Gene expression patterns in the ventral tegmental area relate to oestrus behaviour in high-producing dairy cows

Reduced oestrus behaviour expression or its absence (silent oestrus) results in subfertility in high-producing dairy cows. Insight into the genomic regulation of oestrus behaviour is likely to help alleviate reproduction problems. Here, gene expression was recorded in the ventral tegmental area (VTA) of high milk production dairy cows differing in the degree of showing oestrus behaviour (H - highly expressing versus L - lowly expressing), which was then analysed. Genes regulating cell morphology and adhesion or coding for immunoglobulin G (IgG) chains were differentially expressed in VTA between cows around day 0 and 12 of the oestrus cycle, but only in cows that earlier in life tended to show high levels of oestrus behaviour (H0 versus H12). The comparisons between H and L groups of cows also revealed differential expression of several genes (e.g. those of the IgG family or encoding for pro-melanin-concentrating hormone). However, any significant changes in VTA genes expression were detected in the comparison of L0 versus L12 cows. Altogether, the genes expression profile in VTA of cows highly expressing oestrus behaviour changes together with phases of the oestrus cycle, while in case of cows expressing oestrus behaviour lowly it remains stable. This supports the existence of genomic regulation by centrally expressed genes on the expression of oestrus behaviour in dairy cows.     

Metronidazole pharmacokinetics during rapid growth in turkeys – relation to changes in haemodynamics and drug metabolism

Whereas interspecies variation in pharmacokinetics is a commonly investigated issue, variations in drug kinetics within a species are less documented. The aim of the study was to assess the influence of age‐related changes in haemodynamics on the pharmacokinetics of metronidazole (MTZ) and its hydroxy metabolite (MTZ‐OH) in turkeys. MTZ was administered intravenously and orally at a dose of 25 mg/kg. Plasma drug and metabolite concentrations were assessed by high‐performance liquid chromatography, and pharmacokinetic parameters were calculated by noncompartmental analysis. Haemodynamic parameters (heart rate, stroke volume, cardiac output) were assessed by echocardiography and extraction ratio for MTZ was calculated based on total body clearance (Cl_B). Between the 5th and 15th week of age, Cl_B of MTZ decreased from 3.6 to 1.2 mL/min/kg causing a twofold increase in the mean residence time (MRT) and elimination half‐life (T_1/2el). The MTZ‐OH production decreased threefold and its MRT and T_1/2el increased. Although heart rate significantly decreased with age, cardiac output increased. Extraction ratio was low in all age groups. It is concluded that significant age‐dependent decrease in Cl_B of MTZ in turkeys resulted from decreased perfusion of the clearing organs and their reduced metabolic capacity. This phenomenon is probably species specific and may apply to other therapeutic agents.     

An unusual type of malathion-carboxylesterase in a Japanese strain of house fly

It had been reported that a Japanese multiple-resistant strain of house fly, Hirokawa, had a high malathion-carboxylesterase activity as well as a normal level of esterase activity to α-naphthylacetate (NA). This is different from the situation in several other malathion-resistant strains, where high malathion-carboxylesterase activity goes together with a low level of activity to α-NA. This had been explained by the so-called “mutant ali-esterase theory,” which assumed that the opposite changes in activity to malathion and α-NA were the result of one and the same change in an ali-esterase. In the Hirokawa strain the esterase degrading malathion seems to be responsible for about 64% of the activity to α-NA. This was concluded since the two activities were equally sensitive to denaturation and to two organophosphorus inhibitors. Moreover activity of malathion was inhibited by α-NA, and that of α-NA by malathion. Most of the latter activity was inhibited competitively. Inhibition of activity to malathion was lower, however, than to be expected on the basis of competitive mutual inhibition. This case of resistance to malathion therefore seems to involve a different kind of “mutant ali-esterase” than in other strains. Increased hydrolysis of the insecticide seems to be achieved without loss of activity to α-NA, although K_m is different. The strain further showed an unusually high β-NA hydrolysis and malaoxon-carboxylesterase activity (about 3- and 200-fold, respectively, that of another malathion-resistant strain G).