According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most pe ....According to current National Heart Foundation surveys high blood pressure affects almost 3 million Australians, and accounts for about 6% of the total burden of disease. Unless effectively treated, high blood pressure may result in serious complications such as stroke, heart attacks and heart failure. Despite the fact that there are now many effective blood pressure-lowering medications available, blood pressure control in the community is often poor. The cause of high blood pressure in most people is unknown, but there is consistent information from population studies that low vitamin C intake is associated with high blood pressure. Recently, it has been shown that a diet rich in fruit and vegetables can lower blood pressure. We recently demonstrated in a small study that vitamin C tablets for one month lowered blood pressure, suggesting that vitamin C was the key beneficial element of the fruit and vegetable diet. Interestingly, some recent work suggests that the recommended daily allowances of vitamin C are less than a third of what they need to be to get effective levels of vitamin C in body tissues. Studies in animal models of high blood pressure have shown that oxidant levels are increased. This can affect the ability of blood vessels to relax, and may be a cause, rather than a result of high blood pressure. It seems possible that vitamin C (a strong antioxidant) may be having its beneficial effect by reducing 'oxidant stress' in blood and blood vessel walls. The purpose of this project is to further determine the effect of oxidants and antioxidants (specifically vitamin C) on blood pressure and blood vessel function in patients with high blood pressure. It is clearly prudent to eat a diet rich in fruit and vegetables, but it is important that we understand why this is so, and whether specific dietary components are critical. Vitamin C might potentially make a major impact on the presence and severity of high blood pressure in the Australian community.Read moreRead less
Antioxidants Vitamin C And Vitamin E For The Prevention Of Pre-eclampsia - A Randomised Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$696,750.00
Summary
Women who develop hypertension in pregnancy have a higher risk of complications in pregnancy and their babies are often born smaller than average and earlier. An initial trial to women at high risk of pre-eclampsia suggest that vitamin C and vitmin E supplements may decrease both reduce the risk of developing hypertension in pregnancy and the risk of the infant being born small for dates. These encouraging results need assessment in the Australian population. This study assesses the value of wom ....Women who develop hypertension in pregnancy have a higher risk of complications in pregnancy and their babies are often born smaller than average and earlier. An initial trial to women at high risk of pre-eclampsia suggest that vitamin C and vitmin E supplements may decrease both reduce the risk of developing hypertension in pregnancy and the risk of the infant being born small for dates. These encouraging results need assessment in the Australian population. This study assesses the value of women taking vitamin C and vitamin E supplements during the antenatal period to decrease the risk of developing hypertension during pregnancy and poor fetal growth. Such an easy and inexpensive therapy, if effective, would be an important advance.Read moreRead less
NMR Of Red Cells: Plasma Membrane Oxidoreductase, And Cation Transport
Funder
National Health and Medical Research Council
Funding Amount
$192,388.00
Summary
An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknow ....An interesting paradox exists with respect to the 'central' function of the red blood cell (RBC): it delivers the main oxidising capacity to the body (O2), but it also carries the chemically opposite functionality in its membrane, namely reducing capacity. The reduction of many oxidised proteins and metabolites in blood plasma is mediated by a plasma-membrane oxido-reductase (PMOR). Ascorbic acid (vitamin C) dramatically accelerates this rate of reduction but its precise molecular role is unknown; neither is the immediate source of the reducing equivalents (electrons) known. Novel, non-invasive, 13C NMR methods have been developed, and others are planned in this project, to study the rate of reduction of Otest? compounds, including 13C-ferricyanide, and reactions of 13C-ascorbate. This will provide a quantitative understanding of the kinetics of the redox reactions in the intact cell. The transfer of negative charges (electrons) from the cell, in the longer term (minutes) inevitably must be matched by the movement of cations (positive charges). The main cation flux is mediated by Na+, K+-ATPase, but various cation exchange pathways are also involved in the total Oionic economy? of the cell. Of special interest will be the calcium-activated K+ (or Gardos) channel. This Oopens? inappropriately in malaria, sickle cell anaemia, and under blood bank storage conditions, and this is thought to be the basis of some of the pathological events in these conditions. The alkali-metal cation exchange pathway ( Na+-Li+) is more activate in the red cells of many patients with hypertension. So, multiple-quantum NMR methods will be used to monitor membrane transport and binding of cations to characterise the kinetics and regulation of the K+-channel, and the Na+-Li+ exchange reactions. The significance will lie in a basic understanding of, and possible 'diagnostic methods' for the biochemical processes that occur in red blood cells in health and disease.Read moreRead less
