Development Of Oral Natruiretic Peptides For Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$511,037.00
Summary
Congestive heart failure is fatal disease and a major disease burden for the community affecting nearly half a million Australians. Current therapies are inadequate. We seek to develop a new peptide therapy based on snake venom version of the human B type natriuretic peptide which has to be given by injection. We will produce an orally active, stable and effective treatment using a program of discovery involving testing in animals and cells.
Serial NT-proBNP Monitoring For Predicting Major Cardiovascular Events In The Dialysis Population
Funder
National Health and Medical Research Council
Funding Amount
$288,548.00
Summary
Dialysis patients have a 50-100 fold increased risk of dying from heart disease caused by abnormal heart muscle structure and function. Current tests are unable to accurately identify patients at the highest risk. A test that accurately detects the early stages of heart injury is urgently needed. The aim of our research is to develop a monitoring guide using regular testing of a heart hormone (NT-proBNP) to identify high-risk dialysis patients early allowing treatment before a serious medical co ....Dialysis patients have a 50-100 fold increased risk of dying from heart disease caused by abnormal heart muscle structure and function. Current tests are unable to accurately identify patients at the highest risk. A test that accurately detects the early stages of heart injury is urgently needed. The aim of our research is to develop a monitoring guide using regular testing of a heart hormone (NT-proBNP) to identify high-risk dialysis patients early allowing treatment before a serious medical complication occurs.Read moreRead less
Effects Of The Atrial Natriuretic Factor Enhancer And The 5'HS4 Insulator On The Probability Of Gene Expression.
Funder
National Health and Medical Research Council
Funding Amount
$534,628.00
Summary
Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene re ....Complex organisms contain many different types of cells, which can have completely different appearances and functions. All of these cells contain the same genes; the differences between them are achieved by the selective use of the genes. The means by which the selective use of genes is accomplished is a key to understanding how complex organisms develop, and how that development goes awry in cancer, heart disease, and other common disorders. A very large body of evidence indicates that gene regulation is accomplished by the interaction of protein factors with segments of DNA flanking the gene. One hypothesis underlying our work is that the flanking DNA elements act primarily to increase the probability that a gene will be active rather than silent. We will ask if removing a known regulatory element from the gene for Atrial Natriuretic Factor (ANF) in mice reduces the likelihood of ANF being expressed by heart cells when the heart is stressed. This experiment will also shed new light on an extremely common disease state in humans (cardiac hypertrophy). In a second experiment, we will use a new experimental system we have developed to ask if a gene regulatory element is able to dial up the amount of expression from a gene, as well as to switch the gene on. Our previous work suggested this was not the case, but we wish to conduct a more rigorous test. Another hypothesis is that no DNA element is able to completely shield a transferred gene from the regulatory elements surrounding it. Accordingly, we will test a DNA element that has been proposed to insulate any gene from all influences of surrounding genes, and ask if it is able to create an autonomously expressing gene at any site within the genome. Because they deal with functions that are common to all genes, these experiments will provide information that should be applicable to a broad array of efforts to manipulate gene expression.Read moreRead less
Development Of Oral Natriuretic-like Peptides For Chronic Treatment Of Congestive Heart Failure
Funder
National Health and Medical Research Council
Funding Amount
$389,533.00
Summary
Congestive heart failure is fatal disease and a major disease burdon for the community affecting nearly half a million Australians.. Current therapies are inadequate and very limited in prolonging life. We seek to develop a new peptide therepy based on the effectivness of human B type natriuetic peptide which has to be given by injection. Our aim is to produce an orally active and effective treatment based on peptides discovered in snake venom. The program involves testing in animals and cells
Effects Of Atrial Natriuretic Peptide On The Sarcolemmal Na-K Pump In Rabbit Myocytes
Funder
National Health and Medical Research Council
Funding Amount
$225,500.00
Summary
The sodium pump transports sodium ions across cell membranes from the inside of cells to the outside. This maintains the concentration of sodium more than ten-fold lower on the inside than the outside. This transmembrane concentration gradient is essential for normal cell function. It is well established that the sodium pump is regulated by a variety of hormones. In a pilot study we have demonstrated that a hormone secreted by the heart, atrial natriuretic peptide, stimulates the sodium pump in ....The sodium pump transports sodium ions across cell membranes from the inside of cells to the outside. This maintains the concentration of sodium more than ten-fold lower on the inside than the outside. This transmembrane concentration gradient is essential for normal cell function. It is well established that the sodium pump is regulated by a variety of hormones. In a pilot study we have demonstrated that a hormone secreted by the heart, atrial natriuretic peptide, stimulates the sodium pump in single heart cells. This has not been reported previously. This study will examine the cellular mechanisms that mediate the stimulation of the sodium pump by atrial natriuretic peptide. A study on the effect of atrial natriuretic peptide on the regulation of sodium in heart cells is particularly important from the perspective of heart failure, a condition characterised by an inability of the heart to pump a sufficient amount of blood. While the underlying causes of heart failure vary widely activation of several hormone systems is a common feature regardless of the aetiology. It has already been well established in clinical practice that interfering with hormone activation by drugs improves symptoms as well as survival. Drugs have recently been developed that can increase levels of atrial natriuretic peptide. Since raised levels of sodium may contribute to important heart cell abnormalities in heart failure the effect of atrial natriuretic peptide on sodium export from the cells by the pump may have important implications for treatment of this serious and common condition.Read moreRead less