New Targets for the Prevention of Stroke Disability
First Published: Enews - August 2010
Flinders neuroscientists are looking for ways to work with the brain's own adaptive responses to prevent the long term damage and permanent disability which often follows a stroke.
Stroke is Australia's second biggest killer after heart disease, and is the leading cause of disability in Australia. It occurs when there is an interruption of the blood supply to vessels in the brain, which can be caused by a lack of blood flow, a blockage or a haemorrhage.
There is a very short window of time where emergency treatments can be effective in halting and reversing the damage to cells caused by the lack of oxygen and other nutrients.
Professor Neil Sims from the Centre for Neuroscience and Discipline of Medical Biochemistry is looking to readdress the medical belief that a patient needs to have presented to hospital within a few hours of the onset of symptoms in order for treatments to be effective.
"Our research is now asking the question whether we can do anything after initial damage has developed," Professor Sims said.
"During the first few months following their stroke, the brains of patients often show what could be described as an 'adaptive response'. During this time these patients can improve and regain some of the movement they had lost."
Research has shown that scarring of the brain tissue can develop in the months following a stroke, which can limit this ability of the brain to make new connections between nerve cells and to restore neurological function.
"We know changes in brain cells known as glial cells lead to this type of scarring," Professor Sims said. "We are now using a rat model of stroke to determine what the critical changes in the glial cells are, and how we can interfere to prevent scarring."
The research team hope to identify new targets and to develop drug treatments which could promote a patient's recovery.
"Because not all patients realise they are having a stroke, or are unable to present to hospital quickly, the advantage of this approach is that the key events we are trying to modify occur 12 hours to one week after the initial stroke," Professor Sims said.
World First for Parkinson's Team
First Published: Enews - April 2010
A team of Flinders researchers are the first and only group in the world able to isolate the abnormal clusters of proteins which cause the death of brain cells in Parkinson's and related degenerative diseases.
Dr Wei Ping Gai, Senior Research Fellow in the Department of Human Physiology at Flinders Medical Centre, has been researching the causes of brain cell death in degenerative diseases for the past 20 years.
His research has had a particular focus on Lewy bodies - abnormal clusters of proteins which are found in the brain cells of both Alzheimer's and Parkinson's sufferers and in some types of dementia.
Dr Gai and his team have developed a world-first technique that uses antibodies attached to magnetic beads to bind to a particular protein (Alpha-synuclein) that is the largest component of Lewy bodies. They are then able to extract the Lewy bodies from Parkinson's affected brain tissue for detailed protein analysis.
This has allowed the Flinders team to be the first in the world to describe the internal structure of the Lewy body formations (which have a very precise structure), and to work in collaboration with teams from Elan Pharmaceuticals and Harvard Medical School to identify other proteins and components of the Lewy bodies.
The collaboration has recently uncovered that the addition or lack of phosphates on this target protein could play a role in the formation of the Lewy bodies. This interaction of this protein with the phosphates may also explain why the Lewy bodies react with the cell membrane to cause the cell's death.
The team hope that if they identify why proteins such as Alpha-synuclein form Lewy bodies, their research will pave the way for developing new diagnostic markers and drugs which can modify this process in both Alzheimer's and Parkinson's disease.
Genetic Discovery For Multiple Sclerosis
First Published: Investigator - June 2009
An Australasian multiple sclerosis (MS) study has discovered variations in two genes which could contribute to the development of the disease.
MS is an inflammatory disorder of the brain and spinal cord and affects almost 20,000 people in Australia. It is the most common cause of neurological disability in young people; however its cause is a mystery.
The research is one of the largest genetic studies in MS ever to be undertaken. It involved scanning the DNA of more than 5,000 people – 1,600 with MS and 3,400 without MS.
The study was conducted by The Australian and New Zealand Multiple Sclerosis genetics consortium (ANZGENE). ANZGENE is a collaboration of MS clinicians and scientists, supported by Multiple Sclerosis Research Australia and the Australian Research Council.
