Plasma membrane calcium/calmodulin-dependent calcium ATPases (PMCAs) are high affinity calcium pumps regulating many calcium-dependent processes and advances in its characterisation have discovered that it may play a novel role in signal transduction pathways. It was the aim of …
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Introduction: Nitric oxide (NO) is an integral molecule implicated in the control of vascular function. It has been suggested that vascular dysfunction may lead to the development of acute mountain sickness (AMS), high-altitude cerebral oedema (HACE) and high-altitude pulmonary …
Cardiovascular disease (CVD) is the world-leading cause of mortality. The pathophysiological process underlying CVD is atherosclerosis, often preceded by dysfunction of the endothelium, the inner layer of the artery wall. The endothelium is sensitive to hemodynamic stimuli, incl…
Moyamoya (MMA) is a progressive cerebral steno-occlusive angiopathy which can lead to strokes. Its natural history derives from adult East Asian cohorts with idiopathic disease. Clinical differences in pediatric, non-Asian and syndromic patients are reported but understudied. Th…
Opioids and opioid-conditioned stimuli (CS) negatively alter host immunity, impairing the response to pathogens during opioid use and following drug cessation. Using male rats, our laboratory has determined that heroin or heroin-CS exposure preceding an endotoxin challenge marke…
Since the discovery of cytoglobin (Cygb) a decade ago, growing amounts of data have been gathered to characterise Cygb biochemistry, functioning and implication in human pathologies. Its molecular roles remain under investigation, but nitric oxide dioxygenase and lipid peroxidas…
Tetrahydrobiopterin (BH4) is an essential cofactor for neuronal nitric oxide synthase (nNOS), yet the question of whether neurons that secrete nitric oxide (NO) synthesize BH4 remains unanswered. Cerebellar granule cell cultures (CGC) offer a model system of NO-producing neurons…
Homocysteine (Hcy) has been identified as a primary risk factor for atherosclerosis as it induces endothelial cell (EC) activation/dysfunction and thus potentially initiating atherosclerotic plaque formation. There is accumulating evidence indicating a key role for oxidative str…
The aim of this thesis was to examine the ability of metal organic frameworks (MOFs) to store and controllably release biologically significant amounts of nitric oxide (NO). Initial work involved the synthesis of a series of isostructural MOFs, known as M-CPO-27, which display c…
The design of new, improved NO-donor drugs is an important pharmacological objective due to the biological importance of nitric oxide. N-Hydroxyguanidines represent a useful class of NO donors where the mechanism of action is based on the biosynthetic pathway for NO. Thirty new …