How Important Is Collagen Destruction In Arthritis? A Study With Collagenase-resistant Knockin Mice
Funder
National Health and Medical Research Council
Funding Amount
$529,723.00
Summary
Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is n ....Aggecan and collagen are important structural molecules in cartilage. Together they allow cartilage to bear weight and resist compression. In arthritis, collagen is degraded by collagenases and aggrecan is degraded by aggrecanases. Aggrecan loss is a feature of cartilage disease. Early aggrecan loss is well documented and usually precedes clinical symptoms, suggesting that it is the initiating step in cartilage pathology. Aggrecan loss precedes collagen damage in explant culture, however it is not known whether inhibiting aggrecanases is sufficient to block cartilage damage long-term. In contrast, other studies suggest that aggrecan is only lost after damage to the collagen scaffold. These studies propose that clipping of the collagen scaffold may initiate aggrecan release; with progressive degeneration and collagen clipping, more aggrecan is lost, until ultimately the scaffold is severely damaged and aggrecan is severely depleted. Cartilage can only withstand a limited degree of collagen degradation and any significant damage to the network is widely considered to be irreparable. It is unclear what role aggrecanases and collagenases have in initiating and perpetuating cartilage damage. We have mice with aggrecan resistant to aggrecanases and mice with inactive aggrecanase. We will also create mice with collagen resistant to collagenase. We will use these mice to determine the contribution of collagenases and aggrecanases to the initiation and progression of cartilage damage, in three models of joint disease. We will identify differences in time of disease onset, rate of disease progression and disease severity. The results will show whether one or both activities is important for the initiation and progression of joint disease. This will reveal whether single or combination therapies are required for the management of arthritis. The research will inform the pharmaceutical industry on directions for the development of new drugs to prevent joint disease.Read moreRead less
Determining The Potential For Porcine Foetal Islet Xenotransplantation.
Funder
National Health and Medical Research Council
Funding Amount
$351,660.00
Summary
Tight glucose control by insulin injection minimises diabetic complications but restricts lifestyle. An alternative, pancreatic islet transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term foetal pig islet function in the absence of an immune response. It will outline the genetic characteristics of this pig colony and carefully catalogue the type, number and distribution o ....Tight glucose control by insulin injection minimises diabetic complications but restricts lifestyle. An alternative, pancreatic islet transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term foetal pig islet function in the absence of an immune response. It will outline the genetic characteristics of this pig colony and carefully catalogue the type, number and distribution of endogenous retroviruses within pig genes. It may provide a basis from which new strategies can be developed to overcome rejection. Ultimately a unique Australian resource will be developed which may provide unlimited islets for safe, large-scale transplantation of diabetics before they develop debilitating complications.Read moreRead less
Evaluating And Disseminating The Implementation Success Of A Surgical Training Program
Funder
National Health and Medical Research Council
Funding Amount
$181,065.00
Summary
Removal of the uterus (hysterectomy) is the most commonly performed major surgical procedure in women (30,000/yr in Australia). Internationally, only about 25% of hysterectomies are still performed through an open abdominal approach, compared to 40% in Australia. This means that too many women in Australia will suffer unnecessary side-effects, pain and long recovery, keeping them away from their family and usual tasks longer than necessary.
NON IMMUNOLOGICAL BARRIERS TO SUCCESSFUL TREATMENT OF DIABETES BY XENOTRANSPLANTATION
Funder
National Health and Medical Research Council
Funding Amount
$310,500.00
Summary
Tragically patients whom suffer from diabetes mellitus develop major secondary complications such as renal failure, even with today's tight glucose control. Insulin injections minimise diabetic complications but restricts lifestyle and an alternative, pancreatic islet cell transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term pig fetal and neonatal islet cell function in ....Tragically patients whom suffer from diabetes mellitus develop major secondary complications such as renal failure, even with today's tight glucose control. Insulin injections minimise diabetic complications but restricts lifestyle and an alternative, pancreatic islet cell transplantation, is limited by donor shortage. With genetic technology, pig donor tissue is a feasible donor source. This project will use an inbred pig colony to assess long term pig fetal and neonatal islet cell function in combination with a kidney graft in the absence of an immune response. Using this specifically inbred pig colony we will carefully catalogue the type, number and distribution of endogenous retroviruses within pig genes. Using new and novel techniques we will develop a new strategy by which we can block and overcome this major concern of xenotransplantation. Ultimately a unique Australian resource will be developed which may provide unlimited islets for safe, large-scale transplantation of diabetics before they develop debilitating secondary complications from their diabetes and provide an alternative to the only current method of curing endstage renal failure with a combined pancreas and kidney transplant.Read moreRead less
THE CONTROL OF TYPE 2 DIABETES THROUGH WEIGHT LOSS IN INDIGENOUS AUSTRALIANS: THE FEASIBILITY AND ACCEPTABILITY OF LAGB
Funder
National Health and Medical Research Council
Funding Amount
$600,854.00
Summary
Our recent clinical trial showed that 3 out of every 4 obese people with type 2 diabetes who undergo substantial weight loss have their diabetes go into remission. In this project we recognise in the Indigenous people specific cultural and socio-economic factors and family and community approach to health care and seek to test if the Lap-Band procedure is acceptable to them and if it is feasible to achieve substantial weight loss and control of diabetes as was seen in a European population.
