Effect of the metabolic inhibitor, methimazole on the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) is altered in the presence of a metabolic inhibitor. The flavin monooxygenase system (FMO) was inhibited using methimazole (MTZ) to see whether a TCBZ-resistant isolate could be made more sensitive to TCBZ action. The Oberon TCBZ-resistant and Cullompton TCBZ-sensitive isolates Were used for these experiments. The FMO system was inhibited by a 2-h pre-incubation in methimazole (100 mu M). Flukes were then incubated for I further 22 h in NCTC medium containing either MTZ; MTZ+nicotinamide adenine dinucleotide phosphate (NADPH) (1 nm); MTZ+NADPH+TCBZ (15 mu g/ml); or MTZ+NADPH+triclabendazole sulphoxide (TCBZ.SO) (15 mu g/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed Using scanning electron microscopy'. After treatment with either TCBZ or TCBZ.SO alone, there was greater surface disruption to the triclabendazole-susceptible than -resistant isolate. However, co-incubation with MTZ and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant isolate than with each drug oil its own; this was not seen for the TCBZ-susceptible Cullompton isolate. Results of this study support the concept of altered drug metabolism in TCBZ-Resistant flukes and this process may play a role in the development of drug resistance.

Inhibition of cytochrome P450-mediated metabolism enhances ex vivo susceptibility of Fasciola hepatica to triclabendazole

A study has been carried out to investigate whether the action of triclabendazole (TCBZ) against Fasciola hepatica is altered by inhibition of drug metabolism. The cytochrome P450 (CYP P450) system was inhibited using piperonyl butoxide (PB). The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP P450 system was inhibited by a 2 h pre-incubation in PB (100 mu M). Flukes were then incubated for a further 22 h in NCTC medium containing either PB; PB + nicotinamide adenine dinucleotide phosphate (NADPH) (1 nM); PB + NADPH + TCBZ (15 mu g/ml); or PB + NADPH + TCBZ.SO (15 mu g/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible than the resistant isolate. However, co-incubation with PB and TCBZ/TCBZ.SO lead to more severe surface changes to the TCBZ-resistant Oberon isolate than with each drug on its own. With the TCBZ-susceptible Cullompton isolate, there was limited potentiation of drug action, and only with TCBZ.SO. The results support the concept of altered drug metabolism in TCBZ-resistant flukes and this process may play a role in the development of drug resistance.

Schistosoma mansoni cercariae experience influx of macromolecules during skin penetration

We have observed that when cercariae penetrate the skin of mice, there is influx into their tissues of Lucifer Yellow and certain labelled molecules of up to 20 kDa molecular weight. This observation was made using a variety of fluorescent membrane-impermeant compounds injected into the skin before the application of cercariae. This unexpected phenomenon was investigated further by transforming cercariae in vitro in the presence of the membrane-impermeant compounds and examining the distribution by microscopy. In schistosomula derived from this procedure, the nephridiopore and surface membrane were labelled while the pre- and post-acetabular glands were not labelled. The region associated with the oesophagus within the pharyngeal muscle clearly contained the fluorescent molecules, as did the region adjacent to the excretory tubules and the germinal mass. We used cercariae stained with carmine to aid identification of regions labelled with Lucifer Yellow. Although the mechanism of this influx is unclear, the observation is significant. From it, we can suggest an hypothesis that, during skin penetration, exposure of internal tissues of the parasite to external macromolecules represents a novel host-parasite interface.

Factors influencing eating a varied diet in old age

OBJECTIVE:
To investigate the influences of resources and food-related goals on the variety of food choice among older people.
DESIGN:
A questionnaire-based survey in eight European countries: Poland, Portugal, United Kingdom, Germany, Sweden, Denmark, Italy and Spain.
SUBJECTS:
Participants (n 3200) were above 65 years of age and living in their own homes. The samples were quota samples, eight groups of fifty in each country, based on gender, age and living circumstances, reflecting the diversity of each of the national populations based on education, income and urbanization of living environment.
RESULTS:
Hierarchical multiple regression analysis showed that income, health status, access to a car and living arrangement affected the level of dietary variety. The perceived level of different food-related resources impacted the consumption of a varied diet over and above actual resource levels. Food-related goals contributed to variety of food intake that was not accounted for by the amount of material resources possessed or the social and other resources perceived to be possessed.
CONCLUSIONS:
Older people's variety of food intake depended on material resources (e.g. monthly income, access to a car, living arrangement, physical and mental health). However, in addition to these variables, the way older people perceived other resources, such as their level of appetite, their food knowledge, their perception of the distance to the shops, access to high-quality products, having better kitchen facilities, access to good service providers and support from friends and neighbours, all contributed to how varied a diet they ate.

