Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stick ....Microparticles as effectors of microvascular alterations in brain inflammation. Cerebral malaria (CM) kills many children worldwide, but we do not understand why their small blood vessels in the brain become obstructed. We found that tiny elements detached from cell membranes, called microparticles (MP), are dramatically elevated in the blood during CM. Our results strongly suggest that these MP are important in CM development. We have found that some drugs block the release of MP and the stickiness of malaria parasites to blood vessels. Our project will tackle the conditions of MP production and define new drugs to prevent it. It also will explain how the brain becomes affected by high numbers of MP. Our results will cast new light on why the brain functions abnormally when its blood vessels become modified.Read moreRead less
Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Austra ....Molecular response to interferon beta treatment in multiple sclerosis. Inteferon beta (IFNb) is the frontline drug for treatment of multiple sclerosis. However, in many patients this expensive drug provides no benefit, resulting in unnecessary, uncontrolled disease progression, and in a waste of many millions of dollars each year. A common explanation for this treatment failure is the development of neutralising antibodies (NABs). We will establish the prevalence and effects of NABs in Australian patients, use novel techniques to identify biomarkers for IFNb response, evaluate the diagnostic and therapeutic value of the biomarkers, and develop a new test for NABs. Tailored use of this drug, and possible new therapeutic targets, will result, benefiting the patient and community.Read moreRead less
Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in t ....Central nervous system cytokines and morphine analgesia. Morphine remains the drug of choice for the management of moderate-to-severe pain, however its clinical effectiveness is compromised by the fact that morphine's analgesic (pain reducing) efficacy becomes less effective the more it is administered.. This project will examine how analgesic tolerance develops from a completely new approach: Namely, how stimulation of the immune system within the central nervous system is a crucial factor in the development of tolerance. Modulation of analgesia by the immune system has not been systematically studied and provides a potentially fertile ground for the development of new techniques in the management of clinical pain.Read moreRead less