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B J Howard

Publications and source records attributed to B J Howard.

At least 55 records · Page 3Linked to original sources

Spatial variation in the vulnerability of Norwegian Arctic counties to radiocaesium deposition.

Under the Arctic Monitoring and Assessment Programme (AMAP), studies have been undertaken to compare potential fluxes of radiocaesium via important food products. The results for three Norwegian Arctic counties are presented in this paper. The comparative importance of different foodstuffs in contributing to collective dose varies spatially due to differing rates of production and transfer. Although reindeer meat is an important contributor to the radiocaesium flux following a nuclear release, other food products such as cow milk and lamb have been identified as potentially important. Assuming an even deposition following a nuclear release the radiocaesium flux was estimated to be highest for reindeer meat in Finnmark and Troms, whereas cow milk gave the highest flux in Nordland. The total number, geographical distribution and diet composition of indigenous peoples within different Arctic regions is an important factor affecting individual and collective doses arising from a nuclear release. Finnmark has been shown to be the most vulnerable of the three counties because it has the highest flux of radiocaesium and the largest number of indigenous people. The potential contribution of foodstuffs which are known to readily accumulate radiocaesium needs further consideration, in particular, mushrooms, freshwater fish and berries.

Arctic Regions↗

Free radical oxidation of brain proteins in accelerated senescence and its modulation by N-tert-butyl-alpha-phenylnitrone.

According to the free radical theory of aging, reactive oxygen species cause oxidative damage, proposed to be an underlying factor of the aging process. In the current study, we have used electron paramagnetic resonance spin labeling, measurements of protein carbonyl content, an index of protein oxidation, and determination of the activity of glutamine synthetase (an oxidatively sensitive enzyme) to report that cortical synaptosomal membranes from the senescence accelerated-prone (SAMP8) mouse showed structural characteristics of free radical oxidative stress relative to the senescence accelerated-resistant (SAMR1) mouse. The SAMP8 mouse exhibited a decrease in the relevant EPR parameter consistent with oxidative stress (P < 0.002), a decreased glutamine synthetase activity (P < 0.05), and an increased protein carbonyl content (P < 0.01) compared with these parameters in the SAMR1 mouse. Further, because free radical trapping compounds have been demonstrated to extend maximum life span and improve cognition in SAMP8 mice, we investigated the protective nature of the known free radical scavenger, N-tert-butyl-alpha-phenylnitrone (PBN), on the physical state of cortical synaptosomal membrane proteins. For 14 days, SAMR1 and SAMP8 mice were injected with 30 mg/kg PBN while the controls were injected with the corresponding volume of saline. Characteristic of less oxidized systems, cortical synaptosomal membranes from the PBN-injected SAMP8 mouse exhibited a return toward normal values of the relevant EPR parameter [the M1 = +1 low-field weakly immobilized line/M1 = +1 low-field strongly immobilized line (W/S) ratio of a protein-specific spin label] (P < 0.001) compared with that from saline-injected SAMP8 mice. In SAMR1 mice, in contrast to SAMP8, there was no significant change in the conformation of membrane proteins or protein carbonyl content of cortical synaptosomal membranes from the PBN-injected and saline-injected SAMR1 mice, showing that PBN itself did not induce conformational changes in cortical synaptosomal membrane proteins. The results are discussed with reference to the use of free radical scavengers as potential anti-aging agents.

Aging↗

The use of dietary calcium intake of dairy ruminants to predict the transfer coefficient of radiostrontium to milk.

Transfer coefficients (the equilibrium ratio between radionuclide activity concentration in milk or meat and the daily intake of radionuclide) are widely used to predict the contamination of animal products following the release of radionuclides into the environment. For a transfer coefficient to be generally applicable, its value must be constant for a range of circumstances. However, this is not the case for radiostrontium, the behaviour of which is strongly influenced by that of the homeostatically controlled nutrient, calcium. In this study, a relationship is derived between radiostrontium transfer coefficients and dietary calcium intake which takes into account the observed ratio for strontium:calcium transfer to milk. This relationship is tested against a range of observed data collated from the literature (n = 30) and found to account for 93% of the variability in transfer coefficient values. Model calculations show that a reduction in Fm of at least 40%-60% would be expected if dairy cattle, fed rations typical for well-managed herds, were supplemented with 100-200 g per day. Larger reductions would be predicted when dietary calcium intake is low.

