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Antioxidant Glutathione Peroxidase (GPx) Mimetics And Atherosclerosis: A Role For Targeted Antioxidant Therapy.
Funder
National Health and Medical Research Council
Funding Amount
$358,319.00
Summary
This proposal investigates the use of antioxidant therapy, targeted at increasing the function of the body's important antioxidant enzyme GPx1, to reduce atherosclerosis both in a non-diabetic and diabetic setting. Strong clinical evidence and our recently published data support an important role for GPx1 in limiting atherosclerosis. We will now investigate the molecular mechanisms involved in mediating these effects and whether compounds that mimic GPx1 function reduce atherosclerosis.
Gamma-Tocopherol: An Important Dietary Factor For Protection Against Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$341,575.00
Summary
Heart disease is one of the most common causes of death in Western Countries. Oxidative damage is thought to be a major contributor to the development of a number of chronic diseases such as heart disease. Oxidative damage can occur in states of oxidative stress when the body's antioxidant defences cannot prevent damage caused by free radicals or other oxidants. Antioxidant vitamins help defend against oxidative injury and therefore should help to protect against such diseases as heart disease ( ....Heart disease is one of the most common causes of death in Western Countries. Oxidative damage is thought to be a major contributor to the development of a number of chronic diseases such as heart disease. Oxidative damage can occur in states of oxidative stress when the body's antioxidant defences cannot prevent damage caused by free radicals or other oxidants. Antioxidant vitamins help defend against oxidative injury and therefore should help to protect against such diseases as heart disease (atherosclerosis). Population studies support the view that dietary antioxidants such as vitamin E help to protect against heart disease. However, several large studies giving subjects vitamin E supplements (pure alpha tocopherol) showed no benefits or protection against heart disease. There is a cruicial difference between supplements and dietary intake of vitamin E. Supplements contain only alpha tocopherol while dietary sources derived from seeds, nuts, grain and oils is a mixture of different forms of tocopherol. Recent evidence suggests that one of these forms (gamma-tocopherol) has different properties to alpha-tocopherol and can protect against certain oxidants in ways that alpha-tocopherol cannot. We have developed a specialised assay to detect forms of gamma-tocopherol in human plasma that have reacted with toxic oxidants. Using this assay we have shown that people with heart desease may have higher levels of these products in their blood than people without heart disease. This project will investigate the effects of gamma and alpha tocopherol dietary supplements on risk factors for heart disease. It will also investigate how gamma tocopherol may be working to protect against the development of heart disease. These studies could have important implications for what type of diet or dietary supplement is most beneficial to protect against heart disease.Read moreRead less
Are Novel Nitric Oxide Mimetics Protective In Vascular Disease?
Funder
National Health and Medical Research Council
Funding Amount
$634,044.00
Summary
Nitric oxide (NO) is a biologically active gas which controls blood flow and blood pressure. New drugs which mimic the effects of NO show promise in the treatment of cardiovascular disease. This study investigates the ability of NO mimetics to protect blood vessels in disease, by limiting the production of toxic molecules, improving blood flow and preventing blood clot formation. The information gained may lead to the development of new therapies for blood vessel diseases such as stroke.
I have discovered particular factors produced by our white blood cells have the ability to shut down or boost protein production in the gut, pancreas and lung. My vision is to harness these to devise new strategies for treatments for infectious and non-infectious diseases (inflammatory bowel disease, diabetes) that have a high burden on our healthcare system.
Induction Of Reactive Oxygen Species By Hepatitis C Virus And Its Role In Liver Pathogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that vira ....The majority of individuals infected with hepatitis C virus (HCV) show a slow progression of liver disease over a period of 20-30 years. There is increased scaring of the liver which can result in liver failure and in some individuals liver cancer. Due to the lack of suitable model systems to study HCV infection and disease progression there is no currently available vaccine and treatment options are limited. While the host defense mechanisms to HCV are relatively well studied the role that viral proteins and viral replication play in the development of liver disease are not well characterized. Previous experiments in the laboratory have shown that one of the hepatitis C virus proteins results in the formation of toxic oxygen molecules known as a reactive oxygen species. This toxic oxygen molecules can have an effect on liver cells that may enhance the progression of the liver disease process in hepatitis C virus infected individuals. The role that these molecules play in liver cells is unknown but experiments are planned in laboratory model systems and in specimens obtained from hepatitis C virus infected individuals to further examine potential mechanisms. This will hopefully lead to the identification of new treatments for hepatitis C virus liver disease. Some patients with hepatitis C will develop liver cancer, however, all the reasons are not known. Using new technology known as microarray, a consequence of the human genome project, we have been able to look at the expression levels of thousands of genes in liver cancer. Experiments are planned to determine if these genes are important in liver cancer and if they can be used as targets for therapy or to more easily diagnose liver cancer.Read moreRead less
The Role Of Lycopene Supplementation In The Management Of Asthma
Funder
National Health and Medical Research Council
Funding Amount
$332,875.00
Summary
Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or ....Asthma is a significant and increasing health problem for Australia and is now listed as a National Health Priority Area. There is immense community interest in dietary factors affecting asthma. This project examines the potential for dietary carotenoids to be used to manage asthma. Carotenoids are antioxidants that are found in orange and red fruits and vegetables, such as tomatoes, carrots and mangoes. Research suggests that dietary carotenoids may be protective against asthma symptoms and -or onset. It is also likely that increasing intake of carotenoid-rich foods may be more effective than taking dietary supplements, as the key nutrients or combination of nutrients may not be known. This project will examine whether carotenoids such as lycopene can reduce the tendency of asthmatic airways to overreact to common triggers. It also investigates whether carotenoids can be used to prevent or reduce the severity of asthma attacks. The project will determine whether tomato juice or lycopene capsules are more effective in this role. This work will provide the necessary information to develop a large trial testing the ability of carotenoids to improve quality of life for people with asthma. While there is evidence to suggest that carotenoids may be helpful in asthma, the data to date is inconclusive. This study provides a scientific approach to evaluating the potential for carotenoids to be used as a treatment for asthma.Read moreRead less