Efficacy of gallium maltolate against Lawsonia intracellularis infection in a rabbit model

Antimicrobial efficacy against Lawsonia intracellularis is difficult to evaluate in vitro, thus, the effects of gallium maltolate's (GaM) were investigated in a rabbit model for equine proliferative enteropathy (EPE). Juvenile (5–6‐week‐old) does were infected with 3.0 × 10⁸ L. intracellularis/rabbit and allocated into three groups (n = 8). One week postinfection, one group was treated with GaM, 50 mg/kg; one, with doxycycline, 5 mg/kg; and one with a sham‐treatment (control). Feces and blood were collected daily and weekly, respectively, to verify presence of L. intracellularis fecal shedding using qPCR, and seroconversion using immunoperoxidase monolayer assay. Rabbits were sacrificed after 1 week of treatment to collect intestinal tissues focusing on EPE‐affected sections. Intestinal lesions were confirmed via immunohistochemistry. No difference was noted between treatments regarding EPE‐lesions in jejunum (P = 0.51), ileum (P = 0.74), and cecum (P = 0.35), or in L. intracellularis fecal shedding (P = 0.64). GaM and doxycycline appear to have similar efficacy against EPE in infected rabbits.     

Reduction in absorption of gallium maltolate in adult horses following oral administration with food: chemistry and pharmacokinetics

Gallium (Ga) is under study for the treatment of osteolytic disorders in equines. Previous studies indicate that oral gallium maltolate (GaM) would provide a higher bioavailability than oral Ga salts. However, oral administration to adult horses of 2 mg/kg of GaM, in the form of a solution mixed with food, did not lead to detectable Ga levels in plasma. Therefore, a study was performed to model the chemical behaviour of GaM in the digestive tract. The equilibrium formation constants for Ga(III) and maltol were calculated by means of UV–visible measurements and validated by ¹H‐NMR measurements at selected pH values. Data indicate that the dissociation of GaM in aqueous solutions is very rapid, while the re‐association is slower. Based on these results, poor Ga absorption seems to be due to the equilibrium dissociation of GaM in the stomach and to its slow formation rate in the intestine. The concomitant presence of high concentrations of phytates (strong charged metal chelating agents, which represent about 1% of dry matter in vegetables) might also explain the low absorption of GaM by the gastrointestinal tract. Methods of optimizing Ga absorption after oral administration of GaM require further investigation.     

Effects of different gestation housing types on reproductive performance of sows

This study evaluated the effects of different gestation housing types on reproductive performance of sows. A total of 60 sows (218 ± 24 kg body weight) with mixed parity were used. During gestation, 28 sows were housed in groups with electronic sow feeders (space allowance = 1.26 m²/sow) and 32 sows were housed in individual stalls (space allowance = 1.20 m²/sow). Sows from both housing types were moved to farrowing crates on day 109 of gestation and stayed until weaning (18 days post‐farrowing). Typical corn‐soybean meal diets were provided to sows during gestation and lactation. Measurements were reproductive performance of sows at farrowing as well as performance of sows and their litter during lactation. Similar total numbers of piglets born at farrowing were observed for sows gestated in both housing types. However, group‐housed gestation sows had more mummies (0.321 vs. 0.064; P < 0.05) and stillbirths (0.893 vs. 0.469; P = 0.073) at farrowing than individual‐housed gestation sows. Consequently, individual‐housing type had higher percentage of piglets born alive (95.5 vs. 90.4%; P < 0.05) than the group‐housing type. Therefore, improved reproductive performance of sows from individual gestating housing was confirmed in this study.     

