Continuous infusion of gentamicin into the tarsocrural joint of horses

OBJECTIVE: To develop a method for continuous infusion of gentamicin into the tarsocrural joint of horses, to determine pharmacokinetics of gentamicin in synovial fluid of the tarsocrural joint during continuous infusion, and to evaluate effects of continuous infusion of gentamicin on characteristics of the synovial fluid. ANIMALS: 12 healthy adult horses. PROCEDURE: An infusion catheter consisting of flow control tubing connected to a balloon infuser was used. Gentamicin solution (100 mg/ml) was infused in the right tarsocrural joint and balanced electrolyte solution was infused in the left tarsocrural joint for 5 days. Synovial fluid and serum gentamicin concentrations were measured by use of a fluorescence polarization immunoassay. RESULTS: 17 of the 24 (71%) infusion catheters initially placed functioned without complications for the entire 5-day infusion period. Median gentamicin concentration in synovial fluid from treated joints during the 5-day infusion period ranged from 2875 to 982 microg/ml. Median serum gentamicin concentration during this period ranged from 2.31 to 2.59 microg/ml. Mean (+/- SD) elimination half-life and total clearance of gentamicin from the synovial fluid were 6.25+/-1.01 hours and 1.52+/-0.96 ml/min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: An infusion catheter can be used for continuous infusion of gentamicin into the tarsocrural joints of horses for up to 5 days. At a gentamicin dosage of 0.17+/-0.02 mg/kg/h, continuous intra-articular infusion results in synovial fluid gentamicin concentrations greater than 100 times the minimal inhibitory concentration reported for common equine pathogens.     

Gentamicin concentrations in synovial fluid and joint tissues during intravenous administration or continuous intra-articular infusion of the tarsocrural joint of clinically normal horses

OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints. PROCEDURE: Horses were assigned to 3 groups (6 horses/group) and administered gentamicin (6.6 mg/kg, IV, q 24 h for 4 days; group 1), a continuous IA infusion of gentamicin into the tarsocrural joint (50 mg/h for 73 hours; group 2), or both treatments (group 3). Serum, synovial fluid, and joint tissue samples were collected for measurement of gentamicin at various time points during and 73 hours after initiation of treatment. Gentamicin concentrations were compared by use of a Kruskal-Wallis ANOVA. RESULTS: At 73 hours, mean +/- SE gentamicin concentrations in synovial fluid, synovial membrane, joint capsule, subchondral bone, and collateral ligament of group 1 horses were 11.5 +/- 1.5 microg/mL, 21.1 +/- 3.0 microg/g, 17.1 +/- 1.4 microg/g, 9.8 +/- 2.0 microg/g, and 5.9 +/- 0.7 microg/g, respectively. Corresponding concentrations in group 2 horses were 458.7 +/- 130.3 microg/mL, 496.8 +/- 126.5 microg/g, 128.5 +/- 74.2 microg/g, 99.4 +/- 47.3 microg/g, and 13.5 +/- 7.6 microg/g, respectively. Gentamicin concentrations in synovial fluid, synovial membrane, and joint capsule of group 1 horses were significantly lower than concentrations in those samples for horses in groups 2 and 3. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.     

Effect of intra-articular gentamicin sulfate on normal equine synovial membrane

Gentamicin sulfate (3 ml; 50 mg/ml) was administered intra-articularly into 30 normal equine radiocarpal joints after arthrocentesis. Arthrocentesis alone was performed on 10 normal radiocarpal joints. Synovial fluid evaluations and gross and microscopic examinations were performed on synovial fluid and synovial membrane of designated joints at selected daily intervals over a period of 10 days. Synovial fluid from gentamicin-injected joints had greater turbidity, higher RBC and WBC counts, and higher refractive indices than did joints not injected with gentamicin. The largest increases developed on days 1 or 2 after gentamicin injection, with mean total WBC, large mononuclear cell, small mononuclear cell, and polymorphonuclear cell counts of 23,860, 11,853, 857, and 11,150 cells/microliter, respectively. Arthrocentesis alone resulted in smaller increases in these counts. Microscopic changes seen in the synovial membrane of gentamicin-injected joints included edema, leukocytic infiltration, and loss of synovial lining cells. These inflammatory changes resolved within 7 days after gentamicin injection.     

