Role Of Endogenous Opioid Peptides In Endometrial Receptivity And Placentation
Funder
National Health and Medical Research Council
Funding Amount
$523,884.00
Summary
Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth w ....Infertility affects 1 in 10 couples. In early pregancy miscarriage is the commonest complication resulting in the loss of 10-15% of all conceptions. During the latter part of pregnancy, complications such fetal growth restriction and preeclampsia, affects up to 10% of women resulting in considerable suffering to the mother and her newborn. Many of these births are premature with neonates requiring intensive care. There is also good evidence that children who are born prematurely with low birth weight are much more likely to develop a host of diseases including cardiovascular disease, diabetes and obestiy in adult life increasing the long term burden of health care support. Infertility is often due to the lack of uterine endometrial receptivity while the pregnancy complications arise from the reduced growth of the placenta and sub-optimal interactions between the mother's uterus and the growing placenta. Endometrial infertility, placental growth and interactions with the endometrium is stringently regulated by substances produced at the maternal endometrial- placental interface. To understand how infertility and pregnancy complications arise, develop diagnostic, monitoring and therapeutic tests it is critical to understand the roles played by these regulatory substances. We have novel data suggesting that small proteins known as endogenous opioids could be enchancing endometrial receptivity and the growth and development of the placenta. Interstingly these substances are closely related to exogenous opioids such as heroin and morphine. We will investigate the manner in which these substances regulate endometrial immune cell function, maintain the endometrial stromal cell bed in preparation for pregnancy and direct the growth and differentiation of the placenta. The findings will give novel insights into infertility, improve the success rates of in vitro fertilization, reduce maternal and neonatal complications of pregnancy.Read moreRead less
Matrix Metalloproteinases, Leukocytes And Menstruation
Funder
National Health and Medical Research Council
Funding Amount
$191,812.00
Summary
Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the norm ....Menstrual bleeding problems are a common cause of pain and discomfort for women and often are satisfactorily treated only by hysterectomy. Despite this, little is known about the processes causing menstruation. Recently, we and others have demonstrated a role for a family of biological catalysts (enzymes) which break down the structure of the tissue lining the uterus (the endometrium) and are thought to cause menstrual bleeding. However, the mechanisms regulating their production during the normal menstrual cycle is still largely unknown. Cells which come initially from the blood (leukocytes, particularly neutrophils and eosinophils) dramatically increase in numbers immediately prior to menstruation and these along with other cells, known as mast cells, start to produce a number of factors which we postulate are important for regulation of the enzymes. These cells, are also present in high numbers in endometrium of women with menstrual bleeding problems. This study will demonstrate that both the enzymes, and the leukocytes play a critical role in menstruation and will determine how the leukocytes in the endometrium are regulated. The studies have important implications for understanding and treating menstrual bleeding disorders.Read moreRead less
Chemoradiation And Adjuvant Chemotherapy Versus Radiation Alone In High Risk And Advanced Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$460,832.00
Summary
This trial is evaluating whether adding chemotherapy during and after radiotherapy is better than giving radiotherapy alone in patients who have advanced or high risk endometrial cancer. One group of patients will be treated after surgery with both radiotherapy and chemotherapy, followed by additional cycles of chemotherapy and the other group will receive the standard treatment which is pelvic radiation alone. This study may result in a change in the management of these patients.
Identification Of A New Thrombosis Mechanism Triggered By Dying Platelets
Funder
National Health and Medical Research Council
Funding Amount
$608,742.00
Summary
A severe reduction in blood flow (ischemia) to the intestines can trigger blood clot formation (thrombosis) in multiple organs, including the lungs. We have identified a new thrombosis mechanism that is triggered by the clumping of white blood cells in the intestines, leading to widespread thrombosis in the lung. Here we will investigate the mechanisms triggering this thrombosis mechanism with the ultimate aim of identifying more effective antithrombotic approaches.
Modulation Of Endothelial Junctions As Selective Immunotherapy
Funder
National Health and Medical Research Council
Funding Amount
$911,387.00
Summary
We have developed a new drug (CD5-2) that targets the junctions of endothelial cells, the cell that lines all vessels. CD5-2 reduces oedema in diseases such as diabetic retinopathy and tumours. Thus it has potential as a new therapeutic in chronic inflammatory diseases where leaky blood vessels are central to the pathology. This grant will provide fundamental understanding of how CD5-2 induces such profound effects to alter the levels of oedema and alter inflammatory cell infiltrates in tissues.
First-in-Field Study Of Mechanisms Operating In Post-Ebola Eye Disease
Funder
National Health and Medical Research Council
Funding Amount
$748,985.00
Summary
Ebola virus disease is a life-threatening illness with no treatment. Survivors of the disease are at risk of uveitis - inflammation inside the eye - related to the ability of Ebola virus to persist in the eye. Our research will examine the cellular and molecular events that occur in an eye that harbours Ebola virus. This work will be an important step towards the development of treatments for uveitis caused by Ebola virus.