Plasma disposition kinetics of moxidectin after subcutaneous administration to pregnant sheep

The plasma kinetic profile of moxidectin (MXD) in ewes during the last third of pregnancy was studied after the subcutaneous dose of 0.2 mg/kg of body weight (bw). Two groups of sheep (n = 7) that were equally balanced in body weight were used. Group I (control) was maintained unmated, while Group II (pregnant) was estrous‐synchronized and mated with fertile rams. Both groups were maintained under similar conditions regarding management and feeding. When the ewes from Group II fulfilled 120 days of pregnancy, both groups were treated with a subcutaneous injection of 0.2 mg of MXD/kg bw. Blood samples were collected at different set times between 1 h and 40 days post‐treatment. After plasma extraction and derivatization, the samples were analyzed using high‐performance liquid chromatography with fluorescence detection. A noncompartmental pharmacokinetic analysis was performed, and the data were compared using Student's t‐test. The mean pharmacokinetic parameters, including C_max, T_max, and the area under the concentration–time curve (AUC), were similar for both groups of sheep. The average of elimination half‐life was significantly lower (P = 0.0023) in the pregnant (11.49 ± 2.2 days) vs. the control (17.89 ± 4.84 days) sheep. Similarly, the mean residence time (MRT) for the pregnant group (20.6 ± 3.8 days) was lower (P = 0.037) than that observed in the control group (27.4 ± 9.1 days). It is concluded that pregnancy produces a significant decrease in mean values of half‐life of elimination of MXD, indicating that pregnancy can increase the rate of elimination of the drug reducing their permanence in the body.     

Effect of Reproductive Seasonality on Gamete Quality in the North American Bison (Bison bison bison)

The objective was to investigate the effects of reproductive seasonality on gamete quality in plains bison (Bison bison bison). Epididymal sperm (n = 61 per season), collected during the breeding season (July–September), had significantly higher post‐thaw total motility (36.76 ± 14.18 vs 31.24 ± 12.74%), and lower linearity (0.36 ± 0.06 vs 0.39 ± 0.04) and wobbliness (0.49 ± 0.04 vs 0.51 ± 0.03; mean ± SD) compared to non‐breeding season (January–March) samples. Representative samples (n = 4) from each season were used in heterologous IVF trials using cattle oocytes. Cleavage, morulae and blastocyst percentage were higher for breeding vs non‐breeding season sperm samples (81.88 ± 6.8 vs 49.94 ± 6.77; 41.89 ± 13.40 vs 27.08 ± 23.21; and 30.49 ± 17.87 vs 13.72 ± 18.98%, respectively). Plains bison ovaries collected during the breeding (n = 97 pairs) and non‐breeding (n = 100 pairs) seasons were classified as luteal or follicular. Oocytes recovered from these ovaries were classified into five grades based on morphology. There was no significant difference in the number of luteal ovaries or grades of oocytes recovered. Oocytes were matured, fertilized (with frozen sperm from three bison bulls) and cultured in vitro. Cleavage percentage was higher for oocytes collected during breeding vs non‐breeding season (83.72 ± 6.42 vs 73.98 ± 6.43), with no significant difference in subsequent development to blastocysts. In summary, epididymal sperm from non‐breeding season had decreased total motility and resulted in reduced embryo production in vitro. Oocytes collected during non‐breeding season had reduced ability to be matured, fertilized and/or undergo cleavage in vitro. Data suggested that season influenced gamete quality in plains bison.     

Plasma‐Free Metanephrine and Free Normetanephrine Measurement for the Diagnosis of Pheochromocytoma in Dogs

Background

Measurement of plasma‐free metanephrines is the test of choice to identify pheochromocytoma in human patients.

Objectives

To establish the sensitivity and specificity of plasma‐free metanephrine (fMN) and free normetanephrine (fNMN) concentrations to diagnose pheochromocytoma in dogs.

Animals

Forty‐five client‐owned dogs (8 dogs with pheochromocytoma, 11 dogs with adrenocortical tumors, 15 dogs with nonadrenal disease, and 11 healthy dogs.)

Methods

A prospective study. EDTA plasma was collected from diseased and healthy dogs and submitted for fMN and fNMN measurement by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS).

