Peptides Bound To Commonly Used Orthopaedic And Dental Biomaterials:In Vitro And In Vivo Effect On Osteogenesis.
Funder
National Health and Medical Research Council
Funding Amount
$273,428.00
Summary
In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, ....In 1992, the orthopaedics industry fitted some 300,000 prosthetic devices, artificial hips, knees, giving this industry a global market of $2.1 billion with a projected market growth exceeding 10% per annum. In (1994-5) 5,717 prosthetic hips and 4,593 knees were surgically implanted in NSW of which 14% of hips and 9.5% of knees were revisions. Considerable health funding is allocated to joint replacement for the nation, although successful, outcomes are finite. Importantly, and aside from costs, patients morbidity is high. The major cause of long-term failure of these prosthetic replacements is aseptic loosening, the result of bone loss at the bone-device interface. Novel approaches to development of more efficient implant materials would ultimately lead to major contributions to the mobility and and quality of life for these patients. Considerable effort has been devoted to alter surface characteristics of orthopaedic implants to improve the interlocking of device and skeleton. We were the first to demonstrate that surface chemical modification of biomaterials using selected ions resulted in an enhanced bone formation. This proposal is aimed at chemically modifying the surfaces of commonly used orthopaedic and dental materials, to improve the biocompatibility of new devices and the surface coatings for existing prostheses. Furthermore, this application will build on the in vitro data showing that particular peptides specifically bind osteoblasts and therefore have the potential to provide a surface on a prosthesis that is conducive to bone formation. To date, we have coupled these peptides to metallic surfaces and will proceed to study the osteoblastic phenotype and subsequent osteogenesis. Development of these novel biocompatible surfaces is anticipated to reduce patient morbidity and result in significant health care savings.Read moreRead less
Characterising Protein And Membrane Changes In Age-related Cataract Lenses.
Funder
National Health and Medical Research Council
Funding Amount
$441,624.00
Summary
Cataract is the major cause of blindness worldwide. At present the only treatment for cataract, is surgery. This, however, is associated with complications (e.g. posterior capsule opacification), is expensive (a major component of the Health budget) and cannot keep pace with the incidence of cataract in developing nations. In addition, due to the greying of the community , this problem will be of increasing importance in the future. For prevention, we need to understand why cataract develops.
Molecular Characterization Of The Gingipains Of Porphyromonas Gingivalis
Funder
National Health and Medical Research Council
Funding Amount
$394,000.00
Summary
Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic perio ....Chronic periodontitis is a bacteria-associated inflammatory disease of the supporting tissues of the teeth, which results in the destruction of tooth support and ultimately leads to tooth loss. The disease is a major public health problem with a large economic burden and has been associated with an increased risk of cardiovascular disease and pre-term birth and low birth weight. The bacterium Porphyromonas gingivalis has now been identified as a major pathogen in the development of chronic periodontitis. We have identified a major virulence factor of P. gingivalis which is an extracellular complex of proteins involved in binding and destroying host proteins. The aim of this proposal is to characterize the secretion, molecular processing and assembly of the cell surface complex using state-of-the-art proteomic techniques. This study will provide valuable insight into the molecular processes of a bacterial pathogen that leads to virulence. Detailed knowledge on the unique molecular events involved in secretion, processing and assembly of a major virulence factor will provide molecular targets for the development of specific inhibitors that may have utility as an adjunctive therapeutic and-or as part of a preventive regime or maintenance program for the control of chronic periodontitis. Further, the molecular insight that will result from this study will have broader application in the understanding of virulence factor processing of a Gram-negative pathogen that will provide paradigms for other bacterial pathogens.Read moreRead less
Impact Of The Extension Of The Sydney Light Rail System On The Prevalence Of Physical Activity Participation
Funder
National Health and Medical Research Council
Funding Amount
$105,647.00
Summary
Regular participation in physical activity is associated with a range of physical and mental health benefits in adults, including reduced risk for cardiovascular disease, non-insulin dependent diabetes, overweight, hypertension, osteoporosis, some cancers and anxiety and depression. Regular participation in physical activity also improves the ability to meet the demands of work and to engage in leisure activities. Approximately half of all adult Australians are insufficiently active to gain the ....Regular participation in physical activity is associated with a range of physical and mental health benefits in adults, including reduced risk for cardiovascular disease, non-insulin dependent diabetes, overweight, hypertension, osteoporosis, some cancers and anxiety and depression. Regular participation in physical activity also improves the ability to meet the demands of work and to engage in leisure activities. Approximately half of all adult Australians are insufficiently active to gain the many health benefits associated with participation in regular physical activity. Modification of the physical environment is one avenue through which the prevalence of physcial activity participation might be increased. More specifically, there has been considerable speculation about the role of public transportation systems in increasing the proportion of adults who are adequately physically active, but no empirical evidence is available. This study will employ a quasi-experimental design to determine if the extension of the Sydney Light Rail System to Lilyfield results in an increase in the prevalence of physical activity (primarily walking) in the affected area, in comparison with a demographically similar area which is not affected by the light rail extension.Read moreRead less
Understanding The Role Of Human Lens UV Filters In Age-Related Cataract
Funder
National Health and Medical Research Council
Funding Amount
$227,036.00
Summary
Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). ....Cataract is the most common cause of blindness worldwide, The cause of cataract is currently unknown and the only treatment available at present is surgery. This represents a huge burden on the Health budgets of all developed nations, including Australia. It has been estimated that if a treatment could be developed that simply delayed the onset of cataract by 10 years, the need for surgery would be halved. The savings to the Health budget in the USA alone would be approximately $2 billion (US). We believe, on the basis of our previous research, that human lens UV filter compounds play a major role in the protein modification that is the hallmark of age-related cataract and indeed may be the key factor in precipitating cataract. This proposal seeks to confirm this hypothesis. If this theory is confirmed, it opens the door to pharmacological intervention for cataract by, for example, treating patients (or possibly all people in middle age) with drugs that inhibit the synthesis of the UV filter compounds.Read moreRead less
Remodelling Of Bacterial Outer Membranes: Implications For Vaccine Development.
