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OBJECTIVE To investigate the effects of meloxicam administration before long-distance transport on inflammatory mediators and leukocyte function of cattle at feedlot arrival. ANIMALS 60 healthy yearling beef steers. PROCEDURES Single-source steers were assigned to a transported (n = 40) or nontransported (20) group. Then, half of the steers within each group were assigned to receive meloxicam (1 mg/kg, PO) or a lactose placebo (1 bolus/steer, PO). All steers were transported approximately 1,300 km overnight to a feedlot; however, the nontransported group was moved before treatment (meloxicam or placebo) administration and allowed a 17-day acclimation period, whereas the transported group was moved immediately after treatment administration on day -1. Blood samples for measurement of inflammatory mediators and leukocyte function were collected from all steers on days -1, 0, and 3. RESULTS For steers that received meloxicam, mean plasma meloxicam concentration for the transported group was significantly greater than that for the nontransported group on day 0. For steers that received the placebo, mean haptoglobin-matrix metalloproteinase-9 complex for the transported group was significantly greater than that for the nontransported group on day 0. Mean haptoglobin concentration, neutrophil L-selectin intensity, and polymorphonuclear leukocyte count for the transported group were significantly greater than those for the nontransported group. Mean substance P concentration for nontransported steers that received meloxicam was significantly lower than that for the other 3 treatment groups. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated meloxicam administration to healthy steers immediately before long-distance transport did not significantly mitigate the effects of transport-induced stress on leukocyte function or inflammatory markers.

OBJECTIVE To evaluate the effects of meloxicam on movement, feeding, and drinking behaviors of transported and nontransported cattle. ANIMALS 100 crossbred beef steers. PROCEDURES During experiment 1 of a 2-experiment study, calves from a livestock auction received meloxicam (1 mg/kg, PO; n = 50) or a lactose placebo (1 capsule/calf; 50; control), then calves were transported approximately 1,000 km overnight to a feedlot, where they were instrumented with a real-time location-monitoring ear tag, placed in randomly assigned pens (n = 5 pens/treatment), and monitored for 21 days. During experiment 2, calves in pens were administered the treatment opposite that of experiment 1, returned to their pens without undergoing transportation, and monitored for another 21 days. For each experiment, mean daily distance traveled and percentage time spent near feed (PNF) and water (PNW) were calculated on a pen basis and compared between treatments. RESULTS During experiment 1, mean daily distance traveled, PNF, and PNW did not differ significantly between meloxicam-treated and control calves; however, all 3 behaviors varied significantly by day. During experiment 2, although mean distance traveled was significantly associated with the interaction between day and treatment, it did not differ significantly between meloxicam-treated and control calves within any specific day. Mean PNF and PNW were significantly associated with day only, although no pattern in that effect was evident. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a single dose of meloxicam prior to transportation did not significantly affect the behaviors of transported and nontransported calves.

A study was conducted to evaluate the effect of tail docking on the welfare and performance of victimized pigs by tail biting and tail biters. Pigs ( = 240; 25.7 ± 2.9 kg average weight), including 120 pigs that were tail docked at birth and 120 pigs that remained with intact tails, were used. Pigs were housed in 8 pens of 30 pigs in a confinement barn for 16 wk, with 4 pens each housing pigs of both sexes with docked or intact tails. Tail biters and victimized pigs with damaged tails were identified during outbreaks of tail biting. Growth performance was monitored, and skin lesions on the tail, ears, and body were assessed. Blood samples were collected from focal tail biters, victimized pigs, and nonvictimized pigs for analysis of total serum protein, IgG, and substance P concentrations. When pigs were marketed, carcass weights and the number of pigs with carcass trim loss were recorded. During the growing-finishing period, 48% of pigs with docked tails and 89% of pigs with intact tails experienced lesions on their tails, including 5% of docked pigs and 30% of intact pigs identified as victimized pigs that experienced puncture wounds with signs of infection on their tails or loss of tails ( < 0.001). Victimized pigs tended to gain less weight ( = 0.07) between 17 and 21 wk of age than other pigs when tail biting prevailed in this study. Victimized pigs were more frequently ( = 0.04) sold for less than full value and had a lower dressing percentage ( < 0.001) compared with nonvictimized pigs. For victimized pigs, total serum protein and IgG concentrations were elevated 5 d after tails were injured, suggesting that tail damage can cause inflammation, which may lead to carcass abscesses and trim loss. Compared with victimized pigs and nonvictimized pigs, tail biters had lower total serum protein ( = 0.01) and IgG ( = 0.01) concentrations, indicating that tail biters may experience poor immune functions. Results of this study demonstrated that tail docking reduced tail damage in pigs kept in a confinement system. Tail damage can cause inflammation and reduce the value of market pigs. More research is needed to test whether compromised immune functions predispose pigs to tail biting.

The pharmacokinetics of intramuscularly administered ceftiofur crystalline-free acid (CCFA) were determined in pigs that were clinically healthy (n = 8), vaccinated with a Porcine reproductive and respiratory syndrome modified live virus (PRRS MLV) (n = 10), challenged with wild-type porcine reproductive and respiratory syndrome virus (PRRSv) VR-2385 (n = 10), or vaccinated with PRRS MLV and later challenged with wild-type PRRSv VR-2385 (n = 10). Animals were given a single dose of CCFA intramuscularly at 5 mg/kg body weight. Blood was collected at 0 (pretreatment), 0.25, 0.5, 1, 6, 12, 24, 48, 96, 144, 192, and 240 h postinjection. Plasma was analyzed using liquid chromatography-mass spectrometry. Plasma concentration-time curves for each group were evaluated with noncompartmental modeling. When compared to control animals, those receiving the PRRSv wild-type challenge only had a lower AUC 0-last , higher Cl/F, and higher Vz/F. The PRRSv wild-type challenge only group had the longest T 1/2λ . The C max did not differ among all four treatments. Control animals had no statistically significant differences from animals vaccinated with PRRS MLV alone or animals vaccinated with PRRS MLV and later challenged with wild-type PRRSv. Our results suggest that PRRSv wild-type infection has the potential to alter CCFA pharmacokinetics and PRRS MLV vaccination may attenuate those changes., (© 2016 John Wiley & Sons Ltd.)

Lameness affects the cattle industry via both economic losses and welfare considerations. In addition to production deficits, the pain and distress associated with lameness have been documented. Evaluation and prevalence of lame cattle are among the primary factors in third-party welfare audit programs. Mean lameness prevalence in herds has been reported to be as high as 36.8%, although a less than 10% prevalence of lame cattle was reported by some producers. Note that lameness is usually underreported by producers compared with independent observers, potentially because of a decreased sensitivity in detecting lame cattle., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The objective of this study was to evaluate the analgesic properties of transdermal flunixin meglumine when given at the time of dehorning on pain biomarkers. Twenty-four weaned male Holstein calves, 6 to 8 wk of age were enrolled into the study. The calves were randomly assigned to 1 of 3 treatment groups: 1) transdermal flunixin and dehorn (DH-FLU); 2) transdermal flunixin and sham dehorn (SHAM-FLU); and 3) placebo and dehorn (DH-PLBO). Transdermal flunixin at a label dose of 3.33 mg/kg (or placebo at an equivalent volume) was administered as a pour-on along the top-line of the calves in each treatment group concurrently with electrocautery dehorning or sham dehorning. Biomarker parameters collected and analyzed included: infrared thermography (IRT), mechanical nociception threshold (MNT), plasma cortisol, and substance P (SP). There were no differences in maximal temperatures detected for the IRT measurements of the medial canthus of the eye for the DH groups. Mean control point MNT measurements at 48 h were 3.14 kgF, 3.46 kgF, and 1.43 kgF for the DH-FLU, Sham-FLU, and DH-PLBO groups, respectively (P = 0.0001). No other differences of MNT were detected between the dehorned groups for the other test sites and time points. Plasma cortisol reached peak concentration at 20 min postdehorning for the DH-FLU and DH-PLBO groups and 10 min for SHAM-FLU group. Peak plasma cortisol concentrations were 32.0 ng/mL, 12.7 ng/mL, and 28.8 ng/mL for the DH-FLU, SHAM-FLU, and DH-PLBO groups, respectively. Cortisol concentrations were lower for the DH-FLU group at 90 min postdehorning compared to the SHAM-FLU and DH-PLBO groups ( = 0.04). Area under the effect curve (AUEC) were similar for all groups ( = 0.93). No statistical differences in SP concentrations between groups were detected for any of the time points. In conclusion, transdermal flunixin meglumine given at the time of dehorning did not provide substantial analgesia based on the pain biomarkers investigated. Further investigation into its role as part of a multimodal analgesic plan is warranted.

