Objective—To investigate effects of osteochondral injury on high-mobility group box chromosomal protein 1 (HMGB-1) concentrations in synovial fluid (SF) from Thoroughbreds and to compare these results with radiographic and arthroscopic scores of severity of joint injury.
Animals—40 clinically normal rested Thoroughbreds (group 1) and 45 Thoroughbreds with osteochondral injury as a result of racing.
Procedures—SF was obtained from the metacarpophalangeal (MCP) joints, metatarsophalangeal (MTP) joints, middle carpal joints, and radiocarpal joints. For group 2, radiographic and arthroscopic scores were determined. Concentrations of SF HMGB-1 were determined by use of an ELISA.
Results—SF HMGB-1 concentrations in osteochondral-injured MCP-MTP joints were significantly higher than in normal MCP-MTP joints. Similarly, SF HMGB-1 concentrations in osteochondral-injured carpal joints were significantly higher than in normal carpal joints. Radiographic and arthroscopic scores were not correlated with SF HMGB-1 concentrations. Synovial fluid HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints and ≥ 9 ng/mL for carpal joints discriminated osteochondral-injured joints from normal joints. Horses with HMGB-1 concentrations ≥ 11 ng/mL for MCP-MTP joints were twice as likely to have an osteochondral injury, and horses with HMGB-1 concentrations ≥ 9 ng/mL for carpal joints were 4 times as likely to have an osteochondral injury.
Conclusions and Clinical Relevance—Osteochondral injury was associated with a significant increase in SF HMGB-1 concentrations in MCP-MTP and carpal joints, compared with results for clinically normal Thoroughbreds. Analysis of SF HMGB-1 concentrations may be useful for evaluation of joint injury in horses.
Objective—To determine the effects of horse age, osteochondral injury, and joint type on a synthesis biomarker and 3 degradative biomarkers of type II collagen in Thoroughbreds.
Animals—Healthy rested adult (3- to 12-year-old) Thoroughbreds (n = 19), yearling (1- to 2-year-old) Thoroughbreds (40), and Thoroughbred racehorses (2 to 7 years old) undergoing arthroscopic surgery for removal of osteochondral fragments that resulted from training or racing (41).
Procedures—Samples of blood and metacarpophalangeal, metatarsophalangeal, or carpal joint synovial fluid (SF) were collected from all horses. Commercially available assays were used to analyze SF and serum concentrations of type II collagen biomarkers of synthesis (carboxy propeptide of type II collagen [CPII]) and degradation (cross-linked C-telopeptide fragments of type II collagen [CTX II], neoepitope generated by collagenase cleavage of type I and II collagen [C1,2C], and neoepitope generated by collagenase cleavage of type II collagen [C2C]).
Results—Osteochondral injury affected concentrations of CPII, CTX II, C1,2C, and C2C in SF, serum, or both, compared with concentrations in healthy adult horses. Compared with adult horses, yearling horses had increased SF or serum concentrations of degradative biomarkers (CTX II, C1,2C, and C2C). Concentrations were higher in carpal than metacarpophalangeal or metatarsophalangeal joints for all biomarkers in osteochondral-injured horses. Variable differences in SF concentrations between joint types were detected in healthy adult and yearling horses.
Conclusions and Clinical Relevance—Horse age, osteochondral injury, and joint type all significantly affected type II collagen biomarker concentrations in SF and serum of Thoroughbreds.
Objective—To investigate the effects of exercise and osteochondral injury on concentrations of carboxy-terminal telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) and serum of Thoroughbred racehorses and to compare findings with radiographic and arthroscopic scores of joint injury severity.
Animals—78 Thoroughbreds with (n = 38) and without (40) osteochondral injury.
Procedures—Serum and metacarpophalangeal or carpal joint SF samples were collected from noninjured horses before and at the end of 5 to 6 months of race training (pre- and postexercise samples, respectively) and from horses with osteochondral injury (1 joint assessed/horse). Synovial fluid and serum CTX-II concentrations were determined by use of an ELISA. Radiographic and arthroscopic scores of joint injury severity were determined for the injured horses.
Results—The CTX-II concentrations in SF and SF:serum CTX-II ratio were significantly higher for horses with joint injuries, compared with pre- and postexercise findings in noninjured horses. Serum CTX-II concentrations in postexercise and injured-horse samples were significantly lower than values in pre-exercise samples. On the basis of serum and SF CTX-II concentrations and SF:serum CTX-II ratio, 64% to 93% of serum and SF samples were correctly classified into their appropriate group (pre-exercise, postexercise, or injured-joint samples). In horses with joint injuries, arthroscopic scores were positively correlated with radiographic scores, but neither score correlated with SF or serum CTX-II concentration.
Conclusions and Clinical Relevance—Results suggested that serum and SF CTX-II concentrations and SF:serum CTX-II ratio may be used to detect cartilage degradation in horses with joint injury.
