Inhaled Mannitol For The Treatment Of Mucociliary Dysfunction- Its Effect And Mechanisms On The Clearance Of Mucus
Funder
National Health and Medical Research Council
Funding Amount
$324,100.00
Summary
Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patient ....Excessive secretion of mucus is a problem in asthma and bronchiectasis. Mucus is secreted from submucosal glands and goblet cells as a result of inflammation present in the airways. Excessive mucus is not easily transported by the cilia (hair like structures) in the airways and accumulation leads to productive cough and to recurrent infections. Cough is a secondary mechanism to clear mucus when the mucociliary system fails. Cough generates high airflow rates that can move mucus. However, patients with moderately to severely obstructed airways cannot generate high airflow rates. In addition, cough becomes very inefficient in moving mucus if it is sticky and viscous. As the cilia cannot transport large quantities of mucus the best approach is to alter the properties of mucus that would facilitate cough clearance. Increased hydration of mucus could change its surface and rheological properties. Increased hydration can be achieved by the osmotic movement of water into the airway lumen in response to inhaling an aerosol of salt or sugar. We have evidence using radioactive aerosols, that mannitol, a sugar, increases clearance of mucus acutely in patients with excessive secretions. We also have new evidence that mannitol taken daily over two weeks increases the health status in patients with bronchiectasis. Further we now have preliminary data demonstrating that mannitol changes the surface properties of mucus. We aim to study the properties of mucus in relation to its clearance in vivo in humans. This has not been done before. If we can demonstrate that changes in clearance in response to mannitol relate to the changes in mucus then we will be able to easily evaluate current treatments and doses for patients with excessive secretions and to identify new treatments. Mannitol is a potential treatment for diseases with excessive secretions and understanding of how it works will hopefully lead to better outcomes for patients.Read moreRead less
Spatio-temporal Analysis Of Rat Intestinal Motility In Physiological And Disease Models
Funder
National Health and Medical Research Council
Funding Amount
$358,750.00
Summary
This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping ....This project addresses the question of how the movements of the gut are controlled in health and disease. The progress of food along the gut is due to movements of the involuntary muscle of the wall of the intestine. Three fundamental mechanisms are involved. One is the spontaneous ability of the intestinal muscle to contract rhythmically and is driven by a delicate net of pacemaker cells. Fast propulsion of food contents depends on nerve circuits in the gut wall that generate a powerful pumping behaviour to prevent over-filling or to eject toxic or irritating substances (eg: some laxatives activate this mechanisms). This is often called peristalsis. A third mechanism consists of activity of nerve cells in the gut, that slowly propagates along the intestine and causes the muscle to contract, sweeping along any remnants. The movements generated by these three mechanisms occur in segments of intestine isolated from rats. The major difficulty up until now has been to relate the actual movements in living animals to these fundamental mechanisms. It is now possible to bridge this gap because we have developed methods to record, display and measure graphically the actual movements. Movements are transformed into spatio-temporal maps which show all of the contractions over a period of time. Coordinated activity is visible in these maps as recognisable patterns or visual objects. Measurements can be readily made with conventional statistics. The literature in gastroenterology is full of descriptions of motility based on indirect methods of recordings. In this project we will be able to correlate the previous indirect methods with the new graphic methods and thus establish a clearer, simpler and more accurate classification of normal patterns of intestinal motility. We will then use this to establish what goes wrong in a number of experimental diseases known to affect adversely the movements of the intestine.Read moreRead less