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Research Topic : heart attack
Scheme : NHMRC Project Grants
Australian State/Territory : NSW
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  • Funded Activity

    Targeting PI3K-regulated MicroRNAs To Treat Heart Failure

    Funder
    National Health and Medical Research Council
    Funding Amount
    $532,593.00
    Summary
    Current therapeutics largely delay heart failure progression rather than regressing it. New therapeutic strategies with the capability of improving function of the failing heart are thus greatly needed. The primary goal of this study is to determine whether novel regulatory genes can enhance cardiac function in a setting of heart failure. Ultimately, technologies that target these genes may lead to innovative pharmacotherapies in the clinical management of heart failure.
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    THE VASCULAR CONSEQUENCES OF SNORING AND OBSTRUCTIVE SLEEP APNOEA

    Funder
    National Health and Medical Research Council
    Funding Amount
    $476,052.00
    Summary
    Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading .... Snoring refers to a condition where the throat narrows significantly during sleep, and allows the soft tissues which surround this part of the airway to vibrate and create the typical snoring noise. Habitual snoring is a very common problem in the adult population, with a prevalence of between 20-40%. More severe forms of snoring are associated with the obstructive sleep apnoea syndrome, which is a condition in which the throat completely blocks behind the tongue and palate during sleep leading to cessation of breathing for short periods of time. Sleep apnoea is among the commonest chronic disorders of adult males occurring in 5% of men over the age of 45 years. Increasingly, it is now recognised that snoring, without sleep apnoea, may be an independent risk factor for the development of both of these very common and significant medical disorders. However, there have been no studies exploring the mechanisms by which snoring might contribute to the development of stroke and hypertension. In this proposal, we will explore the hypothesis that chronic snoring transmits a pressure wave through the tissues of the neck to the carotid artery which is the main blood supply to the brain. We propose that the chronic vibration of this artery leads to disease such as atherosclerosis and hypertension. Our studies will help to prove that this is a common mechanism whereby both snoring and sleep apnoea may contribute to the development of important vascular diseases. Studies will also establish the prevalence of carotid atherosclerosis in snorers (with and without OSA), and the prevalence of habitual snoring and OSA in patients at risk of developoing completed stroke. The recognition of snoring as an independent risk factor for vascular disease will clearly have important and wide ranging implications for the future management of snoring in the prevention of stroke and hypertension.
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    Funded Activity

    A Supervised Exercise Programme Following Hospitalisation For Heart Failure: Does It Add To Disease Management?

    Funder
    National Health and Medical Research Council
    Funding Amount
    $730,966.00
    Summary
    Congestive heart failure (CHF) is a common, disabling condition. Outcomes are improved by a post-hospital disease management programme (DMP) including education, support and followup from a team of nurses, doctors and other health professionals. This study looks at whether adding a supervised exercise programme to a DMP can reduce death rates and hospital stays, and improve physical function and depression in patients with a recent hospital stay for CHF.
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    Funded Activity

    Can Skin Infection With Group A Streptococcus Cause Acute Rheumatic Fever?

    Funder
    National Health and Medical Research Council
    Funding Amount
    $459,450.00
    Summary
    It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of .... It is traditionally taught that the cause of acute rheumatic fever (ARF) is always infection of the throat with the bacterium group A streptococcus (GAS). However, in Aboriginal communities of the Top End of the Northern Territory the incidence of ARF is the highest reported in the world, yet GAS is uncommonly isolated from the throat. There is further information to suggest that GAS skin sores may underlie many cases of ARF. If this were proven, it would completely alter the traditional view of the cause of ARF, and have important implications for prevention of ARF around the world. Presently, these approaches focus on diagnosing and treating sore throat, but no country has proven that such a program can be successful in substantially reducing new cases of ARF. If it was known that skin infection could lead to ARF, then countries (including Australia) could emphasise the importance of skin health programs. A further benefit of this knowledge would be to influence GAS vaccine development, which presently is largely focused on the prevention of sore throat. A different possibility has recently been raised - that the cause of ARF may not always be GAS, but instead that the related bacteria GCS and GGS may have the potential to cause this disease. Proof of this hypothesis would even more dramatically alter our understanding of disease causation, prevention, and vaccine development. We propose to determine the cause of ARF in Aboriginal communities by regularly swabbing families of people with a history of ARF, and using genetic fingerprinting of the bacteria from the skin and throat swabs. When cases of ARF occur, we will be able to determine the site and type of infection that precipitated the attack. We will conduct a related study in more communities, in which we will swab family members of people with ARF and of control families (without ARF) to determine the bacteria most commonly isolated from ARF families.
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    Funded Activity

    Molecular Mechanisms Of Receptor Activation And Signalling

    Funder
    National Health and Medical Research Council
    Funding Amount
    $571,980.00
    Summary
    Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several .... Fundamental to our ability to respond to both immediate and long-term environmental changes and stresses is the coordinated regulation of cellular functions by hormonal and neurotransmitter stimuli. The great majority of such stimuli are sensed by G-protein coupled receptors (GPCR), complex glycoprotein molecules on the surface of most cells that selectively bind and are activated by various hormones and neurotransmitters. Although GPCRs are a superfamily of proteins that now compromise several hundred distinct but structurally-related members, the molecular mechanisms involved in their activation and, thus, their regulation of vital cellular functions, remains unclear. Based on insights that we have gained from the development and characterisation of several alpha1-adrenergic receptor mutants, we have developed a model of receptor activation. In this application we are proposing to further test and to extend the hypotheses underlying this model. Importantly, the functions regulated by GPCR include vital responses, such as the maintenance of circulatory homeostasis by augmenting heart pump function and by constricting vascular smooth muscle to maintain blood pressure. In addition, disordered cellular regulation by GPCR has been implicated in a wide variety of diseases, including hypertension, congestive heart failure and cardiac hypertrophy. Thus, the studies detailed here to further understand the molecular mechanisms of receptor activation have broad implications for our knowledge of critical physiological control systems, and may lead to novel therapeutic approaches to treat a variety of diseases.
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