Search Results

You are looking at 1 - 8 of 8 items for

  • Author or Editor: J. P. Caron x
  • Refine by Access: All Content x
Clear All Modify Search

Objective

To determine the patterns of use and perceived efficacy of polysulfated glycosaminoglycan (PSGAG) for the treatment of degenerative joint disease in horses.

Design

Cross-sectional mail survey.

Sample Population

1,522 equine practitioners.

Procedure

Information was obtained on frequency and route of administration of PSGAG for the treatment of each of 4 forms of degenerative joint disease, the efficacy of PSGAG, and its efficacy compared with that of sodium hyaluronate. Data were analyzed by nonparametric and multivariate regression methods.

Results

Response rate was 40.5%. Of practitioners responding, 26% were classified as having a special interest in lameness and 74% as general practitioners. Use of PSGAG was reported by 90.5% of all practitioners, but lameness practitioners used PSGAG more frequently than general practitioners. Use of PSGAG also was significantly more common among practitioners involved predominately with racing Thoroughbreds, Standardbreds, or show horses. Use of PSGAG was reported to be moderately effective in the treatment of the 4 joint disease conditions. Practitioners treating Thoroughbred racehorses gave highest efficacy scores, and pleasure horse practitioners gave lowest efficacy scores. Use of PSGAG was considered more effective than sodium hyaluronate for the treatment of subacute degenerative joint disease and less effective for idiopathic joint effusion and acute synovitis.

Clinical Implications

Use of PSGAG is regarded as moderately effective overall and is considered most useful in the treatment of subacute degenerative joint disease. The efficacy of PSGAG for incipient and chronic forms of degenerative disease is considered comparable to that of sodium hyaluronate. (J Am Vet Med Assoc 1996;209:1564–1568)

Free access
in Journal of the American Veterinary Medical Association

Summary

Middle carpal cartilage explants from 4 horses with mild osteoarthritis involving that joint were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan (psgag) on proteoglycan synthesis and degradation. Cultures were exposed to 0.025 or 25 mg of psgag/ml for 48 hours, after which the medium was replaced with medium containing similar doses of psgag and 35S. Subsequently, the sulfated proteoglycan content of the medium and extracts of the explants was measured. Gel filtration chromatography was used to estimate the size and to purify the principal, large proteoglycan monomer, which was further characterized by digestion, using glycosidic enzymes. In a second experiment, explants were incubated with 35S for 48 hours, and were subsequently exposed to the same concentrations of the psgag for an additional 48 hours. The amount of remaining labeled proteoglycan was determined for culture medium and cartilage extracts. Gel filtration chromatography was used to assess the hydrodynamic size of the large proteoglycan monomer. Aliquots of proteoglycans from the second experiment were incubated in high-molecular weight hyaluronate and chromatographed to assess reaggregation.

Polysulfated glycosaminoglycan caused a significant (P ≤ 0.04) decrease in sulfated proteoglycan synthesis by cartilage explants. Radioactive proteoglycan content in explants labeled prior to exposure to psgag were similar. Large proteoglycan monomer size was similar in both experiments (median partition coefficient [KAV] = 0.40), and was not influenced by psgag treatment. Prelabeled explants exposed to hyaluronate and chromatographed under associative conditions had similar proportions of the radiolabel eluting as proteoglycan aggregate. Enzymatic digestion of newly synthesized large monomer revealed a mild dose-dependent increase in the proportion of keratan sulfate substitution on core protein. It was concluded that psgag in vitro, at the dosages evaluated, caused a decrease in proteoglycan synthesis, had little effect on labeled proteoglycan degradation, did not influence the size of large monomer, and caused a modest increase in the concentration of keratan sulfate in proteoglycans synthesized by osteoarthritic equine chondrocytes.

Free access
in American Journal of Veterinary Research

SUMMARY

Articular cartilage explants from 3 horses were maintained in tissue culture to test the effects of a polysulfated glycosaminoglycan on proteoglycan biosynthesis. Cultures were exposed to concentrations of 0, 50, or 200 μg of the drug/ml for either 2 days or 6 days, and labeled with 35S, before measuring the content of sulfated proteoglycan in the culture media and in extracts of cartilage. In a second experiment, the explants were incubated with the isotope and subsequently exposed to the same concentrations of the polysulfated glycosaminoglycan for 4 days. Subsequently, the amount of remaining labeled proteoglycan was determined. Gel filtration chromatography was used to compare the hydrodynamic size of proteoglycans from the cartilage explants in each experiment.

Polysulfated glycosaminoglycan caused a dose-dependent depression of sulfated proteoglycan synthesis, which was statistically significant after 6 days of exposure. Radioactive proteoglycan content in explants was similar in the experiment involving isotopic labeling prior to exposure to the drug. Proteoglycan monomer size was similar in all treatment groups. It was concluded that polysulfated glycosaminoglycan caused a modest depression in proteoglycan synthesis, had little effect on endogenous proteoglycan degradation, and did not influence the size of sulfated proteoglycans synthesized by normal equine chondrocytes in explant culture.