Plasma and synovial fluid concentrations of gentamicin in horses after intra-articular administration of buffered and unbuffered gentamicin

The concentration of gentamicin in plasma and synovial fluid of normal adult horses was measured periodically for 24 hours after IV (2.2 mg/kg of body weight), intra-articular (IA; 150 mg), and simultaneous IV and IA administrations. Gentamicin also was buffered with sodium bicarbonate (3 mEq) and then was administered IA and simultaneously IV and IA. Synovial fluid specimens were obtained via an indwelling catheter placed into the antebrachiocarpal joint. The peak mean plasma gentamicin concentration (8.30 micrograms/ml) after IV administration was significantly (P less than 0.05) greater than that (0.69 microgram/ml) after IA administration of gentamicin and that (0.55 microgram/ml) after administration of gentamicin buffered with sodium bicarbonate. Gentamicin concentration greater than a therapeutic concentration was not attained in the plasma after IA administration of buffered or unbuffered gentamicin. The peak mean synovial fluid concentration (1,828 micrograms/ml) after IA administration of unbuffered gentamicin was significantly (P less than 0.05) greater than that (2.53 micrograms/ml) after IV administration and significantly (P less than 0.05) less than that (5,720 micrograms/ml) after simultaneous IV and IA administration. The peak mean synovial fluid concentration after IA administration of buffered gentamicin, with and without simultaneous IV administration (2,128 and 2,680 micrograms/ml, respectively), was not significantly different than that after IA treatment with unbuffered gentamicin. Mean synovial fluid concentration did not differ significantly between groups after IA administration of gentamicin in any combination at postinjection hours 8, 12, and 24, but remained significantly (P less than 0.05) greater than that at the same times after IV administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in articular cartilage after intra-articular injections of methylprednisolone acetate in horses

Eight mature horses with no prior signs of joint disease or history of intra-articular therapy were treated with 8 weekly intra-articular injections of methylprednisolone acetate. Treatments were given at a dose of 120 mg/joint into the right radiocarpal and intercarpal joints, with the left joints as untreated controls. Articular cartilage samples were obtained at necropsy 1, 4, and 8 weeks after the last injection. Compared with controls, cartilage from injected joints had a loss of hematoxylin basophilia and decreased intensity of staining in safranin O fast green dye. Chondrocyte necrosis and hypocellularity were observed in all samples of cartilage from treated joints. Proteoglycan content and its rate of synthesis were reduced. There was a progressive loss of proteoglycan content, whereas proteoglycan synthesis increased somewhat 4 and 8 weeks after treatment. Collagen content was unchanged, but its rate of synthesis was markedly inhibited. Collagen synthesis did not recover, but remained decreased at 5 to 15% of the values from untreated cartilage. Water percentage was increased, but fibronectin content was not significantly different. A single injection of methylprednisolone acetate was also given into the right metacarpophalangeal joints of 3 of the 8 horses in this group, with the left joints serving as untreated controls. Sixteen weeks after the treatment, cartilage of the treated joints had a loss of histochemical staining and proteoglycan content was reduced to 50% of control values. The mean rate of proteoglycan synthesis and mean fibronectin content were increased, but the differences were not statistically significant (P greater than 0.05). Other variables were essentially unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Identification of infrared absorption spectral characteristics of synovial fluid of horses with osteochondrosis of the tarsocrural joint

