Novel Cell Therapy For Hirschsprung Disease: From Patient IPS Cells To Large Animal Trials
Funder
National Health and Medical Research Council
Funding Amount
$1,011,764.00
Summary
In Hirschsprung disease the lower bowel has no nerve cells. It does not function so it is surgically removed but quality of life is poor. A new idea is to replace the missing cells with new ones. Human infants are very large so we will use new stem cell technologies to create large numbers of cells. We will use polymer chemistry to devise a method of getting the cells into such a large organ as the bowel, and trial these on a model, the piglet, which closely resembles in size the human baby.
ProbioticTreatment Of Diarrhoeal Disease And Malnutrition In Top End Aboriginal Children
Funder
National Health and Medical Research Council
Funding Amount
$332,036.00
Summary
Aboriginal children in the Top End of Australia have high rates of hospital admission for diarrhoea and malnutrition. We have discovered that underlying small intestinal damage in these children is an important contributor to the high complication rates and longer lengths of stay in hospital compared to non-Aboriginal children. This research proposes to continue our work on small intestinal damage by using two non-invasive tests of gut function, namely a sugar absorption test and novel breath te ....Aboriginal children in the Top End of Australia have high rates of hospital admission for diarrhoea and malnutrition. We have discovered that underlying small intestinal damage in these children is an important contributor to the high complication rates and longer lengths of stay in hospital compared to non-Aboriginal children. This research proposes to continue our work on small intestinal damage by using two non-invasive tests of gut function, namely a sugar absorption test and novel breath test. The sugar permeability test involves the children drinking a solution of the two sugars lactulose and rhamnose, and measuring their absorption into the blood 90 minutes later using a sophisticated measuring instrument called HPLC, which can measure minuscule amounts of sugars and is set up at Royal Darwin Hospital. The breath test involves children drinking another sugar solution with a special non-radioactive marker called a stable isotope of carbon, and measuring changes in the amount of this marker in carbon dioxide from the breath at timed periods after drinking the sugar solution. The breath is analysed in Adelaide using another sophisticated instrument. These tests are being used to measure abnormal sugar absorption due to intestinal damage, which is particularly common in Aboriginal children during the weaning period of 4-18 months. Our hypothesis is that treatment with 'healthy germs' (probiotics) like those in certain yoghourts will colonise the gut, stimulate immunity and reduce the presence of 'nasty germs' (pathogenic bacteria) in the intestines of Aboriginal children which contribute to the need for their hospitalisation with diarrhoea and malnutrition. If this hypothesis is correct, then this research will provide the best kind of evidence for reducing the need for hospital treatment by treating all cases of diarrhoea with these probiotics and possibly even decreasing the gut damage of children in the weaning period by including probiotics in their dietsRead moreRead less
Previous research has shown that SIDS victims have a number of subtle abnormalities that set them apart from the normal population. These include the occurrence of upper airway obstruction in sleep, a reduced ability to awaken from sleep and abnormalities of the automatic control of heart rate and blood pressure in sleep. These body functions are controlled by a component of the brain called the autonomic nervous system which controls the heart and other internal functions by means of nerves cal ....Previous research has shown that SIDS victims have a number of subtle abnormalities that set them apart from the normal population. These include the occurrence of upper airway obstruction in sleep, a reduced ability to awaken from sleep and abnormalities of the automatic control of heart rate and blood pressure in sleep. These body functions are controlled by a component of the brain called the autonomic nervous system which controls the heart and other internal functions by means of nerves called the parasymmpathetic and sympathetic systems. The purpose of this project is to undertake studies of the autonomic system in normal infants and in those infants who are considered to be at risk for SIDS. As SIDS occurs almost exclusively in sleep it is important to study the infant?s heart rate and blood pressure responses to various challenges whilst asleep. All infants (both controls and subjects) enrolled in the protocol will therefore undergo overnight sleep studies during which their automatic responses to a variety of stimuli will be measured. Once we have established the normal response to these stimuli we can then compare them to the results of the at risk group. If, as we anticipate, there is a difference between our at risk group and the normal controls in automatic function then we will measure some of the stress hormones in the body which reflect the function of the autonomic nervous system. If there is a difference in the levels of these hormones between the normal and the at risk groups which correlates with the expected subtle abnormalities in function we may be able to devise an accessible and quantifiable measure for those infants at risk of SIDSRead moreRead less