Background: It has been suggested that the dose requirement for spinal anesthesia (SA) is lower in obese patients for cesarean delivery (CD). In this prospective, observational, noninferiority study, we tested the hypothesis that obesity would not have a clinically important effect on vasopressor requirements or block height., Methods: Two groups of 25 parturients, group O (body mass index [BMI] >40 kg/m) and group N (BMI <32 kg/m) requiring elective CD were recruited. All patients received 10 mg intrathecal hyperbaric bupivacaine coadministered with 10 μg fentanyl. Dermatomal levels were assessed at 5 and 25 minutes after SA, and at completion of surgery, using light touch and cold sensation in response to ethyl chloride. The primary outcomes were phenylephrine requirement in the first 30 minutes after SA, and maximum block height, measured by the sensation of touch and cold. Secondary outcomes were total phenylephrine dose required, changes in hand grip strength, and peak flow rate., Results: There were no significant between-group differences in median block height as assessed by touch at 5 or 25 minutes or by temperature at 5 minutes. At 25 minutes, there was a 2-dermatome difference in median block height for loss of temperature sensation between group O and group N (T2 vs T4, 95% confidence interval [CI] of the difference in medians 0-2 dermatomes). No blocks extended to cervical dermatomes. The median (range) phenylephrine dose for the first 30 minutes was 150 µg (0-900 µg), and 100 µg (0-1250 µg) in group N and group O, respectively. The 95% CI for the difference between the 2 median doses was -150 µg to 100 µg. There were no differences in median percentage reductions in peak flow rate or median hand grip strength after SA. Mean surgical time was longer in group O than in group N (49.1 vs 39.4 min, 95% CI difference 1.7-17.7 min). The mean time for recovery of touch sensation to T10 was longer in group O (152 vs 132 min, 95% CI difference 3.8-36.2 min). No analgesic supplementation was required., Conclusion: Only a minor increase in block height as assessed by temperature occurred in group O at 25 minutes. Vasopressor requirements during the first 30 minutes of SA were equivalent. Time for regression of SA block level was longer in the group O, which may be beneficial considering the longer surgical time. A dose of spinal bupivacaine 10 mg for single-shot SA should not be reduced in morbidly obese parturients.

This study describes the pharmacokinetics of topical and intravenous (IV) flunixin meglumine in Holstein calves. Eight male Holsteins calves, aged 6 to 8 weeks, were administered flunixin at a dose of 2.2 mg/kg intravenously. Following a 10-day washout period, calves were dosed with flunixin at 3.33 mg/kg topically (transdermal). Blood samples were collected at predetermined times from 0 to 48 h for the intravenous portions and 0 to 72 h following topical dosing. Plasma drug concentrations were determined using liquid chromatography with mass spectroscopy. Pharmacokinetic analysis was completed using noncompartmental methods. The mean bioavailability of topical flunixin was calculated to be 48%. The mean AUC for flunixin was determined to be 13.9 h × ug/mL for IV administration and 10.1 h × ug/mL for topical administration. The mean half-life for topical flunixin was 6.42 h and 4.99 h for the intravenous route. The C max following topical application of flunixin was 1.17 μg/mL. The time to maximum concentration was 2.14 h. Mean residence time (MRT) following IV injection was 4.38 h and 8.36 h after topical administration. In conclusion, flunixin when administered as a topical preparation is rapidly absorbed and has longer half-life compared to IV administration., (© 2016 John Wiley & Sons Ltd.)

Metritis is a frequent problem in postpartum dairy cows. Intrauterine therapy with the antimicrobial oxytetracycline (OTC) is often used, although this therapy has not been shown to be superior to systemic therapy. The objectives of this study were to (1) determine the plasma and milk concentrations of OTC following intrauterine infusion in postpartum dairy cows with varying degrees of metritis severity; (2) determine the depletion time of OTC in an attempt to provide veterinarians withdrawal guidelines, should they use this therapy; and (3) correlate metritis severity scores with OTC concentrations in plasma and milk. Our hypothesis was that cows with more severe metritis would have higher OTC concentrations in milk following intrauterine therapy. Thirty-two cows were selected to participate in the study after farm personnel had determined that they had metritis based on evaluation of vaginal discharge between 4 and 14 DIM, in accordance with the farm's treatment protocols. Metritis scores (1-4) were assigned based on a published scheme: 1 represented yellow-to-orange thick discharge or translucent mucus with no fetid smell; 2 represented blood-tinged vaginal mucus, slightly watery, with little or no fetid smell; 3 represented red to red/brown watery discharge with moderate fetid smell; and 4 represented red to red/brown watery discharge containing pieces of placenta and an intense fetid smell. Trial cows received a single treatment of 4g of OTC (approximately 6.7mg/kg) via intrauterine infusion. Blood samples were collected over 96h, and milk samples were collected before intrauterine therapy and 3 times a day for 4 d following infusion. Following treatment, OTC rapidly diffused to plasma and subsequently to milk. Maximum OTC concentrations in plasma and milk occurred within the first 24h following intrauterine infusion, and 25 of the 32 cows had detectable OTC concentrations in milk at 4 d after intrauterine infusion. Cows with clinical metritis (metritis severity scores of 3 or 4) at the initiation of treatment were significantly and positively correlated with higher milk OTC concentrations at the second [time (T)9 h; r=0.43], fourth (T25 h; r=0.42), and fifth milking following treatment (T33 h; r=0.38) compared with cows with normal vaginal discharge. We also observed a positive correlation between initial metritis score and milk maximum concentration (r=0.36) and milk area under the concentration curve (r=0.36). Given that intrauterine administration of OTC is an extra-label therapy, dairy producers should consult with their veterinarian to ensure that milk is being tested at or below the established tolerance for OTC. This will ensure that violative drug residues do not enter the human food supply., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Bovine respiratory disease is the most economically important disease of feedlot cattle in North America. Choice of antibiotic is a critical factor for producers and veterinarians. We previously published a mixed-treatment comparison meta-analysis that combined evidence from published trials and published estimates of comparative efficacy for 12 antibiotics registered for use in the USA. Some of the comparative efficacy estimates were based only on indirect evidence. Since the original review was published, new studies that provide direct evidence of comparative efficacy have been published. We updated the original review to include the current evidence. We also compared the results from the indirect estimates from the prior model with the observed results from randomized control trials. We repeated the original search and found that five of the new studies met the criteria for inclusion in the updated review. Four of these studies provided new data on direct comparisons of active drugs. The results from one study (performed in 2002) that compared ceftiofur pinna and enrofloxacin were inconsistent with the network and were excluded from the analysis. Three new direct comparison studies examined gamithromycin compared with tulathromycin, florfenicol, and tilmicosin. The results of our analysis suggested that the indirect estimates from the prior model provided reasonable estimates of the risk ratios revealed by the primary studies. For example, for the comparison of gamithromycin (referent) with tulathromycin, the original model predicted a risk ratio of re-treatment of 0.54 (95% credible interval 0.27-0.87). The subsequent randomized controlled trial revealed that the observed risk ratio of re-treatment was 0.59 (95% confidence interval 0.45-0.78). The results of other comparisons were also similar. For the gamithromycin (referent) to florfenicol comparison, the observed randomized trial RR was 1.17 (95% confidence interval 0.83-1.64) and the indirect estimate of RR from the prior model was 0.84 (95% credibility interval 0.48-1.3). The gamithromycin to tilmicosin (referent) observed RR from the randomized trial was 0.99 (95% confidence interval 0.67-1.47) and the indirect estimate of RR from the prior model was 1.09 (95% credible interval 0.64-1.79). The results suggested that indirect estimates provided reasonable estimates of RR when direct data were not available., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The objective of this study was to investigate the impact of oral meloxicam (MEL) and long-distance transportation on cell-mediated immunity (CMI) in preconditioned steers receiving a booster vaccination on arrival. We hypothesized that steers treated with MEL at 1mg/kg body weight, 6h before night-time transport, would be less immunocompromised on arrival (day 0) and after 7days, and that CMI following vaccination with a modified live bovine viral diarrhea virus (BVDV) recall antigen would be increased. Brahman crossbreed steers, 13-17 months of age (n=87), were randomly assigned to one of four treatment groups: MEL, transported (MTR) (n=22), MEL, non-transported (MNT) (n=22), lactose placebo, transported (CTR) (n=21), and lactose placebo, non-transported (CNT) (n=22). MTR and CTR steers were transported for approximately 16h non-stop on a truck from Mississippi to Iowa (approximately 1300km), whereas steers in the MNT and CNT groups remained in Mississippi as non-transported controls. Body weight was measured and jugular blood was collected at -1, 0, and 7days from all steers at the same time, regardless of location. Multi-parameter flow cytometry (MP-FCM) was used to identify T-cell subsets and detect the expression of three activation markers (CD25 [interleukin (IL)-2 receptor], intracellular interferon-gamma [IFNγ], and IL-4) after in vitro stimulation with BVDV recall antigen. Plasma cortisol concentration was measured on day -1, 0, and 7 as a marker of transport-associated stress. Serum antibody titer to BVDV was assessed on day -1 and day 7 post-booster vaccination. Whole-blood samples were analyzed using MP-FCM on days 0 and 7. Results were log transformed and analyzed using repeated measures of analysis of variance. Compared with non-transported controls, transport led to an increase in BVDV-induced expression of CD25, IFNγ, and IL-4 in CD4(+), CD8(+), and γδ(+) T-cell subsets (P<0.05). MEL treatment mitigated the transportation-associated increase in CD25 expression by peripheral blood mononuclear cells (PBMCs), CD4(+), and γδ(+) T cells. CMI outputs for the MTR group were less than those of the CTR group (P<0.05); however, the MTR and NT groups did not differ (P>0.10). A treatment*transport interaction was noted for the increase in IL-4 expression by CD8(+) T cells after transport, with a significant difference between the CTR and MTR groups at day 7. In conclusion, the use of oral MEL prior to transport appears to have inhibitory or homeostatic effects, but further research is needed to validate the effect of MEL treatment on specific T-cell subsets in transported cattle., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Infectious bovine keratoconjunctivitis (IBK) is a common and important disease of calves. Without effective vaccines, antibiotic therapy is often implemented to minimize the impact of IBK. This review updates a previously published systematic review regarding comparative efficacy for antibiotic treatments of IBK. Available years of Centre for Biosciences and Agriculture International and MEDLINE databases were searched, including non-English results. Also searched were the American Association of Bovine Practitioners and World Buiatrics Congress conference proceedings from 1996 to 2016, reviews since 2013, reference lists from relevant trials, and U.S. Food and Drug Administration New Animal Drug Application summaries. Eligible studies assessed antibiotic treatment of naturally-occurring IBK in calves randomly allocated to group at the individual level. Outcomes of interest were clinical score, healing time, unhealed ulcer risk, and ulcer surface area. A mixed-effects model comparing active drug with placebo was employed for all outcomes. Heterogeneity was assessed visually and using Cochran's Q-test. Thirteen trials assessing nine treatments were included. Compared with placebo, most antibiotic treatments were effective. There was evidence that the treatment effect differed by day of outcome measurement. Visually, the largest differences were observed 7-14 days post-treatment. These results indicate improved IBK healing with many antibiotics and suggest the need for randomized trials comparing different antibiotic treatments.