Animal Feed↗

Health impacts of large releases of radionuclides. The radioecological significance of semi-natural ecosystems.

The transfer of radiocaesium to many food products either produced in or harvested from semi-natural ecosystems is high compared with intensive agricultural areas. Radiocaesium contamination levels in semi-natural foods are highly variable and difficult to predict. Spatial analysis may help to explain some of the variability and give improved estimates of the total output of radiocaesium in food products produced or harvested from semi-natural ecosystems. Consumption of foodstuffs from semi-natural ecosystems can contribute significantly to radiocaesium ingestion by humans. The long effective half-lives that occur for some semi-natural products lead to an increase with time in their importance compared with agricultural products. In determining the importance of semi-natural food products, the diet needs to be considered for both the average population and for special groups who utilize these environments to a greater extent than normal. Effective countermeasures have been developed to reduce radiocaesium levels in some semi-natural products.

Agriculture↗

Development and testing of a revised dynamic model of radiocaesium transfer to sheep tissues.

The model of radiocaesium transfer to sheep presented by Galer et al. provides reliable predictions only for sheep of a similar body weight to those used in the development of the model (approximately 30 kg). To extend the applicability of the model, it was necessary to re-parameterise it in terms of activity concentrations in tissues rather than total activities within them (although for gut compartments the use of activity has been retained). The rate coefficients for the new model have been estimated by fitting the model to the data used by Galer et al. which was derived from a single "calibration" experiment. The new model was found to account for 94% of the observed variation in the data (n = 42), a result similar to that obtained by Galer et al. The model has also been tested against data not used in its development but obtained from four separate experiments undertaken by three different laboratories. Good agreement between the predictions of the new model and observations was found for most circumstances and for several breeds of sheep with different body weights. It is concluded that the new model provides a useful dynamic description of radiocaesium transfers to the tissues of sheep of different breeds and under different contamination scenarios.

Administration, Oral↗

Use of the true absorption coefficient as a measure of bioavailability of radiocaesium in ruminants.

Limitations of existing methods to describe the bioavailability of dietary radionuclides to ruminants (the transfer coefficient and apparent absorption coefficient) have led to the alternative suggestion of using the true absorption coefficient (A(t)). Various approaches to estimating A(t) for radiocaesium, involving the intravenous administration of a second isotope, are presented and discussed with reference to results from studies in which a range of radiocaesium sources were examined in sheep. Although estimates of A(t) differed between the sources, they were reasonably consistent between measurement techniques. Those methods which involved the estimation of endogenous faecal excretion of radiocaesium could be used with previously contaminated animals and did not require continuous administrations of radiocaesium isotopes, but gave unreliable results for sources of low bioavailability. Methods based on estimating the turnover rate of dietary radiocaesium through blood plasma were sufficiently sensitive to measure A(t) for the range of sources studied. However, they require previously uncontaminated animals and continuous administration of both isotopes for approximately 7 days. Bioavailability is more effectively measured as A(t) than as the transfer or apparent absorption coefficients since A(t) does not incorporate factors relating to the metabolism of radiocaesium in the tissues of the animal. The results of these studies show that differences in transfer coefficients between sheep and cattle and between sheep of differing ages are not due to variation in absorption across the gut. The potential for applying these approaches to other radioactive elements is discussed.

Animals↗

A review of radionuclides in tide-washed pastures on the Irish Sea coast in England and Wales and their transfer to food products.

Close to the Sellafield Reprocessing Plant activity concentrations of many radionuclides including the long-lived 137Cs and actinides on tide-washed pastures bordering the Irish Sea are high compared with other terrestrial ecosystems in the United Kingdom. Despite the comparatively high deposition of radionuclides, contamination of agricultural products from tide-washed pastures is lower than would be predicted from studies in terrestrial ecosystems. This is because the main source of contamination in tide-washed pasture, radionuclides associated with sedimentary particles, has low availability for uptake by plant roots and in the gut of ruminants. Generalised Derived Limits (GDLs), published by the National Radiological Protection Board (NRPB) are estimates of environmental radioactivity concentrations which would potentially be radiologically significant. These provide a benchmark against which environmental measurements can be assessed. In the past, several comparisons of radioactivity concentrations in tide-washed pastures with GDLs have been made, but only some of these comparisons are valid since current approaches used to assess doses are not always strictly appropriate to these ecosystems. Directly applicable GDLs are needed, and are currently being developed by the NRPB.

