Recent studies have shown the numerous advantages associated with specific drug delivery to the colon, highlighting its favourable conditions and long transit time as the main advantages. A number of in vitro studies also show that the delivery of liposomes to the colon could pr…
At the height of its popularity, mephedrone was the most common recreationally used cathinone. This is thought to be due to its perceived likeness to MDMA. Therefore the aim of this thesis was to examine mephedrone-induced changes in behaviour, body temperature or neurochemistry…
HIV continues to be a global healthcare challenge, with estimates suggesting there are currently 35.5 million infected people globally. To date, there have been an estimated 36 million HIV/AIDS related deaths worldwide. The story is changing however, with the advent of Highly Ac…
Adverse drug reactions (ADR) are a major concern for the pharmaceutical industry and health practitioners as they can cause morbidity and in severe cases mortality. ADRs are one of the major reasons why drugs fail during clinical trials so research directed at predicting ADRs to…
Drug-induced liver injury (DILI) is a major cause of attrition during drug development, and also a leading cause of hospital admissions. In order to identify novel biomarkers that may improve the diagnosis and treatment of DILI, well characterised hepatotoxins such as acetaminop…
Malaria is one of the most prevalent and deadliest parasitic diseases affecting various systems of the body and leading to death. Resistance against antimalarial treatment is a major threat in controlling and eliminating malaria. New drugs are urgently needed especially when art…
Type 1 diabetes is an autoimmune disorder caused by the destruction of insulin secreting ß cells in the pancreas. The aim of this project is to explore the potential of using solid-coated microneedles to target skin dendritic cells with an auto-antigen to induce tolerance for th…
Stroke is a common disorder with dire consequences for the patient and for society and will increase in prevalence over the coming years. Following stroke, many patients unfortunately suffer a further stroke, and recurrent strokes account for approximately 25% of the total. Cons…
CML is treated effectively with TKI, however two key problems remain - the insensitivity of CM HSC to TKI and the emergence of TKI-resistant BCR-ABL mutations. BCR-ABL activity is associated with increased proteasome activity and PI are cytotoxic against CML cell lines. We demon…
As resistance to current therapies remains one of the major hurdles to the successful treatment of advanced colorectal cancer, we need to understand the mechanisms by which cancer cells evade therapy-induced cell death. I have investigated whether there is a link between epithel…
Cerebrovascular disease, has an enormous, and increasing, impact on global health. As well as causing clinical stroke, cerebrovascular disease is thought to be a major contributor to cognitive decline and dementia. Socioeconomic status (SES) is associated with risk of stroke. Th…
Abstract Clinical trials are at the centre of advances in our understanding of stroke and its optimal treatment. In this thesis the uses and properties of outcome assessment scales for stroke trials are described, with particular attention given to the modified Rankin Scale (mRS…
Abstract Background: Pulmonary hypertension (PH) is a rare condition that can occur as a primary disease process, Idiopathic Pulmonary Hypertension (IPH) or secondary to other disorders. In Familial IPH mutations have been identified in the bone morphogenetic protein receptor II…
In the present study, the function and the mechanism of action of RGS4, a member of a family of proteins called Regulators of G protein Signalling (RGS) was investigated. A C-terminal fluorescent tag on RGS4 confirmed that transiently transfected RGS4 was predominantly cytosolic…
Nrf2 is a transcription factor that, under conditions of chemical stress, is able to evade its cytosolic repression and translocate to the nucleus to initiate the transcription of a battery of cytoprotective genes, such as those involved in the detoxication of xenobiotics. Nrf2 …
Introduction. HIV-associated neurocognitive disorders appear to remain common despite access to antiretroviral therapy (ART). Penetration of ART into the central nervous system (CNS) is highly variable between drugs and between individuals. Cerebrospinal fluid (CSF) concentratio…
Human herpes virus 6 (HHV6) infects the majority of individuals in childhood, followed by a lifelong asymptomatic latent infection. However, in immunosuppressed individuals reactivation of HHV6 can cause significant clinical pathology. Recent successes with adoptive T cell thera…
Artemisinin-derived endoperoxide drugs find widespread employment as frontline treatment against malaria. Although evidence of their potential to express toxicity within a clinical setting remains limited, outcomes derived from animal studies attest their ability to induce neuro…
Acute pancreatitis (AP) is a leading cause for hospitalisation and has significant quality of life implications for the patient and cost implications for the National Health Service. Although most episodes of AP are mild and self-limiting, the severe form of the disease is assoc…