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Anaplasma marginale is a tick-borne pathogen of cattle that causes bovine anaplasmosis in tropical and subtropical regions throughout the world. Killed vaccines derived from infected erythrocytes have been used for control of this disease with limited success. Recently, we described a targeted deletion mutation in the phage head-to-tail connector protein gene of A. marginale which caused bacterial attenuation in vivo and provided protection as a modified live vaccine (MLAV). Following intravenous injection of susceptible steers, the MLAV induced protective immunity against disease progression. In the current study, we demonstrated that the immunity resulting from MLAV in cattle prevents the disease progression resulting from virulent A. marginale intrastadial transmission from infected Dermacentor variabilis male ticks. The nonimmunized control steers receiving the infection from ticks developed fever, lethargy, and inappetence for several days post tick exposure with significant decreases in the packed cell volume and increases in bacteremia. In contrast, the MLAV immunized steers remained healthy after being challenged with infected ticks and this group of animals had a significant reduction in bacteremia as compared with the controls. This study demonstrated that the A. marginale MLAV provided protection against acute tick-transmitted anaplasmosis, in addition to protection documented in steers challenge-exposed with infected blood as reported previously.
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Gabapentin is used in goats to treat chronic pain associated with lameness. However, pharmacokinetic data and clinical effectiveness trials are lacking. The objective of the study was to describe the pharmacokinetics of gabapentin in goats following a single oral dose. Six Spanish-crossbred goats were enrolled. Each goat was administered gabapentin at a target dose of 15 mg/kg per os. Serial blood samples were collected out to 60 h post-gabapentin administration for plasma gabapentin concentration determination. Plasma samples were analyzed for gabapentin concentration using ultra-high-pressure liquid chromatography coupled with mass spectroscopy. Individual animal pharmacokinetic outcomes were determined using non-compartmental analysis. Gabapentin was detectable in the plasma of all goats at 60 h post-administration. The mean (±SD) Cmax was 2.01 ± 0.62 µg/mL which occurred at 8.47 ± 1.9 h. The mean terminal half-life (T1/2) and mean resident time were determined to be 8.52 ± 1.8 and 18.7 ± 4.0 h, respectively. This study indicates gabapentin is absorbed from the gastrointestinal tract of goats. Further research is needed to determine an optimal dose for clinical efficacy in goats.
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Analgésicos , Gabapentina , Cabras , Animales , Gabapentina/farmacocinética , Gabapentina/administración & dosificación , Gabapentina/sangre , Semivida , Administración Oral , Analgésicos/farmacocinética , Analgésicos/administración & dosificación , Analgésicos/sangre , Masculino , Femenino , Área Bajo la CurvaRESUMEN
OBJECTIVE: This study sought to determine whether firocoxib (FIRO) or meloxicam (MEL) was effective at providing analgesia after surgical castration in goats. ANIMALS: 18 intact male crossbred goats (6 to 8 months old) were enrolled with a mean weight of 32.6 (± 2.9) kg. METHODS: Surgical castration was done under injectable anesthesia by a licensed veterinarian. Twelve bucks were surgically castrated and given either FIRO (n = 6) or MEL (n = 6). Six bucks served as controls (CNTLs) and were not castrated. Outcome measurements included visual analogue scale, infrared thermography, plasma cortisol, plasma substance P, and kinetic gait analysis. All outcome measurements were obtained at -24, 4, 8, 24, 48, and 72 hours. RESULTS: All 3 treatments were significantly different from each other at the 24- and 48-hour time points, with MEL animals having lower visual analogue scale scores when compared to FIRO animals; CNTL animals exhibited the lowest plasma cortisol levels (3.19 ng/mL; 95% CI, -1.21 to 7.59 ng/mL) followed by FIRO (7.45 ng/mL; 95% CI, 3.10 to 11.80 ng/mL) and MEL (10.24 ng/mL; 95% CI, 5.87 to 14.60 ng/mL). FIRO had an average mean decrease in gait velocity change (-54.17 cm/s; 95% CI, -92.99 to -15.35 cm/s), while MEL had an increase in gait velocity when compared to baseline values (14.54 cm/s; 95% CI, -24.27 to 53.36 cm/s). Control animals had an average mean of -3.06 cm/s (95% CI, -41.88 to 35.75 cm/s). CLINICAL RELEVANCE: Results from this study showed that there were some analgesic effects from administering MEL when compared to bucks that received a placebo treatment (CNTL).