Dr Mark Slee, Neurologist from the Flinders Multiple Sclerosis Service and Department of Neurology, is part of the consortium. He said findings from the research provide a platform to target new therapies aimed at early treatment or disease prevention.
‘The chance of developing MS comes from environmental factors acting on a genetically susceptible person,’ he said.
The ANZGENE study, recently published in the prestigious scientific journal Nature Genetics, found that people with MS are more likely to have several genetic variants on Chromosome 12 and Chromosome 20 which are linked to immune function and contribute to the development of MS. Previous genetic studies in MS have implicated other immune related genes in MS susceptibility.
On Chromosome 12, one of the genetic variations contributing to MS risk was found to be involved in the metabolism in Vitamin D (the CYP27B1 gene). Other auto-immune diseases, such as Type 1 Diabetes are also associated with changes in the same gene.
‘The new gene variation associated with Vitamin D metabolism is very important,’ Dr Slee said. ‘This gene variation may provide a link between genetic risk and environmental factors which determine MS susceptibility.’
On Chromosome 20, a further MS susceptibility gene was found – the CD40 gene.
Variations in this gene are also associated with other autoimmune diseases such as Rheumatoid Arthritis and Graves’ disease. This gene is important in regulating activity in many parts of the immune system and how immune cells become activated to cause inflammation in the nervous system.
Researchers will now ‘fine map’ the newly discovered genes to gain a better understanding of their role in MS which could lead to the development of new therapies for treatment of the disease.
New Era In Sleep Disorder Diagnosis
First Published: Investigator - June 2009
A Southern Adelaide Health Service research team has developed an award-winning diagnostic tool for GPs to quickly and easily diagnose patients with obstructive sleep apnoea.
Obstructive sleep apnoea is estimated to affect up to 10 percent of the Australian adult population, and is associated with a number of health problems including high blood pressure, daytime sleepiness, and increased risk of heart attack and stroke.
Despite this, Dr Chai said the condition is widely undiagnosed. ‘This is because traditional diagnosis and treatment involves patients undergoing a multi-channel sleep study recording and awaiting review by a Sleep Specialist – a process that can take several months,’ she said. However, the research team’s diagnosis tool may be set to change all that.
The test – developed and validated in patients from six GP clinics across South Australia since 2007 - consists of two simple steps: a short four-item verbal questionnaire and the overnight use of a portable single-channel sleep monitor for those patients identified as possible sleep apnoea sufferers from the questionnaire.
‘We have been able to show that the two-step strategy is a very accurate way of diagnosing obstructive sleep apnoea,’ Dr Chai said.
A second stage of the study involves a larger group of GPs across urban, rural and remote South Australia using the diagnosis tool and patients identified with obstructive sleep apnoea being randomly assigned to the care of either their GP or to usual management in a sleep specialist clinic for a total of six months of follow-up. The research team will then compare the outcomes of care between the two groups.
‘We will look at outcomes in terms of sleepiness levels, symptoms of obstructive sleep apnoea, health care costs, patient satisfaction and adherence to treatment.’
‘Hopefully we will be able to demonstrate that GP-based care is comparable to care by a sleep specialist, which will ultimately mean reduced waiting times and better health outcomes for patients.’
Flinders Clinicians Trust Fund Supports Tomorrow’s Doctors
First Published: Investigator - February 2009
Dr Ching Li Chai of the Adelaide Institute for Sleep Health is the recipient of a three year PhD Flinders Clinicians Trust Fund research scholarship to explore ways to simplify and improve the diagnosis and treatment of patients with obstructive sleep apnoea (OSA).
OSA is a common condition in Australia, which as the name suggests is caused by repetitive obstructions of the upper airway during sleep. The condition is characterised by pauses in breathing lasting longer than 10 seconds which are followed by an arousal and a gasp for breath.
