Is Periosteal Bone Formation Responsible For Sexual Dimorphism In Bone Fragility
Funder
National Health and Medical Research Council
Funding Amount
$316,320.00
Summary
Men and women sustain fractures as they age because their bones become fragile. Women sustain fractures more often than men. Bone thinning occurs in both sexes but it is usually believed that this thinning or loss of bone is greater in women than men. We have evidence to suggest that this may not be correct. In fact, it is likely that men and women lose a similar amount of bone, about half what they started with, but during ageing, men lay down more bone on the outside surface of the bone than w ....Men and women sustain fractures as they age because their bones become fragile. Women sustain fractures more often than men. Bone thinning occurs in both sexes but it is usually believed that this thinning or loss of bone is greater in women than men. We have evidence to suggest that this may not be correct. In fact, it is likely that men and women lose a similar amount of bone, about half what they started with, but during ageing, men lay down more bone on the outside surface of the bone than women compensating for the similar amount lost on the inside of the bone. We also have evidence to suggest than men and women who get spine fractures do so because the process of laying down bone may fail to occur normally. We will study these processes of bone loss inside the bone and bone gain outside the bone to try to better understand why bones become weak. We will measure the bone size and its density in healthy men and women and patients with fractures to determine how the increasing size of the bone produced by laying down bone on its outside helps to keep it strong and to preserve the bone that would otherwise be lost if it didn't occur or if a disease developed that might reduce the compensatoryRead moreRead less
Does Pregnancy Cause Morphological Changes In Central As Well As Peripheral Nerve Pathways That Control Blood Pressure?
Funder
National Health and Medical Research Council
Funding Amount
$382,538.00
Summary
Pregnancy changes blood pressure but the mechanism is unknown. We will use state-of-the-art anatomical methods to define how pregnancy alters nerves controlling blood pressure. We will identify changes in the information the nerve cells receive, in their shape and in the way they communicate with other blood pressure-controlling nerve cells. This information will help to develop new ways to prevent and treat pre-eclampsia, a major cause of death and disability for mothers and their newborns.
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
Morphometric Analysis Of Normal Airway Structure In Childhood And The Influence Of A History Of Asthma On This Structure
Funder
National Health and Medical Research Council
Funding Amount
$186,113.00
Summary
The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For ex ....The architectural structure of the airways of the lung is thought to have profound effects on airway function. Changes in this structure are believed to be partly responsible for limiting the flow of air into the lung in conditions such as constant wheezing, bronchitis and asthma. Pathological studies carried out on adult lungs have shown that the structure of the airways is indeed altered in patients with lung disease when compared with patients with no history of breathing difficulties. For example, the walls of the airways are much thicker in patients with lung disease. This thickening means that the airways are much narrower and therefore not able to carry as much air as in people with healthy lungs. In addition, the muscle within the airway wall, which is normally very sparse, is much denser in people with asthma and bronchitis. Thus, the airways can be squeezed closed more easily. It is not known if these changes are present in children who have lung disease. X-rays and sophisticated breathing tests suggest that these children may also have thicker walls and more muscle in their airways. The major difficulties in assessing whether such changes are present in children, is the lack of information on the normal structure in infants; how this changes as they grow to adulthood; or if there are any gender differences. This project aims to obtain this information from the airways of male and female children from 0-18 years. This information can then be used as a basis for comparison with the structure found in children with lung disease, in particular asthma, and therefore assist in making assessments as to the cause of their breathing difficulties. With more knowledge about these causes, we will be in a better position to design new and better treatments and produce ways of preventing them ever occurring.Read moreRead less
Interaction Between Estrogen And The Renin-angiotensin System In The Regulation Of Arterial Pressure
Funder
National Health and Medical Research Council
Funding Amount
$638,525.00
Summary
Women before menopause are protected from cardiovascular disease. Estrogen is thought to provide this protection. Yet post-menopause estrogen replacement has not always proven beneficial. We are investigating the idea that estrogen within a narrow window modulates the hormone angiotensin (a major regulator of blood pressure) to lower blood presssure but outside this range (higher or lower) the benefits are lost.
