Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation

Pelligand, L., King, J. N., Toutain, P. L., Elliott, J., Lees, P. Pharmacokinetic/pharmacodynamic modelling of robenacoxib in a feline tissue cage model of inflammation. J. vet. Pharmacol. Therap.  35 , 19–32. Robenacoxib is a novel nonsteroidal anti‐inflammatory drug developed for use in cats. It is a highly selective COX‐2 inhibitor. Results from previous feline studies showed that, despite a short half‐life in blood, the effect of robenacoxib persisted for 24 h in clinical studies. A tissue cage model of acute inflammation was used to determine robenacoxib’s pharmacokinetics and its ex vivo and in vivo selectivity for COX‐1 and COX‐2 using serum TxB₂ and exudate PGE₂ as surrogate markers for enzyme activity, respectively. After intravenous, subcutaneous and oral administration (2 mg/kg), the clearance of robenacoxib from blood was rapid (0.54–0.71 L·h/kg). The mean residence time (MRT) in blood was short (0.4, 1.9 and 3.3 h after intravenous, subcutaneous and oral administration, respectively), but in exudate MRT was approximately 24 h regardless of the route of administration. Robenacoxib inhibition of COX‐1 in blood was transient, occurring only at high concentrations, but inhibition of COX‐2 in exudate persisted to 24 h. The potency ratio (IC₅₀ COX‐1: IC₅₀ COX‐2) was 171:1, and slopes of the concentration–effect relationship were 1.36 and 1.12 for COX‐1 and COX‐2, respectively. These data highlight the enzymatic selectivity and inflamed tissue selectivity of robenacoxib and support the current recommendation of once‐daily administration.     

Employing a Monte Carlo algorithm in expectation maximization restricted maximum likelihood estimation of the linear mixed model

Multiple‐trait and random regression models have multiplied the number of equations needed for the estimation of variance components. To avoid inversion or decomposition of a large coefficient matrix, we propose estimation of variance components by Monte Carlo expectation maximization restricted maximum likelihood (MC EM REML) for multiple‐trait linear mixed models. Implementation is based on full‐model sampling for calculating the prediction error variances required for EM REML. Performance of the analytical and the MC EM REML algorithm was compared using a simulated and a field data set. For field data, results from both algorithms corresponded well even with one MC sample within an MC EM REML round. The magnitude of the standard errors of estimated prediction error variances depended on the formula used to calculate them and on the MC sample size within an MC EM REML round. Sampling variation in MC EM REML did not impair the convergence behaviour of the solutions compared with analytical EM REML analysis. A convergence criterion that takes into account the sampling variation was developed to monitor convergence for the MC EM REML algorithm. For the field data set, MC EM REML proved far superior to analytical EM REML both in computing time and in memory need.     

Successful reduction of a monozygotic equine twin pregnancy via transabdominal ultrasound‐guided cardiac puncture

In horses, twin pregnancy is pathological and represents a potentially life‐threatening condition to the mare and foal. Twinning occurs in approximately 2% of pregnancies. Of these, the majority of cases are dizygotic twins, resulting from 2 ovulations and monozygotic twins are rare. A 12‐year‐old Quarter Horse mare was presented for breeding management with shipped cooled semen and embryo transfer. Seven days post ovulation, a single late morula/early blastocyst was recovered and transferred immediately to a recipient mare. Thirty‐six days after transfer, transrectal ultrasound examination revealed the presence of 2 embryos. A transcutaneous reduction of one of the fetuses was performed successfully at 128 days of gestation. This report is the first to describe a successful reduction of monozygotic twins by transcutaneous ultrasound‐guided cardiac puncture.     

Horses' behavior and heart rate in a preference test for shorter and longer riding bouts

