The Interactions Between Sleep Disordered Breathing, Metabolic Syndrome And Vascular Risk.
Funder
National Health and Medical Research Council
Funding Amount
$361,030.00
Summary
We will look at two common diseases in the Australian community, the metabolic syndrome and obstructive sleep apnoea (OSA), and explore the common links they have to the risk of disease of the heart and blood vessels. We will then take a group of patients who have both diseases, treat the OSA, and assess the impact of this treatment on their cardiovascular health. Metabolic syndrome is a term given to patients who have high blood sugar, obesity, high lipid levels and raised blood pressure. The A ....We will look at two common diseases in the Australian community, the metabolic syndrome and obstructive sleep apnoea (OSA), and explore the common links they have to the risk of disease of the heart and blood vessels. We will then take a group of patients who have both diseases, treat the OSA, and assess the impact of this treatment on their cardiovascular health. Metabolic syndrome is a term given to patients who have high blood sugar, obesity, high lipid levels and raised blood pressure. The Australian Bureau of Statistics estimates that half the Australian population is overweight, and US studies suggest that nearly of the adult population has metabolic syndrome. This is strongly linked to diseases of the heart and blood vessels, eg heart attacks and stroke. Patients with OSA stop breathing during the night when their throat closes over. The blood oxygen falls, which causes the patient to wake momentarily, then start breathing again. This cycle repeats itself throughout the night. The usual treatment is an air pump (CPAP) connected to a nose mask, which blows air into the throat and prevents closure. This disease is strongly linked to high blood pressure, raised blood sugar levels and heart and blood vessel disease. Patients with the metabolic syndrome will have an overnight sleep study to diagnose OSA, giving the likelihood of having OSA in this group of patients. They will then have extensive investigations of the health of their heart and blood vessels. From these, we will determine which aspects of OSA are more likely to result in cardiovascular disease. Those patients diagnosed with OSA will be treated with CPAP for 3 months. Half the patients will receive normal CPAP; the other half will receive ineffective CPAP. They will then be re-tested and we will compare the results before and after treatment. Thus we will measure likelihood of OSA in this large group of patients, and the health benefits they may gain from treatment of their OSA.Read moreRead less
The Nutritional Geometry Of Ageing In A Rodent Model
Funder
National Health and Medical Research Council
Funding Amount
$979,269.00
Summary
A central belief in ageing research is that eating fewer calories prolongs life, and that the source of calories (carbohydrate, fat or protein) is irrelevant. However, a critical assessment indicates that this conclusion is premature. We will use recent techniques in nutrition to define for the first time in mammals the relationship between diet and ageing in a normal and a prematurely ageing strain of mice. The project will provide a novel nutritional approach for promoting healthy ageing.
Improving Breathing Support For Newborn Infants In Non-Tertiary Centres: The HUNTER Trial
Funder
National Health and Medical Research Council
Funding Amount
$1,203,844.00
Summary
Every year in Australia, thousands of newborn babies have breathing difficulties. Our trial will study a new, simple method of providing breathing support to newborn babies in special care nurseries, called high-flow (HF). HF is cheaper, easier to use, and more comfortable for babies than the current standard treatment, called CPAP. If HF is as good as CPAP at supporting babies' breathing, it will change practice in Australia and around the world.
My projects are associated with three research themes: psychological stress, obesity and hypertension. While these projects may appear diverse they are linked, both in terms of the significant co morbidity that they share, and that the underlying pathologies are initiated and sustained, at least in part, by disturbances in sympathetic nervous regulation. My research program will focus on these conditions and, in their content, will aim to develop and implement improved treatment srategies in the ....My projects are associated with three research themes: psychological stress, obesity and hypertension. While these projects may appear diverse they are linked, both in terms of the significant co morbidity that they share, and that the underlying pathologies are initiated and sustained, at least in part, by disturbances in sympathetic nervous regulation. My research program will focus on these conditions and, in their content, will aim to develop and implement improved treatment srategies in these areas of major clinical need.Read moreRead less
Old age is the main risk factor for atherosclerosis, which is the main cause of mortality and morbidity in the World. We found age-related changes in the microcirculation of the liver called pseudocapillarization that provide a mechanism linking old age with atherosclerosis. Pores in the endothelium called fenestrations disappear, impairing the ability of the liver to breakdown fats. New therapies to treat and prevent age-related pseudocapillarization are being developed.
