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- Author or Editor: Dean W. Richardson x
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Abstract
Objective—To determine the effects of interleukin- 1β (IL-1β) and tumor necrosis factor-α (TNF-α) on expression and regulation of several matrix-related genes by equine articular chondrocytes.
Sample Population—Articular cartilage harvested from grossly normal joints of 8 foals, 6 yearling horses, and 8 adult horses.
Procedure—Chondrocytes maintained in suspension cultures were treated with various doses of human recombinant IL-1β or TNF-α. Northern blots of total RNA from untreated and treated chondrocytes were probed with equine complementary DNA (cDNA) probes for cartilage matrix-related genes. Incorporation of 35S-sulfate, fluorography of 14C-proline labeled medium, zymography, and western blotting were used to confirm effects on protein synthesis.
Results—IL-1β and TNF-α increased steady-state amounts of mRNA of matrix metalloproteinases 1, 3, and 13 by up to 100-fold. Amount of mRNA of tissue inhibitor of metalloproteinase-1 also increased but to a lesser extent (1.5- to 2-fold). Amounts of mRNA of type-II collagen and link protein were consistently decreased in a dose-dependent manner. Amount of aggrecan mRNA was decreased slightly; amounts of biglycan and decorin mRNA were minimally affected.
Conclusions and Clinical Relevance—Treatment of cultured equine chondrocytes with IL-1β or TNF-α resulted in marked alterations in expression of various matrix and matrix-related genes consistent with the implicated involvement of these genes in arthritis. Expression of matrix metalloproteinases was increased far more than expression of their putative endogenous inhibitor. Results support the suggestion that IL-1β and TNF-α play a role in the degradation of articular cartilage in arthritis. (Am J Vet Res 2000;61: 624–630)
Abstract
Case Description—A 16-year-old Thoroughbred gelding was examined because of chronic right forelimb lameness.
Clinical Findings—On radiographs of the right front foot, the distal interphalangeal (DIP) joint space was narrow, and osteophytes and periarticular bony proliferation indicative of severe osteoarthritis were seen. Arthrodesis of the right DIP joint was recommended to improve the horse's comfort on the limb.
Treatment and Outcome—The horse was anesthetized, and palmar and dorsal arthroscopic approaches were used to remove as much of the articular cartilage as was accessible. Holes were then drilled through the dorsal aspect of the hoof wall, and 3 transarticular, 5.5-mm cortical screws were placed in lag fashion through these holes across the distal phalanx and into the middle phalanx. Defects in the hoof wall were filled with gentamicin-impregnated polymethyl methacrylate plugs and sealed with cyanoacrylate. Eight months after surgery, fusion of the DIP joint was evident radiographically and the horse was sound at a walk.
Clinical Relevance—Transarticular placement of cortical screws through a dorsal hoof wall approach combined with arthroscopically guided cartilage removal can result in fusion of the DIP joint in horses.
Abstract
Objective—To determine effects of interleukin (IL)-1β and glucocorticoids on total glycosaminoglycan (GAG) loss and aggrecanase-mediated matrix degradation in equine cartilage.
Sample Population—Cartilage from 24 equine cadavers free of sepsis and musculoskeletal disease.
Procedures—Effects of IL-1β, IL-1β with glucocorticoids (dexamethasone and triamcinolone, 10−6 and 10−7M), and glucocorticoids alone on degradation of equine articular and nasal cartilage explants were assessed by measuring GAG release in media and GAG content in cartilage. Aggrecanase-mediated cleavage within the interglobular domain at Glu373-Ala374 was evaluated via western blot analysis and ELISAs. Steady-state mRNA concentrations of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4, and ADAMTS5 were assessed by use of real-time reverse transcriptase PCR assay (cartilage explants) and northern blot analysis (cell culture).
Results—IL-1β increased GAG release and aggrecanase activity (11-fold). The MMP-3, MMP-13, and ADAMTS4 mRNA were upregulated with IL-1β, whereas ADAMTS5 mRNA was increased (13-fold), but significantly less than ADAMTS4 mRNA (27-fold), suggesting a role for both ADAMTS4 and ADAMTS5 in degradation of cytokine-stimulated cartilage. Despite downregulation of MMP-3 and MMP-13 mRNA, glucocorticoids did not alter GAG degradation. A further increase in aggrecanase activity was detected with ELISAs and western blot analysis, whereas ADAMTS4 mRNA was downregulated and ADAMTS5 mRNA was maintained or upregulated.
Conclusions and Clinical Relevance—MMP-3, MMP-13, and ADAMTS4 were regulated differently than ADAMTS5. Glucocorticoids increased aggrecanase activity despite down-regulation of ADAMTS4 mRNA, suggesting a major role of ADAMTS5. Effects of glucocorticoids on aggrecanase activity have important implications in terms of treatment.
