Associations Between Periodontal Disease And Cardiovascular Surrogate Endpoints In An Adult Indigenous Population
Funder
National Health and Medical Research Council
Funding Amount
$413,242.00
Summary
The relationship between periodontal disease and cardiovascular risk markers, both of which are high among the Indigenous Australian population, is established. This study seeks to explore the prevalence of periodontal disease and cardiovascular risk markers among this population, and to determine if implementation of a periodontal intervention leads to improved cardiovascular risk outcomes. There may be benefit in applying this model to other areas of Indigenous health promotion and research.
Procoagulant Expression In The Antiphospholipid Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
This study proposes to investigate how white blood cells contribute to clotting that occurs in patients with an immune disorder called the Antiphospholipid Syndrome. This condition is more common than is generally known, and accounts for about one fifth of clots in the legs and about one third of strokes that occur in young people. It is also a common cause of miscarriages. The study focuses on how activation of the immune system, and inflammation interact to make certain white blood cells expre ....This study proposes to investigate how white blood cells contribute to clotting that occurs in patients with an immune disorder called the Antiphospholipid Syndrome. This condition is more common than is generally known, and accounts for about one fifth of clots in the legs and about one third of strokes that occur in young people. It is also a common cause of miscarriages. The study focuses on how activation of the immune system, and inflammation interact to make certain white blood cells express a molecule called Tissue Factor, which initiates blood clots.Read moreRead less
Monomeric C-reactive Protein As Pathogenic Factor And Therapeutic Target In Atherothrombotic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$674,880.00
Summary
CRP is a plasma marker that can identify individuals at high risk for heart attack and stroke. Our preliminary data suggests that plasma CRP is not only an innocent marker, but can also be activated and thereby become a strong inflammatory stimulus by changing from a five unit to a single unit form on the surface of activated platelets. We will investigate this CRP activation in vitro, in animal models and in patients, and aim to develop new drug therapies for diseases such as heart attack.
Activated Protein C As A Promoter Of Wound Healing
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physi ....The healing of wounds is a complex process involving a number of stages, including coagulation, inflammation, remodelling and finally development of full strength skin. Impaired wound healing and-or skin ulcers occur in patients with peripheral arterial occlusive disease, deep vein thrombosis, diabetes, pressure sores and burns. Despite intense investigation, the precise mechanisms associated with impaired healing are poorly understood. APC is a serine protease that plays a central role in physiological anticoagulation. APC potently activates gelatinase A, an enzyme that plays a prominent role during the remodelling phase of wound healing and angiogenesis. Our preliminary experiments provide very strong evidence that APC accelerates wound healing using both cultured cells and a rat skin wounding model. There are three aims to this study. The first will use cell culture techniques to investigate the mechanisms of action of APC during wound healing. Secondly, we will expand our pilot studies on the effect of APC as a promoter of wound healing in vivo. These studies will examine the exact dosing and timing regime for APC, using a rat wound healing model. In addition, we will test the effect of APC on slow healing wounds, present in diabetic rats. Thirdly, we will determine whether APC is quantitatively or functionally deficient in human wound fluid derived from slow-healing wounds compared to wounds that heal normally. This is the first time that APC has been implicated in wound healing. It is envisaged that this work will ultimately lead to a novel topical treatment of APC to accelerate slow-healing wounds.Read moreRead less
Hepatic Oxidative Stress, PTPs & STAT Signalling In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$1,086,547.00
Summary
Obesity is increasing at an alarming rate worldwide and is a leading cause of morbidity and mortality. Obesity is causally linked to the development of insulin resistance, a prelude to type 2 diabetes. In this proposal we will define a novel liver centric mechanism by which insulin resistance and oxidative stress may promote the development of morbid obesity, type 2 diabetes and liver disease.
Targeting Protein Kinase C In Diabetes Management Using Novel Polyunsaturated Fatty Acids
Funder
National Health and Medical Research Council
Funding Amount
$150,000.00
Summary
PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synth ....PKC regulates a diverse range of cellular processes in an isozyme-specific manner. There is strong recent evidence to implicate PKC, especially PKC _, in mediating the actions of glucose in diabetes. This includes the action of glucose in renal glomeruli, retina, aorta and heart of diabetic animals and in cultured cells from these organs. More importantly, inhibition of PKC_ with the PKC_-specific inhibitor, LY333531, blocks the actions of glucose. Recently, our research group designed and synthesised a family of novel polyunsaturated fatty acids. One of these, MP5 (_-oxa- 21:3n-3), inhibited high glucose-induced activation of PKC? in cultured mesangial cells as well as in glomeruli of diabetic rats in a relatively selective manner. The overall aim of this proposal is to evaluate the potential for a chemically engineered novel polyunsaturated fatty acid, MP5 (_-oxa-21:3n-3), to treat pathogenesis associated with diabetes by targeting the PKC system. The specific aims are to: 1. Characterise the effects of MP5 on glucose- or advanced glycosylation end product-stimulated activation of protein kinase C (PKC). 2. Determine whether esterification of MP5 into diacylglycerol is essential for the action of MP5 3. Investigate whether MP5 is efficacious at preventing the actions of glucose in vitro e.g. glucose stimulated TGF_ production in mesangial cells, and in vivo in streptozotocin-diabetic rRead moreRead less
There are ~1.6 billion overweight adults worldwide & this is predicted to rise to 2.3 billion by 2015. In Australia > 2/3 of adults are overweight or obese. Obesity is a key factor in the progression of many human malignancies. Obesity poses the greatest risk for the development hepatocellular carcinoma (HCC), a deadly cancer refractory to nearly all available anti-cancer therapies. This application will delineate the molecular mechanisms by which obesity promotes HCC development.