The Effect Of Loading On The Size, Shape And Strength Of Cortical Bone During Different Stages Of Maturation
Funder
National Health and Medical Research Council
Funding Amount
$180,000.00
Summary
Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the break ....Osteoporosis is a condition in which the skeleton becomes fragile and susceptible to fractures. It is a public health problem that affects both men and women over the age of sixty. Although osteoporosis affects the elderly, the most opportune time to prevent osteoporosis may be during childhood. Physical activity is a lifestyle factor known to affect the strength of the skeleton. Bone density is commonly used as a measure of bone strength because it is easily measured and is related to the breaking strength of bones. However changes in the shape of bones can also affect bone strength with or without an increase in bone density. Changes in bone shape in response to exercise in children or adults have rarely been investigated, and little is known about the effects of exercise on bone shape during different stages of growth. This study is the first to investigate how exercise during childhood may affect bone strength by changing bone shape. 45 elite female tennis players aged between 6 to 18 years have completed two years of this study. 90 novice and competitive male tennis players aged between 6 to 20 years and 60 healthy age matched controls will be asked to participate in this study. Measurements will be made annually for three years. The bone shape and density of the dominant and non-dominant arms of the players will be compared with the children who don't play tennis - comparisons will also be made between i) different stages of puberty and ii) girls and boys. The findings of this study are important because the lifestyle of children today may predispose them to a greater risk of osteoporosis late in life. Physical activity may be the most important modifiable protective factor against fragile bones in old age. The findings of this study will be the first to provide insight into whether there is a unique time during growth when exercise will result in the greatest increase in bone strength by changing bone shape.Read moreRead less
THE BIOLOGY OF HUMAN DEC-205: A POTENTIAL ANTIGEN LOADING RECEPTOR FOR DENDRITIC CELLS
Funder
National Health and Medical Research Council
Funding Amount
$227,017.00
Summary
Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with ....Dendritic Cells (DC) represent a unique subset of white blood cells which play a critical role in initiating the immune response. Foreign material from bacteria-viruses and potentially cancer cells are recognised by DC, taken inside, processed and presented with other signals to T and B Lymphocytes for a response. Several DC surface molecules may beinvolved in the recognition of foreign material. We have cloned human DEC-205, a molecule which is predicted to bind the sugar groups associated with bacteria-viruses and to act as a foreign material recognition and loading receptor. This project seeks to synthesise components of DEC-205 to test the binding capacities of its different components to different sugars and other molecules. We will also establish its expression pattern and how this is regulated on different white blood cell types. It is also possible that DEC-205 transmits signals which activate the DC, and we will test for that possibility. Finally, we will attempt to exploit this knowledge for loading cancer target molecules into DC via DEC-205 to initiate a cancer vaccine response.Read moreRead less
Patellofemoral Arthritis: Efficacy Of Physiotherapy And Understanding The Role Of Joint Stress
Funder
National Health and Medical Research Council
Funding Amount
$616,430.00
Summary
Arthritis of the kneecap leads to considerable pain and difficulty with daily activities. This project is testing whether a physiotherapy treatment (8 sessions over 12 weeks) designed specifically for people with kneecap arthritis is effective. In order to understand more about kneecap arthritis, this project will calculate the force on the kneecap and its relationship to pain and other factors, including thigh and hip muscle strength, knee alignments and knee movements.
Effects And Mechanisms Of Direct Cardiac Compression In Interruption Of Myocardial Remodelling In Chronic Heart Failure.
Funder
National Health and Medical Research Council
Funding Amount
$392,250.00
Summary
Heart failure (HF) is a disease where the heart pumping function is insufficient to provide adequate blood supply to the rest of the body. It is a highly debilitating disease affecting nearly 10 million people worldwide and has a <50% one-year survival in severe cases. Despite significant advances in pharmacotherapy, heart transplant is the only alternative for severe HF but is restricted by lack of donor organs to only ~ 5% of those requiring it. Research has shown that progression of HF is ....Heart failure (HF) is a disease where the heart pumping function is insufficient to provide adequate blood supply to the rest of the body. It is a highly debilitating disease affecting nearly 10 million people worldwide and has a <50% one-year survival in severe cases. Despite significant advances in pharmacotherapy, heart transplant is the only alternative for severe HF but is restricted by lack of donor organs to only ~ 5% of those requiring it. Research has shown that progression of HF is related to many subsequent changes after an initial insult. In addition to pumping failure, HF is associated with deranged compensatory responses such as neurohumoral over-activation, heart chamber enlargement, loss of functional cells, increase of inflammatory mediators and changes in cardiac skeleton (extracellular matrix). The changes in the heart are collectively known as remodelling. Mechanical heart assist is now considered a potential destination therapy for severe HF, superior to pharmacotherapy alone. Improvement of cardiac pumping function and even successful weaning from devices has been reported, along with observations of reverse remodelling. The success of this approach has been limited however, particularly with HF due to coronary disease, the most prevalent form. We developed a novel HeartPatch mechanical assist device to compress the heart from its outer surface. It gives support to both main chambers and avoids blood contact, a feature of currently available devices associated with complications such as blood clotting and infection. Our device has proved effective in animals with acute HF and even with cardiac arrest. We propose to study the effects of our device on the process of remodelling in HF with coronary disease in a controlled manner. The project will enhance understanding of the mechanisms involved in reverse remodelling and further the development of a device which may potentially benefit many severe HF patients.Read moreRead less
Optimising Lung Protective Resuscitation Using A Newborn Premature Lamb Model
Funder
National Health and Medical Research Council
Funding Amount
$392,218.00
Summary
Premature babies are at risk of severe, and potentially long-term, lung damage. These complications can be minimised if babies are optimally resuscitated at birth. This project will use promising new imaging technologies to examine the influence of different strategies, using mechanical ventilators, to help inflate the lung at birth, and their interactions with other therapies used to enhance lung maturity. It will provide new insights into resuscitating preterm babies.