CROSSFIRE: Combined Randomised And Observational Study Of Surgery For Fractures In The Distal Radius In The Elderly
Funder
National Health and Medical Research Council
Funding Amount
$551,077.00
Summary
Fractures (breaks) near the wrist are the most common fractures treated. Treatment previously consisted of straightening and plaster casting in the emergency department, but standard treatment now includes admission to hospital and surgery to apply a plate and screws to the bone. The best evidence we have (which is limited) is that surgical plating does not provide important benefits over plastering. We aim to perform a multicentre trial comparing plating to plaster for these common fractures.
The WA Safety And Quality Of Surgical Care Project: Improving The Safety, Quality And Provision Of Surgical Care.
Funder
National Health and Medical Research Council
Funding Amount
$583,500.00
Summary
The basis of this application is a three-year project which aims to improve the safety, quality and the provision of surgical care. This application constitutes the core of the WA Safety and Quality of Surgical Care Project (SQSCP), which was established in 1996 to evaluate the clinical epidemiology, health care utilisation, patient safety and health outcomes following admission to hospital for specific surgical and medical procedures in Western Australia (WA). The study will use data from the W ....The basis of this application is a three-year project which aims to improve the safety, quality and the provision of surgical care. This application constitutes the core of the WA Safety and Quality of Surgical Care Project (SQSCP), which was established in 1996 to evaluate the clinical epidemiology, health care utilisation, patient safety and health outcomes following admission to hospital for specific surgical and medical procedures in Western Australia (WA). The study will use data from the WA Data Linkage System, which brings together 15 million records from hospital morbidity, death, cancer, midwives notification and mental health databases. Surgical procedures have been selected for review based on national priorities and after consultation with the WA Branch of the Royal Australasian College of Surgeons (RACS) and other clinical Colleges. This application proposes to continue the core research activities of the SQSCP. A special focus will be on the use of minimally invasive surgical techniques including laparoscopic, endoscopic and endoluminal procedures, which have increased dramatically during the last decade. The study will also evaluate differences in the outcomes of surgical care in rural and metropolitan settings. The findings of the SQSCP will be comprehensively disseminated to surgeons, the RACS, hospital managers, health policy makers and consumers. The rationale of this project is that by providing high quality data on the epidemiology, utilisation and outcomes of surgical care, we will be able to increase the knowledge-base that will contribute to improvements in the safety, quality and provision of surgical care in Australia and internationally. The aims of the SQSCP are consistent with national health priorities and the recommendations of the Taskforce on Quality of Australian Health Care Study, the Australian Council for Safety and Quality in Health Care and the National Institute of Clinical Studies.Read moreRead less
A Randomised Controlled Trial Of The Effect Of Substantial Weight Loss On Obstructive Sleep Apnoea.
Funder
National Health and Medical Research Council
Funding Amount
$404,061.00
Summary
Obstructive sleep apnea is now commonly recognized as a major health problem and frequently ocurrs in overweight or obese individuals. Several studies have now demonstrated that weight loss can be an effective treatment for sleep apnea in those with a weight problem. But, it is extremely difficult to achieve and sustain the major weight loss required to adequately treat this condition. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in very obese ....Obstructive sleep apnea is now commonly recognized as a major health problem and frequently ocurrs in overweight or obese individuals. Several studies have now demonstrated that weight loss can be an effective treatment for sleep apnea in those with a weight problem. But, it is extremely difficult to achieve and sustain the major weight loss required to adequately treat this condition. Modern obesity surgery is the only reliable method of achieving and sustaining major weight loss in very obese individuals, and several studies have found that along with weight loss there are major improvements in sleep symptoms, and sleep apnea following weight loss surgery. Despite these findings surgery is rarely advised and has never been formally tested as a therapy for sleep apnea. We propose to formally test, for the first time, the effectiveness of weight loss surgery, as an addition to best conventional therapy, in those individuals with the combination of problems; obesity and significant sleep apnea. We propose that significant weight loss, following surgery, may indeed be the best therapy for those with these combined problems, and that weight loss may have additional benefits for other common problems related to obesity, including high blood pressure, poor body image and impaired quality of life. Forty appropriate patients who suffer these combined problems will be randomly allocated to either conventional therapy for their sleep apnea and weight problems or to a similar program that includes placement of a Lap-Band, a minimially invasive form of obesity surgery. We will follow the patients for 2-years and serially measure a broad range of health and quality of life outcomes and compare the effects of each program. This study will help us assess the role of obesity surgery in this group of patients with major health problems.Read moreRead less
Developing A Novel Glaucoma Surgery For Clinical Use And Commercialisation
Funder
National Health and Medical Research Council
Funding Amount
$565,893.00
Summary
Glaucoma is a potentially blinding eye condition that affects more than 60 million people. The greatest risk factor in glaucoma is high intraocular pressure. Surgical treatment for glaucoma seeks to lower the pressure inside the eye by increasing the drainage of fluid from the eye. There are numerous techniques available but all have risks of complications. This grant seeks to develop a novel approach to the problem using intra-ocular delivery of laser pulses to cut a drainage channel.