Pharmacological Strategy For Blocking Lung Cell Damage By Toxic Smoke Constituents.
Funder
National Health and Medical Research Council
Funding Amount
$457,267.00
Summary
People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, ....People retrieved from burning buildings or other hazardous situations involving fires are often at risk of death due to the effects of inhaled smoke. This reflects the presence of some very toxic substances in smoke that are products of the combustion of wood, vegetation and synthetic building materials. The most toxic substance present within smoke is acrolein, a very reactive chemical that attacks cells in the lining of the lung. This can result in a life-threatening condition known as oedema, where the lung is flooded with fluids and is unable to perform its respiratory function. At present, the clinical approaches used to treat smoke inhalation victims are mostly directed against offsetting the symptoms of lung injury and do not take into account the role of lung cell injury by toxic substances in smoke such as acrolein. This project will provide a better understanding of the chemical events underlying the injury caused by smoke to lung cells, and also into possible drug strategies for treating victims of smoke inhalation. The work will explore the ability of a range of compounds that are chemically related to a blood pressure-lowering medicine (hydralazine) to protect lung cells against such smoke-induced damage. The work will employ a range of modern research techniques to understand the events occurring in lung cells exposed to smoke. Once this is understood, these approaches will be used to test the various drug compounds for their abilities to prevent the death of cells exposed to smoke or its toxic constutuent acrolein. This work will yield new information on a series of compounds concerning their ability to block the toxicity of smoke to lung cells. The goal is to identify one or two molecules that can be carried forward to testing in smoke-exposed animals.Read moreRead less
Experience drives changes in the connections between neurons in the brain. This neuroplasticity is a fundamental property of the nervous system, critical for learning and memory, but also important for recovery from injury and development of some nervous system disorders. This study will improve understanding of how, with practice, the human brain adapts to functional demands in the development of motor skill. Musicians are used as exemplars of fine motor skill who show long-term experience-driv ....Experience drives changes in the connections between neurons in the brain. This neuroplasticity is a fundamental property of the nervous system, critical for learning and memory, but also important for recovery from injury and development of some nervous system disorders. This study will improve understanding of how, with practice, the human brain adapts to functional demands in the development of motor skill. Musicians are used as exemplars of fine motor skill who show long-term experience-driven plasticity in the brain. This study will provide specific and detailed quantitative information about how motor cortex circuits important for control of the hand are altered in musicians. The study will also improve understanding of basic mechanisms involved in short-term neuroplasticity associated with motor learning in musicians and non-musicians, and hemispheric or training-related differences in these properties which may contribute to different abilities to use the hand for fine motor tasks.Read moreRead less
External Therapeutic Device To Support Rehabilitation Of The Hand Following Trauma Or Surgery
Funder
National Health and Medical Research Council
Funding Amount
$175,000.00
Summary
The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and ....The loss of hand function will affect every aspect of an individual’s life. This includes the ability to feed and care for themselves and the ability to work and participate in family life. For people recovering from problems such as trauma, burns or surgery affecting the hand, careful management of hand rehabilitation can influence the outcome for the patient significantly. In order to reduce the possibility of mobility difficulties occurring, including loss of joint range of motion, muscle and tendon sheath adhesions or non-functional scar tissue formation, continuous passive motion (CPM) is often indicated. Additionally, for people with reduced mobility of the hand due to upper limb paralysis, such as those with cervical spinal cord injury, stroke, cerebral palsy or peripheral nerve injury, disregard for management of the maintenance of the joint range of motion of the effected hand will result in contracture and limited joint range of motion. Such syndromes will reduce hand function, which is already limited by paralysis, and will negatively affect potential outcomes for aggressive rehabilitation techniques, such as tendon transfer surgery and functional neuromuscular stimulation. Therefore, in such cases, CPM is also indicated. Current