Ankle Brachial Index Determination By Oscillometric Method IN General Practice (ABIDING)
Funder
National Health and Medical Research Council
Funding Amount
$128,935.00
Summary
People who have peripheral arterial disease (PAD) have blockages of the circulation to their legs. If you have PAD you have blood vessel disease throughout the body and are very likely to have a heart attack or experience a stroke. PAD can be diagnosed simply by comparing the blood pressure in the arms and legs. Until now this needed a special costly instrument. New blood pressure machines can do this without this instrument. We want to know how reliably this can be done by practice nurses.
Fenofibrate In The Management Of AbdoMinal Aortic AnEurysm (FAME)
Funder
National Health and Medical Research Council
Funding Amount
$455,713.00
Summary
Approximately 5% of men and 1% of women aged over 60 years develop weakening of the main abdominal artery. Currently the management of artery weakening is focused on surgery with no effective medications available. In this study we will assess whether a drug which limits artery weakening in pre-clinical testing also shows evidence of inhibiting processes important in artery damage in patients. We believe this is a critical next step in the assessment of a promising new treatment.
Mechanisms, Biomarkers And New Therapies For Abdominal Aortic Aneurysm
Funder
National Health and Medical Research Council
Funding Amount
$551,370.00
Summary
Approximately 5% of men and 1% of women aged over 60 years develop artery weakening. The management of artery weakening is currently focused on radiological imaging and surgery. In this fellowship work will be performed to better understand the mechanisms involved in artery weakening, assess new ways of monitoring disease progression and evaluate new medical therapies. It is envisaged that the work will identify a number of new management stratergies for this common condition.
Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessel ....Our studies are aimed at examining how blood flow and pressure is controlled in the various tissues of the body. In particular, we hope to improve our understanding of how blood flow is matched to local metabolic requirements and how a constancy of conditions can be maintained despite changes in overall blood pressure. This ability to control local blood flow occurs through the ability of very small arteries to rapidly adjust their diameters through vasoconstriction or vasodilatation. The vessels can thus act as valves regulating the transfer of blood flow and pressure to smaller vessels downstream. One particular response that small arteries exhibit is the ability to constrict when pressure within the vessels increases. The increase in pressure appears to stretch the vessel wall which in turn initiates a series of mechanical and biochemical steps that ultimately lead to contraction of muscle cells within the vessel wall. By contracting, the vessels limit the increase in downstream flow and pressure that would be expected to occur. The vessels being studied are very small, typically less than 100 micron. They are studied under isolated and controlled conditions using microscope and computer-based imaging techniques. While this allows us to directly monitor changes in vessel diameter to various stimuli (e.g. a change in pressure) we have also had to miniaturize biochemical measurements so we can understand the chemistry which underlies these vasoconstrictor responses. Understanding of how these local blood regulatory mechanisms occur is not only relevant to our understanding of the normal situation but is also vital to understanding disease states. For example, this work is very relevant to common cardiovascular disorders such as hypertension. It is hoped that a detailed understanding of the biochemical pathways by which small arteries contract will allow the design and targeting of pharmaceutical approaches for treatment of vascular disease states.Read moreRead less
Developing Improved Management For Peripheral Artery Diseases
Funder
National Health and Medical Research Council
Funding Amount
$569,219.00
Summary
~1 million Australians have peripheral artery disease. The current application is for a Practitioner Fellowship to support my research aimed at improving care of artery disease. The aim of the work is to develop improved management approaches for patients with blocked and weakened arteries. This work is particularly important given the recognised management deficiencies for patients with artery disease and the relative little research being undertaken in this area.