A Y-maze preference test was used to investigate whether horses prefer a shorter riding treatment over a longer riding treatment. In a pilot study (n = 4 horses), the maze was positioned with the 2 arms each pointing toward one of the short sides of the indoor arena, and in the main study (n = 14), the maze was rotated by 90°. Horses were 11 ± 4.4 years old and ridden regularly for at least 5 times/wk. They were conditioned to associate 1 exit of the maze with 1 lap of riding (R1), covering a distance of approximately 40 m at the walk or trot according to a predetermined schedule, and the other exit with 2 such laps (R2). Immediately afterward, riders dismounted, horses were led into the maze, and horses were let loose to make their choice in the maze. After exiting the maze, the rider mounted again and rode according to the chosen treatment. This procedure was repeated on the same day until statistical significance (P < 0.05) of preference was reached or up to a maximum of 35 trials. In addition, behavioral observations and heart rates were recorded. In the pilot study, all horses, regardless of the associated treatment, chose the left arm, which, unfortunately, pointed toward the arena's exit door. If horses were not caught immediately after exiting the maze (n = 5 occasions), they walked or trotted straight to the door. In the main study, 4 horses significantly preferred R1, 2 horses significantly preferred R2, and 8 horses had no significant preference. Heart rates were significantly (P < 0.05) higher during R2 (87.4 ± 2.6 bpm) than during R1 (79.5 ± 2.4 bpm). Except for tail swishing, no significant differences were found for the frequency of occurrence of behavior patterns between R1 and R2. Over the course of repeated trials, some horses became increasingly reluctant to enter and walk through the maze, and most showed increasing resistance to being remounted (e.g., sidestepping). Overall, the experimental setup did not seem to be appropriate to answer the research question. It is likely that the repeated mounting and dismounting caused discomfort or confused many of the horses to an extent that they did not actively select a treatment but rather searched for ways to evade further mounting (and riding). In conclusion, horses did not show a clear preference for either shorter or longer riding bouts, but their behavioral reactions indicate that they perceived mounting as uncomfortable and that their motivation to rejoin their herd-mates and/or to obtain feed in the barn was greater than their motivation to being ridden at all. Nevertheless, pronounced individual differences also seem to exist, with some horses showing little aversion to, and perhaps enjoyment of, being ridden, whereas others clearly preferring not to be ridden.     

基因组学和生理学在家禽福利育种中的应用

<正>1最近十年的欧洲家禽福利经验在欧洲,农场动物福利是一个主要的问题。近年来人们对动物福利法规及其相关方面的科学研究日益增多。由于家禽福利状况堪忧,导致标准化家禽生产的话题被关注。选育的影响经常遭到质疑。事实上,在进行商业选育的最初,很少考虑家禽的适应能力,因此出现了某些性状的退化。但是现在,对福利相关性状和遗传选育的越来越关注,     

Effect of restricted suckling on milk yield,milk composition and udder health in cows and behaviour and weight gain in calves,in dual-purpose cattle in the tropics

The study was conducted to evaluate the effects of restricted suckling (RS) in dual-purpose cows and calves compared to artificial rearing (AR). Twelve Holstein-Zebu cows with calves were assigned to each treatment. Cows were milked once daily in the morning with calves present to stimulate milk let-down. RS calves suckled 30 min after milking and 30 min in the afternoon, whereas AR calves were milk-fed from nipple bottles. The daily saleable milk yield was higher in RS than in AR cows (p < 0.01; 7.44 vs 6.50 kg/day), whereas RS cows had lower milk-fat content (p < 0.001). AR cows had higher California Mastitis Test scores (p < 0.001) and lower lactose content (p < 0.001) compared to RS cows, which indicates an improved udder health in RS cows. AR calves displayed more ‘cross-suck’ during suckling/milk feeding (p < 0.001) and during observations of general behaviour (p < 0.05), and more ‘lick and sniff interior’ during milking (p < 0.05) and suckling/milk feeding (p < 0.01), compared to RS calves. During observations of general behaviour the RS calves were more often observed to ‘walk’ (p < 0.01) and ‘lick self’ (p < 0.05) and less frequently to ‘eat concentrate’ (p < 0.05) than AR calves. Results support the hypothesis that RS increases milk yield, influences milk composition and improves udder health in cows, and decreases abnormal sucking in calves.     

Effects of the Administration of Lactobacilli,Maltodextrins and Fructooligosaccharides upon the Adhesion of <Emphasis Type="Italic">E. coli</Emphasis> O8:K88 to the Intestinal Mucosa and Organic Acid Levels in the Gut Contents of Piglets

The influence of the administration of Lactobacillus plantarum, maltodextrin Maldex 150 and Raftifeed IPX fructooligosaccharides on the inhibition of adhesion of E. coli O8:K88 to the mucosa of the jejunum, ileum and colon as well as on the organic acid levels was investigated in 33 conventional piglets. The counts of E. coli K88 adhering to the jejunal mucosa were significantly decreased (p < 0.05) in Lact. plantarum + Maldex 150 and Lact. plantarum + Maldex 150 + Raftifeed IPX groups. The counts of E. coli K88 adhering to the colonic mucosa of Lact. plantarum + Maldex 150 + Raftifeed IPX and Lact. plantarum + Raftifeed IPX groups were significantly lower (p < 0.05) than in Lact. plantarum and Lact. plantarum + Maldex 150 animals. The acetic acid levels in the ileum and colon of the Lact. plantarum + Maldex 150 + Raftifeed IPX group and Lact. plantarum + Raftifeed IPX group were significantly higher (p < 0.05) than in the Lact. plantarum and Lact. plantarum + Maldex 150 group. The combination of Lact. plantarum, maltodextrin Maldex 150 and Raftifeed IPX proved to be the most effective one to inhibit the counts of E. coli O8:K88 adhering to the intestinal mucosa of the jejunum and colon of conventional piglets.