Comparison Between AICAR And Exercise-induced Stimulation Of Skeletal Muscle AMP-K On Fat/glucose Metabolism In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-ins ....Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-insulin factors. The chemical catalyst AMP activated protein kinase (AMP-K), which has been investigated only in normal exercising rats, is an important alternative regulator of acute sugar processing and energy supply for exercising SkM. No studies of AMP-K activity are available in diabetes. Our studies will focus on i) how important is the stimulation of SkM AMP-K in diabetes to efficient SkM sugar processing and energy production; ii) if the benefits of exercise can be simulated by pharmacological stimulation of AMP-K in sedentary diabetic subjects. We aim to i) compare the metabolic effects of exercise vs pharmacological stimulation of AMP-K in normal and diabetic subjects; ii) define the molecular mechanisms which trigger the AMP-K metabolic responses; iii) determine if the circulating levels of insulin, blood sugar and-or blood fat influence the AMP-K metabolic responses. Likely Outcomes: pharmacological stimulation of AMP-K will improve SkM sugar metabolism, but less so in diabetes. The associated AMP-K stimulation of SkM fat metabolism may blunt the beneficial SkM sugar responses, particularly in diabetes. This information will be used in future drug developments for diabetics which aim to simulate the beneficial AMP-K metabolic effects of exercise.Read moreRead less
Strengthening Functional Connectivity In The Ageing Brain.
Funder
National Health and Medical Research Council
Funding Amount
$320,891.00
Summary
Age-related deficits in the ability to perform meaningful, voluntary movements markedly increase the likelihood of experiencing falls, a major cause of injury among older adults. Using advanced neurophysiological techniques, this project will (1) define the role of functional connectivity decline in age-related movement deficits and (2) gain a mechanistic understanding of improvements in voluntary movement control through a promising intervention for reversing age-related functional decline.
Orthostatic Tolerance During FES-evoked Stepping In Paraplegia: A Safety And Viability Study
Funder
National Health and Medical Research Council
Funding Amount
$244,900.00
Summary
In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES ....In the past 30 years, there has been growing interest in the potential benefits of functional electrical stimulation (FES) of the paralysed leg muscles as a means of restoring movement in the lower limbs. FES uses electrical impulses generated by a stimulator to elicit purposeful muscle contractions via skin-surface electrodes placed over the muscles. Although traditionally limited to health-related activities such as stationary cycling exercise, recent bioengineering advances in the area of FES present the SCI person with a means of restoring upright mobility and reinstating functional tasks. Yet, while this technological innovation remains promising for optimising functional outcomes after SCI, there remains a distinct lack of knowledge of the physiological stresses placed upon the individual. In this preliminary safety and viability study, the physiological implications central to enhanced upright mobility will be investigated during FES-evoked prolonged stepping. The responses during FES-stepping will be contrasted with the responses observed during stepping performed without FES. The study will investigate the blood pressure responses during FES-gait, but also address possible physiological mechanisms underlying those blood pressure responses. The findings from this study will identify whether there is a phsiological limitation to the performance of FES-evoked functional mobility. Current physiotherapy practice recognises blood pressure control and orthostatic hypotension as a significant barrier to functional standing and stepping, yet little is known about the physiology underpinning the condition. If FES does present a limitation to the performance of upright functional activities, this study will also assist in devising alternative physiotherapy gait training regimens.Read moreRead less
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.
A Novel Approach To The Training Of Functional Standing Following Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$412,706.00
Summary
The study will employ a new type of functional electrical stimulation (FES), strength-endurance muscle conditioning and standing training to improve stance in SCI victims with incomplete paralysis. We will evaluate an innovative combination of muscle training and novel FES protocols which allow paralysed people to stand and perform upper limb functional tasks. The primary outcomes will be duration of standing, number of repetitions of standing and sitting and upper limb function while standing.
Investigating Caloric Vestibular Stimulation As A Novel Therapeutic Intervention For Chronic Pain, Mania And Depression.
Funder
National Health and Medical Research Council
Funding Amount
$340,963.00
Summary
Chronic pain, mania and depression are common health problems worldwide and represent an enormous burden of illness. Current treatments may be costly, invasive and have serious side-effects. In the proposed project, demonstration of therapeutic benefit with a novel, simple method of brain stimulation without such limitations could change how these disorders are managed. Moreover, the findings would be of substantial significance in developing countries where treatments are often non-existent.
The Role Of Dendritic Cells In Graft-versus-host Disease After Allogeneic Stem Cell Transplantation.
Funder
National Health and Medical Research Council
Funding Amount
$317,633.00
Summary
Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this proced ....Allogeneic bone marrow transplantation (BMT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. Graft-versus-Host Disease (GVHD) ocurrs when the newly transplanted bone marrow (which includes the immune system) recognises the transplant recipient as foreign and mounts an immune attack against patient tissues. GVHD is the major complication of BMT and is responsible for the death of up to half of the patients who receive this procedure. Research to date by Dr Hill and colleages has provided substantial detail on how and why this process occurs. This information has led to a number of advances in the field which are already improving patient survival after BMT. This includes a new type of bone marrow transplantation that uses a naturally ocurring growth factor (called a cytokine) to allow the collection of immature bone marrow cells from the blood of transplant donors. The transplantation of these cells rather than bone marrow appears to reduce the chance of dying during BMT and also improves the cure rates from the underlying leukemia. In addition, Dr Hill has developed a novel method for preventing GVHD using different types of naturally ocurring growth factors called cytokine shields that help protect patient tissue from attack by the immune system. It has recently become clear that the immune system is directed by a subtype of white cells called dendritic cells and Professor Hart at the Mater Medical Research Institute has been a pioneer in this field. As initiators of the immune system it is likely that dendritic cells play a pivotal role in GVHD and Dr Hill and Prof Hart at the Mater Medical Research Institute will study DC within the context of Dr Hills newly developed therapies with the aim of further understanding the processes of GVHD. This work will allow manipulation of these cells during BMT in order to improve patient survival.Read moreRead less
Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invi ....Allogeneic stem cell transplantation (SCT) remains the most effect curative treatment for patients with a number of malignant conditions, especially leukemia. The ability to cure leukemia by this procedure relates to a process known as Graft-versus-Leukaemia effects (GVL) which ocurrs when the newly transplanted stem cells (which includes the immune system) recognises the leukemia as foreign and mounts an immune attack against it. These studies will focus on the effect of a cellular pathway invilving NKT cells that preliminary data suggests is critical to the development of GVL. Methods to augment this activation pathway will be studied in preclinical models that may then be studied in clinical trials with the aim of improving the outcome of patients transplanted for leukemias.Read moreRead less