Acute pancreatitis is an acute abdominal inflammatory process (the pancreas attempts to digest itself) with significant mortality in those patients having the severe form of the disease. The commonest causes of the disease are gallstones and excessive alcohol consumption. Approximately 80% of patients with acute pancreatitis recover, but 20% experience the severe form of the disease. In severe pancreatitis, 30% of patients die. Severe pancreatitis is associated with necrosis (cell death) of the ....Acute pancreatitis is an acute abdominal inflammatory process (the pancreas attempts to digest itself) with significant mortality in those patients having the severe form of the disease. The commonest causes of the disease are gallstones and excessive alcohol consumption. Approximately 80% of patients with acute pancreatitis recover, but 20% experience the severe form of the disease. In severe pancreatitis, 30% of patients die. Severe pancreatitis is associated with necrosis (cell death) of the pancreas which, results from reduced blood flow in the organ. This reduced blood flow may be secondary to increased pressure in the pancreatic duct following occlusion of the duct. Preliminary studies suggest that the reason why the pancreas may be susceptible to necrosis is the anatomical arrangement of its blood supply, being made up of many end arterioles (very small arteries) that do not connect with other arteries. The consequence of this arrangement is that if a particular end arteriole becomes blocked, the area of the tissue cannot obtain a blood supply from neighbouring arterioles (as in other organs). Blood supply is partly controlled by nerves. The nerve transmitter nitric oxide is one of the major chemicals involved in this regulation. Nitric oxide also regulates the pressure in the pancreatic duct by acting on the sphincter of Oddi, situated at the opening of the pancreatic duct. Consequently, the action of nitric oxide during pancreatitis may be crucial to the development of the severe disease. This proposal seeks to define the blood supply of the pancreas, its regulation, the effect that increased pancreatic duct pressure has on it and the role that nitric oxide plays in this. If the hypotheses regarding the role of nitric oxide on pancreatic blood flow is proven, then drugs which influence nitric oxide levels can be used to limit the production of pancreatic necrosis. In turn, such an effect will reduce the mortality and morbidity of acute pancreatitis.Read moreRead less
The sphincter of Oddi is a valve-like structure, which regulates the flow of bile and pancreatic juice into the gut. The sphincter of Oddi is under complex control involving nerves and hormones. We know that abnormal sphincter of Oddi function (sphincter of Oddi dysfunction) is associated with a number of human diseases including acute pancreatitis. We are able to recognise abnormal sphincter activity, but we do not know what causes it. One possible reason may be that the nerves going to the sph ....The sphincter of Oddi is a valve-like structure, which regulates the flow of bile and pancreatic juice into the gut. The sphincter of Oddi is under complex control involving nerves and hormones. We know that abnormal sphincter of Oddi function (sphincter of Oddi dysfunction) is associated with a number of human diseases including acute pancreatitis. We are able to recognise abnormal sphincter activity, but we do not know what causes it. One possible reason may be that the nerves going to the sphincter along the bile duct (which carries bile from the liver and gallbladder) may be damaged due to the passage of gallstones or during surgery on the bile ducts or gallbladder. We know that the main bile duct is able to sense pressure changes within and communicate this information (via nerves) to the sphincter which inturn alters its activity to relieve the pressure. Where these nerves are located and the chemical messages they use, are unknown. The aim of this project is to gain some of this information. This knowledge may allow us to design different surgical procedures or develop drugs to prevent or manage the abnormal sphincter of Oddi.Read moreRead less
Cooperative Motor Control Of The Pyloric Junction By Myogenic And Neuronal Mechanisms
Funder
National Health and Medical Research Council
Funding Amount
$271,527.00
Summary
The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little infor ....The coordinated muscle movement in the junction between the stomach and small intestine is an essential mechanism for controlling the speed of gastric content moving into the intestine for further digestion. The muscle movement determines the gastric emptying at an optimal rate and prevents intestinal contents reflux to the stomach. Failure of this coordination is likely to be involved in a variety of clinical conditions including accelerated or delayed gastric emptying. Up to date, little information is available about the interaction between nerve, muscle and pacemaker cells during this coordinated movement. In this project, we will investigate how the nerve, muscle and pacemaker cells work together to control this coordinated movement. We will study this mechanism at both cellular and organ levels and try to establish the patterns of muscle movement and their coordination between the stomach and the small intestine. The interaction between the nerve and pacemaker cells will be characterised in these studies. Our work will provide structural evidence for this activity. It includes identification of the nerve pathways connecting between the small intestine and stomach and determination of whether the pacemaker cell network is an uniform continuous or a discontinuous or a transitional structure across the junction. These studies will reveal the correlation between pacemaker cell mediated activity and the density of these cells in each junctional region. We will also determine whether the difference in propagation activity across the junction is due to differences in the number of cells for signal conduction or electrical connections between the cells. This study will advance our knowledge for understanding how the nerve, muscle and pacemaker cells work in concert in this junction, which is an important step for further clinical investigation of related disease.Read moreRead less
Maternal Gut Microbiome During Pregnancy Influences Offspring Atopy And Asthma.
Funder
National Health and Medical Research Council
Funding Amount
$46,622.00
Summary
Allergic diseases such as food allergy and asthma have increased significantly as our exposure to bacteria has reduced. Many studies have explored exposure to bacteria in early life but few have examined the maternal bacteria we are exposed to while we develop in the womb. New studies indicate that we are exposed to many different components of our mothers gut bacteria and this might change our developing immune system and determine whether or not we get diseases like food allergy and asthma.
Platelet And Endothelial Function In Atrial Fibrillation
Funder
National Health and Medical Research Council
Funding Amount
$105,825.00
Summary
Atrial fibrillation is the most common heart rhythm disturbance in the adult population and leads to substantial increased death and disability from stroke. In this research scheme, we will study the contribution of platelet (clot forming cells) and endothelial (lining of blood vessels) dysfunction in atrial fibrillation. The successful outcome of this project will lead to a better understanding of the underlying mechanisms of clot formation and may lead to a better target for future drugs.