Funder
National Health and Medical Research Council
Funding Amount
$558,189.00
Summary
We have identified proteins located in bacteria that are responsible for growth and the transport of essential nutrients. We will use a combination of bacterial genetics, protein biochemistry and immunological techniques to fully characterize these proteins. This strategic knowledge has direct implications for vaccine development and National security, since similar species of bacteria were amongst the first biological weapons.
Extension Of The Calcium Intake Fracture Outcome Study
Funder
National Health and Medical Research Council
Funding Amount
$272,025.00
Summary
Osteoporosis is a largely preventable disease yet 1 in 10 Australians have osteoporosis. Every year >64,000 osteoporotic fractures occur, which is one every 8.1 minutes and women are three times as likely to have the disease than men. The Bone and Calcium Research Group at the University of Western Australia, is studying how to prevent osteoporosis in elderly women. This study is called the Calcium Intake Fracture Outcome Study or CAIFOS. During 1998, 1,500 women were recruited to study wheth ....Osteoporosis is a largely preventable disease yet 1 in 10 Australians have osteoporosis. Every year >64,000 osteoporotic fractures occur, which is one every 8.1 minutes and women are three times as likely to have the disease than men. The Bone and Calcium Research Group at the University of Western Australia, is studying how to prevent osteoporosis in elderly women. This study is called the Calcium Intake Fracture Outcome Study or CAIFOS. During 1998, 1,500 women were recruited to study whether a daily calcium supplement for 5 years helps to prevent fractures compared to a diet without a supplement. To do this only half of the women were given calcium supplements and the other half were given matched placebo tablets. Each year the study participants are reviewed and asked whether or not they have broken any bones and have other measurements to monitor their bone health and overall health. The subjects are entering their last year of treatment and will finish the study during 2003. At this appointment all subjects will undergo the same series of measurements that they had at the beginning of the study to determine whether or not they have fractured any bones, improved their bone mass and overall health during the treatment stage. The main outcome of the study is to determine whether calcium is useful as a supplement to prevent osteoporotic fracture in elderly women. If this study finds that fewer women fractured in the calcium treated group compared to the non treated group, given that both groups were similar to begin with, we can say that supplementation with calcium prevents fractures. Thus, public health messages about preventing osteoporosis will be able to direct the community to take supplements to prevent a disease that creates pain and disability in later life. The advantage of this study is that it is studying other aspects of these women health, so we can determine whether the calcium is safe to use and improves people's quality of life.Read moreRead less
GPI Anchored Forms Of The Dengue Virus NS1 Protein: Production And Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$203,448.00
Summary
Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we h ....Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.Read moreRead less
Identification And Function Of Posttranslational Modifications In The Dioxin Receptor/Arnt Transcription Factor
Funder
National Health and Medical Research Council
Funding Amount
$448,500.00
Summary
Polycyclic aromatic hydrocarbons (PAHs) are prevalent environmental pollutants which cause a wide range of deleterious health effects. Metabolic activation of PAHs occurs primarily through a set of intracellular oxidising enzymes which are induced by the presence of PAHs. The dioxin receptor is a gene regulatory protein that is pivotal in the metabolic pathway as it links the presence of contaminating PAHs to induction of the enzymes responsible for initiating their metabolism. While in many cas ....Polycyclic aromatic hydrocarbons (PAHs) are prevalent environmental pollutants which cause a wide range of deleterious health effects. Metabolic activation of PAHs occurs primarily through a set of intracellular oxidising enzymes which are induced by the presence of PAHs. The dioxin receptor is a gene regulatory protein that is pivotal in the metabolic pathway as it links the presence of contaminating PAHs to induction of the enzymes responsible for initiating their metabolism. While in many cases PAHs are oxidised to compounds which are water soluble and excretable (and therefore harmless), some substrates, such as benzo[a]pyrene found in cigarette smoke, can become inadvertently transformed into carcinogens. Other pollutants such as dioxin are resistant to metabolism and are extremely toxic. We have an ongoing interest in deciphering the biochemical pathways which lead to aberrant metabolism, and as such are studying the mechanistic role of the dioxin receptor in this process.Read moreRead less