Alcoholic Chronic Pancreatitis: Induction, Progression And Reversal
Funder
National Health and Medical Research Council
Funding Amount
$632,211.00
Summary
Pancreatitis (inflammation of the pancreas) is a serious complication of alcohol abuse. Patients suffer from severe and often intractable abdominal pain, maldigestion and diabetes, We have recently shown that gut toxins (endotoxins) may act as a trigger factor for pancreatitis in alcoholics. The proposed project aims to characterise the effects of gut toxins on the pancreas during alcohol abuse so as to identify pathways that may be therapeutically targeted to prevent or retard the disease.
Alcoholic Pancreatitis : Role Of Alcohol, Endotoxin And Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$501,653.00
Summary
The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and i ....The pancreas is the major digestive organ of the body. It contains many proteins (enzymes) which break down food. One of the more serious complications of alcohol (ethanol) abuse is pancreatitis, a condition that has both acute and chronic manifestations. Patients with acute pancreatitis suffer from acute abdominal pain; in severe cases the condition can be fatal. Repeated attacks of acute pancreatitis can lead to chronic pancreatitis, a condition in which, normal pancreatic tissue is lost and is replaced by scarring. This disease causes chronic pain, inability to digest food with consequent malnutrition and destruction of the insulin producing cells of the gland leading to diabetes. The mechanisms by which alcohol causes pancreatitis are not yet known. Although it is well established that the risk of developing pancreatitis increases with increasing intake of alcohol, suggesting that alcohol exerts toxic effects on the gland, it is also clear that not all alcoholics develop pancreatitis, indicating that an additional trigger factor-susceptibility factor is required to produce overt disease. The proposed project aims to determine the mechanisms responsible for alcohol-induced acute and chronic pancreatitis. It seeks i) to determine whether toxins from gut bacteria (endotoxins) may act as the trigger factor for acute alcoholic pancreatitis; and ii) to characterise the effects of alcohol and endotoxin on the cells responsible for pancreatic scarring, namely, pancreatic stellate cells. Our experiments will involve an animal model of alcohol feeding as well as pancreatic cells grown in dishes (cultured cells). Identification of the pathways by which alcohol causes pancreatic injury may enable the development of treatment strategies to prevent and-or retard the progress of alcoholic pancreatitisRead moreRead less
Expression And Secretion Of Large Clostridial Toxins From The Pathogenic Clostridia.
Funder
National Health and Medical Research Council
Funding Amount
$332,258.00
Summary
The large clostridial toxins are an important family of bacterial virulence factors that includes toxins from many disease-causing clostridial species. Despite their impact on public health, pathogenesis of disease caused by these bacteria is poorly understood. We will analyse how these bacteria regulate the production and secretion of the large toxins, which will give us a better understanding of the mechanisms of disease causation as well as identifying novel common therapeutic targets.
The Role Of Clostridium Difficile Spore Interactions With The Host In Gastrointestinal Infection And Disease
Funder
National Health and Medical Research Council
Funding Amount
$511,467.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
The Impact Of Clostridium Difficile Infection And The Host Immune Response On Colonic Homeostasis And Regeneration.
Funder
National Health and Medical Research Council
Funding Amount
$932,212.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with highly virulent isolates emerging overseas in 2002 and in Australia in 2010. These have spread through our hospitals and are also found in the community. This project will increase our understanding of how these strains cause severe gut disease, which is critical for the development of improved strategies for preventing and treating these infections and reducing antibiotic use.
The Role Of Clostridium Difficile Virulence Factors In Mediating The Host-pathogen Interactions That Lead To Gastrointestinal Disease
Funder
National Health and Medical Research Council
Funding Amount
$444,351.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains cause disease and why they are more harmful, which is critical for the development of improved strategies for preventing and treating these infections.
The Role Of Clostridium Difficile Spore Surface Structures In Initiating Gastrointestinal Infection And Disease.
Funder
National Health and Medical Research Council
Funding Amount
$467,556.00
Summary
Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infection ....Hospital-acquired infections with the bacterium Clostridium difficile are a major global public health concern with more virulent isolates emerging overseas since 2000. These strains were detected in Australia in 2010 and are now spreading throughout our hospitals. This project will increase our understanding of how these strains are transmitted to susceptible hosts and why they are so harmful, which is critical for the development of better strategies for preventing and treating these infections.Read moreRead less
Some of the world's most important diseases, including important diseases of indigenous chilren and the hospitalised elderly are caused by bacteria that carry a surface coating called a capsule. It is not clear how this capsule is retained by bacteria. Resolution of this question could lead to the development of new disinfectants that will stop hospital-acquired infections, to new reagents that can be incoporated into medical devices where bacteria frequently grow, and new antibiotics.
The Role Of Host Proteases In Modulating Enteric Infectious Disease
Funder
National Health and Medical Research Council
Funding Amount
$1,267,155.00
Summary
Bacterial pathogens that cause gut diseases result in 2.5 million deaths per year. The gut is a complex environment consisting of numerous factors that must be balanced to maintain enteric health. When these factors are unbalanced, disease can occur, and infections can cause imbalances. This project will increase our understanding of the role that host proteins play in gut infections, providing knowledge critical for developing improved strategies for disease treatment and prevention.