Validating an empiric sulfadiazine–trimethoprim dosage regimen for treatment of Escherichia coli and Staphylococcus delphini infections in mink (Neovison vison)

Antimicrobial agents are used extensively off‐label in mink, as almost no agents are registered for this animal species. Pharmacokinetic (PK) and pharmacodynamic (PD) data are required to determine antimicrobial dosages specifically targeting mink bacterial pathogens. The aims of this study were to assess, in a PKPD framework, the empirical dosage regimen for a combination of trimethoprim (TMP) and sulfadiazine (SDZ) in mink, and secondarily to produce data for future setting of clinical breakpoints. TMP and SDZ PK parameters were obtained experimentally in 22 minks following IV or oral administration of TMP/SDZ (30 mg/kg, i.e. 5 mg/kg TMP and 25 mg/kg SDZ). fAUC/MIC with a target value of 24 hr was selected as the PKPD index predictive of TMP/SDZ efficacy. Using a modeling approach, PKPD cutoffs for TMP and SDZ were determined as 0.062 and 16 mg/L, respectively. By incorporating an anticipated potentiation effect of SDZ on TMP against Escherichia coli and Staphylococcus delphini, the PKPD cutoff of TMP was revised to 0.312 mg/L, which is above the tentative epidemiological cutoffs (TECOFF) for these species. The current empirical TMP/SDZ dosage regimen (30 mg/kg, PO, once daily) therefore appears adequate for treatment of wild‐type E. coli and S. delphini infections in mink.     

Anthropogenic landscapes support fewer rare bee species

Landscape Ecology - The response of rare species to human land use is poorly known because rarity is difficult to study; however, it is also important because rare species compose most of...     

Effect of feeding intensity and milking system on nutritionally relevant milk components in dairy farming systems in the North East of England

There is increasing concern that the intensification of dairy production reduces the concentrations of nutritionally desirable compounds in milk. This study therefore compared important quality parameters (protein and fatty acid profiles; α-tocopherol and carotenoid concentrations) in milk from four dairy systems with contrasting production intensities (in terms of feeding regimens and milking systems). The concentrations of several nutritionally desirable compounds (β-lactoglobulin, omega-3 fatty acids, omega-3/omega-6 ratio, conjugated linoleic acid c9t11, and/or carotenoids) decreased with increasing feeding intensity (organic outdoor ≥ conventional outdoor ≥ conventional indoors). Milking system intensification (use of robotic milking parlors) had a more limited effect on milk composition, but increased mastitis incidence. Multivariate analyses indicated that differences in milk quality were mainly linked to contrasting feeding regimens and that milking system and breed choice also contributed to differences in milk composition between production systems.     

Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation

Glycogen synthase kinase 3beta (GSK3beta) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3beta activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3beta by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3beta substrate beta-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3beta by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of beta-catenin. p38 MAPK-mediated phosphorylation of GSK3beta occurs primarily in the brain and thymocytes. Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues.     

Effectiveness of capillary electrophoresis fluoroimmunoassay of blood PrpSc for evaluation of scrapie pathogenesis in sheep.

Management of prion diseases in livestock would benefit greatly from availability of a validated blood test. A promising immunocapillary electrophoresis technique (also known as capillary electrophoresis fluoroimmunoassay) to detect abnormal prion protein in blood from live sheep is evaluated here. Capillary electrophoresis fluoroimmunoassay was applied to analysis of extracted blood from scrapie-exposed sheep (n = 87; 347 samples) at various stages of incubation, and to control sheep (n = 194; 489 samples). Overall, test values for the control and test populations were not significantly different, and a similar proportion of control (7%) and test (10%) sheep were classified as positive. Over 2-3 month intervals from birth until clinical disease, test specificity and sensitivity ranged from 66.7% to 100% and 0% to 66.7%, respectively, indicating poor diagnostic performance at all stages of pathogenesis. In routine application, in its present form, the capillary electrophoresis fluoroimmunoassay procedure proved to be insufficiently robust for use as a blood test for scrapie diagnosis.