A Temporal Profile Of Signaling Via Phosphorylation During Myocardial Ischemia - Reperfusion Injury
Funder
National Health and Medical Research Council
Funding Amount
$369,641.00
Summary
Cardiovascular disease (CVD) is the major cause of death in Australians and sequelae post-myocardial ischemia - reperfusion (I-R) are responsible for the greatest proportion of CVD-related mortality. Despite this burden, there is little known of the molecular events that mediate I-R. This project will utilize cutting-edge technology to elucidate the molecular signaling events that lead to I-R injury, as well as determine the basis for protection afforded by clinical pre- and post-conditioning.
Clinical Feasibility Study Of Omega-3 PUFA Therapy For The Reduction Of Post-cardiac Surgery Atrial Arrhythmias
Funder
National Health and Medical Research Council
Funding Amount
$442,092.00
Summary
The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be li ....The aim of this study is to determine the molecular and clinical impact of omega-3 polyunsaturated fatty acids (PUFA) pre-treatment 2 weeks before cardiac surgery in 150 patients. The outcome of this proposal will indicate proof of molecular concepts, clinical feasibility and specific design elements of a future, large scale, placebo controlled, prospective randomised trial of oral therapy with omega-3 polyunsaturated fatty acids (PUFA). Recently, omega-3 PUFA via fish diet was reported to be linked to low incidence of AF. The main aim is to provide a cheap and safe preventative therapy against post-operative atrial fibrillation (AF), a key heart rhythm disorder that occurs in at least 1 in 4 patients after heart surgery and increases post-operative complications, limits recovery and increases hospital stay and cost. Biochemical study elements are important to gain valuable insight into the molecular mechanisms (directly in human heart) that underlie post-operative heart rhythm disorder and may delineate new more precise molecular targets for therapy. No previous clinical study has ever examined whether omega-3 PUFA therapy prevents post-operative heart rhythm disorder. Use of 3g-day omega-3 PUFA pre-treatment in the surgical setting has been shown to be safe in a number of small studies, including our own. Our preliminary data indicates that therapy increases heart and blood content of omega-3 PUFA ~2-fold, and reduces the incidence of AF. Post-operative AF is an expensive resource burden in all cardiothoracic surgery units of Australian hospitals and targets key health priorities. Due to the non-patentable nature of omega-3 PUFA, significant industry based support for clinical research is limited. A positive outcome would rapidly pave the way for widespread use in elective surgery. Reduced length of hospital stay, cost-savings, and the increase in productivity as healthy individuals return to their communities would nationally repay the investment many fold.Read moreRead less
Neurocircuitry Of A Novel Gastrointestinal-circulatory Reflex
Funder
National Health and Medical Research Council
Funding Amount
$515,625.00
Summary
The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digesti ....The gastrointestinal tract receives about one third of the blood pumped around the body by the heart. This implies that the gut circulation plays a major role in blood pressure control. Gut blood flow changes according to the demands imposed by altered behavioural activity. Engagement in physical exercise results in increased blood flow to the working muscles of the limbs and diversion away from the gut. Alternatively, food consumption promotes an increase in blood flow to the gut to aid digestion. While this is a normal bodily process, there are also adverse implications of the re-distribution of blood flow: in the elderly compensation for these changes is often impaired and can result in low blood pressure and fainting. In addition, the incidence of angina-related heart pain is greater after food consumption and this may be associated with re-distribution of blood flow to the gut. Cholecystokinin (CCK), a hormone which is released from special cells that line the intestine, plays a role in the control of blood flow to the gut. We have developed the hypothesis that CCK acts on nerves which send a signal to the brain which, in turn, acting through other nerves, produces an increase in the flow of blood to the gut. This project is designed to study the nerve pathways in the brain which control this novel mechanism. We will record the activity of specific brain cells and nerves which are involved in the control of the blood supply to the gut. We will also examine which chemicals the brain cells and nerves use for communication with each other and so build up a model of the brain areas which are involved in gut blood flow control. This project will shed new light on the mechanisms of gut blood flow control and identify the associated brain pathways. The information will be of importance in the treatment of diseases of the circulation and food consumption-related cardiovascular changes in the elderly and obese as well as in sufferers of angina.Read moreRead less
Examining The Metabolic And Cognitive Deficits Caused By Insulin Resistance In The Ventral Striatum
Funder
National Health and Medical Research Council
Funding Amount
$400,372.00
Summary
Brain insulin resistance is thought to cause metabolic and cognitive deficits, but the underlying neural mechanisms remain elusive. This project addresses this gap in our knowledge by examining how brain insulin resistance disrupts the metabolic regulation of food intake and the cognitive control of actions. The outcomes will provide new insights in disorders characterised by brain insulin resistance such as obesity and dementia.
Schizophrenia is a serious and debilitating psychotic illness often characterized by delusions: fixed, false beliefs that preoccupy the patient and affect behaviour, and which are resistant to current drug treatments. This project investigates dysfunctions in belief mechanisms that allow delusions to form and be maintained. This will help clinicians design more effective programs of cognitive behavioural therapy for psychosis by allowing more focussed interventions to reduce delusions.
Neuroprotection Against Parkinson’s Disease With Remote Photobiomodulation
Funder
National Health and Medical Research Council
Funding Amount
$314,818.00
Summary
Treating the head of rodents with low-intensity 670nm light protects against Parkinson’s disease (PD), but the large size of the human skull and brain precludes clinical translation of this treatment. We have discovered that the brain is also protected when light is targeted at peripheral tissues (e.g. a limb), overcoming problems of delivery. This project aims to optimise this treatment and better understand how it works, to lay the scientific basis for a clinical trial.
Disorders Of Action Control And Learning-related Plasticity In The Basal Ganglia
Funder
National Health and Medical Research Council
Funding Amount
$434,874.00
Summary
Disorders of the basal ganglia have long been known to produce severe cognitive symptoms including a deficit in the control of voluntary action. This project will assess the learning processes through which humans and other animals acquire such actions. We will systematically investigate changes in cellular plasticity associated with the acquisition of new actions to establish the role that it plays in action control under normal and pathological conditions.