Identifying The Mechanisms By Which Ascorbate Stimulates Cellular Iron Uptake From Transferrin.
Funder
National Health and Medical Research Council
Funding Amount
$302,123.00
Summary
Vitamin C (ascorbate)-deficiency leads to anaemia and other symptoms of scurvy. Iron supplementation cannot alone correct this anaemia, with ascorbate being crucial. Almost all iron in plasma is bound to transferrin, and I have recent data showing that ascorbate stimulates transferrin-iron uptake. This research will identify how this stimulation occurs. This work has important biomedical implications for understanding iron uptake and anaemia, which affects 500 million people globally.
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
Environmental And Genetic Factors In Childhood Acute Lymphoblastic Leukaemia: A Case-control Study.
Funder
National Health and Medical Research Council
Funding Amount
$1,788,500.00
Summary
In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the develo ....In most countries, acute lymphoblastic leukaemia is the commonest cancer in children. One in 2000 children will develop this disease before their 15th birthday. New methods of treatment introduced over the last 30 years have resulted in cure for many children. However, one third of children diagnosed with this type of leukaemia still die and, even in those whose lives are saved, cure is achieved at a significant cost to the child, the family and the community. Greater understanding of the development of childhood leukaemia may lead to preventive measures. Most children with this type of leukaemia are very young, suggesting that factors to which parents are exposed may affect future children. For this reason, as well as investigating the health and lifestyle of the child, it is essential to study the parents. Recent research suggests an association between the mother's intake of folate during pregnancy and her child's risk of developing the most common type of childhood leukaemia. It is also apparent that genetic differences result in varying abilities to deal with toxins, which may alter the risk of developing some cancers. Diet and lifestyle probably also affect this risk. These observations and interactions need to be examined in greater detail. In this large Australia-wide study specific genes will, for the first time, be examined and analysed in conjunction with rigorous assessment of exposures thought to be related to the development of childhood leukaemia. Results obtained from children with leukaemia and their parents will be compared with those from healthy children and their parents. This study is unique in its attempt to assess gene-environment interactions in Australian children and their parents. It will clarify the role of folate and other potential environmental agents in the development of childhood leukaemia and examine gene variations that may affect cancer risk.Read moreRead less
Genotypes And Phenotypes Of Human Primary Non-congenital Antibody Deficiency
Funder
National Health and Medical Research Council
Funding Amount
$544,692.00
Summary
Antibodies represent a key component of the immune system, and a particularly important in defence against bacterial and viral infections. In some individuals, antibody production fails, rendering them more susceptible to infection. In most cases, the mechanism of antibody failure is unknown. This project seeks to determine the genetic and cellular mechanisms of antibody failure. This could improve diagnosis for immune deficiency, and improve our overall understanding of the immune system.
Secretion is an essential step in memory and learning, control of metabolism and reproduction and the functioning of most organs. Secretory dysfunction also underlies many diseases including type 2 diabetes. We plan experiments to test for a new model of control of insulin secretion.