OBJECTIVE: To determine the feasibility of the use of Fourier-transform infrared (FTIR) spectroscopy within the midinfrared range to differentiate synovial fluid samples of joints with osteochondrosis from those of control samples. ANIMALS: 33 horses with osteochondrosis of the tarsocrural joint and 31 horses free of tarsocrural joint disease. PROCEDURES: FTIR spectroscopy of synovial fluid was used. Sixty-four synovial fluid samples from the tarsocrural joint were collected. Of these, 33 samples were from horses with radiographic evidence of osteochondrosis of the tarsocrural joint and 31 from control joints. Disease-associated features within infrared spectra of synovial fluid were statistically selected for spectral classification, and the variables identified were used in a classification model. Linear discriminant analysis and leave-one-out cross-validation were used to develop a classifier to identify joints with osteochondrosis. RESULTS: 12 significant subregions were identified that met the selection criteria. The stepwise discriminant procedure resulted in the final selection of 6 optimal regions that most contributed to the discriminatory power of the classification algorithm. Infrared spectra derived from synovial fluid of joints with osteochondrosis were differentiated from the control samples with accuracy of 77% (81% specificity and 73% sensitivity). CONCLUSIONS AND CLINICAL RELEVANCE: The disease-associated characteristics of infrared spectra of synovial fluid from joints with osteochondrosis may be exploited via appropriate feature selection and classification algorithms to differentiate joints with osteochondrosis from those of control joints. Further study with larger sample size including age-, breed-, and sex-matched control horses would further validate the clinical value of infrared spectroscopy for the diagnosis of osteochondrosis in horses.     

Lontophoretic administration of dexamethasone into the tarsocrural joint in horses

OBJECTIVE: To determine whether iontophoretic administration of dexamethasone to horses results in detectable concentrations in synovial fluid, plasma, and urine. ANIMALS: 6 adult mares. PROCEDURE: Iontophoresis was used to administer dexamethasone. Treatments (4 mA for 20 minutes) were administered to a tarsocrural joint of each mare. The drug electrode contained 3 ml of dexamethasone sodium phosphate at a concentration of 4 or 10 mg/ml. Samples of synovial fluid, blood, and urine were obtained before and 0.5, 4, 8, and 24 hours after each treatment. All samples were tested for dexamethasone using an ELISA. Synovial fluid also was evaluated for dexamethasone, using high-performance liquid chromatography. RESULTS: The lower and upper limits of detection for dexamethasone in synovial fluid with the ELISA were 0.21 and 1.5 ng/ml, respectively. Dexamethasone administered at a concentration of 10 mg/ml was detected by the ELISA in synovial fluid of 5 mares from 0.5 to 24 hours and in urine of 4 mares from 0.5 to 8 hours after each treatment, but it was not detected in plasma. Mean synovial fluid concentration of dexamethasone was 1.01 ng/ml. Dexamethasone administered at a concentration of 4 mg/ml was detected by the ELISA in urine of 2 mares at 0.5 and 4 hours after treatment, but it was not detected in synovial fluid or plasma. CONCLUSIONS AND CLINICAL RELEVANCE: Iontophoresis cannot be considered an effective method for delivery of dexamethasone to synovial fluid of horses, because drug concentrations achieved in this study were less than therapeutic concentrations.     

Measurement of articular cartilage stiffness of the femoropatellar, tarsocrural, and metatarsophalangeal joints in horses and comparison with biochemical data

