Animal grazing selectivity and plant chemistry issues impact on the potential of Rhagodia preissii as an anthelmintic shrub.

Rhagodia preissii had shown significant in vitro anthelmintic activity in a previous study, we examined the effect of including this shrub in the diet of sheep infected with Trichostrongylus colubriformis. Worm-infected merino wethers were grazed for 7 weeks on either R. preissii or annual pasture, and faecal egg counts (FECs) were conducted weekly. Plant material was collected weekly from eaten and uneaten plants, and analysed for levels of plant secondary metabolites (tannins, oxalates, saponins) and in vitro anthelmintic activity. While mean FECs were consistently lower in sheep grazing R. preissii compared to pasture (reductions of 20-74%), the differences were not significant. There was no relationship between grazing preference (eaten or uneaten) and in vitro anthelmintic activity of plant extracts. The levels of saponins and oxalates did not correlate with grazing preference or in vitro anthelmintic activity, while tannins were not responsible for the anthelmintic activity. While the identity of the grazing deterrent and in vitro anthelmintic compounds remain unknown, the presence of plants which were both highly preferred by the sheep and showed in vitro anthelmintic activity indicates a potential to develop the species as an anthelmintic shrub through selection of shrub populations dominated by such plants.

Iron content of eggs from hens given diets containing organic forms of iron, serine and methyl group donors, or phytoestogens.

1. This investigation included three experiments to determine whether the iron content of egg yolks could be enriched by supplementation of the laying diet with iron bound to organic compounds (Experiment 1), serine and methyl group donors methionine and choline (Experiment 2) or phytoestrogens (Experiment 3). 2. Hens at 34, 54 and 56 weeks of age were given experimental diets for 6, 4 and 4 weeks, respectively, in Experiments 1-3. Yolks from eggs laid over three successive days in the final week of feeding were pooled for each hen for analysis of iron by inductively coupled plasma mass spectrometry. 3. Iron concentration in egg yolk averaged 68-70, 66-71 and 62-69 microg/g in the respective experiments. 4. The addition of bloodmeal (1.22 mg Fe/egg) or phytoestrogens (1.25 mg Fe/egg) increased the total iron content of yolks by over 15% compared with the control diet (1.10 mg Fe/egg), and although this increase was not statistically significant it suggests that the iron content of eggs could be sufficiently manipulated to justify a nutritional claim of iron enrichment.

Exploring the anthelmintic properties of Australian native shrubs with respect to their potential role in livestock grazing systems.

We measured in vitro anthelmintic activity in extracts from 85 species of Australian native shrub, with a view to identifying species able to provide a degree of worm control in grazing systems. Approximately 40% of the species showed significant activity in inhibiting development of Haemonchus contortus larvae. The most active extracts showed IC50 values of 60-300 microg/ml. Pre-incubation with polyvinylpolypyrrolidine removed the activity from some extracts, implicating tannins as the bioactive agent, while in other cases the pre-incubation had no effect, indicating the presence of other anthelmintic compounds. Plant reproductive maturity (onset of flowering or fruiting) was associated with increasing anthelmintic activity in some species. Variability was observed between plants of the same species growing in different environments, while variation between individual plants of the same species within a single field suggests the existence of distinct chemotypes. Significant activity against adult H. contortus worms in vitro was also demonstrated in a limited number of extracts tested against this life stage. Our study indicates that there is potential for Australian native shrubs to play an anthelmintic role in grazing systems, and highlights some plant biology factors which will need to be considered in order to maximize any anthelmintic effects.

Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease.

During a program to investigate the biochemical basis of side effects associated with the antimalarial drug mefloquine, the authors made the unexpected discovery that the (-)-(R,S)-enantiomer of the drug is a potent adenosine A2A receptor antagonist. Although the compound was ineffective in in vivo animal models of central adenosine receptor function, it provided a unique nonxanthine adenosine A2A receptor antagonist lead structure and encouraged the initiation of a medicinal chemistry program to develop novel adenosine A2A antagonists for the management of Parkinson's disease (PD). The authors have synthesized and screened more than 2,000 chemically diverse and novel adenosine A(2A antagonists. Early examples from two distinct chemical series are the thieno[3,2-dy]pyrimidine VER-6623 and the purine compounds VER-6947 and VER-7835, which have high affinity at adenosine A2A receptors (K(i) values 1.4, 1.1, and 1.7 nmol/L, respectively) and act as competitive antagonists. In particular, VER-6947 and VER-7835 demonstrate potent in vivo activity reversing the locomotor deficit caused by the D2 receptor antagonist haloperidol, with minimum effective doses comparable with that of KW6002 (0.3 to 1 mg/kg). In conclusion, the authors have discovered potent, selective, and in vivo active nonxanthine adenosine A2A antagonists that have considerable promise as a new therapy for PD.