Objective—To determine whether stromal cell-derived factor-1 (SDF-1) concentrations in serum, plasma, and synovial fluid differed among untrained, race-trained, and osteochondral-injured Thoroughbred racehorses.
Animals—22 racehorses without osteochondral injury and 37 racehorses with osteochondral injury.
Procedures—Horses without osteochondral injury were examined before and after 5 to 6 months of race training. Horses with osteochondral injury were undergoing arthroscopic surgery for removal of osteochondral fragments from carpal or metacarpophalangeal or metatarsophalangeal joints (fetlock joints). Serum, plasma, and fetlock or carpal synovial fluid samples were obtained and analyzed for SDF-1 concentration by use of an ELISA.
Results—In horses with fetlock or carpal joint injury, mean synovial fluid SDF-1 concentrations were significantly higher, serum SDF-1 concentrations were significantly lower, and synovial fluid-to-serum SDF-1 ratios were significantly higher than in untrained and trained horses. Synovial fluid SDF-1 concentrations were not significantly different between trained and untrained horses. Plasma SDF-1 concentrations were not different among the 3 groups. Results obtained with serum, compared with synovial fluid and plasma, had better sensitivity for differentiating between osteochondral-injured horses and uninjured horses. In horses with fetlock joint osteochondral injury, serum SDF-1 concentrations were correlated with radiographic and arthroscopic inflammation scores, but not arthroscopic cartilage scores.
Conclusions and Clinical Relevance—Results suggested that serum SDF-1 concentrations were more sensitive than plasma and synovial fluid concentrations for detection of osteochondral injury in the fetlock or carpal joint of racehorses. Analysis of serum and synovial SDF-1 concentrations in horses with experimentally induced joint injury may help define the onset and progression of post-traumatic osteoarthritis and aid in the evaluation of anti-inflammatory treatments.
Objective—To determine regional and zonal variation
in sulfation patterns of chondroitin sulfate in normal
equine corneal stroma.
Sample Population—22 normal eyes from 11 horses.
Procedure—Corneas were collected within 24 hours
of death from equine necropsy specimens. After
papain-chondroitinase digestion of corneal tissue, disaccharides
ΔDi4S and ΔDi6S were quantified by use
of capillary zone electrophoresis in the superficial,
middle, and deep zones of central and peripheral
regions of the cornea.
Results—For the 2 regions combined,ΔDi6S/ΔDi4S
values were significantly lower in the deep and middle
zones, compared with that of the superficial zone.
In the central region, deep and middle zones had significantly
lower ΔDi6S/ΔDi4S values than the superficial
zone did. In the peripheral region, the deep zone
had significantly lower ΔDi6S/ΔDi4S values, compared
with superficial and middle zones. In the deep
zone, the peripheral region had significantly lower
ΔDi6S/ΔDi4S values than the central region did.
Conclusion and Clinical Relevance—Distribution
of ΔDi6S/ΔDi4S values follows a gradient across the
healthy equine cornea, being smallest in the deep and
middle zones of the central region and the deep zone
of the peripheral region. Regional and zonal differences
in the distribution of stromal ΔDi6S and ΔDi4S
may influence the role of glycosaminoglycans in
health, disease, and wound repair of the equine
cornea. (Am J Vet Res 2002;63:143–147)
Objective—To determine the disposition of orally
administered cefpodoxime proxetil in foals and adult
horses and measure the minimum inhibitory concentrations
(MICs) of the drug against common bacterial
pathogens of horses.
Animals—6 healthy adult horses and 6 healthy foals
at 7 to 14 days of age and again at 3 to 4 months of
Procedure—A single dose of cefpodoxime proxetil
oral suspension was administered (10 mg/kg) to each
horse by use of a nasogastric tube. In 7- to 14-day-old
foals, 5 additional doses were administered intragastrically
at 12-hour intervals. The MIC of cefpodoxime
for each of 173 bacterial isolates was determined by
use of a commercially available test.
Results—In 7- to 14-day-old foals, mean ± SD time to
peak serum concentration (Tmax) was 1.7 ± 0.7 hours,
maximum serum concentration (Cmax) was 0.81 ±
0.22 µg/mL, and elimination half-life (harmonic mean)
was 7.2 hours. Disposition of cefpodoxime in 3- to 4-month-old foals was not significantly different from
that of neonates. Adult horses had significantly higher
Cmax and significantly lower Tmax, compared with
values for foals. The MIC of cefpodoxime required to
inhibit growth of 90% of isolates for Salmonella enterica,
Escherichia coli, Pasteurella spp, Klebsiella spp,
and β-hemolytic streptococci was 0.38, 1.00, 0.16,
0.19, and 0.09 µg/mL, respectively.