Abstract
Objective—To report the outcome of surgical treatment of comminuted fractures of the proximal phalanx in horses.
Design—Retrospective study.
Animals—64 horses.
Procedure—Medical records and radiographs were reviewed to obtain information regarding signalment, fracture classification, and treatment. Follow-up information was obtained by telephone conversation or evaluation of production records.
Results—Thirty-eight horses had moderately comminuted fractures of the proximal phalanx. Two horses were euthanatized immediately. Fractures of the proximal phalanx in 36 horses were repaired with open reduction and internal fixation with a successful outcome in 33 (92%) horses. Reconstruction of the fracture was performed in most horses by use of a long curved incision, transection of the collateral ligament of the metacarpophalangeal or metatarsophalangeal joint, and open exposure of the proximal articular surface of the proximal phalanx. Twenty-six horses had severely comminuted fractures of the proximal phalanx. Six horses were euthanatized immediately. One horse was euthanatized after 9 days of treatment with a cast alone. Severely comminuted fractures of the proximal phalanx in 13 horses were treated with an external skeletal fixation device, and fractures healed in 8 of those horses. Six horses with severely comminuted fractures of the proximal phalanx were treated with transfixation pins incorporated into a fiberglass cast, and fractures healed in 4 horses.
Conclusions and Clinical Relevance—Moderately comminuted fractures of the proximal phalanx can be successfully repaired; however, fractures that are too severe to permit accurate reconstruction of the fragments remain difficult to treat and horses have only a fair prognosis for survival. (J Am Vet Med Assoc 2004; 224:254–263)
Abstract
Objective—To investigate the effects of insulin-like growth factor-II (IGF-II) on DNA and glycosaminoglycan (GAG) synthesis and the expression of matrix-related genes in equine articular cartilage explants and chondrocytes, respectively, with and without interleukin 1-β (IL1-β).
Sample Population—Articular cartilage from 12 adult horses.
Procedure—Articular cartilage was incubated in standard media with and without equine IL1-β (10 ng/mL) containing various concentrations of IGF-II for 72 hours. Synthesis of DNA and GAG was determined by incorporation of thymidine labeled with radioactive hydrogen (3H) and sulfate labeled with radioactive sulfur (35S), respectively. Total GAG content of the explants and spent media was determined by use of the 1,9-dimethylmethylene blue assay. Northern blots of RNA from cultured equine articular cartilage chondrocytes were hybridized with cDNA of major matrix molecules.
Results—Insulin-like growth factor-II stimulated DNA and GAG synthesis at concentrations of 25 and 50 ng/mL, respectively. In cartilage explants conditioned with IL1-β, IGF-II stimulated DNA and GAG synthesis at concentrations of 500 and 50 ng/mL, respectively. Insulin-like growth factor-II had no effect on total GAG content as determined by the 1,9-dimethylmethylene blue assay. No specific effects on steady-state levels of messenger RNAs were observed.
Conclusions and Clinical Relevance—Insulin-like growth factor-II stimulated DNA and GAG synthesis in equine adult cartilage and may have potential application in vivo. (Am J Vet Res 2004;65:238–244)
Abstract
Objective—To investigate the effects of enrofloxacin and magnesium deficiency on explants of equine articular cartilage.
Sample Population—Articular cartilage explants and cultured chondrocytes obtained from adult and neonatal horses.
Procedure—Full-thickness explants and cultured chondrocytes were incubated in complete or magnesium- deficient media containing enrofloxacin at concentrations of 0, 1, 5, 25, 100, and 500 µg/ml. Incorporation and release of sulfate 35S over 24 hours were used to assess glycosaminoglycan (GAG) synthesis and degradation. An assay that measured binding of dimethylmethylene blue dye was used to compare total GAG content between groups. Northern blots of RNA from cultured chondrocytes were probed with equine cDNA of aggrecan, type-II collagen, biglycan, decorin, link protein, matrix metalloproteinases 1, 3, and 13, and tissue inhibitor of metalloproteinase 1.
Results—A dose-dependent suppression of 35S incorporation was observed. In cartilage of neonates, 35S incorporation was substantially decreased at enrofloxacin concentrations of 25 mg/ml. In cartilage of adult horses, 35S incorporation was decreased only at enrofloxacin concentrations of ≥ 100 µg/ml. Magnesium deficiency caused suppression of 35S incorporation. Enrofloxacin or magnesium deficiency did not affect GAG degradation or endogenous GAG content. Specific effects of enrofloxacin on steadystate mRNA for the various genes were not observed.
Conclusion and Clinical Relevance—Enrofloxacin may have a detrimental effect on cartilage metabolism in horses, especially in neonates. (Am J Vet Res 2001;62:160–166)
Abstract
OBJECTIVE To determine interval (1-year) prevalence of and factors associated with colic in horses hospitalized for ocular or orthopedic disease.
