Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs

Florfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC₅₀ (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC_24 hr, AUC_0–∞, T_max, T_1/2, C_max, CL_b, and K_e were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr^?1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr^?1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.     

MC1R c.310G>‐ and c.871G > A determine the coat color of Kumamoto sub‐breed of Japanese Brown cattle

Coat color is one of the important factors characterizing breeds for domestic animals. Melanocortin 1 receptor (MC1R) is a representative responsible gene for this phenotype. Two single‐nucleotide polymorphisms (SNPs) in bovine MC1R gene, c.296T > C and c.310G>‐, have been well characterized, but these SNPs are not enough to explain cattle coat color. As far as we know, MC1R genotypes of Kumamoto sub‐breed of Japanese Brown cattle have not been analyzed. In the current study, genotyping for c.296T > C and c.310G>‐ was performed to elucidate the role of MC1R in determining the coat color of this sub‐breed. As a result, most animals were e/e genotype, suggesting the coat color of this sub‐breed is derived from the e allele of MC1R gene. However, we found six animals with E/e genotype, which coat color would be black theoretically. Subsequently, sequence comparison was performed with these animals to identify other polymorphisms affecting coat color, elucidating that these animals possessed the A allele of c.871G > A commonly. c.871G > A was a non‐synonymous mutation in the seventh transmembrane domain, suggesting alteration of the function and/or the structure of MC1R protein. Our data indicated that the A allele of c.871G > A might be a loss‐of‐function mutation.     

Effective population size of an indigenous Swiss cattle breed estimated from linkage disequilibrium

Effective population size is an important parameter for the assessment of genetic diversity within a livestock population and its development over time. If pedigree information is not available, linkage disequilibrium (LD) analysis might offer an alternative perspective for the estimation of effective population size. In this study, 128 individuals of the Swiss Eringer breed were genotyped using the Illumina BovineSNP50 beadchip. We set bin size at 50 kb for LD analysis, assuming that LD for proximal single nucleotide polymorphism (SNP)‐pairs reflects distant breeding history while LD from distal SNP‐pairs would reflect near history. Recombination rates varied among different regions of the genome. The use of physical distances as an approximation of genetic distances (e.g. setting 1 Mb = 0.01 Morgan) led to an upward bias in LD‐based estimates of effective population size for generations beyond 50, while estimates for recent history were unaffected. Correction for restricted sample size did not substantially affect these results. LD‐based actual effective population size was estimated in the range of 87–149, whereas pedigree‐based effective population size resulted in 321 individuals. For conservation purposes, requiring knowledge of recent history (<50 generations), approximation assuming constant recombination rate seemed adequate.     

Pharmacokinetic–pharmacodynamic relationship of marbofloxacin for Escherichia coli and Pasturella multocida following repeated intramuscular administration in goats

The pharmacokinetics (PK) and pharmacodynamics (PD) of marbofloxacin (MBF) were determined in six healthy female goats of age 1.00–1.25 years after repeated administration of MBF. The MBF was administered intramuscularly (IM) at 2 mg kg^?1 day^?1 for 5 days. Plasma concentrations of MBF were determined by high‐performance liquid chromatography, and PK parameters were obtained using noncompartmental analysis. The MBF concentrations peaked at 1 hr, and peak concentration (C_max) was 1.760 µg/ml on day 1 and 1.817 µg/ml on day 5. Repeated dosing of MBF caused no significant change in PK parameters except area under curve (AUC) between day 1 (AUC_0–∞D1 = 7.67 ± 0.719 µg × hr/ml) and day 5 (AUC_0‐∞D5 = 8.70 ± 0.857 µg × hr/ml). A slight difference in mean residence time between 1st and 5th day of administration and accumulation index (AI = 1.13 ± 0.017) suggested lack of drug accumulation following repeated IM administration up to 5 days. Minimum inhibitory concentration (MIC) demonstrated that Escherichia coli (MIC = 0.04 µg/ml) and Pasturella multocida (MIC = 0.05 µg/ml) were highly sensitive to MBF. Time‐kill kinetics demonstrated rapid and concentration‐dependent activity of MBF against these pathogens. PK/PD integration of data for E. coli and P. multocida, using efficacy indices: C_max/MIC and AUC_0–24hr/MIC, suggested that IM administration of MBF at a dose of 2 mg kg^?1 day^?1 is appropriate to treat infections caused by E. coli. However, a dose of 5 mg kg^?1 day^?1 is recommended to treat pneumonia caused by P. multocida in goats. The study indicated that MBF can be used repeatedly at dosage of 2 mg/kg in goats without risk of drug accumulation up to 5 days.     

