Does Maladaptive Remodelling Of The Heart And Vasculature In Response To Preterm Birth Lead To Long-term Cardiovascular Risk?
Funder
National Health and Medical Research Council
Funding Amount
$535,086.00
Summary
Being born prematurely is linked to the development of high blood pressure (a major risk factor for cardiovascular disease) later in life. In this project we will examine whether injury to the cells lining the cardiovascular system and/or structural changes in the wall of the arteries and the heart, as a result of being born early, lead to an elevation in blood pressure and heart dysfunction in adulthood.
The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhib ....The aim of this proposal is to evaluate a novel therapy option for children with a genetic disorder called mucopolysaccharidosis (MPS). MPS arise from the build up of complex carbohydrates in cells within the body due to the deficiency of an enzyme required for their degradation. By decreasing the synthesis of carbohydrate we can manipulate the level of stored carbohydrate and alleviate the pathology associated with MPS. The novel therapy is based on a chemical modification of glucose that inhibits carbohydrate synthesis and is termed substrate deprivation therapy.Read moreRead less
Does Adenotonsillectomy Change Vascular Function In Children With Sleep Breathing Disorders?
Funder
National Health and Medical Research Council
Funding Amount
$522,105.00
Summary
Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase th ....Sleep breathing disorders affect 10% of all children and when severe, obstruction in the upper airways causes serious deficits in growth, development, brain function and heart health. But even mild snoring (without obstruction) may also cause poor health in the arteries that supply blood to the brain and heart, as well as the smaller arteries in the arms and legs. In both adults and children with conditions like diabetes and obesity, poor blood vessel health has been shown to greatly increase the future risk of heart attacks, angina and strokes. Children with severe sleep breathing disorders (such as sleep apnoea syndrome) are currently treated by removal of the tonsils and adenoids, which typically resolves snoring and improves sleep, but it is not yet known whether there are any benefits for blood vessel health. The earliest signs of blood vessel disease in children are abnormal function of the lining of the blood vessels (endothelial dysfunction) and thickening of the lining of blood vessels (intima media thickness). They precede the adult diseases of atherosclerosis - which causes heart attacks and strokes, and diabetic kidney and eye disease. These changes can be measured accurately and non-invasively using ultrasound imaging of arteries in the neck and arm. Our primary aim is to assess whether changes in blood vessel health occur in children with sleep breathing disorders across the range of severity, with a secondary aim to measure any changes in cardiovascular control during both sleep (when snoring occurs). Most importantly, by assessing children before and after surgery, we will be able to see for the first time whether treatment of childhood snoring improves blood vessel health. This study may have major implications for the clinical management of snoring children, who may require treatment at an earlier age to prevent poor blood vessel health and an increased risk of cardiovascular diseases later in life.Read moreRead less
Metabolic Complications Of Obstructive Sleep Apnea During Early Development
Funder
National Health and Medical Research Council
Funding Amount
$320,375.00
Summary
Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes ....Adults with OSA are known to have increased risk for heart disease. We will study children with OSA, and an animal model of the disease during early development, to help clarify how this disease of adulthood actually has its origins in childhood. We have already shown that obese children with obstructive sleep apnea (OSA) are more prone to diabetes (metabolic problems) than those without OSA. More recently, we found that this is also true for children who are not overweight. This early diabetes is known to be to show a future risk for heart disease. This study will examine why OSA in children is linked to metabolic problems. First, we will continue our study in children who are not overweight. We need to study more children to be sure that OSA is truly linked to metabolic problems - whether or not a child is overweight, because this means that children with OSA are at risk for metabolic and future cardiac problems, whether they are overweight or not. Since weight does not usually change after treatment of OSA, we will also study children again, after they have been treated for OSA. We expect to show that treatment of OSA resolves the metabolic problems. Since hypoxia (low oxygen) occurs in OSA we believe that this is the fundamental cause of the metabolic problems. To test whether this is true, we will look for metabolic problems in piglets exposed to similar, low levels of oxygen as those seen in children with OSA, comparing them to piglets that have not been so exposed. We believe that the tendency to develop OSA and diabetes is inherited. To test this, we will study the genes of a very large family whose members have OSA and-or diabetes, and try to find which genes are associated with OSA and with diabetes. This will help determine if the two genes are linked in some way.Read moreRead less
Skeletal disease is a major problem for children with mucopolysaccharidoses (MPS). Patients suffer from early onset osteoporosis and osteoarthritis, severely affecting their quality of life. We will evaluate a lentiviral gene therapy vector developed in-house for its capacity to transduce bone, cartilage, synovial and ligament cells in a mouse model of MPS VI. Our goal is to generate high level, sustained expression of the deficient MPS enzyme and alter the course of skeletal disease in MPS.
Family And Environment In The Development Of Obesity And Precursors Of Diabetes And Heart Disease In Adolescence
Funder
National Health and Medical Research Council
Funding Amount
$284,770.00
Summary
Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 199 ....Obesity is a serious public health problem in Australia. The rate of obesity appears to be rising. Currently 19-23% of children and adolescents are overweight or obese. Adolescence is a critical period for the development of obesity in both males and females. It is a time when new dietary habits, likely to promote fatness, are adopted and physical activity declines. Understanding the factors that drive these behaviours is essential for effective prevention of obesity and related diseases. In 1996-7, our research group studied a group of over 400 children who were aged 7-8 years, were living in western Sydney and were born at Nepean Hospital. In our new study, we plan to re-study this group of children, now in early adolescence. This will allow us to assess the family and environmental factors influencing physical activity and eating behaviour at the beginning of adolescence. The aims of our study are to: Measure changes during early adolescence in eating and physical activity behaviours that are likely to increase obesity risk Measure anthropometric and biochemical markers for future risk of type 2 diabetes and cardiovascular disease in both adolescents and their parents Identify factors in the family environment that influence changes in food intake and physical activity in early adolescence The study will be done in two phases, 18 months apart. The measurements will be done in the study centre at Nepean Hospital in western Sydney. We will measure the height, weight and skinfold thickness of the adolescents and, if possible, their parents. We will also ask the young people and their parents to complete questionnaires about the family food and activity environment and their level of physical activity and food intake. In addition, the adolescents will wear a light-weight activity monitor for 3 days ( to measure the level of activity), blood pressure will be measured and cholesterol and blood sugar levels checked.Read moreRead less
RCT Of The Intragastric Balloon And Lifestyle Intervention Versus Lifestyle Intervention Alone In Obese Adolescents
Funder
National Health and Medical Research Council
Funding Amount
$598,976.00
Summary
For the first time in adolescents, Perth researchers will trial placement of a fluid-filled silicone balloon in the stomach. It will be used in conjunction with a lifestyle intervention, and so is expected to increase weight loss. The balloons are safe, effective at adult weight loss and an alternative to invasive surgery. Adolscent obesity rates are rising and treatment options are limited. The non-surgical balloon may be the alternative for adolescents who would previously had to have surgery.