Objective: To investigate the accuracy of a minimally invasive, 2-step, lookup method for determining mixed venous oxygen saturation compared with conventional techniques., Design: Single-center, prospective, nonrandomized, pilot study., Setting: Tertiary care hospital, university setting., Participants: Thirteen elective cardiac and vascular surgery patients., Interventions: All participants received intra-arterial and pulmonary artery catheters. Minimally invasive oxygen consumption and cardiac output were measured using a metabolic module and lithium-calibrated arterial waveform analysis (LiDCO; LiDCO, London), respectively. For the minimally invasive method, Step 1 involved these minimally invasive measurements, and arterial oxygen content was entered into the Fick equation to calculate mixed venous oxygen content. Step 2 used an oxyhemoglobin curve spreadsheet to look up mixed venous oxygen saturation from the calculated mixed venous oxygen content. The conventional "invasive" technique used pulmonary artery intermittent thermodilution cardiac output, direct sampling of mixed venous and arterial blood, and the "reverse-Fick" method of calculating oxygen consumption., Measurements and Main Results: LiDCO overestimated thermodilution cardiac output by 26%. Pulmonary artery catheter-derived oxygen consumption underestimated metabolic module measurements by 27%. Mixed venous oxygen saturation differed between techniques; the calculated values underestimated the direct measurements by between 12% to 26.3%, this difference being statistically significant., Conclusion: The magnitude of the differences between the minimally invasive and invasive techniques was too great for the former to act as a surrogate of the latter and could adversely affect clinical decision making., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.

The objective of this study was to investigate the effects of carprofen administered immediately before cautery dehorning on nociception and stress. Forty Holstein calves aged approximately 6 to 8 wk old were either placebo treated and sham dehorned ( = 10) or cautery dehorned following administration of carprofen (1.4 mg/kg) subcutaneously ( = 10) or orally ( = 10) or a subcutaneous and oral placebo ( = 10) in a randomized, controlled trial. All animals were given a cornual nerve block using lidocaine before dehorning. Response variables including mechanical nociception threshold, ocular temperature, heart rate, and respiratory rate were measured before and following cautery dehorning for 96 h. Blood samples were also collected over 96 h following dehorning and analyzed for plasma cortisol and substance P concentrations by RIA. Plasma carprofen concentration and ex vivo PGE concentrations were also determined for this time period. Average daily gain was calculated for 7 d after dehorning. Data were analyzed using a linear mixed effects model with repeated measures, controlling for baseline values by their inclusion as a covariate in addition to planned contrasts. Dehorning was associated with decreased nociception thresholds throughout the study and a stress response immediately after dehorning, following the loss of local anesthesia, and 48 h after dehorning compared with sham-dehorned calves. Carprofen was well absorbed after administration and reached concentrations that inhibited ex vivo PGE concentrations for 72 h (subcutaneous) and 96 h (oral) compared with placebo-treated calves ( < 0.05). Carprofen-treated calves tended to be less sensitive ( = 0.097) to nociceptive threshold tests. Overall, at the dosing regimen studied, the effect of carprofen on sensitivity and stress following cautery dehorning was minimal. Consideration of route of administration and dose determination studies may be warranted.

Previous research has shown that postpartum administration of the nonsteroidal antiinflammatory drug (NSAID) sodium salicylate can increase 305-d milk yield in older dairy cattle (parity 3 and greater). However, in this prior work, sodium salicylate was delivered to cows via the drinking water, a method that does not align well with current grouping strategies on commercial dairy farms. The objective of the current study was to replicate these results on a commercial dairy farm with a simplified treatment protocol and to compare sodium salicylate with another NSAID, meloxicam. Dairy cattle in their second lactation and greater (n=51/treatment) were alternately assigned to 1 of 3 treatments at parturition, with treatments lasting for 3d. Experimental treatments began 12 to 36 h after parturition and were (1) 1 placebo bolus on the first day and 3 consecutive daily drenches of sodium salicylate (125 g/cow per day; SAL); (2) 1 bolus of meloxicam (675 mg/cow) and 3 drenches of an equal volume of water (MEL); or (3) 1 placebo bolus and 3 drenches of water (CON). Blood samples were collected on the first day of treatment, immediately following the last day of treatment, and 7d after the last day of treatment; plasma was analyzed for glucose, β-hydroxybutyrate (BHB), free fatty acids, haptoglobin, and paraoxonase. Milk production, body condition score, reproductive status, and retention in the herd were monitored for 365 d posttreatment, and effects of treatment, parity, days in milk, and interactions were evaluated in mixed effects models. Significance was declared at P<0.05. Whole-lactation milk and protein yields were greater in NSAID-treated cows, although 305-d fat production was not affected. There was a significant interaction of treatment and parity for plasma glucose concentration; MEL increased plasma glucose concentrations compared with CON and SAL in older cows. Sodium salicylate decreased plasma BHB concentration compared with MEL at 7d posttreatment, although no difference was detected immediately following treatment. Haptoglobin concentrations were elevated in SAL cows compared with CON. There was a tendency for CON cows to be removed from the herd more quickly than MEL cows (42 vs. 26% at 365 d posttreatment). Body condition score, concentrations of plasma free fatty acids and paraoxonase, and time to pregnancy were not affected by treatment. These results indicate that NSAID administration in postpartum cows has the potential to be a viable way to improve productivity and potentially longevity in commercial dairies, although further research is necessary to optimize recommendations for producers., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Mastitis is a frequent problem among dairy cows, reducing milk yield and increasing cull rates. Systemic therapy with the cephalosporin antimicrobial ceftiofur hydrochloride (CEF) may improve therapeutic outcomes, but the incidence of CEF violative residues has increased annually since 2011. One potential explanation is that disease status may alter the pharmacokinetics (PK) of CEF. To test this hypothesis, we compared the plasma PK of CEF in healthy cows with those with severe endotoxic mastitis. Eight cows with naturally occurring mastitis and 8 clinically healthy cows were treated with 2.2 mg of CEF per kilogram of body weight once daily for 5d via the intramuscular route. Blood was collected at 0, 0.33, 0.67, 1, 1.5, 2, 3, 4, 8, 16, and 24h after the first CEF administration and every 8h thereafter until 120 h after the final dose. Plasma samples were analyzed for CEF concentrations using liquid chromatography coupled with mass spectrometry. With the exception of time 0, CEF was detected at all time points. The disease group had a significantly higher plasma CEF concentration at t=3h after the first injection and a significantly lower plasma concentration from 40 to 152 h following the first injection, with the exception of the t=64 h time point. Data following the first injection (time 0-24 h) were fit to a single-dose, noncompartmental PK model. This model indicated that the disease group had a shorter plasma half-life. A multidose, noncompartmental model was used to determine steady-state PK. Compared with control cows, the disease group had an initially higher peak concentration and a higher volume of distribution and drug clearance rates. The disease group also had a lower area under the curve per dosing interval, steady-state concentration maximum, and dose-adjusted peak steady-state concentration. All other PK parameters were not different between the 2 groups. Altered PK, as suggested by this trial, may contribute to an increased risk for the development of a violative residue in meat. Further research is needed to more completely characterize drug distribution in diseased cattle and to study the effect of coadministration of other drugs on drug distribution., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to investigate the pharmacokinetics and tissue disposition of meloxicam after repeated oral administration in calves. Thirteen male British × Continental beef calves aged 4 to 6 months and weighing 297-392 kg received 0.5 mg/kg meloxicam per os once daily for 4 days. Plasma meloxicam concentrations were determined in 8 calves over 6 days after first treatment. Calves were randomly assigned to be euthanized at 5, 10, 15 (n = 3/timepoint), and 19 days (n = 4) after final administration. Meloxicam concentrations were determined in plasma (LOQ= 0.025 μg/mL) and muscle, liver, kidney, and fat samples (LOQ = 2 ng/g) after extraction using validated LC-MS-MS methods. The mean (± SD) Cmax , Cmin , and Caverage plasma meloxicam concentrations were 4.52 ± 0.87 μg/mL, 2.95 ± 0.77 μg/mL, and 3.84 ± 0.81 μg/mL, respectively. Mean (± SD) tissue meloxicam concentrations were highest in liver (226.67 ± 118.16 ng/g) and kidney samples (52.73 ± 39.01 ng/g) at 5 days after final treatment. Meloxicam concentrations were below the LOQ in all tissues at 15 days after treatment. These findings suggest that tissue from meloxicam-treated calves will have low residue concentrations by 21 days after repeated oral administration., (© 2015 John Wiley & Sons Ltd.)

