A Prospective Study Of Traumatic Stress In Children Involved In Motor Vehicle Accidents
Funder
National Health and Medical Research Council
Funding Amount
$185,889.00
Summary
Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient severity to warrant attendance at hospital. This project is of significa ....Motor vehicle accidents (MVAs) are relatively frequent major life trauma that represent significant life threatening experiences. Not surprisingly evidence suggests that MVAs represent a frequent trigger for the development of post traumatic stress disorder (PTSD), although studies have typically focussed upon adult survivors. Local statistics indicate a significant proportion of children will experience a MVA of sufficient severity to warrant attendance at hospital. This project is of significance because it will provide badly needed information about the prevalence and course of emotional and behavioural problems in children following exposure to a serious MVA. More broadly the study should provide valuable information on post-traumatic stress responses in children. Furthermore, it will enable us to identify the factors that place children at particular risk of developing psychological problems following a MVA. This will provide information to help design of interventions to prevent the development of PTSD and other forms of psychopathology following MVAs. Such data will also permit identification of those children who are at particular risk of psychological morbidity after MVA trauma and for whom preventive interventions are most likely to be beneficial.Read moreRead less
Mitochondrial Iron Overload And Friedreich's Ataxia: The Role Of Frataxin In Iron And Haem Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$606,000.00
Summary
Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that c ....Friedreich's ataxia (FA) is due to the lack of a protein known as frataxin. A variety of studies using Baker's yeast and conditional frataxin knockout (KO) mice have shown that deletion of frataxin leads to the accumulation of toxic iron in their mitochondrion. More recently, a variety of studies have shown that FA patients have iron-loading within their mitochondrion. Iron in the highly redox active environment of the mitochondrion could contribute to the generation of cytotoxic radicals that cause severe damage. Further, cells deficient in frataxin are sensitive to oxidant stress and Fe chelators rescue oxidant-mediated death of cells from FA patients. Indeed, free radical scavengers have shown to be of use in the treatment of this disease. Studies in DR's lab during this NHMRC grant have shown that frataxin is down-regulated by erythroid differentiation or the haem precursor, protoporphyrin IX (BLOOD 2002;99:3813-22). These data indicate a role for frataxin in Fe metabolism and the pathogenesis of FA. In this study we will continue to examine the role of frataxin in the way cells handle Fe using experimental models developed under the current NHMRC grant. These include transfected cell lines with low frataxin expression generated using an expression vector containing anti-sense frataxin cDNA. Further we obtained the frataxin conditional KO mouse and generated a breeding colony. These animals display many of the pathological features of FA and are the best current model of the disease. Indeed, they will be critical for assessing the role of frataxin in Fe metabolism and as a model to test the ability of Fe-binding drugs to prevent the pathology observed. We designed lipid-soluble chelators that can enter the mitochondrion to bind Fe (Biochim Biophys Acta 2001;1536:133-140) and these ligands will be tested to prevent disease progression in the KO mice. This exciting research is crucial for understanding the pathogenesis of FA and in creating new therapies.Read moreRead less
Enhancing Treatment Effectiveness In Acute Stress Disorder
Funder
National Health and Medical Research Council
Funding Amount
$235,330.00
Summary
Posttraumatic stress disorder (PTSD) is the most common psychiatric condition to develop after trauma. Early intervention of PTSD following a trauma is indicated because chronic PTSD can be resistant to treatment. Early intervention is possible because acute stress disorder immediately after a trauma identifies those people who will develop chronic PTSD. Although cognitive behaviour therapy of acute stress disorder can effectively prevent PTSD in many cases, many people do not benefit from this ....Posttraumatic stress disorder (PTSD) is the most common psychiatric condition to develop after trauma. Early intervention of PTSD following a trauma is indicated because chronic PTSD can be resistant to treatment. Early intervention is possible because acute stress disorder immediately after a trauma identifies those people who will develop chronic PTSD. Although cognitive behaviour therapy of acute stress disorder can effectively prevent PTSD in many cases, many people do not benefit from this treatment because this treatment involves exposure to distressing memories