Lifestyle And Pharmacological Regulation Of Lipoprotein Metabolism In The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$504,504.00
Summary
Visceral obesity is an increasing problem in Australia. Elevated blood fat levels are associated with visceral obesity and increased risk for heart disease. Effective management of lipid disorders is important to reduce the risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In viscerally obese subjects, the level of blood fats is elevated compared with lean individuals. These abnormalities are partly caused by overproduction of fat in the li ....Visceral obesity is an increasing problem in Australia. Elevated blood fat levels are associated with visceral obesity and increased risk for heart disease. Effective management of lipid disorders is important to reduce the risk for heart disease. Fats in the blood originate from dietary sources and from synthesis by the liver. In viscerally obese subjects, the level of blood fats is elevated compared with lean individuals. These abnormalities are partly caused by overproduction of fat in the liver and impaired clearance of fat from the blood. Two particular proteins, called apolipoprotein A and B-100, are important fat carriers responsible for transporting fat in the blood. Viscerally obese subjects have abnormal levels of these apoproteins and we hypothesised that they are responsible for the impaired movement of fat in the blood. Viscerally obese subjects are insulin resistant and are prone to diabetes. This condition will impair the regulation of apolipoproteins A and B-100. In this research project, we will investigate the effect of a fibrate (a regulator of fat production and breakdown) and ezetimibe (a regulator of dietary cholesterol absorption) on the production and clearance rates of apolipoprotein A and B in a group of obese subjects who are on weight loss program . If our hypothesis is correct, these studies will demonstrate new mechanisms of action of the two drugs that will complements the favourable effect of weight loss in the treatment of elevated blood fats and reduction in risk of heart disease in an important groups of subject in the population.Read moreRead less
Characterising An Important Control Point In Cholesterol Synthesis Beyond HMG-CoA Reductase
Funder
National Health and Medical Research Council
Funding Amount
$480,739.00
Summary
The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol- ....The statins are the ‘go-to’ drugs for treating heart disease; blocking a very early, highly-controlled step in the pathway producing cholesterol. However, they inhibit the production of other vital molecules which explains why some patients do not tolerate them. We have identified that a later enzyme in this pathway is also highly controlled and here aim to characterise the molecular mechanisms involved. This work could translate into the development of even safer drugs for treating cholesterol-related diseases.Read moreRead less
Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s diseas ....Our goal is to discover new mechanisms involved in our cells’ delicate balancing act with respect to cholesterol levels. Understanding how production of cholesterol is controlled in our cells is key to developing new drugs aimed at preventing its excessive accumulation. This will have long-term benefits for health considering that a cellular imbalance in cholesterol is involved in two of the most common conditions threatening the health of Australians, namely heart disease and Alzheimer’s disease.Read moreRead less
Structural Characterization Of A Novel AB5 Cytoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$210,760.00
Summary
The proposed research program, using a combinantion of structural biology and biophysical techniques will provide insight into the role of novel AB5 toxin from E. coli. This study will not only improve our fundamental understanding the mode of action of this toxin from this devastating pathogen, but could lead to the design of rational antimicrobials. The knowledge gained will increase Australian international research profile.
A Randomised Trial Of The Effects Of Cholesterol Lowering Therapy Among Patients With Chronic Renal Impairment
Funder
National Health and Medical Research Council
Funding Amount
$333,250.00
Summary
People with kidney disease are well known to be at high risk of developing major health problems earlier in life than people without kidney problems. In particular, people with kidney disease are more likely to suffer from heart attacks and strokes. For a number of other high-risk patient groups (such as people with heart disease), studies have clearly shown that cholesterol-lowering treatment can significantly reduce the risks of serious complications. However, until now, patients with kidney d ....People with kidney disease are well known to be at high risk of developing major health problems earlier in life than people without kidney problems. In particular, people with kidney disease are more likely to suffer from heart attacks and strokes. For a number of other high-risk patient groups (such as people with heart disease), studies have clearly shown that cholesterol-lowering treatment can significantly reduce the risks of serious complications. However, until now, patients with kidney disease have generally been excluded from such studies because of concerns about drug side effects. New, better-tolerated cholesterol lowering drugs now offer an opportunity to see if this highly effective treatment is also protective among people with kidney disease. The HARP (Heart And Renal Protection) trial is a large new study that will be done as a collaboration between Australian researchers and researchers from the University of Oxford in the UK. The aim of the study is to see if low doses of two cholesterol-lowering drugs can reduce the risks of stroke and heart attack. The study will include about 9,000 people with chronic kidney disease followed for an average of 4 years. It is hoped that by using low doses of two treatments, rather than a high dose of one, it will be possible to get substantial benefits without side effects. There are presently many tens of thousands of individual in Australia with chronic kidney disease and many millions of such individuals worldwide. The results of the HARP study will therefore influence the care of a very large number of people. If the results were positive, implementation of this new treatment would be expected to prevent many tens of thousands of premature strokes and heart attacks around the world each year.Read moreRead less
Improving Patient Outcomes In Familial Hypercholesterolaemia Across The Continuum Of Care
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
'Familial' means it runs in families and 'hypercholesterolaemia' means high blood cholesterol. Familial Hypercholesterolaemia (FH) is the most common and serious form of inherited high cholesterol. People with FH are at an increased risk of developing cardiovascular disease. High cholesterol also placed an estimated $4 billion burden on the Australian economy in 2017-18. Practical research on prevention strategies will improve cardiovascular health outcomes and lower the burden of health costs.
Distribution Kinetics Of Opioids Used In Substitution Programs
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Heroin addiction is a major national and international problem costing hundreds of millons of dollars to Australia alone. The major form of treatment is methadone taken as maintenance treatment once a day. While methadone is effective in most addicts, about one third of them complain that it does not last long enough and they either tolerate this inadequate form of treatment or are prescribed a newer drug as part of a clinical trial or drop out and revert to heroin. We have previously shown that ....Heroin addiction is a major national and international problem costing hundreds of millons of dollars to Australia alone. The major form of treatment is methadone taken as maintenance treatment once a day. While methadone is effective in most addicts, about one third of them complain that it does not last long enough and they either tolerate this inadequate form of treatment or are prescribed a newer drug as part of a clinical trial or drop out and revert to heroin. We have previously shown that the blood levels of methadone are important in determining its best use and specifically, that those addicts for whom methadone does not hold have a greater drop in their blood levels after methadone has been absorbed into the body. This drop in blood levels is mainly due to methadone's redistribution throughout the body. Very little is known about how methadone distributes and redistributes throughout the body but it appears that the lung is the most important organ. A number of questions need to be answered to improve methadone's use: 1. How quickly is methadone taken up into the lung compared to the brain; 2. Why is the lung able to take up and release a large amount of methadone; 3. How does decreased respiration influence the lung and brain uptake of methadone; 4. What happens when another drug is prescribed (such as an antidepressant) which reduces the lung uptake of methadone; 5. Do some of the newer drugs for heroin addiction have better lung distribution and binding properties. We will perform studies of the concentrations of methadone and newer drugs in sheep that will provide the scientific basis for answering these questions and permit better use of drug treatment for heroin addiction.Read moreRead less