This review identifies priorities for beef cattle welfare research in the USA. Based on our professional expertise and synthesis of existing literature, we identify two themes in intensive aspects of beef production: areas where policy-based actions are needed and those where additional research is required. For some topics, considerable research informs best practice, yet gaps remain between scientific knowledge and implementation. For example, many of the risk factors and management strategies to prevent respiratory disease are understood, but only used by a relatively small portion of the industry. This is an animal health issue that will require leadership and discussion to gain widespread adoption of practices that benefit cattle welfare. There is evidence of success when such actions are taken, as illustrated by the recent improvements in handling at US slaughter facilities. Our highest priorities for additional empirical evidence are: the effect of technologies used to either promote growth or manage cattle in feedlots, identification of management risk factors for disease in feedlots, and management decisions about transport (rest stops, feed/water deprivation, climatic conditions, stocking density). Additional research is needed to inform science-based recommendations about environmental features such as dry lying areas (mounds), shade, water and feed, as well as trailer design.

This study determined the impact of porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis coinfection on the pharmacokinetic (PK) profile of ceftiofur hydrochloride in pigs after intramuscular (i.m.) injection. Eighteen clinically normal crossbred gilts were assigned by weight into a challenge group (10 pigs) and control group (eight pigs). Pigs in both groups received a single i.m. injection of ceftiofur hydrochloride (Excenel RTU Sterile Suspension; Zoetis) at a 5 mg/kg BW dose. Serial blood samples were collected to characterize the plasma concentration curve. After a 10 days drug washout period, the challenge group was inoculated with 2 mL of PRRSV isolate VR-2385 (10(5.75) 50% tissue culture infective doses per mL) intranasally and 8 days later inoculated S. suis. When clinical disease was evident, the second PK assessment began in both challenge and control groups. Coinfected pigs demonstrated lower values of AUC and CMAX , but higher values of Cl/F and Vz/F indicating drug kinetics were altered by infection. The data from this study have implications on ceftiofur treatment regimens in diseased pigs., (© 2015 John Wiley & Sons Ltd.)

Development and use of on-farm assays to detect antimicrobial residues in milk is important to reduce the risk of violative residues in marketed milk. The objective of this study was to evaluate the effectiveness of a lateral-flow immunodiagnostic assay (BetaStar Plus, Neogen Corp., Lansing, MI) in detecting ceftiofur residues in milk from individual cows treated for mastitis. This assay is currently approved by the US Federal Drug Administration (FDA) for detecting β-lactam residues in commingled milk. Forty-five dairy cows with clinical mastitis from 4 dairy farms were enrolled and treated intramammary with 125 mg of ceftiofur hydrochloride (Spectramast LC, Zoetis, Madison, NJ) according to the manufacturer's label recommendation. Composite milk samples were collected (A) before first intramammary antimicrobial treatment, (B) before the last intramammary antimicrobial treatment, (C) the last milking of the product-labeled milk withhold, (D) the first milking after the product-labeled milk withhold had been met, and (E) 72 h after the product-labeled milk withhold had been met. Samples were tested using the BetaStar Plus assay within 48 h of collection. Parallel samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and for somatic cell count and milk components. The BetaStar Plus assay identified 6.7, 60.0, 46.7, 22.2, and 6.7% positive samples at each of the respective time points. The assay had sensitivity and specificity of 100 and 84.7%, respectively, compared with liquid chromatography-tandem mass spectrometry analysis using FDA published residue tolerance levels for ceftiofur (or ceftiofur metabolites) as a threshold. The BetaStar Plus assay could be useful for detecting ceftiofur residues in milk from individual cows following intramammary treatment for mastitis before the milk is shipped for processing., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Perioperative analgesic effects of oral firocoxib following cautery disbudding were investigated in preweaned calves. Twenty Holstein calves approximately 4 to 6wk old received a single oral dose of firocoxib, a nonsteroidal antiinflammatory, at 0.5mg/kg (n=10) or placebo (n=10) in a randomized controlled clinical trial. Responses, including ocular temperature determined by infrared thermography, pressure algometry measuring mechanical nociception threshold, and heart rate, were evaluated at 2, 4, 7, 8, and 24h after cornual nerve block and cautery disbudding. Blood samples were collected over 96h and analyzed for plasma cortisol and substance P concentrations by RIA. Additionally, ex vivo prostaglandin E2 concentrations were determined over a 72-h study period using an enzyme immunoassay. Data were analyzed using a linear mixed effects model with repeated measures. An inhibition of ex vivo prostaglandin E2 synthesis was observed from 12 to 48h following disbudding in calves treated with firocoxib. Cautery disbudding was associated with an increased nociception for the duration of sampling (24h). During the initial 24-h period following disbudding, no difference in response between treatment groups was noted. Following 24h, mean cortisol concentrations diverged between the 2 study groups with placebo-treated calves having increased cortisol concentrations at approximately 48h after disbudding. Furthermore, the overall integrated cortisol response as calculated as area under the effect curve tended to be reduced in firocoxib-treated calves. The prolonged effects of cautery dehorning require further investigation. Moreover, the effect of firocoxib on cortisol reduction observed in this study requires additional exploration., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Gabapentin (1-[aminomethyl] cyclohexane acetic acid) is a γ-aminobutyric acid analogue that has been shown to be efficacious for neuropathic pain control in humans. Plasma gabapentin concentrations >2 μg/ml are considered effective in treating epilepsy in humans and are suggested to provide analgesia for neuropathic pain. This study investigated the pharmacokinetics of a single oral dose of gabapentin suspension (11 mg/kg) in great horned owls ( Bubo virginianus ). Plasma gabapentin concentrations were determined in six healthy birds for 48 hr using high-performance liquid chromatography with mass spectrometric detection. Plasma gabapentin concentrations were estimated by noncompartmental pharmacokinetic analysis. The harmonic mean (±SD) maximum concentration (Cmax), time to maximum concentration (Tmax), and elimination half-life (tv2λZ) for gabapentin (11 mg/kg) were 6.17±0.83 μg/ml, 51.43±5.66 min, and 264.60±69.35 min, respectively. In this study, plasma gabapentin concentrations were maintained above 2 μg/ml for 528 min (8.8 hr), suggesting that gabapentin administered orally every 8 hr may be appropriate in great horned owls.

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of tulathromycin after a single subcutaneous administration in the cervical region in sheep using the cattle labeled dose of 2.5 mg/kg. Six adult healthy ewes were administered tulathromycin on day 0. Blood samples were collected just prior to dosing and at selected time points for 360 h. Plasma samples were analyzed to determine tulathromycin concentrations, and noncompartmental analysis was performed for pharmacokinetic parameters. The mean maximum plasma concentration was 3598 ng/mL, the mean time to maximum concentration was 1.6 h, and the apparent elimination half-life ranged from 68.1 to 233.1 h (mean 118 h). When comparing our results to goats and cattle, it appears sheep are more similar to cattle in regard to the concentrations observed and pharmacokinetic parameters. In summary, the pharmacokinetics of tulathromycin in sheep appear to be similar enough to those in goats and cattle to recommend similar dosing (2.5 mg/kg SC), assuming that the target pathogens have similar inhibitory concentrations., (© 2014 John Wiley & Sons Ltd.)

