Characterization Of Sex-Specific Differences In Cardiovascular Adaptation In The First Three Years Of Life
Funder
National Health and Medical Research Council
Funding Amount
$567,725.00
Summary
Male babies born significantly premature are up to twice likely to die than females. The reasons for this are unknown. This study will determine the cardiovascular differences in male and female babies born preterm and will examine how they adapt over the first 5 days. Defining the mechanisms that contribute to the difference in mortality between the sexes will also show how changes starting around birth affect the way the blood pressure system functions for life, a major lifetime stroke risk.
Temporal And Spatial Regulation Of Caspases In Development And Metamorphosis
Funder
National Health and Medical Research Council
Funding Amount
$369,072.00
Summary
Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in g ....Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in general to maintain the correct number of cells in the body. As such, dysregulation of apoptosis is associated with the pathogenesis of a wide array of diseases such as autoimmune diseases, many forms of cancer and neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), heart disease, ischaemia and other conditions. To understand, manage and treat disorders that result from aberrant apoptosis, we need to know at molecular and cellular level, how apoptosis is brought about and how it is regulated. We have been studying these processes in detail for several years. Central to the apoptotic execution of cell death are a group of proteases that target many cellular proteins for specific cleavage. The activation of these proteases is the crucial step in the initiation of apoptosis and therefore each cell has developed complex ways to control this process. If we understand how these regulatory mechanisms operate, we can then formulate strategies that are targeted towards pathologies involving abnormal apoptosis. Various molecules that are involved in the execution and regulation of apoptosis are potentially excellent targets for therapeutic intervention in a number of disorders and will lead to the development of novel drugs for the treatment and prevention of many pathological conditions. In the present proposal, we aim to study what type of caspases are involved in sculpting of various organs and tissues during development.Read moreRead less
Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in g ....Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in general to maintain the correct number of cells in the body. As such, misregulation of apoptosis is associated with the pathogenesis of a wide array of diseases such as autoimmune diseases, many forms of cancer and neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), heart disease, ischaemia and other conditions. To understand, manage and treat disorders that result from aberrant apoptosis, we need to know at molecular and cellular level, how apoptosis is brought about and how it is regulated. We have been studying these processes in detail for several years. Central to the apoptotic execution of cell death are a group of proteases that target many cellular proteins for specific cleavage. The activation of these proteases is the crucial step in the initiation of apoptosis and therefore each cell has developed complex ways to control this process. If we understand how these regulatory mechanisms operate, we can then formulate strategies that are targeted towards pathologies involving abnormal apoptosis. Various molecules that are involved in the execution and regulation of apoptosis are potentially excellent targets for therapeutic intervention in a number of disorders and will lead to the development of novel drugs for the treatment and prevention of many pathological conditions.Read moreRead less
Temporal And Spatial Regulation Of Caspases In Development And Metamorphosis
Funder
National Health and Medical Research Council
Funding Amount
$473,250.00
Summary
Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in g ....Cell death by a special process called apoptosis is a means of deleting unwanted and harmful cells from the body. Extensive apoptosis occurs during foetal development which is required to get rid of many excess cells produced during the growth of the embryo. Selective apoptosis is also essential for the formation of different tissues and organs in developing foetus. In the adult, apoptosis is required for proper functioning of the immune system, to remove virus infected and cancer cells and in general to maintain the correct number of cells in the body. As such, misregulated apoptosis is associated with the pathogenesis of a wide array of diseases such as autoimmune diseases, many forms of cancer and neurodegenerative disorders (such as Alzheimer's and Parkinson's diseases), heart disease, ischaemia and other conditions. To understand, manage and treat disorders that result from aberrant apoptosis, we need to know at molecular and cellular level, how apoptosis is brought about and how it is regulated. We have been studying these processes in detail for several years. Central to the apoptotic execution of cell death are a group of proteases that target many cellular proteins for specific cleavage. The activation of these proteases is the crucial step in the initiation of apoptosis and therefore each cell has developed complex ways to control this process. In the present proposal, we aim to study regulation of caspases that are involved in developmental apoptosis. Furthermore, we plan to identify proteins that are responsible for the regulation of caspase activation.Read moreRead less
Salt And Cardiovascular Disease: Does Acute Salt-Sensitivity Convey Greater Cardiovascular Risk?
