INTER-ETHNIC DIFFERENCES IN TOLERANCE OF ANTI-CANCER DRUGS
Funder
National Health and Medical Research Council
Funding Amount
$345,894.00
Summary
In 2 previous studies we have shown that Asian cancer patients experience more side-effects than their Caucasian counterparts when treated with the same dose and schedule of treatment. This does not appear to be related to any difference in size. We wish to explain this difference as it may avoid Asian patients receiving overdoses of treatment. Possible causes include dietary and nutritional differences
Molecular Mechanisms Of Human Cytochrome P450 CYP3A4 Gene Regulation
Funder
National Health and Medical Research Council
Funding Amount
$196,059.00
Summary
Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. Cytochrome P450 3A4 (CYP3A4) is arguably the single most important factor is how humans handle therapeutic drugs. It has been estimated that over 60% of all ....Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. Cytochrome P450 3A4 (CYP3A4) is arguably the single most important factor is how humans handle therapeutic drugs. It has been estimated that over 60% of all drugs presently on the market are broken down, either in full or in part, by this enzyme. The amounts of CYP3A4 expressed in the liver differs markedly between individuals, and explains a great deal of the large variation in the way people break down drugs. Also, variations in the levels of CYP3A4 in the liver may be an important factor in both prostate cancer (the most common cancer in men) and the risk of developing leukemia after receiving chemotherapy for other cancers. The present projects builds on discoveries concerning the regulation of cytochrome P450 enzymes made by our group over the last few years, including an in-depth understanding of the way the production of CYP3A4 is increased by some drugs. In this project we seek to understand why individuals differ so much in terms of the amount of CYP3A4 in the liver (up to 10-fold) and why this enzyme is predominantly expressed in the liver and to as lesser extent, the intestine, while not being found at all in many other tissues. An understanding of these issues will allow us to: Y predict how patients will respond to drugs (pharmacogenetic testing). Y determine susceptibility to certain diseases (e.g., prostate cancer). Y develop novel drugs that can influence CYP3A4 production in the liverRead moreRead less
How Does Early Life Adversity “get Under The Skin” To Influence Lifelong Health? - Identifying Opportunities For Prevention Among Aboriginal And Ethnic Minority Peoples
Funder
National Health and Medical Research Council
Funding Amount
$425,048.00
Summary
This Fellowship will build upon my research to discover patterns and pathways of early life risk and resilience involved in long-term health outcomes for Aboriginal and ethnic minority children. This research will inform the planning of better targeted policy, public health and primary health care solutions for Aboriginal and ethnic minority children, families and communities in the critical early years of children’s lives.
Spirometry And Fractional Exhaled Nitric Oxide (FeNO) Reference Values For Aboriginal And Torres Strait Islander Australians
Funder
National Health and Medical Research Council
Funding Amount
$78,790.00
Summary
Lung diseases are one of the leading contributors to the health gap between Indigenous and non-Indigenous Australians. Simple tests, such as spirometry, are needed for early diagnosis and good management of lung diseases. My study aims to develop healthy reference values which are lacking for this population. Results from my study will improve the accuracy of test interpretation, aid in diagnosis and clinical care, and reduce morbidity of lung disease for Indigenous Australians.
Improving Dosing Of Common Antibiotics Used In Critically Ill Australian Indigenous Patients
Funder
National Health and Medical Research Council
Funding Amount
$98,148.00
Summary
Optimal antibiotic dosing in patients in the intensive care unit saves lives. However, the way antibiotics move through the body of an intensive care unit patient can be different to other patients. Therefore, research that identifies specific dosing for these patients is essential. Further to this, no research in an Indigenous population is available. The aim of this research is to address this gap by developing optimal antibiotic doses for Indigenous Australians in the intensive care unit.