Results

Free MN concentration (median [range]) was significantly higher in dogs with pheochromocytoma (8.15 [1.73–175.23] nmol/L) than in healthy dogs (0.95 [0.68–3.08] nmol/L; P < .01) and dogs with adrenocortical tumors (0.92 [0.25–2.51] nmol/L; P < .001), but was not different from dogs with nonadrenal disease (1.91 [0.41–6.57] nmol/L; P ≥ .05). Free NMN concentration was significantly higher in dogs with pheochromocytoma (63.89 [10.19–190.31] nmol/L) than in healthy dogs (2.54 [1.59–4.17] nmol/L; P < .001), dogs with nonadrenal disease (3.30 [1.30–10.10] nmol/L; P < .001), and dogs with adrenocortical tumors (2.96 [1.92–5.01] nmol/L); P < 0.01). When used to diagnose pheochromocytoma, a fMN concentration of 4.18 nmol/L had a sensitivity of 62.5% and specificity of 97.3%, and a fNMN concentration of 5.52 nmol/L had a sensitivity of 100% and specificity of 97.6%.

Conclusions and Clinical Importance

Plasma fNMN concentration has excellent sensitivity and specificity for the diagnosis of pheochromocytoma in dogs, whereas fMN concentration has moderate sensitivity and excellent specificity. Measurement of plasma‐free metanephrines provides an effective, noninvasive, means of identifying dogs with pheochromocytoma.     

Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals

Chaffin, M. K., Fajt, V., Martens, R. J., Arnold, C. E., Cohen, N. D., O’Conor, M., Taylor, R. J., Bernstein, L. R. Pharmacokinetics of an orally administered methylcellulose formulation of gallium maltolate in neonatal foals. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365‐2885.2009.01150.x. Gallium is a trivalent semi‐metal with anti‐microbial effects because of its incorporation into crucial iron‐dependent reproductive enzyme systems. Gallium maltolate (GaM) provides significant gallium bioavailability to people and mice following oral administration and to neonatal foals following intragastric administration. To study the prophylactic and therapeutic effects of GaM against Rhodococcus equi pneumonia in foals, we developed a methylcellulose formulation of GaM (GaM‐MCF) for oral administration to neonatal foals. Normal neonatal foals were studied. Six foals received 20 mg/kg and another six foals received 40 mg/kg of GaM‐MCF orally. Serial serum samples were collected and serum gallium concentrations were determined using inductively coupled plasma mass spectroscopy. Gallium was rapidly absorbed (T_max of 4 h), and a mean C_max of 0.90 or 1.8 μg/mL was achieved in foals receiving 20 or 40 mg/kg respectively. Marked variability existed in C_max among foals: only half of the foals receiving 20 mg/kg attained serum concentrations of >0.7 μg/mL, a level suggested to be therapeutic against R. equi by previous studies. Mean elimination half‐life was 32.8 or 32.4 h for foals receiving 20 or 40 mg/kg respectively. The results of this study suggest that at least 30 mg/kg orally every 24 h should be considered in future pharmacodynamic and efficacy studies.     

Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous,subcutaneous and oral administration

The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high‐performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (V_z) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (V_ss) of 0.22 ± 0.12 L/kg. Median plasma terminal half‐life (t_1/2) was 1.19 h (range 0.71–1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C_max 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4–8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5‐hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate.     

Anti‐Mullerian Hormone Concentration and Antral Ovarian Follicle Population in Murrah Heifers Compared to Holstein and Gyr Kept Under the Same Management

