OBJECTIVE To compare the plasma pharmacokinetics of tulathromycin between 3-week-old (preweaned) and 6-month-old (weaned) calves and to characterize the distribution of tulathromcyin into pulmonary epithelial lining fluid (PELF) and interstitial fluid (ISF) of preweaned and weaned calves following SC administration of a single dose (2.5 mg/kg). ANIMALS 8 healthy 3-week-old and 8 healthy 6-month-old Holstein steers. PROCEDURES A jugular catheter and SC ultrafiltration probe were aseptically placed in the neck of each calf before tulathromycin administration. Blood, ISF, and bronchoalveolar lavage fluid samples were collected at predetermined times before and after tulathromycin administration for quantification of drug concentration. A urea dilution method was used to estimate tulathromycin concentration in PELF from that in bronchoalveolar lavage fluid. Tulathromycin–plasma protein binding was determined by in vitro methods. Plasma pharmacokinetics were determined by a 2-compartment model. Pharmacokinetic parameters and drug concentrations were compared between preweaned and weaned calves. RESULTS Clearance and volume of distribution per fraction of tulathromycin absorbed were significantly greater for weaned calves than preweaned calves. Tulathromycin–plasma protein binding was significantly greater for weaned calves than preweaned calves. Maximum PELF tulathromycin concentration was significantly greater than the maximum plasma and maximum ISF tulathromycin concentrations in both groups. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that age affected multiple pharmacokinetic parameters of tulathromycin, likely owing to physiologic changes as calves mature from preruminants to ruminants. Knowledge of those changes may be useful in the development of studies to evaluate potential dose adjustments during treatment of calves with respiratory tract disease.

Ultrasonography is not often used in feline dermatology. The purpose of this study was to assess the usefulness and applicability of ultrasonography for skin evaluation in 21 clinically healthy cats. Ultrasonographic examination was conducted in 4 cutaneous regions (frontal, dorsal neck, sacral, and abdominal) using an 18-MHz linear-sequential-array transducer. Findings were assessed using histomorphometric analysis of skin samples set as reference standards. Morphologic evaluation, thickness measurements, measurement variability, and comparison between regions and genders were carried out. The ultrasonographic pattern of feline skin was characterized by 3 distinct layers of different echogenicity and echostructure. Skin was thickest at the dorsal neck region and thinnest at the abdominal region. Skin at the frontal region and dorsal neck region was thicker in males. Variability was < 10% in all regions. No apparent correspondence was found between ultrasonographic and histometric measurements of skin thickness. Collectively, these findings suggest that ultrasonography is a simple, noninvasive, and reproducible technique that allows cutaneous layers to be identified and accurately measures skin thickness in cats.

Objective—To determine the pharmacokinetics of cefovecin sodium after SC administration to Hermann's tortoises (Testudo hermanni). Animals—23 healthy adult Hermann's tortoises (15 males and 8 females). Procedures—Cefovecin (8.0 mg/kg) was injected once in the subcutis of the neck region of Hermann's tortoises, and blood samples were obtained at predetermined time points. Plasma cefovecin concentrations were measured via ultraperformance liquid chromatography coupled to tandem mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Plasma protein concentration was quantified, and the percentage of cefovecin bound to protein was estimated with a centrifugation technique. Results—Cefovecin was absorbed rapidly, reaching maximum plasma concentrations between 35 minutes and 2 hours after administration, with the exception of 1 group, in which it was reached after 4 hours. The mean ± SD time to maximum concentration was 1.22 ± 1.14 hours; area under the concentration-time curve was 220.35 ± 36.18 h•μg/mL The mean protein-bound fraction of cefovecin ranged from 41.3% to 47.5%. No adverse effects were observed. Conclusions and Clinical Relevance—Administration of a single dose of cefovecin SC appeared to be well-tolerated in this population of tortoises. Results of pharmacokinetic analysis indicated that the 2-week dosing interval suggested for dogs and cats cannot be considered effective in tortoises; however, further research is needed to determine therapeutic concentrations of the drug and appropriate dose ranges.

A radiopaque marker was injected, using needles of various lengths, into the cervical musculature, the lumbar epaxial musculature, and the cranial and caudal muscular masses of the thighs of anesthetized dogs. After this procedure, the dogs were euthanatized and deep-frozen. The bodies were then sectioned, and the slices were radiographed to determine the fate of the injected material. Material that was injected into the neck or caudal region of the thigh was determined to be located in the muscle bellies or dispensed throughout the intermuscular fascial sheaths. In contrast, material injected into the lumbar area and cranial region of the thigh was located entirely in the muscle bellies. It was concluded that the best sites for injection in dogs are the lumbar epaxial musculature or the quadriceps femoris muscle when IM administration is imperative.

