Targeting Alpha-conotoxin MII To Inhibit Neuronal Nicotinic Acetylcholine Alpha3beta2 Receptors Of The CNS
Funder
National Health and Medical Research Council
Funding Amount
$218,334.00
Summary
Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique ....Nicotinic acetylcholine receptors (nAChRs) play a central role in nerve signal transmission, neurite growth and development and are the representative model of the ligand-gated ion channel superfamily. Recent studies, including those from Dr Lewis' and A-Prof Alewood's laboratories, have identified alpha-conotoxin peptides which can discriminate among the different nAChRs, apparently by binding to the specific interfaces formed by different subunit combinations. Thus alpha-conotoxins are unique tools with which to identify and determine the physiological role, played by the different native neuronal nAChRs. Moreover, they are unusually stable peptides and can withstand enzyme and acid treatment. These findings have encouraged us to pursue the viability of alpha-conotoxin MII as a new and selective antagonist for the neuronal nictotinic receptor alpha3 beta2 which is involved in nicotine addiction. The challenge and major goal of this project is to deliver alpha-conotoxin MII efficiently into the brain. A-Prof Toth has developed a novel drug-delivery system for the oral administration of drugs and peptides, which in their unmodified form are poorly absorbed or biologically unstable. In this project alpha-conotoxin MII will be combined with a specifically designed lipopolysaccharide delivery system . The delivery system can be specifically tailored to transport a wide variety of peptides through the different biological barriers. The peptides can be conjugated to the delivery system in such a way as to release the peptide after it has been absorbed (prodrug), or to form a biologically stable and active novel molecule. The outcomes of this work will include the first delivery system of nicotinic antagonists to the brain and new knowledge concerning the importance of the neuronal nictotinic receptor alpha3 beta2 in nicotine addiction.Read moreRead less
Lipoceramic Technologies: A Solution To Low And Variable Bioavailability Of Poorly Soluble Anti-inflammatory Drugs
Funder
National Health and Medical Research Council
Funding Amount
$200,600.00
Summary
A novel oral drug delivery platform will be developed that improves the absorption of poorly soluble drugs from the GI tract, leads to improved clinical outcomes and has significant commercial value. This development will be based on the combination of formulation, in vitro analysis and in vivo animal model studies. An advanced prototype formulation will be established for celecoxib (a non-steroidal anti-inflamatory drug) that will be suitable for human phase 1 clinical trials.
Bisphosphonate Use, Oral Flora, Saliva, Gingival Crevicular Fluid And Bone Markers In Patients With Jaw Osteonecrosis
Funder
National Health and Medical Research Council
Funding Amount
$121,751.00
Summary
Bisphosphonates are used in patients with bones that break easily due to conditions such as osteoporosis. Recent research suggests a possible association between these drugs and jaw bone breakdown called jaw osteonecrosis - a devastating condition with no current effective treatment. It is unclear why this condition affects only jaw bones. This study seeks to investigate if bacteria in the mouth, gum disease and saliva are involved in jaw osteonecrosis, which can then help to improve management.
The CCRE for Oral Health will focus on the prevention and treatment of oral diseases and disorders and their clinical consequences. Research will emphasise three areas of clinical care that are critical to the management of oral health, systemic health and general well-being: 1.Primary prevention to prevent disease onset 2. Diagnosis and risk prediction for oral conditions 3. Clinical intervention
Caries Initiation Across Childhood To Adulthood By Exposure To Water Fluoridation
Funder
National Health and Medical Research Council
Funding Amount
$198,297.00
Summary
This research program is expected to contribute to filling significant gaps in the understanding of factors determining the oral health of Australian children and young adults. The purpose of the project is to develop a better understanding of the outcome of long-term exposure to fluoridated water among young adults.
The South Australian Dental Longitudinal Study has been the first comprehensive dental longitudinal study of older adults to be conducted in Australia. Participants were aged 60+ years at the 1991 baseline data collection, and were a random sample of community-dwelling older adults in urban Adelaide and rural Mount Gambier. The 11-year follow-up data collection will build upon the previous study findings to provide important and new information about the onset and progression of oral diseases in ....The South Australian Dental Longitudinal Study has been the first comprehensive dental longitudinal study of older adults to be conducted in Australia. Participants were aged 60+ years at the 1991 baseline data collection, and were a random sample of community-dwelling older adults in urban Adelaide and rural Mount Gambier. The 11-year follow-up data collection will build upon the previous study findings to provide important and new information about the onset and progression of oral diseases in older Australians. It will also assist with the identification of general health and other characteristics (socio-demographic, medical, functional, cognitive, nutritional, swallowing, dental history, oral hygiene care, financial, social support and oral disorder social impact characteristics) that are associated with oral diseases in various groups of older adults. Groups of older adults within the study include those who are healthy and living in the community, those who are frail and use support services, and those who have moved into residential care. This information will assist both private and public health sectors, dental professionals and other health professionals with the identification of those older adults who are at high risk for developing oral diseases, such as those with dementia, those with physical disabilities, and those living in residential care. This 11-year data collection will be one of only 4 similar international studies currently being conducted, and will provide important comparison data for future studies of older Australians.Read moreRead less
Squamous Cell Carcinomas Of The Head And Neck: Exploring The Role Of Human Papillomavirus Infection
Funder
National Health and Medical Research Council
Funding Amount
$217,213.00
Summary
Human papillomavirus (HPV) is the major cause of cervical cancer and the cause of 5% of all human cancers. HPV has recently also been associated with oral cancer, especially in patients younger than 50 years of age. In this project we will investigate how common HPV infection is in oral cancers in Australia. In these patients we will also investigate mutations in genes that have been found to play a critical role to clear persistent HPV infections and how cells respond to HPV infection.