Genome‐wide linkage disequilibrium in the Blonde d'Aquitaine cattle breed

We present here the first genome‐wide characterization of linkage disequilibrium (LD) in the French Blonde d'Aquitaine (BLA) breed, a well‐muscled breed renowned for producing high‐yielding beef carcasses. To assess the pattern and extent of LD, we used a sample of 30 unrelated bulls and 36 923 single nucleotide polymorphisms (SNPs) covering all cattle autosomes. The squared correlation of the alleles at two loci (r²) was used as a measure of LD. The analysis of adjacent marker pairs revealed that the level of LD decreases rapidly with physical distance between SNPs. Overall mean r² was 0.205 (±0.262). Strong LD (r² > 0.8) and useful LD (measured as r² > 0.2) were observed within genomic regions of up to 720 and 724 kb, respectively. We analysed the genetic structure of the BLA population and found stratification. The observed genetic sub‐structuring is consistent with the known recent demographic history that occurred during BLA breed formation. Our results indicate that LD mapping of phenotypic traits in the BLA population is feasible; however, because of this sub‐structuring, special care is needed to reduce the likelihood of false‐positive associations between marker loci and traits of interest.     

Comparative pharmacokinetics of florfenicol in healthy and Pasteurella multocida‐infected Gaoyou ducks

Pasteurella multocida is the causative agent of fowl cholera, and florfenicol (FF) has potent antibacterial activity against P. multocida and is widely used in the poultry industry. In this study, we established a P. multocida infection model in ducks and studied the pharmacokinetics of FF in serum and lung tissues after oral administration of 30 mg/kg bodyweight. The maximum concentrations reached (C_max) were lower in infected ducks (13.88 ± 2.70 μg/ml) vs. healthy control animals (17.86 ± 1.57 μg/ml). In contrast, the mean residence time (MRT: 2.35 ± 0.13 vs. 2.27 ± 0.18 hr) and elimination half‐life (T_½β: 1.63 ± 0.08 vs. 1.57 ± 0.12 hr) were similar for healthy and diseased animals, respectively. As a result, the area under the concentration curve for 0–12 hr (AUC_0–12 hr) for FF in healthy ducks was significantly greater than that in infected ducks (49.47 ± 5.31 vs. 34.52 ± 8.29 μg hr/ml). The pharmacokinetic differences of FF in lung tissues between the two groups correlated with the serum pharmacokinetic differences. The C_max and AUC_0–12 hr values of lung tissue in healthy ducks were higher than those in diseased ducks. The concentration of FF in lung tissues was approximately 1.2‐fold higher than that in serum both in infected and healthy ducks indicating that FF is effective in treating respiratory tract infections in ducks.     

Pharmacokinetics of xylazine after 2-, 4-, and 6-hr durations of continuous rate infusions in horses

Intravenous (i.v.) bolus administration of xylazine (XYL) (0.5 mg/kg) immediately followed by a continuous rate infusion (CRI) of 1 mg kg⁻¹ hr⁻¹ for 2, 4, and 6 hr produced immediate sedation, which lasted throughout the duration of the CRI. Heart rate decreased and blood pressure increased significantly (p > .05) in all horses during the first 15 min of infusion, both returned to and then remained at baseline during the duration of the infusion. Compartmental models were used to investigate the pharmacokinetics of XYL administration. Plasma concentration–time curves following bolus and CRI were best described by a one-compartment model. No differences were found between pharmacokinetic estimates of the CRIs for the fractional elimination rate constant (K_e), half-life (t_1/2e), volume of distribution (V_d), and clearance (Cl). Median and range were 0.42 (0.15–0.97)/hr, 1.68 (0.87–4.52) hr, 5.85 (2.10–19.34) L/kg, and 28.7 (19.6–39.5) ml min⁻¹ kg⁻¹, respectively. Significant differences were seen for area under the curve ( ) (p < .0002) and maximum concentration (C_max) (p < .04). This indicates that with increasing duration of infusion, XYL may not accumulate in a clinically relevant way and hence no adjustments are required in a longer XYL CRI to maintain a constant level of sedation and a rapid recovery.     