OBJECTIVE: To determine normal cartilage stiffness values in different weight-bearing and non-weight-bearing areas of 3 different equine joints, and to evaluate the relationship between cartilage stiffness and glycosaminoglycan (GAG) and collagen content. STUDY DESIGN: Compressive stiffness of the articular cartilage was measured in 8 horse cadaver femoropatellar (FP), tarsocrural (TC), and metatarsophalangeal (MT) joints. Gross evaluation, collagen content, GAG content, and histologic appearance were assessed for each measurement location. ANIMALS: Eight equine cadavers (4 intact females, 4 castrated males; 7 Quarter Horse or Quarter Horse type, 1 Arabian; aged 4-12 years, weighing 400-550 kg). METHODS: The articular surfaces of 8 equine cadaver FP, TC, and MT joints were grossly evaluated for signs of articular cartilage pathology. Stiffness at preselected sites (FP joint-6 sites; TC joint-3 sites; MT joint-4 sites) was determined using an arthroscopic indentation instrument. Biochemical composition (collagen, GAG content) and histologic evaluation (modified Mankin score) were assessed for each measurement site. RESULTS: All cartilage from all sites evaluated was determined to be normal based on macroscopic and histologic assessments. No significant correlation between Mankin scores and cartilage stiffness values was observed. Site differences in cartilage stiffness were measured in all 3 joints (P<.001). GAG or collagen content had a significant positive correlation with stiffness values in 6 of 13 sites (P<.05, r>0.622, r2>0.387). CONCLUSION: Relative cartilage stiffness values measured in healthy equine joints are site dependent and can be measured using an indentation device intended for arthroscopic application. CLINICAL RELEVANCE: An indentation instrument provided an objective means of determining relative compressive stiffness of articular cartilage. Further research needs to be performed to confirm the site and joint differences observed in this study in clinically normal horses and to determine if the tester can be used clinically to predict articular cartilage pathology.     

Effects of intra-articular administration of methylprednisolone acetate on normal articular cartilage and on healing of experimentally induced osteochondral defects in horses.

The effects of intra-articular administration of methylprednisolone acetate (MPA) on the healing of full-thickness osteochondral defects and on normal cartilage were evaluated in 8 horses. In group-1 horses (n = 4), a 1-cm-diameter, full-thickness defect was created bilaterally in the articular cartilage on the dorsal distal surface of the radial carpal bone. Cartilage defects were not created in group-2 horses (n = 4). One middle carpal joint was randomly selected in each horse (groups 1 and 2), and treated with an intra-articular injection of 100 mg of MPA, once a week for 4 treatments. Injections began 1 week after surgery in group-1 horses. The contralateral middle carpal joint received intra-articular injections of an equivalent volume of 0.9% sodium chloride solution (SCS), and served as a control. Horses were evaluated for 16 weeks, then were euthanatized, and the middle carpal joints were examined and photographed. Synovial and articular cartilage specimens were obtained for histologic and histochemical evaluation. Gross morphometric evaluation of the healing defects in group-1 horses revealed that 48.6% of the defect in control joints and 0% of the defect in MPA-treated joints was resurfaced with a smooth, white tissue, histologically confirmed as fibrocartilage. This replacement tissue was a firmly attached fibrocartilage in control joints and a thin fibrous tissue in MPA-treated joints. The articular cartilage in joints treated with MPA had morphologic changes, including chondrocyte cluster formation, loss of palisading architecture, and cellular necrosis in both groups of horses.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of intra-articular administration of methylprednisolone acetate on normal equine articular cartilage

The effects of the corticosteroid 6-alpha-methylprednisolone acetate on normal equine articular cartilage were evaluated, using the middle carpal joint in 4 clinically normal young horses. One middle carpal joint of each horse was injected 3 times with 100 mg of 6-alpha-methylprednisolone acetate, at 14-day intervals. The opposite middle carpal joint (control) was injected with 2.5 ml of lactated Ringer solution at the same intervals. Effects were studied until 8 weeks after the first injection. Evaluation included clinical and radiographic examination, and gross, microscopic, and biochemical evaluation of joint tissues. Horses remained clinically normal during the study, and significant radiographic changes were not observed. Safranin-0 matrix staining intensity and uronic acid content were significantly (P less than 0.05) lower and hydroxyproline content was significantly (P less than 0.05) higher in articular cartilage of corticosteroid-injected joints vs control joints.     

