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Neural Mechanisms Mediating Inhibitory Influences Of Hyperthermia, Fever And Age On Water Intake
Funder
National Health and Medical Research Council
Funding Amount
$324,125.00
Summary
An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand ....An adequate intake of fluid following losses of body water that can occur as the result of sweating in hot weather, exercise, vomiting or diarrhoea is necessary so that dangerous levels of dehydration do not occur. Thus, it is important for our health that thirst is properly stimulated when we do become dehydrated, in order that we are aware that we must drink water. There may be conditions in which the thirst mechanism is inhibited, and the aim of these experiments is to identify and understand mechanisms by which the thirst mechanism in the brain is supressed. We have observed that a high body temperature may have an inhibitory influence on thirst in rats, and it is also known that thirst mechanisms are depressed in elderly people. If we can identify the regions of the brain that are involved and the mechanisms underpinning this reduced thirst, then it will be possible to identify and alert people at risk and to design strategies to prevent dangerous levels of dehydration occurring due to reduced thirst, particularly in the elderly. This may also apply to to people who may be working or undertaking vigorous exercise in hot weather or taking certain medications.Read moreRead less
Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will ....Fluid intake is essential for survival. Disorders of thirst whether they be excessive or inadequate have dire conseqences as evidenced in recent heat waves in Europe and Indiawhere thousands of lives were lost primarily in the elderly whose thirst mechanisms are often disrupted. The excessive fluid intake, seen in psychotic disorders such as schizophrenia, is equally damaging. Much of the research over the last 50 years has concentrated on the hypothalamic regulation of thirst. This project will attempt, for the first time, to define the location in the cerebral cortex of the drive to ingest water (perception of thirst).Read moreRead less
Effects Of Increased Endolymph Volume On Cochlear And Vestibular Function And Morphology Of Inner Ear Tissues
Funder
National Health and Medical Research Council
Funding Amount
$313,391.00
Summary
Our recent research suggests that the vertigo attacks associated with enlarged fluid volumes in the inner ear, in diseases such as Ménière's Disease, maybe triggered when the fluid pressure forces open tissue valves located in the fluid-ducts connecting the hearing and balance organs. This project aims to identify the functional role of these valves, and to develop an animal model of abrupt changes in vestibular activity due to hydrops, to allow future treatments to be developed.
Acute Exercise And Digoxin Effects On Skeletal Muscle Na+,K+ATPase Regulation, K+ Homeostasis And Fatigue In Humans:
Funder
National Health and Medical Research Council
Funding Amount
$177,000.00
Summary
This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined ....This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.Read moreRead less
A Randomised Controlled Trial Of A Fluid Containing 140mmol/L Of Sodium Compared To A Fluid Containing 77mmol/L Of Sodium For Maintenance Intravenous Fluid Therapy In Hospitalised Children.
Funder
National Health and Medical Research Council
Funding Amount
$183,959.00
Summary
Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treat ....Intravenous fluid therapy is one of the most common and important treatments for children in hospital. In spite of this we know very little about what fluid should be used and there is now good evidence that children are experiencing adverse outcomes because of fluid treatment. The aim of this trial is to determine which intravenous fluid is best in children. It will be the largest and most relevant intravenous fluid trial performed in children. The results will have an immediate impact on treating children worldwide.Read moreRead less
Lung Injury: Influence Of Sodium, Water, Albumin, Gravity And Body Position
Funder
National Health and Medical Research Council
Funding Amount
$117,331.00
Summary
Although patients with poor oxygenation often require mechanical ventilation, only therapies that reduce lung damage improve outcome whereas therapies that improve oxygenation have not been shown to improve outcome. This project will examine the role of two common interventions in critically ill patients, fluid resuscitation and posture change, on lung injury. It is anticipated this will lead to clinical trials that will further improve survival in ventilated patients with respiratory failure.
Neural Circuits Which Limit Alcohol And Soft Drink Intake
Funder
National Health and Medical Research Council
Funding Amount
$523,949.00
Summary
Alcohol and soft drinks are ubiquitous, and often harmful, particularly in excess. This project will examine the specific roles of fluid and food satiation neural circuits in suppressing intake, to determine whether either or both could be therapeutic targets for alcohol/soft drink overconsumption, especially as cessation aids for binge-drinking behaviour.
Open-label Randomised Trial Of Tolvaptan Versus Fluid Restriction In Hospitalised Patients With Moderate-severe Hyponatraemia
Funder
National Health and Medical Research Council
Funding Amount
$132,743.00
Summary
Low blood sodium level, known as hyponatraemia, is the most common electrolyte problem. It occurs in 15% of hospital patients, and can cause confusion, seizure and fatal brain swelling. Standard treatment for hyponatraemia is limiting oral fluid, but this is slow and not always effective. The drug tolvaptan works in mild hyponatraemia, but hasn't been formally tested in severe cases. We will compare benefits and risks of tolvaptan versus fluid restriction in patients with severe hyponatremia.
Restrictive Versus Liberal Fluid Therapy In Major Abdominal Surgery: The RELIEF Trial
Funder
National Health and Medical Research Council
Funding Amount
$2,477,820.00
Summary
Major surgery can result in serious complications, some of which lead to permanent disability and early death. All patients undergoing major surgery require intravenous fluids to maintain a healthy circulation, but too much fluid can cause tissue swelling (oedema) and "drown" the vital organs. There are probable benefits of a restrictive IV fluid regimen. This could have major benefits to patients having surgery.