Investigating Role Of Insulin Resistance And Sympathetic Nervous System In Metabolic Features Of PCOS
Funder
National Health and Medical Research Council
Funding Amount
$150,468.00
Summary
PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences assoc ....PCOS affects 9-18% of Australian reproductive aged women. Whilst reproductive features are prominent, PCOS has major psychological and metabolic consequences. Emerging data implicate the involvement of the sympathetic nervous system in PCOS. The aim of this PhD is to investigate the role of the sympathetic nervous system in insulin resistance and other metabolic features of PCOS and determine whether modification of this system's activity will favorably influence the metabolic consequences associated with PCOS.Read moreRead less
Genetic And Molecular Dissection Of Laterality In The Developing Heart
Funder
National Health and Medical Research Council
Funding Amount
$379,370.00
Summary
Vertebrate animals display an external bilateral symmetry. However, most internal organs are located asymmetrically and show profound left-right structural asymmetries during development. For each species, these laterality characteristics are constant. Inherited laterality disorders occur in humans and, although rare, are associated with high mortality rates due to discordant cardiovascular development. Moreover, subtle anomalies of laterality may underlie a host of congenital heart abnormalitie ....Vertebrate animals display an external bilateral symmetry. However, most internal organs are located asymmetrically and show profound left-right structural asymmetries during development. For each species, these laterality characteristics are constant. Inherited laterality disorders occur in humans and, although rare, are associated with high mortality rates due to discordant cardiovascular development. Moreover, subtle anomalies of laterality may underlie a host of congenital heart abnormalities. In early embryogenesis, the newly-formed heart tube loops to the right, an event which establishes the correct alignment of the future cardiac chambers. The direction of heart looping is determined by genetic pathways that establish laterality in the early embryo. A component of this pathway is a TGFbeta-family signalling molecule, nodal, which is activated on the left side of the forming heart and other organs. Nodal then activates the transcription factor gene Pitx2. The aim of this project is to examine the consequences of genetic inactivation of the mouse nodal and Pitx2 genes in the heart, and to discover cardiac genes downstream of these genes. We will specifically test the hypothesis that laterality contributes to heart chamber formation in addition to setting the direction of looping. Ablation of these genes in the whole embryo leads to complex defects that preclude analysis of their functions in the heart. To achieve heart-specific deletion, we will use a conditional gene ablation technology that exploits the bacteriophage recombinase, Cre. Genes downstream of Pitx2 and Nodal will be discovered using microarray technology, which allows us to screen exhaustively for changes in gene expression between different tissues. This project will help us solve the complex genetic basis of congenital cardiac abnormalities in humans, and will contribute to our understanding of how heart chambers form, potentially useful in stem cell-based therapies for the failing heart.Read moreRead less
Physiological, Biological And Genetic Abnormalitities Associated With The Postural Tachycardia Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$462,290.00
Summary
Postural Orthostatic Tachycardia Syndrome (POTS) is a clinical syndrome characterized by the development of excessive tachycardia (heart rate increases by 30 beats or more per min) when the upright position is assumed. The condition is accompanied by weakness, dizziness, presyncope or fainting. POTS has only recently come to international medical attention as the number of patients with the condition is steadily rising. The symptoms and ongoing disability in POTS appear to primarily result from ....Postural Orthostatic Tachycardia Syndrome (POTS) is a clinical syndrome characterized by the development of excessive tachycardia (heart rate increases by 30 beats or more per min) when the upright position is assumed. The condition is accompanied by weakness, dizziness, presyncope or fainting. POTS has only recently come to international medical attention as the number of patients with the condition is steadily rising. The symptoms and ongoing disability in POTS appear to primarily result from a supernormal reflex sympathetic activation on standing, in ways which are readily apparent for some symptoms, such as tachycardia, but obscure for others, such as postural syncope in the absence of postural hypotension. Poorly defined diagnostic criteria and the likelihood of multiple causes have made it difficult to clarify the underlying pathophysiology of POTS. In this project I will investigate the sympathetic nervous system response to head-up tilt in patients with POTS as well as possible genetic and epigenetic mechanisms which might underpin the syndrome. Preliminary results are encouraging and merit to be taken further.Read moreRead less