Urotensin-II In Human Heart: Investigation Of Mechanisms Involved In Cardiac Function
Funder
National Health and Medical Research Council
Funding Amount
$255,990.00
Summary
The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our finding ....The normal function of the body is maintained by naturally occurring compounds. Some for example affect the heart, fine tuning it to make it beat faster or slower, or beat with greater or less force when required in different situations in health and disease. We were the first to show just recently that a small protein which occurs naturally in the body, called urotensin-II can affect the way the heart beats. We showed that extremely tiny amounts increase the force of the heart beat. Our findings indicate that urotensin-II is the most potent heart stimulator identified to date. In patients with heart failure, short term stimulation of heart contraction is beneficial, supplying the heart and other organs with vital oxygen and nutrients. However, in the long term excessive stimulation causes worsening of the patients condition. Very little is currently known about the way in which urotensin-II alters heart function. The goal of our study is to understand the mechanism involved in urotensin-II mediated effects on the heart. This will involve identifying the location of urotensin-II and its receptors in the heart, and determining what signalling changes occur after the interaction of urotensin-II with its receptors. Urotensin-II must first be cleaved from a larger drug. We will determine where in the heart this cleavage occurs and whether the process is crucial to the ability of urotensin-II to stimulate contraction of the heart. Since stimulators of heart contraction are detrimental to patients with heart failure in the long term, we will determine whether these patients have more urotensin-II in their blood than patients who do not have heart failure. If the levels of urotensin-II are higher in heart failure patients, it may indicate a need to interfere with the interaction of urotensin-II with its receptors.Read moreRead less
STudy Of Risk Assessment To Reduce Complications In Patients Following Noncardiac SurgerY (STRATIFY)
Funder
National Health and Medical Research Council
Funding Amount
$436,000.00
Summary
Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduce ....Cardiac problems account for many complications in patients undergoing major non-cardiac surgery, and even apparently minor cardiac damage is a marker of high risk for subsequent adverse events. Unfortunately, while money and effort is expended on identifying patients at risk, the appropriate response to this risk is quite unclear. The performance of bypass surgery or balloon angioplasty in order to treat the underlying coronary disease of at-risk patients is used in other situations, and reduces longterm risk. However, in many patients undergoing major noncardiac surgery, this approach may be inappropriately aggressive, as these patients are often elderly, have other diseases that make heart operations more difficult and risky than usual, and in any case may have a reduced life expectancy from the disease necessitating the operation. As the most critical issue is to ensure that patients undergo their surgery uneventfully, an alternative is the use of intensive medical therapy to protect the heart. This multicentre study, based at Brisbane hospitals that perform large numbers of major operations, will follow up patients for complications, and outcome (including quality of life) will be assessed six months after the operation. We will address two important questions about the efficacy and cost of risk reduction strategies. First, in patients at higher levels of risk and with a positive stress test, could a combination of medical therapy designed to protect the heart be as effective as current approaches, which include the performance of bypass surgery or coronary balloon angioplasty? Second, in patients identified as being at some risk - but low risk - are drugs sufficiently effective to avoid the need for further testing to quantify risk? As the population continues to age, the numbers of at risk patients undergoing major surgery will increase, and answers to these questions will provide important information to guide their management.Read moreRead less
Enhancing Erythropoietin Therapy In Ischaemia-reperfusion Injury Of Heart And Kidney
Funder
National Health and Medical Research Council
Funding Amount
$361,021.00
Summary
Heart attacks and kidney disease from a lack of blood flow are common causes of morbidity and have poor treatment options. Erythropoietin (epo) is a useful new treatment, but there remain some caveats to its use in humans: eg. it may cause excessive scarring during repair. Use of epo with an anti-inflammatory drug may decrease scarring and provide benefit to long-term health. We plan to carefully define the biomolecular pathways of injury and repair, to better plan this therapy for human use.
The role of the immune system in pain is emerging from recent discoveries, and may hold the key to novel pain treatments. Most people experience brief gut infections from food or contagion without long-term consequences. Many others suffer symptoms for years afterwards - probably the best example of immune-based pain. Our project investigates how immune cells communicate with sensory nerves, and how these communications change from both angles after gut infection or inflammation.
Transient Receptor Potential Channels (TRPs) As Transducers And Targets In Primary Visceral Afferents
Funder
National Health and Medical Research Council
Funding Amount
$669,130.00
Summary
Transient receptor potential, or TRP channels, are involved in generating many of the sensations we perceive, such as heat, cold, touch and pain. Some TRP channels are specialized to signal pain from visceral organs, which we must investigate if we are to find treatments for visceral pain, which are currently lacking.
Cognitive Impairments And Post Traumatic Stress Symptoms In Children With Traumatic Brain Injury: A Longitudinal Study
Funder
National Health and Medical Research Council
Funding Amount
$482,250.00
Summary
Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic ....Traumatic brain injury in children is common with more than 2000 new cases a year in Queensland and Victoria alone. Many children who experience a brain injury go on to have long-term difficulties such as significant educational and social problems. Post-traumatic stress occurs in children following traumatic physical injury. However it is not clear to what extent this is so for children who have received a traumatic brain injury. Furthermore, when there is a traumatic brain injury and traumatic stress, it is not clear how these interact, how they influence long-term outcomes, and what factors such as pre-injury functioning and family support and distress mediate outcomes. These issues are very important since effective rehabilitation of children following traumatic brain injury is essential to maximise long-term functioning and minimise disability. To be effective, rehabilitation must be guided by the knowledge about key factors that determine the recovery process. This study aims to provide answers to these questions by following two cohorts of children (aged 6-14) over 18 months after receiving a traumatic brain injury. In total 240 children will be recruited from Brisbane and Melbourne hospitals. They will be assessed at three, six, twelve and eighteen months post-injury using measures of cognitive, psychological and social functioning. Information on parent distress and behaviours will also be obtained. The information obtained will provide the basis for the development of a specific rehabilitation strategy for children with traumatic brain injury, including information on strategies to help prevent any confounding impact of post-traumatic stress on recovery.Read moreRead less