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4-Butirolactona/análogos & derivados , Antiinflamatorios no Esteroideos , Sulfonas , Tiazinas , Masculino , Animales , Meloxicam/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Hidrocortisona , Cabras , Tiazinas/uso terapéutico , Tiazoles/uso terapéutico , Orquiectomía/veterinaria , Orquiectomía/métodos , Dolor/veterinariaRESUMEN
Lameness continues to be a critical health and welfare concern associated with goat production. Amphotericin B (amp B) is an antimicrobial successful in inducing transient lameness for research purposes previously in livestock animals. The objectives of this study were to (1) identify which of three varying doses of amp B would be most effective in inducing lameness in meat type goats and (2) develop a facial grimace scale for goats. Lameness was produced by an intra-articular injection of amphotericin B into the left hind lateral claw distal interphalangeal joint with either a 5 mg/0.25 mL (high-low, 5 mg of amphotericin B in a volume of 0.25 mL), 5 mg/0.5 mL (high-high, 5 mg of amphotericin B in a volume of 0.5 mL), or a 2.5 mg/0.25 mL (low-low, 2.5 mg of amphotericin B in a volume of 0.25 mL). A saline treatment of 0.5 mL was used as control (0.9% sterile saline solution). Lameness response was analyzed by infrared thermography (IRT) at the induced joint, mechanical-nociception threshold (MNT), visual lameness scoring (VLS), a visual analogue scale (VAS), kinetic gait analysis (KGA), plasma cortisol (CORT), substance P (Sub P), and behavior scoring. The IRT and MNT values differed by timepoint (Pâ ≤â 0.0001). Results from VLS showed the HL treatment was the most effective at inducing lameness (6/6 goats became lame compared to HH 4/6 and LL 2/6). At 24, 48, and 72 h, VAS scores were significantly higher when comparing HL to all other treatment groups (Pâ =â 0.0003). Both behavior observers (1 and 2) reported a significant time effect (Pâ =â 0.05), with goats exhibiting more facial grimacing at 24 h post-lameness induction. From these data, an optimal dose for a repeatable lameness induction model in goats was aquired. An effective Goat Grimace Scale (GGS) was also developed to evaluate pain responses in goats.
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Pain management in rabbits is a challenging task that is complicated by the rabbit's ability to hide signs of distress and the limited pharmacologic data available for this species. Pharmacokinetic data has shown that in rabbits, meloxicam, a nonsteroidal anti-inflammatory NSAID, reaches plasma concentrations that are known to provide analgesia in dogs and cats; these concentrations could theoretically alleviate pain in rabbits. However, the inhibitory effects of meloxicam on cyclooxygenase (COX) isoforms have not been studied in rabbits. In this study, we measured the products of COX-1 and COX-2 after the oral administration of a single 1 mg/kg dose of meloxicam to New Zealand White rabbits (n = 6). Blood samples were collected before drug administration (T0) and then at predetermined time points over 48 h. Plasma prostaglandin E2 (PGE2 ) and thromboxane (TxB2) concentrations were measured as surrogate markers for COX-1 and COX-2, respectively, by using commercial ELISA kits. After meloxicam administration, both TxB2 and PGE2 plasma concentrations fell significantly below baseline, with maximal mean reductions to 80% and 60% of baseline at 8 h, respectively. The reduction in PGE2 concentrations was followed by a significant increase that moved its mean plasma concentrations toward baseline between 8 and 24 h. Adverse effects such as lethargy, inappetence, or changes in fecal production were not observed in any rabbits. In conclusion, meloxicam appeared to significantly inhibit both COX-1 and COX-2 with a time course similar to previously reported meloxicam plasma concentration-time profiles in rabbits. Our data suggest that a dosage of 1 mg/kg given orally could provide analgesia to rabbits, but a more frequent dosing interval than the currently recommended daily dosing may be required to maintain clinical efficacy.
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Enfermedades de los Gatos , Enfermedades de los Perros , Tiazinas , Conejos , Animales , Gatos , Perros , Meloxicam , Ciclooxigenasa 2 , Dinoprostona , Tiazoles , Antiinflamatorios no Esteroideos , Isoformas de Proteínas , Dolor , Administración OralRESUMEN
Adverse effects associated with overdose of NSAIDs are rarely reported in cattle, and the risk level is unknown. If high doses of NSAIDs can be safely administered to cattle, this may provide a longer duration of analgesia than using current doses where repeated administration is not practical. Meloxicam was administered to 5 mid-lactation Holstein dairy cows orally at 30 mg/kg, which is 30 times higher than the recommended 1 mg/kg oral dose. Plasma and milk meloxicam concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was performed by using noncompartmental analysis. The geometric mean maximum plasma concentration (Cmax) was 91.06 µg/mL at 19.71 h (Tmax), and the terminal elimination half-life (T1/2) was 13.79 h. The geometric mean maximum milk concentration was 33.43 µg/mL at 23.74 h, with a terminal elimination half-life of 12.23 h. A thorough investigation into the potential adverse effects of a meloxicam overdose was performed, with no significant abnormalities reported. The cows were humanely euthanized at 10 d after the treatment, and no gross or histologic lesions were identified. As expected, significantly higher plasma and milk concentrations were attained after the administration of 30 mg/kg meloxicam with similar half-lives to previously published reports. However, no identifiable adverse effects were observed with a drug dose 30 times greater than the industry uses within 10 days of treatment. More research is needed to determine the tissue withdrawal period, safety, and efficacy of meloxicam after a dose of this magnitude in dairy cattle.