Pharmacokinetics of harpagoside in horses after intragastric administration of a Devil's claw (Harpagophytum procumbens) extract

Devil's claw is used for the treatment of inflammatory symptoms and degenerative disorders in horses since many years, but without the substantive pharmacokinetic data. The pharmacokinetic parameters of harpagoside, the main active constituent of Harpagophytum procumbens DC ex Meisn., were evaluated in equine plasma after administration of Harpagophytum extract FB 8858 in an open, single‐dose, two‐treatment, two‐period, randomized cross‐over design. Six horses received a single dose of Harpagophytum extract, corresponding to 5 mg/kg BM harpagoside, and after 7 days washout period, 10 mg/kg BM harpagoside via nasogastric tube. Plasma samples at certain time points (before and 0–24 hr after administration) were collected, cleaned up by solid‐phase extraction, and harpagoside concentrations were determined by LC‐MS/MS using apigenin‐7‐glucoside as internal standard. Plasma concentration‐time data and relevant parameters were described by noncompartmental model through PKSolver software. Harpagoside could be detected up to 9 hr after administration. C_max was found at 25.59 and 55.46 ng/ml, t_1/2 at 2.53 and 2.32 hr, respectively, and t_max at 1 hr in both trials. AUC_0–inf was 70.46 and 117.85 ng hr ml^?1, respectively. A proportional relationship between dose, C_max and AUC was observed. Distribution (V_z/F) was 259.04 and 283.83 L/kg and clearance (CL/F) 70.96 and 84.86 L hr^?1 kg^?1, respectively. Treatment of horses with Harpagophytum extract did not cause any clinically detectable side effects.     

Extinction probabilities of Jordan indigenous cattle using population viability analysis

Estimation of expected loss of genetic diversity in a population or breed within a defined future time horizon requires initially population viability analysis (PVA). The PVA needs estimates of probability of extinction (PE). In this study, the PE of Jordan indigenous cattle breed was simulated by PVA using Vortex^® modeling program. The annual numbers of recorded cows, bulls and their progeny were used as census data. Using the census data, effective population size (N_e) was calculated and found to be almost half (N_e = 40) of what is recommended (N_e = 82) by FAO [FAO, 1995. World Watch List for Domestic Animal Diversity. 2nd Ed. Rome, Italy] to escape endangerment. Furthermore, the EP, growth rate, heterozigosity and inbreeding rate were simulated using the PVA for a past and future time horizon. The estimates of EPs were sensible and depended heavily on the time horizon, physiological parameters and catastrophic events considered. The catastrophes were exotic breed competition and drought of 25% severity each on the population living. The model concludes that, while perhaps more or less variation in simulated population dynamic compared to real population dynamic in the past, the simulation was a fairly simulation of the likely fate under assumed living conditions. Further, the future simulated model concluded that the population is currently expected to decline rapidly toward extinction within the coming 10 years considering the same assumed conditions and absence of conserving genetic program. In such situation, it is recommended that an ex-situ live conservation program can only be a successful tool to conserve this endangered breed.     

Selection of core animals in the Algorithm for Proven and Young using a simulation model

The Algorithm for Proven and Young (APY) enables the implementation of single‐step genomic BLUP (ssGBLUP) in large, genotyped populations by separating genotyped animals into core and non‐core subsets and creating a computationally efficient inverse for the genomic relationship matrix ( G ). As APY became the choice for large‐scale genomic evaluations in BLUP‐based methods, a common question is how to choose the animals in the core subset. We compared several core definitions to answer this question. Simulations comprised a moderately heritable trait for 95,010 animals and 50,000 genotypes for animals across five generations. Genotypes consisted of 25,500 SNP distributed across 15 chromosomes. Genotyping errors and missing pedigree were also mimicked. Core animals were defined based on individual generations, equal representation across generations, and at random. For a sufficiently large core size, core definitions had the same accuracies and biases, even if the core animals had imperfect genotypes. When genotyped animals had unknown parents, accuracy and bias were significantly better (p ≤ .05) for random and across generation core definitions.     

