Mechanisms Underlying Disordered Skin Blood Flow Following Nerve Injury
Funder
National Health and Medical Research Council
Funding Amount
$408,000.00
Summary
Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding ....Many people who recover from traumatic injury or who have chronic conditions such as diabetes or neuropathy from exposure to a toxic chemical suffer from peripheral vascular disorders leading to poor circulation in the extremities. These conditions are characterised by impaired wound healing, cold hands and feet and ongoing pain. These people must face a long life with progressively increasing disability. Even normal ageing can lead to similar problems. This project is directed at understanding the role of the nerve supply to blood vessels in the skin in these disorders. The experiments will be conducted in skin blood vessels of rats with various forms of nerve lesion that will mimic these conditions in patients. We will use our knowledge of the structure and behaviour of nerve-blood vessel connections to analyse the changes in the properties of vascular smooth muscle and relate it to the state of the innervation. Skin arteries normally receive two types of nerve - sympathetic (which release noradrenaline) and afferent ( which release peptides) - that have opposing actions on the vessel (constriction and dilation respectively). We hypothesize that removal of part or all of the innervation changes the contractile mechanism of the smooth muscle in the wall of the vessel so that it becomes much more sensitive to calcium ions and produces larger and more prolonged contractions. We will combine electrophysiology and contraction studies with immunohistochemistry and biochemical analysis to define the relation between the nerve deficit and the vascular responses. The aim is to identify appropriate drug targets for which local application in the affected region can alleviate the symptoms without causing widespread side effects.Read moreRead less
Role For Zinc And ZIP2 In The Action Of Nitric Oxide And In Vascular Protection Against Cigarette Smoke And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$685,941.00
Summary
The NO/cGMP signalling pathway, which is central to cardiovascular physiology and protection against disease, is only fully effective when there are adequate levels of zinc in the vascular endothelium. This is especially important where zinc stores are depleted (elderly, smokers, diabetics and kidney disease). There is an urgent clinical need to implement strategies to monitor vascular Zn status. This application will explore the underlying science and translate these to the clinic.
Novel Soluble Guanylate Cyclase Activators For Pulmonary Artery Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$474,087.00
Summary
Pulmonary hypertension (elevated blood pressure in the lungs) is a life-threatening condition with few treatment options. We have recently identified a new class of drug that may improve blood vessel function in the lungs and thereby provide a new drug for the management of this group of patients.
Targeting Aldosterone Receptors In Cerebrovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$857,712.00
Summary
Stroke represents a major health (accounting for 6% of all deaths) and economic (costs Australia $2.14 billion per year) burden on society, thus clearly more effective treatments are needed. This project will investigate the role of two substances produced in the body – angiotensin II and aldosterone – in stroke outcome, and whether targeting their receptor(s) may prevent poor outcomes following stroke.
Exported Epoxide Hydrolases Of The Malaria Parasite, Plasmodium Falciparum, And Their Role In Modulation Of Host Vasoregulation
Funder
National Health and Medical Research Council
Funding Amount
$342,054.00
Summary
The major aim of this study is to define the physiological role of the parasite EHs, and to establish whether they modulate levels of EETs within infected erythrocytes. I will examine if infected erythrocytes have impaired vasoactive properties and also determine if this pathway has therapeutic potential
A New Target For Allergic Inflammation: The Sphingolipid Pathway
Funder
National Health and Medical Research Council
Funding Amount
$588,617.00
Summary
Collectively, allergic diseases contribute immensely to the burden of health care in Australia. Notably, allergic reactions are symptomatic responses to a normally innocuous environmental antigen. Allergic diseases include asthma, hay fever, food allergy, anaphylaxis, insect sting and drug allergy. This project aims to understand the underlying mechanisms associated with allergic reactions such that it may aid in the identification of novel targets for the development of new treatments.
The Role Of Angiotensin-(1-7), Angiotensin Converting Enzyme-2 And The Mas Receptor In Liver Fibrosis And The Development And Maintenance Of Portal Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$55,575.00
Summary
Chronic liver disease is widespread in our community, and is increasing due to fatty liver disease and viral hepatitis. Liver disease leads to permanent liver scarring, liver cancer and other life-threatening complications. This research investigates the role of a hormone system called the renin-angiotensin system in liver disease, and investigated the use of drugs that act on this system for the prevention and treatment of liver scarring and these complications.