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Effective rabbit analgesia is challenging, and there are few studies available on the newer COX-2 selective NSAIDs, such as robenacoxib. This study aimed to establish the pharmacokinetics of oral and subcutaneous robenacoxib, describe its inhibitory actions on COX enzymes, and develop dosing, using six healthy New Zealand white rabbits. Pharmacokinetics were determined from plasma concentrations after oral administration of robenacoxib (0.83-0.96 mg/kg) and also after subcutaneous administration (2 mg/kg). The inhibitory actions of robenacoxib were evaluated by measuring plasma concentrations of thromboxane B2 (TBX2 ) and prostaglandin E2 (PGE2 ) as surrogate markers of cyclooxygenase enzyme isoform inhibition. The mean maximum concentration for oral and subcutaneous administration was 0.23 µg/ml and 5.82 µg/ml, respectively. Oral robenacoxib administration did not demonstrate a significant difference between any time point for PGE2 or TBX2 , though subcutaneous administration did for both. There was no significant difference in PGE2 or TBX2 concentrations at any time point when comparing subcutaneous versus oral routes. Although the results support that plasma robenacoxib exceeds the therapeutic levels compared to dogs and cats, there was little significance in the difference in the changes associated with COX-1 and COX-2 inhibition. Further studies are warranted to determine appropriate dosing, safety, and efficacy in rabbits.
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Enfermedades de los Gatos , Enfermedades de los Perros , Conejos , Gatos , Animales , Perros , Ciclooxigenasa 2/uso terapéutico , Isoenzimas/uso terapéutico , Enfermedades de los Gatos/tratamiento farmacológico , Enfermedades de los Perros/tratamiento farmacológico , Antiinflamatorios no Esteroideos/farmacocinética , Fenilacetatos , Ciclooxigenasa 1/uso terapéutico , Difenilamina , Dinoprostona , Inhibidores de la Ciclooxigenasa 2/farmacocinéticaRESUMEN
Bovine respiratory disease (BRD) is an economically important disease in feedyards influencing both animal welfare and antimicrobial utilization. Major pathogens associated with BRD have been identified in previous research, but little information is available on the relationship between nasopharyngeal microbiota and health outcomes. The objective of this study was to identify potential associations between nasopharyngeal microbiota and antimicrobial resistance patterns of clinical cases that lived or died compared to non-diseased controls. Enrolled animals were subdivided based on clinical disease status and case outcome (subsequent mortality). Deep nasopharyngeal swabs were collected on enrolled animals and submitted for bacterial isolation, antimicrobial susceptibility determination, and metagenomics analysis. Enrolled cattle were represented in three groups: animals at first treatment for BRD that subsequently died (BRDM, n = 9), animals at first treatment for BRD that subsequently lived (BRDL, n = 15), and animals that were never treated for BRD during the feeding phase (CONT, n = 11). Antimicrobial resistance patterns for Pasteurella multocida illustrated cattle in each outcome category had isolates that were pan-susceptible or only showed resistance to oxytetracycline. The relative abundance of species and genera illustrated few differences among the three outcomes. Higher alpha diversity was identified in BRDL compared to CONT at the species level, and both BRDL and BRDM showed increased alpha diversity compared to CONT at the general level. Overall, this work illustrated nasopharyngeal microbiota showed relatively few differences among BRD cases that lived or died compared to animals without BRD.
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The American Veterinary Medical Association recommends the use of practices that reduce or eliminate pain and discomfort associated with dehorning. Identification of an effective, long-acting local anesthetic that is practical for producers to implement and reduces pain from dehorning would benefit animal welfare. Thirty-two Holstein bulls and heifers were enrolled. The objective of this study was to compare the efficacy and duration of activity of bupivacaine liposome suspension (BUP; n = 8), ethanol (ETH; n = 8), or meloxicam (LID + MEL; n = 8) co-administered with lidocaine compared with lidocaine only (LID; n = 8), and to quantify their effect on pain biomarkers and behaviors after scoop dehorning with cauterization in approximately 20-wk-old calves. Outcome variables collected included infrared thermography (IRT), mechanical nociceptive threshold (MNT), visual analog scale (VAS) scoring, and blood sampling for serum cortisol and prostaglandin E2 metabolites (PGEM). There was evidence of a sex effect for MNT, with bulls demonstrating a higher threshold (13.74 kgf) compared with heifers (12.12 kgf). There was a treatment by time interaction for cortisol concentrations (ng/mL). At 2 h, the BUP group had higher cortisol values (17.32 ng/mL) than the LID + MEL group (3.10 ng/mL). Heifers also had higher mean cortisol values (13.88 ng/mL) compared with bulls (6.96 ng/mL). There was a treatment by time interaction for PGEM concentration. Calves in the LID + MEL group had lower PGEM values at 4 and 8 h (10.23 and 9.12 pg/mL) than at -24, 0, and 0.5 h (20.38, 27.27, and 22.59 pg/mL, respectively). At 4 h, the LID + MEL group had lower PGEM concentrations (10.23 pg/mL) than the ETH group (27.08 pg/mL). At 8 h, the LID + MEL group had lower PGEM concentrations (9.12 pg/mL) than both the ETH and BUP groups (24.80 and 20.52 pg/mL). Thus, LID + MEL reduced cortisol and prostaglandin metabolite concentrations more effectively than ETH + LID or BUP + LID administered as a local infiltration and cornual block, respectively, before scoop dehorning followed by cauterization. The treatments administered in the present study did not seem to extend the duration of analgesia beyond the currently recommended multimodal approach, including local anesthesia and systemic analgesia such as lidocaine and meloxicam. Evidence from the current study suggests that sex influences pain biomarkers such as nociceptive threshold and cortisol concentration, with males having a higher nociceptive threshold and lower cortisol responses.
