Studies Of Metabolites Of Synthetic Flavonols For The Treatment Of Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$207,440.00
Summary
Cardiovascular disease, including heart attack and stroke, is the leading killer of Australians. A promising new drug, NP202, can reduce the amount of tissue damaged from a heart attack; however, its mechanism of action remains obscure. NP202 is metabolized to a range of compounds, one of which is partly responsible for its beneficial effects. In this project we will identify other metabolites of NP202 and characterize their biological activity to gain insight into its mechanism of action.
Eco-RESIDE: An Economic Evaluation Of Urban Design As A Means Of Promoting Physical Activity
Funder
National Health and Medical Research Council
Funding Amount
$422,612.00
Summary
The significance of this project lies in the health problem that it seeks to address and the intervention that is being evaluated. Physical inactivity ranks second only to tobacco use in terms of the costs of diseases associated with behavioural risk factors. Declining rates of physical activity have been associated with increasing rates of obesity and overweight in Australian children and adults. The association that one sees between features of the urban environment and physical activity level ....The significance of this project lies in the health problem that it seeks to address and the intervention that is being evaluated. Physical inactivity ranks second only to tobacco use in terms of the costs of diseases associated with behavioural risk factors. Declining rates of physical activity have been associated with increasing rates of obesity and overweight in Australian children and adults. The association that one sees between features of the urban environment and physical activity levels suggests that urban planning guidelines may be a cost-effective means of promoting health and achieving other social objectives such as sustainable use of natural resources. Furthermore, not enough is known about the economic value of investing in health promoting interventions and this project is among the first to measure the costs and benefits of intervening at the environmental level. The information that it provides will be highly useful for local government and health service planners alike.Read moreRead less
Which Neurons Maintain Sympathetic Vasomotor Tone?
Funder
National Health and Medical Research Council
Funding Amount
$567,918.00
Summary
High blood pressure is a major risk factor for cardiovascular disease, a major burden of disease worldwide. High levels of nerve activity that cause the blood vessels to constrict elevating blood pressure are characteristic of hypertension. We do not know which brain cells set and maintain this nerve activity. We will identify these cells, determine how they function and what regulates them. Ultimately we could control these cells treating the cause of hypertension or when clinical need arises.
Neural Control Of Renal Function: Functionally Specific Populations Of Sympathetic Nerves
Funder
National Health and Medical Research Council
Funding Amount
$286,250.00
Summary
The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney wi ....The kidneys are supplied with a dense network of nerves. Working properly, these nerves help maintain normal filtering of the blood by the kidneys. Over-activity of the nerves going to the kidney is associated with congestive heart failure, liver cirrhosis, chronic renal failure and hypertension. We have recently made several major discoveries about these nerves. Our studies suggest, based on structural and functional evidence, that stimulation of subgroups of nerve fibers going to the kidney will causes different effects with in the kidney . We therefore suggest that salt excretion , the control of blood flow to the kidney and the release of hormones by the kidney can be seperately regulated by the nerves. Using techinques only practise in a handful of laboratories around the world, we aim to determine to how the nerves control kidney function normally. These studies will suggest new directions in which the renal nerves may be implicated in disease.Read moreRead less
Characterisation Of MiRNAs That Regulate Vascular Leakage.
Funder
National Health and Medical Research Council
Funding Amount
$167,493.00
Summary
Vascular permeability or leak is a major problem in diseases such as cancer and in cardiovascular diseases . MicroRNAs (miRNAs) are small control genes that influence dveleopment and disease. We have identified a miRNA cluster in endothelial cells, the cells that line the blood vessels, that is important in the control of vascular leak. This project is focused on understanding the impact of these miRNAs in disease.
Selectivity And Mode Of Action Of Rho-conopeptide TIA: A Novel Inhibitor Of Alpha1-adrenoceptors.
