Regulation Of Intestinal Stem Cells And Intestinal Growth
Funder
National Health and Medical Research Council
Funding Amount
$419,018.00
Summary
How the small intestine grows is important for preterm babies and those with short bowel syndrome. This study investigates the mechanisms of growth in the normal situation and in animal model of short bowel syndrome. It investigates particular growth pathways that regulate growth and particularly that of intestinal stem cells.
Intestinal Adaptation Following Massive Small Intestinal Resection: Mechanisms And Management
Funder
National Health and Medical Research Council
Funding Amount
$256,980.00
Summary
Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation follo ....Short bowel syndrome (SBS) remains a major clinical problem in paediatric and adult clinical practice. The Department of Gastroenterology and Clinical Nutrition at the Royal Children's Hospital has gained recognition as a national centre of excellence for the management of infants and children with SBS and intestinal failure. Due to the significant personal and heath-care burden related to SBS there has been an urgent need to improve understanding about the process of intestinal adaptation following massive small bowel resection (MSBR) in order to develop new treatments aimed at improving clinical outcome for patients with SBS. Over the past 5 years we have developed a preclinical model for the study of intestinal adaptation in infants using the juvenile pig. Our recent studies in this model have revealed that elemental formula is inferior to whole protein formula suggesting that the current clinical recommendations need urgent re-evaluation. Using the preclinical model in this proposal, we aim to define the mechanisms underlying the adaptive response and evaluate novel therapies aimed at enhancing adaptation following MSBR. Supplementation of enteral feeds with bovine colostrum isolate resulted in normal growth in the preclinical model despite MSBR. In this proposal we plan to advance this observation for the first time to human clinical trials in infants with SBS. Even small gains in enteral tolerance during the early post-operative period may have a significant impact on morbidity and mortality of children with SBS due to parenteral-nutrition related liver disease and gut-related sepsis. This research proposal provides a unique link between studies aimed at providing the scientific basis for understanding the mechanisms of intestinal adaptation using an established preclinical model and translating the results of these studies onto human trials, taking advantage of the clinical expertise available in the management of children with SBS.Read moreRead less
The Effects Of Acute And Chronic Hyperglycaemia On Short And Long-term Outcomes In The Critically Ill
Funder
National Health and Medical Research Council
Funding Amount
$263,513.00
Summary
Dr Adam Deane is an intensive care clinician/scientist who is an emerging leader in the field of critical care. His research activities are almost exclusively clinically based and relate primarily to the effects of critical illness on gastrointestinal function, nutrition and blood sugar control. This fellowship will allow Dr Deane to continue and grow his internationally recognised work in these areas.
Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older peop ....Human ageing is characterised by reduced appetite and food intake, so that average body weight decreases after 70-75 years. This physiological anorexia predisposes to pathological weight loss and malnutrition, worsening of other illnesses, and increased mortality. This project aims to identify causes of this anorexia of ageing, with a view to developing prevention and treatment strategies. We hypothesise that (1) Satiety signals are overactive in the elderly. We will determine whether older people are more sensitive to gastric distension, which reduces appetite and food intake, by measuring perceptions (fullness, hunger, etc), gastric compliance and food intake during intragastric balloon inflation. This will also be done during nutrient infusion into the small intestine, to assess the interaction between gastric and intestinal satiety factors. The contribution of age-related slowing of gastric emptying to the anorexia of ageing will be assessed and the possibility that reduced energy intake worsens the anorexia of ageing will be examined in a nutrient supplementation study. We will have shown that the release of the satiety hormone cholecystokinin (CCK) is greater in older than young adults and that CCK administration causes a greater suppression of food intake in older people, suggesting that increased CCK activity may be a cause of the anorexia of ageing. We will pursue these findings by attempting to increase appetite and food intake in the lderly by administration of a CCK antagonist (blocker). We will also measure the satiating effects of two other probable satiety hormones, amylin and glucagon like peptide 1 in older and young people. (2) The feeding drive is reduced in the elderly Opioids stimulate feeding. In animals this effect is reduced by ageing. To determine whetther this is also so in humans, the suppressive effect of the opioid antagonist naloxone on feeding will be assessed in young and older subjects.Read moreRead less