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Immunocastration relies on the vaccine-mediated stimulation of an immune response to gonadotropin-releasing hormone (GnRH) in order to interrupt spermatogenesis. This approach offers a less painful alternative to traditional castration approaches but the current, commercially available options require multiple doses of vaccine to maintain sterility. Thus, a series of pilot studies were conducted to determine the feasibility of a single-dose immunocastration vaccine implant. These five studies utilized a total of 44 Holstein bulls to determine the optimal vaccine composition and validate the ability of a stainless-steel subcutaneous implant to deliver a vaccine. Outcome measures included the duration of implant retention, scrotal dimensions and temperature, implant site temperature, anti-GnRH antibodies, and serum testosterone concentration. Over the course of several studies, anti-GnRH antibodies were successfully stimulated by vaccine implants. No significant treatment effects on scrotal dimensions or testosterone were detected over time, but changes in spermatogenesis were detected across treatment groups. Results indicate that a single-dose implantable immunocastration vaccine elicits a humoral immune response and could impact spermatogenesis in bulls. These findings provide opportunities for the refinement of this technology to improve implant retention over longer periods of time. Taken together, this approach will offer producers and veterinarians an alternative to physical castration methods, to improve animal welfare during routine livestock management procedures.
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Hempseed cake is a byproduct of hempseed oil extraction and is potentially a useful source of protein and fiber for use in ruminant diets. However, data are lacking on the appearance and/or clearance of cannabinoids in tissues of animals fed hempseed cake. To this end, a rapid method for quantifying cannabinol (CBN), cannabidiol (CBD), cannabinolic acid (CBNA), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabichromenic acid (CBCA), cannabidivarin (CBDV), cannabidivarinic acid (CBDVA), tetrahydrocannabinol (THC) and tetrahydrocannabinolic acid (THCA) in cattle tissues, plasma, and urine was developed using rapid screen electrospray ionization mass spectrometry (RS-ESI-MS). Regression coefficients of matrix-matched standard curves ranged from 0.9946 to >0.9999 and analyte recoveries averaged from 90.2 ± 15.5 to 108.7 ± 18.7% across all compounds. Limits of detection and quantification ranged from 0.05 to 2.79 ng · mL-1 and 0.17 to 9.30 ng · mL-1, respectively, while the inter-day relative standard deviation ranged from 5.1 to 15.1%. Rapid screening electrospray ionization mass spectrometry (RS-ESI-MS) returned no false positives for any cannabinoid in plasma, urine, and tissue (liver, skeletal muscle) samples from 6 non-dosed control animals (n = 90 samples; of which 72 samples were plasma or urine and 18 samples were tissues). Across-animal cannabinoid concentrations measured in 32 plasma samples of cattle dosed with ground hemp were quantified by RS-ESI-MS; analytical results correlated well (r2 = 0.963) with independent LC-MS/MS analysis of the same samples.
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Cannabidiol , Cannabinoides , Animales , Cannabidiol/análisis , Cannabinoides/análisis , Cannabinol/análisis , Cannabis , Bovinos , Cromatografía Liquida/métodos , Dronabinol/análisis , Extractos Vegetales , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem/métodosRESUMEN
OBJECTIVE: To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus). ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition. RESULTS: The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2. CLINICAL RELEVANCE: Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits.