Free access
in American Journal of Veterinary Research

Summary

In this double-blind study, the effectiveness of and dose response to intra-articular administration of modified hyaluronan (hylan) was determined in an equine carpal lameness model over a 23-day period, using a computerized three-dimensional motion analysis system, synovial fluid variables, and synovial histologic examination.

In 24 clinically sound horses, baseline motion data was acquired from horses trotting at 4 m/s on a high-speed treadmill. Then, to induce lameness, 25 mg of amphotericin B in 5 ml of sterile water was injected into the left middle carpal joint of each horse every other day for 3 treatments. Phenybutazone (2.2 mg/kg of body weight, PO, once) and butorphanol tartrate (0.1 mg/kg, IM, q 6 h, for 36 hours) were used to control signs of discomfort. Horses were assigned at random to 4 equal groups and received intracarpal administration of either 1, 2, 4 ml of hylan (8 mg/ml), or 2 ml of balanced electrolyte solution (control).

Intracarpal administration of amphotericin B caused significant (P ≤ 0.01) increase in subjective lameness grades over the 2-week evaluation period, and hylan administration did not significantly (P ≤ 0.01) change the subjective lameness grade. Lameness induction caused significant (P ≤ 0.01) decrease in head and withers excursions during the lame forelimb support phase and significant (P ≤ 0.05) increase in head and withers excursions during the sound forelimb support phase. Synovitis induction was further characterized by significant (P ≤ 0.05) increases in total wbc, polymorphonuclear, and large and small mononuclear cell numbers, and synovial fluid total protein concentrations. Also, subjective scores for synovial sections were significantly (P ≤ 0.05) different from baseline values, but hylan treatment at the 1-, 2-, or 4-ml dose did not significantly (P ≤ 0.05) alter these variables, compared with baseline values or values in control horses. Hyaluronan concentrations were not altered by induction of synovitis or hylan treatment.

Although clinical use of hyaluronan for treatment of traumatic joint disease in horses is well accepted, the beneficial effect of hylan was not detectable in this study. Further studies are required to more fully characterize the possible beneficial effects of hyaluronan-based products for treatment of joint disease in equids.

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of prostaglandin E2 (PGE2) on recombinant equine interleukin (IL)-1β-stimulated expression of matrix metalloproteinases (MMP 1, MMP 3, MMP 13) and tissue inhibitor of matrix metalloproteinase 1 (TIMP 1) in vitro.

Sample Population—Cultured equine chondrocytes.

Procedure—Stationary monolayers of first-passage chondrocytes were exposed to graduated concentrations of PGE2 with or without a subsaturating dose (50 pg/ml) of recombinant equine IL-1β (reIL-1β) to induce expression of MMP 1, MMP 3, MMP 13, and TIMP 1, followed by RNA isolation and northern blotting. In subsequent experiments, gene expression was similarly quantified from mRNA isolated from cultures pretreated with phenylbutazone to quench endogenous PGE2 synthesis, followed by exposure to reIL-1β and exogenous PGE2 (5 mg/ml) with appropriate controls.

Results—Exogenous PGE2 (10 mg/ml) significantly reduced reIL-1β-induced expression of MMP 1, MMP 3, MMP 13, and TIMP 1. Abrogation of cytokine induction with this dose of PGE2 was comparable to that for dexamethasone (10–5 M) control. Similarly, pretreatment with phenylbutazone, followed by exposure to reIL-1β and PGE2 (5 mg/ml), was associated with a reduced expression of the genes of interest, an effect that was significant for MMP 1, MMP 13, and TIMP 1.

Conclusions and Clinical Relevance—The MMP and TIMP 1 are important mediators in the pathophysiologic events in osteoarthritis. The potential for physiologically relevant regulation of expression of these genes by PGE2 is a consideration in the use of drugs that inhibit prostanoid synthesis in the treatment of equine arthropathies. (Am J Vet Res 2002;63:987–993)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the effects of recombinant equine interleukin -1β (reIL-1β) and 4 anti-inflammatory compounds on the expression and activity of cyclooxygenase (COX)-2 in cultured equine chondrocytes.

Sample Population—Articular cartilage from 9 young adult horses.

Procedure—Reverse transcriptase-polymerase chain reaction methods were used to amplify a portion of equine COX-2 to prepare a cDNA probe. Northern blot analysis was used to quantify the expression of COX-2 in first-passage cultures of equine articular chondrocytes propagated in media containing dexamethasone (DEX), phenylbutazone (PBZ), polysulfated glycosaminoglycan, and hyaluronan, each at concentrations of 10 and 100 µg/ml and each with or without reIL-1β. A commercial immunoassay was used to determine prostaglandin E2 (PGE2) concentrations in conditioned medium of similarly treated cells to quantify COX-2 activity.