Conclusions and Clinical Relevance—Oral administration
at a dosage of 10 mg/kg every 6 to 12 hours
would appear appropriate for the treatment of equine
neonates with bacterial infections. (Am J Vet Res 2005;66:30–35)
Objective—To determine the pharmacokinetics of
azithromycin and its concentration in body fluids and
bronchoalveolar lavage cells in foals.
Animals—6 healthy 6- to 10-week-old foals.
Procedure—Azithromycin (10 mg/kg of body weight)
was administered to each foal via IV and intragastric
(IG) routes in a crossover design. After the first IG
dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to
measure azithromycin concentrations in serum, peritoneal
fluid, synovial fluid, pulmonary epithelial lining
fluid (PELF), and bronchoalveolar (BAL) cells.
Results—Azithromycin elimination half-life was 20.3
hours, body clearance was 10.4 ml/min·kg, and apparent
volume of distribution at steady state was 18.6
L/kg. After IG administration, time to peak serum concentration
was 1.8 hours and bioavailability was 56%.
After repeated IG administration, peak serum concentration
was 0.63 ± 0.10 µg/ml. Peritoneal and synovial
fluid concentrations were similar to serum concentrations.
Bronchoalveolar cell and PELF concentrations
were 15- to 170-fold and 1- to 16-fold higher than concurrent
serum concentrations, respectively. No
adverse reactions were detected after repeated IG
Conclusions and Clinical Relevance—On the basis
of pharmacokinetic values, minimum inhibitory concentrations
of Rhodococcus equi isolates, and drug
concentrations in PELF and bronchoalveolar cells, a
single daily oral dose of 10 mg/kg may be appropriate
for treatment of R equi infections in foals. Persistence
of high azithromycin concentrations in PELF and bronchoalveolar
cells 48 hours after discontinuation of
administration suggests that after 5 daily doses, oral
administration at 48-hour intervals may be adequate.
(Am J Vet Res 2001;62:1870–1875)
Objective—To compare isolated limb retrograde venous injection (ILRVI) and isolated limb infusion (ILI) for delivery of amikacin to the synovial fluid of the distal interphalangeal and metacarpophalangeal joints and to evaluate the efficacy of use of an Esmarch tourniquet in standing horses.
Animals—6 healthy adult horses.
Procedures—Horses were randomly assigned in a crossover design. In ILRVI, the injection consisted of 1 g of amikacin diluted to a total volume of 60 mL administered during a 3-minute period. In ILI, the infusion consisted of 1 g of amikacin diluted to 40 mL administered during a 3-minute period followed by administration of boluses of diluent (82 mL total) to maintain vascular pressure. During ILI, the infusate and blood were circulated from the venous to the arterial circulation in 5-mL aliquots. Synovial fluid and serum samples were obtained to determine maximum amikacin concentrations and tourniquet leakage, respectively.
Results—Both techniques yielded synovial concentrations of amikacin > 10 times the minimum inhibitory concentration (MIC) for 90% of isolates (80 μg/mL) and > 10 times the MIC breakpoint (160 μg/mL) of amikacin-susceptible bacteria reported to cause septic arthritis in horses. These values were attained for both joints for both techniques. Esmarch tourniquets prevented detectable loss of amikacin to the systemic circulation for both techniques.
Conclusions and Clinical Relevance—Both techniques reliably achieved synovial fluid concentrations of amikacin consistent with concentration-dependent killing for bacteria commonly encountered in horses with septic arthritis. Esmarch tourniquets were effective for both delivery techniques in standing horses.
Objective—To characterize lameness during training and compare exercise variables and financial returns among yearling Thoroughbreds that were bought for the purpose of resale for profit.
Animals—40 yearling Thoroughbreds.
Procedures—Horses purchased at yearling sales (summer 2004) were trained prior to resale at 2-year-olds in training sales (spring 2005). Horses were monitored daily for diagnosis and treatment of lameness during training. Selected variables, including sex, age, purchase price, lameness, distance (No. of furlongs) galloped during training, and financial returns, were compared among horses that had performance speeds (assessed at 2-year-olds in training sales) classified as fast, average, or slow.
Results—37 of 40 horses became lame during training, most commonly because of joint injury. Eighteen of the lame horses had hind limb injuries only; 5 horses had injuries in forelimbs and hind limbs. The frequency of new cases of lameness increased as the date of the 2-year-olds in training sales approached. At the sales, 4, 21, and 15 horses were classified as fast, average, or slow, respectively; median financial return was slightly (but significantly) different among horses classified as fast ($14,000), average ($0), or slow (–$8,000).
Conclusions and Clinical Relevance—Incidence of lameness during training in yearling horses purchased for the purpose of resale for profit was high. Lameness more commonly affected hind limbs than forelimbs and was attributable to joint injury in most horses. Financial returns differed between horses classified as fast and average or slow at the 2-year-olds in training sales.