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4-Butirolactona , Sulfonas , 4-Butirolactona/análogos & derivados , 4-Butirolactona/farmacología , Administración Oral , Animales , Ciclooxigenasa 2 , Perros , Conejos , Sulfonas/farmacologíaRESUMEN
Tick-borne Anaplasma species are obligate, intracellular, bacterial pathogens that cause important diseases globally in people, agricultural animals, and dogs. Targeted mutagenesis methods are yet to be developed to define genes essential for these pathogens. In addition, vaccines conferring protection against diseases caused by Anaplasma species are not available. Here, we describe a targeted mutagenesis method for deletion of the phage head-to-tail connector protein (phtcp) gene in Anaplasma marginale. The mutant did not cause disease and exhibited attenuated growth in its natural host (cattle). We then assessed its ability to confer protection against wild-type A. marginale infection challenge. Additionally, we compared vaccine protection with the mutant to that of whole cell A. marginale inactivated antigens as a vaccine (WCAV) candidate. Upon infection challenge, non-vaccinated control cattle developed severe disease, with an average 57% drop in packed cell volume (PCV) between days 26-31 post infection, an 11% peak in erythrocytic infection, and apparent anisocytosis. Conversely, following challenge, all animals receiving the live mutant did not develop clinical signs or anemia, or erythrocyte infection. In contrast, the WCAV vaccinees developed similar disease as the non-vaccinees following A. marginale infection, though the peak erythrocyte infection reduced to 6% and the PCV dropped 43%. This is the first study describing targeted mutagenesis and its application in determining in vivo virulence and vaccine development for an Anaplasma species pathogen. This study will pave the way for similar research in related Anaplasma pathogens impacting multiple hosts.
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Anaplasma marginale , Anaplasmosis , Enfermedades de los Bovinos , Anaplasma , Anaplasma marginale/genética , Anaplasmosis/genética , Anaplasmosis/prevención & control , Animales , Bovinos , Enfermedades de los Bovinos/microbiología , Perros , Humanos , Mutagénesis , Desarrollo de Vacunas , VirulenciaRESUMEN
Industrial hemp (IH) is defined as Cannabis sativa containing < 0.3% delta-9 tetrahydrocannabinol (THC) and was legalized in the 2018 Farm Bill. The impact of cannabinoids in IH fed to livestock, especially after repeat exposure, has not been thoroughly investigated. Sixteen male castrated Holstein cattle weighting (± SD) 447 ± 68 kg were enrolled onto the study. Cattle were allocated into two treatment groups either receiving IH (HEMP, n = 8) or a control (CNTL, n = 8). Cattle in the HEMP group were fed 25 g IH mixed in 200 g of grain once a day for 14 days to target a daily dose of 5.5 mg/kg of cannabidiolic acid (CBDA). Behavior was continuously monitored with accelerometers and blood samples were collected at predetermined time points for plasma cannabinoid, serum cortisol, serum haptoglobin, liver enzymes, serum amyloid A, and prostaglandin E2 concentrations. The HEMP group spent a mean 14.1 h/d (95% CI 13.6-14.6 h/d) lying compared to the 13.4 h/d (95% CI 12.9-13.8 h/d) for the CNTL cattle (P = 0.03). Cortisol concentrations in the HEMP group were lower than the CNTL group (P = 0.001). Cattle in the HEMP group demonstrated an 8.8% reduction in prostaglandin E2 concentrations from baseline compared to a 10.2% increase from baseline observed in the CNTL group. No differences for haptoglobin or serum amyloid A were observed. These results suggest that feeding IH with a high CBDA content for 14 days increases lying behavior and decreases biomarkers of stress and inflammation in cattle.
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Cannabinoides , Cannabis , Animales , Biomarcadores , Bovinos , Haptoglobinas , Hidrocortisona , Inflamación , Masculino , Prostaglandinas , Proteína Amiloide A SéricaRESUMEN
Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the physiological and behavioral effects of oral meloxicam (MEL), compared to a control, administered at the time of hot-iron branding in Angus and Hereford steers and heifers. The secondary objectives were to investigate breed and sex effects on pain biomarkers. A total of 70 yearlings, consisting of 35 heifers and 35 steers (Angus, Hereford, or Angus × Hereford), were enrolled in the study. Animals were blocked by sex, randomized across weight, and assigned to receive MEL (1 mg/kg) or a placebo (CON). Biomarkers were assessed for 48 h after branding and included infrared thermography (IRT), mechanical nociceptive threshold (MNT), accelerometry and a visual analog scale (VAS), and serum cortisol and prostaglandin E2 metabolites (PGEM). Wound healing was assessed for 12 wk. Hair samples to quantify cortisol levels were taken prior to and 30 d post-branding. Responses were analyzed using repeated measures with calf nested in treatment as a random effect, and treatment, time, treatment by time interaction, breed, and sex as fixed effects. There was a treatment by time interaction for PGEM (P < 0.01) with MEL having lower values than CON at 6, 24, and 48 h (MEL: 18.34 ± 3.52, 19.61 ± 3.48, and 22.24 ± 3.48 pg/mL, respectively; CON: 32.57 ± 3.58, 37.00 ± 3.52, and 33.07 ± 3.48 pg/mL; P < 0.01). MEL showed less of a difference in maximum IRT values between the branded (2.27 ± 0.29 °C) and control site (3.15 ± 0.29 °C; P < 0.01). MEL took fewer lying bouts at 0-12 h (4.91 bouts ± 0.56) compared with CON (6.87 bouts ± 0.55; P < 0.01). Compared with Hereford calves, Angus calves exhibited greater serum but lower hair cortisol, greater PGEM, more lying bouts, and less healed wound scores at 3, 4, and 5 wk. Compared with heifers, steers exhibited lower PGEM, lower branding site and ocular IRT, higher MNT, and lower plasma meloxicam levels. Steers spent more time lying, took more lying bouts and had greater VAS pain, and more healed wound scores at 5 wk than heifers. Meloxicam administration at branding reduced branding and control site temperature differences and reduced lying bouts for the first 12 h. Breed and sex effects were observed across many biomarkers. Changes from baseline values for IRT, MNT, lying time, step count, VAS pain, and wound scoring all support that branding cattle is painful.
