activi…
In Chapter 1, I introduce ischaemic stroke, thrombolytic therapy, thrombolysis trials and then discuss the rationale for exclusion criteria in stroke thrombolysis guidelines.In Chapter 2, I describe methods for examining outcomes in patients that are currently recommended for ex…
Based on the study of 34 healthy and 19 osteoarthritic knees in three different age groups (early, middle and late adulthood), this thesis reports the discovery of the potential of knee acoustic emission (AE) as a biomarker for quantitative assessment of joint ageing and degener…
Human African trypanosomiasis (HAT), a lethal disease caused by infection with Trypanosoma brucei rhodesiense or Trypanosoma brucei gambiense, affects a significant number of people in sub-Saharan Africa. Related trypanosome species are also responsible for veterinary trypanosom…
In the last few decades, evidence has been accumulating for a role for xanthine oxidoreductase (XOR)-generated toxic reactive oxygen species (ROS) in a variety of pathological conditions that affect different organ systems. This enzyme in mammals exists in two inter-convertible …
DNA triple helices are an important tool in a variety of medicinal and biotechnological applications, such as gene therapy and chemotherapeutics. DNA triple helices are formed by binding of a triplex-forming oligonucleotide (TFO) to a DNA duplex, via specific recognition of the …
An inability to perform tasks involving reaching is a common problem following stroke. Evidence supports the use of robotic therapy and electrical stimulation (ES) to reduce upper limb impairments following stroke, but current systems may not encourage maximal voluntary contribu…
Over the last 20 years it has been realised that neonates, infants and children experience pain and considerable stress responses to surgical and medical procedures which are harmful and cause fear, anxiety and distress(Walker, 2008). This thesis will describe a body of work pub…
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by chronic inflammation within the synovial tissues in multiple joints leading to progressive, erosive destruction of cartilage and underlying joints. The severity of RA is associated with the overexpr…