OBJECTIVE To use a biopolymer delivery system to investigate the ability of interleukin (IL)-4 to recruit neutrophils into subcutaneous tissues of equids. ANIMALS 16 horses and 2 ponies. PROCEDURES Animals were assigned to 3 experiments (6/experiment). Effects of recombinant equine (Req) IL-4 (100, 250, or 500 ng/site) versus a positive control (ReqIL-8; 100 ng, 250 ng, or 1 μg/site) and a negative control (Dulbecco PBSS or culture medium) on neutrophil chemotaxis were assessed after SC injection into the neck with an injectable biopolymer used as the vehicle. Tissue samples including the biopolymer plug were collected by biopsy at various time points from 3 hours to 7 days after injection. Neutrophil infiltration was evaluated by histologic scoring (experiments 1, 2, and 3) or flow cytometry (experiment 3). RESULTS Histologic neutrophil infiltration scores did not differ significantly among treatments at most evaluated time points. On flow cytometric analysis, log-transformed neutrophil counts in biopsy specimens were significantly greater for the ReqIL-8 treatment (1 μg/site) than the negative control treatment at 3 but not 6 hours after injection; results did not differ between ReqIL-4 and control treatments at either time point. Negative control treatments induced an inflammatory response in most equids in all experiments. CONCLUSIONS AND CLINICAL RELEVANCE Flow cytometry was a more reliable method to estimate neutrophil migration than histologic score analysis. The ReqIL-4 treatment did not induce a detectable neutrophil response, compared with the negative control treatment in this study. Evidence of inflammation in negative control samples suggested the biopolymer is not a suitable vehicle for use in equids.

OBJECTIVE To evaluate IM injection of oxytetracycline as an experimental model to induce pain and assess the analgesic efficacy of flunixin meglumine (FM) in dairy cows. ANIMALS 15 healthy nonlactating Jersey (n = 10) and Holstein (5) cows. PROCEDURES In the first of 2 experiments, 5 Jerseys were administered oxytetracycline (10 mg/kg, IM), divided between the right side of the neck and left hind limb. The left side of the neck and right hind limb received sham injections. Cows were also randomly assigned to receive FM (2.2 mg/kg, IV; n = 3) or an equal volume of saline (0.9% NaCl) solution (0.044 mL/kg, IV; control; 2) once daily for 5 days. The mechanical nociceptive threshold (MNT) was measured before oxytetracycline administration and at predetermined times after each injection of the assigned treatment. Experiment 2 was similar to experiment 1 except it involved 5 Jerseys and 5 Holsteins, oxytetracycline was injected only in a hind limb, and the assigned treatment was administered for 10 days. RESULTS For both experiments, mean MNT for the oxytetracycline injection site was consistently less than that for the sham injection site in the hind limbs, and mean MNT at the hind limb oxytetracycline injection site for FM-treated cows was greater than that for control cows beginning on day 3. CONCLUSIONS AND CLINICAL RELEVANCE IM injection of oxytetracycline in a hind limb reliably induced signs of pain in dairy cows and, with validation, might be useful as an experimental model for assessing pain mitigation strategies in cattle.

Objective—To determine pharmacokinetics of marbofloxacin in water buffalo calves (Bubalus bubalis) after multiple SC administrations and to assess differences in regimen efficacy. Animals—18 healthy buffalo calves. Procedures—Calves (n = 6 calves/group) were assigned to receive marbofloxacin SC in the neck at 1 of 3 dosages (2 mg/kg, q 24 h for 6 days [regimen 1]; 4 mg/kg, q 48 h for 6 days [regimen 2]; and 4 mg/kg, q 24 h for 3 days [regimen 3]). Serum marbofloxacin concentrations were analyzed. Efficacy predictors were estimated on the basis of minimum inhibitory concentration and mutant prevention concentration reported for Pasteurella multocida and Mannheimia haemolytica. Results—Mean ± SD area under the concentration-time curve was 5.92 ± 0.40 μg•h/mL for regimen 1, which differed significantly from that for regimens 2 (14.26 ± 0.92 μg•h/mL) and 3 (14.17 ± 0.51 μg•h/mL). Mean residence time and mean elimination half-life for regimen 2 (9.93 ± 0.20 hours and 8.77 ± 0.71 hours) both differed significantly from those for regimens 1 (721 ± 0.11 hours and 5.71 ± 0.38 hours) and 3 (759 ± 0.13 hours and 737 ± 1.19 hours). Values obtained from indices for P multocida and M haemolytica had an excessively wide range because of the various degrees of antimicrobial susceptibility (low, medium, and high) of the strains. Conclusions and Clinical Relevance—Regimen 3 had the most favorable indices, and it would be conducive for owner compliance and require less handling of animals.