Hot-iron branding uses thermal injury to permanently identify cattle causing painful tissue damage. The primary objective was to examine the effects of oral meloxicam (MEL), compared with a control, administered at the time of hot-iron branding in Angus and Hereford steers and heifers. The secondary objectives were to investigate breed and sex effects on pain biomarkers. A total of 70 yearlings, consisting of 35 heifers and 35 steers (Angus, Hereford, or Angus × Hereford), were enrolled. Animals were assigned to receive MEL or a placebo. Changes from baseline values for infrared thermography (IRT), mechanical nociceptive threshold, lying time, step count, visual analog scale score, and wound scoring all support that hot-iron branding cattle is painful and investigation into analgesic strategies is needed. MEL administration reduced IRT differences from the branding and control site and reduced lying bouts. Breed and sex effects were observed across a wide range of biomarkers and should be considered in future pain studies. The practicality of administering a nonsteroidal anti-inflammatory drug once at the time of branding is attractive. However, a multimodal approach using a combination of analgesics or longer acting analgesic option warrants further investigation to alleviate pain and discomfort caused by hot-iron branding.
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Hierro , Dolor , Animales , Biomarcadores , Bovinos , Femenino , Meloxicam , Dolor/tratamiento farmacológico , Dolor/prevención & control , Dolor/veterinaria , Dimensión del Dolor/veterinariaRESUMEN
The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU; 2.2 mg/kg intravenous injection), or meloxicam (MEL; 2.0 mg/kg per os). The individual animal was the experimental unit. Calves were individually weighed on days 0 and 14 of the trial to evaluate performance outcomes. On study day 0, treatments were administered, according to their random allocation, immediately prior to surgical castration using the Henderson tool method. Visual analog scale (VAS) assessment and categorical attitude score (CAS) were collected on days -1, 0 (6 h post-castration), 1, 2, 3, and 4 in the study. The VAS was assigned using a 100 mm horizontal line with "normal" labeled at one end of the line and "moribund" at the other end of the horizontal line. The masked observer assigned a mark on the horizontal line based upon the observed severity of pain exhibited by that individual animal. The CAS was assigned by the same observer using five different categories with a score of 0 being "normal". Average daily gain tended (P = 0.09) to be associated with the treatment group, and MEL had a greater (P = 0.04) average daily gain through day 14 compared with CON. A significant (P < 0.01) treatment by day interaction was indicated for VAS score, and MEL had lower VAS scores on days 0, 1, 2, and 3 post-castration compared with CON; FLU had lower VAS scores on days 0 and 1 compared with CON. A significant treatment by day interaction was not present (P = 0.25) for CAS. The FLU had lesser percent CAS ≥1 (17.5%; P = 0.05) compared with CON (29.4%); MEL has lesser percent CAS ≥1 observations (14.9%; P = 0.01) compared with CON. The median VAS increased as CAS was more severe. Results indicated MEL and FLU calves temporally improved behavioral responses following surgical castration with positive numerical trends for a 14 d average daily gain (ADG). The VAS system appeared to be an effective method of subjective evaluation of pain in beef calves in this study. Route of administration, duration of therapy, and low relative cost make oral meloxicam a reasonable analgesic treatment in calves when administered at the time of surgical castration.