Is neutral genetic diversity related to quantitative variation in semen traits in bulls?

Conservation decisions based on neutral genetic diversity have been observed to promote retention of useful quantitative variation in biological populations. An experiment was undertaken to determine the association between microsatellite marker polymorphisms and phenotypic variation in semen production and cryosurvival traits in bulls. Thirty-five ejaculates were collected from ten bulls of two breeds and evaluated before and after cryopreservation for several semen traits. The bulls were also genotyped using a set of sixteen bovine-specific microsatellite marker loci. Fixation indices (F_ST), heterozygosity and Nei's genetic distance measures were computed from allele frequency data for each of the bulls. Molecular and phenotypic data were used to compute tri-distance matrices for the ten bulls and correlated using Mantel's test in GenAIEx 6.5. The study revealed extensive heterogeneity in semen traits, heterozygosity and F_ST values among the bulls. Large pairwise phenotypic and genetic distances were also observed. Correlation between pairwise genetic distances and phenotypic distances was significant and highly positive for sperm viability (r = .61, p < .001) and moderately positive for sperm motility (r = .40–42, p < .05) variables. For sperm morphology, ejaculate volume and sperm concentration, correlation with genetic distances was positive, low and not significantly different from zero (p > .05). A tendency for a triangular-shaped relationship between genetic and phenotypic distances for post-thaw motility and viability traits was also observed. Accordingly, association with neutral genetic diversity was absent for semen production traits and moderate to highly positive for sperm cryosurvival traits. Given these findings, conservation decisions based on neutral genetic diversity may capture variation in some adaptive traits, but not others.     

Clinical pharmacokinetics and outcomes of oral fluconazole therapy in dogs and cats with naturally occurring fungal disease

This multi-institutional study was designed to determine the clinical pharmacokinetics of fluconazole and outcomes in client-owned dogs (n = 37) and cats (n = 35) with fungal disease. Fluconazole serum concentrations were measured. Pharmacokinetic analysis was limited to animals at steady state (≥72 hr of treatment). The mean (range) body weight in 31 dogs was 25.6 (2.8–58.2) kg and in 31 cats was 3.9 (2.4–6.1) kg included in pharmacokinetic analyses. The dose, average steady-state serum concentrations (C_SS), and oral clearance in dogs were 14.2 (4.5–21.3) mg/kg/d, 26.8 (3.8–61.5) µg/mL, and 0.63 ml min⁻¹ kg⁻¹, respectively, and in cats were 18.6 (8.2–40.0) mg/kg/d, 32.1 (1.9–103.5) µg/mL, and 0.61 ml min⁻¹ kg⁻¹, respectively. Random inter-animal pharmacokinetic variability was high in both species. Two dogs had near twofold increases in serum fluconazole when generic formulations were changed, suggesting lack of bioequivalence. Median C_SS for dogs and cats achieving clinical remission was 19.4 and 35.8 µg/ml, respectively. Starting oral doses of 10 mg/kg q12h in dogs and 50–100 mg total daily dose in cats are recommended to achieve median C_SS associated with clinical remission. Due to the large pharmacokinetic variability, individualized dose adjustments based on C_SS (therapeutic drug monitoring) and treatment failure should be considered.     