Background: The theme of the 2014 Southern African Rural Health Conference was 'Building resilience in facing rural realities'. Retaining health professionals in South Africa is critical for sustainable health services. Only 12% of doctors and 19% of nurses have been retained in the rural areas. The aim of the workshop was to understand from health practitioners why they continued working in their rural settings. CONFERENCE WORKSHOP: The workshop consisted of 29 doctors, managers, academic family physicians, nurses and clinical associates from Southern Africa, with work experience from three weeks to 13 years, often in deep rural districts. Using the nominal group technique, the following question was explored, 'What is it that keeps you going to work every day?' Participants reflected on their work situation and listed and rated the important reasons for continuing to work., Results: Five main themes emerged. A shared purpose, emanating from a deep sense of meaning, was the strongest reason for staying and working in a rural setting. Working in a team was second most important, with teamwork being related to attitudes and relationships, support from visiting specialists and opportunities to implement individual clinical skills. A culture of support was third, followed by opportunities for growth and continuing professional development, including teaching by outreaching specialists. The fifth theme was a healthy work-life balance., Conclusion: Health practitioners continue to work in rural settings for often deeper reasons relating to a sense of meaning, being part of a team that closely relate to each other and feeling supported.

The objective of this study was to evaluate the pharmacokinetic properties and physiologic effects of a single oral dose of alprazolam in horses. Seven adult female horses received an oral administration of alprazolam at a dosage of 0.04 mg/kg body weight. Blood samples were collected at various time points and assayed for alprazolam and its metabolite, α-hydroxyalprazolam, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of alprazolam was analyzed by a one-compartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single-dose administration of alprazolam were as follows: Cmax 14.76 ± 3.72 ng/mL and area under the curve (AUC0-∞ ) 358.77 ± 76.26 ng·h/mL. Median (range) Tmax was 3 h (1-12 h). Alpha-hydroxyalprazolam concentrations were detected in each horse, although concentrations were low (Cmax 1.36 ± 0.28 ng/mL). Repeat physical examinations and assessment of the degree of sedation and ataxia were performed every 12 h to evaluate for adverse effects. Oral alprazolam tablets were absorbed in adult horses and no clinically relevant adverse events were observed. Further evaluation of repeated dosing and safety of administration of alprazolam to horses is warranted., (© 2014 John Wiley & Sons Ltd.)

The purpose of this study was to compare the pharmacokinetics of meloxicam in mature swine after intravenous (i.v.) and oral (p.o.) administration. Six mature sows (mean bodyweight ± standard deviation = 217.3 ± 65.68 kg) were administered an i.v. or p.o. dose of meloxicam at a target dose of 0.5 mg/kg in a cross-over design. Plasma samples collected up to 48 h postadministration were analyzed by high-pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by noncompartmental pharmacokinetic analysis. Mean peak plasma concentration (CMAX ) after p.o. administration was 1070 ng/mL (645-1749 ng/mL). TMAX was recorded at 2.40 h (0.50-12.00 h) after p.o. administration. Half-life (T½ λz ) for i.v. and p.o. administration was 6.15 h (4.39-7.79 h) and 6.83 h (5.18-9.63 h), respectively. The bioavailability (F) for p.o. administration was 87% (39-351%). The results of this study suggest that meloxicam is well absorbed after oral administration., (© 2014 John Wiley & Sons Ltd.)

Pain associated with lameness on farm is a negative affective state and has a detrimental impact on individual farm animal welfare. Animal pain can be managed utilizing husbandry tools and through pharmacological approaches. Nonsteroidal anti-inflammatory drugs including meloxicam and flunixin meglumine are compounds used in many species for pain management because they are easy to administer, long lasting, and cost-effective. Assessing an animal's biomechanical parameters using such tools as the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system provides an objective, sensitive, and precise means to detect animals in lame states. The objectives of this study were to determine the efficacy of meloxicam and flunixin meglumine for pain mitigation in lame sows using the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Lameness was induced in 24 mature mixed-parity sows using a chemical synovitis model and compared 3 treatments: meloxicam (1.0 mg/kg per os), flunixin meglumine (2.2 mg/kg intramuscular) and sterile saline (intramuscular). Weight distribution (kg) for each foot was collected twice per second for a total of 5 min for each time point using the embedded microcomputer-based force plate system. Stride time, stride length, maximum pressure, activated sensors, and stance time were collected using 3 quality walks (readings) for each time point using the GAITFour pressure mat gait analysis walkway system. Sows administered flunixin meglumine or meloxicam tolerated more weight on their lame leg compared with saline sows (P < 0.005). Sows administered flunixin meglumine or meloxicam had smaller differences in stance time, maximum pressure, and activated sensors between the sound and lame legs compared with saline-treated sows between 37 and 60 h after lameness induction (P < 0.03). In conclusion, flunixin meglumine and meloxicam administration mitigated pain sensitivity in sows after lameness induction when pain sensitivity was evaluated with the embedded microcomputer-based force plate system and GAITFour pressure mat gait analysis walkway system. Analgesic drugs may be a key tool to manage negative pain affective states associated with lameness.

Providing pain relief in cattle is challenging. In the absence of labeled drugs, the Animal Medicinal Drug Use Clarification Act regulates the extralabel drug use of analgesics in cattle within the United States. Given the variety of pharmacokinetic and pharmacodynamic properties of pain-relieving drugs, evidence needs to drive the development of analgesic protocols for cattle during pain-related events. This article reviews the commonly used analgesics investigated in cattle including local anesthetics, nonsteroidal anti-inflammatory drugs, opioids, α2-agonists, N-methyl-d-aspartate receptor antagonists, and gabapentin. These compounds are examined with respect to evidence of analgesia in cattle during pain states., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Deep digital septic conditions represent some of the most refractory causes of severe lameness in cattle. The objective of this study was to determine the distribution of tulathromycin, gamithromycin and florfenicol into the synovial fluid of the metatarsophalangeal (MTP) joint of cattle after single subcutaneous administration of drug to evaluate the potential usefulness of these single-dose, long-acting antimicrobials for treating bacterial infections of the joints in cattle., Results: Twelve cross-bred beef cows were randomly assigned to one of the drugs. Following subcutaneous administration, arthrocentesis of the left metatarsophalangeal joint was performed at various time points up to 240 hours post-injection, and samples were analyzed for drug concentration. In synovial fluid, florfenicol pharmacokinetic parameters estimates were: mean Tmax 7 +/- 2 hours, mean t½ 64.9 +/- 20.1 hours and mean AUC0-inf 154.0 +/- 26.2 ug*h/mL. Gamithromycin synovial fluid pharmacokinetic parameters estimates were: mean Tmax 8 hours, mean t½ 77.9 +/- 30.0 hours, and AUC0-inf 6.5 +/- 2.9 ug*h/mL. Tulathromycin pharmacokinetic parameters estimates in synovial fluid were: Tmax 19 +/- 10 hours, t½ 109 +/- 53.9 hours, and AUC0-inf 57.6 +/- 28.2 ug h/mL., Conclusions: In conclusion, synovial fluid concentrations of all three antimicrobials were higher for a longer duration than that of previously reported plasma values. Although clinical data are needed to confirm microbiological efficacy, florfenicol achieved a synovial fluid concentration greater than the MIC90 for F. necrophorum for at least 6 days.

Previous studies have shown that surgical castration wounds take between 10 and 61 d to heal. The objectives of this work were to describe healing, inflammation, lying behavior, and serum concentration of substance P after surgical castration in beef calves and to evaluate the effect of a possible intervention, a single injection of flunixin meglumine (1.1 mg/kg IV, a NSAID), on the healing process. Calves (mean±SE: 25±2.0 d of age; 54±1.4 kg BW) were surgically castrated with or without an injection of flunixin immediately before the procedure (n=24/treatment). Healing was measured with a 5-point scale (1=fresh wound, 5=no visible incision or inflammation) as well as weight gain, scrotal size, and scrotal surface temperature, on d 1, 2, 3, 7, 14, 21, 28, 35, 49, and 63 after castration. Serum concentration of substance P was recorded on all d, including d 0, but not d 63. Lying behavior was recorded with loggers from 2 d before to 29 d after castration. Inflammation, as measured by scrotal size, peaked on d 2 and 3 after the procedure (e.g., 51±1.0 mm on d 2 versus 28±1.3 mm before castration) and then declined with time (P<0.001). The first wound to score as fully healed (i.e., 5/5) was seen on d 28; by d 63, 98% of wounds were fully healed. The greatest changes in healing score occurred between d 21 and 35; this was also the peak of wound surface temperature and may correspond with revascularization. Serum concentration of substance P was highest before castration (41±1.2 pg/mL), possibly because the sample was collected after the lidocaine ring block was administered, which was likely painful, and because of separation from the dam and restraint. Values began to drop by d 3 (34±1.2 pg/mL) and leveled out by d 21 (30±1.2 pg/mL; P<0.001). Calves given flunixin had more lying bouts than those that received saline (flunixin by time interaction; P=0.052), but this pattern emerged on and after d 8, well after the 3 to 8 h half-life of this NSAID. In conclusion, castration caused inflammation in the days that followed, and the wounds required a minimum of 4 wk to heal. Provision of an NSAID had no effect on these outcomes.

