Sympathetic Control Of Cutaneous Blood Flow And Blood Pressure In Human Spinal Cord Injury
Funder
National Health and Medical Research Council
Funding Amount
$242,002.00
Summary
While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracol ....While spinal cord injury can cause devastating changes in the nervous system paralysis and loss of sensation relatively little is known about changes to the sympathetic nervous system. The sympathetic nervous system is intimately involved in the ongoing control of blood pressure, blood flow and temperature control. Loss of sympathetic control can occur following spinal cord injury. Interruption of descending pathways can result in partial or complete loss of sympathetic outflow from the thoracolumbar segments. Complete decentralization can result in autonomic dysreflexia (autonomic hyperreflexia), in which sensory stimuli originating below the lesion evoke a reflex increase in sympathetic drive to the blood vessels, causing them to constrict. Because of this, blood pressure may rise suddenly and remain at such high levels that stroke and (occassionally) cardiac arrest may occur. This phenomenon, autonomic dysreflexia, is considered a medical emergency. The typical subjective signs of autonomic dysreflexia include a throbbing headache, tingling in the head or nasal congestion; sweating and flushing above the lesion are clinical signs that prompt medical staff to measure blood pressure and to locate the source of sensory irritation (usually a distended bladder or impacted colon, sometimes a pressure sore or ingrown toenail). Commonly, however, subclinical episodes go undetected, and this phenomenon of silent dysreflexia is of increasing concern. This project will develop means of assessing the integrity and state of the sympathetic nervous system below a lesion in patients with spinal cord injury and characterize the firing properties of reflexly activated sympathetic neurones.Read moreRead less
Prevention Of Multi-drug Resistant Tuberculosis In A High Prevalence Setting: ‘Connecting The DOTS’ In Vietnam
Funder
National Health and Medical Research Council
Funding Amount
$3,382,020.00
Summary
The close contacts of people with multi-drug resistant tuberculosis (MDR-TB) have a high risk of developing the disease. The V-QUIN MDR-TB Trial will evaluate the effectiveness of an oral antibiotic (levofloxacin) in preventing drug resistant TB among infected household contacts of TB patients. Household contacts from 10 Provinces in Vietnam will be randomly allocated to receive six-months of either levofloxacin or a placebo, and then followed for two years to see if they develop tuberculosis.
Multidrug Resistance Protein 1 Inhibitors To Sensitise Cancers To Chemotherapy
Funder
National Health and Medical Research Council
Funding Amount
$840,166.00
Summary
Multidrug resistance protein 1 (MRP1) is often present at high levels in cancer cells, where it pumps chemotherapy drugs back out, causing drug resistance. Inhibitors that block MRP1 would increase the effectiveness of chemotherapy. We have developed MRP1 inhibitors with promising activity in cancer cells and mouse tumours and will now develop these inhibitors for clinical application and commercialisation.
Modelling The Impact Of Strategies To Control Gonorrhoea And Minimise The Threat Of Antimicrobial Resistance In Remote Indigenous And Other High Risk Populations
Funder
National Health and Medical Research Council
Funding Amount
$467,079.00
Summary
Gonorrhoea is a serious public health issue in Australia. Notification rates are disproportionately high among Aboriginal and Torres Strait Islander people and men who have sex with men, and there is evidence of an emerging epidemic in the general heterosexual population. Additionally, available treatments are under threat from resistant strains. We will use mathematical modelling to evaluate strategies for controlling gonorrhoea and for minimising the threat of antimicrobial resistance.
Neisseria Gonorrhoeae Antmicrobial Resistance: Detection And Propagation
Funder
National Health and Medical Research Council
Funding Amount
$435,129.00
Summary
Neisseria gonorrhoeae, the pathogen that causes gonorrhoea, has developed resistance to multiple classes of antibiotics. The last remaining class of antibiotics that can successfully be used for general treatment of gonorrhoea is extended spectrum cephalosporins (ESCs). However, we are now starting to see Neisseria gonorrhoeae isolates with early signs of ESC resistance. This research will use molecular technology and mathematical modelling to investigate Neisseria gonorrhoeae antimicrobial resi ....Neisseria gonorrhoeae, the pathogen that causes gonorrhoea, has developed resistance to multiple classes of antibiotics. The last remaining class of antibiotics that can successfully be used for general treatment of gonorrhoea is extended spectrum cephalosporins (ESCs). However, we are now starting to see Neisseria gonorrhoeae isolates with early signs of ESC resistance. This research will use molecular technology and mathematical modelling to investigate Neisseria gonorrhoeae antimicrobial resistance in Australia.Read moreRead less
Understanding Sphingolipid Mediators Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$643,447.00
Summary
Sphingolipids are a class of lipid metabolites that have a variety of functions within cells. It has been known for some time that an accumulation of excess lipid, including certain sphingolipids, can adversely impact insulin action and glucose metabolism in cells. In this project we will a combination of strategies to test the hypothesis that the sphingolipid profile can be manipulated to have favourable effects on metabolism.
Horizontal And Vertical Transmission Mechanisms Of Staphylococcus Aureus Multiresistance Plasmids
Funder
National Health and Medical Research Council
Funding Amount
$408,993.00
Summary
Strains of Golden Staph bacteria resistant to many antibiotics are a major cause of serious hospital-acquired, and increasingly community-acquired, infections. The bacteria have mechanisms that cause efficient transmission of resistance genes to their offspring as well as to other strains. This project aims to elucidate key features of these mechanisms so that treatments can be devised that disrupt the maintenance and transfer of resistance, so as to prolong the effectiveness of antibiotics.
Four Dimensional Epigenome Remodelling: Implications For Endocrine Resistance In Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$828,560.00
Summary
Patients with estrogen receptor positive breast cancer receive endocrine therapy, however half fail to respond and relapse. Endocrine resistant breast cancer currently represents the most significant challenge to breast cancer treatment. We suggest that three-dimensional epigenetic remodelling is an underlying mechanism that determines endocrine sensitivity that we will exploit as a novel therapeutic strategy to effectively treat patents with recurrent disease.
I am a cancer cell biologist investigating molecular mechanisms of leukaemia cell resistance to chemotherapeutic drugs, and novel strategies for the management of high risk or relapsed disease. For these purposes I have developed orthotopic xenograft mode