Comparative effects of nonsteroidal anti-inflammatory drugs at castration and tail-docking in neonatal piglets.

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.

Plasma, urine and tissue concentrations of Flunixin and Meloxicam in Pigs.

BACKGROUND: The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues. RESULTS: Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g). CONCLUSIONS: These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

Pharmacokinetics of 14 C-ortho-phenylphenol following intravenous administration in pigs.

Workers in the USA are exposed to industrial formulations, which may be toxic. These formulations often contain preservatives or biocides such as ortho-phenylphenol (OPP). There are limited data describing OPP following intravenous administration to assess truly the clearance of this chemical in humans and other species. In vivo experiments were conducted in pigs to determine related pharmacokinetic parameters. 14 C-OPP was administered as an intravenous bolus dose. Blood, feces, urine and tissue samples were collected for analysis by liquid scintillation. Data were analyzed using non-compartmental and compartmental pharmacokinetic model approaches. These data fitted a three-compartment model and showed that the half-life of 14 C-OPP following the intravenous bolus in pigs was 46.26 ± 10.01 h. The kidneys play a crucial role in clearance of 14 C-OPP with a large percentage of the dose being found in the urine (70.3 ± 6.9% dose). Comparisons with other species suggest that 14 C-OPP clearance in pigs (2.48 ml h-1 kg-1 ) is less than that in humans (18.87 ml h-1 kg-1 ) and rats (35.51 ml h-1 kg-1 ). Copyright © 2016 John Wiley & Sons, Ltd.

Evaluation of peripheral lymphocytes after weaning and vaccination for Mycoplasma hyopneumoniae.

This study evaluated immune cell populations in pigs following weaning and vaccination for Mycoplasma hyopneumoniae. Piglets (n=24) were weaned (day 0) at 16 (±1) days of age, and randomly assigned to the vaccination group (n=16) or control group (n=8). Complete blood cell counts, flow cytometry and serology were completed for blood samples collected on days 0 (within hours of weaning), 3, 7, 14, 30 and 60. The M. hyopneumoniae S:P ratios (sample optical density: positive control optical density) were negative in the vaccination group until days 30 and 60, when the S:P ratios were 1.3 and 1.0, respectively. Control animals remained serologically negative. The percentage of CD4(+) T cells was less (P<0.01) in control pigs than vaccinated pigs at day 3. In contrast, numbers of CD8(+) and CD4(+)CD8(+) T cells were greater (P<0.01) in control pigs than in vaccinated pigs at days 3 and 7. After day 7, few differences in immune cell types were evident between the groups. Differences in lymphocyte populations could not be solely attributed to vaccination, due at least in part, to the confounding influence of weaning. It was difficult to distinguish the influence of vaccination from the impact of weaning on peripheral immune cell populations.

Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA with adjuvant monophosphoryl lipid A protects swine from a homologous but not a heterologous challenge.

Haemophilus ducreyi, the etiological agent of chancroid, has a strict requirement for heme, which it acquires from its only natural host, humans. Previously, we showed that a vaccine preparation containing the native hemoglobin receptor HgbA purified from H. ducreyi class I strain 35000HP (nHgbAI) and administered with Freund's adjuvant provided complete protection against a homologous challenge. In the current study, we investigated whether nHgbAI dispensed with monophosphoryl lipid A (MPL), an adjuvant approved for use in humans, offered protection against a challenge with H. ducreyi strain 35000HP expressing either class I or class II HgbA (35000HPhgbAI and 35000HPhgbAII, respectively). Pigs immunized with the nHgbAI/MPL vaccine were protected against a challenge from homologous H. ducreyi strain 35000HPhgbAI but not heterologous strain 35000HPhgbAII, as evidenced by the isolation of only strain 35000HPhgbAII from nHgbAI-immunized pigs. Furthermore, histological analysis of the lesions showed striking differences between mock-immunized and nHgbAI-immunized animals challenged with strains 35000HPhgbAI but not those challenged with strain 35000HPhgbAII. Mock-immunized pigs were not protected from a challenge by either strain. The enzyme-linked immunosorbent assay (ELISA) activity of the nHgbAI/MPL antiserum was lower than the activity of antiserum from animals immunized with the nHgbAI/Freund's vaccine; however, anti-nHgbAI from both studies bound whole cells of 35000HPhgbAI better than 35000HPhgbAII and partially blocked hemoglobin binding to nHgbAI. In conclusion, despite eliciting lower antibody ELISA activity than the nHgbAI/Freund's, the nHgbAI/MPL vaccine provided protection against a challenge with homologous but not heterologous H. ducreyi, suggesting that a bivalent HgbA vaccine may be needed.