The objectives of this study were to determine plasma concentrations and pharmacokinetic parameters of feed-grade chlortetracycline (CTC) in sheep after oral administration of 80 or 500 mg/head daily, divided into two equal doses given at 12-h intervals for 8 days. These are the approved, and commonly used but unapproved, feed additive doses, respectively, in the United States for the prevention of ovine infectious abortion. Blood samples were collected just prior to dosing at 0, 12, 24, 72, 96, and 192 h, as well as 4, 8, 12, 24, and 36 h after the last dose, and noncompartmental pharmacokinetic analysis was performed to estimate elimination half-life and area under the plasma concentration-time curve (AUC). Mean observed maximum CTC concentrations (Cmax ) were 20.0 ng/mL (80 mg dose) and 101 ng/mL (500 mg dose). Mean apparent elimination half-life was 18 h (80 mg dose) and 20 h (500 mg dose). Although published data do not exist to estimate plasma CTC concentrations necessary for the prevention of ovine infectious abortion, concentrations reached in our study suggest that either the FDA-approved and FDA-unapproved dosages are not high enough or that the pharmacodynamic parameter relating preventive dose to pathogen minimum inhibitory concentrations is yet to be determined., (© 2014 John Wiley & Sons Ltd.)

To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT). Ten sows received either meloxicam (30 mg/kg) (n = 5) or whey protein (placebo) (n = 5) in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean) meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2) synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059). There was a time-by-treatment interaction for plasma cortisol (p = 0.0009), with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67). Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015). This study demonstrates the successful transfer of meloxicam from sows to piglets through milk and corresponding analgesia after processing, as evidenced by a decrease in cortisol and PGE2 levels and maintenance of cranial skin temperature.

The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14-day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography-tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two-compartment model for i.v. administration and a one-compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T1/2K10 and T1/2β were 6.7 (4.6-9.7) and 37.2 (23.5-160.4) h, respectively, Vss was 3.10 (2.10-7.22) L/kg, and CL was 121.7 (100.1-156.7) mL/h/kg. Following oral administration, geometric mean (range) Cmax was 127.9 (102.5-151.3) ng/mL, Tmax was 4.0 (2.6-5.6) h, and T1/2K10 was 18.8 (14.2-25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1-117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half-life in preweaned calves., (© 2014 John Wiley & Sons Ltd.)

The objective of this study was to quantify pain sensitivity differences using mechanical nociception threshold (MNT) and thermal nociception threshold (TNT) tests when sows were in painful and nonpainful transient lameness phases. A total of 24 mixed parity crossbred sows (220.15 ± 21.23 kg) were utilized for the MNT test, and a total of 12 sows (211.41 ± 20.21 kg) were utilized for the TNT test. On induction day (D0), all sows were anesthetized and injected with Amphotericin B (10mg/mL) in the distal interphalangeal joint space in both claws of one randomly selected hind limb to induce transient lameness. Three days were compared: (1) D-1 (sound phase, defined as 1 d before induction), (2) D+1 (most lame phase, defined as 1 d after induction), and (3) D+6 (resolution phase, defined as 6 d after induction). After completion of the first round, sows were given a 7-d rest period and then the procedures were repeated with lameness induced in the contralateral hind limb. During the MNT test, pressure was applied perpendicularly to 3 landmarks in a randomized sequence for each sow: 1) middle of cannon on the hind limb (cannon), 2) 1 cm above the coronary band on the medial hind claw (medial claw), and 3) 1 cm above the coronary band on the lateral hind claw (lateral claw). During the TNT test, a radiant heat stimulus was directed 1 cm above the coronary band. The data were analyzed using the MIXED procedure in SAS with sow as the experimental unit. Differences were analyzed between sound and lame limbs on each day. For the MNT test, pressure tolerated by the lame limb decreased for every landmark (P < 0.05) when comparing D-1 and D+1. The sound limb tolerated more pressure on D+1 and D+6 than on baseline D-1 (P < 0.05). Thermal stimulation tolerated by the sound limb did not change over the 3 d (P > 0.05). However, the sows tolerated less heat stimulation on their lame limb on D+1 compared to D-1 levels (P < 0.05). Both MNT and TNT tests indicated greater pain sensitivity thresholds when sows were acutely lame.

The objective of this study was to investigate the pharmacokinetics and effect of nalbuphine administered intravenously to calves immediately prior to surgical castration. Ten healthy calves were randomly assigned to two treatments (n = 5): (i) 0.9% sodium chloride (CONT) placebo, (ii) nalbuphine hydrochloride (NAL) (0.4 mg/kg). Blood samples collected over 10 h postcastration were analyzed for nalbuphine and cortisol concentrations. Additionally, heart rate, respiratory rate, rectal temperature, and step count was compared between groups using a random-effects mixed model. Changes in behavior and attitude were assessed using a six-point ordinal scoring system and compared using chi-square analysis. Plasma NAL concentrations were only detectable for 3 h postadministration (T½ = 0.68 h; Range: 0.53-0.79 h). There was no effect of NAL treatment prior to castration on cortisol concentrations (P = 0.99), heart rate (P = 0.73), respiratory rate (P = 0.59), rectal temperature (P = 0.22), and step count (P = 0.08) but fewer calves showed signs of head shaking, kicking, and tail flicking in the NAL group compared with the CONT group (P = 0.036). Therefore, we conclude that a single intravenous injection of nalbuphine at 0.4 mg/kg reduced some pain-related behaviors but did not significantly eliminate the physiological signs of distress in calves after surgical castration., (© 2013 John Wiley & Sons Ltd.)

Objective: The present study is a comparison of two point-of-care (POC) tests as endpoints of protamine titration after CPB. The authors hypothesized that using the heparinase-kaolin thromboelastography (TEG-HK) R-time difference would more readily identify residual heparin necessitating additional protamine than when using activated coagulation time (ACT). The primary endpoint was the between-group difference in protamine dose. Whether this approach would lessen postoperative bleeding and sequelae also was investigated., Design: Single center, blinded, prospective, randomized study., Setting: University teaching hospital., Participants: Eighty-two adult patients for on-pump coronary artery bypass and/or valve surgery., Interventions: Patients were randomized. In the ACT group, protamine was titrated until ACT did not exceed baseline by more than 10%. In the TEG group, a TEG-HK R-time difference less than 20% was targeted. Protamine was repeated to achieve the endpoints. Clinicians in the ACT group were blinded to TEG data and vice versa., Measurements and Main Results: There was no between-group difference in total protamine dose (3.9 ± 0.6 and 4.2 ± 0.7; 95% CI of the difference between means: -0.544 to 0.008 mg/kg; p = 0.057) or protamine:heparin ratios (1.3:1 and 1.4:1; 95% CI of the difference between means: -0.05 to 0.03 mg/mg; p = 0.653). In the ACT group, 17% of patients required a second protamine dose, and in the TEG group, 24% of patients required a second protamine dose. No between-group differences in the postoperative transfusion requirements or intensive care unit length of stay were demonstrated., Conclusion: No difference was identified in protamine dosing using either ACT or TEG-HK R-time difference as endpoints. Heparinase TEG may be useful for monitoring heparin reversal., (© 2013 Elsevier Inc. All rights reserved.)

Transportation stress can result in significant economic losses to producers due to decreased animal productivity and increased medication costs associated with sickness such as bovine respiratory disease (BRD). Meloxicam (MEL) provides pain relief and anti-inflammatory effects in cattle for several days after a single oral treatment. Our hypothesis was that MEL administration before shipping would reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef steers. Ninety-seven beef steers were blood sampled for baseline biomarker determination and then randomly assigned to receive either 1 mg/kg MEL (n = 49) or a placebo (CONT; n = 48) per os before a 1,316-km transportation event lasting approximately 16 h. Calves were then blood sampled on arrival and 5 d later. Changes in the hemogram, circulating plasma proteins, total carbon dioxide (TCO2), fibrinogen, substance P (SP), cortisol, haptoglobin (Hp)-matrix metalloproteinase-9 (MMP-9) complexes, and tumor necrosis factor α (TNFα) between treatments over time were compared using a mixed effects model with statistical significance designated as P < 0.05. Analysis of covariance was conducted to assess the relationship between circulating MEL concentrations and biomarker changes over time. An increase in neutrophil, platelet, monocyte, white blood cell, and red blood cell counts occurred after transportation (P < 0.0001) and a decrease in lymphocyte count were observed (P < 0.0001). Meloxicam treatment reduced the stress-induced neutrophilia (P = 0.0072) and circulating monocyte count (P = 0.013) on arrival. Mean corpuscle hemoglobin (P = 0.05), mean corpuscle volume (P = 0.05), and lymphocyte count (P = 0.05) were also greater in the CONT calves compared with MEL calves after transportation. Furthermore, Hp-MMP-9 complexes, TCO2, TNFα, plasma proteins, and SP increased and cortisol decreased after shipping (P < 0.01). Meloxicam treatment tended to reduce serum cortisol concentrations (P = 0.08) and there was evidence of a time × treatment interaction (P = 0.04). An inverse relationship between plasma MEL concentrations and circulation cortisol concentrations (P = 0.002) and neutrophil (P = 0.04) and basophil counts (P = 0.03) was also observed. The results suggest that MEL administration may reduce the impact of long-distance transportation on circulating physiological biomarkers of stress and inflammation in beef calves.