devices applying CPM have shown to be effective in minimising the syndromes indicated above and these results are summarised in the Background and Research Plan attached to this proposal. Unfortunately, the use of such devices is not always prescribed by clinicians. This is due, mainly, to the limitations of these devices that are in the marketplace. These limitations include lack of secure finger placement, lack of portability, the inability to provide specialised therapy to specific joints and inflexible programming. This proposal introduces an improved device to be developed and these improvements form the proposal aims below. Given such an improved device, which can overcome many of the problems with current CPM machines, it is likely that that the clinical application of CPM will achieve the greater degree of prescription and application in hand rehabilitation. These improvements should overcome the clinical reticence to use these devices and restore a balance by increasing their use to the level that the scientific literature indicates they should have. The overall aim of the proposal is to take the device to a stage where it is ready for clinical trial.Read moreRead less
METHODS - A Randomised Controlled Trial Of METhotrexate To Treat Hand Osteoarthritis With Synovitis
Funder
National Health and Medical Research Council
Funding Amount
$770,014.00
Summary
Hand osteoarthritis (OA) is common, but has no treatment. Almost 50% of people with hand OA will have joint swelling (synovitis). The hand joint of people with synovitis are 3.5 times more likely to experience joint destruction within as little as 2 years. Drugs used to treat synovitis may reduce pain and joint destruction. We propose that treating patients with symptomatic hand OA and synovitis with the anti-synovitis drug, methotrexate, will be a major medical advance.
Novel Assessments Of The Central And Peripheral Control Of The Human Hand
Funder
National Health and Medical Research Council
Funding Amount
$365,105.00
Summary
This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the t ....This is a study of how the human hand works. The hand is supremely adapted for manual skills ranging from writing and playing a musical instrument to non-verbal communications via gesture and pointing. How is the range of hand skills achieved? We are motivated to study this because the ability of the hand to recovery from some neurological disorders, particularly stroke, is very poor. One important element in virtually all activities of the hand is precise movement of the thumb. The tip of the thumb is flexed by a single muscle, a muscle only present in humans. We want to determine how this muscle works, and how the force it produces affects the whole hand. We will use specialised neurophysiological techniques to do this in human volunteers. There is no comparable animal model for this type of work due to significant differences at both the level of the brain and the level of the muscle. Second, we want to understand better how the cells in the spinal cord which control the hand (and other) muscles work. We have two new ways to do this, including a novel technique which can activate these cells with a form of stimulation that may help us improve functional electrical stimulation. Finally, with 27 bones and more than 25 muscles which operate it, the hand is not simple to control. We will use a new apparatus to measure how well it is controlled, and we will directly stimulate the motor areas of the brain to evaluate the control. From this, we will come up with new understanding, as well as new stimulus and measurement techniques that can be applied to patients with impaired hand function, as occurs all too often after stroke.Read moreRead less
Alveolar Macrophage Zinc And Zinc Transporters And Their Role In Phagocytosis
Funder
National Health and Medical Research Council
Funding Amount
$288,975.00
Summary
Zinc is an essential dietary component that serves a number of functions in the lungs. It is both an anti-oxidant and anti-inflammatory agent. Some airway inflammatory diseases such as emphysema may involve a critical loss of lung zinc. We believe that cigarette smoke causes the loss of zinc and this prevents the lung macrophages from working properly to clear bacteria and dead cells. This will provide a foundation for our long term goals of better clinical management of emphysema.
Reducing Tobacco Harm During Pregnancy, Infancy And Early Childhood Among Groups With High Smoking Prevalence
Funder
National Health and Medical Research Council
Funding Amount
$346,449.00
Summary
This research will contribute to the evidence base for reducing harm from tobacco during pregnancy, infancy and early childhood, among groups with high smoking prevalence. It will: generate evidence on a program to help pregnant Indigenous women quit smoking; develop tools and evidence to support implementation of smoking cessation guidelines in public antenatal services; and explore people’s understanding regarding protecting children from harms of passive smoking at home.