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Assessment Of The Mechanisms Involved And Severity Of Arterial Disease In Insulin Resistant States
Funder
National Health and Medical Research Council
Funding Amount
$64,631.00
Summary
Type 2 Diabetes is a major risk factor towards atherosclerosis or blood vessel narrowing. This can lead to vascular complications such as heart attacks, strokes and amputations. This research aim to examine the relationship between some of the mechanisms and their contribution towards vascular disease in the progression from normal health, through insulin resistance to diabetes. This understanding will provide diagnostic tools and treatment targets for diabetic vascular disease.
Mechanisms Linking Insulin-mediated Muscle Capillary Recruitment And Glucose Uptake
Funder
National Health and Medical Research Council
Funding Amount
$315,990.00
Summary
A number of studies over recent years including our own have suggested that insulin acts in normal humans and animals to improve blood supply to muscle and that a contributing factor to Type 2 diabetes is an impaired ability of insulin to achieve this effect. Our key contribution to this field is the finding that insulin acts to alter blood flow in muscle to improve access for itself and nutrients such as glucose. This discovery of blood flow redistribution in muscle was made possible by newly d ....A number of studies over recent years including our own have suggested that insulin acts in normal humans and animals to improve blood supply to muscle and that a contributing factor to Type 2 diabetes is an impaired ability of insulin to achieve this effect. Our key contribution to this field is the finding that insulin acts to alter blood flow in muscle to improve access for itself and nutrients such as glucose. This discovery of blood flow redistribution in muscle was made possible by newly developed in-house methods. Using these methods we now wish to explore (a) the mechanism by which insulin mediates this effect and (b) when this effect of insulin to improve muscle blood flow is impaired in diabetes, how it might be recovered. We expect to find that insulin-mediated capillary recruitment in muscle results from a signal substance released from muscle that permeates nearby tissue reacting with the blood vessels to improve blood flow. It is also expected that new therapeutic approaches for enhancing insulin action in muscle and targeted at the blood vessels will be identified.Read moreRead less
Angiopoietin-2, Aortic Inflammation And Cardiovascular Events
Funder
National Health and Medical Research Council
Funding Amount
$332,161.00
Summary
Based on detailed preliminary data, we plan to investigate the importance of a novel protein (the cytokine angiopoietin-2) in cardiovascular disease. The results of this study will clarify the role of this cytokine in vascular pathology and may provide an important target for novel therapy and-or diagnostic markers for cardiovascular disease progression.
Importance Of Pulmonary Venous Electrophysiology In The Development Of Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$196,219.00
Summary
(ii) Transplant rejection can be inhibited by expression in the graft of CTLA4-Fc a reagent that blocks T cell co-stimulation enhancing allo-graft acceptance (Transplantation 2000 69:1806). High-level expression for over 100 days is expected to correlate with optimal graft acceptance. Our ability to use Kunjin to express beta galactosidase for several months in vivo without inflammation illustrates the potential for this approach (CIB ref 15). Initially we intend to use P815 cells injected i.p. ....(ii) Transplant rejection can be inhibited by expression in the graft of CTLA4-Fc a reagent that blocks T cell co-stimulation enhancing allo-graft acceptance (Transplantation 2000 69:1806). High-level expression for over 100 days is expected to correlate with optimal graft acceptance. Our ability to use Kunjin to express beta galactosidase for several months in vivo without inflammation illustrates the potential for this approach (CIB ref 15). Initially we intend to use P815 cells injected i.p. into C57BL-6, where they are usually rejected within a few days. In contrast, P815 cells with Kunjin replicon-mediated CTLA4-Fc expression should survive for an extended period. Graft survival is easily monitored using FACS and anti-H-2d antibodies.Read moreRead less
Molecular Mechanisms Of Cardiac Function And Disease
Funder
National Health and Medical Research Council
Funding Amount
$10,053,131.00
Summary
Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as wel ....Adult-onset heart disease remains the leading cause of death and disability in our society, with almost 2 million Australians affected. Furthermore, structural heart malformations are the most common type of abnormality at birth and the leading cause of deaths in infants dying from non-infectious causes. Many of these problems are due to defects in the development, repair and-or function of heart muscle cells or cardiomyocytes. Thus, we propose to understand, in fine detail, cardiomyocyte as well as integrated heart development, biology, physiology and function as a prerequisite for the development of major advances in the prevention and treatment of these disorders.Read moreRead less
Linkage And Sequence Analysis Of A Locus On The X Chromosome That Contributes To Population Variation In Blood Pressure
Funder
National Health and Medical Research Council
Funding Amount
$458,080.00
Summary
High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic obs ....High blood pressure is a prominent risk factor for heart attack and stroke which kill over 30,000 Australians each year. Blood pressure is determined by the combination of inherited predisposition and lifestyle factors such as diet. Understanding these combinations offers new opportunities for reducing the incidence of cardiovascular disease. We have discovered recently that genes on the sex chromosome known as chromosome X appear to be linked with high blood pressure. Building on this basic observation, we shall extend our studies to place the findings beyond reasonable doubt. We shall investigate the gene sequences in this region of the X chromosome to discover what changes in the DNA code might lead to high blood pressure and how this might happen. Our studies capitalise on the recent release of the draft sequence of the entire human genome. These investigations in almost 800 healthy volunteer families have the potential to provide new opportunities for prevention and treatment of cardovascular disease.Read moreRead less
A Randomised Double Blinded Placebo Controlled Trial Of Adrenaline In Cardiac Arrest.