Often the condition is present for years without detection as many sufferers are unaware of their sleeping habits, and frequently fail to report their symptoms to their general practitioners.
Common symptoms include daytime sleepiness, fatigue, restless sleep and loud snoring with pauses and gasps, but can also include morning headaches, insomnia and an increased heart rate/blood pressure.
A steady increase of OSA in Australia has created a high demand for sleep centres where diagnosis and treatment is undertaken, with some waiting lists as long as 6-12 months.
“Alternative, simplified and low-cost models of care for OSA are needed to address this growing burden of disease,” said Dr Chai.
“General practitioners who regularly manage chronic disorders such as hypertension and obesity, which are important risk factors of OSA, are ideally positioned to take on a greater role in the diagnosis and management of this condition.”
To help GPs Dr Chai has created a simple screening technique to assess a patient’s risk of OSA and to help with diagnosis she has validated the use of a portable home monitor called an ApneaLink (ResMed) that measures oxygen saturation during sleep.
A Link Between Down Syndrome And Alzheimer’s
First Published: Investigator - February 2009
A group of scientists based at Flinders Medical Centre are investigating a protein that is over-expressed in both Down syndrome and Alzheimer’s disease with the intent of identifying if there is a common link between these two conditions.
“Down syndrome is a genetically-based disorder which results in multiple conditions for sufferers,” said Dr Damien Keating, Head of the Molecular and Cellular Neuroscience Lab.
“Amongst these conditions, Down syndrome individuals normally develop Alzheimer's disease at an early age, often as young as their mid 30s or early 40s.”
Those born with Down syndrome have a trisomy (three copies) of the human chromosome 21 rather than the normal two.
This means that every cell in the body has an extra copy of the genes that make up chromosome 21, which leads to the symptoms and physical characteristics associated with Down syndrome.
One of the proteins that make up chromosome 21, called RCAN1, is over expressed in neurons in the brain of those with both Down syndrome and Alzheimer’s disease. Dr Keating has found that RCAN1 works as a regulator of a process called exocytosis which controls the firing of messages from one neuron to another (neurotransmission) in the brain.
Dr Keating’s lab, which is a leader in measuring cell signalling, has been testing different levels of RCAN1 expression and has discovered that both under and over expression of the protein reduces this neurotransmission.
This reduction of neurotransmission causes brain function and performance problems and can lead to brain cell death, as is often seen in both Down syndrome and Alzheimer’s.
“We hope to understand why changing the normal expression of RCAN1 affects neuron function and communication, to better understand what happens in the brain in conditions where RCAN1 levels are increased,” said Dr Keating.
“For example, could the risk of Alzheimer’s and the effects of Down syndrome be reduced by normalising the expression of RCAN1?”
Dr Keating and his team continue their investigations in the hopes of contributing to a better understanding of these conditions.
Tailoring Treatment For Stroke Brain Damage
First Published: Investigator - December 2008
Flinders researchers are investigating whether tailoring treatments to individual brain cell populations can help stroke victims recover more quickly.
The research team is working on new ways to selectively target different cell populations in the brain and to modify their function by introducing new genes.
‘We’ve already made good progress in this area by delivering genetic material via an uptake mechanism that is normally used by the cells themselves,’ Dr Hakan Muyderman, a researcher in the Centre for Neuroscience at Flinders said.
‘The next step is to see if we can use this technique on selected brain populations to treat the effects of stroke in animal models of this disease.’
Stroke is the second biggest killer after heart disease in Australia. More than 60,000 people suffer stroke or recurring stroke each year. A common effect of stroke is damage to the brain and changes in behaviour and personality.
Delivering treatment to specific cells of the brain has not been possible before now and researchers hope their work may create better treatments for stroke and other diseases of the central nervous system such as Alzheimer’s, Parkinson’s and motor neuron disease in the future.
The research will also help shine light on the role of glial cells, also known as astrocyctes. Glial cells greatly outnumber neurons in the brain and it is believed that they play many essential roles in normal brain function.