Regulation And Activity Of Fatty Acid Delta-6 Desaturase (D6D)
Funder
National Health and Medical Research Council
Funding Amount
$527,683.00
Summary
Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these a ....Fish and fish oils contain fats known as omega-3 fats. These have health benefits in adult conditions such as rheumatoid arthritis and heart disease, and they are necessary for proper brain and eye development in infants. However, much of the population does not like to eat fish and also, world fish stocks are under stress. Thus, a sustainable alternative source of omega-3 fats needs to be explored. Some vegetable oils such as canola, echium, and flaxseed oils have omega-3 fats. However, these are not the same as the omega-3s in fish oil. In general, vegetable omega-3s are known as short-chain omega-3s whereas those in fish are long-chain. When the vegetable oil omega-3s are consumed in the diet, the body must convert them to the fish-type, or long-chain, omega-3s in order to gain the health benefits. Currently, human metabolism is poor at doing this conversion. Our studies suggest that the amounts and blends of fats in most diets are well below optimal for conversion to long-chain omega-3s in the body. In particular, our studies show that there may be no point in simply adding more vegetable omega-3 fats to the diet. This project will examine the enzymes that convert the short-chain to the long-chain omega-3 fats. In particular, it will examine how the dietary fats interact with each other in detrimental ways to suppress activity of the conversion enzymes necessary for long-chain omega-3 formation. Evidence for the health benefits of fish-based omega-3 fats is very strong and it is an approach to health that most people can undertake on their own. Our lack of knowledge of the best way to use plant-based omega-3 fats is a large impediment for a more sustainable and broader based use of omega-3 fats. The results from this study will begin to fill in this knowledge gap. The results will be useful across a range of activities that are determinants of the kinds of fat that we eat. These include oil seed breeding, food manufacture, and dietetics.Read moreRead less
Fatty Acid Biosynthesis In The Malaria Chloroplast As A Drug Target
Funder
National Health and Medical Research Council
Funding Amount
$131,035.00
Summary
Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasite ....Malarial parasites contain a chloroplast similar to that of plants. We recently found genetic evidence suggesting the malaria chloroplast makes fats in the same way as plant chloroplasts. Additionally, we have found that drugs and herbicides that block plant chloroplast fat production stop growth of malaria cultures. Parasitologists had assumed that malaria was unable to make fats and would scavenge them from its human host so we have probably discovered a new metabolic pathway in these parasites. We now propose to prove that the drugs work by blocking essential, chloroplast-based fat production in parasites. This could lead to novel treatment of malaria and related parasites.Read moreRead less
Inhibition Of Glucose-stimulated Insulin Secretion By Protein Kinase C Epsilon
Funder
National Health and Medical Research Council
Funding Amount
$555,693.00
Summary
Type 2 diabetes is a chronic disease which occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and is strongly linked to obesity. We have discovered that fat oversupply activates an enzyme in the pancreas causing defects in insulin release due to glucose. Inhibiting this enzyme helps overcome diabetes, through poorly defined mechanisms that we aim to clarify here. Our work could lead to new therapies for diabetes.
Mechanisms Of Fatty-acid Mediated Destruction Of Pancreatic Beta Cells
Funder
National Health and Medical Research Council
Funding Amount
$510,476.00
Summary
Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the be ....Type 2 diabetes is associated with obesity, but not all obese individuals develop the disease. Non-diabetic obese subjects are able to compensate for diminished sensitivity to insulin (a general feature of obesity) by enhanced output of insulin from the pancreatic beta-cells of the islet of Langerhans. In diabetics this compensatory mechanism is disrupted. Obesity and Type 2 diabetes are also associated with elevated levels of fatty acids (FAs) in the bloodstream. These can be taken up by the beta-cells where they exert both short and long-term effects. In the longer term FAs can be toxic to beta-cells and this is thought to be important in the failure of beta-cell compensation. The project is aimed at a better understanding of the manner by which different types of FAs influence the susceptibility of beta-cells to destruction. It builds on our preliminary results suggesting that the capacity of the beta-cell to convert saturated FAs to unsaturated FAs helps protect them from destruction. Our aim is to examine the mechanisms underlying this protection.Read moreRead less