Mechanisms Of Repair And Adaptation In The Gastric Mucosa: Roles Of COX-2 And Growth Factors
Funder
National Health and Medical Research Council
Funding Amount
$391,650.00
Summary
The stomach lining is continually threatened by its own acid and by hazards such as bacteria and ingested drugs. The drugs called COX inhibitors, which include aspirin, are widely used for treating arthritis and other inflammatory diseases and for preventing heart attacks and strokes. Despite their value in these conditions, COX inhibitors are responsible for about 5-10,000 hospital admissions annually in Australia due to complications from the side effect of stomach ulcers. A recent advance has ....The stomach lining is continually threatened by its own acid and by hazards such as bacteria and ingested drugs. The drugs called COX inhibitors, which include aspirin, are widely used for treating arthritis and other inflammatory diseases and for preventing heart attacks and strokes. Despite their value in these conditions, COX inhibitors are responsible for about 5-10,000 hospital admissions annually in Australia due to complications from the side effect of stomach ulcers. A recent advance has been the development of a sub-class called COX-2 inhibitors. In a very short time, one of these has become among the most prescribed drugs in Australia. The advantage of the COX-2 inhibitors is that they produce many less stomach ulcers. However, they have only been tested in patients who have not had a recent history of ulcer. Our preliminary experiments, together with some related information from two overseas groups, suggests that COX-2 is useful in the stomach, and is markedly increased around a healing ulcer. Our data suggest that blocking it delays the healing of experimental ulcers. This project aims to understand the roles of COX-2 in the stomach, and to clarify the effects of inhibiting it when the stomach is damaged or threatened. The project will also look for links between COX-2's functions and another protective process we have discovered called 'adaptation'. When anti-inflammatory drugs are given regularly to rats or humans under certain conditions, the stomach develops resistance after a few days so that the damage caused by each subsequent dose is markedly reduced. We have uncovered a number of mechanisms responsible for this during a current NH and MRC grant, and plan to explore some of the leads this work has given. The SIGNIFICANCE of the project is its potential to lead to safer use of anti-inflammatory drugs or eventually to new agents, and its potential to give new knowledge about how the lining of organs such as the stomach protects itself.Read moreRead less
Antidepressants In Irritable Bowel: A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$227,546.00
Summary
Irritable bowel syndrome is a common costly disorder in Australia; one in six Australians suffer with the condition. IBS can cause very substantial disability; some become housebound because of the need to have toilet facilities nearby. The currently available treatments for irritable bowel syndrome only provide at best partial relief or are completely ineffective. The literature suggests that individuals who suffer from an irritable bowel may benefit from the use of an antidepressant medication ....Irritable bowel syndrome is a common costly disorder in Australia; one in six Australians suffer with the condition. IBS can cause very substantial disability; some become housebound because of the need to have toilet facilities nearby. The currently available treatments for irritable bowel syndrome only provide at best partial relief or are completely ineffective. The literature suggests that individuals who suffer from an irritable bowel may benefit from the use of an antidepressant medication. Antidepressant medications have been shown to affect the function of the gastrointestinal system, in addition to relieving some of the psychological symptoms, such as depression and anxiety that are common in individuals with irritable bowel syndrome. To date, there have been no proper controlled trials of antidepressant medications in IBS, and there have been no studies at all into the new class of antidepressant medications, the selective serotonin reuptake inhibitors, in treating IBS. In this study we aim to investigate whether antidepressant medications are effective in treating irritable bowel syndrome by directly comparing a tricyclic (older class of antidepressant) with a selective serotonin reuptake inhibitor (new class of antidepressant) and with a placebo. All study participants will be closely monitored during the study. Patients will have their gastrointestinal symptoms, psychological symptoms, disability, quality of life and tolerance to the medication assessed. This will be the first comprehensive study of antidepressant medications assessed and the irritable bowel syndrome to be undertaken. The study will be conducted at the Nepean Hospital and the Royal North Shore Hospital; both of these centres have a well established treatment and research programs into the irritable bowel syndrome.Read moreRead less