Altered secretion of LH does not explain seasonal effects on early pregnancy in gilts.

This work was undertaken to study the effects of energy intake and gut fill on LH secretion in the early pregnant gilt to investigate the role of the hypothalamo-pituitary-gonadal axis in the seasonal disruption of pregnancy. Four groups of mated gilts (N = 23 in total) were individually housed and fed four different energy levels (23, 46, 47 and 55 megajoules digestible energy per day, MJ DE day-1) for two weeks after mating during the season identified as a period of increased rate of early pregnancy failures from January till April (summer-autumn). The energy content of base feed (13 MJ kg-1) was increased by means of adding a fat supplement (soybean oil) to the feed of two groups of gilts, while the other two groups were given different levels of the basic feed. The groups gained weight and backfat according to energy intake levels during the two-week period. Frequent blood samples (15-min interval) collected on day 14 revealed a significant treatment effect on LH pulse amplitude: the group on the highest energy intake level (55 MJ DE day-1) had higher LH pulse amplitude compared with the other groups (1.01 +/- 0.04, 0.74 +/- 0.04, 0.72 +/- 0.08 and 0.66 +/- 0.05 ng ml-1 in the descending order of energy intake, P < 0.01). There was no effect of energy intake on LH pulse frequency, mean level, area under the curve or mean nadir (P > 0.10). Plasma insulin concentrations tended to increase (P < 0.08) in each group with time after feeding, but no significant differences between the treatment groups were found. Plasma free fatty acid (FFA) concentrations were decreased 1 h after feeding (P < 0.05) in all but the group on 55 MJ DE day-1. This group also had higher postprandial FFA concentrations in comparison with other groups (P < 0.05). In conclusion, these results show that energy density of feed and energy intake have little effect on LH secretion in the early pregnant gilt. Protective effect of high feeding level against seasonal disruption of pregnancy appears to be mediated by mechanisms other than an alteration in LH secretion.

The importance of transmethylation reactions to methionine metabolism in sheep: effects of supplementation with creatine and choline.

The influence of administering the methylated products choline and creatine on methionine irreversible-loss rate (ILR) and recycling from homocysteine has been investigated in sheep fed close to energy and N equilibrium. Two methods to estimate methionine recycling were compared. The first involved [U-13C]methionine infused as part of a labelled amino acid mixture obtained from hydrolysed algal protein. In this approach the isotope dilution of methionine with all five C atoms labelled (m + 5) will represent the ILR which does not recycle through homocysteine, while that which includes molecules with C-1-C-4 labelled will allow for loss of the labelled methyl (5)-C atom and replacement by an unlabelled moiety in the remethylation of homocysteine. The second method involved a combined infusion of [1-13C]- and [S-methyl-2H3]methionine. These two approaches gave similar data for methionine ILR which does not include label recycled to the amino acid from homocysteine but differed for recycled methionine fluxes. Consequently the two procedures differed in the calculated extent of homocysteine methylation under control conditions (6 v. 28%). These extents of remethylation are within the range observed for the fed human subject, despite the fact that fewer dietary methyl groups are available for the ruminant. Using combined data from the infusions, significant depression of methionine recycling occurred in blood (P < 0.05), with a similar trend for plasma (P = 0.077), when choline plus creatine were infused. Wool growth, assessed by intradermal injection of [35S]cysteine, was not altered by supplementation with the methylated products. From changes in the label pattern of free methionine in aortal, hepatic portal and hepatic venous blood during U-13C-labelled algal hydrolysate infusion, the major sites of homocysteine remethylation appear to be the portal-drained viscera and the liver. This was confirmed by analysis of free methionine enrichments in various tissues following dual infusion of [1-13C]- and [S-methyl-2H3]methionine, with the greatest activities occurring in rumen, jejunum and liver. Of the non-splanchnic tissues examined, only kidney exhibited substantial methionine cycling; none was detected in muscle, heart, lung and skin. The implications of methyl group provision under net production conditions are discussed.