A Prospective Study Of The Psychiatric & Medical Characteristics Of Post-infective Fatigue & Chronic Fatigue Syndrome.
Funder
National Health and Medical Research Council
Funding Amount
$500,000.00
Summary
This project forms the central component of a larger set of studies which investigate competing psychiatric, immunological and infective models of the causes of a number of chronic fatigue syndromes, including post-infective fatigue. The study takes place in western NSW where certain viral illnesses (Glandular Fever, Ross River Virus) and a non-viral infection (QF) are common and have been associated with prolonged fatigue states. The study follows patients from laboratory-documented infections ....This project forms the central component of a larger set of studies which investigate competing psychiatric, immunological and infective models of the causes of a number of chronic fatigue syndromes, including post-infective fatigue. The study takes place in western NSW where certain viral illnesses (Glandular Fever, Ross River Virus) and a non-viral infection (QF) are common and have been associated with prolonged fatigue states. The study follows patients from laboratory-documented infections with appropriate infective, immunological and psychological measures throughout the course of their acute illness, the early recovery period and for the next 12 months. These patients are compared with people who present to their doctor with other forms of medically-unexplained fatigue. Very few previous studies have used an appropriate prospective design and followed patients with documented illness from the onset through to the development of specific forms of chronic fatigue. Further, the study is unique in terms of the range of viral and non-viral agents being investigated. It relies on the combined psychiatric, immunological and infective disease expertise of a group of researchers with an international reputation for the successful completion of such multidisciplinary projects. The initial phase of the study has demonstrated that the research team has the capacity to complete this project. Initial results have already demonstrated the potential roles of psychological and immunological factors in causing some cases of prolonged fatigue. Further, the initial results indicate that two key symptom sets (fatigue, psychological distress) can be adequately measured during the recovery phase and are predicted by differing psychological factors. The study will result in the identification of different psychiatric risk factors to chronic fatigue, assist development of clear diagnostic guidelines for post-infective fatigue and guide relevant aetiological and treatment research.Read moreRead less
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
Energy Use And Work Output By Cross-bridges In Fast- And Slow-twitch Muscles
Funder
National Health and Medical Research Council
Funding Amount
$191,177.00
Summary
All voluntary movement is produced by the action of skeletal muscles. The muscles provide the mechanical power required to move the limbs and the body. To do so, they require energy which is ultimately derived from the breakdown of food. Therefore, we can describe the fundamental process underlying muscular contraction as the conversion of energy from a chemical form into a mechanical form. This project investigates the relationship between the breakdown of molecules that provide energy and the ....All voluntary movement is produced by the action of skeletal muscles. The muscles provide the mechanical power required to move the limbs and the body. To do so, they require energy which is ultimately derived from the breakdown of food. Therefore, we can describe the fundamental process underlying muscular contraction as the conversion of energy from a chemical form into a mechanical form. This project investigates the relationship between the breakdown of molecules that provide energy and the production of mechanical energy or work. Normal contraction involves many cyclic interactions between two proteins, actin and myosin. Each cycle produces a tiny force that contributes to the shortening of the muscle. For over 30 years, it has been thought that energy required for each force producing cycle was provided by the breakdown of one energy-providing molecule, called ATP. Almost all current models of muscle contraction are based on this idea. Recently, data from studies using isolated actin and myosin and observing their interaction in vitro have indicated that many force-producing cycles may be performed with the energy from just one ATP. If this is correct, it will revolutionise our ideas about the way muscles convert chemical energy into mechanical energy. However, the interaction of proteins in a dish is far removed from a normal muscle and the aim of this project is to determine the relationship between force producing cycles and energy use in intact muscles. If multiple force-producing cycles can be powered by one ATP molecule in intact muscle too, then the current idea that the biochemical processes that release energy from ATP are intimately linked to the mechanical changes in myosin that occur as it produces force will be untenable. In short, we will have to rediscover how muscles convert chemical energy into mechanical energy and find out how that energy can be stored from one force-producing cycle to the next.Read moreRead less
The Relationship Between Fatigue, Sleepiness And Crash Risk While Driving
Funder
National Health and Medical Research Council
Funding Amount
$444,070.00
Summary
Driver fatigue is a major road safety problem that is currently managed by encouraging drivers to take breaks when they feel tired. Unfortunately we dont know whether drivers really are able to detect when they are too tired to drive safely or, if they can make this judgement, whether and what motivates them to stop driving. This research will look at driver awareness of fatigue effects and what indicators and motivators can be used to encourage them to respond to signs of impaired driving.
Muscle fatigue is common after exercise in healthy people. In many tasks, some muscles become more fatigued than others. Thus, the nervous system must often coordinate fatigued muscles (which produce less force) with unfatigued muscles. We will investigate how fatigue of one muscle alters the way the brain controls other muscles that are engaged in the same task or in unrelated tasks. This will aid understanding of the failures of coordination that lead to poor performance and injury.
