ProbioticTreatment Of Diarrhoeal Disease And Malnutrition In Top End Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Aboriginal children in the Top End of Australia have high rates of hospital admission for diarrhoea and malnutrition. We have discovered that underlying small intestinal damage in these children is an important contributor to the high complication rates and longer lengths of stay in hospital compared to non-Aboriginal children. This research proposes to continue our work on small intestinal damage by using two non-invasive tests of gut function, namely a sugar absorption test and novel breath te ....Aboriginal children in the Top End of Australia have high rates of hospital admission for diarrhoea and malnutrition. We have discovered that underlying small intestinal damage in these children is an important contributor to the high complication rates and longer lengths of stay in hospital compared to non-Aboriginal children. This research proposes to continue our work on small intestinal damage by using two non-invasive tests of gut function, namely a sugar absorption test and novel breath test. The sugar permeability test involves the children drinking a solution of the two sugars lactulose and rhamnose, and measuring their absorption into the blood 90 minutes later using a sophisticated measuring instrument called HPLC, which can measure minuscule amounts of sugars and is set up at Royal Darwin Hospital. The breath test involves children drinking another sugar solution with a special non-radioactive marker called a stable isotope of carbon, and measuring changes in the amount of this marker in carbon dioxide from the breath at timed periods after drinking the sugar solution. The breath is analysed in Adelaide using another sophisticated instrument. These tests are being used to measure abnormal sugar absorption due to intestinal damage, which is particularly common in Aboriginal children during the weaning period of 4-18 months. Our hypothesis is that treatment with 'healthy germs' (probiotics) like those in certain yoghourts will colonise the gut, stimulate immunity and reduce the presence of 'nasty germs' (pathogenic bacteria) in the intestines of Aboriginal children which contribute to the need for their hospitalisation with diarrhoea and malnutrition. If this hypothesis is correct, then this research will provide the best kind of evidence for reducing the need for hospital treatment by treating all cases of diarrhoea with these probiotics and possibly even decreasing the gut damage of children in the weaning period by including probiotics in their dietsRead moreRead less
Exertional Dyspnoea With Increased Filling Pressure - Mechanisms And Treatment Strategies
Funder
National Health and Medical Research Council
Funding Amount
$387,793.00
Summary
Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and theref ....Patients with early heart disease often present with shortness of breath with exercise, as myocardial reserve at that stage is usually sufficient to maintain normal function at rest . Indeed, much myocardial dysfunction may originate from the modern lifestyle, including inactivity, obesity, the metabolic syndrome and type II diabetes. The potential benefits of making a definitive early diagnosis are large, because it seems more likely that an impact can be made on the disease process (and therefore, outcome) than with late stage disease. Current treatment strategies are expensive and because they are directed at end-organ damage (heart failure, heart attacks etc), rather ineffective. This multispecialty, multidisciplinary group will undertake a series of unique studies aimed at identifying early cardiovascular disease. The strategy will involve detection of abnormal filling behaviour at stress echocardiography, with randomization into longterm and short-term trials to examine various therapeutic strategies. Sensitive new cardiovascular imaging techniques will be used to detect preclinical abnormalities in the structure and function of the heart and vasculature, facilitating a mechanistic understanding of the process of increasing filling pressure with exercise.Read moreRead less
Understanding The Metabolic Consequences Of Impaired AMPKa2 And NNOS� In Skeletal Muscle: Implications For The Metabolic Syndrome
Funder
National Health and Medical Research Council
Funding Amount
$575,527.00
Summary
The inability of muscle to utilise sugar from the blood is a major problem that contributes to obesity and Type 2 diabetes. Since the number of people with these diseases will at least double by 2030, we need to find out what causes this problem. We will examine whether two muscle proteins that are impaired in obesity and Type 2 diabetes are also responsible for impaired sugar utilisation. We think that increasing these muscle proteins will fix the _sugar problem�, and remedy these diseases.
The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
Developing A Standard Dyspnea Challenge To Explore Mechanisms And Therapies In Clinical Populations
Funder
National Health and Medical Research Council
Funding Amount
$454,383.00
Summary
COPD is Australia's most burdensome respiratory disease with over 200,000 new cases diagnosed each year. Shortness of breath is a cardinal feature of this disease.This project will examine the mechanisms of this symptom in patients with chronic lung disease. Four studies will be completed in total, each exploring different factors that may contribute to shortness of breath observed in patients. This research is likely to lead to improved management of this distressing condition into the future.
Cytokines In Milk Modulate The Development Of Immune Responses In The Infant
Funder
National Health and Medical Research Council
Funding Amount
$188,912.00
Summary
There is substantial epidemiological evidence that formula fed infants are more susceptible than breast fed infants to auto-immune diseases later in life. However direct evidence is lacking and the mechanism is not understood. We aim to provide direct experimental evidence to test the hypothesis that maternal milk regulates infant immune responses by providing the factors that modulates antigen presentation and priming in the neonatal gut. The significance of the study lies in the absence of the ....There is substantial epidemiological evidence that formula fed infants are more susceptible than breast fed infants to auto-immune diseases later in life. However direct evidence is lacking and the mechanism is not understood. We aim to provide direct experimental evidence to test the hypothesis that maternal milk regulates infant immune responses by providing the factors that modulates antigen presentation and priming in the neonatal gut. The significance of the study lies in the absence of these regulatory factors in infant formula. The results will allow more fully informed decisions regarding breast feeding, and may lead to the development of infant formula that modulate immune responses in a manner analogous to natural maternal milk.Read moreRead less
Improving Functional Capacity In Patients With Chronic Lung Disease With High Intensity Respiratory Muscle Training
Funder
National Health and Medical Research Council
Funding Amount
$340,880.00
Summary
Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these gene ....Patients with chronic respiratory disease have limited exercise capacity, which severely impairs their quality of life. The mechanisms responsible for this impairment may relate to their lung disease, or to the long-term effects that inactivity has on the cardiovascular and musculoskeletal systems. Pulmonary rehabilitation programs involving whole-body exercise are now widely used as an addition to standard medical therapy as a way of decreasing symptoms and optimising function. While these generalised, broad-based programs result in modest improvements in peripheral muscle function, cardiovascular function, functional exercise capacity and quality of life, it is now apparent they have little or no effect on respiratory muscle function, which is also greatly impaired in COPD. The aims of this study are to answer two longstanding questions that are fundamental to rehabilitation programs in patients with COPD (i) does a program of specific respiratory muscle training alone improve whole-body exercise capacity, dyspnoea, and-or quality of life? and (ii) does the addition of a program of specific respiratory muscle training to a standard whole-body exercise rehabilitation program result in improvemed exercise capacity, dyspnoea and-or quality of life to a greater degree than a program of whole-body exercise training alone? The study is of importance to patients with COPD by investigating the mechanisms underlying the improvement in exercise capacity following a rehabilitation program and the role of respiratory muscle training in such a program. By more accurately defining the mechanisms of exercise limitation we may be able to maximise the benefits obtained during a rehabilitation program, including improved work capacity, reduction in the degree of breathlessness and improved quality of life.Read moreRead less