Prostaglandin G/H Synthase-2 (PGHS-2) Is A Key Regulator Of Skeletal Adaptation And Remodelling
Funder
National Health and Medical Research Council
Funding Amount
$301,018.00
Summary
Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inh ....Knowledge of the biology underlying bone formation is important for developing novel approaches to stimulate new bone formation in skeletal diseases associated with ageing or disability, or for maintenance of new bone around orthopaedic or dental implants. The discovery that a prostaglandin enzyme (PGHS-2) is a key factor in activity-related bone formation and normal bone turnover, as well as a pharmacological target for reducing inflammation, has considerable clinical significance. Specific inhibition of PGHS-2 by recent anti-inflammatory drugs avoids formation of gastric ulcers, but their influence on normal bone remodelling and fracture repair is not known and must be investigated. Many such inhibitors are in advanced clinical trials, but their effect on bone metabolism has not been published. This project is important because it employs novel experimental models to advance our knowledge of prostaglandin biology in skeletal adaptation, and elucidates important clinical consequences for specific inhibition of PGHS-2 in the skeleton. This project will investigate the regulation of prostaglandin production by PGHS enzymes following mechanical loading in vivo. It will use cell, molecular and histochemical techniques to determine if the genes that regulate the enzymes are influenced by mechanical stimuli, and if they are dependent on other molecules, associated with structural proteins (stress fibres) within the cell. It will investigate if inhibition of PGHS-2 by antiinflammatory drugs or stress-fibre inhibitors, depresses normal bone turnover and healing responses. The outcome of these experiments could indicate new approaches to stimulate bone formation, preserve bone mass, or minimise adverse skeletal effects of anti-inflammatory treatments related to orthopaedic or dental procedures.Read moreRead less
Does Variable Ventilation Offer Physiological And Biological Benefits For The Preterm Lung?
Funder
National Health and Medical Research Council
Funding Amount
$320,278.00
Summary
Lung disease is a significant cause of illness at birth, subsequent breathing problems and death in very premature babies. We know that chronic preterm lung disease results in part from the immature state of the lung at birth, but it appears that inflammation of the lung also plays an important role. We, and others, have shown that this lung inflammation can be a response to injury from mechanical ventilation after birth. In the past, we have sought to strictly control the way that babies are ve ....Lung disease is a significant cause of illness at birth, subsequent breathing problems and death in very premature babies. We know that chronic preterm lung disease results in part from the immature state of the lung at birth, but it appears that inflammation of the lung also plays an important role. We, and others, have shown that this lung inflammation can be a response to injury from mechanical ventilation after birth. In the past, we have sought to strictly control the way that babies are ventilated. We have regulated the pressures used to inflate their lungs, the amount of volume delivered to the lung, the amount of time that the baby has to take a breath. This is a marked contrast to breathing patterns in healthy infants and adults, in which each of these things vary considerably from breath to breath. Recent studies have shown that the presence of variability in breathing patterns is actual essential to the process of staying healthy and maintaining resting lung volume above a critical lower limit. This study will provide unique insights into a new and potentially highly beneficial approaches to ventilation for preterm infants. We will determine if there is a significant clinical benefit of incorporating variability into the ventilatory waveform used to treat newborn babies with lung disease. has the potential to cause a paradigm shift in current concepts of preterm infant ventilatory strategies. Potential long term outcomes include significantly reducing illness and death associated with preterm birth, and promoting a healthier start to life for the over 6000 infants who require ventilatory assistance each year within the Australian and New Zealand neonatal network.Read moreRead less