Structural And Biomechanical Basis Of Differences In Bone Fragility In Asian And Caucasian Men And Women
Funder
National Health and Medical Research Council
Funding Amount
$188,500.00
Summary
Lay Summary Fractures occur less commonly in males than females because males have greater periosteal apposition than females during ageing. This increases bone size (reducing load per unit area - stress), and reduces net bone loss, more in males than females so that the increase in bone fragility with advancing age seen in both sexes is less in males than females. Few males than females have a fracture risk index for vertebral fractures (FRI or ratio of load-bone strength) above unity. The purp ....Lay Summary Fractures occur less commonly in males than females because males have greater periosteal apposition than females during ageing. This increases bone size (reducing load per unit area - stress), and reduces net bone loss, more in males than females so that the increase in bone fragility with advancing age seen in both sexes is less in males than females. Few males than females have a fracture risk index for vertebral fractures (FRI or ratio of load-bone strength) above unity. The purpose of this study is to define the structural and biomechanical basis responsible for the racial differences in fracture rates between Asians and Caucasians. Following the same biomechanical principles as published in Caucasian males and females, we hypothesise that racial differences in periosteal expansion during aging may contribute, in part, to the racial differences in bone fragility at the spine and hip. A cross-sectional study will be conducted in 500 healthy Chinese men and 500 Chinese women age ranged 18 to 90 years living in Melbourne, Australia. We have recruited larger numbers of Caucasian men and women in our Centre. BMD and bone size will be measured at the spine, hip and total body by using dual x-ray bone densitometer (DXA). Vertebral body width, depth, height, cross-sectional area (CSA), stress (load per unit CSA) and fracture risk index (load-strength) at the third lumbar vertebrae will be measured by PA and lateral scanning. Femoral neck periosteal-endocortical diameter, cortical thickness, cross-section moment of inertia (CSMI), section modulus buckling index will be measured by using hip structural analysis program. Just as insight into bone fragility in women has been obtained by studies in men, we believe that the results of this study will provide important insights into the pathogenesis of bone fragility in both racial groups.Read moreRead less
The Fremantle Diabetes Study Phase II: A Community-based Study Of Diabetes Care, Control, Complications And Cost
Funder
National Health and Medical Research Council
Funding Amount
$1,307,780.00
Summary
In Phase I of the Fremantle Diabetes Study (FDS), valuable and detailed data on a wide range of subjects were obtained from a community-based patient cohort between 1993 and 2001. There is a large body of evidence that the nature and treatment of diabetes in Australia is changing rapidly. In order to provide up to date information to health care providers and government agencies, to confirm observations made in FDS I and to venture into new research areas, Phase II will be conducted.
Bile Acid Detoxification By Nuclear Receptor-mediated CYP3A Regulation
Funder
National Health and Medical Research Council
Funding Amount
$196,527.00
Summary
Liver diseases in which there is obstruction to bile flow (cholestatic liver diseases) can lead to liver failure, liver cirrhosis as well as a diminished quality of life. Patients suffer from severe itching which may prove difficult to control. It is thought that many of these adverse effects of obstructed bile flow are due to the retention of a component of bile, called bile acids, within the body. Bile acids are detergent-like compounds formed from cholesterol. Some bile acids are highly toxic ....Liver diseases in which there is obstruction to bile flow (cholestatic liver diseases) can lead to liver failure, liver cirrhosis as well as a diminished quality of life. Patients suffer from severe itching which may prove difficult to control. It is thought that many of these adverse effects of obstructed bile flow are due to the retention of a component of bile, called bile acids, within the body. Bile acids are detergent-like compounds formed from cholesterol. Some bile acids are highly toxic and cause the death of cells in the liver if their concentration becomes too high. Evidence has emerged that the body has control mechanisms to try and combat rising levels of bile acids in cholestatic liver diseases. One such mechanism, which is the subject of this application, is the metabolism of bile acids to less toxic forms, by a process called hydroxylation. A particular class of liver enzymes, known as cytochromes P450 CYP3As, appear to mediate these hydroxylation reactions. Liver cytochrome P450 enzymes are important to medicine in areas as broad as drug breakdown, steroid hormone regulation and the formation or elimination of cancer causing chemicals. These enzymes are present in high concentration in the human liver, but the factors governing how much of these enzymes are produced have been poorly understood. The present projects builds on discoveries concerning the regulation of cytochrome P450 enzymes made by our group over the last few years, including an in-depth understanding of the way the production of CYP3As are increased by some drugs. We intend to determine the mechanism by which bile acids increase the level of CYP3A enzymes are how effective these enzymes are in hydroxylating bile acids. An understanding of these issues will allow us to better manage patents with cholestatic liver diseases and develop new strategies for treating these diseases, for example, development of novel drugs that increase bile acid hydroxylation in the liver.Read moreRead less
Sex Differences In Long-Term Outcomes Of Young Patients With Acute Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$333,900.00
Summary
Young women (?55 years) are more likely to die after having a heart attack and face more difficult recoveries compared to similar aged men. However the cause of this difference is unknown. This project seeks to improve the prevention, care and longer term outcomes for young women following a heart attack. Information obtained from will provide evidence-based and actionable information for physicians to inform and manage their patients so that we may ultimately improve the lives of young women.
Generating New Evidence To Better Guide Stroke Management
Funder
National Health and Medical Research Council
Funding Amount
$568,293.00
Summary
I wish to produce sound knowledge on the management of blood pressure and nursing monitoring for patient affected by stroke. I plan to address gaps in stroke management that exist between men and women around the world in order for there to be equity of care and an ability for every patient to have the best chances of receiving proven therapies to optimise their chances of recovery. Finally, I will use data that considers patients’ own view of wellbeing that can be used to direct stroke care.