Role Of Transition Metal Ions And Redox Activity In The Development Of Atherosclerotic Plaques
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability ....Metal ions such as iron and copper have been reproted to be present in the lesions present in diseased human arteries and it has been suggested that these metal ions contribute to the development of atherosclerosis (hardening of the arteries) via their ability to catalyse the formation of highly reactive molecualr fragments called free radicals. Though metal ions are known to catalyse such reactions in test-tube experiments, both the presence of metal ions in diseased arteries and their ability to generate free radicals is controversial. This study will employ a novel, minimally-invasive, technique to assess the nature and quantity of metal ions present in well-defined human and animal lesions at different stages of lesion development. The ability of these metal ions to catalyse free radical formation from components present in the artery wall will also be assessed. The release of these metal ions from the artery wall to added organic molecules will be assessed as this might minimise their potential to cause damage, and provide a possible therapeutic strategy. These studies will therefore provide valuable information as to the significance and role of reactive metal ions in the development of human artery disease and the possible prevention, or minimisation, of such processes.Read moreRead less
Saccadic Eye Movements And The Neural Basis Of Visual Perception
Funder
National Health and Medical Research Council
Funding Amount
$570,828.00
Summary
The eye has a restricted central area that has good vision. We must make very frequent eye movements to build up a high resolution picture of a particular image. The term active vision is used to describe the requirement of coordinating the eye movements with the visual system. The study of active vision at the neural level requires experiments that combine single cell recording with behaviour. This study will explore which parts of the brain are involved in active vision in monkeys.
HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional thro ....HIV-1 infection is characterised by high levels of virus replication and a progressive loss of immune cells, particularly CD4+ T lymphocytes. Highly active antiretrovial therapy (HAART) for HIV-1 infection results in profound suppression of viral replication, a substantial increase in CD4+ T lymphocytes and a decrease in morbidity and mortality. The primary source of T lymphocytes in early human development is the thymus. Recently, it has been demonstrated that the thymus remains functional throughout adult life. The role of the thymus in HIV-1 infection remains controversial. Studies of the role of the thymus in HIV-1-infected individuals has been limited by the lack of a marker of thymic function in vivo. We have recently developed a novel assay to quantify cells of recent thymic origin by taking advantage of certain molecular events that occur in the thymus during the production of new T lymphocytes. This molecular event creates a circular piece of DNA, called a T-cell receptor excision circles (TREC). TREC concentration in the periphery will increase with an increase in thymic output but will reduce in the presence of T cell proliferation or cell death. In order to determine the contribution of the thymus to immune reconstitution following HAART, we plan to study the dynamics of thymus function in HIV-1 infection by measuring TREC and T cell turnover in HIV-1 infection prior to and following HAART. In a subgroup of individuals, more commonly seen following treatment of HIV-1 infection in children, there is an increase in CD4+ T lymphocytes in the absence of a significant reduction in viral suppression. The role of the thymus in this unique subset of individuals will be studied.Read moreRead less
Purinergic P2X7 Receptor As A Target For Antidepressant Drug Discovery
Funder
National Health and Medical Research Council
Funding Amount
$567,760.00
Summary
Depression is the most common mental disease. Around one million Australian adults and 100,000 young people live with depression each year resulting in significant economic, social and personal costs. Despite multiple treatments of depression, there are still several serious unmet needs with most current antidepressants showing limited effectiveness. We have identified a novel protein in the brain that represents an innovative approach to providing a platform for antidepressant drug discovery.
Analysis Of HIV Virologic Response-rebound Data: Prognostic Indicators Of Post-HAART Viral Control
Funder
National Health and Medical Research Council
Funding Amount
$144,000.00
Summary
The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to ....The introduction of potent anti-retroviral therapy into standard clinical management of HIV infected individuals has been associated with high rates of reduction in plasma viral loads over short periods of time. However, there remains considerable variation in the degree of longer-term viral control as a result of viral resistance, toxicity, timing of treatment initiation and choice of drug regimen. In particular, the most appropriate time to initiate treatment remains clouded, with the need to initiate treatment sufficiently early in order to avoid irreversible damage balanced by the problems of potential viral resistance or toxicity if started too soon. Determination of factors which will assist practitioners to optimise the timing of treatment initiation remains a high priority. Our aim in this project is to develop and study the use of novel statistical mixed-effects models designed to analyse factors associated with visit-time viral load data following commencement of therapy, taking account of the entire follow-up profiles of responses over time. The project involves both theoretical and empirical analyses of the estimation and inferential properties of the mixed-model method in conjunction with comprehensive analyses of prognostic factors associated with post-treatment virologic control in patients from the Western Australian HIV Cohort Study. These include demographic, virologic, immunologic, adherence and host genetic factors. The statistical methods developed will have wide applicability and add significantly to the suite of procedures available for the analysis of longitudinal response data.Read moreRead less
Statistical Methods To Assist The Control Of Communicable Diseases, And Their Application
Funder
National Health and Medical Research Council
Funding Amount
$211,527.00
Summary
A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River viru ....A range of programs, such as vaccination schedules and intervention in outbreaks, is in place to reduce our burden of illness from infectious diseases. This project aims to develop new methods, based on models and associated statistical analyses, to help ensure that our control programs are based on the best available evidence. There are five specific themes: 1. Developed methods for predicting major outbreaks of diseases and appy them to Australian data on measles, pertussis and Ross River virus. The new methods will enable timely intervention to reduce the population risk from these diseases, and to guide the proposed elimination of measles from Australia. 2. The current concept of vaccine efficacy, which is central to the epidemiological assessment of vaccines, performs poorly when the vaccine provides only partial protection, when immunity wanes over time and when infected vaccinees have a lower infectivity. A concept of vaccine efficacy will be developed that overcomes these weaknesses. This concept will find widespread use in epidemiology. 3. Data available from 80 outbreak investigations of transmissible diseases will be analysed to assess the relative effectiveness of various intervention steps. 4. A comprehensive model, and associated computer software, will be developed as a tool for assessing the relative merits of different vaccination schedules. It will be applied to address Australian policy issues for vaccination against pertussis, chickenpox and rubella. 5. The method of backprojection for estimating trends in HIV infection and predicting AIDS incidence will be enhanced to incorporate newly available data in which HIV and AIDS diagnoses are linked. This will enable a precise assessment of infection incidence among heterosexuals and other exposure categories with relatively few cases, to ensure that HIV does not spread more widely.Read moreRead less