Intravascular Leukocyte Trafficking During Thromboinflammation
Funder
National Health and Medical Research Council
Funding Amount
$668,742.00
Summary
Unblocking blood vessels to treat heart attack and stroke can unfortunately cause a paradoxical worsening of organ damage, due to increased inflammation upon blood flow restoration. We have identified a novel way in which this side-effect is regulated by the small blood clotting cells platelets, and the protein fibrin. We will investigate ways to reduce the pro-inflammatory role for platelets, and define safer clot busting treatments.
The Role Of The Plasminogen Activators (PAs), Urokinase-PA And Tissue-type PA In Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA ( ....Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA (u-PA) and tissue-type PA (t-PA) convert plasminogen into plasmin which can then breakdown the accumulated fibrin. Their presence in RA patients would therefore be beneficial. However, u-PA is also implicated in cell migration leading to inflammatory cells accumulating in the joint, and cartilage destruction, both of which are detrimental to disease outcome. In the joints of RA patients there are high levels of u-PA and low levels of t-PA. We, and our collaborators, have found that in the absence of t-PA, disease is exacerbated, whilst in the absence of u-PA, the outcome depends on the type of disease, either exacerbating or ameliorating disease. This highlights the different roles u-PA can have. The current proposal aims to determine the role of u-PA in inflammation and arthritis, and whether enhancing t-PA can have beneficial outcomes with respect to disease severity. In addition, we will also study whether intra-articular fibrin deposition can, in fact, drive the inflammatory reaction and cartilage destruction seen in RA. The findings will be important for our understanding of the role of fibrin accumulation in the inflammatory and destructive processes that occur in RA, and the roles of u-PA and t-PA in enhancing and preventing them respectively. Information gained will provide clues for useful strategies for the treatment of human inflammatory diseases, including RA.Read moreRead less
Understanding And Preventing Airborne Transmission Of Infectious Respiratory Aerosols
Funder
National Health and Medical Research Council
Funding Amount
$393,894.00
Summary
This project aims to significantly advance our understanding of how infectious bacteria are transmitted through the air, and what basic control measures are most effective at preventing this. This research is focused on persons with cystic fibrosis (CF), as they may be particularly susceptible to such transmission, but our results will also help us better understand how other infections are spread through the air. This is especially important given the recent global influenza pandemic.
Distribution Of Monodisperse Aerosols Inhaled By Children For Determination Of Optimal Therapeutic Inhaler Formulations
Funder
National Health and Medical Research Council
Funding Amount
$326,000.00
Summary
Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inha ....Inhalers are the primary form of treatment for asthma, allowing the delivery of lower doses of medication directly to the lungs. Consistent daily use of these inhalers is often necessary to effectively control the symptoms of asthma. Inhalers are now increasingly used to treat infants with lung problems. Many of these inhalers are not designed for use by such young children, who may be unable to perform the breathing techniques necessary for effective use of these inhalers. Not all the drug inhaled by patients will end up in the lungs where it is needed; a large proportion is left in the mouth, throat and stomach. Our earlier studies have shown that there is a large amount of variability in the amount of drug received by children using inhalers. We intend to assess the important factors involved in improving the efficiency of inhaler therapy for children, such as the size of the inhaled particles and the breathing pattern of the child. The results obtained from this study will enable us to determine the best method of delivering these drugs to children so that they only receive the lowest effective dose for treatment of the symptoms of asthma while minimising unwanted effects.Read moreRead less