A Novel Mechanism For Intestinal Propulsion: Transit Without Neurons Or Pacemakers
Funder
National Health and Medical Research Council
Funding Amount
$256,973.00
Summary
A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the dev ....A significant complication of premature births is that the mechanisms that regulate normal intestinal movements have not yet fully developed. We have recently identified a novel pattern of contraction that is seen predominantly in the colon of mice that have not yet developed either the normal nerve circuits that control gut movement and also lack the pacemaker cells that are intrinsic to the muscle coat. This motor pattern appears to be responsible for the movement of gut content during the development and maturation of the nerve circuits that regulate this process in more adult animals. However, the mechanisms responsible for this process have not been identified. This project is directed at identifying these mechanismsRead moreRead less
Role Of Pacemaker Cells In The Generation Of Slow Wave Activity In The Prostate Gland
Funder
National Health and Medical Research Council
Funding Amount
$231,500.00
Summary
The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are of ....The prostate gland commonly enlarges in ageing males resulting in a condition known as benign prostatic hyperplasia which is poorly understood. Because of the strategic position of the prostate, its enlargement physically compresses the segment of the urinary system passing through it causing inconvenient and distressing symptoms, such as difficulty and hesitancy in urination, which often require surgical or medical intervention. Indeed patients diagnosed with benign prostatic hyperplasia are often treated with pharmacological agents that reduce the size of the prostate or relax the prostate and bladder, thus relieving some of the symptoms. However, the precise cellualr mechanisms by which many of these drugs mediate their effects have not been confirmed. Moreover, although previous studies of the prostate gland have clearly established many of the basic properties of the tissue, there is currently a lack of information regarding the prostate gland at a cellular level. We have recently identified a specialised group of 'interstitial cells' in the prostate gland, which resemble the well-described 'interstitial cells of Cajal' in the gut. In the gut, these cells perform a wide variety of functions including the initiation of contractile activity. Interstitial cells are also thought to play a role in diseases of the bowel. This project aims to investigate the role of the interstitial cells in the functioning of the prostate gland. In addition, the effects of age and hormones on the interstitial cells will be considered, which may lead to a better understanding of conditions such as benign prostatic hyperplasia. Finally, identifying nerve-released substances that may affect the activity of these cells may also help identify alternative targets for treatment of benign prostatic hyperplasia.Read moreRead less
Neuro-muscular Apparatus In Human Colon And In Children With Chronic Constipation
Funder
National Health and Medical Research Council
Funding Amount
$195,660.00
Summary
NIDKIDS is a support group for children with chronic constipation. There are 200 patients at the Royal Childrens Hospital in Melbourne who are in this group because their constipation has not responded to any treatments. Movement of food along the intestine requires muscle in the wall of the intestine to contract in a coordinated pattern. Coordination of the muscle contractions is provided by the nervous system. The nervous system controlling the gut has cell bodies located within the gut wall, ....NIDKIDS is a support group for children with chronic constipation. There are 200 patients at the Royal Childrens Hospital in Melbourne who are in this group because their constipation has not responded to any treatments. Movement of food along the intestine requires muscle in the wall of the intestine to contract in a coordinated pattern. Coordination of the muscle contractions is provided by the nervous system. The nervous system controlling the gut has cell bodies located within the gut wall, that send processes to the muscle and lining of the gut. There are sensory neurons, motor neurons and neurons that connect between the other neurons (interneurons). Nerves communicate between each other and cause muscles to contract by releasing chemicals (transmitters). In the last decade, we have discovered that communication between the nerve and muscle cells occurs through a third cell type- interstitial cells of Cajal. These cells also have a role as pacemaker cells for the muscle cells. In a small study, we have found that the muscle can contract in response to transmitters but that activation of the nerves does not result in muscle contraction in NIDKIDs. This result shows that transmission from neurons to muscle is not occuring in large bowel from NIDKIDs. In this study, we will examine a larger group of patients to determine if a functional defect in the muscle, a defect in the nerve chemical transmitters or a lack of the intermediate cells (the interstitial cells of Cajal) is causing the problem in the NIDKIDs. Further treatment of each patient will be easier if the defect causing his-her problem is known. We would then be able to target their problem with drugs that would work specifically at the point of breakdown in their individual gut.Read moreRead less
Motor Patterns Of Colonic Transit And Pathophysiology Of Severe Constipation.
Funder
National Health and Medical Research Council
Funding Amount
$196,018.00
Summary
This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions and flow of content along the colon in these patients. The aim will be to try and identify abnormal patterns responsible for the constipation so that future studies can target appropriate drugs at the responsible defect. A better unde ....This project aims to clarify the contractile patterns of the human colon which underlie the very common and distressing condition of constipation. We will be relating symptoms of constipation from a large number of sufferers with actual measurements of contractions and flow of content along the colon in these patients. The aim will be to try and identify abnormal patterns responsible for the constipation so that future studies can target appropriate drugs at the responsible defect. A better understanding of clusters or symptoms and how they might predict such underlying abnormalities is crucial for the safer and more cost effective diagnosis and treatment of affected patients. Pharmacological studies in the human as well as on tissue obtained from affected patients at surgery will be conducted to better understand the presumptive abnormalities affecting the nerves within the colon in constipation.Read moreRead less
Mechanisms Of Action Of Neurochemicals And Modulators In Human Intestine: Changes In Disease
Funder
National Health and Medical Research Council
Funding Amount
$442,500.00
Summary
Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in r ....Inflammatory bowel disease (IBD) and idiopathic chronic constipation (ICC) are two serious gastrointestinal disorders, for which no effective medical treatment is known. We will investigate the hypothesis that abnormalities in the nerve chemicals found in the gut contribute to the aetiology of these diseases. Our studies will examine the sites of action (receptors) for these chemicals (neurotensin and acetylcholine) in the small and large intestine. The mechanisms governing motility changes in response to these chemicals have been well studied in animal intestine, but there is little detailed information from the human intestine. This study will provide insight into the mechanisms operating in the normal bowel, providing a base for comparing bowel obtained from patients with IBD or ICC. We will also study bowel removed at surgery for acute diverticular disease (DD), representing another type of inflammation. Studies on isolated segments of colon from ICC patients will determine whether the contractility of the muscle is abnormal in general or only with respect to the chemicals under investigation. Other studies will investigate the inflammatory processes occurring in the bowel and whether this differs in IBD. Our work will facilitate understanding of the function of the bowel in health and in gastrointestinal disorders and may lead to new medical treatments for IBD and ICC.Read moreRead less