Results—Addition of reIL-1β increased the expression of COX-2 in a dose-dependent manner, which was paralleled by an increased concentration of PGE2 in culture medium. Concentration of PGE2 in spent medium from reIL-1β-treated chondrocytes was significantly reduced by DEX and PBZ; however, only DEX significantly reduced gene expression of COX-2.

Conclusions and Clinical Relevance—Prostaglandin E2 is considered to be an important mediator in the pathophysiologic processes of arthritis, and cultured chondrocytes respond to interleukin-1 with enhanced expression and activity of COX-2. Palliative relief in affected horses is probably attributable, in part, to inhibition of PGE2 synthesis; however, analysis of these data suggests that of the 4 compounds tested, only DEX affects pretranslational regulation of the COX-2 gene in cultured equine chondrocytes. (Am J Vet Res 2002;63:1134–1139)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To characterize potential mechanisms of action of glucosamine inhibition of matrix metalloproteinase (MMP) expression and activity in lipopolysaccharide (LPS)-stimulated equine chondrocytes.

Sample Population—Chondrocytes cultured from samples of metacarpophalangeal articular cartilage collected from cadaveric limbs of horses.

Procedure—The effect of glucosamine on MMP activity in conditioned medium from LPS-stimulated cartilage explants was determined by a colorimetric assay with azocoll substrate. Treatments consisted of negative and positive controls, glucose (50mM), and glucosamine (50, 25, 6.25, 3, and 1.5mM). The influence of glucosamine on MMP synthesis was determined in chondrocytes in pellet culture incubated with LPS (20 µg/mL). Concentration of MMP-13 was quantified in spent medium via ELISA; nonspecific MMP activity was determined via azocoll digestion in organomercurial- activated medium. Effects of glucosamine on MMP mRNA concentration in similarly treated chondrocytes were determined by northern blot hybridization with MMP-1, -3, and -13 probes. Statistical analyses were performed with 2-way ANOVA.

Results—Glucosamine had no effect on activated MMP activity but inhibited MMP protein expression, as determined by azocoll digestion (glucosamine, 3 to 50mM) and MMP-13 ELISA (glucosamine, 1.5 to 50mM). Resting mRNA concentrations for MMP-1, -3, and -13 mRNA were significantly lower in cultures exposed to glucosamine at concentrations of 50 and 25mM than those of positive controls.

Conclusions and Clinical Relevance—Glucosamine appears capable of pretranslational, and possibly also translational, regulation of MMP expression; data suggest a potential mechanism of action for chondroprotective effects of this aminomonosaccharide. ( Am J Vet Res 2003;64:666–671)

Full access
in American Journal of Veterinary Research

Summary

To determine whether the distal interphalangeal (dip) joint directly or indirectly communicates with the navicular bursa (bursa podotrochlearis) and to identify sensory nerves in these synovial structures that might be desensitized by intra-articular injections of anesthetics, Evans blue dye in physiologic saline solution, Luxol fast blue dye with mepivicaine, or commercial latex was injected into the dip joint (5 ml) or the navicular bursa (3 ml) of 152 digits obtained from horses or ponies at necropsy. The digits were frozen, cut with a band saw, and examined for distribution of dye or latex.

Of 122 digits that had injections into the dip joint, 120 did not have evidence of a communication between the dip joint and either the navicular bursa or digital flexor tendon sheath. Of 16 digits that had injections into the navicular bursa, 14 did not have evidence of a direct communication with the dip joint.

Injection of dye into the dip joint resulted in diffusion of dye and staining of other structures, including the synovial linings of the collateral sesamoidean ligaments and of the distal sesamoidean impar ligament and the medullary cavity of the navicular bone. In addition, a blue tinge was observed in the navicular bursa after dye was injected into the dip joint, suggesting an indirect, and potentially functional, communication between the dip joint and the navicular bursa. Injection of dye into the navicular bursa resulted in staining only of the bursa's synovial lining.

Immunocytochemical analysis revealed nerves immunoreactive for the peptidergic neurotransmitters substance P, and calcitonin gene-related peptide located in structures that were stained after dye was injected into the dip joint. Our results suggest that sensory nerves innervating the synovial membranes along the dorsal aspect of the collateral sesamoidean ligaments, sensory nerves of the distal sesamoidean impar ligament, and sensory nerves that directly innervate parts of the navicular bone would, in all likelihood, be desensitized by injections of anesthetics into the dip joint. Therefore, the issue of a communication between the dip joint and the navicular bursa becomes less important during clinical evaluation of syndromes associated with pathologic changes in these 2 synovial cavities (eg, navicular syndrome).

Free access
in Journal of the American Veterinary Medical Association