A model to assess the efficacy of vaccines for control of liver fluke infection

Fasciola hepatica, common liver fluke, infects cattle and sheep causing disease and production losses costing approximately $3billion annually. Current control relies on drugs designed to kill the parasite. However, resistance is evident worldwide and widespread in some areas. Work towards a vaccine has identified several antigens of F. hepatica that show partial efficacy in terms of reducing worm burden and egg output. A critical question is what level of efficacy is required for such a vaccine to be useful? We have created the first mathematical model to assess the effectiveness of liver fluke vaccines under simulated field conditions. The model describes development of fluke within a group of animals and includes heterogeneity in host susceptibility, seasonal exposure to metacercariae and seasonal changes in temperature affecting metacercarial survival. Our analysis suggests that the potential vaccine candidates could reduce total fluke burden and egg output by up to 43% and 99%, respectively, on average under field conditions. It also suggests that for a vaccine to be effective, it must protect at least 90% of animals for the whole season. In conclusion, novel, partial, vaccines could contribute substantially towards fasciolosis control, reducing usage of anthelmintics and thus delaying the spread of anthelmintic resistance

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/&#43;) littermates and wild-type (&#43;/&#43;) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/&#43; mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a

Using Parahydrogen Induced Polarization to Study Steps in the Hydroformylation Reaction.

A range of iridium complexes, Ir(η3-C3H5)(CO)(PR2R’)2 (1a-1e) [where 1a, PR2R’ = PPh3, 1b P(p-tol)3, 1c PMePh2, 1d PMe2Ph and 1e PMe3] were synthesized and their reactivity as stoichiometric hydroformylation precursors studied. Para-hydrogen assisted NMR spectroscopy detected the following intermediates: Ir(H)2(η3-C3H5)(CO)(PR2R’) (2a-e), Ir(H)2(η1-C3H5)(CO)(PR2R’)2 (4d-e), Ir(H)2(η1-C3H5)(CO)2(PR2R’) (10a-e), Ir(H)2(CO-C3H5)(CO)2(PR2R’) (11a-c), Ir(H)2(CO-C3H7)(CO)2(PR2R’) (12a-c) and Ir(H)2(CO-C3H5)(CO)(PR2R’)2 (13d-e). Some of these species exist as two geometric isomers according to their multinuclear NMR characteristics. The NMR studies suggest a role for the following 16 electron species in these reactions: Ir(η3-C3H5)(CO)(PR2R’), Ir(η1-C3H5)(CO)(PR2R’)2, Ir(η1-C3H5)(CO)2(PR2R’), Ir(CO-C3H5)(CO)2(PR2R’), Ir(CO-C3H7)(CO)2(PR2R’) and Ir(CO-C3H5)(CO)(PR2R’)2. Their role is linked to several 18 electron species in order to confirm the route by which hydroformylation and hydrogenation proceeds