Brain insult or injury activates these cells which initiate responses that can have both protective and damaging effects on the surrounding neurons.
Hakan said understanding the role of these cells has been limited as there have been few specific approaches that have allowed the properties of the cells to be selectively targeted in an intact living brain.
‘A gene delivery system like the one we are creating that can selectively target these cells and produce short-term changes in gene expression will be of significant value in creating a better understanding of the role of these cells,’ said Hakan.
Repairing Brain Damage In Stroke
First Published: Investigator - August 2008
Scientists at Flinders Medical Centre are fine-tuning new technology that could target and deliver treatment to specific groups of brain cells that have been damaged by stroke.
There are billions of different types of cells in the brain, each with their own function and response to injury. Targeting treatment to specific groups of these cells has not been possible before now.
Dr Håkan Muyderman from the Department of Medical Biochemistry and his colleagues have developed a technique that utilises a natural function of cells to deliver genetic material directly into specific brain cells to either repair them or alter their function so they are no longer damaging to the brain.
They have been making good progress and will soon see if this approach can be used to treat the brain damage and behavioural changes that develop in stroke.
Stroke has become the second biggest killer after heart disease in the developed world and is the leading cause of disability in Australia.
An attack can be caused either by a sudden disruption of blood flow to the brain or a haemorrhage that leaks blood into the brain, causing devastating damage to brain tissue.
Dr Muyderman’s research will also help shine light on the role of glial cells (also known as astrocytes), as they have not yet been well defined. Glial cells greatly outnumber nerve cells in the brain and are believed to play many essential roles in normal brain function.
Understanding the role of these cells has been limited as there have been few scientific approaches that have allowed the properties of the cells to be selectively targeted in an intact living brain.
“A gene delivery system capable of selectively targeting sub-populations of brain cells will be of significant value in creating a better understanding of the contribution of these cells to normal brain function and disease,” said Dr Muyderman.
This research could also contribute to better treatments for other diseases of the central nervous system such as Alzheimer’s, Parkinson’s and motor neuron disease.
Fellowship Winner Sets His Sights On Stroke
First Published: Investigator - July 2008
A Flinders Medical Centre consultant neurologist is spearheading a campaign to increase the efficiency of stroke diagnosis and treatment by emergency medical services.
Dr Andrew Lee will use a two year NICS Fellowship awarded by the National Health and Medical Research Council to improve formal stroke education among emergency department staff and paramedics.
‘If clot busting drugs can be given within three hours of the onset of stroke symptoms, the number of people dying or becoming disabled after suffering an ischaemic stroke (stroke caused by blood clots) can be reduced.’
‘But to achieve this we need ambulance paramedics trained in stroke treatment and the seamless transfer of these patients to stroke units.’
Andrew said formal stroke education for emergency department staff and paramedics was lacking in Australia.
‘The NICS Fellowship will allow me to develop and deliver this knowledge for ambulance paramedics. I’ll also implement standardised systems to assess stroke severity and provide pre-hospital notification of incoming stroke patients.’
Andrew said best practice therapy for patients who had experienced stroke within the previous three hours was to be administered clot-busting agents.
‘I want to translate that therapy - that has been proven from 10 years research – and implement it into normal clinical practice.
‘It’s not always easy to identify a stroke patient, because stroke can masquerade as many other conditions. That’s what I hope to change with education and systems, so that paramedics and emergency department staff can quickly and effectively recognise and treat stroke patients.’
Andrew said if stroke patients were treated with the appropriate therapy in the shortest time there was a 30 percent increased chance that they would recover without disabling side effects.
BankSA Golf Day
First Published: Investigator - February 2008
Professor Neil Sims is investigating stroke and the chemically-induced changes that take place in the brain in response to treatments.
This project is focusing on characterising the effects of these changes in brain cell function to understand if they reduce the damage brought on from impaired blood flow caused by a stroke.