Metalloproteinases and tumor necrosis factor-alpha activities in synovial fluids of horses: correlation with articular cartilage alterations

Early detection of osteoarthritis in horses represents a challenge for equine practitioners. Several biological markers have been implicated in the pathological processes involved in articular cartilage destruction. To further document cartilage matrix proteases production, synovial fluid was collected from 14 horses (90 joints) before they were subjected to euthanasia. Growth macroscopic examination of the joints gave information on cartilage alterations. Samples were analyzed for matrix metalloproteinase (MMPs) activities by gelatin zymography and tumor necrosis factor alpha (TNF-alpha) cytotoxicity using L929 cells. Significant increase of MMP-9 monomer and dimer were found in synovial fluids of joints with severe cartilage alterations. On the contrary, the activity of TNF-alpha was not correlated to the degree of joint damage. The levels of MMP-9 monomer and dimer in the synovial fluid could reflect cartilage alteration in arthritis in the horse.     

Biochemical analysis of normal articular cartilage in horses

Articular cartilage specimens from the distal articular surface of 32 radiocarpal bones from 24 2- to 5-year-old horses were analyzed. The total collagen content was determined on the basis of the 4-hydroxyproline content, using a colorimetric method. A method for estimating the proportions of types-I and -II collagen by measuring spectrophotometric densities of specific cyanogen bromide peptide bands from mixtures of types-I and -II collagen on sodium dodecyl sulfate-polyacrylamide gels was used. The cyanogen bromide peptides representative of each collagen types-I and -II were identified. The peptide ratios were then computed for each of several standards of type-I and -II mixtures. A standard curve was derived from the correlation between these ratios and the corresponding proportions of type-II collagen in standard mixtures. Galactosamine and glucosamine content (hexosamines) were measured by ion chromatography. The galactosamine-to-glucosamine ratio, chondroitin sulfate and keratan sulfate values, and total glycosaminoglycan content were derived from the measured hexosamine content. The total collagen content averaged 556 mg/g (55.6 mg/100 mg) of tissue (dry weight, [dw]). Type-II collagen was the major collagen type in normal articular cartilage specimens. The ratio of the area under the alpha 1 (II)CB10 peak to the area under the alpha 1 (I)CB 7,8 + alpha 1 (II)CB11 peak was a second-order polynomial function of the proportion of type-II collagen in the specimens. The mean galactosamine and glucosamine content were 20.6 mg/g and 7.9 mg/g (dw), respectively. The mean galactosamine-to-glucosamine ratio was 3.74 +/- 0.62.(ABSTRACT TRUNCATED AT 250 WORDS)     

Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses

Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.     

Effects of oral administration of phenylbutazone to horses on in vitro articular cartilage metabolism.

OBJECTIVE: To evaluate the effects of orally administered phenylbutazone on proteoglycan synthesis and chondrocyte inhibition by IL-1beta in articular cartilage explants of horses. ANIMALS: 11 healthy 1- to 2-year-old horses. PROCEDURE: Horses were randomly assigned to the control (n = 5) or treated group (4.4 mg of phenylbutazone/kg of body weight, p.o., q 12 h; n = 6). Articular cartilage specimens were collected before treatment was initiated (day 0), after 14 days of treatment, and 2 weeks after cessation of treatment (day 30). Proteoglycan synthesis and stromelysin concentration in cartilage extracts were assessed after 72 hours of culture in medium alone or with recombinant human interleukin-1beta (IL-1beta; 0.1 ng/ml). RESULTS: On day 0, proteoglycan synthesis was significantly less in cartilage explants cultured in IL-1beta, compared with medium alone. Mean proteoglycan synthesis in explants collected on days 14 and 30 was significantly less in treated horses, compared with controls. However, incubation of explants from treated horses with IL-1beta did not result in a further decrease in proteoglycan synthesis. Significant differences in stromelysin concentration were not detected between or within groups. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of phenylbutazone for 14 days significantly decreased proteoglycan synthesis in articular culture explants from healthy horses to a degree similar to that induced by in vitro exposure to IL-1beta. Phenylbutazone should be used judiciously in athletic horses with osteoarthritis, because chronic administration may suppress proteoglycan synthesis and potentiate cartilage damage.     