Genetic diversity,structure and individual assignment of Casta Navarra cattle: a well‐differentiated fighting bull population

The Casta Navarra lineage was one of the populations used to establish the fighting bull (FB) breed, and it has also been reproductively isolated from the others FBs. A total of 1284 individuals from two generations of 16 Casta Navarra herds were sampled to analyse their diversity, their genetic structure and the ability of 28 microsatellite markers to assign individuals to closely related populations. These animals were compared with closely related phylogenetic (FB) or geographical (Pirenaica and Monchina) populations. Hardy–Weinberg equilibrium analysis showed that 82% of the loci had a significant heterozygote deficit as a consequence of the Wahlund effect. The average proportion of genetic variation explained by farm differences was 9% by Wright's F_ST index. A phylogenetic tree constructed with a neighbour‐joining method based on Reynolds genetic distances and a Bayesian Markov chain Monte Carlo clustering approach revealed clear differences between farm groups that generally corresponded to historical information and could unambiguously differentiate Casta Navarra cattle from the other populations. The percentage of animals correctly assigned to the Casta Navarra population was 91.78% for a q threshold of >0.9. Admixture was only detected in 4.45% (q < 0.8) of the cattle. These results are relevant for the maintenance and development of diversity and conservation in the Casta Navarra population.     

Genetic Characterization of Cryptosporidium spp. in Diarrhoeic Children from Four Provinces in South Africa

The diversity of Cryptosporidium at species, subtype family and subtype level in diarrhoeic children was investigated in four provinces in South Africa. A total of 442 stool samples from children <5 years of age were collected under a large rotavirus surveillance programme and analysed by Ziehl–Neelsen acid‐fast staining. Fifty‐four (12.2%) were positive for Cryptosporidium, of which 25 were genotyped by polymerase chain reaction (PCR)–restriction fragment length polymorphism (RFLP) and DNA sequence analyses of the 18S rRNA gene. The majority of genotyped specimens were identified as C. hominis (76%), and a high genetic diversity was found with five different C. hominis subtype families (Ia, Ib, Id, Ie and If). Cryptosporidium parvum was found in 20% of the isolates, and three subtype families were identified (IIc, IIe and IIb), with subtype family IIc being the most common. One specimen was identified as C. meleagridis of the subtype family IIId. These results are in accordance with findings from other developing countries and report for the first time the presence in South Africa of C. meleagridis, various subtypes of C. parvum and the subtype family Ie of C. hominis. The results suggest that C. hominis and anthroponotic C. parvum subtypes are the major cause of cryptosporidiosis in South Africa. Further molecular studies are needed to better understand the epidemiology and public health importance of Cryptosporidium in humans in South Africa.     

Detection of Invasive Borrelia burgdorferi Strains in North‐Eastern Piedmont,Italy

Following reports of human cases of Lyme borreliosis from the Ossola Valley, a mountainous area of Piemonte, north‐western Italy, the abundance and altitudinal distribution of ticks, and infection of these vectors with Borrelia burgdorferi sensu lato were evaluated. A total of 1662 host‐seeking Ixodes ricinus were collected by dragging from April to September 2011 at locations between 400 and 1450 m above sea level. Additional 104 I. ricinus were collected from 35 hunted wild animals (4 chamois, 8 roe deer, 23 red deer). Tick density, expressed as the number of ticks per 100 m², resulted highly variable among different areas, ranging from 0 to 105 larvae and from 0 to 22 nymphs. A sample of 352 ticks (327 from dragging and 25 from wild animals) was screened by a PCR assay targeting a fragment of the 16S rRNA gene of B. burgdorferi s.l. Positive samples were confirmed with a PCR assay specific for the 5S‐23S rRNA intergenic spacer region and sequenced. Four genospecies were found: B. afzelii (prevalence 4.0%), B. lusitaniae (4.0%), B. garinii (1.5%) and B. valaisiana (0.3%). Phylogenetic analysis based on the ospC gene showed that most of the Borrelia strains from pathogenic genospecies had the potential for human infection and for invasion of secondary body sites.     