Seeking Answers For A Rare Brain Disease
First Published: Investigator - July 2007
A team of researchers and counsellors at Flinders Medical Centre (FMC) are attempting to provide better outcomes for individuals with a rare neurological condition called Huntington’s disease. Huntington’s is a hereditary disease caused by a gene defect that triggers the death of brain cells in the central region of the brain, the basal ganglia, which controls motor function, cognition and emotions.
Currently there is no cure for the disease, but symptoms can be managed with medication and care. The symptoms usually develop later in life, however the severity and progression differ in each case. Most sufferers will eventually exhibit uncontrolled movements and eating and mobility may become an issue, whereas full time care is required.
Flinders researchers Dr Xin-Fu Zhou and PhD student Miss Linyan Wu are looking into the mechanisms that lead to Huntington’s disease in the hopes of improving treatments.
In Huntington’s disease, the death of brain nerve cells is caused by a dysfunction of the mechanism that transports a neurotrophic factor called BDNF to nerve terminals. Neurotrophic factors are made of a family of proteins that are responsible for the proper function of nerve cells. Brain cells die if the balance of these factors is disturbed.
It is currently unknown how BDNF is transported to these nerve terminals. However, the research team are interested in a protein called HAP1, whose job is to transport biological cargo throughout the nervous system.
“Our project will examine how HAP1 interacts with BDNF,” said Dr Zhou. “It may be that the defective gene interferes with this healthy relationship causing the BDNF to not be delivered to nerve cells.”
“Understanding how BDNF is transported to brain nerve tissue will create a better understanding of how Huntington’s develops and could aid in the development of a treatment for this disease and others like it,” he said.
Flinders also houses the SA Huntington Disease Unit where individuals can be screened for the gene defect which leads to the disease, the only place in South Australia that performs the test and provides a support and counselling service to those who receive a positive result.
Researchers Need Brains
First Published: Investigator - July 2007
In 1986 the first Brain Bank in South Australia was established at Flinders Medical Centre (FMC) to provide access to important human tissue for research purposes.
Since this time the SA Brain Bank has joined the Australian Brain Bank Network (ABBN), a collection of state-based brain banks which work collaboratively to facilitate brain donations, including the collection, handling and distribution of human tissue for neurological research.
Currently the SA Brain Bank houses 214 donated brains and has 185 future donors.
Research into neurological diseases such as Alzheimer’s, Parkinson’s, Motor Neuron disease, Huntington’s and other neurological and psychiatric conditions rely heavily on comparing diseased and normal brain tissue.
“Brain donation is important for neurological research to progress,” said Ms Robyn Flook, Coordinator of the SA Brain Bank.
Ms Flook went on to say that “current brain imaging technology provides us with excellent insights into the changes that have occurred in diseased and damaged brains, however more detailed cellular examination of the living brain is not possible without doing damage.”
Understanding how brain cells function, or why they are malfunctioning, is greatly advanced by analysis of brain tissue after death. This is vital in creating a better understanding of and treatments for degenerative neurological and psychiatric conditions.
Registration to become a brain donor is slightly different from becoming an organ donor. Brains are never used for transplantation but purely for research purposes and all donor details are kept confidential. For more information contact Robyn Flook at the SA Brain Bank on 8204 4107.
Investigating Ecstasy Related Deaths
First Published: Investigator - January 2007
Every year we hear of young Australians who, after consuming MDMA (Ecstasy), develop such a high body temperature which despite urgent hospital treatment can result in death.
Professor Bill Blessing, Dr Youichirou Ootsuka and their team at Flinders Medical Centre are internationally recognised for their investigations as to how MDMA causes the body temperature to increase to such extreme levels.
“We have found that MDMA causes an abnormal reaction within the brain centres regulating the body temperature,” said Professor Blessing, Senior Consultant Neurologist. “This results in more heat being produced and less heat being lost.”