Funder
National Health and Medical Research Council
Funding Amount
$399,300.00
Summary
A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-cono ....A major obstacle to the development of safer and more effective treatments for cardivascular diseases and benign prostatic hyperplasia is the inability to find small molecules with sufficient specificity to be safe and effective. The applicant team brings together a unique set of complementary research interests and skills in using conotoxins to define, at the molecular level, how rho-conotoxins act at the alpha1-adrenoceptor, a major drug target for cardiovascualr and related diseases. Rho-conotoxins are novel peptide inhibitors of the alpha1-adrenoceptor that appear to act at an undescribed allosteric site. This Project will use rho-conotoxins and analogues to characterise structurally and functionally how and where this class of conopepides act. The structure activity relationship for rho-conotoxins will be established to guide the development of subtype specific inhibitors. Pairwise interactins between the alpha1-adrenoceptorand TIA will be used to dock TIA onto a homolgy model of the alpha1-adrenoceptor. The long-term goal of the project is to develop new and safer treatments for cardiovascular and related disorders.Read moreRead less
Role Of Epigenomic Changes In Conferring Hyperglycemic Memory
Funder
National Health and Medical Research Council
Funding Amount
$636,146.00
Summary
The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment h ....The major burden of type I diabetes remains its vascular complications including diabetes-accelerated athersclerosis. Despite improved glucose control, diabetic individuals develop complications as a result of prior poor glycemic control. Although the development and progression of these diabetic complications is strongly associated with mean levels of glucose, recent studies suggest that the deleterious effects of early exposure to high levels of glucose persist for years even after treatment has returned glucose levels towards normal.Read moreRead less
Preventing Recurrence Of Leg Ulcers In Older Adults With Peripheral Vascular Disease: Identifying Predictors And Evaluating Strategies.
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Peripheral vascular disease – disease of the arteries and veins in the limbs – leads to chronic leg ulcers for 1–4% of adults aged over 60. The ulcers are slow and difficult to heal and after healing, up to 70% recur, many within a few weeks. The aim of this research is to identify predictors and evaluate strategies to prevent recurrence of chronic leg ulcers; and improve our understanding of relationships between biology, localised disease and health in adults suffering from chronic leg ulcers.
Taking A Break For Brain Health: Interacting Effects Of Exercise Bouts With Breaks In Sitting Time On Cognitive And Cerebrovascular Function In Overweight Adults
Funder
National Health and Medical Research Council
Funding Amount
$775,055.00
Summary
Whether people do or do not exercise or not, there are serious health consequences – including adult-onset diabetes and heart disease – arising from the 7 to 10 hours of sitting that most Australian adults do each day. Exercise helps to delay Alzheimer's disease and other declines in brain function with ageing. This study will test whether, among overweight adults, combining exercise with breaking up prolonged sitting time can improve markers of brain health and mental functioning.
Early Events In Arteriolar Remodeling: Adaptation To Prolonged Vasoconstriction
Funder
National Health and Medical Research Council
Funding Amount
$415,750.00
Summary
Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes ....Small arteries, while acutely responding to their environment with changes in diameter to regulate local blood flow and pressure, also undergo structural adaptation or remodelling. These events occur over a range of time-frames and involve both non-genetically and genetically regulated events. Thus a contractile event, while initially decreasing vessel diameter, also activates longer time frame processes which can span from rearrangment of cellular junctions-contacts to overt structural changes within the vessel wall (for example thickening of the muscle layer). These adaptive processes may enable the forces of contraction to be maintained without continued energy expenditure and damage to the vessel per se. However, they can also contribute to long-term alterations in the control of blood pressure and perhaps contribute to states of hypertension as well as other common vascular diseases. For these studies we will use arterioles, isolated by microsurgical techniques, together with sophisticated computer and video-based approaches. These techniques allow arterioles to be studied under controlled conditions and relevant biochemical measurements performed. We will also use a cell model where cultured cells will be studied after defined periods of mechanical stimulation (for example stretch). Cells will be probed using a novel microscopic technique (atomic force microscopy) which enables the cell membrane to be studied with respect to changes in composition as well as physical characteristics (for example stiffness). The studies are relevant to our understanding of the normal adaptive processes occurring within blood vessels to control blood flow and pressure. The studies are also of direct relevance to our understanding of common vascular disease states including hypertension, complications of diabetes and chronic inflammatory disorders.Read moreRead less