Novel Genes And Protein In Non-alcoholic Fatty Liver Disease: Potential Basis Of A Serum-based Assessment Of Disease Sta
Funder
National Health and Medical Research Council
Funding Amount
$200,000.00
Summary
The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infe ....The most common cause of elevated liver function tests is non-alcoholic fatty liver disease (NAFLD). NALFD is a spectrum of disease ranging from steatosis, to non-alcoholic steatohepatitis (NASH), a condition associated with the development of fibrosis in the majority of individuals. Approximately 20% and 3% of adults are affected with NAFLD and NASH, respectively, and NAFLD is expected to become the next major liver epidemic facing the western world, far exceeding the prevalence of chronic infection with the hepatitis C virus. We obtained liver biopsies from patients with NAFLD, 80% of whom had NASH, and determined the expression profile analysis of each subject using 19,200 element microarrays. Our data demonstrates the concordant differential expression of 130 genes, in subjects with NAFLD that were categorizes into 6 major metabolic and regulatory pathways. Many of these genes represented uncharacterised genes. Utilising an extensive bioinformatics approach we have been able to define the genes and their protein product. The use of these proteins as a diagnostic tool for the detection of NAFLD forms the basis of a provisional patent application. However, measurements of protein levels in tissue and sera from patients with NAFLD are needed for the development of a diagnostic method. Such information would also provide significant insight into the pathogenesis of NAFLD. The AIMS are: 1) Production of antibodies against proteins encoded by candidate genes Expression profile of candidate genes 3) Expression of proteins encoded by candidate genes in patients with NAFLDRead moreRead less
Development Of Anti-CXCR7 MAbs For The Treatment Of Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$399,998.00
Summary
Fibrosis is a serious biological process that occurs in many disease conditions, including cancer, inflammation and infections. We have produced antibodies to CXCR7, and these antibodies completely inhibit fibrosis in a mouse model. We plan to develop these antibodies in to a suitable drug for human clinical trials.
Acoustic Blood Pressure Measurement On Implanted Biomedical Surfaces
Funder
National Health and Medical Research Council
Funding Amount
$184,687.00
Summary
Measurement of local blood pressure in is of great clinical importance. An application of particular interest is the pressure measurement in and around endoluminal stents grafts, which are used for the treatment of Abdominal Aortic Aneurysms (AAAs). These grafts are implanted by keyhole surgery and are used to reduce the pressure on the aneurysm walls so that the artery can revert to its more anatomically correct shape on a timescale of one to two years. If the seal between the graft and the art ....Measurement of local blood pressure in is of great clinical importance. An application of particular interest is the pressure measurement in and around endoluminal stents grafts, which are used for the treatment of Abdominal Aortic Aneurysms (AAAs). These grafts are implanted by keyhole surgery and are used to reduce the pressure on the aneurysm walls so that the artery can revert to its more anatomically correct shape on a timescale of one to two years. If the seal between the graft and the artery wall is not blood tight, then the aneurysm can become repressurised and may keep on expanding. Over time, an untreated, expanding AAA is likely to rupture with severe consequences for the patient. Thus a convenient, non-invasive means of measuring the pressure within the aneurysm and within the graft is highly desirable. In this proposal, we seek to produce a device that can be incorporated into the walls of the endoluminal graft, which can measure absolute pressure inside and outside the graft and where the pressure measurements can be obtained via standard acoustic or medical ultrasound equipment. To do this, we would use specially designed 'bubbles' which can be incorporated onto either side of the graft walls, where the resonant frequency of the bubbles provides a direct measurement of the pressure around the bubbles. Trials at the CSIRO have found that pressures can be measured to a resolution of better than 10 mmHg by using this technique on air bubbles in water. In this proposal, we wish to develop flexible, but semi-permanent bubbles that can be incorporated onto a biomedical implant surface. If such bubbles can be made, the researchers will use CSIRO-developed software and acoustic equipment such that local blood pressure can be measured in real time.Read moreRead less
An Inside-out Approach To Muscosal Vaccination: MAdCAM Targeting
Funder
National Health and Medical Research Council
Funding Amount
$174,250.00
Summary
The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the ....The mucosal surfaces are the entry site for many pathogens (eg. cholera, rotaviruses, helicobacter, SARS and sexually transmitted diseases including HIV infections). The ideal vaccine would elicit both systemic and mucosal immune response, enhancing immunity at this first line of defence. The oral route has formidable barriers to antigen uptake such as digestive enzymes, commensal microbes, mucous layers and gastric acid. Our strategy targets the vascular addressin found in immune tissues of the gut (called MAdCAM) so that the vaccine is linked to an antibody against MAdCAM. Thus for the first time we believe that a parenteral vaccine ie. injected im or iv (bypassing the oral barriers) can induce mucosal immunity.Read moreRead less
EBC46 is a novel compound from the rain forest, being developed for cancer treatment by QBiotics Ltd and Queensland Institute of Medical Research. Injection of EBC46 into tumors in 5 different animal species rapidly destroyed the tumor, with good healing and no adverse effects. EBC46 therefore has potential for local control, perhaps cure, of a wide range of tumor types in humans.
Effects Of Pin Biomechanics, Coating Material And Surface Roughness On The Pin-bone Interface In External Repair
Funder
National Health and Medical Research Council
Funding Amount
$470,000.00
Summary
Some fractures require external fixation, anchored with metal pins in the bone fragments. The reatment is generally successful, although the pin tracts often loosen and become infected. This complication may jeopardise fracture healing and must be treated. The purpose of this project is to determine what aspects of pin design predispose to these problems at the pin-bone interface. Is it the way the pins are initially inserted, perhaps not tightly enough so that the pin is unstable, or perhaps to ....Some fractures require external fixation, anchored with metal pins in the bone fragments. The reatment is generally successful, although the pin tracts often loosen and become infected. This complication may jeopardise fracture healing and must be treated. The purpose of this project is to determine what aspects of pin design predispose to these problems at the pin-bone interface. Is it the way the pins are initially inserted, perhaps not tightly enough so that the pin is unstable, or perhaps too tight, causing microcracks in the bone? Is it the material of the pin, which might be improved with a bioactive coating? Is it the surface roughness which causes different responses of bone cells? Would it help to have an antibiotic pin? This proposal is designed to answer these questions. The biomechanics of the pin will first be studied with computer models and then tested in the laboratory. The loosening and infection associated with different types of pin will then be studied biologically. The results of the study will clarify the roles of pin biomechanics, coating and surface roughness, leading to improvements in design and better outcomes in fracture patients.Read moreRead less