This study was performed to evaluate plasma concentrations of anti‐Mullerian hormone (AMH) and the ovarian antral follicle population (AFP) in different genetic groups. Cyclic heifers (13 Bubalus bubalis [Murrah]; 15 Bos taurus [Holstein] and 10 Bos indicus [Gyr]) were maintained under the same management and were synchronized with two doses of 150 μg IM d‐cloprostenol administered 14 days apart. After the second d‐cloprostenol treatment, heifers had their ovaries scanned daily by ultrasound to define the day of ovulation. On the same day, the AFP was determined and a plasma sample was collected to measure AMH. Murrah heifers had less AFP (25.6 ± 2.1 follicles; p = 0.01) and plasma AMH concentration (0.18 ± 0.03 ng/ml; p < 0.001) than Gyr (60.0 ± 12.2 follicles and 0.60 ± 0.12 ng/ml of AMH); however, data were similar when compared to Holstein (35.9 ± 6.8 follicles and 0.24 ± 0.06 ng/ml of AMH) heifers. Regardless of genetic background, there was a positive relationship between the AFP and plasmatic AMH concentration (Murrah [r = 0.62; p < 0.01], Holstein [r = 0.66; p < 0.001] and Gyr [r = 0.88; p < 0.001]). Also, when heifers were classified according to high‐ or low‐AMH concentration based on the average within each genetic group, high‐AMH heifers had greater (p < 0.0001) AFP than low‐AMH heifers. In conclusion, both Murrah and Holstein heifers presented lower plasma AMH concentration and AFP when compared to Gyr.     

Body weight and range usage affect net energy utilisation in commercial free-range laying hens when evaluated in net energy chambers

Within a given free-range flock, some hens prefer to spend the majority of their time in the shed (stayers), while others frequently access the range (rangers). Laying performance has been associated not only with the development of these sub-populations but also with different body weights (BW). The purpose of this study was to determine if range usage, BW or a combination of both is associated with energy metabolism and as such contribute to improved hen performance. Forty-eight Lohmann Brown hens at 74 wk of age were selected from a commercial free-range farm based on their BW and range usage over a 56-week period. Using a 2 × 2 factorial arrangement, hens were either classified as heavy (mean ± SEM; 2.01 ± 0.02 kg, n = 24) or light (1.68 ± 0.01 kg, n = 24), and also classified as rangers (accessed the range for 84.1% of available days, 242 ± 3.75 d; n = 24) or stayers (accessed the range for 7.17% of available days; 23.4 ± 6.08 d, n = 24). Stayers had significantly higher metabolizable energy (ME) intake per metabolic BW per d (0.852 vs. 0.798 MJ/kg BW^0.75 per d; P = 0.025), higher heat production (0.637 vs. 0.607 MJ/kg BW^0.75 per d; P = 0.005), higher heat increment (0.267 vs. 0.237 MJ/kg BW^0.75 per d; P = 0.005) and retained more nitrogen (1.59 vs. 1.46 g/hen per d; P = 0.023) compared to the rangers. Light hens had significantly higher metabolic energy intake per metabolic BW (0.854 vs. 0.796 MJ/kg BW^0.75 per d; P = 0.018), net energy (NE) intake (0.595 vs. 0.551 MJ/kg BW^0.75 per d; P = 0.032), and retained energy (0.225 vs. 0.181 MJ/kg BW^0.75 per d; P = 0.032), as well as lower heat production (0.936 vs. 1.003 MJ/hen per d; P = 0.002) compared to heavier hens. An interaction was observed across levels of analysis i.e. between light stayers and light rangers. The light rangers had significantly higher NE intake compared to the light stayers (9.77 vs. 9.27 MJ/kg BW^0.75 per d; P = 0.024). In conclusion, light hens were more energy efficient compared to heavy hens. Moreover, light rangers had a more efficient feed utilisation compared to the light stayers.     

Pharmacokinetics of an extended‐release formulation of eprinomectin in healthy adult alpacas and its use in alpacas confirmed with mange