and emotions, and this contributes to many people dropping out of treatment. This project aims to extend the utility of early intervention following trauma by assessing approaches that can be used by most trauma survivors. The project compares early intervention with either exposure, cognitive therapy, combined exposure and cognitive therapy, or supportive counseling. All therapy will be conducted in the initial four weeks and will comprise 6 sessions. Assessments will be conducted posttreatment, six-months follow-up, and one-year follow-up. The outcomes of this project will have significant public health benefits because they will lead to increased treatment effectiveness for acutely traumatized people, and will markedly reduce the incidence of PTSD in the community.Read moreRead less
Mitochondrial Dysfunction And Pathways Of Cell Death In Drug-induced Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$301,650.00
Summary
Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Furt ....Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Further, several herbal medicines have been implicated as causing liver disease. This project is designed to help us understand why and how 3 particular drugs damage the liver. We will study panadol, diterpenoids the active ingredients of skullcap, a herbal medicine, and azathioprine (imuran), a drug commonly used to suppress rejection after kidney or liver transplantation which occasionally causes very severe liver disease. Our main hypothesis is that these drugs damage mitochondria, the energy generating structures that form the engine of all living cells. We already know a little about how drug metabolites of panadol and the diterpenoids can damage mitochondria, but no-one has proven that this is the most important way in which they damage the liver. For drugs like azathioprine in which liver damage is rare, we are proposing that genetic defects in the mitochondrial DNA are what could predispose to liver injury. Thus our measurements will include how much mitochondrial DNA damage is caused by the drugs. Panadol, diterpenoids and azathioprine cause liver cell death by differing pathways (called apoptosis and necrosis). There are plausible ways in which mitochondrial damage could start off either (or both) cell death pathways during drug-induced liver injury, and we plan to test these. The new knowledge gained about how drugs damage the liver will be instrumental in allowing us to design new approaches to treat this important problem.Read moreRead less
How well people perform in everyday situations is often determined by memory function. When required to perform under stress memory performance is often affected. The effect of a psychological stress test on memory function in healthy volunteers and the ability of a dietary supplement, tyrosine, to prevent the effects will be studied. The data may suggest that depletion amino acids is responsible for the decrements in performance that are evident after an acute stressor.
I have discovered particular factors produced by our white blood cells have the ability to shut down or boost protein production in the gut, pancreas and lung. My vision is to harness these to devise new strategies for treatments for infectious and non-infectious diseases (inflammatory bowel disease, diabetes) that have a high burden on our healthcare system.
Central Control Of Stress-induced Changes In Immune Function.
Funder
National Health and Medical Research Council
Funding Amount
$411,724.00
Summary
LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol ....LONG-TERM STRESS CAN ALTER OUR BRAIN'S ATTEMPTS TO FIGHT INFECTION Long-term stress is often blamed for causing illness but precisely how this occurs is now only beginning to be realised. It is especially disturbing that long-term stress can increase one's susceptibility to infections. Stress can alter the way our brain can help deal with assaults by bacteria and viruses. Normally, at the start of an infection, we release a hormone called cortisol from our adrenal glands. A low level of cortisol in our body is beneficial because it can prevent the infection from taking hold in our body and spreading. However if we are chronically stressed our brains tell the adrenal glands to secrete excessive amounts of cortisol over long periods of time and this imbalance can actually hinder the ability of one's immune system to fight an infection. The unfortunate consequence is that the infection is more likely to win the battle and spread to cause further havoc. The present study will identify which areas of the brain are important in driving the secretion of cortisol during infection and how long-term stress can influence those areas. Because we might be exposed to long-term psychological stress that is repeated regularly or irregularly we will determine which pattern of stress has the greatest effect. An investigation into how the brain operates during long-term stress and infection will help us develop ways to prevent stress from disrupting our immune systems.Read moreRead less