Pharmacokinetic/pharmacodynamic evaluation of marbofloxacin as a single injection for Pasteurellaceae respiratory infections in cattle using population pharmacokinetics and Monte Carlo simulations

Population pharmacokinetic of marbofloxacin was investigated with 52 plasma concentration–time profiles obtained after intramuscular administration of Forcyl® in cattle. Animal's status, pre‐ruminant, ruminant, or dairy cow, was retained as a relevant covariate for clearance. Monte Carlo simulations were performed using a stratification by status, and 1000 virtual disposition curves were generated in each bovine subpopulation for the recommended dosage regimen of 10 mg/kg as a single injection. The probability of target attainment (PTA) of pharmacokinetic/pharmacodynamic (PK/PD) ratios associated with clinical efficacy and prevention of resistance was determined in each simulated subpopulation. The cumulative fraction of response (CFR) of animals achieving a PK/PD ratio predictive of positive clinical outcome was then calculated for the simulated dosage regimen, taking into account the minimum inhibitory concentration (MIC) distribution of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni. When considering a ratio of AUC_0‐24 hr/MIC (area under the curve/minimum inhibitory concentration) greater than 125 hr, CFRs ranging from 85% to 100% against the three Pasteurellaceae in each bovine subpopulation were achieved. The PTA of the PK/PD threshold reflecting the prevention of resistances was greater than 90% up to MPC (mutant prevention concentration) values of 1 μg/ml in pre‐ruminants and ruminants and 0.5 μg/ml in dairy cows.     

Physiological Predictors in Calves of Dairy Breeds: Part 1. Genetic Parameters of Basal and Induced Growth Hormone Secretion

Abstract

Genetic variation in plasma growth hormone (GH) concentration before and after GRF (growth hormone releasing factor) stimulation was studied in young bulls (N=284) and heifers (N=212), the progeny of 53 sires of four dairy and dual-purpose breeds (Danish Jersey, Red Dane, Danish Friesian and Danish Red and White). Male and female calves were reared, fed and tested on separate experimental stations; thus sex, station and feeding were completely confounded effects. The animals were tested at about 9 months of age, after a 24 h fast. GH concentration was measured in serial plasma samples collected for 1 h before and 1 h following intravenous administration of 2.0 ug synthetic GRF(1–29)NH₂/kg live weight^>0.75. Prior to statistical analysis, concentrations were log_e-transformed. Response variables were BASELINE (mean GH in -15, -5 and 0 min samples) and PEAK (mean GH in 10, 15 and 20 min samples). A statistical model taking at least three generations of ancestral relationships into account was used to estimate variance and covariance components for traits in male and female calves by use of restricted maximum likelihood methods.

Heritability of BASELINE was low (0.04 ± 0.12) in males but high in females (0.60 ± 0.16). The heritability of PEAK was high in both sexes (males, 0.42 ± 0.16; females, 0.60 ± 0.16). Genetic correlations between the same trait measured in males and females were low for BASELINE (r _g = 0.32±0.55) but high for PEAK (r _g = 0.82±0.15). Within sex, BASELINE and PEAK were both highly genetically correlated (males, r _g=0.62 ± 0.40; females, r _g= 1.00 ± 0.07).

We conclude that growth hormone concentration is a highly heritable trait in juvenile cattle of both sexes, and that GRF stimulation is benificial to the uncovering of genetic differences among animals.     

Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration

The pharmacokinetics of orphenadrine (ORPH) following a single intravenous (i.v.) dose was investigated in six camels (Camelus dormedarius). Orphenadrine was extracted from the plasma using a simple sensitive liquid–liquid extraction method and determined by gas chromatography/mass spectrometry (GC/MS). Following i.v. administration plasma concentrations of ORPH decline bi-exponentially with distribution half-life (t_1/2α) of 0.50 ± 0.07 h, elimination half-life (t_1/2β) of 3.57 ± 0.55 h, area under the time concentration curve (AUC) of 1.03 ± 0.10 g/h l⁻¹. The volume of distribution at steady state (Vd_ss) 1.92 ± 0.22 l kg⁻¹, volume of the central compartment of the two compartment pharmacokinetic model (V_c) 0.87 ± 0.09 l kg⁻¹, and total body clearance (Cl_T) of 0.60 ± 0.09 l/h kg⁻¹. Three orphenadrine metabolites were identified in urine samples of camels. The first metabolite N-desmethyl-orphenadrine resulted from N-dealkylation of ORPH with molecular ion m/z 255. The second N,N-didesmethyl-orphenadrine, resulted from N-didesmethylation with molecular ion m/z 241. The third metabolite, hydroxyl-orphenadrine, resulted from the hydroxylation of ORPH with molecular ion m/z 285. ORPH and its metabolites in camel were extensively eliminated in conjugated form. ORPH remains detectable in camel urine for three days after i.v. administration of a single dose of 350 mg orphenadrine aspartate.     