The study objective was to determine the pharmacokinetics and clinical effects of an extended‐release 5% eprinomectin formulation (Longrange^®) following subcutaneous (s.c.) injection in healthy (n = 6) and mange‐infected (n = 4) adult alpacas. High‐performance liquid chromatography was used to analyze plasma samples obtained at regular intervals for 161 days following a single 5 mg/kg injection s.c. in healthy alpacas, and for 5 days following each dose (3 treatments, 2 months apart) in mange‐affected animals. Skin scrapings and biopsies were performed pre‐ and post‐treatment at two comparable sites in alpacas with mange. Four alpacas served as healthy controls. Eprinomectin plasma concentrations showed a biphasic peak (C_MAX‐1: 5.72 ± 3.25 ng/mL; C_MAX‐2: 6.06 ± 2.47 ng/mL) in all animals at 3.88 ± 5.16 days and 77 ± 12.52 days, respectively. Eprinomectin plasma concentrations remained above 1.27 ± 0.96 ng/mL for up to 120 days. Hematocrit (35.8 vs. 31.3%, P < 0.003) and albumin (3.5 vs. 2.8 g/dL P < 0.006) reduced significantly over 6 months in multidose animals, while fecal egg counts did not differ between groups. Self‐limiting injection site reactions occurred in 9 of 10 animals. Pre‐ and post‐treatment skin biopsies showed reduced hyperkeratosis, but increased fibrosis, with 1 of 4 alpacas remaining positive on skin scraping for mange. In conclusion, alpacas require a higher eprinomectin dose (5.0 mg/kg s.c.) than cattle, to reach comparable plasma concentrations.     

Pharmacokinetics of florfenicol after intravenous administration in Escherichia coli lipopolysaccharide‐induced endotoxaemic sheep

Experiments in different animal species have shown that febrile conditions, induced by Escherichia coli lipopolysaccharide (LPS), may alter the pharmacokinetic properties of drugs. The objective was to study the effects of a LPS‐induced acute‐phase response (APR) model on plasma pharmacokinetics of florfenicol (FFC) after its intravenous administration in sheep. Six adult clinically healthy Suffolk Down sheep, 8 months old and 35.5 ± 2.2 kg in body weight (bw), were distributed through a crossover factorial 2 × 2 design, with 4 weeks of washout. Pairs of sheep similar in body weight were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 μg/kg bw of E. coli LPS before FFC treatment. Group 2 (control) was treated with an equivalent volume of saline solution (SS) at similar intervals as LPS. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples (5 mL) were collected before drug administration and at different times between 0.05 and 48.0 h after treatment. FFC plasma concentrations were determined by liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using a Mann–Whitney U‐test. The mean values of AUC_0–∞ in the endotoxaemic sheep (105.9 ± 14.3 μg·h/mL) were significantly higher (P < 0.05) than values observed in healthy sheep (78.4 ± 5.2 μg·h/mL). The total mean plasma clearance (CL_T) decreased from 257.7 ± 16.9 mL·h/kg in the control group to 198.2 ± 24.1 mL·h/kg in LPS‐treated sheep. A significant increase (P < 0.05) in the terminal half‐life was observed in the endotoxaemic sheep (16.9 ± 3.8 h) compared to the values observed in healthy sheep (10.4 ± 3.2 h). In conclusion, the APR induced by the intravenous administration of E. coli LPS in sheep produces higher plasma concentrations of FFC due to a decrease in the total body clearance of the drug.     

Ovarian and Hormonal Responses to Follicular Phase Administration of Investigational Metastin/Kisspeptin Analog,TAK‐683, in Goats

This study evaluated the effects of follicular phase administration of TAK‐683, an investigational metastin/kisspeptin analog, on follicular growth, ovulation, luteal function and reproductive hormones in goats. After confirmation of ovulation by transrectal ultrasonography (Day 0), PGF_2α (2 mg/head of dinoprost) was administered intramuscularly on Day 10 to induce luteal regression. At 12 h after PGF_2α administration, intravenous administration of vehicle or 35 nmol (50 μg)/head of TAK‐683 was performed in control (n = 4) and treatment (n = 4) groups, respectively. Blood samples were collected at 6‐h intervals for 96 h and then daily until the detection of subsequent ovulation (second ovulation). After the second ovulation, ultrasound examinations and blood sampling were performed every other day or daily until the subsequent ovulation (third ovulation). Mean concentrations of LH and FSH in the treatment group were significantly higher 6 h after TAK‐683 treatment than those in the control group (12.0 ± 10.7 vs 1.0 ± 0.7 ng/ml for LH, 47.5 ± 28.2 vs 15.1 ± 3.4 ng/ml for FSH, p < 0.05), whereas mean concentrations of oestradiol in the treatment group decreased immediately after treatment (p < 0.05) as compared with the control group. Ovulation tended to be delayed (n = 2) or occurred early (n = 1) in the treatment group as compared with the control group. For the second ovulation, ovulatory follicles in the treatment group were significantly smaller in maximal diameter than in the control group (3.8 ± 0.5 vs 5.4 ± 0.2 mm, p < 0.05, n = 3). Administration of TAK‐683 in the follicular phase stimulates gonadotropin secretion and may have resulted in ovulation of premature follicles in goats.     