Normally, when body temperature increases, for example when you exercise, blood will flow closer to the skin so that heat can be released and the body temperature is reduced. When you are cold the reverse occurs. The brain sends messages to constrict the skin blood vessels (vasoconstriction), so that the flow of blood is directed away from the body surface, thus preventing loss of heat from the body.
Through experiments the team at Flinders Medical Centre has noted an abnormal response within the brain heat regulation mechanisms when MDMA is in the system. When a dose of MDMA is taken the skin blood vessels constrict, just as they normally do in the cold. Even though the body is becoming hot, it reacts as though the environment is cold. This is dangerous as the body also continues to create heat.
The combination of increased heat production and decreased heat loss causes the body temperature to rise to dangerous levels, causing muscle meltdown, kidney failure and fits, so that death may occur.
“Another stream of our research has been to identify a drug which can reverse the effects of MDMA,” said Professor Blessing. “We have found that the antipsychotic drug Clozapine, commonly known for its use in the treatment of schizophrenic patients, almost miraculously both reverses the extra heat production and the vasoconstriction caused by MDMA.”
Professor Blessing and his team continue to investigate the affects of MDMA with the aim of providing important information in the treatment of Ecstasy related overdoses to help save lives.
Nerve damage in Diabetes
First Published: Investigator - July 2006
Understanding diabetic associated nerve damage in the anorectal region is a key focus for Dr Penny Lynn, Senior Research Officer within the Department of Human Physiology at Flinders.
Diabetes forms when blood sugar levels are not controlled either through a decreased production of insulin within the body or the body’s inability to respond to the insulin that is produced. Keeping the blood sugar levels within a normal limit is the best way to reduce or prevent the complications associated with diabetes such as cardiovascular diseases, chronic renal failure, retinal and nervous system damage.
For many with diabetes, the nerve damage can lead to embarrassing complications such as faecal incontinence. This is due to the nerves in the anorectal area being no longer able to properly control the defecation process.
Up to 20% of diabetics experience some sort of defecation related complication such as faecal incontinence over the course of their disease. Understanding which nerves are damaged and in what order they are damaged will lead to a better awareness of the mechanisms causing this symptom and could lead to a better way of controlling or preventing this distressing problem.
“This symptom, while not the most serious, is indicative of an awful lot of nerve damage,” says Dr Lynn. “Many people don’t report this problem as they are too embarrassed, however it is quite common and with more awareness in the processes that lead to this issue we may be able to create a solution.”
Currently little is known about the groups of nerves within this area. A large portion of Dr Lynn’s project will be to identify which types of nerves sense activity in the anorectal area. Once these have been identified it will be easier to trace how diabetes causes this damage.
If the groups of nerves which are predisposed to this type of damage are successfully identified the Flinders team will be one step closer to creating a drug which can protect them.
New Insights Into Parkinson’s Disease
First Published: Investigator - October 2005
Updated: World First for Parkinson's Team
Dr Wei Ping Gai, Senior Research Fellow in the Department of Human Physiology, and his team of researchers here at Flinders are focusing on the cause of brain cell death associated with Parkinson’s.
Sufferers of Parkinson’s experience a range of symptoms that affect the sensory system, musculature problems such as body tremors and stiffness, and psychological difficulties such as depression, panic attacks and fatigue.
This disease largely affects the elderly community, however of the thousands of Australians diagnosed each year, approximately 10% are under the age of 40.
A recent discovery into the processes behind this disease has found that a typically normal protein, alpha-synuclein (AS), acts as a major component in the creation of Lewy bodies, abnormal clusters of proteins within nerve cells in the brain. This toxic substance has been linked to the brain cell death associated with the development of degenerative brain diseases such as Parkinson’s, Alzheimer’s and dementia.
Working with the human brain Dr Gai and his team of researchers are keenly interested in the reactions that take place within this AS protein, which are caused by outside antagonists such as gene mutation or environmental factors, leading to the toxicity that causes brain cell death.