Biochemical changes in articular cartilage opposing full- and partial-thickness cartilage lesions in horses

Using arthroscopic technique, identical diameter defects were created in the proximal articular surface of both intermediate carpal bones of 6 horses. One of each pair of defects was deepened to penetrate the subchondral plate. Removed cartilage was assayed for [35S] sulfate incorporation, total hexosamine content, and DNA content. Six weeks later, cartilage was harvested and similarly analyzed from the distolateral portion of the radius directly opposite the created lesions and the distomedial portion of the radius distant from the lesion. The repair tissue filling the full-thickness defect and the cartilage at the periphery of the partial-thickness lesion also were analyzed. There was a marked increase in synthetic activity (35S sulfate incorporation) opposite the full-thickness defect, compared with the cartilage opposite the partial-thickness defect. A marked decrease in glycosaminoglycan content in the cartilage opposite the full-thickness defect was found as compared with that opposite the partial-thickness defect. The repair tissue filling the full-thickness defect was highly cellular, high in synthetic activity, but low in glycosaminoglycan content. Insignificant changes occurred in the cartilage adjacent to the partial-thickness defect. On the basis of these results, we suggest that full-thickness defects at 6 weeks result in more detrimental change to the cartilage opposite it than do partial-thickness lesions of the same diameter.     

Effects of atracurium administered by continuous intravenous infusion in halothane-anesthetized horses

Atracurium (0.4 mg/ml in isotonic NaCl solution) was administered by IV infusion to 7 healthy adult horses for 2 hours. Over the 2-hour period, a 95 to 99% reduction of train-of-four hoof-twitch response was maintained by 0.17 +/- 0.01 mg of atracurium/kg of body weight/h, for a total of 161 +/- 6 mg of atracurium (mean +/- SEM) for horses 1 to 4, 6, and 7. Horse 5, a mare in estrus, required 0.49 mg of atracurium/kg/h to maintain comparable relaxation. Hoof-twitch recovery time from 10 to 75% of baseline strength was 19.8 +/- 2.5 minutes for all horses. The 10 to 75% recovery time for horse 5 was 18 minutes. Recovery time from discontinuation of halothane until standing was 86 +/- 14 minutes (range, 55 to 165 minutes). Horse 5 had a 165-minute recovery. Regarding recovery from anesthesia, 3 recoveries were rated as excellent, 1 recovery good, and 2 recoveries as fair. Horse 5 laid quietly until she stood with 1 strong, smooth effort.     

Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints of horses after implantation of gentamicin-impregnated collagen sponges

OBJECTIVE: To determine synovial fluid gentamicin concentrations and evaluate adverse effects on the synovial membrane and articular cartilage of tarsocrural joints after implantation of a gentamicin-impregnated collagen sponge. ANIMALS: 6 healthy adult mares. PROCEDURES: A purified bovine type I collagen sponge impregnated with 130 mg of gentamicin was implanted in the plantarolateral pouch of 1 tarsocrural joint of each horse, with the contralateral joint used as a sham-operated control joint. Gentamicin concentrations in synovial fluid and serum were determined for 120 hours after implantation by use of a fluorescence polarization immunoassay. Synovial membrane and cartilage specimens were collected 120 hours after implantation and evaluated histologically. RESULTS: Median peak synovial fluid gentamicin concentration of 168.9 microg/mL (range, 115.6 to 332 microg/mL) was achieved 3 hours after implantation. Synovial fluid gentamicin concentrations were < 4 microg/mL by 48 hours. Major histologic differences were not observed in the synovial membrane between control joints and joints implanted with gentamicin-impregnated sponges. Safranin-O fast green stain was not reduced in cartilage specimens obtained from treated joints, compared with those from control joints. CONCLUSIONS AND CLINICAL RELEVANCE: Implantation of a gentamicin-impregnated collagen sponge in the tarsocrural joint of horses resulted in rapid release of gentamicin, with peak concentrations > 20 times the minimum inhibitory concentration reported for common pathogens that infect horses. A rapid decrease in synovial fluid gentamicin concentrations was detected. The purified bovine type I collagen sponges did not elicit substantial inflammation in the synovial membrane or cause mechanical trauma to the articular cartilage.