An Evaluation Of The Validity Of Measureing Salivary Oxycodone Concentrations For Pharmacokinetic Studies In Patients
Funder
National Health and Medical Research Council
Funding Amount
$49,135.00
Summary
In many countries, oxycodone is replacing morphine as the opioid of first choice for the treatment of moderate to severe pain. Despite this, very little is known about how the drug is processed in the body or how its ability to control pain is affected by such factors as other drugs, age or organ function. Studies to determine this usually require multiple blood tests from individual patients over set time periods. Our team is able to measure drug levels in saliva and has shown this to be a vali ....In many countries, oxycodone is replacing morphine as the opioid of first choice for the treatment of moderate to severe pain. Despite this, very little is known about how the drug is processed in the body or how its ability to control pain is affected by such factors as other drugs, age or organ function. Studies to determine this usually require multiple blood tests from individual patients over set time periods. Our team is able to measure drug levels in saliva and has shown this to be a valid substitute for the measurement of drug levels in blood. Furthermore, one of us has developed a computer modelling system that shows how drugs are handled in the body using only a few samples from each patient. Palliative care patients are generally frail and unwell. We are reluctant to expose them to invasive tests such as repeated blood sampling. If we can prove that saliva sampling is as good as blood sampling, we will have identified a simple non-invasive means of greatly increasing our knowledge of oxycodone and how it behaves in individual patients. This in turn may allow us to tailor drug doses according to the unique characteristics of each patient and to optimise their pain control.Read moreRead less
Chronic Oral Graft-versus-host Disease: Clinical Risk Factors, Biochemical Markers Of Disease Activity And Novel Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$134,184.00
Summary
Chronic graft-versus-host disease (GVHD) is a serious complication of bone marrow transplantation. The oral cavity is often affected. Aims: 1.Identify and validate risk factors for oral GVHD 2.Assess if specific salivary components reflect disease activity 3.Trial novel therapeutic for GVHD-associated dry mouth Saliva testing may offer a non-invasive method to monitor oral GVHD. Also, new and effective topical agents are greatly needed and will improve therapeutic options in oral GVHD
T Helper Cytokines In Immunity And Organ-specific Autoimmunity
Funder
National Health and Medical Research Council
Funding Amount
$443,946.00
Summary
The overall goal of these studies is to identify mechanisms underlying the effects of cytokines on T cell-mediated immunity, how defects in these processes can result in organ specific autoimmune disease, and whether exploiting these mechanisms may result in improved therapies for individuals with autoimmune diseases. The proposed aims build on my previous work on interleukin-21 and interleukin-21-producing T helper cells in both immunity and autoimmunity.
The Physiological And Pathophysiological Roles Of Melanotransferrin
Funder
National Health and Medical Research Council
Funding Amount
$227,485.00
Summary
Melanotransferrin (MTf) is a membrane bound molecule that was originally identified in the malignant melanoma skin cancer and other tumours. Interestingly, MTf has many similarities to the serum iron-binding protein, transferrin, and initially MTf was thought to play a role in iron uptake by these cells. However, a series of studies by the applicant demonstrated that MTf did not play a major role in iron uptake by melanoma cells (Richardson et al. 1990, 1991a,b). In fact, most iron taken up by t ....Melanotransferrin (MTf) is a membrane bound molecule that was originally identified in the malignant melanoma skin cancer and other tumours. Interestingly, MTf has many similarities to the serum iron-binding protein, transferrin, and initially MTf was thought to play a role in iron uptake by these cells. However, a series of studies by the applicant demonstrated that MTf did not play a major role in iron uptake by melanoma cells (Richardson et al. 1990, 1991a,b). In fact, most iron taken up by these cells was via the binding of transferrin to the transferrin receptor. More recently, under the current NHMRC grant, we have been able to confirm and signficantly extend our previous studies to convincingly show that MTf is not involved in iron uptake by melanoma cells where it is expressed at very high levels (Richardson 2000 Eur. J. Biochem. 267 (in press). In addition, we showed that the expression of MTf in 50 human tissues was very different to transferrin and the transferrin receptor (TfR) that are well known to be involved in iron transport. For example, the TfR is expressed at high levels in tissues that require large amounts of iron eg. the placenta and bone marrow. In contrast, MTf was not expressed at high levels in these tissues, but was found in large amounts in unexpected locations such as the salivary gland. Furthermore, the expression of MTf was widespread through a variety of tissues, and in contrast to expectations, was found at higher levels in normal rather than fetal tissues. It is also intesting that MTf is found in the blood and brain of Alzheimer's disease patients. Our results suggest that MTf may play other unexpected roles apart from iron uptake. The present proposal will assess the roles of MTf in cellular functioning. This information will be very important in understanding the function of MTf in cancer cells, Alzheimer's disease and also in other tissues (eg. the salivary gland) where it is expressed at very high levels.Read moreRead less
Determinants Of Cytomegalovirus Salivary Gland Persistence
Funder
National Health and Medical Research Council
Funding Amount
$566,308.00
Summary
Human cytomegalovirus (HCMV) persists for extended periods in the salivary gland, an organ of viral transmission. It is not clear how the virus avoids immune mediated control in this tissue. This aspect of viral pathology will be assessed in a mouse model using two strains of murine CMV which exhibit marked differences in salivary gland persistence. The role of tissue tropism (inhibition of apoptosis), viral immune evasion and host immunity in salivary gland persistence will be studied.