Acute Traumatic Coagulopathy- Mechanisms And Measurement
Funder
National Health and Medical Research Council
Funding Amount
$188,226.00
Summary
Acute traumatic coagulopathy (ATC) refers to impaired blood clotting post major trauma and is associated with high, early mortality. Inability to predict this disorder and poor knowledge regarding its detailed biochemical mechanism has hindered development of evidence based guidelines to manage patients with ATC. This project aims to correlate early biochemical disorders with clinical management and outcomes post trauma to determine mechanisms leading to ATC and determine management strategies.
A Novel Point Of Care (PoC) Device For Predicting And Monitoring Bleeding And Clotting (haemostasis)
Funder
National Health and Medical Research Council
Funding Amount
$608,979.00
Summary
Manipulating the bleeding/clotting system is a critical but expensive part of modern medicine, eg some people need blood thinners while others can bleed too much. Thrombin generation is the ideal overall test for the bleeding/clotting of blood, but current methods have major problems. We developed and patented a test that deals with most of the problems. This proposal will create an assay that is easy for doctors to perform without a specialised laboratory.
Molecular Investigations Of Antithrombin Instability And Heparin Binding Mechanism
Funder
National Health and Medical Research Council
Funding Amount
$195,691.00
Summary
Thrombosis is a significant disease affecting a large number of people. The primary treatment for episodes of acute thrombosis is administration of the anticoagulant, heparin. The effector molecule through which heparin carries out its action is the serine proteinase inhibitor, antithrombin. This molecule regulates blood clotting by inhibiting the proteinases which carry out this process. Antithrombin is converted from a poor inhibitor of coagulation proteases to a very good inhibitor on binding ....Thrombosis is a significant disease affecting a large number of people. The primary treatment for episodes of acute thrombosis is administration of the anticoagulant, heparin. The effector molecule through which heparin carries out its action is the serine proteinase inhibitor, antithrombin. This molecule regulates blood clotting by inhibiting the proteinases which carry out this process. Antithrombin is converted from a poor inhibitor of coagulation proteases to a very good inhibitor on binding heparin. This provides a control point for coagulation. The mechanism by which antithrombin is converted to a very good inhibitor of coagulation proteases involves a large change in the structure of this protein. These changes in structure are linked to the changes which occur when antithrombin becomes inactive through the process of polymerisation. Certain patients with thrombosis have been found to have changes in both the stability and heparin affinity of their antithrombin molecules, which forms the underlying basis for the disease. We wish to study the reasons for the effects of mutations in the antithrombin variants by making recombinant mutants which mimic the molecules in the thrombotic patients and carrying out detailed, sophisticated molecular analyses of their interaction with heparin and proteases and their stability under various conditions. Additionally we will engineer recombinant mutants of antithrombin which we believe will stabilise the molecule and potentially act as an improved supplement for therapy. This analysis will provide important insights into the functioning of both heparin and antithrombin and thereby significantly improve our understanding of the control of coagulation.Read moreRead less
Defining The Roles Of Platelet Protease-activated Receptors In Thrombosis
Funder
National Health and Medical Research Council
Funding Amount
$330,690.00
Summary
Inappropriate blood clot formation is the cause of most heart attacks and some strokes. Platelets are the blood cells responsible for such clots. We are interested in the signals which control platelet incorporation into clots because drugs that interfere with this may be effective at inhibiting unwanted clot formation. Our studies determining the importance of platelet signals will provide strong clues to the likely effectiveness of blocking such signals as anti-clotting agents.
Development Of Recombinant RsolCD39-PSGL As A Novel Therapeutic With Anti-thrombotic And Anti-inflammatory Effects
Funder
National Health and Medical Research Council
Funding Amount
$186,367.00
Summary
Heart disease and stroke are due to a narrowing of arteries followed by occlusion, due a combination of clot formation initiated by platelet clumping, and inflammation surrounding the vessel wall. The currently available drugs are often limited by the adverse reaction of bleeding. We will investigate the efficiency of a new drug to prevent clot formation and inflammation.
The Role Of Tissue Factor In The Regulation Of Extracellular Matrix Remodelling And Angiogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$241,980.00
Summary
The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal me ....The aim of the project is to understand how some blood clotting factors may be involved with the regulation of the extracellullar matrix (the material that exists between cells) and angiogenesis (new blood vessel formation). New blood vessel growth occurs in a wide variety of situations including: healing of a flesh wound, the healing phase following a heart attack, development of the eye disease associated with sugar diabetes, in and around a cancerous growth, in the uterus during the normal menstrual cycle, and for the normal growth and development of the placenta and a new baby. The processes by which these new blood vessels form and the factors contributing to the maintenance of their structure are incompletely understood. However, it is known that the interaction of cells and the surrounding extracellular matrix is critical for normal cell function and in particular for new blood vessel formation. Studies in this project will seek to define a relationship between some of the factors which regulate blood clotting, and those that regulate turnover of the extracellular matrix and new blood vessel formation. In particular, how blood clotting factors may be invovled in the regulation of the extracellular matrix will be studied in a rapidly developing tissue, the mouse placenta. The role of blood clotting factors in regulation of new blood vessel formation into an artificial avascular tissue will also be examined. These studies will employ some of the new genetic techniques to understand new roles for proteins which have been traditionally thought to act in only one way. This research has the potential to provide new insights into how blood vessels are formed and are subsequently maintained. This increased understanding will provide the knowledge required for the development of new therapeutic strategies to correct the process when it goes wrong, is unwanted or underdeveloped in human disease.Read moreRead less
Factor XII Dependent Coagulation, Thrombin And Platelet Glycoprotein 1ba In Arterial Thrombosis And Bleeding Disorders
Funder
National Health and Medical Research Council
Funding Amount
$104,664.00
Summary
Clot formation is the key event underlying heart attacks and strokes. There is new data that Factor XII (FXII) can play an important role in clot formation-thrombosis. We aim to examine the role FXII plays in clot formation, in particular the role of FXII in thrombin generation, which is the central event of clot formation, and its interaction with platelet glycoprotein 1ba (another important molecule in thrombosis). New insights into clotting and new therapies can result from our research.
This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to dev ....This research is directed by a team of medical and basic scientists with expertise in mechanisms of inflammation relevant to human disease. The program will investigate the molecular and cellular events that are responsible for inflammation in the kidneys, joints and blood vessels which lead to diseases such as glomerulonephritis, arthritis and atherosclerosis. The aim of the research is to find new therapeutic targets which may be specific to certain organs or disease processes, in order to develop more effective and selective treatments ofchronic inflammatory disease in humans.Read moreRead less
Safety And Quality Of Life Of Peri-operative Transdermal Estradiol Continuation During Gender Affirmation Surgery In Transgender Women: A Randomised Placebo-controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$92,335.00
Summary
Despite no clear evidence, transgender women are told to stop their feminising estrogen treatment several weeks before gender surgery, but this causes severe 'menopausal symptoms' with hot flushes, depression and distress compounding an already stressful preparation for and recovery from major surgery. This trial will establish if continuing estrogen gel around the time of surgery is safe and effective at improving 'menopausal symptoms'.