Objective—To evaluate the effect of intra-articular injection of gelatin hydrogel microspheres containing basic fibroblast growth factor (bFGF) on experimentally induced defects in third metacarpal bones (MC3s) of horses, in vivo.
Animals—6 healthy adult Thoroughbreds.
Procedures—Horses were anesthetized, and a hole (diameter, 4.5 mm) was drilled into the medial condyle of both MC3s of each horse. One milliliter (100 μg) of a solution of gelatin hydrogel microspheres (2 mg) containing bFGF was injected into the joint capsule of the right metacarpophalangeal joint of each horse (bFGF joint). One milliliter of saline (0.9% NaCl) solution was injected into the left metacarpophalangeal joint (control joint). Radiography was performed 1 day and 4, 8, 12, and 16 weeks after surgery to evaluate bone defect refilling. Sixteen weeks after surgery, multidetector-row computed tomography (MDRCT) was performed to determine the degree of refilling at the bone defect site.
Results—Radiography revealed healing of bone defects at 4 to 12 weeks after surgery in bFGF joints and at 8 to 16 weeks after surgery in control joints. In addition, MDRCT revealed a higher degree of healing in bFGF versus control joints. Mean ± SD MDRCT score for bFGF joints (411.7 ± 135.6 Hounsfield units) was significantly higher than that for control joints (240.8 ± 133.1 Hounsfield units).
Conclusions and Clinical Relevance—Treatment of horses with gelatin hydrogel microspheres that contained bFGF enhanced bone regeneration and healing of experimentally induced defects. This treatment strategy may be useful for treating horses with fractures.
To determine plasma pharmacokinetics of metronidazole and imipenem following administration of a single dose PO (metronidazole, 15 mg/kg) or IV (imipenem, 10 mg/kg) in healthy Thoroughbreds and simulate pleural fluid concentrations following multiple dose administration every 8 hours.
4 healthy Thoroughbreds.
Metronidazole and imipenem were administered, and samples of plasma and pleural fluid were collected at predetermined time points. Minimum concentrations of metronidazole and imipenem that inhibited growth of 90% of isolates (MIC90), including 22 clinical Bacteroides isolates from horses with pleuropneumonia, were calculated. For the computer simulation, the target ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was > 70, and the target percentage of time per day that the pleural fluid concentration of imipenem exceeded the MIC90 was > 50%.
Mean ± SD pleural fluid concentrations of metronidazole and imipenem were 12.7 ± 3.3 μg/mL and 12.1 ± 0.9 μg/mL, respectively, 1 hour after administration and 4.9 ± 0.85 μg/mL and 0.3 ± 0.08 μg/mL, respectively, 8 hours after administration. For both antimicrobials, concentrations in the pleural fluid and plasma were similar. The ratio for area under the pleural fluid concentration-versus-time curve during 24 hours to the MIC90 for metronidazole was 84.9, and the percentage of time per day the pleural fluid concentration of imipenem exceeded the MIC90 was 70.9%.
CONCLUSIONS AND CLINICAL RELEVANCE
Results suggested that administration of metronidazole (15 mg/kg, PO, q 8 h) or imipenem (10 mg/kg, IV, q 8 h) resulted in their accumulation in the pleural fluid in healthy horses and concentrations were likely to be effective for the treatment of pneumonia and pleuropneumonia caused by Bacteroides spp.