Assessment Of Hypoxia And Hepatic Metabolism In Cirrhotic Rats Using NMR
Funder
National Health and Medical Research Council
Funding Amount
$355,341.00
Summary
Liver function and hepatic drug metabolism are impaired in patients with cirrhosis but there is currently no adequate explanation to account for this. As a direct consequence, there is no useful therapy beyond liver transplantation. We propose studies aimed at confirming a hypothesis on the mechanisms underlying the development of cirrhosis. From this mechanistic hypothesis, a testable therapeutic hypothesis has been derived. Our primary mechanistic hypothesis is that cirrhosis is associated wit ....Liver function and hepatic drug metabolism are impaired in patients with cirrhosis but there is currently no adequate explanation to account for this. As a direct consequence, there is no useful therapy beyond liver transplantation. We propose studies aimed at confirming a hypothesis on the mechanisms underlying the development of cirrhosis. From this mechanistic hypothesis, a testable therapeutic hypothesis has been derived. Our primary mechanistic hypothesis is that cirrhosis is associated with reduced oxygen delivery from the blood supply into the liver due to a process known as capillarisation (i.e., The Oxygen Limitation Theory). It is proposed that this reduced oxygen availability leads to impairment of liver function. The major aim of this research project is to confirm or refute the presence of intracellular hypoxia (i.e., decreased oxygen in cells) using nuclear magnetic resonance (NMR) techniques and cirrhotic rats. The nature of any metabolic disturbances or changes in cellular components resulting from intracellular hypoxia will then be characterised. The project will also aim to confirm the impairment of oxygen-dependent drug metabolism in cirrhosis by using NMR to measure the degradation or elimination of a fluorinated drug. Our hypothesis for therapy is that intracellular hypoxia may be reversed, and global liver function improved, by oxygen supplementation and-or an increase in hepatic arterial flow by using oral hepatic arterial vasodilators. Vasodilators exert their action by direct relaxation of blood vessels or by blocking the action of vasoconstrictors. Vasodilators that act solely on the hepatic artery and their influence upon blood pressure will be studied using treated rat livers so that such vasodilators can be tested for their ability to modify liver function in cirrhotic rats in vivo. The ultimate goal will be to carry these observations into studies in normal healthy volunteers and cirrhotic patients in the future.Read moreRead less
Development Of Improved Vaccine Strategies For Measles Using Plant-derived Edible Vaccines
Funder
National Health and Medical Research Council
Funding Amount
$331,980.00
Summary
Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the cur ....Measles is a highly contagious viral disease that is contracted via the respiratory tract. Severe infection may lead to complications such as otitis media, pneumonia, encephalitis. Despite our current vaccination strategy outbreaks still occur in Australia and measles is a major problem in developing countries. In developing nations the case fatality rate of measles is several hundred times that of developed nations. Over 800,000 children still die each year due to measles. Problems with the current vaccination strategy are: a) doesn't work in children less than 1 year of age, b) must be kept cold c) must be given by injection. We believe that a plant derived edible vaccine for measles will address the limitations of currently available vaccine i.e. we can give it children under the age of 1 year, it can be eaten and doesn't have to be kept cold.Read moreRead less
Predictors Of Cardiovascular Disease Mortality In The Melbourne Collaborative Cohort Study
Funder
National Health and Medical Research Council
Funding Amount
$350,544.00
Summary
The Melbourne Collaborative Cohort Study was set up in the early 1990s to investigate prospectively the role of diet and other lifestyle factors in causing common chronic diseases including common cancers and cardiovascular disease. Between 1990 and 1994, 41,500 people, aged 40-69 were recruited into the MCCS. About 30% of the cohort are southern European migrants to Australia who were deliberately over-sampled to extend the range of dietary and lifestyle exposures. Migrants from southern Europe ....The Melbourne Collaborative Cohort Study was set up in the early 1990s to investigate prospectively the role of diet and other lifestyle factors in causing common chronic diseases including common cancers and cardiovascular disease. Between 1990 and 1994, 41,500 people, aged 40-69 were recruited into the MCCS. About 30% of the cohort are southern European migrants to Australia who were deliberately over-sampled to extend the range of dietary and lifestyle exposures. Migrants from southern Europe have an adverse risk factor profile in relation to obesity, body fat distribution, physical activity patterns, diabetes, smoking, blood pressure and cholesterol levels, yet their death rates from heart disease are 30-40% lower than the Australian average. A major objective of this study is to investigate the possibility that particular aspects of the diet and cuisine of migrants from southern Europe (olive oil as the major dietary fat, and high intakes of a variety of vegetables and fruit) protect against heart disease and stroke by providing high levels of a wide range of natural antioxidants. It represents the most comprehensive prospective study of diet and cardiovascular disease mortality ever conducted in Australia. A particularly powerful feature is the combination of detailed self-reported dietary intake, the very wide range of exposures to dietary factors implicated in CVD (as risk factors or protective agents), and the objective markers of dietary intake (biochemical markers of dietary intake patterns in blood collected at recruitment, body weight, body fat and body fat distribution). The data should provide a strong rationale for specific dietary recommendations as part of population-based strategies to reduce the incidence of premature mortality from heart disease and stroke in the Australian population.Read moreRead less