CBS Domain Modulation Of Muscle Chloride Channels; Molecular Mechanism And Physiological Role.
Funder
National Health and Medical Research Council
Funding Amount
$523,455.00
Summary
Muscle chloride channels regulate how readily muscles are activated, particularly during muscle fatigue. Recently we have identified a feed-back mechanism linking chloride channel function to muscle acidosis and energy depletion, key factors in fatigue. Here we will investigate the molecular details of this mechanism and its role in muscle physiology and fatigue. This mechanism may present a future target for the treatment of myotonia, a condition where muscles are too readily activated.
How Changes In The Motor Cortex And Spinal Cord With Exercise Contribute To Fatigue In Humans
Funder
National Health and Medical Research Council
Funding Amount
$311,250.00
Summary
Fatigue with exercise is a common experience in healthy people and can be a problem in many illnesses. With fatigue people are less able to produce force with their muscles. Much of this weakness occurs because of events in the muscles but some results from changes in the nervous system. The size of the contribution of the nervous system to fatigue is not known for the kinds of exercise that cause fatigue in everyday life e.g. prolonged weak contractions like holding the shopping or a plate of f ....Fatigue with exercise is a common experience in healthy people and can be a problem in many illnesses. With fatigue people are less able to produce force with their muscles. Much of this weakness occurs because of events in the muscles but some results from changes in the nervous system. The size of the contribution of the nervous system to fatigue is not known for the kinds of exercise that cause fatigue in everyday life e.g. prolonged weak contractions like holding the shopping or a plate of food, rhythmic contractions like walking or painting a wall, and more vigorous exercise that causes changes in breathing and body temperature. The behaviour of nerve cells in the brain and spinal cord is altered in fatigue but how and why many of these changes occur, and how they affect the control of movements, is poorly understood. Three approaches are planned. In the first set of studies, we will use brain and nerve stimulation to measure the impact of sustained low-level activities on people's ability to drive their muscles fully. We will identify whether such activities, as well as increased demands on other body systems, can cause fatigue in the nervous system. In the second set of studies, we will investigate whether changes in the motor areas of the brain can alter peoples' performance of fatiguing motor tasks or their perception of how much effort the tasks take. Finally, we will use stimulation of the spinal cord to work out why motor nerve cells in the spinal cord fire more slowly with fatigue. Fatigue is an important symptom which is not confined to diseases of any one system in the body. For example, it is a major complaint in multiple sclerosis, cardiac failure, chronic obstructive airway disease, depression and cancer, as well as after chemotherapy, surgery, and viral illness. The implications of better understanding of the contribution of the nervous system to fatigue range from targeting treatments in patients to improving the performance of athletes.Read moreRead less
Role Of Nitric Oxide And Reactive Oxygen Species In Excitation-contraction Coupling In Skeletal Muscle.
Funder
National Health and Medical Research Council
Funding Amount
$163,250.00
Summary
Excitation-contraction (E-C) coupling is a term used to broadly describe the sequence of cellular events that starts with an electrical signal at the surface membrane of a muscle cell and which then ultimately leads to muscle contraction. Although the overall sequence is known, there remain many gaps in our understanding of the mechanisms involved not only related to normal muscle function but to how this function may be impaired by excessive exercise and disease. Many cellular metabolites contr ....Excitation-contraction (E-C) coupling is a term used to broadly describe the sequence of cellular events that starts with an electrical signal at the surface membrane of a muscle cell and which then ultimately leads to muscle contraction. Although the overall sequence is known, there remain many gaps in our understanding of the mechanisms involved not only related to normal muscle function but to how this function may be impaired by excessive exercise and disease. Many cellular metabolites contribute towards the normal control of muscle contraction, while others contribute to its impairment. Reactive oxygen species (ROS), which includes nitric oxide (NO) and related molecules, are metabolic factors often referred to as cellular oxidants. They are thought to have an essential role in controlling normal muscle function. Paradoxically, they are also implicated in the impairment of muscle function associated with fatigue, disease and aging. How these molecules both control normal muscle activity and also contribute to impairment of such function remains unclear. Thus, the central aim of this project is to identify the mechanisms by which the cellular oxidants, NO and other ROS, both control normal E-C coupling in skeletal muscle fibres and how they contribute to muscle fatigue. Clearly, understanding how skeletal muscle normally contracts is essential in order to better understand how muscle function can become impaired with exercise, disease and age. The work from this study will provide insight into both normal muscle physiology and how muscles fatigue and ultimately provide new methodologies and drugs that may combat fatigue, disease and age related changes to muscle function.Read moreRead less