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
COX-2 INHIBITORS AS A CAUSE OF HEART AND RENAL FAILURE
Funder
National Health and Medical Research Council
Funding Amount
$271,610.00
Summary
Non-steroid anti-inflammatory drugs (NSAIDs) have pain-killing and anti-inflammatory properties. For many years Australia had a higher use of these drugs than other countries. The drugs are quite toxic, and in susceptible individuals may cause ulceration and bleeding from the stomach and duodenum, kidney damage and fluid congestion leading to heart failure. Each of these conditions carries a high morbidity, particularly in the elderly. Because of concerns about toxicity, the use of NSAIDs in Aus ....Non-steroid anti-inflammatory drugs (NSAIDs) have pain-killing and anti-inflammatory properties. For many years Australia had a higher use of these drugs than other countries. The drugs are quite toxic, and in susceptible individuals may cause ulceration and bleeding from the stomach and duodenum, kidney damage and fluid congestion leading to heart failure. Each of these conditions carries a high morbidity, particularly in the elderly. Because of concerns about toxicity, the use of NSAIDs in Australia fell during the 1990s by around 40%. Newer allegedly safer forms of NSAIDs called COX-2 inhibitors have been introduced into the Australian market. The first 2 drugs to be marketed are called Celebrex and Vioxx. These drugs appear to be safer for the stomach and duodenum, but the true effects on the kidney and heart are as yet unclear. COX-2 inhibitors have been very widely used with over 1.7 million prescriptions issued since their listing on the Pharmaceutical Benefits Scheme in August 2000. Most of this use appears to be in addition to prescribing of the older NSAIDs rather than as a replacement for them. The purpose of this study is to compare the safety of the new COX-2 inhibitors with that of the older NSAIDs. We are interested in how often they cause renal failure and heart failure. The investigators will use well-established research methods to estimate the risk of heart failure and kidney failure with these drugs in the Australian community. Data from the study will form the basis of clinical practice guidelines for the safe use of these drugs in Australia.Read moreRead less
The Role Of The Pro-survival Bcl-2 Family Member A1 In The Development And Sustained Growth Of Lymphomas.
Funder
National Health and Medical Research Council
Funding Amount
$628,459.00
Summary
The death of cells, which is regulated by a complex interaction between cell survival and killer proteins, is an important mechanism to prevent cancer. In this proposal we aim to understand the function of one of the cell survival proteins in cancer development and maintenance. This will help to develop novel therapeutic drugs specifically targeting this cell survival protein, thereby eliminating specifically the cancer cells and minimizing collateral damage of healthy tissues.
The Role Of Attention In Modifying Neural Plasticity In The Adult Human Cortex
Funder
National Health and Medical Research Council
Funding Amount
$391,242.00
Summary
The human brain is constantly changing in response to experience. These changes, known as plasticity, are necessary to respond to new environments, to learn new skills and to recover from brain injury. This project will determine how selective attention, a process that filters sensory information in the brain, alters brain plasticity. The outcomes will inform the design of rehabilitation treatments for individuals with a brain injury.
COX-2 Inhibitors And The Development Of Unstable Angina And Myocardial Infarction
Funder
National Health and Medical Research Council
Funding Amount
$171,450.00
Summary
Anti-inflammatory drugs (sometimes called NSAIDs) are widely used in the treatment of arthritis and also as general purpose pain killers. Up to 10 million prescriptions are written each year for these drugs in Australia. Some of the older versions of these drugs like ibuprofen (eg Brufen) and naproxen (trade name Naproxen) cause side effects which can be serious. Damage to the stomach is a particular problem and this can lead to serious bleeding or perforation of ulcers. Less well recognized are ....Anti-inflammatory drugs (sometimes called NSAIDs) are widely used in the treatment of arthritis and also as general purpose pain killers. Up to 10 million prescriptions are written each year for these drugs in Australia. Some of the older versions of these drugs like ibuprofen (eg Brufen) and naproxen (trade name Naproxen) cause side effects which can be serious. Damage to the stomach is a particular problem and this can lead to serious bleeding or perforation of ulcers. Less well recognized are the adverse effects of these drugs on the heart and the kidneys. The older fashioned members of this class of drug are rapidly being replaced by newer agents known as COX-2 inhibitors. Popular examples in Australia are celecoxib (trade name Celebrex) and rofecoxib (trade name Vioxx). These drugs are heavily promoted as being safer than the older NSAIDs. In the case of the stomach, this claim seems to be correct. However, the effects of the new COX-2 inhibitors on the circulation have not been fully assessed. Recently, claims have been made that these drugs may increase the risk of heart attacks. If this were true, it would be an effect that was unique to COX-2 inhibitors as it has not been reported with the older NSAIDs. We plan to carry out a 3 year study in Newcastle hospitals in which we compare the use of COX-2 inhibitors in a group of patients admitted to hospital with a heart attack or unstable angina with that of a control group of patients who were admitted to hospital around the same time, but not for heart problems. We are interested in whether COX-2 inhibitors are associated with an increased risk of heart attacks and whether use of small doses of aspirin protects against this effect. Depending on the results we may be able to improve the safety of these drugs in patients at risk of heart attacks.Read moreRead less
Chronic pain is a common and debilitating condition. One in five people in the Australian community have been found to experience chronic pain at any one time. Although there is no evidence of a consistent increase in rates of chronic pain, the rate of permanent disability has increased dramatically in recent decades. This has contributed to the growing cost of chronic pain. For example, back pain is the most common reason for filing workers' compensation claims and leads to loss of 101.8 millio ....Chronic pain is a common and debilitating condition. One in five people in the Australian community have been found to experience chronic pain at any one time. Although there is no evidence of a consistent increase in rates of chronic pain, the rate of permanent disability has increased dramatically in recent decades. This has contributed to the growing cost of chronic pain. For example, back pain is the most common reason for filing workers' compensation claims and leads to loss of 101.8 million workdays annually. The annual costs of medical care for back pain alone have been estimated at $AUD50 billion in the US and $10 billion in Australia. Not only is chronic pain a considerable economic burden, it is also a considerable personal burden to patients. Pain is one of the strongest predictors of poor quality of life and has consistently been found to be associated with high rates of depression. Although there is a large body of research that investigates what factors are associated with chronic pain, there is surprisingly little research that investigates the mechanisms that cause chronicity. Theories of chronic pain suggest that psychological characteristics increase the propensity for people to develop chronic pain. Specifically, theories argue that those people who tend to be fearful of pain will over-attend to painful sensations and avoid pain-provoking activities and as a result are at risk of developing chronic pain. This study will test those theories. If it is found that over-attending to pain does predispose patients to develop chronic pain, this will have important implications for preventing the development of chronic pain. These findings could help to devise early interventions to prevent chronicity and thereby reduce the economic burden to health services and the emotional burden to patients in terms of reduced quality of life.Read moreRead less
Development Of Reversible Inhibitors Of Factor XIa
Funder
National Health and Medical Research Council
Funding Amount
$444,318.00
Summary
Blood usually clots in response to injury, but unwanted clots can cause thrombosis, as well as leading to stroke and heart disease. Existing drugs to treat thrombosis suffer from drawbacks such as invasive monitoring, interaction with diet and other medicines, and bleeding complications. New drugs are clearly needed. Our expert group of researchers will discover new anti-thrombotic compounds based upon our previous identification of natural products with anticoagulant properties.