Asunto(s)
Antiinflamatorios no Esteroideos , Dolor , Animales , Antiinflamatorios no Esteroideos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Bovinos , Clonixina/análogos & derivados , Masculino , Meloxicam/farmacología , Orquiectomía/métodos , Orquiectomía/veterinaria , Dolor/tratamiento farmacológico , Dolor/veterinariaRESUMEN
Pleuritic chest pain from bacterial pneumonia is often reported in human medicine. However, studies investigating pain associated with bovine respiratory disease (BRD) are lacking. The objectives of this study were to assess if bacterial pneumonia elicits a pain response in calves with experimentally induced BRD and to determine the analgesic effects of transdermally administered flunixin. A total of 26 calves, 6-7 mo of age, with no history of BRD were enrolled into one of three treatment groups: 1) experimentally induced BRD + transdermal flunixin at 3.3 mg/kg twice, 24 h apart (BRD + FTD); 2) experimentally induced BRD + placebo (BRD + PLBO); and 3) sham induction + placebo (CNTL + PLBO). Calves induced with BRD were inoculated with Mannheimia haemolytica via bronchoalveolar lavage. Outcomes were collected from -48 to 192 h post-treatment and included serum cortisol, infrared thermography, mechanical nociceptive threshold, substance P, kinematic gait analysis, visual analog scale (VAS), clinical illness score, computerized lung score, average activity and rumination level, prostaglandin E2 metabolite, plasma serum amyloid A, and rectal temperature. Outcomes were evaluated using either a generalized logistic mixed model for categorical variables or a generalized linear mixed model for continuous variables. Right front force differed by treatment (P = 0.01). The BRD + PLBO had lower mean force applied to the right front limb (85.5 kg) compared with BRD + FTD (96.5 kg; P < 0.01). Average VAS differed by a treatment by time interaction (P = 0.01). The VAS scores differed for BRD + PLBO at -48 (3.49 mm) compared with 168 and 192 h (13.49 and 13.64 mm, respectively) (P < 0.01). Activity for BRD + PLBO was higher at -48 h (27 min/h) compared with 48, 72, 120, and 168 h (≤ 22.24 min/h; P < 0.01). Activity differed by a treatment by time interaction (P = 0.01). Activity for BRD + FTD was higher at -48 and 0 h (28.2 and 28.2 min/h, respectively) compared to 48, 72, 96, and 168 h (≤23.7 min/h; P < 0.01). Results show a combination of reduced activity levels, decreased force on the right front limb, and increased VAS pain scores all support that bacterial pneumonia in cattle is painful. Differences in right front force indicate that flunixin transdermal may attenuate certain pain biomarkers in cattle with BRD. These findings suggest that BRD is painful and analgesic drugs may improve the humane aspects of care for cattle with BRD.
Asunto(s)
Enfermedades de los Bovinos , Neumonía Bacteriana , Animales , Bovinos , Enfermedades de los Bovinos/tratamiento farmacológico , Clonixina/análogos & derivados , Dolor/tratamiento farmacológico , Dolor/veterinaria , Dimensión del Dolor , Neumonía Bacteriana/complicaciones , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/veterinariaRESUMEN
Bovine respiratory disease (BRD) is the most economically significant disease for cattle producers in the U.S. Cattle with advanced lung lesions at harvest have reduced average daily gain, yield grades, and carcass quality outcomes. The identification of biomarkers and clinical signs that accurately predict lung lesions could benefit livestock producers in determining a BRD prognosis. Receiver operating characteristic (ROC) curves are graphical plots that illustrate the diagnostic ability of a biomarker or clinical sign. Previously we used the area under the ROC curve (AUC) to identify cortisol, hair cortisol, and infrared thermography imaging as having acceptable (AUCâ >â 0.7) diagnostic accuracy for detecting pain in cattle. Herein, we used ROC curves to assess the sensitivity and specificity of biomarkers and clinical signs associated with lung lesions after experimentally induced BRD. We hypothesized pain biomarkers and clinical signs assessed at specific time points after induction of BRD could be used to predict lung consolidation at necropsy. Lung consolidation ofâ >â 10% was retrospectively assigned at necropsy as a true positive indicator of BRD. Calves with a score ofâ <â 10% were considered negative for BRD. The biomarkers and clinical signs analyzed were serum cortisol; infrared thermography (IRT); mechanical nociceptive threshold (MNT); substance P; kinematic gait analysis; a visual analog scale (VAS); clinical illness score (CIS); computerized lung score (CLS); average activity levels; prostaglandin E2 metabolite (PGEM); serum amyloid A; and rectal temperature. A total of 5,122 biomarkers and clinical signs were collected from 26 calves, of which 18 were inoculated with M. haemolytica. All statistics were performed using JMP Pro 14.0. Results comparing calves with significant lung lesions to those without yielded the best diagnostic accuracy (AUCâ >â 0.75) for right front stride length at 0 h; gait velocity at 32 h; VAS, CIS, average activity and rumination levels, step count, and rectal temperature, all at 48 h; PGEM at 72 h; gait distance at 120 h; cortisol at 168 h; and IRT, right front force and serum amyloid A, all at 192 h. These results show ROC analysis can be a useful indicator of the predictive value of pain biomarkers and clinical signs in cattle with induced bacterial pneumonia. AUC values for VAS score, average activity levels, step count, and rectal temperature seemed to yield good diagnostic accuracy (AUCâ >â 0.75) at multiple time points, while MNT values, substance P concentrations, and CLS did not (all AUC valuesâ <â 0.75).