Antral Follicle Populations and Embryo Production – In Vitro and In Vivo – of Bos indicus–taurus Donors from Weaning to Yearling Ages

Interest in indicus–taurus cattle has been increasing, as these animals are likely to present the best characteristics of Zebu and European bovine breeds. The aim of this study was to compare the embryo production of indicus–taurus donors with high vs low antral follicle counts obtained by ovum pickup/in vitro production (OPU/IVP) and superovulation (SOV)/embryo collection. Braford females at weaning age (3/8 Nelore × 5/8 Hereford, n = 137, 9 ± 1 month old) were subjected to six serial ovarian ultrasonographs and were assigned to two groups according to the number of antral follicles ≥3 mm as follows: G‐High antral follicular count (AFC, n = 20, mean ≥40 follicles) and G‐Low AFC (n = 20, mean ≤10 follicles). When the females (n = 40) reached 24 months of age, they were subjected to both OPU/IVP and SOV/embryo collection. The average number of follicles remained highly stable throughout all of the ultrasound evaluations (range 0.90–0.92). The mean number of COCs recovered (36.90 ± 13.68 vs 5.80 ± 3.40) was higher (p < 0.05) for females with high AFC, resulting in higher (p < 0.05) numbers of total embryos among females with high vs low AFC (6.10 ± 4.51 vs 0.55 ± 0.83). The mean number of embryos per collection was also higher (p < 0.05) for G‐High vs G‐Low (6.95 ± 5.34 vs 1.9 ± 2.13). We conclude that a single ultrasound performed at pre‐pubertal ages to count antral follicles can be used as a predictor of embryo production following IVP and SOV/embryo collection in indicus–taurus females.     

Influence of a flooding dose of valine on key indicators of metabolic status in the growing pig

A key concern with the flooding dose technique for measuring protein synthesis is that a large dose of amino acid (AA) can potentially change the animals’ hormonal and nutritional status, which in turn can influence protein synthesis. Among stable isotope tracers, 1‐[¹³C]‐valine is the preferred AA for measuring protein synthesis in gut tissue and mucins. A study was conducted to determine the impact of a flooding dose of valine on the metabolic status of pigs. Six barrows [16.5 kg body weight (BW)] were randomly assigned to intravenous infusions of either 150 mm valine (1.5 mmol/kg BW) or physiological saline, following a crossover design. Blood samples were taken 10 min prior to infusion, at the end of infusion, at 10‐min intervals for 60 min post‐infusion, and at 90 and 120 min post‐infusion. Plasma concentrations of insulin, glucose, AA, urea nitrogen and packed cell volume (PCV) were measured. Infusion of valine increased plasma valine concentrations (4129 vs. 582 μm ; P < 0.05) but had no influence on PCV (26.4% vs. 27.2%) and plasma concentrations of glucose (6.0 vs. 5.8 mm ) and insulin (8.2 vs. 8.5 μU/ml; P > 0.10). Plasma urea nitrogen concentration was reduced with valine infusion (8.5 vs. 7.8 mg/dl; P < 0.05). A flooding dose of valine had no impact on plasma concentrations of AA, and specifically branched‐chain AA such as leucine (240 vs. 231 μm ) and isoleucine (310 vs. 331 μm ; P > 0.10). There was, however, a slight increase in the plasma concentrations of threonine (224 vs. 263 μm ; P < 0.05) and a tendency towards reduced glycine (1387 vs. 1313 μm ; P < 0.10). The results indicate that a flooding dose of valine does not cause a substantial change in the metabolic status of growing pigs and is therefore suitable for measuring protein synthesis rates.     