Journal Article↗

Prevention of hyperoxia-induced alterations in synaptosomal membrane-associated proteins by N-tert-butyl-alpha-phenylnitrone and 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol).

Hyperoxia has been considered a model of free radical reactive oxygen species production in aging and age-related disorders. Previously, we studied the membrane protein alterations that occur during hyperoxia; we found that exposure of young animals to 24 h of hyperoxia provided the greatest degree of oxidation of cortical synaptosomal membrane proteins. We reasoned that free radical oxidation was involved in this protein oxidation. In accordance, in the current study we investigated the protective nature of two known free radical scavengers, N-tert-butyl-alpha-phenylnitrone (PBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (Tempol), against 24-h hyperoxia damage. The three techniques used in this study were electron paramagnetic resonance (EPR) protein-specific spin labeling, assay of the activity of the oxidatively sensitive enzyme glutamine synthetase (GS), and measurement of protein carbonyl content. Before hyperoxia, gerbils received intraperitoneal injections of varying concentrations of either of the two free radical scavengers. After 30 min, the gerbils were exposed to 90-100% O2 for 24 h. For the spin labeling experiments, cortical synaptosomes were isolated from gerbils. The membrane proteins were spin labeled with the thiol-specific label MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperidin-1-oxyl). As in our earlier study, the EPR spectral parameter of MAL-6-labeled membranes, the W/S ratio, decreased with hyperoxia (p < 0.00001). This effect was lessened significantly with administration of PBN (p < 0.0003) or Tempol (p < 0.00003). For the GS and protein carbonyl assays, cortical proteins were used. The activity of the GS decreased with hyperoxia (p < 0.000005), and this effect likewise was lessened with administration of PBN (p < 0.004) or Tempol (p < 0.002). The protein carbonyl content increased with hyperoxia (p < 0.0002), and there was a protective effect found with Tempol (p < 0.000001). The optimum doses for PBN and Tempol were 20 and 5 mg/kg, respectively. The results are discussed with reference to the use of free radical scavengers as potential antiaging agents.

Animals↗

A review of countermeasures to reduce radioiodine in milk of dairy animals.

The most effective countermeasure for radioiodine contamination of milk is to provide dairy animals with uncontaminated feed, with the added advantage that it will be effective for other radionuclides in the fallout. Another effective response is to process the milk into storable dairy products for an appropriate length of time to allow for physical decay. The use of additives given to ruminants to reduce radioiodine in milk is an alternative countermeasure which could be effective. Stable iodine administration is a practically feasible option which has the potential to reduce radioiodine levels in milk by at most a factor of three. Stable iodine supplementation should be at sufficiently high rates to be effective (and at least 1 g d-1 for dairy cows), particularly for ruminants already receiving high amounts of iodine in the diet. Currently available data are inadequate to recommend a suitable stable iodine administration rate for different species of ruminants. Other compounds, such as perchlorate and thiocyanate, also reduce the transfer to radioiodine to milk (and thyroid). Some of these compounds seem to be potentially equally as effective as stable iodine. However, currently there is inadequate information on their effectiveness and possible toxicity to both ruminants and humans for these compounds to be considered as suitable countermeasure additives.

Animals↗

beta-Amyloid peptide-derived, oxygen-dependent free radicals inhibit glutamate uptake in cultured astrocytes: implications for Alzheimer's disease.

beta-Amyloid (A beta), the central constituent of senile plaques in Alzheimer's disease (AD) brains, was shown by us recently to generate free radicals in an oxygen dependent mechanism. A beta-derived free radicals were detected directly using electron paramagnetic resonance (EPR) spin trapping techniques employing the spin trap phenyl-alpha-tert-butylnitrone (PBN). We have extended these studies to investigate the nature of the oxyradicals derived from A beta peptides, and we show that these free radicals are able to inhibit glutamate uptake in cultured astrocytes. An implication of inhibited astrocyte glutamate uptake in brain is increased extracellular levels of glutamate, which is excitotoxic to neurons. These results support the hypothesis that A beta neurotoxicity in AD may be due in part to A beta-derived, oxygen-dependent free radical inhibition of glutamate uptake.