Funder
National Health and Medical Research Council
Funding Amount
$597,578.00
Summary
Salt intake of Australian adults is 10X more than required. Further, salt intake in very young children is alarmingly high secondary to high consumption of salty snacks and processed food. High dietary salt intake has been associated with increased cardiovascular disease and death. We will examine the cardiovascular risks for adults and children on a high salt diet and examine whether switching to a low salt diet ameliorates the high blood pressure and heart disease caused by high salt diets
Hypothalamic Regulation Of Cardiovascular Function In Hypertension And Stress
Funder
National Health and Medical Research Council
Funding Amount
$570,880.00
Summary
Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In ....Blood pressure is controlled to a large extent by nerves, known as sympathetic nerves, that supply the heart and blood vessels. The activity of sympathetic nerves is commonly increased in people with high blood pressure, particularly younger patients. This has the effect of constricting blood vessels and increasing heart rate, which places an additional load on the heart, and increasing the risk of heart attacks and stroke. Sympathetic nerves are also activated strongly in response to stress. In some people stress can trigger an extreme reaction, called a panic disorder, characterised by intense sympathetic activation, which also increases the risk of heart attacks. A region in the brain called the hypothalamus plays a key role in generating these increases in sympathetic nerve activity. This project aims first to identify the precise region or regions in the hypothalamus that are responsible for causing increased sympathetic activity in high blood pressure, and also in response to acute stress. There is also evidence from studies in humans that drugs which act on a particular type of receptor in the brain (called a serotonin receptor) can strongly inhibit the normal response to stress. We also aim to determine exactly where and how such drugs work. These studies may lead to much more effective treatments for high blood pressure and stress-related disorders.Read moreRead less
Sympathetic Nervous System Contribution To Hypertension : CNS Pathways, Neurotransmitters And Neuroeffector Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$450,750.00
Summary
High blood pressure (hypertension) is a major public health problem in Western society with approximately 20% of adults affected. If left untreated, serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyle, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely d ....High blood pressure (hypertension) is a major public health problem in Western society with approximately 20% of adults affected. If left untreated, serious damage to organs can occur and the risk of sudden cardiac death or stroke is greatly increased. While many factors contribute to the development of hypertension such as lifestyle, genes, diet, weight and exercise levels, a common feature in the early stages is an overactive nervous system in the kidney and in the heart which is most likely due to altered signals from the brain. We need to understand why this occurs. One possibility is that renin (a chemical released from the kidney) that is known to control body fluid, also acts in the brain to increase nerve activity to the kidney and heart and in this way contributes to high blood pressure. It does this indirectly by producing another hormone called angiotensin. Our research has shown that in conditions where the kidney releases excess of the hormone renin, which may occur if the blood supply to the kidney is reduced, a change occurs in the way in which the nervous system affects blood pressure. The nervous system is activated to increase the release of renin from the kidney. The effect of this is to make blood pressure increase further in what can become a vicious circle. At present it is not understood why and how this change occurrs. The major thrust of this project is to determine the mechanims by which the renal hormones signal the central nervous system to change the nature of the nervous activity back to the kidney. We want to know what parts of the brain are involved, how the nature of the activity in the nerves changes and also how the nervous control of the kidney changes (i.e. how the kidney changes its responsivness to the nerve activity). Because similar processes probably occur in nearly all forms of high blood pressure, our results will greatly improve our understanding of how this dangerous condition develops.Read moreRead less
Hypertension (high blood pressure) is the commonest chronic condition in western societies, and can lead to strokes, heart attacks and kidney failure. In a disease known as primary aldosteronism (PAL), hypertension results from the excessive production of the salt-retaining hormone, aldosterone, by the the body's adrenal glands. In some patients, this is due to the growth of an aldosterone-producing adrenal tumour. Recent work performed within the Hypertension Unit at Greenslopes Hospital and co ....Hypertension (high blood pressure) is the commonest chronic condition in western societies, and can lead to strokes, heart attacks and kidney failure. In a disease known as primary aldosteronism (PAL), hypertension results from the excessive production of the salt-retaining hormone, aldosterone, by the the body's adrenal glands. In some patients, this is due to the growth of an aldosterone-producing adrenal tumour. Recent work performed within the Hypertension Unit at Greenslopes Hospital and continued by these investigators within the Hypertension Unit at Princess Alexandra Hospital has shown that PAL is the commonest potentially curable form of hypertension, accounting for at least 5% and possibly 10% of patients. Several lines of evidence accumulated by these investigators, including the detection of a new familial variety of PAL (Familial Hyperaldosteronism Type II or FH-II), suggest that PAL is a genetic disorder. The study sets out to locate the genetic defect causing PAL by comparing genetic material collected from affected members of these families with that from non-affected members, and by comparing genes from patients with PAL with those of unrelated, unaffected individuals. Once the genetics of this condition is understood, affected persons can be detected early in life, and even at birth, and the ill-effects of their developing conditions prevented.Read moreRead less
Improved Gene Therapy Strategies For Primary Pulmonary Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$370,517.00
Summary
Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened bo ....Many people develop problems with the blood vessels in the lungs, which then leads to a narrowing of these vessels and consequently a back-pressure strain on the heart. These disorders can arise from inherited diseases of the blood vessels themselves, or from accquired lung disease (for example due to smoking or chronic infections). At present there are few treatments which have any benefits for these patients and many must undergo lung or heart-lung transplantation. This project is desigened both to find out new information about the disease process that affects the lung blood vessels and to offer a strategy for new treatments. The project will use a crippled form of the cold virus to deliver genes to the lining of the lung blood vessels, then see what impact that has on the pressure within the vessels and the ways in which they respond to certain stresses. These studies will be carried out using laboratory animals. If successful, it may be possible to eventually design such viruses to deliver genes which have a helpful therapeutic impact on the disease in patients.Read moreRead less
HYPE: Hypertension And Preeclampsia After Non-steroidal Use For Post-partum Pain Relief; A Prospective, Stratified, Randomised Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$174,504.00
Summary
After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms be ....After caesarean delivery of a baby most women will require analgesia. Traditionally anti-inflammatory medications (eg.diclofenac) have been given. Evidence exists that this medicine may increase the mother�s blood pressure. This can result in a longer hospital stay, blood pressure medications and exposure to the risks of high blood pressure (eg.stroke and increased bleeding). This study examines the effect of diclofenac on the mother�s blood pressure, analgesia and investigates the mechanisms behind the increased blood pressure.Read moreRead less