Pharmacokinetics and pharmacodynamics of dermorphin in the horse

Dermorphin is a μ‐opioid receptor‐binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2‐compartment model best with distribution and elimination half‐lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respectively. Data from intramuscular administrations fit a noncompartmental model best with a terminal elimination half‐life of 0.68 ± 0.24 (h). Bioavailability following intramuscular administration was variable (47–100%, n = 3). The percentage of dermorphin excreted in urine was 5.0 (3.7–10.6) %. Excitation accompanied by an increased heart rate followed intravenous administration only and subsided after 5 min. A plot of the mean change in heart rate vs. the plasma concentration of dermorphin fit a hyperbolic equation (simple Emax model), and an EC₅₀ of 21.1 ± 8.8 ng/mL was calculated. Dermorphin was detected in plasma for 12 h and in urine for 48 or 72 h following intravenous or intramuscular administration, respectively.     

The acute phase response induced by Escherichia coli lipopolysaccharide modifies the pharmacokinetics and metabolism of florfenicol in rabbits

The aim of this study was to determine the effect of Escherichia coli lipopolysaccharide (LPS)‐induced acute phase response (APR) on the pharmaco‐kinetics and biotransformation of florfenicol (FFC) in rabbits. Six rabbits (3.0 ± 0.08 kg body weight (bw)) were distributed through a crossover design with 4 weeks of washout period. Pairs of rabbits similar in bw and sex were assigned to experimental groups: Group 1 (LPS) was treated with three intravenous doses of 1 μg/kg bw of E. coli LPS at intervals of 6 h, and Group 2 (control) was treated with an equivalent volume of saline solution (SS) at the same intervals and frequency of Group 1. At 24 h after the first injection of LPS or SS, an intravenous bolus of 20 mg/kg bw of FFC was administered. Blood samples were collected from the auricular vein before drug administration and at different times between 0.05 and 24.0 h after treatment. FFC and florfenicol‐amine (FFC‐a) were extracted from the plasma, and their concentrations were determined by high‐performance liquid chromatography. A noncompartmental pharmacokinetic model was used for data analysis, and data were compared using the paired Student t‐test. The mean values of AUC_0–∞ in the endotoxaemic rabbits (26.3 ± 2.7 μg·h/mL) were significantly higher (P < 0.05) than values observed in healthy rabbits (17.2 ± 0.97 μg·h/mL). The total mean plasma clearance (CL_T) decreased from 1228 ± 107.5 mL·h/kg in the control group to 806.4 ± 91.4 mL·h/kg in the LPS‐treated rabbits. A significant increase (P < 0.05) in the half‐life of elimination was observed in the endotoxaemic rabbits (5.59 ± 1.14 h) compared to the values observed in healthy animals (3.44 ± 0.57 h). In conclusion, the administration of repeated doses of 1 μg/kg E. coli LPS induced an APR in rabbits, producing significant modifications in plasma concentrations of FFC leading to increases in the AUC, terminal half‐life and mean residence time (MRT), but a significant decrease in CL_T of the drug. As a consequence of the APR induced by LPS, there was a reduction in the metabolic conversion of FFC to their metabolite FFC‐a in the liver, suggesting that the mediators released during the APR induced significant inhibitory effects on the hepatic drug‐metabolizing enzymes.     

Effects of partial replacement of barley grain with beet pulp on performance,ruminal fermentation and plasma concentration of metabolites in transition dairy cows