This study examined the pharmacokinetics and analgesic effect of oral meloxicam (MEL) administered alone or in combination with gabapentin (GABA) in an experimental bovine lameness model. Eighteen male British × Continental beef calves aged 4 to 6 mo and weighing 297 to 392 kg were randomly assigned to receive either 1) 0.5 mg/kg lactose monohydrate placebo (PLBO; n = 6), 2) 0.5 mg/kg MEL (n = 6), or 3) 0.5 mg/kg MEL combined with 15 mg/kg GABA (MEL-GABA; n = 6) once daily for 4 d. The first treatment was administered 4 h after a chemical synovitis/arthritis was induced with injection of 15 mg amphotericin B into the left hind lateral distal interphalangeal joint. Changes in activity were evaluated continuously with pedometers. Contact force, contact area, contact pressure, impulse, and stride length were recorded once daily with a pressure mat and visual lameness scores were determined by a masked observer using a 5-point scale. Cortisol and drug concentrations were determined daily by immunoassay and HPLC-mass spectrometry, respectively. Outcomes were compared statistically using a random effects mixed model and analysis of covariance. There was a positive association between lameness scores and serum cortisol concentrations (P = 0.02) and a negative association between lameness score and step count (P < 0.0001), total force (P = 0.001), force applied to the lateral claw (P = 0.02), contact pressure (P = 0.005), and impulse of the lateral claw (P = 0.01). Step count was greater in MEL calves compared with PLBO (P = 0.008) and MEL-GABA (P = 0.04) calves. Impulse was greater in the MEL-GABA calves compared with the PLBO calves (P = 0.03). There was an inverse relationship between plasma MEL concentrations and lameness score (P = 0.02) and a positive association between MEL concentrations and force applied to the lateral claw (P = 0.03), total contact pressure (P = 0.03), and impulse on the lateral claw (P = 0.02). There was a tendency towards a positive association between GABA concentrations, total impulse, and impulse on the lateral claw (P = 0.08) and a negative associate between GABA concentrations and step count (P = 0.08). The results of this study suggest that MEL administered alone or in combination with GABA reduced the severity of lameness in calves following induction of lameness with amphotericin B. These findings have implications for developing analgesic protocols in lame calves that address both production and welfare concerns.

Objective: To determine the effects of protease inhibitors and holding times and temperatures before processing on the stability of substance P in bovine blood samples., Samples: Blood samples obtained from a healthy 6-month-old calf., Procedures: Blood samples were dispensed into tubes containing exogenous substance P and 1 of 6 degradative enzyme inhibitor treatments: heparin, EDTA, EDTA with 1 of 2 concentrations of aprotinin, or EDTA with 1 of 2 concentrations of a commercially available protease inhibitor cocktail. Plasma was harvested immediately following collection or after 1, 3, 6, 12, or 24 hours of holding at ambient (20.3° to 25.4°C) or ice bath temperatures. Total substance P immunoreactivity was determined with an ELISA; concentrations of the substance P parent molecule, a metabolite composed of the 9 terminal amino acids, and a metabolite composed of the 5 terminal amino acids were determined with liquid chromatography-tandem mass spectrometry., Results: Regarding blood samples processed immediately, no significant differences in substance P concentrations or immunoreactivity were detected among enzyme inhibitor treatments. In blood samples processed at 1 hour of holding, substance P parent molecule concentration was significantly lower for ambient temperature versus ice bath temperature holding conditions; aprotinin was the most effective inhibitor of substance P degradation at the ice bath temperature. The ELISA substance P immunoreactivity was typically lower for blood samples with heparin versus samples with other inhibitors processed at 1 hour of holding in either temperature condition., Conclusions and Clinical Relevance: Results suggested that blood samples should be chilled and plasma harvested within 1 hour after collection to prevent substance P degradation.

Dehorning in cattle has been associated with behavioral, physiological, and neuroendocrine responses indicative of pain. Unaddressed, the pain associated with a routine production procedure could contribute to a negative public perception of livestock production practices. Alternative considerations of dehorning include the selection of polled cattle within herds, thereby avoiding pain and production loss. As polledness results from an autosomal dominant pattern of inheritance, genetic selection for polled cattle could reduce the prevalence of the horned trait. Herein we discuss 3 strategies to incorporate polled genetics into a cow herd and the estimated impact on the overall genetic merit of the herd. Furthermore, the availability and genetic merit of polled artificial insemination bulls in the United States is summarized. Both Holstein and Jersey dairy bulls registered with the National Association of Animal Breeders from December 2010 through April 2013 were queried. Polled bulls were identified as either being homozygous (PP) or heterozygous (Pp) and the average net merit (NM) predicted transmitting ability (PTA) of each sire group was calculated. The percentage of polled calves born each year over a 10-yr period was calculated for the following 3 scenarios: (A) various percentages of horned cows were randomly mated to Pp bulls, (B) various percentages of horned cows were preferentially mated to Pp bulls, and (C) horned cows were selectively mated to PP bulls, heterozygous cows to Pp bulls, and homozygous polled cows to horned bulls. Additionally, the change in NM PTA of the cow herd was calculated over the same period. The highest percentage of polled animals (87%) was achieved in scenario C. An evaluation of the herd NM PTA highlights the trade-offs associated with increasing polled genetics. Given the current genetic merit of horned and polled bulls, increasing the percentage of polled calves will decrease the NM PTA in Holstein, but may have minimal impact in Jersey herds. Decisions regarding selective breeding to increase polled genetics will need to be evaluated in the context of production objectives, cost of dehorning, and impact on overall genetic merit., (Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration., (© 2013 John Wiley & Sons Ltd.)

Two experiments evaluated the effects of band castration and oral administration of an analgesic in association with castration on performance and behavioral and physiological responses in yearling beef bulls. In Exp. 1 Angus and Charolais-crossbred bull calves (n = 127; 309.8 ± 59.04 kg BW) and in Exp. 2 Hereford, Angus, and Hereford × Angus crossbred bulls (n = 30; 300.8 ± 4.96 kg BW) were stratified by BW and randomly assigned to 1 of 3 treatments: 1) band castration (BAND), 2) band castration with oral administration of meloxicam (BAND-MEL), and 3) sham castration (SHAM). The BAND and SHAM procedures were completed on d 0. The SHAM treatment consisted of all animal manipulations associated with band castration without band application. Meloxicam was administered on d -1, 0, and 1 (1.0, 0.5, and 0.5 mg/kg, respectively) via an oral bolus. Body weight and a subjective chute score (CS) were collected on d -1, 0, 1, 7, 14, and 21 (d 28 Exp. 1 only). In Exp. 2, jugular blood samples were collected immediately before castration and 24 h postcastration for substance P (SP) analysis. In Exp. 2, video documentation on d 0 was used to determine range of vertical head motion (DIST) on a subset of animals during treatment administration. In both experiments, ADG was similar (P ≥ 0.50) between BAND and BAND-MEL, but ADG in SHAM cattle was greater (P < 0.001) and tended (P = 0.07) to be greater than castrates in Exp. 1 and 2, respectively. In Exp. 1, CS did not differ (P ≥ 0.26) between BAND and BAND-MEL on any day, but castrates exhibited less desirable CS on d 1 and 28 than SHAM cattle. In Exp. 2, CS was not affected (P ≥ 0.41) by castration or the presence of meloxicam. In Exp. 2, DIST did not differ (P = 0.57) between BAND and BAND-MEL, but when pooled, castrates exhibited greater (P = 0.04) DIST than SHAM. In Exp. 2, plasma SP concentrations were similar between BAND and BAND-MEL (P = 0.81) and between castrates vs. sham cattle (P = 0.67). Results indicate no impact of meloxicam administration on performance or behavioral and physiological responses to band castration. However, there was a negative impact of castration on ADG and DIST.

