Introduction: Chronic heart failure (CHF) is associated with an increased incidence of atrial fibrillation (AF) and elevated levels of catecholamines and endothelin-1 (ET-1), each of which affects the atrial L-type calcium current (ICaL) and consequently action potentials. Hypot…
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Even though spinal cord research has expanded enormously during the past decades, we still lack a precise understanding of how spinal interneuron networks perfectly integrate sensory feedback with motor control, and how these neuron circuits give rise to specific functions. The …
The thesis commences with a review of trends in declining psychological disorders as a person ages. These findings are understood in terms of differences between older and younger adults’ emotion processing. Socio-emotional selectivity theory is introduced as one account of thes…
COPD (Chronic Obstructive Pulmonary Disease) worldwide has a prevalence of 10% in men and 8.5% in women. Exacerbations of COPD account for approximately 10% of all acute medical admissions. Projected prevalence figures suggest that by 2020 COPD will be the third leading cause of…
Liver fibrosis has a range of aetiologies and is a global cause of mortality. A critical effect of liver fibrosis which also increases mortality is portal hypertension. The hepatic stellate cell is accepted as a major progenitor of liver myofibroblasts, which have been shown to …
Multidrug resistance (MDR) describes the phenomenon whereby cancer cells exposed to a single cytotoxic drug develop cross resistance to numerous other structurally unrelated chemotherapeutics. The development of MDR is a major cause of cancer chemotherapy treatment failure in al…
Evoked otoacoustic emissions (EOAEs) are produced by the cochlea and provide an objective and non-invasive measure of cochlear function. A new technique, based on Maximum Length Sequences (MLSs) enables stimulus rates of up to 5000 clicks/s to be used, and gives increased speed …
Microvolt T-wave alternans is thought to predict the risk of ventricular arrhythmias in patients with heart disease, although recent clinical studies have conflicting results. Understanding the cellular basis for alternans may not only inform more effective utilisation of the cl…
The ghrelin receptor (GRLN-R) was cloned in 1996 after the discovery that a series of synthetic growth hormone-releasing compounds (the growth hormone secretagogues) acted through a receptor distinct from the growth hormone-releasing hormone receptor. In 1999 the endogenous liga…
The endothelium acts to maintain vascular homeostasis, including the regulation of vascular tone, blood fluidity and coagulation. Endothelial dysfunction, a condition largely characterised by reduced NO bioavailability, is an important feature associated with the aetiology of se…
Since the emergence of Kenyan endurance runners on the world stage at the 1968 Mexico Olympics, where they won 8 medals ranging from 400m relay to the 10 000m, Kenyan success has grown year on year. The staggering success of a country that compromises just 0.5 % of the world pop…
INTRODUCTION: The focus of this MD thesis has been relaxin, a member of the insulin family, which is a protein composed of two disulphide linked chains of approximately 6000 Daltons. Relaxin has been traditionally recognised as a hormone of parturition, though more recently it h…
Chronic myeloid leukaemia (CML) is a stem cell (SC) disorder initiated by the reciprocal translocation between chromosome 9 and 22, giving rise to the Philadelphia (Ph) chromosome and the resulting expression of the oncogenic fusion protein BCR-ABL. The current first line of tre…
Epidemiological studies have suggested associations between the consumption of plant foods and beverages, especially those rich in phenolic compounds, and the prevention of chronic diseases, and there is a growing evidence indicating that these dietary phytochemicals are involve…
In 1979, Donald Zilversmit published a landmark paper suggesting a role for postprandial metabolism in the development and progression of atherosclerosis, and in subsequent years, a number of postprandial metabolic perturbations have been highlighted as potential risk factors fo…
The chronic treatment of patients with a β-adrenoceptor antagonist is associated with prolongation of the atrial cell action potential duration (APD), potentially contributing to the ability of these drugs to prevent atrial fibrillation (AF). The mechanisms underlying this APD p…
There is a wealth of evidence to support the anti-inflammatory properties of the prototypical second messenger cyclic-AMP (cAMP), notably with regard to endothelial function. Many studies have shown that cAMP can limit vascular permeability by enhancing barrier function and redu…
Stereotypic behaviour is characterised as repetitive, topographically invariant, rigid behaviour patterns, often displayed by captive, domestic and laboratory animals. The cause of these behaviours is thought primarily to be related to impoverished or species-atypical living env…
The history of newborn resuscitation in the twentieth century presented thus far in the writings of practitioner-historians describes a ‘hands-off’ attitude to newborn care prior to the 1950s. These practioner-historians tend to recount a positivist narrative with the rapid expa…