An FMRI Analysis Of The Functional Organization Within The Brain Of Experimental Superficial And Deep Orofacial Pain
Funder
National Health and Medical Research Council
Funding Amount
$307,526.00
Summary
This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a dee ....This project will investigate how the human brain processes a number of important aspects of human jaw muscle pain that are clinically relevant but poorly understood. For example, we do not understand why jaw muscle pain has such different behavioural effects to skin pain. Jaw muscle pain is associated with a significant emotional component not seen in with skin pains. Also, skin pain usually has a sharp or burning quality, is well-localized and is readily treated, while jaw muscle pain is a deep pain that has a dull, aching quality that may be referred to related sites of the face, head and neck. It is also not known why jaw muscle pain is more common in females in comparison to males. Chronic jaw muscle pain is a major symptom of patients with Temporomandibular Disorders, the most common form of non-dental orofacial pain and that involves pain in or about the jaw joint and-or jaw muscles, and often limitation of jaw movement. Chronic jaw muscle pain can have a severe effect on quality of life but its diagnosis and management is difficult. Despite the widespread prevalence of chronic orofacial pains, we have little information on the central processing of chronic human orofacial pain. This proposal will improve our fundamental understanding of how jaw muscle pain is processed in the brain. The way that the central nervous system processes and represents jaw muscle pain will help explain why these pains present differently in the clinic and should provide important information on the differences between females and males in the representation of jaw muscle pain. This information on the central processing of chronic orofacial pain is crucial to inform the direction of novel or specific management strategies. Our long-term goal is to improve the diagnosis and management of patients with Temporomandibular Disorders, and the present application represents a major new direction of research.Read moreRead less
Sex Differences In The Mechanisms By Which Stress Inhibits The Secretion And Actions Of GnRH
Funder
National Health and Medical Research Council
Funding Amount
$408,055.00
Summary
It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have differ ....It is well known that stress can impair reproduction in humans and animals but it is not understood how this occurs. Consequently there are no therapies available to overcome the detrimental effects of stress on reproduction. Stress can take many forms, such as psychological stress, surgical trauma, strenuous exercise, undernutrition, all of which may inhibit reproduction. We now know that males and females respond differently to stress and we have shown that stress is also likely to have different effects on reproduction in males and females. In this project we aim to determine how stress impairs reproduction in males and females. A major effect of stress appears to be to inhibit the secretion of a substance produced by the brain that is necessary for the regulation of reproduction. This substance is called gonadotrophin releasing hormone (GnRH) and it acts on a small gland at the base of the brain to cause the release of hormones that are essential for reproduction in both males and females. It is also possible that stress may inhibit the actions of GnRH. Our research suggests that there may be differences between males and females in the extent to which stress inhibits the secretion of GnRH from the brain and its actions to cause the release of other reproductive hormones. In this project we will determine how stress acts in the brain to affect the secretion and actions of GnRH in males and females. Our research will make a major contribution to our knowledge of the way that stress inhibits reproduction in males and females. This information is essential in order to develop specific remedies to overcome reproductive disorders caused by stress and to improve reproductive health in both sexes.Read moreRead less
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
Studying The Interaction Of Reelin Deficiency And Environmental Factors In The Development Of Schizophrenia Using Animal Behavioural Models
Funder
National Health and Medical Research Council
Funding Amount
$438,695.00
Summary
Schizophrenia is caused by an interaction of genetic predisposition and environmental risk factors such as stress or drug abuse. Reelin is a protein involved in the normal development of the brain but its levels are markedly reduced in schizophrenia. We will use mice with low levels of reelin in their brain and assess the effect of environmental stress and drugs of abuse. These studies could elucidate gene-environment interaction in schizophrenia and lead to new treatment strategies.