For many years Dr Gai has undertaken a great deal of research into the abnormal brain matter associated with neurodegenerative diseases. During this time two new elements were discovered that seem to play major roles in Parkinson’s and similar diseases.
A molecule LRRK2 was found to have a detrimental effect on the brain and more importantly an ubiquitin, a protein that marks unhealthy proteins for destruction, was also found.
“We found that this ubiquitin somehow specifically labels the aggregated protein AS for destruction,” says Dr Gai.
Further research is hoped to be undertaken here at Flinders in the near future to investigate the interactions that take place between these three important factors; the alpha-synuclein protein, the LRRK2 molecule and the ubiquitin, within Parkinson’s disease.
This research could provide another stepping stone in ascertaining the mechanisms behind Parkinson’s and other similar debilitating diseases. It will also provide new information in the use of antibodies for better diagnosis and treatments.
First Published: Investigator - April 2005
Epilepsy is a common neurological disorder which affects 1-2% of Australians. It is a disruption of brain function resulting in recurrent seizures or convulsions.
The processes leading to spontaneous convulsions in epilepsy are not yet known but, thanks to a generous bequest, the Epilepsy Research Group at Flinders has been working toward finding out exactly which electrical brain rhythms are disturbed and what mechanisms lead to epileptic convulsions.
The research involves measuring the brain's electrical rhythms (EEG) to find out which rhythms might be disturbed in people prone to epileptic disorders and determine whether these rhythms can disrupt the brain to cause attacks.
Tests were able to show that just before convulsions take place, the type of brain rhythm which is normally active when humans think became very much more powerful. Furthermore, studies also showed that some epileptic brain rhythms have surprising similarities with normal brain rhythms seen during sleep.
In addition to developing a better diagnostic test for people with epilepsy, Professor Willoughby is hopeful that the findings may enable individuals, with some forms of epilepsy, to test themselves for their immediate risk of seizure allowing at least some individuals to adjust their day’s plans.
Award Winning Sleep Research
First Published: Investigator - October 2004
For the third time in four years, the Adelaide Institute for Sleep Health based at the Repat Hospital, has won the New Investigator Award at the Australasian Sleep Association Annual Scientific Meeting.
This most prestigious annual award, offered in the field of sleep research in Australia and New Zealand, was awarded to Dr Michael Hlavac who presented findings on the effects of low blood oxygen on arousability from sleep.
Dr Hlavac’s work has shown that low levels of oxygen (hypoxia) in sleep, as experienced by many patients with advanced respiratory disease, depresses the ability to arouse from sleep, rendering patients less able to defend against respiratory challenges such as sudden blockages to breathing.
“Hypoxia during sleep is characteristic of a number of respiratory diseases including emphysema, asthma and obstructive sleep apnoea. In such conditions, airway obstruction or low oxygen levels themselves trigger a brief arousal from sleep, which is thought to be an important protective reflex which serves to restore normal breathing”, said Dr Hlavac.
“Our results have confirmed that hypoxia prolongs the time to arouse from sleep in response to airway obstruction”
This latest award is testament to the very high quality of clinical sleep research conducted at the Adelaide Institute for Sleep Health.
First Published: Investigator - July 2004
Researchers at Flinders are hoping a drug used to treat mental illness could be a key to help control the symptoms of Raynauds Disease.
Professor Bill Blessing and Dr Stephen Hedger from the Departments of Medicine and Neurology are working on the theory that Olanzapine could help relieve the symptoms of Raynauds Disease - a painful and debilitating condition - and are working towards a clinical study to begin in 2005.
Dr Jack Walsh, from Vascular Surgery and Professor Peter Roberts-Thomson from Medicine, Immunology, Allergy and Arthritis will also contribute to the study.
Raynauds Disease is a condition in which some of the body’s blood vessels constrict, most commonly in the hands and toes, either apparently spontaneously or in response to cold or emotional stress. This severe constriction hinders blood flow and is distinguished by colour changes of the skin.