Effect of plane of nutrition of 1-and 2-year-old ewes in early and mid-pregnancy on ewe reproduction and offspring performance up to weaning

The objective of the present study was to determine the effect of plane of nutrition in early pregnancy (EP) and mid-pregnancy (W), on the productive performance of 1- and 2-year-old ewes and their offspring. Over 2 successive years, between days 0 and 39 after synchronized mating (EP), 1- (n=117) and 2- (n=52) year-old ewes were allowed 60% (low, L-EP), 100% (medium, M-EP) or 200% (high, H-EP) of requirements for maintenance (M). Between days 40 and 90 (MP), 1-year-old ewes were allowed 140% (M-MP) or 200% (H-MP), while 2-year-old ewes were allowed 80% (M-MP) or 140% (H-MP) of their M requirement. After day 90, all ewes were fed to meet requirements for late pregnancy. Increasing the plane of nutrition between days 0 and 39 resulted in increases in live weight (LW) (PM-EP>LEP), differences that in 1-year-old ewes were sustained to lambing (P0.05). These ewes exhibited more positive maternal behaviours (e.g. increased grooming frequency and duration, P

Nutritonal status of adult ewes during early and mid-pregnancy. 1. Effects of plane of nutrition on ewe reproduction and offspring performance to weaning

The objective of this study was to determine the effects of plane of nutrition during early and mid-pregnancy on the performance of mature ewes and their offspring. From day 0 to day 39 post mating (early pregnancy, EP), 82 multiparous ewes were fed to provide either 60% (low, L), 100% (medium, M) or 200% (high, H) of predicted metabolisable energy (ME) requirements for maintenance, following a synchronised mating. From day 40 to day 90 (mid-pregnancy, MP), ewes were provided with either 80% (M) or 140% (H) of ME requirements. After 90 days of gestation, all ewes were fed to meet requirements for late pregnancy. During EP, mean live weight (LW) and body condition score (BCS) change of ewes were -6.3, -0.8 and +6.0kg and -0.02, +0.10 and +0.22 units in the L-, M- and H-EP treatments, respectively. During MP, mean LW and BCS change were -0.8 and +4.9kg and -0.09 and +0.09 units in the M- and H-MP treatments, respectively (P 0. 05) on conception rate, although there tended to be an inverse relationship (P = 0.085) between plane of nutrition in EP and plasma progesterone concentrations at day 42 of gestation. EP nutrition influenced foetal development with lambs from ewes offered diet L-EP being smaller (P

Nutritional status of adult ewes during early and mid-pregnancy. 2. Effects of supplementation with selenised yeast on ewe reproduction and offspring performance to weaning

The objective of this study was to determine the effects of selenium (Se) supplementation of mature ewes in the period from day - 14 to day 90 post mating on Se status, productivity and viability of ewes and their offspring. Multiparous crossbred ewes (n = 82) were randomly assigned to receive a standard dried grass-based diet (control) or dried grass diet supplemented with 1 g of selenised yeast (Selplex (R)), providing 0.5 mg Se per ewe per day. After day 90 post mating, all ewes were offered grass-based diets supplemented with a standard multivitamin and mineral mix, up to lambing. Ewes that were fed additional Se had increased (P 0,05). Supplemented ewes weaned lambs on average 2 kg heavier than control ewes, due to the higher (P

A survey of formalisms for representing and reasoning with scientific knowledge

With the rapid growth in the quantity and complexity of scientific knowledge available for scientists, and allied professionals, the problems associated with harnessing this knowledge are well recognized. Some of these problems are a result of the uncertainties and inconsistencies that arise in this knowledge. Other problems arise from heterogeneous and informal formats for this knowledge. To address these problems, developments in the application of knowledge representation and reasoning technologies can allow scientific knowledge to be captured in logic-based formalisms. Using such formalisms, we can undertake reasoning with the uncertainty and inconsistency to allow automated techniques to be used for querying and combining of scientific knowledge. Furthermore, by harnessing background knowledge, the querying and combining tasks can be carried out more intelligently. In this paper, we review some of the significant proposals for formalisms for representing and reasoning with scientific knowledge.