Funder
National Health and Medical Research Council
Funding Amount
$200,500.00
Summary
It is estimated that in excess of 30,000 Australians per year suffer a cardiac arrest, mostly occurring outside of hospital. This sudden and often unpredictable event commonly occurs as a result of acute heart disease, injury, drug overdose and many other illnesses which affect both males and females of all ages. Unfortunately, the survival of those suffering a cardiac arrest remains poor. Best evidence to date suggests overall survival from cardiac arrest to be in the order of about 5%. While t ....It is estimated that in excess of 30,000 Australians per year suffer a cardiac arrest, mostly occurring outside of hospital. This sudden and often unpredictable event commonly occurs as a result of acute heart disease, injury, drug overdose and many other illnesses which affect both males and females of all ages. Unfortunately, the survival of those suffering a cardiac arrest remains poor. Best evidence to date suggests overall survival from cardiac arrest to be in the order of about 5%. While the survival for those suffering cardiac arrest remains poor, the rapid initiation of cardiopulmonary resuscitation (CPR) and defibrillation has been clearly shown to improve outcome. While defibrillation and CPR have been shown to be beneficial, the use of vasoactive drugs such adrenaline has not been proven to improve survival in cardiac arrest. This is despite adrenaline being internationally recommended as first line drug therapy in the advanced life support (ALS) management of cardiac arrest. It is now well acknowledged that clinical trials need to be undertaken to determine the clinical effects of adrenaline when used for cardiac arrest. The purpose of this study is to randomise patients suffering a cardiac arrest to receive either adrenaline (according to standard ALS guidelines) or a placebo. All other care for both groups will be the same and in accordance with current ALS guidelines. In this way we will be able to determine the effects of adrenaline on outcome, particularly survival, following cardiac arrest. The study will run for three years and involve all cardiac arrests attended by the Ambulance Service in Perth.Read moreRead less
Centre For Training In Clinical Cardiovascular And Cerebrovascular Research
Funder
National Health and Medical Research Council
Funding Amount
$2,000,000.00
Summary
This Centre proposes to expand its highly successful Centre of Clinical Excellence funded by NHMRC from 1998-2001. The Centre provided the opportunity in Western Australia for the highest quality clinical research training in comprehensive spheres relevant to the pathogenesis, prevention and therapeutics of cardiovascular disease, with an emphasis on the role of nutrition and lifestyle in relation to high blood pressure, arteriosclerosis, dyslipidaemia and the function of blood vessels. The new ....This Centre proposes to expand its highly successful Centre of Clinical Excellence funded by NHMRC from 1998-2001. The Centre provided the opportunity in Western Australia for the highest quality clinical research training in comprehensive spheres relevant to the pathogenesis, prevention and therapeutics of cardiovascular disease, with an emphasis on the role of nutrition and lifestyle in relation to high blood pressure, arteriosclerosis, dyslipidaemia and the function of blood vessels. The new Centre will broaden the scope of its research and training activities, through the inclusion of clinical projects related to heart failure, clinical and epidemiological research into cerebrovascular disease and stroke and research training opportunities with respect to clotting disorders and therapeutics for thrombosis.Read moreRead less
Biomarkers And Genetic Determinants Of Cardiovascular Risk In Diabetes: The FIELD Study
Funder
National Health and Medical Research Council
Funding Amount
$1,961,718.00
Summary
The patient characteristics and blood factors determining the risk of heart attack, stroke, kidney and eye disease in people suffering from diabetes are not well understood. The FIELD Study, by analysing these characteristics and many blood factors hopes to shed light on ways to prevent these complications for future patients. The project proposes to measure factors on blood samples collected on more than 9000 patients with diabetes and analyse these over the next three years. It hopes to help d ....The patient characteristics and blood factors determining the risk of heart attack, stroke, kidney and eye disease in people suffering from diabetes are not well understood. The FIELD Study, by analysing these characteristics and many blood factors hopes to shed light on ways to prevent these complications for future patients. The project proposes to measure factors on blood samples collected on more than 9000 patients with diabetes and analyse these over the next three years. It hopes to help doctors identify patients who are at particular risk of complications for special attention and early treatment.Read moreRead less