Prevention Of Pleural Adhesion Formation By Treatment With Growth Factors
Funder
National Health and Medical Research Council
Funding Amount
$268,000.00
Summary
Damage to the lining of the chest and abdominal cavities and to cells covering the lungs and other internal organs by infection or surgery almost always results in the formation of adhesions. Adhesions are bridges of fibrous material between organs and the body wall. In the chest cavity they can prevent the effective drainage of fluids that build up during infection or after injury leading to deterioration of health and even death. In the abdominal cavity they are a major cause of intestinal obs ....Damage to the lining of the chest and abdominal cavities and to cells covering the lungs and other internal organs by infection or surgery almost always results in the formation of adhesions. Adhesions are bridges of fibrous material between organs and the body wall. In the chest cavity they can prevent the effective drainage of fluids that build up during infection or after injury leading to deterioration of health and even death. In the abdominal cavity they are a major cause of intestinal obstruction and female infertility. In Australia, adhesions affect 9,500 patients annually, accounting for 6% of all hospital readmissions at a cost of over $100 million. This project will use animal models to investigate the specific role of a growth factor called hepatocyte growth factor (HGF) on the healing of the cells lining the internal body cavity and its effect on inhibiting adhesion formation. Using genetically manipulated mice, drug delivery and gene therapy approaches, the effect of changing the levels of HGF in tissues lining the internal body cavities on repair and adhesion formation will be assessed and mechanisms of action elucidated . A better understanding of the way cells lining these cavities heal and the factors that can improve the healing process, may lead to the development of novel therapies to prevent adhesion formation, which will benefit all future patients with chest cavity infections and those who undergo thoracic and abdominal surgery.Read moreRead less
The Role Of The Cytoplasmic Domain Of Tissue Factor In Maintenance Of The Glomerular Filtration Barrier.
Funder
National Health and Medical Research Council
Funding Amount
$487,066.00
Summary
This research aims to understand mechanisms of normal kidney function and the development of chronic kidney damage associated with diseases such as nephritis and diabetes. These diseases represent a significant burden of illness in Australia.
Antiphospholipid Antibody-mediated Foetal Loss: Identifying Mechanisms And Developing New Treatments
Funder
National Health and Medical Research Council
Funding Amount
$547,970.00
Summary
Certain immune diseases (Lupus, Anti-phospholipid syndrome) are associated with foetal loss. It is thought to be due to inflammation and blood clotting on the blood vessel lining (endothelium). This proposal will study the mechanisms that stimulate inflammation and blood clotting, and also devise new treatments.
Procoagulant Expression In The Antiphospholipid Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
This study proposes to investigate how white blood cells contribute to clotting that occurs in patients with an immune disorder called the Antiphospholipid Syndrome. This condition is more common than is generally known, and accounts for about one fifth of clots in the legs and about one third of strokes that occur in young people. It is also a common cause of miscarriages. The study focuses on how activation of the immune system, and inflammation interact to make certain white blood cells expre ....This study proposes to investigate how white blood cells contribute to clotting that occurs in patients with an immune disorder called the Antiphospholipid Syndrome. This condition is more common than is generally known, and accounts for about one fifth of clots in the legs and about one third of strokes that occur in young people. It is also a common cause of miscarriages. The study focuses on how activation of the immune system, and inflammation interact to make certain white blood cells express a molecule called Tissue Factor, which initiates blood clots.Read moreRead less
Role And Mechanism Of Connective Tissue Growth Factor In Diabetic Cardiomyopathy
Funder
National Health and Medical Research Council
Funding Amount
$382,820.00
Summary
Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen pa ....Diabetic cardiomyopathy is a condition where the heart muscle is directly damaged by diabetes. It is being recognised as a prominent cause of both acute and chronic heart failure in diabetes. It is common and occurs in up to 60% of diabetic patients . At present however, no treatments are available to directly treat the cardiomyopathy. This condition can also occur in people with diabetes who have high blood pressure and-or coronary artery disease and may combine with these problems to worsen patient outcomes. We have generated data in experimental diabetes in rodents that strongly implicates a heart growth factor in causing diabetic cardiomyopathy. This protein, called connective tissue growth factor (CTGF), is increased in diabetic cardiomyopathy, and is elevated by high glucose and other factors in diabetes. We have published data showing that CTGF causes tissue scarring like that which occurs in cardiomyopathy, by affecting signals in cells called fibroblasts. It increases the laying down of extracellular matrix (ECM) and also inhibits the degradation of ECM by the proteins that break down matrix, known as the MMPand PAI systems. Such accumulation of ECM is thought to be a major factor leading to abnormal muscle function in cardiomyopathy. We now plan to block CTGF in this diabetic heart model to determine if we can prevent diabetic cardiomyopathy. We have generated two methods to inhibit CTGF in the animal model. Echocardiography (a heart ultrasound test), and molecular analysis of the heart tissue will determine if we can prevent the otherwise adverse functional and structural changes of diabetes in the heart. We will also study our baboon model of diabetes to determine if diabetic cardiomyopathy with increased heart CTGF is present in the primates. Cell culture studies from rat heart fibroblasts and myocytes will determine how CTGF has the effect on cells to cause cardiomyopathy and how we might further prevent this condition developing in diabetes.Read moreRead less
Regulation Of Tissue-type Plasminogen Activator Gene Expression In Endothelial Cells And In Transgenic Mice
Funder
National Health and Medical Research Council
Funding Amount
$244,009.00
Summary
Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how t ....Tissue-type plasminogen activator (t-PA) is an enzyme which plays an important role in the removal of blood clots from the circulation. One of the major sites of production of t-PA are endothelial cells which line the blood vessel wall. The rate of t-PA production is greatly influenced by factors released from other cells. One of these factors is tumour necrosis factor (TNF). The t-PA gene is switched off in endothelial cells exposed to TNF. One of the aims of this project is to understand how the t-PA gene is suppressed by TNF in human endothelial cells and in transgenic mice. The transgenic mice we have available express the regulatory region of the t-PA gene (called the gene promoter) connected to a reporter gene called LacZ. We will use these animals to visualise the expression pattern of LacZ expression under normal conditions and in mice treated with TNF. The results of these experiments will provide new information as to how the t-PA gene is controlled in cells and in the body.Read moreRead less
Non-alcoholic steato-hepatitis (NASH) is a common disease of liver inflammation and scarring, which may progress to cirrhosis or liver cancer. While type 2 diabetes causes a higher rate of NASH and more rapid NASH progression the reasons for this are not clear. We have developed a novel animal model of NASH with diabetes added to dietary induced obesity. We show that a growth factor is elevated in the affected livers. We plan to block the growth factor to see if we can prevent NASH worsening.