Improving production efficiency in the presence of genotype by environment interactions in pig genomic selection breeding programmes

We simulated a genomic selection pig breeding schemes containing nucleus and production herds to improve feed efficiency of production pigs that were cross‐breed. Elite nucleus herds had access to high‐quality feed, and production herds were fed low‐quality feed. Feed efficiency in the nucleus herds had a heritability of 0.3 and 0.25 in the production herds. It was assumed the genetic relationships between feed efficiency in the nucleus and production were low (r_g = 0.2), medium (r_g = 0.5) and high (r_g = 0.8). In our alternative breeding schemes, different proportion of production animals were recorded for feed efficiency and genotyped with high‐density panel of genetic markers. Genomic breeding value of the selection candidates for feed efficiency was estimated based on three different approaches. In one approach, genomic breeding value was estimated including nucleus animals in the reference population. In the second approach, the reference population was containing a mixture of nucleus and production animals. In the third approach, the reference population was only consisting of production herds. Using a mixture reference population, we generated 40–115% more genetic gain in the production environment as compared to only using nucleus reference population that were fed high‐quality feed sources when the production animals were offspring of the nucleus animals. When the production animals were grand offspring of the nucleus animals, 43–104% more genetic gain was generated. Similarly, a higher genetic gain generated in the production environment when mixed reference population was used as compared to only using production animals. This was up to 19 and 14% when the production animals were offspring and grand offspring of nucleus animals, respectively. Therefore, in genomic selection pig breeding programmes, feed efficiency traits could be improved by properly designing the reference population.     

Occupational swine exposure and Hepatitis E virus,Leptospira, Ascaris suum seropositivity and MRSA colonization in Austrian veterinarians, 2017–2018—A cross‐sectional study

We investigated the prevalence of Hepatitis E Virus (HEV), Leptospira and Ascaris suum (A. suum) seropositivity, and of nasal methicillin‐resistant Staphylococcus aureus (MRSA) colonization among Austrian practising veterinarians, and assessed the association with occupational swine livestock exposure. The 261 participants completed a questionnaire on demographics, intensity of occupational swine livestock contact and glove use during handling animals and their secretions. Participants' blood samples were tested for HEV, Leptospira and A. suum seropositivity and nasal swabs cultured for MRSA. We compared swine veterinarians (defined as >3 swine livestock visits/week) to non‐swine veterinarians (≤3 swine livestock visits/week) with regard to the outcomes through calculating prevalence ratio (PR) and 95% confidence interval (CI). Furthermore, the relationship between occupational swine livestock contact and the study outcomes was examined by age (</≥55 years) and glove usage. The prevalence of nasal MRSA colonization was 13.4% (95% CI: 9.3–17.6), of HEV seropositivity 20.8% (95% CI: 15.8–25.7) and A. suum seropositivity 44% (95% CI: 37.7–50.2). The highest anti‐leptospiral antibodies titres were 1:200 (L. hebdomadis) and 1:100 (L. autumnalis, L. caicola) found in three non‐swine veterinarians. Compared to non‐swine veterinarians, swine veterinarians were 1.9 (95% CI: 1.0–3.4) and 1.5 (95%CI: 1.0–2.3) times more likely HEV seropositive and A. suum seropositive, respectively, and 4.8 (95%CI: 2.5; 9.3) times more likely nasally colonized with MRSA. Among glove‐using veterinarians, occupational swine contact was no longer a determinant for HEV seropositivity (PR 1.6; 95% CI: 0.8–2.9). Similar was found for A. suum seropositivity, which was no longer associated with occupational swine livestock contact in the subgroup of glove using, ≥55‐year‐old veterinarians (PR: 1.07; 95% CI: 0.4–3.3). Our findings indicate that >3 occupational swine livestock visits per week is associated with HEV and A. suum seropositivity and nasal MRSA colonization and that glove use may play a putative preventive role in acquiring HEV and A. suum. Further analytical epidemiological studies have to prove the causality of these associations.