Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C 0) 11,653 µg/L and mean peak plasma concentrations (C max) 6,543 µg/L (IM), 4,883 µg/L (PO), and 31.5 µg/L (TD) were measured. The time points of peak FM concentrations (t max) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability (F) of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported C max of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low F of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.
Tylvalosin (TVN) is a water soluble macrolide used in swine production to treat enteric, respiratory, and arthritic pathogens. There is limited data on its distribution to synovial fluid beyond gavage studies, which do not represent field conditions. This study measured water disappearance, TVN concentration in the medicated water, daily dose, and concentrations of TVN and 3-O-acetyltylosin (3AT) in the synovial fluid and plasma of treated pigs over the administration period. The study emphasized understanding variation in tissue TVN concentrations within the context of a field setting. Sixty finisher pigs were housed individually with individual waterers. Six pigs were randomly allocated to the following time points for sample collection: 0, 48, 60, 72, 84, 96, 102, 108, 114, and 120 hr on medication. TVN was administered daily in the water for 5 days. Water disappearance and medicated water concentration were measured daily. At each time point, six pigs were euthanized and plasma and synovial fluid were collected for analysis. Median TVN synovial fluid concentrations ranged between <1 ng/ml (hour 0) to 3.6 ng/ml (hour 84). There was substantial variation between individual pigs for water disappearance (mean 4.36L and range 0-7.84). Median TVN water concentration was 59 ppm (range 38-75 ppm).
The objective of this study was to investigate the effects of dietary metabolizable energy (ME) level and the ratio of linoleic acid:α-linolenic acid (LA:ALA) on the growth performance, lipid metabolism, circulatory and joint inflammatory status, and synovial fluid proteome of grow-finish pigs. A total of 224 pigs (BW = 41.5 ±6.1 kg; PIC Genus 337 ×1050, Hendersonville, TN) were randomly assigned to either a high (3.55 Mcal/kg; HE) or low (3.29 Mcal/kg; LE) ME dietary treatment with a high (23:1) or low (12:1) LA:ALA in a 2 × 2 factorial arrangement. Diets were fed across three 28-day phases. Pigs were housed either 4 barrows or 4 gilts per pen. Blood samples were collected on d 0, 21, 42, and 84. Synovial fluid was collected from the hock and carpus joints on d 0 and d 84. Liver and adipose tissue samples were collected on d 84. Data were analyzed as repeated measures using PROC MIXED (SAS 9.4) with pen as the experimental unit and energy level, essential fatty acid ratio, sex, phase, and their interactions as fixed effects. Compared to LE, HE increased d 28, d 56 and d 84 body weight (BW; P = 0.005). For the overall period, HE increased average daily gain (ADG) compared to LE (P < 0.001) and improved feed efficiency (P = 0.001), while LE increased feed intake compared to HE (P < 0.001). Gilts receiving diets with low LA:ALA had similar final BW to barrows receiving a low LA:ALA at d 28, d 56 and d 84 (P = 0.024), resulting from improved overall d 0–84 ADG compared to gilts receiving the high LA:ALA (P = 0.031). In the liver, HE decreased the mRNA abundance of acetyl CoA carboxylase (ACACA; P = 0.004), cluster of differentiation 36 (P = 0.034), and tended to decrease fatty acid synthase (FASN; P = 0.056). In adipose tissue, HE decreased ACACA (P = 0.001) and FASN (P = 0.017). Plasma inflammatory markers C-reactive protein (CRP) and tumor necrosis factor-α (TNFα) were reduced on d 84 compared to d 0 (P ≤ 0.014). In the hock and carpus synovial fluid, LE tended to reduce CRP and TNFα (P ≤ 0.096). Hock and carpus synovial fluid CRP were also reduced on d 84 compared to d 0 (P = 0.001). Age of the pig impacted serum and hock synovial fluid protein abundance, but not energy level, LA:ALA, or their interactions (P < 0.05). To conclude, the high and low LA:ALA ratios utilized in this study can be fed at varying energy levels without impacting growth. Additionally, LA:ALA ratios can differentially impact the growth of barrows and gilts.
OBJECTIVE To determine reference intervals for total nucleated cell count, total protein concentration, pH, RBC count, and percentages of neutrophils, lymphocytes, and large mononuclear cells in synovial fluid samples (SFSs) obtained from the carpal and tarsal joints of healthy swine. ANIMALS 54 healthy commercial finisher pigs that had no evidence of lameness or gross joint swelling. PROCEDURES Each pig was anesthetized, and SFSs were collected from 1 carpal and 1 tarsal joint for fluid analysis, cytologic evaluation, bacterial culture, and PCR analyses for common swine joint pathogens. Each pig was euthanized after SFS collection, and synovial tissue samples were collected for histologic assessment. If necessary, postmortem SFSs were collected. RESULTS Overall, 37 of 50 tarsal and 46 of 53 carpal SFSs met inclusion criteria of sufficient volume, no gross blood contamination, and negative results of bacterial culture and PCR analyses, and were from joints with histologically normal synovial tissues. For the carpal and tarsal joints, upper reference limits were as follows: total nucleated cell count, 3,281 cells/μL and 2,368 cells/μL, respectively; total protein concentration, 3.6 g/dL and 3.6 g/dL, respectively; pH, 7.2 and 7.0, respectively; RBC count, 0.8 × 10 cells/μL and 0.1 × 10 cells/μL, respectively; and percentage of neutrophils, 46.5% and 33.7%, respectively; percentage of lymphocytes, 40.6% and 56.3%, respectively; and percentage of large mononuclear cells, 92.0% and 95.3%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results have provided reference intervals for selected variables in SFSs obtained from the carpal and the tarsal joints of healthy swine, which should be useful in diagnostic investigations of swine lameness and arthritis.
Objective: Evaluate the effectiveness of a staged market pig loading procedure for reducing contaminant transfer from livestock trailers to the barn. Materials and methods: A conventional loading procedure was compared to a staged procedure, with 10 replicates each. In the staged procedure, one loadout crew member was stationed between two lines of separation and could not cross onto the livestock trailer or into the center alleyway of the barn. The remaining loadout crew members within the barn could not cross into the loadout alleyway or chute. In the conventional procedure, a loadout crew member moved pigs from the center alleyway, through the loadout alleyway, and up the chute, but did not cross onto the livestock trailer. Fluorescent powder was mixed with obstetrical lubricant and wood shavings and spread evenly on the livestock trailer floor, just inside the roll-up door that opens to the chute. After each loadout, fluorescent powder contamination was evaluated at 8 locations: one in the chute, two in the loadout alleyway, and five in the center alleyway of the barn. Results: Four of five center alleyway locations had significantly lower contamination (P < .05) for the staged protocol compared to the conventional protocol. The level of contamination at the fifth center alleyway location was not statistically different (P = .057). The contamination level at all other locations was not statistically significant between the two groups (P > .05). Implications: The staged loading procedure effectively reduced the transfer of fluorescent powder from the livestock trailer to the barn.
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