DESIGN Cross-sectional study.
ANIMALS 105 horses with ocular disease and 197 horses with orthopedic disease admitted to a veterinary teaching hospital between July 1, 2011, and June 30, 2012.
PROCEDURES Medical records were reviewed to determine whether colic (abnormal behavior prompting abdominal palpation per rectum or nasogastric intubation) was observed during hospitalization. Data were collected on putative risk factors for colic, including reason for admission, signalment, and medical or surgical interventions received.
RESULTS No significant difference in interval prevalence of colic was identified between horses with ocular disease (8/105 [8%]) or orthopedic disease (9/197 [5%]). However, horses with ocular disease differed significantly from other horses in median age (10 vs 3 years, respectively); proportions of sexually intact males (3% vs 30%), Thoroughbreds (28% vs 62%), and those receiving general anesthesia (65% vs 80%); and median duration of hospitalization (3 vs 2 days). For every 1 mg/kg increase in daily NSAID dose, the odds of colic increased by 98%. No difference between groups was identified in median duration of colic (1 day), hospitalization (7 vs 3 days), or systemic NSAID administration (7 vs 5 days). Colic in both groups resolved with medical management for all but 1 horse with ocular disease.
CONCLUSIONS AND CLINICAL RELEVANCE Horses hospitalized for ocular disease were at no greater odds for colic than were horses hospitalized for orthopedic disease. Medical management of colic appeared adequate for most horses.
Abstract
Objective—To describe the pool-raft recovery system protocol and to evaluate the clinical outcome inhorses that underwent recovery from general anes-thesia using this system.
Design—Retrospective study.
Animals—393 horses that underwent recovery fromgeneral anesthesia in the pool-raft system.
Procedure—Anesthetic records were examined fromhorses recovered from anesthesia in the pool-raft sys-tem between January 1984 and December 2000.Complete medical records of horses were examinedwhen available. Information regarding the anestheticand recovery period was recorded. Horses first recov-ered from general anesthesia in the pool-raft and,once awake, were transported to a recovery stall andlowered to the floor in a standing position.
Results—351 horses underwent 1 pool-raft recovery,and 42 horses underwent multiple pool-raft recover-ies. Most horses were recovered from general anes-thesia within the pool-raft system to safeguard repairof a major orthopedic injury. During 471 pool-raftrecoveries, 34 (7%) horses had complications withinthe recovery pool and 62 (13%) had complicationswithin the recovery stall. Deaths resulted from complete failure of internal fixation, pulmonary dysfunc-tion, or a combination of pulmonary dysfunction andfixation failure in 2% (10/471) of horses that under-went pool-raft recoveries.
Conclusions and Clinical Relevance—The pool-raftsystem is a good option for recovery from generalanesthesia. Although not a fail-safe system, itappears to decrease the complications of recoveringhorses in a high-risk category. Potential disadvan-tages of this system are added expense and man-power necessary in building, maintenance, andusage, as well as size limitations of the raft itself. (J Am Vet Med Assoc 2002;221:1014–1018)
Abstract
Objective—To evaluate the use of hydrothermal ablation of articular cartilage for arthrodesis in horses through investigation of the effects of joint lavage with physiologic saline (0.9% NaCl) solution (80°C) for various treatment times on chondrocyte viability in the articular cartilage of the metacarpophalangeal and metatarsophalangeal joints of cadaveric horse limbs.
Sample Population—7 pairs of metacarpophalangeal and 8 pairs of metatarsophalangeal joints from 8 Thoroughbreds.
Procedure—The horses were euthanatized for reasons unrelated to musculoskeletal disease. On a random basis, 1 joint of each pair underwent intra-articular lavage for 5, 10, or 15 minutes with heated saline solution (80°C); the other joint underwent sham treatment of similar duration with saline solution at 22°C (control). Cartilage samples from the distal articular surface of metacarpus III (or metatarsus III), the proximal surface of the proximal phalanx, and the lateral and medial proximal sesamoid bones were assessed for chondrocyte viability via confocal microscopy and viability staining following enzymatic digestion.
Results—Compared with the control joints, findings of both viability assays indicated that the percentage of sites containing viable chondrocytes in heat-treated joints was decreased. Treatment hazard ratios of 0.048 (confocal microscopy) and 0.2 (digestion assay) were estimated. Histologically, periarticular soft tissues had minimal detrimental effects after heat treatment.
Conclusions and Clinical Relevance—Ex vivo intraarticular lavage with saline solution at 80°C resulted in the death of almost all articular chondrocytes in the joint. This technique may be a satisfactory method for extensive cartilage ablation when performing arthrodesis by minimally invasive techniques. (Am J Vet Res 2005;66:36–42)