Bioengineering Of Cyclotides With Angiogenic Properties
Funder
National Health and Medical Research Council
Funding Amount
$488,273.00
Summary
Atherosclerosis, a gradual clogging of the arteries, is the single leading cause of death in Australia, Europe, the USA and Japan. Coronary heart disease (CHD; clogging of the coronary arteries), while secondary to atherosclerosis in most of the world, accounts for nearly 2 million deaths per year in Europe alone. In Australia CHD is the single leading cause of death. This project is aimed at developing lead molecules for the development of therapeutics capable of stimulating revascularization ( ....Atherosclerosis, a gradual clogging of the arteries, is the single leading cause of death in Australia, Europe, the USA and Japan. Coronary heart disease (CHD; clogging of the coronary arteries), while secondary to atherosclerosis in most of the world, accounts for nearly 2 million deaths per year in Europe alone. In Australia CHD is the single leading cause of death. This project is aimed at developing lead molecules for the development of therapeutics capable of stimulating revascularization (that is, opening up blocked vessels to improve blood flow) of tissues with slow or retarded circulation. Such therapeutics would improve the treatment of atherosclerosis and CHD. Peptides, small proteins, are generally not stable enough to be used as drugs. In this project we plan to engineer protein molecules based on an unusually stable family of proteins, known as the cyclotides. We will chemically synthesise analogues of cyclotides that have been altered to incorporate the activities of less stable small peptides that are able to induce therapeutic angiogenesis. Given the prevalence of CHD, the development of effective therapeutics could have a profound impact on the economic cost of the disease, which in the USA amounts to US$133.2 billion per year. This project involves collaboration between researchers from the Institute for Molecular Bioscience, who have expertise in drug design and protein chemistry, and researchers from the Centre for Research in Vascular Biology, who have expertise in vascular biology and vessel engineering. Both of these institutes are part of the University of Queensland.Read moreRead less
Local Microvascular Regulatory Mechanisms In Diabetes: Relevance To Neuropathy
Funder
National Health and Medical Research Council
Funding Amount
$212,036.00
Summary
In diabetes mellitus, the excessive levels of sugar in the blood may cause changes in metabolic processes within cells that lead to disturbances in the function of the circulatory and nervous systems. Such disturbances have been shown to occur in the early stages of diabetes and ultimately lead to longterm consequences including poor wound healing (often culminating in limb amputations), increased risk of blindness, kidney disease and heart failure. At present it is not possible to restore norma ....In diabetes mellitus, the excessive levels of sugar in the blood may cause changes in metabolic processes within cells that lead to disturbances in the function of the circulatory and nervous systems. Such disturbances have been shown to occur in the early stages of diabetes and ultimately lead to longterm consequences including poor wound healing (often culminating in limb amputations), increased risk of blindness, kidney disease and heart failure. At present it is not possible to restore normal metabolism, leaving patients at risk of developing complications involving the circulatory and nervous systems. An understanding of the processes involved in the development of such complications would allow alternate treatment strategies to be devised in order to improve the quality of life and life expectancy of diabetic patients. The events leading to abnormalities in the function of the circulatory and nervous systems are uncertain, however, studies have demonstrated that in diabetes there may be an insufficient blood supply to nerves and this would be expected to cause nerve damage. At present, our understanding of the factors involved in regulating blood flow to nerves is limited. The studies described in this proposal are aimed at testing the hypothesis that nerve blood vessels are themselves involved in the regulation of flow through an intrinsic ability to change their diameter in response to tissue demands and that in diabetes alterations in the capacity of nerve blood vessels to constrict or dilate compromises their role in the control of nerve blood flow . Information obtained from these studies will improve our understanding of the early disturbances in the function of circulatory and nervous systems leading to alterations in blood flow which precede the development of overt changes characteristic of the complications associated with diabetes. This will provide insight into developing new treatment strategies for diabetic patients.Read moreRead less
The Effect Of Stress/strain And Fatigue Fracture Sites On Durability Of Modular Aortic Endografts And Arterial Walls
Funder
National Health and Medical Research Council
Funding Amount
$300,919.00
Summary
Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxi ....Aneurysmal disease is an age related phenomenon. The mean life expectancy of western populations has doubled in 100 years because of the reduction in deaths from preventable and treatable diseases, and prolongation of life with chronic and incurable diseases. The older community (>65 years) continues to be active and productive contrary to prior predictions. Aneurysmal disease has emerged as a result of the changing pattern of diseases in the community. As with many other diseases, prophylaxis against aneurysmal disease is the most effective approach since 80% of those that rupture will result in death. Endoluminal grafting provides a much less invasive procedure and provides an attractive and elegant alternative to open surgery. The danger is that structural strengths will be compromised with failures due to lack of strength and inadequate device durability. The most practical endografts are those that are built up from modules but vulnerable sites affected by fatiguing and disruptive forces are being identified, in particular where a tube divides into two outflow channels – the bifurcation - and joins. To improve and protect the current device, and enable sound engineering for future devices, we need to know the nature, magnitude and location of these forces. The existing collaboration with medical specialist, Cook Aust., the Advanced Fluid Dynamics Laboratory (CSIRO, Melb.) and University of WA combines a multidisciplinary team working towards the design and durability of the next generation of endoluminal devices and percutaneous insertions. While Australia is at the forefront of development, its current place in the market can only be maintained by further product development. Optimising and improving endoluminal grafts will reduce the suffering of major surgery while prolonging a higher quality of life with a much less invasive procedure whose long-term effectiveness, and thereby acceptance is dependent upon reliable durability.Read moreRead less
Targeting Arginase In Peripheral Arterial Occlusive Disease
Funder
National Health and Medical Research Council
Funding Amount
$243,945.00
Summary
Peripheral artery occlusive disease causes narrowing of large peripheral blood vessels which can result in severe pain, gangrene and stroke. Its prevalence is steadily increasing in western countries. This proposal aims to characterize the role of an enzyme (arginase) in PAOD and determine whether it may be a new drug target for treatment of this disease.