The objective of this study was to determine the effect of partial replacement of barley grain with beet pulp (BP) on dry matter intake (DMI), ruminal fermentation, plasma concentration of metabolites and milk yield of transition dairy cows. Twenty‐four multiparous Holstein cows [735 ± 26 kg of body weights and 3.5 ± 0.05 of body condition score (BCS)] were used in a randomized complete block design. Cows were assigned randomly on day 28 relative to expected parturition date to one of three treatments containing (i) 0% BP, (ii) 25% BP or (iii) 50% BP substituted for barley grain on a DM basis. During the pre‐partum period, DMI and energy intake were greater (P < 0.01) in cows fed the BP diet compared with cows fed the barley grain diet. During the post‐partum period, substituting BP for barley grain caused a response in DMI and energy intake, with the highest amount for the 25% BP diet and lowest for the 50% BP diet (P < 0.01). Milk yield was lowest (P < 0.01) for 50% BP diet than the other treatments. During the post‐partum period, cows fed the 50% BP diets had greater rumen pH, molar proportion of butyrate and acetate: propionate ratio (P < 0.01) in the rumen compared with cows fed the 0% BP diets. In addition, cows fed the BP diets had greater (P < 0.01) plasma β‐hydroxybutyrate and lower plasma glucose (P < 0.05) and blood urinary nitrogen (BUN) (P < 0.01) concentrations than cows fed the barley grain diets. Results showed that substituting BP for barley grain was effective in increasing DMI, but it did not have a significant effect on net energy balance during the post‐partum period. However, replacing BP for barley grain at 50% had adverse effects on DMI, milk yield and metabolic status, as indicated by key blood metabolite concentrations.     

Pharmacokinetics of cefuroxime after intravenous,intramuscular, and subcutaneous administration to dogs

Cefuroxime pharmacokinetic profile was investigated in 6 Beagle dogs after single intravenous, intramuscular, and subcutaneous administration at a dosage of 20 mg/kg. Blood samples were withdrawn at predetermined times over a 12‐h period. Cefuroxime plasma concentrations were determined by HPLC. Data were analyzed by compartmental analysis. Peak plasma concentration (C_max), time‐to‐peak plasma concentration (T_max), and bioavailability for the intramuscular and subcutaneous administration were (mean ± SD) 22.99 ± 7.87 μg/mL, 0.43 ± 0.20 h, and 79.70 ± 14.43% and 15.37 ± 3.07 μg/mL, 0.99 ± 0.10 h, and 77.22 ± 21.41%, respectively. Elimination half‐lives and mean residence time for the intravenous, intramuscular, and subcutaneous administration were 1.12 ± 0.19 h and 1.49 ± 0.21 h; 1.13 ± 0.13 and 1.79 ± 0.24 h; and 1.04 ± 0.23 h and 2.21 ± 0.23 h, respectively. Significant differences were found between routes for K_a, MAT, C_max, T_max, t_½(a), and MRT. T > MIC = 50%, considering a MIC of 1 μg/mL, was 11 h for intravenous and intramuscular administration and 12 h for the subcutaneous route. When a MIC of 4 μg/mL is considered, T > MIC = 50% for intramuscular and subcutaneous administration was estimated in 8 h.     

Pregnancy‐Induced ISG‐15 and MX‐1 Gene Expression is Detected in the Liver of Holstein–Friesian Heifers During Late Peri‐Implantation Period

The bovine embryonic signal interferon‐τ (IFN‐τ) produced by the trophoblast is known to pass through the uterine fluid towards the endometrium and further into the maternal blood, where IFN‐τ induces specific expression of interferon‐stimulated gene expression (ISG), for example in peripheral leucocytes. In sheep, it was shown experimentally by administration of IFN‐τ that ISG is also detectable in the liver. The objective was to test whether ISG can be detected in liver biopsy specimens from Holstein–Friesian heifers during early pregnancy. Liver biopsies were taken on day 18 from pregnant and non‐pregnant heifers (n = 19), and the interferon‐stimulated protein 15 kDa (ISG‐15) and myxovirus‐resistance protein‐1 (MX‐1) gene expression was detected. The expression of both MX‐1 (p: 24.33 ± 7.40 vs np: 9.00 ± 4.02) and ISG‐15 (p: 43.73 ± 23.22 vs 7.83 ± 3.63) was higher in pregnant compared to non‐pregnant heifers (p < 0.05). In conclusion, pregnancy induced ISG‐15 and MX‐1 gene expression in the liver already at day 18 in cattle.