Involvement Of Interstitial Cells Of Cajal In The Pathogenesis Of Diabetic Gastroparesis
Funder
National Health and Medical Research Council
Funding Amount
$386,104.00
Summary
Diabetics commonly suffer from gastrointestinal symptoms such as bloating and nausea. We have preliminary evidence that interstitial cells of Cajal (ICC), which are essential for normal gut motility, are particularly vunerable to damage in diabetes. The goal of this study is to determine how the loss of ICC in diabetes leads to delayed gastric emptying. Our overall aim is to identify potential therapeutic targets for improved treatment of diabetes-related gastrointestinal motility disorders.
The Role Of Connexins In Blood Pressure Regulation: Use Of A Conditional Gene Expression System
Funder
National Health and Medical Research Council
Funding Amount
$583,767.00
Summary
Cell coupling through gap junctions is said to play an important role in regulating blood flow and blood pressure. However data obtained from mice, in which specific gap junctions are deleted, may be compromised by compensatory changes in other junctions. We have validated a new method for rapidly and reversibly altering gap junctions in adult mice with oral sugar. This technique will enable us to directly determine whether interference with cell coupling affects blood flow and blood pressure.
Airway Smooth Muscle Contribution To Remodelling In Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$211,320.00
Summary
Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflamma ....Asthma is an airway disease that affects more than 10% of adults and 25% of children in Australia and in 1998 caused 675 deaths. The cost to the community is in excess of $720 million a year. The abnormality in asthma is not fully understood, however inflammation, changes to the structure of the airways and excessive airway narrowing are key factors. Inflammation and the allergic reactions which accompany asthma cause fluid to leak from tiny blood vessels in the lung. This fluid and the inflammation are linked to changes in the airway which include structural protein deposition - breakdown and an overgrowth of the smooth muscle that lines the walls of the airway. Our work is focussed on understanding the relationship between the structural protein deposition - breakdown and excess muscle growth. We also hope to gain a better understanding of the way asthma treatments combat these changes in the asthmatic airways.Read moreRead less
Myoendothelial Gap Junctions: Their Composition And Role In Vasodilator Responses Attributed To EDHF
Funder
National Health and Medical Research Council
Funding Amount
$282,750.00
Summary
Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important ....Cardiovascular disease, including coronary heart disease and stroke, continues to be the major cause of death in Australia and hypertension is a significant risk factor. The endothelium, which lines blood vessels of all sizes, is critical to the control of blood flow to the organs of the body. Endothelial cells release factors which can cause blood vessels to constrict or to relax, thus decreasing or increasing blood flow, respectively. Under normal conditions, the endothelium is more important as a source of relaxing factors, while under hypertensive conditions, the balance is shifted in favour of the release of constricting factors. Thus, restoration of the vasodilatory function of the endothelium is seen as an important new therapeutic target in the treatment of vascular disorders. Present data suggests that the action of one of the major endothelial derived vasodilatory factors, the so-called endothelium-derived hyperpolarizing factor, EDHF, requires the presence of particular structures within the vascular wall, but little is known about the molecules of which they are comprised. We have identified two unique situations, during development and during hypertension, when these structures are present in vessels in which they are absent in normal adults. We will use gene microarrays to identify the specific molecules involved in these structures and use physiological studies to test the role of these proteins and structures in vasodilatory responses. The results of these studies may identify new targets for therapeutic intervention to restore the action of EDHF in hypertension.Read moreRead less
Detecting Bioactivity In A Naturally-occurring Aggrecan Fragment
Funder
National Health and Medical Research Council
Funding Amount
$407,634.00
Summary
The dynamic balance of anabolic and catabolic processes in healthy cartilage is disturbed in arthritis, with increased catabolism leading to irreparable cartilage damage. We will study the ability of a naturally-occuring aggrecan fragment to modulate cartilage catabolism. Our in vitro and in vivo experiments suggest that the aggrecan fragment limits cartilage destruction. This study tests our hypothesis that the aggrecan fragment antagonises cartilage damage and promote cartilage repair.
Oxidation Of Arterial Extracellular Matrix By Myeloperoxidase-derived Oxidants
Funder
National Health and Medical Research Council
Funding Amount
$183,266.00
Summary
It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on al ....It is well established that changes occur in the composition and nature of the extracellular matrix present in the artery wall during the development of atherosclerosis. The changes that occur in this matrix affect both the mechanical and physical properties of the arterial wall (e.g. its ability to cope with the high pressures genrated by the pumping of blood from the heart) and the adhesion of cells. It is well established that certain key cell types do not adhere well, or grow properly, on altered or damaged matrix and this can result in either the loss of key cell types from the artery wall (e.g. loss of endothelial cells) and - or the proliferation and invasion of cells from other sources (e.g. smooth muscle cell invasion into the intimal space). There is circumstantial evidence that some of these changes occur via the formation of oxidants by the heme enzyme myeloperoxidase which is released from activated white cells. In this study we will employ recently developed analytical techniques to examine the nature of the alterations that are present in atherosclerotic plaques in comparison to normal human artery samples, and investigate the mechanisms by which such alterations arise. We will seek evidence for, or against, the involvement of myeloperoxidase-derived oxidants in the observed changes using specific markers which we have developed for the presence of such damage. This information will allow the rational design of strategies to interfere with the progression of atherosclerosis, which is the major killer of Australians.Read moreRead less
Novel Pathways Involving APC And PAR-2 In Cartilage Degradation In Osteoarthritis
Funder
National Health and Medical Research Council
Funding Amount
$448,834.00
Summary
Loss of the cartilage that normally lines the ends of bones is central to joint failure in arthritis and the need for replacement surgery. There are presently no treatments that stop cartilage breakdown in joint disease. This project investigates the role of a new pathway not previously thought to be active in cartilage, in the progressive damage seen in arthritis. Successful completion of these studies may provide a novel new strategy to treat joint disease.