Management And Risk Prediction Of Paracetamol Overdose
Funder
National Health and Medical Research Council
Funding Amount
$98,950.00
Summary
Paracetamol overdose is the most common pharmaceutical poisoning in developed countries and incidence is increasing in the developing world. Overdose can lead to liver failure and death. Our research will evaluate a novel antidote regimen and whether early cessation of antidote for paracetamol toxicity in a specific cohort is safe, with implications of decreasing time in hospital. We will also identify risk prediction tools to help early identification of patients needing intensive treatment
Long-term Implications And Outcomes Of Anti Hepatitis B Virus (HBV) Treatment In HIV-HBV Co-infection
Funder
National Health and Medical Research Council
Funding Amount
$293,931.00
Summary
Chronic hepatitis B (HBV) infection may cause serious liver disease in some people, including liver failure or liver cancer. Being infected with both HBV and HIV increases the chances of these complications occurring and the rate they develop. The optimal long term management of HIV-HBV co-infection remains unclear; and the effects of antiretroviral therapy on liver disease progression outcome is unknown in the setting of HIV-HBV co-infection.
Store-operated Calcium Channels And Liver Function
Funder
National Health and Medical Research Council
Funding Amount
$241,477.00
Summary
The liver is responsible for regulating the metabolism of carbohydrates and lipids , the synthesis of proteins responsible for the transport of lipids in the blood, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are regulated by the changes in the free calcium concentration in the cytoplasmic space of liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulat ....The liver is responsible for regulating the metabolism of carbohydrates and lipids , the synthesis of proteins responsible for the transport of lipids in the blood, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are regulated by the changes in the free calcium concentration in the cytoplasmic space of liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulation of calcium concentrations in liver cells is abnormal. The cytoplasmic calcium signal can come either from the extracellular space, through channels in plasma membrane, or from the intracellular calcium-storing organelles. The aims of the present proposal are to investigate the properties of the calcium channels in the liver cell plasma membrane, and the mechanisms by which they are regulated. The experiments will involve the direct estimation of calcium inflow into liver cells, measured as an electric current through the plasma membrane by patch-clamp technique. The results should show how calcium channels in liver cells work and provide knowledge that can be used for better treatment of diabetes, fat malabsorption and liver failure.Read moreRead less
Intracellular Calcium Signalling And Liver Disease
Funder
National Health and Medical Research Council
Funding Amount
$295,357.00
Summary
The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat mal ....The liver is responsible for regulating the metabolism of carbohydrates and fats, the synthesis of proteins which transport fats around the body, the synthesis of bile required for fat digestion, and for the removal of toxic chemicals from the body. Many of these processes are controlled by hormones such as adrenaline and insulin. The actions of these and other hormones on the liver involves changes in the concentration of calcium in liver cells. In a number of diseases such as diabetes, fat malabsorption, and liver failure, the balance and regulation of calcium in liver cells is abnormal. The aims of the present experiments are to investigate the mechanisms by which hormones regulate the flow of calcium into liver cells. The experiments will involve the measurement of calcium in different regions of liver cells using fluorescent dyes and high resolution microscopy, and the identification of structural proteins and organelles within the liver cell which are required to control calcium inflow. The results should show how an important type of calcium channel in liver cells works and is controlled. This knowledge will allow better treatment of diabetes, fat malabsorption and liver failure. The knowledge should also lead to improvements in liver transplant operations.Read moreRead less
Mitochondrial Dysfunction And Pathways Of Cell Death In Drug-induced Liver Injury
Funder
National Health and Medical Research Council
Funding Amount
$301,650.00
Summary
Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Furt ....Drugs are an important cause of liver disease that can result in fatal liver damage or require liver transplantation. More than 500 drugs are reported to cause liver disease, but we know almost nothing about how drugs injure the liver. As well as prescribed drugs: panadol, either after self-poisoning or inadvertently taken in too high a dose in someone who is not eating or is taking other medications that interfere with panadol breakdown, is one of most common causes of acute liver failure. Further, several herbal medicines have been implicated as causing liver disease. This project is designed to help us understand why and how 3 particular drugs damage the liver. We will study panadol, diterpenoids the active ingredients of skullcap, a herbal medicine, and azathioprine (imuran), a drug commonly used to suppress rejection after kidney or liver transplantation which occasionally causes very severe liver disease. Our main hypothesis is that these drugs damage mitochondria, the energy generating structures that form the engine of all living cells. We already know a little about how drug metabolites of panadol and the diterpenoids can damage mitochondria, but no-one has proven that this is the most important way in which they damage the liver. For drugs like azathioprine in which liver damage is rare, we are proposing that genetic defects in the mitochondrial DNA are what could predispose to liver injury. Thus our measurements will include how much mitochondrial DNA damage is caused by the drugs. Panadol, diterpenoids and azathioprine cause liver cell death by differing pathways (called apoptosis and necrosis). There are plausible ways in which mitochondrial damage could start off either (or both) cell death pathways during drug-induced liver injury, and we plan to test these. The new knowledge gained about how drugs damage the liver will be instrumental in allowing us to design new approaches to treat this important problem.Read moreRead less