Alzheimer Disease↗

Membrane protein alterations in rodent erythrocytes and synaptosomes due to aging and hyperoxia.

We have applied the technique of electron paramagnetic resonance (EPR) protein-specific spin labeling to the study of membrane protein alterations occurring during age and exposure to isobaric hyperoxia. Cortical synaptosomes and erythrocyte membranes (ghosts) were isolated from young rodents (Fisher 344 rats or mongolian gerbils, 3-4 months of age) and aged rodents (age 22-27 months for rats, greater than 15 months for gerbils). Membrane proteins were spin labeled with the thiol-specific spin label MAL-6 (2,2,6,6,-tetramehtyl-4-maleimido-piperdin-1-oxyl). The relevant EPR spectral parameter of MAL-6 labeled membranes, the W/S ratio, decreased significantly with age of animal in both synaptosomes and ghosts (P < 0.001). As a paradigm for accelerated oxidative stress, young and aged gerbils were exposed to an atmosphere of 90-100% O2 for 0-48 h. In both young and aged gerbils, the W/S ratio decreased significantly with hyperoxic stress (P < 0.003). The W/S ratio of synaptosomes isolated from aged gerbils decreased continually from 0-48 h hyperoxia, whereas the W/S ratio of synaptosomes from young animals demonstrated a pronounced rebound effect from 24-48 h. The results are discussed with reference to membrane protein oxidation in aging.

Aging↗

Energy status in anoxic rat hepatocytes: effects of isoflurane, solution composition, and hypothermia.

Both cold and warm ischemia occur during liver transplantation. Hypothermia and Wisconsin solution preserve adenine nucleotide energy status, which is crucial to hepatic function and viability. The volatile anesthetic isoflurane has been shown to preserve energy status in anoxic isolated hepatocytes in warm Krebs solution. The present study examined isoflurane effects on energy status during incubation also in Wisconsin or Krebs-plus-adenosine solution at 37 degrees or 4 degrees. Hepatocytes were isolated from rat liver after perfusion with Krebs + collagenase. In 25-mL flasks, 12.5 million cells in 2.5 mL of Krebs, Krebs plus 5 mmol/L adenosine, or Wisconsin solution were incubated under an atmosphere of O2/CO2 or N2/CO2 (19:1) +/- isoflurane (3 volumes% = 2ED50), for 30 minutes at 37 degrees C or 4 degrees C. Adenine nucleotides were measured by high-performance liquid chromatography (HPLC), lactate enzymatically. During warm (37 degrees) anoxia, Wisconsin solution preserved energy status; Krebs plus adenosine did not. Isoflurane further protected energy status in all three solutions. Hypothermia (4 degrees) alone greatly decreased anoxic loss of energy status in all solutions. In Wisconsin solution only, energy status tended to be higher in anoxic than in oxygenated cells and was further enhanced by isoflurane, with corresponding increases in lactate. During 30 minutes of either warm or cold anoxia, isoflurane and Wisconsin solution each helped preserve adenine nucleotide energy status in isolated hepatocytes, at least in part through enhanced glycolysis.

Adenine Nucleotides↗

The use of an in vitro technique to predict the absorption of dietary radiocaesium by sheep.

The validity of an in vitro extraction technique to predict the availability for absorption of radiocaesium in the sheep gut has been assessed. The technique (a 2-h extraction with caesium chloride) was found to be valid for sources with a low availability for transfer across the gut, but inappropriate for ionic radiocaesium or radiocaesium incorporated internally within herbage. For such radiocaesium sources, which have a high in vitro availability, no correlation was found between in vitro extraction and true absorption measurements. A true absorption value of 0.80 is recommended for these sources, although values for individual sheep in the range 0.60 to 1.00 should be expected.

Animal Feed↗

The referral role of pediatricians.

Pediatricians have a vital role in making effective mental health referrals for many children and their families. After selecting families who are appropriate for referral, for which type of resource, and the severity of their problems, the clinician should carry out a careful process to ensure the success of the referral. Special attention should be paid to finding the pain in individual family members, locating appropriate resources, and following up once a referral has been made.

Adult↗