Smoking Cessation And Bone Health: Observational And Intervention Studies In Twins And A Quitline Population
Funder
National Health and Medical Research Council
Funding Amount
$639,050.00
Summary
Osteoporosis is a major health problem that causes bones to break (fracture) easily. Many bones are susceptible, with hip fractures being the worst outcome of osteoporosis. They cause pain, disability, require major health interventions (surgery and rehabilitation), lead to death in about 20% of cases, and the overall care of hip fracture patients is very expensive. Osteoporosis is treated to reduce the risk of fractures. The prevention and treatment of osteoporosis should include avoidance of f ....Osteoporosis is a major health problem that causes bones to break (fracture) easily. Many bones are susceptible, with hip fractures being the worst outcome of osteoporosis. They cause pain, disability, require major health interventions (surgery and rehabilitation), lead to death in about 20% of cases, and the overall care of hip fracture patients is very expensive. Osteoporosis is treated to reduce the risk of fractures. The prevention and treatment of osteoporosis should include avoidance of factors known to bring on or worsen the condition. Smokers are known to have an increased risk of osteoporosis and fractures. However, it is not known how smoking brings on osteoporosis. Importantly, neither is it clear whether quitting smoking leads to improved bone health (and a reduced risk of fractures). These are important questions for the community in general and for smokers with osteoporosis in particular. We will endeavour to answer these questions by studying twins who do and do not smoke and by observing what happens to measures of bone health (bone mineral density and other factors) in people attempting to quit smoking. New information gained from these studies may lead to better ways of avoiding or treating the damage that smoking does to bone. We may also become able to predict the benefit to bone when people quit smoking.Read moreRead less
Novel Regulators Of Glucose Metabolism And Inflammation In Adipose Tissue Of Females
Funder
National Health and Medical Research Council
Funding Amount
$282,830.00
Summary
Obesity is a common problem which can lead to development of diabetes and heart disease. One of the major mechanisms by which obesity leads to these diseases involves a defect in the ability of insulin to stimulate uptake of glucose into cells. We have found that excess of the sex hormone testosterone in women can contribute to this defect in tissues. This study will investigate why testosterone causes this defect in females and whether this defect can be prevented using existing drug therapies.
Mechanisms Of Negative Feedback Regulation Of GnRH By Testosterone In Males
Funder
National Health and Medical Research Council
Funding Amount
$243,336.00
Summary
This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including test ....This project will improve our knowledge of the hormonal control of reproduction in males. The hormone testosterone, produced by the testes, acts on the brain to control the secretion of a substance called gonadotrophin releasing hormone (GnRH). GnRH acts on a small gland at the base of the brain to cause the production of hormones called gonadotrophins, that are essential for reproduction. These gonadotrophins act on the testes to ensure the production of sperm and other hormones, including testosterone. We plan to determine how testosterone acts on the brain to control GnRH secretion. To do this we will use male sheep and conduct a series of experiments designed to show where in the brain testosterone acts to ultimately affect the nerve cells that produce GnRH. Testosterone and similar compounds are increasingly being used as treatments for infertility, as a male contraception and misused as anabolic steroids. A thorough knowledge of how testosterone acts in the brain is necessary to improve treatments for reproductive disorders and ultimately to improve reproductive health in men.Read moreRead less
Characterisation Of A Novel Prostate-expressed Kallikrein-like Protease And Its Target Proteins
Funder
National Health and Medical Research Council
Funding Amount
$724,544.00
Summary
Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones o ....Prostate disease is common in most men in later life and can affect their quality of life adversely. The primary conditions are benign prostatic hyperplasia or BPH and prostate cancer. Symptoms of BPH affect between 50-70% of men over the age of 50 and prostate cancer is now the most common internal cancer diagnosed in men. More importantly, prostate cancer is the second most common cause of cancer deaths. We don't yet fully understand exactly how these diseases occur but the male sex hormones or androgens are known to play an important role. Prostate specific antigen or PSA has become widely accepted as a useful tool in helping to detect prostate cancer and then monitoring the disease. PSA, which is regulated by androgens, is an enzyme that either activates or breaks down many proteins that are important in both the normal function of the prostate and in the development of cancer. PSA belongs to a family of enzymes called the kallikreins. We have recently discovered a new member of this family that, like PSA, is also found in the prostate. We have called this new enzyme, K6, as it is the sixth member of this family to be identified. So , this project is about characterising this new K6 enzyme, finding out if it is also found in the prostates of men with BPH and prostate cancer, whether it is also regulated by androgens and what sort of proteins it may activate in these diseases. We will also compare these findings with what we know about PSA in these diseases. From these studies, we will not only understand more about this K6 enzyme and how it might be important in the prostate but also how it relates to PSA. These findings may ultimately lead to some new approaches in the detection and treatment for BPH and prostate cancer.Read moreRead less
PRE CLINICAL TRIAL WITH FETAL PIG INSULIN-PRODUCING CELLS
Funder
National Health and Medical Research Council
Funding Amount
$292,416.00
Summary
If fetal pig cells are to be of value in normalizing blood glucose levels in diabetic people once transplanted, they must survive and mature after being grafted. The pre-clinical study proposed will examine several novel issues that are of direct relevance to future clinical trials. The diabetic pig will be used as recipient to address when the fetal cell matures after it is transplanted, how long the grafted cells will maintain normal blood glucose levels, and at which site it is most appropria ....If fetal pig cells are to be of value in normalizing blood glucose levels in diabetic people once transplanted, they must survive and mature after being grafted. The pre-clinical study proposed will examine several novel issues that are of direct relevance to future clinical trials. The diabetic pig will be used as recipient to address when the fetal cell matures after it is transplanted, how long the grafted cells will maintain normal blood glucose levels, and at which site it is most appropriate to transplant the cells. The baboon will be used as recipient to address the safety of transplanting the pig cells, especially from the pig endogenous retrovirus, and whether the immunosuppressive regime proposed for use in humans will prevent cellular rejection. The diabetic baboon will be used in the final experiment step to determine if normalization of blood glucose levels can be achieved in this xenografted animal just as it can in the diabetic pig.Read moreRead less
IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged ....In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.Read moreRead less