The cost-effectiveness of the SPHERE intervention for the secondary prevention of coronary heart disease

Objectives: The Secondary Prevention of Heart disEase in geneRal practicE (SPHERE) trial has recently reported. This study examines the cost-effectiveness of the SPHERE intervention in both healthcare systems on the island of Ireland. Methods: Incremental cost-effectiveness analysis. A probabilistic model was developed to combine within-trial and beyond-trial impacts of treatment to estimate the lifetime costs and benefits of two secondary prevention strategies: Intervention - tailored practice and patient care plans; and Control - standardized usual care. Results: The intervention strategy resulted in mean cost savings per patient of 512.77 (95 percent confidence interval [CI], 1086.46-91.98) and an increase in mean quality-adjusted life-years (QALYs) per patient of 0.0051 (95 percent CI, 0.0101-0.0200), when compared with the control strategy. The probability of the intervention being cost-effective was 94 percent if decision makers are willing to pay €45,000 per additional QALY. Conclusions: Decision makers in both settings must determine whether the level of evidence presented is sufficient to justify the adoption of the SPHERE intervention in clinical practice. Copyright © Cambridge University Press 2010.

Red meat from animals offered a grass diet increases plasma and platelet n-3 PUFA in healthy consumers

Red meat from grass-fed animals, compared with concentrate-fed animals, contains increased concentrations of long-chain (LC) n-3 PUPA. However, the effects of red meat consumption from grass-fed animals on consumer blood concentrations of LC n-3 PUFA are unknown. The aim of the present study was to compare the effects on plasma and platelet LC n-3 PUFA status of consuming red meat produced from either grass-fed animals or concentrate-fed animals. A randomised, double-blinded, dietary intervention study was carried out for 4 weeks on healthy subjects who replaced their habitual red meat intake with three portions per week of red meat (beef and lamb) from animals offered a finishing diet of either grass or concentrate (n 20 consumers). Plasma and platelet fatty acid composition, dietary intake, blood pressure, and serum lipids and lipoproteins were analysed at baseline and post-intervention. Dietary intakes of total n-3 PUFA, as well as plasma and platelet concentrations of LC n-3 PUFA, were significantly higher in those subjects who consumed red meat from grass-fed animals compared with those who consumed red meat from concentrate-fed animals (P<0.05). No significant differences in concentrations of serum cholesterol, TAG or blood pressure were observed between groups. Consuming red meat from grass-fed animals compared with concentrate-fed animals as part of the habitual diet can significantly increase consumer plasma and platelet LC n-3 PUFA status. As a result, red meat from grass-fed animals may contribute to dietary intakes of LC n-3 PUFA in populations where red meat is habitually consumed.

Biodiversity among mussels: separating the influence of sizes of mussels from the ages of patches

The role of habitat structure in controlling the composition of assemblages has often been studied, but is rarely manipulated so that it is distinguishable from other factors. Differences in habitat structure as determined by differences in mussel size structure may affect the diversity of assemblages associated with mussel beds. Previous studies examining the effect of the size of individual mussels in a patch on the diversity of associated macro-faunal assemblages confounded the age of the patch with the size of the mussels. We manipulated the age of mussel patches and the size of the mussels within them to test experimentally whether the size of mussels influenced the structure of associated assemblages. At one of the two locations considered, the structure of macro-faunal assemblages in patches of larger mussels differed significantly from those in patches of the same age composed of smaller mussels. At this location, the size of mussels did not affect species richness but the abundance and proportion of organisms present differed depending on the size of the mussels. Here patches of larger mussels contained greater numbers of Nematodes and Oligochaetes and a lower abundance of taxa, such as faera forsmani and Lepidonotus clava. We also found that invertebrate assemblages in general differed between the two locations. The effect of the size structure of mussels, however, varied spatially demonstrating that the effect of habitat structure on the diversity of associated assemblages is context dependent.

UK Food Standards Agency Workshop Report: Diet and Immune Function

The UK Food Standards Agency convened a workshop on 13 May 2009 to discuss recently completed research on diet and immune function. The objective of the workshop was to review this research and to establish priorities for future research. Several of the trials presented at the workshop showed some effect of nutritional interventions (e.g. vitamin D, Zn, Se) on immune parameters. One trial found that increased fruit and vegetable intake may improve the antibody response to pneumococcal vaccination in older people. The workshop highlighted the need to further clarify the potential public health relevance of observed nutrition-related changes in immune function, e.g. susceptibility to infections and infectious morbidity.