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
Targeting The Pathophysiology And Therapy Of Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$484,006.00
Summary
Hepatic fibrosis, or scarring of the liver, is a serious condition which can lead to liver cancer or death. Treatment of liver scarring is currently not effective once the scarring is well developed. This project aims to examine agents which may act to halt liver scarring once it has already developed. Outcomes from this project may help provide potential treatments to reduce the need for liver transplantation or to reduce patient deaths.
THE ROLE OF THE HEPATOCYTE IN EXTRACELLULAR MATRIX INTERACTIONS IN LIVER FIBROGENESIS
Funder
National Health and Medical Research Council
Funding Amount
$540,438.00
Summary
This study focuses on the main cell within the liver, the hepatocyte, and its role in the development of liver fibrosis. Liver fibrosis arising from liver injury has a common progression characterised by loss of liver structure and the development of dense fibrous bands of tissue in the condition known as cirrhosis. The importance of the outlined research plan is that for the first time the hepatocyte has been identified as having a significant role in the development of liver fibrosis.
Role Of Tissue Ferritin As A Proinflammatory Mediator Of Hepatic Stellate Cell Activation In Hepatic Iron Overload.
Funder
National Health and Medical Research Council
Funding Amount
$574,890.00
Summary
The hepatic stellate cell is responsible for liver scarring (fibrosis) in chronic liver diseases such as the iron overload condition Haemochromatosis. Our research has identified a role for tissue-derived ferritin as a proinflammatory cytokine in hepatic stellate cell biology. This proposal will examine the mechanisms associated with ferritin's proinflammatory action and assess its role in the fibrosis which occurs in Haemochromatosis.
The Role Of Adiponectin-mediated Nitric Oxide On Portal Hypertension And Liver Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$526,380.00
Summary
Liver cirrhosis is associated with high portal pressure that can result in severe bleeding and death. Adiponectin, a circulating protein, protects the liver from inflammation and scarring and may reduce portal pressure. We will characterise the mechanisms by which adiponectin induces NO and limits liver damage and determine if adiponectin treatment can reduce portal hypertension and bleeding in liver disease.
Role Of Human Amnion Epithelial Cells In Resolving Hepatic Fibrosis
Funder
National Health and Medical Research Council
Funding Amount
$618,755.00
Summary
When the liver is injured repeatedly by viruses and alcohol, it responds through a wound healing process that can lead to extensive scar tissue in the liver (cirrhosis). This condition may require liver transplantation and lifelong use of drugs to prevent the body from rejecting the new organ. To develop an alternate therapy, we will study if substances secreted by amnion cells from the human placenta (afterbirth), which would normally be discarded, can reduce liver scar tissue in mice .
Epithelial - Stromal Interactions In Pancreatic Cancer: Role Of Pancreatic Stellate Cells
Funder
National Health and Medical Research Council
Funding Amount
$425,750.00
Summary
The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for ....The pancreas is the major digestive organ in the body. It is located in the abdomen, draped across the spine behind the stomach. Pancreatic cancer is a leading cause of death in this country and in Western Society in general. Most patients with this disease survive only a few months after diagnosis. Even for those in whom a curative operation is undertaken, survival is poor. Chemotherapy and radiotherapy (alone and in combination) result in, at best, limited benefit. Clearly, there is a need for novel approaches to this lethal disease. The proposed project involves an examination of the local tissue reaction around pancreatic cancer. This tissue reaction is usually prominent and the cells involved may determine the extent of local and distant spread of the cancer. Modulation of this tissue reaction may limit pancreatic cancer growth and thus improve outcome.Read moreRead less