Interactions Between Advanced Glycation And Oxidative Stress In Diabetic Renal And Cardiac Complications
Funder
National Health and Medical Research Council
Funding Amount
$431,700.00
Summary
Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's a ....Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.Read moreRead less
Neurons And Neurotransmitters That Control Phasic Laryngeal Motoneuron Activity
Funder
National Health and Medical Research Council
Funding Amount
$278,736.00
Summary
Opening and closing of the vocal cords with breathing is an automatic function that is present before birth and is essential for life. Opening the vocal cords allows inspired air to enter the lungs and closure serves to protect the lungs from food and drink. Failure of coordination is associated with a range of life-threatening airway disorders, particularly in newborns. Nerves in the brain and the chemicals they release transmit the rhythm of breathing to the nerves that control the vocal cords ....Opening and closing of the vocal cords with breathing is an automatic function that is present before birth and is essential for life. Opening the vocal cords allows inspired air to enter the lungs and closure serves to protect the lungs from food and drink. Failure of coordination is associated with a range of life-threatening airway disorders, particularly in newborns. Nerves in the brain and the chemicals they release transmit the rhythm of breathing to the nerves that control the vocal cords. However, the specific neurons and chemicals involved are not known. This information is crucial in understanding the chemical disorder in the brain responsible for the loss of coordination between breathing and vocal cord activity, and in formulating strategies to treat these conditions using drugs that correct the chemical disorder. By way of example, we have used our animal studies to develop the first ever drug trial to treat children with congenital vocal cord paralysis, whose vocal cords fail to open with inspiration and require a tracheostomy. We have selected a drug that corrects the proposed disorder of brain chemistry responsible for this condition. This approach will serve as a template for the management of a variety of other life-threatening airway disorders in newborns using drugs that act on the brain. We will now carry out further experiments to identify the nerves and their chemicals that control the motoneurons that drive the vocal cords. The key experiment involves recording from inside an individual vocal cord motoneuron in the brain while simultaneously applying a range of chemicals to its external surface. By recording the response of the nerve, we can determine which chemicals control its activity. Using our knowledge of the pattern of chemicals released by respiratory neurons, we will identify neurons for further study, and establish chemical and anatomical relationships between the respiratory nerve and the vocal cord nerve.Read moreRead less
The Role Of Muscle Fatty Acid Oxidation In Regulating Intramyocellular Lipid Accumulation.
Funder
National Health and Medical Research Council
Funding Amount
$169,695.00
Summary
Obesity and the subsequent accumulation of fat in muscle leads to reduced insulin action and an increased risk of type 2 diabetes. This project will investigate the metabolic processes that influence fat accumulation and oxidation primarily in skeletal muscle, the tissue responsible for most fuel utilization in the body. This information will help design therapeutic strategies to prevent the development of type 2 diabetes.