Objective: To compare the effect of extracorporeal shock wave therapy (ESWT) on expression of fibroblast growth factor-7 (FGF-7), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-A (PDGF), and vascular endothelial growth factor-A (VEGF) in skin with surgically created skin wounds and intact skin in horses. Animals: 14 healthy horses. Procedure: 8 horses were treated with ESWT at 6 locations along the neck at 36, 24, 12, 6, 2, or 1 hour prior to collection of full-thickness biopsy specimens from each location; a control specimen was collected from a sham-treated location. In 6 horses, 5 full-thickness wounds were created in each forelimb. Wounds in 1 forelimb/horse received ESWT immediately after creation and subsequently on days 7, 14, and 21; wounds in the contralateral forelimb remained untreated. Biopsy specimens were collected from 1 wound on each forelimb on days 7, 14, 21, 28, and 35. Expression levels of FGF-7, TGF-β1, IGF-1, PDGF, and VEGF were assessed in tissue samples from the horses' necks and forelimbs. Results: In surgically created wounds, ESWT treatment was associated with reduced TGF-β1 expression, compared with expression in control wounds, during the entire study period. At 28 days following wound creation, IGF-1 expression was significantly increased for treated and untreated wounds, compared with findings on days 7, 14, 21, and 35. There was no significant effect of treatment on FGF-7, TGF-β1, IGF-1, PDGF, or VEGF expression in intact skin. Conclusions and Clinical Relevance: Intervention with ESWT to suppress TGF-β1 may decrease granulation tissue production, resulting in improved wound healing on the distal portion of horses' limbs.

Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle. Animals—33 healthy Angus calves approximately 7 to 8 months of age. Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry. Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells. Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.

The position, dimensions, and structure of the thyroid gland, the portion of the esophagus in the neck the cervical lymph nodes, and the major blood vessels of the neck were determined via ultrasonography in cattle. The left and right ventral neck regions of 30 healthy Swiss Braunvieh cows were examined ultrasonographically, using 3.5- and 5.0-MHz linear transducers and a 3.5-MHz convex transducer. The external jugular vein was situated directly beneath the skin in the upper and middle parts of the neck and 2.7 to 6.6 cm from the body surface in the lower part of the neck. In contrast, the common carotid artery was located further from the body surface along the entire ventral neck region; depending on the measuring point, this distance varied from 2.6 to 10.9 cm. The external jugular vein narrowed from caudad to craniad. The diameter of the common carotid artery remained fairly constant along its course in the ventral part of the neck and varied from 0.9 to 1.4 cm. The thyroid gland was identified via ultrasonography caudodorsal to the larynx It appeared as an echogenic spindle-shaped structure with finely granular echogenic pattern. The esophagus appeared as a band-shaped structure in longitudinal section, and it could be followed to the thoracic inlet. Its width increased from craniad to caudad, and mean +/- SD diameter was 2.9 +/- 0.23 cm. The medulla, hilus, cortex, and capsule of the cervical lymph nodes could be clearly differentiated via ultrasonography. Mean length and width of the left cervical lymph node were 3.0 +/- 0.45 and 1.8 +/- 0.23 cm, respectively. To determine reproducibility and reliability of the results, 10 cows were examined by ultrasonography 10 times within 2 weeks. The interassay coefficients of variation determined from these examinations varied from 3.0 to 12.3%; most of the coefficients of variation ranged from 5 to 10%. The smallest coefficients of variation were determined for diameter of the common carotid artery, and the largest were for diameter of the external jugular vein. Description of the ultrasonographic appearance of the structures of the ventral neck region in healthy cattle represents the basis for use of diagnostic ultrasonography in cattle with suspected diseases involving this area. The technique is noninvasive and can be performed on cattle in standing position.