Bovine respiratory disease (BRD) is the most economically significant disease for cattle producers in the United States, affecting 16.2% of cattle on feed. Cattle with advanced lung lesions at harvest have reduced average daily gain, yield grades, and carcass quality outcomes. The identification of biomarkers and clinical signs that accurately predict lung lesions could benefit livestock producers in determining a BRD prognosis. Herein, we used receiver operating characteristic curves to assess the predictive value of biomarkers and clinical signs associated with lung lesions after experimentally induced BRD. In the first 72 h after onset of BRD, right front stride length, gait velocity, visual analog scale score, clinical illness score, average activity level, step count, and rectal temperature yielded the best diagnostic accuracy (AUCâ >â 0.75) for predicting calves with significant lung lesions (>10% consolidation) at necropsy. Biomarkers and clinical signs with the best diagnostic accuracy early in the disease process would likely be the most valuable in field conditions. These results can be used to guide refinement of the optimal time points and biomarkers for the diagnosis of significant lung lesions after BRD.
Asunto(s)
Complejo Respiratorio Bovino , Enfermedades de los Bovinos , Neumonía Bacteriana , Animales , Biomarcadores , Complejo Respiratorio Bovino/diagnóstico , Bovinos , Enfermedades de los Bovinos/diagnóstico , Pulmón , Neumonía Bacteriana/veterinaria , Curva ROC , Estudios RetrospectivosRESUMEN
Castration is a routine procedure performed on beef and dairy operations in the United States. All methods of castration cause behavioral, physiologic, and neuroendocrine changes associated with pain. The American Veterinary Medical Association and the American Association of Bovine Practitioners recommend that anesthesia and analgesia be administered during castration. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at castration. The authors chose to investigate this novel formulation as an alternative to the current industry standards using lidocaine nerve blocks alone or in combination with meloxicam. Thirty male Holstein calves, 16 to 20 wk of age, were enrolled and randomly assigned to one of the four treatment groups prior to surgical castration: 1) bupivacaine liposome suspension blockâ +â oral placebo (BUP), 2) lidocaine blockâ +â oral placebo (LID), 3) lidocaine blockâ +â oral meloxicam (1 mg/kg) (LIDâ +â MEL), and 4) saline blockâ +â oral placebo (CON). Biomarkers were collected at -24 h and from 0 to 120 h post-castration and included infrared thermography, pressure mat gait analysis, chute defense and behavior scoring (pain and activity), and blood sampling for serum cortisol and prostaglandin E2 metabolites (PGEMs). Responses were analyzed using repeated measures, with calf nested in treatment as a random effect, and treatment, time, and their interaction designated as fixed effects. The results from pressure mat gait analysis show that the CON had a shorter front limb stance time from baseline (-8.73%; 95% confidence interval [CI]: -24.84% to 7.37%) compared with BUP and LIDâ +â MEL (>5.70%; 95% CI: -22.91% to 23.79%) (Pâ <â 0.03). The CON tended to have an increase in front limb force from baseline (6.31%; 95% CI: -1.79% to 14.41%) compared with BUP, LID, and LIDâ +â MEL (<-5.06%; 95% CI: -14.22% to 0.95%) (Pâ <â 0.04). The CON displayed higher counts of hunched standing (2.00; 95% CI: 1.68 to 2.32) compared with LIDâ +â MEL (1.43; 95% CI: 1.13 to 1.72) (Pâ =â 0.05). The CON had higher cortisol concentrations at 24 h (7.70 ng/mL; 95% CI: 1.52 to 13.87 ng/mL) relative to BUP (3.11 ng/mL; 95% CI: -2.56 to 8.79 ng/mL) (Pâ =â 0.002). At 4 and 24 h, LIDâ +â MEL had lower PGEM concentrations from baseline (-32.42% and -47.84%; 95% CI: -78.45% to -1.80%) compared with CON (27.86% and 47.63%; 95% CI: 7.49% to 82.98%) (Pâ <â 0.02). The administration of bupivacaine liposome suspension as a local anesthetic block at the time of castration was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam.
Castration is a routine procedure performed on beef and dairy operations in the United States. All methods of castration cause pain. The American Veterinary Medical Association and the American Association of Bovine Practitioners recommend that anesthesia and analgesia be administered during castration. The objective of this study was to evaluate the effectiveness of bupivacaine liposome suspension, a novel, long-acting, local anesthetic formulation administered as a nerve block at castration, as an alternative to current industry standards using lidocaine nerve blocks alone or in combination with meloxicam. Evidence provided in the current study demonstrates that pain from surgical castration can last up to 120 h post-castration, indicated by changes in ocular temperature, gait analysis, and prostaglandin metabolite concentrations. These data show that the administration of bupivacaine liposome suspension as a local anesthetic block at the time of castration was as effective at controlling pain as a multimodal approach of lidocaine and meloxicam. A single injection that alleviates both perioperative and postoperative pain would be an attractive option for livestock producers to alleviate pain at the time of castration. Further research is needed to discover effective ways of managing pain for extended durations following painful husbandry procedures.