A typical episode of Raynauds Disease is the sudden onset of cold fingers, beginning in a single finger spreading to other digits and associated with white skin (white attack). This is followed by blue discolouration lasting 15 to 20 minutes then as the skin recovers it goes through a red phase. The whole process is very uncomfortable and painful.
There are two main forms of Raynauds Disease. The primary form is more common in women and displays a colour change in the hands. The secondary form is more severe.
Professor Blessing says the clinical study will mainly focus on patients with primary Raynauds Disease.
“Evidence based on careful physiological studies in animals suggests that Olanzapine, a drug already used to treat mental illness, interacts with brain neural pathways regulating the sympathetic nerves that control the blood vessels,” said Professor Blessing.
“Our research has shown that Olanzapine inhibits discharge of the sympathetic nerves, reversing the constriction of blood vessels and restoring the blood flow. We hope to begin a clinical study in 2005.”
Signalling A Good Night's Sleep!
First Published: Investigator - January 2004
A new physiological signal amplifier is helping researchers on their quest to solve the mystery of sleep breathing disorders
The Adelaide Institute for Sleep Health at the Repatriation General Hospital is using a brand new signal amplifier to investigate the mechanisms that lead to sleeping disorders.
Their aim is to work out what triggers the tendency for upper airway patency and breathing patterns to become unstable during sleep. Their main focus is to determine why sleep breathing disorders, like sleep apnoea are 2-3 times more prevalent in men compared to women.
An essential component of sleep breathing disorder research is high quality recordings of a range of physiological signals such as muscle activity from the upper airway, airflow, airway pressures, diaphragm muscle activity and blood oxygen levels.
Low blood oxygen is a feature of sleep breathing disorders and is another focus of the research.
Sleep Apnoea (The Greek word Apnoea literally means "without breath") is a condition where the upper airway collapses during sleep. The body is making breathing efforts but not getting any air. Depending on the severity of the apnoea this can happen hundreds of times a night.
Professor Blessing says the clinical study will mainly focus on patients with primary Raynauds Disease.
The upgrade of the physiological signal amplifier was made possible with the help of funding from several sources including the FMC Foundation.
The funding has assisted the Sleep Breathing Unit to replace the out-dated clinical amplifier with a brand new more sophisticated machine and has allowed researchers to continue their clinical investigations into sleep breathing disorders.
Parkinson's Enzyme May Help Alzheimer's
First Published: Investigator - January 2003
Parkinson's disease is a devastating brain disease that effects a significant proportion of our ageing population.
Although we don't know the cause of this disease there is a large body of evidence to suggest that oxidative stress is a major factor.
For some reason as yet unknown, the brain cells in a part of the brain involved in motor control start to die leading to movement problems.
Dr John Power and Dr. Weiping Gai and their team from the Department of Human Physiology at Flinders Medical Centre have been researching the affects of oxidative stress on brain enzymes and have discovered a new enzyme at work in the brains of sufferers of Parkinson's disease.
A paper detailing their findings was published in September 2002 in the highly accredited American Journal of Pathology.
"We have recently shown that brain cells under oxidative stress start to turn on a new anti-oxidant enzyme to try and protect themselves. In addition, other supporting cells also start making more of this enzyme.
In an exciting development since the paper was presented, Dr Power and his team have found evidence to support that the enzyme has a role in Alzheimer's - although it is appears to be different from Parkinson’s disease. For example, in Alzheimer’s disease regions that did not seem to make this enzyme appeared to be more susceptible to oxidative damage and have more pathology.
"We are the only team in the world that has shown that the enzyme is present in the brain as well as being involved in Parkinson's and Alzheimer's.
"A grant from the Foundation has helped keep this research alive. The next step for the team is to acquire funding for a diagnostic test so that further exciting research can occur." Said Dr Power.