Cefovecin is an extended-spectrum long-acting third generation cephalosporin used to treat canine infections. The study objective was to determine the effect of cefovecin on the absolute number and antimicrobial susceptibility of fecal enteric bacteria in healthy dogs. Fourteen Beagles were randomly assigned to a treated (n=7, 8 mg/kg cefovecin subcutaneously on day 1) or untreated (n=7) group. LC/MS was used to determine plasma cefovecin concentration on day 14. E. coli, enterococci, and Salmonella were isolated and enumerated from fecal samples collected on days 0, 3, 7, 14, and 28. Antimicrobial resistance was determined using disc diffusion, MIC, and detected using PCR for the blaCMY-2 gene on select isolates. Mean plasma concentration of cefovecin on day 14 was 9.59 μg/mL in treated dogs; untreated dogs had no measurable plasma cefovecin. The absolute number of E. coli was lower in treated dogs on day 3 (P ≤ 0.0001), and the absolute number of cefovecin-resistant E. coli was higher in treated dogs on days 7 (P=0.002), 14 (P=0.004) and 28 (P ≤ 0.0001), compared to untreated dogs. Enterococci increased and were higher in the treatment group on day 7 (P=0.0226). Isolation of Salmonella was rare. After cefovecin treatment, beta-lactam resistance was more common in fecal E. coli from treated dogs than untreated dogs, while resistance of enterococci was not altered. On day 28, treated dogs were 3.25 times more likely to carry the blaCMY-2 gene than untreated dogs (95% CI 1.27 - 8.35). The implications of these findings in clinically ill patients require further research., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The study objective was to compare serum cortisol as an acute stress measure, chute exit velocity as a behavioral measure, and ADG as an indicator of performance and well-being after castration, dehorning, or concurrent castration/dehorning of calves when performed in parallel and in series. Intact male Holstein calves, 3 to 4 mo, underwent sham handling before 2 procedures performed in series separated by 2 to 3 wk. In Period 1, calves were either dehorned by amputation, surgically castrated, concurrently castrated/dehorned, or served as nonsurgical controls (n = 10/treatment). In Period 2, calves that had been dehorned, castrated, or castrated/dehorned were then castrated, dehorned, or served as nonsurgical controls, respectively. Indicators of distress were measured after all procedures; ADG was assessed for 7 d after each procedure and over the 2 to 3 wk interim. Period 1 cortisol concentrations in dehorned calves were less than in castrated and castrated/dehorned calves at 120 min and from 50 to 240 min, respectively (P < 0.02). There was marginal evidence that cortisol concentrations were greater in castrated/dehorned than castrated calves at 60 min (P = 0.06). Period 2 cortisol concentrations were less in dehorned than castrated calves at 120 min (P = 0.005) but were greater from 360 to 480 min (P < 0.002). The Period 2 cortisol profile of control calves did not differ from the baseline obtained during sham handling, despite the intervening castration/dehorning in Period 1, suggesting that memory did not affect cortisol. The cortisol profile of castrated calves did not differ between periods except at 720 min, when Period 1 concentrations were greater than Period 2 (P = 0.02). Cortisol concentrations of calves dehorned in Period 2 were greater than those dehorned in Period 1 at 20 and 240 to 480 min (P < 0.05). In both periods, castrated calves exited the chute slower than dehorned calves (P < 0.05). The ADG did not differ between surgically treated calves in Period 1; in the interim, the ADG of castrated calves was greater than that of castrated/dehorned calves (difference ± SED, 1.4 ± 0.6 kg/d; P = 0.03), and in Period 2, the ADG of dehorned calves was less than castrated calves (1.8 ± 0.6 kg/d; P = 0.005). Our study supports both the common practice of concurrent castration/dehorning and the sequence of dehorning and castration. Delayed dehorning (vs. delayed castration) appeared to be more acutely stressful and more detrimental to ADG.

Background: The purpose of this study was to determine intravenous (IV), intramuscular (IM) and oral (PO) FM PK in mature swine. Appropriate pain management for lameness in swine is a critical control point for veterinarians and producers, but science-based guidance on optimal housing, management and treatment of lameness is deficient. Six mature swine (121-168 kg) were administered an IV, IM, or PO dose of flunixin meglumine at a target dose of 2.2 mg/kg in a cross-over design with a 10 day washout period between treatments. Plasma samples collected up to 48 hours post-administration were analyzed by high pressure liquid chromatography and mass spectrometry (HPLC-MS) followed by non-compartmental pharmacokinetic analysis., Results: No adverse effects were observed with flunixin meglumine administration for all routes. Flunixin meglumine was administered at an actual mean dose of 2.21 mg/kg (range: 2.05-2.48 mg/kg) IV, IM and PO. A mean peak plasma concentration (CMAX) for IM and PO administration was 3748 ng/ml (range: 2749-6004 ng/ml) and 946 ng/ml (range: 554-1593 ng/ml), respectively. TMAX was recorded at 1.00 hour (range: 0.50-2.00 hours) and 0.61 hours (range: 0.17-2.00 hours) after PO and IM administration. Half-life (T ½ λz) for IV, IM and PO administration was 6.29 hours (range: 4.84-8.34 hours), 7.49 hours (range: 5.55-12.98 hours) and 7.08 hours (range: 5.29-9.15 hours) respectively. In comparison, bioavailability (F) for PO administration was 22% (range: 11-44%) compared to IM F at 76% (range: 54-92%)., Conclusions: The results of the present study suggest that FM oral administration is not the most effective administration route for mature swine when compared to IV and IM. Lower F and Cmax of PO-FM in comparison to IM-FM suggest that PO-FM is less likely to be an effective therapeutic administration route.

Dehorning is a painful husbandry procedure that is commonly performed in dairy calves. Parenteral meloxicam combined with local anesthesia mitigates the physiological and behavioral effects of dehorning in calves. The purpose of this study was to determine the influence of timing of oral meloxicam administration on physiological responses in calves after dehorning. Thirty Holstein bull calves, 8 to 10 wk of age (28-70 kg), were randomly assigned to 1 of 3 treatment groups: placebo-treated control group (n=10), calves receiving meloxicam administered orally (1 mg/kg) in powdered milk replacer 12h before cautery dehorning (MEL-PRE; n=10), and calves receiving meloxicam administered as an oral bolus (1 mg/kg) at the time of dehorning (MEL-POST; n=10). Following cautery dehorning, blood samples were collected to measure cortisol, substance P (SP), haptoglobin, ex vivo prostaglandin E2 (PgE2) production after lipopolysaccharide stimulation and meloxicam concentrations. Maximum ocular temperature and mechanical nociceptive threshold (MNT) were also assessed. Data were analyzed using noncompartmental pharmacokinetic analysis and repeated measures ANOVA models. Mean peak meloxicam concentrations were 3.61±0 0.21 and 3.27±0.14 μg/mL with average elimination half-lives of 38.62±5.87 and 35.81±6.26 h for MEL-PRE and MEL-POST, respectively. Serum cortisol concentrations were lower in meloxicam-treated calves compared with control calves at 4 h postdehorning. Substance P concentrations were significantly higher in control calves compared with meloxicam-treated calves at 120 h after dehorning. Prostaglandin E2 concentrations were lower in meloxicam-treated calves compared with control calves. Mechanical nociceptive threshold was higher in control calves at 1h after dehorning, but meloxicam-treated calves tended to have a higher MNT at 6h after dehorning. No effect of timing of meloxicam administration on serum cortisol concentrations, SP concentrations, haptoglobin concentrations, maximum ocular temperature, or MNT was observed. However, PgE2 concentrations in MEL-PRE calves were similar to control calves after 12h postdehorning, whereas MEL-POST calves had lower PgE2 concentrations for 3 d postdehorning. These findings support that meloxicam reduced cortisol, SP, and PgE2 after dehorning, but only PgE2 production was significantly affected by the timing of meloxicam administration., (Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objective of this study was to determine the effect of pneumonia during conditions of high (maximum ≥ 32°C) ambient temperatures on physiological and behavioral responses of calves. Eighteen black beef heifers averaging 240 kg were blocked by BW and randomly assigned to 1 of 2 treatment groups: 1) pneumonia induced by bronchoselective endoscopic inoculation with Mannheimia haemolytica (MH; n = 10) and 2) noninoculated controls (CN; n = 8). Nasal passage and rectal temperatures were measured every 2 h for 24 h after challenge and then twice daily for 9 d. Accelerometers, pedometers, and positioning devices monitored cattle behavior within the pen for 9 d after challenge. Blood samples were collected on trial d 0, 0.5, 1, 2, 3, 7, and 9 and were analyzed to determine the concentration of substance P, cortisol, haptoglobin, and metalloproteinase. All calves in the MH group were euthanized and necropsied on trial d 9. All MH calves became clinically ill postchallenge. A treatment × time interaction (P < 0.05) was evident for nasal and rectal temperatures, behavior, weight, and blood analysis. Rectal temperatures in MH were higher (P < 0.01) than CN during the period from 6 to 24 h after challenge. Conversely, nasal passage temperatures were less in MH calves compared with CN at 12 to 22 h after challenge. Calves in MH spent less time at the grain bunk, less time at the hay feeder, and more time lying down during the early pneumonia period compared with CN calves. Also, MH calves had significantly greater concentrations of blood biomarkers of pain (substance P) on d 0.5 (P < 0.01); stress (cortisol) on d 0.5 and 1 (P < 0.01); haptoglobin on d 0.5, 1, 2, 3, 7 (P < 0.01); and metalloproteinase on d 1, 2, and 3 (P < 0.01) compared with CN calves. At necropsy, all MH calves had right cranioventral bronchopneumonia (median lung lesions = 6.8%). Mannheimia haemolytica pneumonia caused significantly more changes in behavior and increased biomarkers during high (maximum ≥32°C) ambient temperatures compared with control calves. The results of this study may guide research in the development of objective assessment tools for management of cattle affected with bovine respiratory disease during extreme summer conditions.

The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.