The strategy of suicide gene therapy in cancer is based on the idea of enabling tumour cells, by gene transfer, to convert a non-toxic pro-drug into a toxic product. Previous work has shown that the combination of herpes simplex virus type 1 thymidine kinase gene (HSV1-tk) trans…
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Vigabatrin, a GABA (γ-aminobutyric acid) agonist is a drug widely prescribed in Europe and Asia between 1989 and 1997 for drug resistant, partial epilepsy and has been associated with visual field defects. Uncertainity in the effect of Vigabatrin on vision resulted in decreased …
The lipid-modifying qualities of nicotinic acid, a B3 vitamin, have been exploited for many years to prevent cardiovascular disease and its associated mortality. Despite its widespread availability and clinical use, the clinical target and precise molecular mechanism by which ni…
Introduction The work described in this thesis looks particularly but not exclusively at two recently developed molecules which have dual enzyme inhibitor activity. Omapatrilat, a molecule which inhibits both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), a…
Although traditional Cognitive Behaviour Therapy (CBT) has achieved many clinical successes, approximately 30-50% of patients are resistant to this form of treatment. This trans-diagnostic group of treatment resistant patients typically have chronic, co-morbid, and/or personalit…
Resistance to anthelmintics used to treat parasitic nematodes of veterinary importance represents a serious welfare and economic problem for the livestock production industry. Research into the mechanisms by which parasites develop resistance is necessary to prolong the life of …
This thesis describes the use of mathematical modelling to analyse the treatment of patients with immune disorders; namely, Multiple Myeloma, a cancer of plasma cells that create excess monoclonal antibody; and kidney transplants, where the immune system produces polygonal antib…
Organophosphate compounds have been widely developed as pesticides (e.g. paraoxon) and also as chemical warfare agents (nerve agents, e.g. sarin). These compounds rapidly inhibit the enzyme acetylcholinesterase (AChE), causing overstimulation within the cholinergic nervous syste…
There is increasing awareness of the prevalence of deliberate self-harm (DSH) although the phenomenon is still poorly understood. Those who self-harm often have a poor long-term prognosis, yet systematic focused treatment interventions are scarce. DSH appears to share fundamenta…
Chest physiotherapy is integral to the management of mechanically ventilated children and previous research has confirmed that chest wall vibrations are the manual techniques used most frequently by physiotherapists in this population. Chest wall vibrations involve the applicati…
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…
It is just forty years since the identification of immunoglobulin E (IgE) as the reagin responsible for allergen induced immediate hypersensitivity reactions. IgE exerts its biological actions through the binding of its Fc fragment to specific Fc receptors on effector cells. The…
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…
Smokers with asthma display reduced responses to both inhaled and oral corticosteroids with associated increased symptoms, accelerated decline in lung function and increased use of health care services. Little work has been undertaken to address the possible causes of this reduc…
Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common partners with common problems. Both are chronic systemic disorders incurring significant morbidity and mortality. Although around one third of patients with HF have concurrent COPD,1 remarkably few re…
The steps involved in the medication process for instance prescribing, dispensing and administering medicines (the "medication process") have always posed some risk to individual patient health. Such "medication errors" were sufficiently common in developed countries by the 1960…
African trypanosomiasis is a disease caused by the Kinetoplastida parasites Trypanosoma brucei rhodesiense and T. b. gambiense. The distribution of the disease is split geographically with T. b. rhodesiense found in eastern sub-Saharan Africa and T. b. gambiense in the west of t…
A detailed review of the literature revealed that children report mixed views towards ADHD and medication. They are also reported to experience a lack of control over their symptoms and in turn, report a reliance on medication to control behaviours. Research into children’s sens…