Nitroso-redox Imbalance In Glucocorticoid-induced Hypertension
Funder
National Health and Medical Research Council
Funding Amount
$341,210.00
Summary
High blood pressure (hypertension) affects 20-30 % of Australian adults and in about 90-95 % of these individuals the hypertension is considered essential (cause unknown). Globally, it is the number 1 risk factor for death, and number 3 for disability (World Health Report 2002). The major consequences of hypertension are heart attack and stroke. Glucocorticoid (adrenal steroid hormone) induced hypertension and consequent cardiovascular morbidity-mortality is an important clinical problem. Althou ....High blood pressure (hypertension) affects 20-30 % of Australian adults and in about 90-95 % of these individuals the hypertension is considered essential (cause unknown). Globally, it is the number 1 risk factor for death, and number 3 for disability (World Health Report 2002). The major consequences of hypertension are heart attack and stroke. Glucocorticoid (adrenal steroid hormone) induced hypertension and consequent cardiovascular morbidity-mortality is an important clinical problem. Although naturally occurring glucocorticoid (GC) hypertension (Cushing's syndrome) is relatively rare, synthetic GC are widely used in clinical practice (in numerous inflammatory and autoimmune diseases and transplantation) and produce substantial cardiovascular morbidity and mortality. Further, abnormal GC breakdown (metabolism) and sensitivity to GC have been reported in around a third of essential hypertensive patients. We therefore need to understand how GC raise blood pressure and whether we can prevent and-or reverse these blood pressure raising effects. In the proposed studies, we will explore the role of relative deficiency of blood vessel dilating nitric oxide and nitric oxide inhibition by excess superoxide (nitroso-redox imbalance) in the genesis of GC hypertension. Further, we will identify agents known to be suitable for clinical use which are effective in preventing-reversing GC hypertension in the rat and are thus appropriate for clinical trials to prevent-reverse GC hypertension in humans. These studies will help answer the question of how GC raises blood pressure so that safer steroids can be designed, as well as identify agents that can potentially prevent or treat GC hypertension in humans.Read moreRead less
Defining The Role Of GILZ In Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$675,030.00
Summary
Corticosteroids are commonly used to treat inflammatory diseases such as arthritis. Their action is based on effects on natural inflammation control pathways. One such pathway is that mediated by the protein known as GILZ (glucocorticoid induced leucine zipper). The function of this protein in disease is not well understood, and the research proposed here will increase understanding of its role. This knowledge could yield new treatments for arthritis and other inflammatory diseases.
The Influence Of Glucocorticoid Hormones In T Cell Development And Function
Funder
National Health and Medical Research Council
Funding Amount
$406,980.00
Summary
The defence of the body to disease is a very complex process involving multiple interactions between subsets of white cells, in particular lymphocytes. This immune system, however, does not act in isolation but is subject to constant regulation by a variety of other cells and soluble factors. Particularly important in this regard is the impact of glucocorticoids which are normally associated with stress conditions. These steroids have been proposed to act at several levels in the immune system, ....The defence of the body to disease is a very complex process involving multiple interactions between subsets of white cells, in particular lymphocytes. This immune system, however, does not act in isolation but is subject to constant regulation by a variety of other cells and soluble factors. Particularly important in this regard is the impact of glucocorticoids which are normally associated with stress conditions. These steroids have been proposed to act at several levels in the immune system, usually causing suppression but they can also modify in a positive sense. Defining the targets of glucocorticoids and their precise functional impact will thus have very important implications for not only understanding the regulation of the immune response but also in the clinic. This project will make use of mice which have had the receptor for glucocorticoids genetically deleted. Focussing on T cells (the most important cells of the immune system) these mice will be examined in detail for alterations in the development of T lymphocytes and their function in defending the body against virus and tumours and their involvement in self destruction (autoimmune) diseases including multiple sclerosis.Read moreRead less
The Effect Of Chronic Maternal Asthma And Acute Exacerbations On Placental Function And Fetal Development
Funder
National Health and Medical Research Council
Funding Amount
$224,623.00
Summary
Maternal asthma is the most common disease to complicate pregnancies in Australia. The data we have collected so far suggests that asthma represents a physiological maternal stress during pregnancy that influences placental function and fetal development. The purpose of this grant is to continue to determine what changes occur in the presence of maternal asthma that alter fetal growth. The findings of this work will be applicable to any psycho-social or physiological stressor during pregnancy.
Plasma Exchange And Glucocorticoids In ANCA Associated Vasculitis: A Randomised Controlled Trial (PEXIVAS Australia)
Funder
National Health and Medical Research Council
Funding Amount
$635,243.00
Summary
Vasculitis is a life-threatening disease, and the current treatment for this condition is not satisfactory. This clinical trial aims to determine 1) if plasma exchange can lower mortality and the development of severe kidney failure due to this disease, and 2) if the use of lower doses of corticosteroids can lessen the infectious complications of treatment. This trial is part of a major international effort which will involve a total of 500 patients from Australia, UK, Europe, USA and NZ.