Altered Hepatic Pharmacokinetics As A Consequence Of Drug- And Disease-induced Changes In Hepatic Vascularity.
Funder
National Health and Medical Research Council
Funding Amount
$498,088.00
Summary
Many drugs are broken down by the liver or are removed from the liver out into the intestine by the bile, as well as being removed by the kidney and other organs. The effectiveness of the breakdown and removal by the liver depends both on whether the drug can get into the liver cells and on how well the enzymes in the liver are working. Cardiovascular and liver diseases and certain drugs can affect both of these processes. This work is concentrating on those processes which mainly affect the upt ....Many drugs are broken down by the liver or are removed from the liver out into the intestine by the bile, as well as being removed by the kidney and other organs. The effectiveness of the breakdown and removal by the liver depends both on whether the drug can get into the liver cells and on how well the enzymes in the liver are working. Cardiovascular and liver diseases and certain drugs can affect both of these processes. This work is concentrating on those processes which mainly affect the uptake process. The diseases of most interest are liver cirrhosis, fatty liver disease, atherosclerosis and chronic heart failure, all of which together are leading causes of death in Western countries. They are also associated with liver dysfunction due to effects on liver vessels. We have a poor understanding of how the effects of these diseases and a number of drugs on liver vessels affect the functioning of the liver, especially in terms of how they affect drug breakdown or removal of drugs. This project seeks to understand these effects and proposes a number of animal studies as well as human studies to provide insight. The drugs to be studied are those most commonly used in patients with cardiovascular and liver diseases, as one of our main goals is to provide better therapeutic management in these patients.Read moreRead less
The Role Of Urotensin II In Diabetes-Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$405,594.00
Summary
People with diabetes most commonly die from stroke or heart attack and we need to determine what makes them more prone to these problems. The recently discovered UII system is increased in people with diabetes and has been found in diseased parts of blood vessels. Thus, the aim of this project is to characterise the UII system in the setting of diabetes using 2 unique genetically altered mice and a blocker a to study the effects of high cholesterol, diabetes and a deletion of UII.
Development Of An In Vivo Pharmacokinetic-pharmacodynamic Model For Evaluation Of Antimalarial Drug Therapy Combinations
Funder
National Health and Medical Research Council
Funding Amount
$120,604.00
Summary
The World Health Organization currently estimates that there are 300-500 million cases of malaria annually, with 1.5-2.7 million deaths. These are staggering data, given that almost 20 antimalarial drugs are now in regular clinical use. Multi-drug resistance is present in most tropical countries where malaria is endemic and there has been a rapid escalation in cases of malaria in developed countries over recent decades (imported by travellers). Clearly, there is a need to ensure that current and ....The World Health Organization currently estimates that there are 300-500 million cases of malaria annually, with 1.5-2.7 million deaths. These are staggering data, given that almost 20 antimalarial drugs are now in regular clinical use. Multi-drug resistance is present in most tropical countries where malaria is endemic and there has been a rapid escalation in cases of malaria in developed countries over recent decades (imported by travellers). Clearly, there is a need to ensure that current and new treatment and prevention strategies are rational and effective. This project is based on the premise that improvements can be made in the in vitro testing process of antimalarial drugs. The experiments will be conducted using mice and a form of malaria that is specific to mice but closely resembles human malaria. In the first stage, the relationship between the amount of a new antimalarial drug (dihydroartemisinin) in the body and the effectiveness of the dose will be tested. These experiments will be repeated using conventional antimalarial drugs such as mefloquine. Information from these studies will subsequently be used to evaluate combinations of antimalarials. The results will be used as the basis of extensive, collaborative clinical studies in South-East Asia that are beyond the scope of this project. The methods used for this research will be important for future testing of new antimalarial drugs or combinations of drugs for the treatment and prophylaxis of malaria.Read moreRead less
NADPH Oxidase In Pathological Angiogenesis In Solid Tumours And Retina
Funder
National Health and Medical Research Council
Funding Amount
$581,989.00
Summary
Understanding blood vessel growth has profound clinical implications for many diseases. Blocking vessel growth is a promising strategy for treatment of cancer and eye complications accompanying diabetes, whereas treatments to stimulate new vessel growth will treat ischemic disorders ie. heart attack and stroke. Here we investigate whether targeting an enzyme that grows blood vessels has potential for making drugs to stop tumor growth or eye damage that occurs with diabetes and premature births.
Role Of Transformation And IAPs In Sensitivity Of Cells To TNFalpha
Funder
National Health and Medical Research Council
Funding Amount
$505,786.00
Summary
Current cancer treatments are ineffective and unpleasant for patients. This is because existing cancer treatments target normal as well as cancer cells. New anti-cancer drugs have been designed to encourage cancer cells to kill themselves, by a process called apoptosis, but may still target normal cells. This project aims to discover why cancer cells are susceptible to a novel anti-cancer drug and a natural ligand called TNF but normal cells are not. This will lead to better treatments.
Regulation Of Cellular Responses To Neuropeptides.
Funder
National Health and Medical Research Council
Funding Amount
$83,510.00
Summary
Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction ....Neuropeptides are chemicals released from nerves that are responsible for communication between the nerves, glands, muscles or other nerves. Neuropeptides exert their diverse biological effects by interacting with small structures on the cells they wish to communicate with. These structures bind the neuropeptide and are termed neuropeptide receptors. The responses of tissues to neuropeptides, for example, contraction of muscle, decrease with continued exposure to the neuropeptide. This reduction in response is termed desensitization is thought to turn off the response to cells following stimulation by neuropeptides. In this study, I will investigate the mechanisms behind the desensitization of VPAC receptors which are a found throughout the body and have many important roles for example, gastrointestinal, pancreatic and reproductive function and control of muscle. VPAC receptors are also highly expressed in certain many cancers such as breast, prostate and colon carcinoma. The wide variety of functions that these receptors perform and the wide distribution in the body suggest that these are very important receptors. To date research into the responses and desensitisation of these receptors has been lacking, and the work that has been done has become confusing as more receptors and neuropeptides which bind them are discovered. The current project aims to carefully study these receptors and to determine their role in health and disease. The understanding the interaction of receptor and neuropeptide can perhaps lead to development of new therapeutic agents.Read moreRead less