Understanding How Sepsis Causes Kidney Dysfunction
Funder
National Health and Medical Research Council
Funding Amount
$471,770.00
Summary
Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the las ....Acute renal failure is a serious condition that affects up to 20% of patients in Intensive Care Units. Sepsis and septic shock remain the most important causes of acute renal failure in critically ill patients. Despite our ability to support vital organs and resuscitate patients, the incidence and mortality of septic acute renal failure remain unacceptably high at up to 55%. There have been no major advances in our understanding of its pathogenesis and in its prevention or treatment over the last 50 years. The traditional view is that sepsis-induced renal failure results from reduced perfusion of the kidney secondary to the low blood pressure. In a model of sepsis in sheep with renal failure, we demonstrated, however, that renal blood vessels dilated and blood flow increased. Furthermore, renal function improved following treatment with vasoconstrictor drugs that raised blood pressure and renal blood flow. These findings indicate that renal ischaemia is not the cause of the renal dysfunction in sepsis. We hypothesise that sepsis causes renal vasodilatation, which reduces glomerular filtration rate and renal function, and induces a delayed development of apopotosis. We will study in sepsis 1) the effects of a treatment to increase glomerular filtration rate 2) the development of apoptosis and the effect of an anti-apoptotic drug, and 3) whether there is bioenergetic failure in the kidney in sepsis and the effects of treatments on this. Finally, in septic patients we will measure renal blood flow and determine the effects of our novel treatment on this and renal function. These studies will significantly increase our understanding of the factors causing acute renal failure in sepsis. They are likely to lead to the development of new therapies to improve renal function in sepsis and their effectiveness will be examined in septic animals and patients.Read moreRead less
Potential For Creatine Or Melatonin As Dietary Supplements In Pregnancy To Prevent Perinatal Brain Damage
Funder
National Health and Medical Research Council
Funding Amount
$483,217.00
Summary
Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy su ....Brain damage in the newborn - particularly in prematurely born infants - remains a significant health problem. At present there are very few treatments that can be used to minimize damage when it becomes apparent in the newborn, and none that can be used PROSPECTIVELYduring pregnancy to protect the developing brain from damage. The most likely cause of damage to the fetal brain during pregnancy or at birth is global ASPHYXIA, either by itself or in association with other problems of pregnancy such as infection, preterm birth, or fetal growth retardation. In this project we propose that providing extra amounts of the dietary constituent creatine, or of the hormone melatonin, to the pregnant animal in late gestation, will provide NEUROPROTECTION to the developing brain in the face of an asphyxial challenge that otherwise causes damage. We will use pregnant sheep to investigate the effects of asphyxia in utero on the fetal brain using techniques that allow us to monitor metabolic changes within the brain in real time. In addition, we will use the pregnant Spiny Mouse to investigate the effects of birth asphyxia on the postnatal brain structure and behavioral development. We will study groups of animals fed a normal diet, and compare then to animals that receive additional amounts of creatine or melatonin. We expect to determine if either of these treatments have the potential to protect the developing brain from asphyxial damage, and to recommend if similar treatments could be used in pregnant women where the obstetrician suspects the baby's brain is at risk of damage.Read moreRead less
Roles Of PTHrP And Calcium In Mammary Function In Perinatal Growth Restriction
Funder
National Health and Medical Research Council
Funding Amount
$376,320.00
Summary
Babies that are born small have significant problems around the time of birth and may have limited catch-up growth. A recently discovered protein known as PTHrP influences the nutrition of the growing newborn through breast milk. Because of its potential importance to small babies we intend to study this protein during and after pregnancy in rats and their pups. New treatments may emerge from the knowledge gained from these studies that may improve the growth and health of infants.
Genomic Analysis Of Host Response To Influenza A Infection
Funder
National Health and Medical Research Council
Funding Amount
$168,530.00
Summary
Influenza virus infects millions of people globally. However, it remains poorly understood why some infected individuals succumb to life threatening complications whilst others recovered relatively unaffected. This study use advance molecular technique to study influenza infection. It aims to identify the key steps in our immune systems that are progressively disrupted during influenza infection and how this process lead to a break down in our natural defence against the virus.