Nox4-containing NADPH-oxidase As A Protective Enzyme In The Cerebral Circulation
Funder
National Health and Medical Research Council
Funding Amount
$515,812.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activa ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in a stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent research at the basic level to better understand the processes of normal, and then abnormal, regulation of brain artery function. The project will test the importance of a newly discovered mechanism for increasing brain blood flow. This involves activation of an enzyme, Nox4-containing NADPH-oxidase, to generate oxygen radicals which then relax the wall of blood vessels causing the arteries to let more blood through. We believe that this process plays an important role in the normal, healthy maintenance of blood supply to the brain. Furthermore, we propose that the activity of this enzyme is elevated and therefore protective in brain arteries during high blood presure - which is the major risk factor for stroke. We will specifically test whether the activity of this enzyme actually helps to limit the amount of brain death following stroke. We will use a variety of techniques to assess the importance of this enzyme in brain arteries in the living body, and also in isolated segments of brain artery from animals that are either healthy or have diseased brain arteries. The results are expected to provide major new insight into processes that help maintain brain blood flow under normal conditions and after a stroke, and the knowledge gained here should lead to safer therapies to prevent or treat stroke.Read moreRead less
MECHANISMS OF CEREBROVASCULAR REGULATION IN HEALTH AND DISEASE
Funder
National Health and Medical Research Council
Funding Amount
$216,430.00
Summary
Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the ....Failure of the cerebral circulation to meet the brain's immediate high nutritive requirements results in stroke in just a few minutes. Stroke continues to be a major cause of death and disability, and this major medical challenge requires urgent and significant research at the basic level to better understand mechanisms of normal, and then abnormal, regulation of cerebral artery function. The project will examine the importance of a novel mechanism in regulating brain blood flow by affecting the degree of opening of the cerebral arteries. This mechanism involves activation of an enzyme, Rho-kinase, which is present in the wall of blood vessels. The applicants believe that this process plays an important role in the normal, healthy regulation of blood supply to the brain. Moreover, there are strong reasons for us to speculate that the function of this enzyme is abnormally high in two disease states that are associated with an increased risk of stroke - high blood pressure and subarachnoid haemorrhage. We will employ a variety of techniques to assess the importance of Rho-kinase in cerebral artery function in the living body, and also in isolated segments of artery. The results are expected to provide major new insight into mechanisms that regulate brain blood flow, and the knowledge gained here may lead to better therapies to prevent or treat stroke.Read moreRead less
UTILITY OF NOVEL BIOMARKERS IN THE PREDICTION OF MAJOR COMPLICATIONS OF TYPE II DIABETES MELLITUS
Funder
National Health and Medical Research Council
Funding Amount
$510,639.00
Summary
Diabetes is increasingly common. It can cause a variety of complications, the most serious being heart and kidney disease. The reasons why some patients develop such complications are not fully understood so it is difficult to predict who will be affected. The current project will use samples from a large international study of patients with diabetes to assess whether levels of specific markers in the blood help to predict major complications and clarify why they occur.
Is Sympathetic Activation Beneficial Or Detrimental In Septic Shock?
Funder
National Health and Medical Research Council
Funding Amount
$458,755.00
Summary
Septic shock is a major cause of death in intensive care units. It is associated with large increases in sympathetic nerve activity to the heart and kidneys, which have both beneficial and harmful effects. This project will determine the responses to the increased sympathetic activity in septic shock, the causes of it and whether blocking this activation has an overall beneficial effect. This knowledge is essential before drugs that block sympathetic activation are examined in clinical studies.
Investigation Of The Influence Preterm Birth On Lung Structure And Function In School Age Children.
Funder
National Health and Medical Research Council
Funding Amount
$204,482.00
Summary
Bronchopulmonary dysplasia (BPD) remains the most significant chronic lung complication of premature birth. While some information on the long term respiratory outcomes in BPD exist there are no comprehensive studies linking lung structure, function and respiratory symptoms and relating these changes to neonatal history. Studies of this kind are essential to ensure future healthcare for these children can be planned accordingly.
Influence Of Flavonoid Structure And Function On Cardiovascular Protection
Funder
National Health and Medical Research Council
Funding Amount
$571,447.00
Summary
The proposed research will further explore the hypothesis that dietary flavonoids can protect against cardiovascular disease. The importance of flavonoid structure for bioactivity needs further study. In addition, metabolic changes to flavonoid structure could have a profound effect on their bioactivity. Therefore, our overall aim is to investigate the effects of individual flavonoids and their metabolites on bioactivity relevant to cardiovascular disease.
Role Of The Hypothalamus, Oxidative Stress And Angiotensin In Chronic Stress
Funder
National Health and Medical Research Council
Funding Amount
$535,333.00
Summary
Stress can trigger life threatening cardiovascular events and its impact is much greater when blood pressure is raised. We seek to determine which chemical type of brain neuron and which region is responsible for amplifying the responses to repeated stress in an animal model that closely resembles the human form of the disease. We will focus specifically on the hypothalamus which controls the sympathetic nervous system.
Heart-lung Interactions Determine Right Ventricular Function In The Perinatal Period.
Funder
National Health and Medical Research Council
Funding Amount
$421,980.00
Summary
Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, ....Birth, and the ensuing stress of newborn life, requires the heart to dramatically increase its level of functioning. Understanding how this process occurs remains a key problem as the heart lacks any ability to increase its level of functioning immediately before birth. Failure to effect this increase in heart function promptly at birth has serious implications for the well being of the newborn and represents a major problem in newborn medicine. Of the 250,000 babies born each year in Australia, as many as 5,000 require intensive care primarily for cardiorespiratory complications. Accurate diagnosis and effective treatment of these infants demands knowledge of the normal heart adaptations that accompany birth, adaptations that are critically linked to the way in which the heart and the lungs interact. This project investigates how interactions between the heart and the lungs determines heart function throughout life. By understanding this process we will provide essential information that will aid the diagnosis and treatment of sick neonates undergoing intensive care.Read moreRead less
Invasive Assessment Of Pulmonary Vascular Physiology - Novel Methods For Early Detection Of Pulmonary Vascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$274,352.00
Summary
Pulmonary vascular disease (PVD) is a lethal condition characterised by progressive destruction of the lung blood vessels. One major problem with PVD is that diagnosis is often made very late in the illness, when the pulmonary blood pressure rises. This project aims to develop a novel method to detect the early and clinically silent phase of PVD, by assessing the lung's blood vessel reserves. Early diagnosis of PVD will enable earlier treatment thereby improving prospects for treatment.