A study of the incidence of bovine tuberculosis in the wild red deer herd of Exmoor.

Bovine tuberculosis (bTB) is an infectious disease which thrives at the wildlife-livestock interface. Exmoor has the largest herd of wild red deer (Cervus elaphus) in England, and also a large number of dairy and beef farms. The population, health and well-being of the herd are managed by a combination of hunting with hounds and by stalking. This study used a serological assay to determine the incidence of bTB in the population of 106 wild red deer of Exmoor, the relationship between regional deer densities and the presence of bTB in deer, and domestic cattle. The overall number of bTB positive deer was 28.3% (30/106). Stalked deer had a slightly higher incidence of bTB (19 out of 55, 34.55%) than hunted deer (11 out of 51, 21.57%). There was no clear pattern of distribution except for one region which showed an incidence of 42.22% compared with 16.4% in the remainder of the moor. There was little difference in the incidence of bTB between male and female animals. The age of animals in the study ranged from < 1 year to over 10 years. There was no clear difference in the incidence across the age range (< 1 year- > 10 years) with the exception of a particularly high incidence in those animals aged 1 year or less. There was a significant correlation between the presence of deer with bTB and the number of farms reporting bTB positive cattle, but not between the regional population of red deer and bTB in deer or cattle.

Non-transferrin-bound iron is associated with biomarkers of oxidative stress, inflammation and endothelial dysfunction in type 2 diabetes.

AIMS: To investigate the association between circulating non-transferrin-bound iron [NTBI], and markers of oxidative stress, endothelial function and inflammation in subjects with type 2 diabetes and non-diabetic subjects with varying degrees of obesity. METHODS: Plasma NTBI was measured by HPLC, together with total iron, iron-binding capacity, transferrin saturation and soluble transferrin receptor, together with total and reduced ascorbate, malondialdehyde [MDA], E-selectin and high-sensitivity c-reactive protein [hs-CRP] in groups of 28 subjects with type 2 diabetes, 28 non-obese controls and 17 obese non-diabetic subjects. RESULTS: Levels of NTBI were higher than controls in the diabetes group, but the total serum iron levels were lower. MDA levels were higher than controls in both the diabetes and obese groups, and this was associated with higher levels of oxidised ascorbate. hs-CRP levels were higher in both the diabetes and obese groups, and E-selectin was significantly higher in the diabetes group. There were strong positive correlations between HbA1c levels and NTBI [P<0.01], HbA1c and E-selectin [P<0.001] and NTBI and E-selectin [P<0.02] in the diabetes group. CONCLUSION: These results support the hypothesis that iron-mediated oxidative stress may be a mechanism linking poor glycaemic control with vascular dysfunction in type 2 diabetes.

Iron homeostasis in the neonate.

The regulation of the availability of micronutrients is particularly critical during periods of rapid growth and differentiation such as the fetal and neonatal stages. Both iron deficiency and excess during the early weeks of life can have severe effects on neurodevelopment that may persist into adulthood and may not be corrected by restoration of normal iron levels. This article provides a succinct overview of our current understanding of the extent to which newborns, particularly premature newborns, are able (or not able) to regulate their iron status according to physiologic need. Postnatal development of factors important to iron homeostasis such as intestinal transport, extracellular transport, cellular uptake and storage, intracellular regulation, and systemic control are examined. Also reviewed are how factors peculiar to the sick and premature neonate can further adversely influence iron homeostasis and exacerbate iron-induced oxidative stress, predispose the infant to bacterial infections, and, thus, compromise his or her clinical situation further. The article concludes with a discussion of the areas of relative ignorance that require urgent investigation to rectify our lack of understanding of iron homeostasis in what is a critical stage of development.

Is there a causal relationship between the receipt of blood transfusions and the development of chronic lung disease of prematurity?

The number and total volume of blood transfusions received by premature babies is, after gestational age and birth weight a good predictor of the likelihood of developing chronic lung disease of prematurity (CLD) and retinopathy of prematurity (ROP). Oxidative damage, inflammation and pulmonary infections are also strongly associated with the development of CLD. It is currently not clear whether there is a causal relationship between the receipt of blood transfusions and oxidative damage, infection, inflammation and CLD in these babies. Strong arguments may be made both for and against a causal relationship. The babies who receive blood transfusions are usually smaller than those who do not, and are ventilated, often with high oxygen levels, for a longer period of time. The longer the baby is on a ventilator the more likely it is to develop pulmonary infection and inflammation. All these factors will promote free radical production and oxidative damage irrespective of the receipt of blood transfusion. This would argue against a causal relationship. On the other hand, an argument may be presented which is based on iron promoted free radical generation, infection and fibrosis consequent to the breakdown of haeme released from transfused erythrocytes. Haeme is broken down by haeme oxygenase (HO) to iron, CO and bilirubin. Under normal circumstances the products of HO activity are beneficial to the organism, but when HO activity is excessive, the products are potentially damaging. Free iron, (in the Fe2+ form) if not sequestered with protein or urate, will generate highly toxic free radicals via the Fenton and Heber-Wiess reactions, predispose the tissue to infection and promote fibrosis. The iron chelating ability of the premature baby appears to be limited so that it would be difficult to deal with any increase in free iron production. Free iron will in turn induce HO activity leading to a potentially serious positive feedback process. The lung is particularly sensitive to iron induced HO activity. In addition, HO activity may be enhanced by other events occurring in the premature lung such as the production of proinflammatory cytokines and the reduced level of glutathione. Thus, the possibility of a causal relationship clearly exists and needs to be examined. This can be attempted by measuring the products of HO activity in relation to the receipt of blood transfusions.

Blood transfusion and pulmonary lipid peroxidation in ventilated premature babies.

Urinary malondialdehyde (MDA; a biochemical marker of lipid peroxidation) is increased following the receipt of blood transfusions in premature babies. This indicates an increased level of oxidative damage somewhere in the body. The aim of this study was to determine whether the lung may be a site of increased oxidative damage following blood transfusions. This was achieved by examining the relationship between blood transfusion and levels of MDA in bronchoalveolar lavage (BAL) fluid from ventilated premature babies. The study was a retrospective analysis of data obtained from a group of 42 ventilated premature babies of less than 32 weeks' gestation. Twenty-seven babies received blood transfusions, and 9 received at least one transfusion during the first week of life when daily BAL samples were being taken. Pulmonary epithelial lining fluid (ELF) was sampled by BAL daily during the first week of life and weekly thereafter. MDA was measured by an established high performance liquid chromatography (HPLC) technique. There was a significant positive correlation between volume of blood transfusions received and peak and mean ELF MDA levels (r=0.810, peak; r=0.740, mean; n=21). During the first week of life, when daily samples were being taken, the mean ELF MDA level after blood transfusion (1.829 microM; SE, 0.529) was significantly greater than before transfusion (0.928 microM; SE, 0.297) (n=9). In babies who received 2 transfusions within the first week (n=5), the MDA level was elevated further following the second transfusion (2.825 microM; SE, 0.346). The results of this study indicate that pulmonary oxidative damage increases after the receipt of blood transfusions. Babies receiving blood transfusions show a greater incidence of pulmonary oxidative stress and poor clinical outcome. This may simply reflect that the sickest babies are those most in need of blood transfusion, and that there is no causal relationship. However, the possibility of a causal relationship between blood transfusions and oxidative damage exists and should be investigated.