Associations of horse age, joint type, and osteochondral injury with serum and synovial fluid concentrations of type II collagen biomarkers in Thoroughbreds.

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.

Effect of exercise and osteochondral injury on synovial fluid and serum concentrations of carboxy-terminal telopeptide fragments of type II collagen in racehorses.

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.

High-mobility group box chromosomal protein 1 as a potential inflammatory biomarker of joint injury in Thoroughbreds.

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 > or = 11 ng/mL for MCP-MTP joints and > or = 9 ng/mL for carpal joints discriminated osteochondral-injured joints from normal joints. Horses with HMGB-1 concentrations > or = 11 ng/mL for MCP-MTP joints were twice as likely to have an osteochondral injury, and horses with HMGB-1 concentrations > or = 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.

Disposition of orally administered cefpodoxime proxetil in foals and adult horses and minimum inhibitory concentration of the drug against common bacterial pathogens of horses.

OBJECTIVES: 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 age. 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 microg/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 beta-hemolytic streptococci was 0.38, 1.00, 0.16, 0.19, and 0.09 microg/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.

Regional and zonal variations in the sulfation patterns of chondroitin sulfate in normal equine corneal stroma.

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 deltaDi4S and deltaDi6S 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, deltaDi6S/deltaDi4S 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 deltaDi6S/deltaDi4S values than the superficial zone did. In the peripheral region, the deep zone had significantly lower deltaDi6S/deltaDi4S values, compared with superficial and middle zones. In the deep zone, the peripheral region had significantly lower deltaDi6S/deltaDi4S values than the central region did. CONCLUSIONS AND CLINICAL RELEVANCE: Distribution of deltaDi6S/deltaDi4S 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 deltaDi6S and deltaDi4S may influence the role of glycosaminoglycans in health, disease, and wound repair of the equine cornea.

Concentrations of stromal cell-derived factor-1 in serum, plasma, and synovial fluid of horses with osteochondral 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.