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1.
Reasons for performing study: Meloxicam is a commonly used nonsteroidal anti‐inflammatory drug in equine practice, but little is known about its in vivo effects on joint inflammation and cartilage turnover. Objectives: To study the effects of meloxicam on biomarkers of inflammation, matrix metalloproteinase (MMP) activity, and cartilage biomarkers in joints with experimental synovitis. Methods: In a 2‐period cross‐over study, synovitis was induced at T = 0 h in the L or R intercarpal joint of 6 horses by intraarticular injection of 0.5 ng lipopolysaccharide (LPS). Horses received once daily meloxicam (0.6 mg/kg bwt per os) or placebo starting at post injection hour (PIH) 2, and clinical evaluations as well as blood and synovial fluid (SF) sampling were performed at PIH 0, 8, 24 and 168. Synovial fluid was analysed for prostaglandin E2, bradykinin, substance P, general MMP activity, glycosaminoglycans (GAG), CS846 epitope, type II collagen cleavage fragments (C2C) and type II collagen carboxypropeptide (CPII). Concentrations in meloxicam‐ vs. placebo‐treated joints over time were compared using a linear mixed model. Results: Lipopolysaccharide injection caused marked transient synovitis without systemic effects. Meloxicam caused a significant reduction in lameness at PIH 8 and 24 and tended to reduce effusion. In addition, meloxicam significantly suppressed SF prostaglandin E2 and substance P release at PIH 8 and bradykinin at PIH 24 compared to placebo treatment. General MMP activity at PIH 8 and 24 was significantly lower in meloxicam‐ vs. placebo‐treated joints, as were GAG, C2C and CPII concentrations at PIH 24. Conclusions: Acute transient synovitis leads to substantial increases in SF biomarkers of inflammation, MMP activity and cartilage turnover, which can be significantly suppressed by meloxicam. Potential relevance: Early oral treatment with meloxicam ameliorates not only clinical signs and joint inflammation in acute synovitis, but may also limit inflammation‐induced cartilage catabolism.  相似文献   

2.
REASON FOR PERFORMING STUDY: Diagnosis of osteochondrosis (OC) is based on clinical signs and radiography, but alternative methods for detection at an early stage would be useful. OBJECTIVES: To determine in the juvenile horse the relationship between serum concentrations of a number of biomarkers that reflect changes in cartilage and bone turnover and age, feeding level, growth, and the occurrence of OC. METHODS: Foals were assigned to a high (n = 20) or moderate (n = 19) feeding level group from birth to age 1 year. Bodyweight, withers height and cannon width were measured. Osteoarticular status was assessed radiographically at 5.5 and 11 months in all foals, and by necropsy at 12 months for 8 foals/group. Serum biomarkers of bone (osteocalcin, CTX-1) and cartilage (CPII, C2C) metabolism were assayed at 8 time points between ages 2 and 52 weeks. Ratios between biomarkers of tissue formation and degradation were calculated at each time point. RESULTS: Consistent age-related patterns in biomarker serum concentrates were found, indicating a markedly higher metabolism before age 20 weeks but concentrations were not affected by feeding level. Bodyweight was correlated negatively to C2C and CTX-1, and withers height was positively correlated to osteocalcin and the osteocalcin/CTX-1 and CPII/ C2C ratios. Osteocalcin concentration at 2 weeks and CPII/ C2C ratio at 20 weeks had strong positive correlations to OC, as diagnosed radiographically at 5.5 months. Osteocalcin had a strong correlation with radiographically detected OC at 11 months but at that time there was no significant relationship between CPII/C2C ratio and OC. CONCLUSIONS: Occurrence of OC lesions is significantly associated with anabolic changes in bone metabolism during the first weeks post partum, given the strong relation with osteocalcin. POTENTIAL RELEVANCE: Measuring osteocalcin concentrations during the first few weeks post partum may have potential value for the prediction of risk for OC development.  相似文献   

3.
OBJECTIVE: To determine whether serum or synovial fluid concentrations of chondroitin sulfate epitope 846 and carboxy propeptides of type II collagen (CPII) can be used to diagnose osteochondral fragmentation (OC) in horses. ANIMALS: 38 horses with unilateral OC of the radiocarpal (n = 31) or intercarpal (33) joints and 8 clinically and radiographically normal horses. Procedures-For horses with OC, serum and synovial fluid concentrations of epitope 846, CPII, and keratan sulfate (KS) were determined, along with synovial fluid WBC counts and total protein concentrations. Serum epitope 846, CPII, and KS concentrations were measured in control horses. RESULTS: Synovial fluid epitope 846 and total protein concentrations were significantly higher in the joints with OC than in unaffected joints, but CPII and KS concentrations and WBC counts were not. Synovial fluid total protein and 846 epitope concentrations were linearly related to grade of OC. Serum epitope 846 and CPII concentrations were significantly higher in horses with OC than in control horses. Discriminant analysis allowed 27 of 34 (79%) horses to be correctly classified as having or not having OC on the basis of serum epitope 846 and CPII concentrations. CONCLUSIONS: Results suggest that serum and synovial fluid concentrations of epitope 846 and CPII are associated with OC. Increases in concentrations of epitope 846 and CPII suggest that increased synthesis of cartilage aggrecan and type II procollagen may be associated with OC. CLINICAL RELEVANCE: Measurement of serum epitope 846 and CPII concentrations may be useful in the diagnosis of OC in horses.  相似文献   

4.
OBJECTIVE: To assess whether reported alterations in metabolism of cartilage matrix in young (0 to 24 months old) horses with osteochondritis dissecans (OCD) may also be found in older (24 to 48 months old) horses with clinical signs of OCD and to investigate the role of eicosanoids in initiating these clinical signs. SAMPLE POPULATION: Synovial fluid was collected from 38 tarsocrural joints of 24 warmblood horses with (22 joints of 16 horses) or without (16 joints of 8 horses) clinical signs and a radiographic diagnosis of OCD of the distal intermediate ridge of the tibia. PROCEDURES: Turnover of type II collagen was investigated by use of specific immunoassays for synthesis (carboxypropeptide of type II collagen [CPII]) and degradation (collagenase-cleaved fragments of type II collagen [C2C]) products. Furthermore, glycosaminoglycan (GAG), leukotriene (LT) B(4), cysteinyl LTs, and prostaglandin (PG) E(2) concentrations were determined, and concentrations in joints with OCD were compared with those in joints without OCD. RESULTS: Concentrations of CPII, C2C, and GAG did not differ significantly between affected and nonaffected joints. Fluid from joints with OCD had significantly higher LTB(4) and PGE(2) concentrations than did fluids from nonaffected joints. CONCLUSIONS AND CLINICAL RELEVANCE: Altered collagen or proteoglycan turnover was not detected in 24- to 48-month-old horses at the time they developed clinical signs of OCD of the distal intermediate ridge of the tibia. However, increased concentrations of LTB(4) and PGE(2) in fluid of joints with OCD implicate these mediators in the initiation of clinical signs of OCD.  相似文献   

5.
OBJECTIVE: To determine whether serum concentrations of biomarkers of skeletal metabolism can, in conjunction with radiographic evaluation, indicate severity of osteochondrosis in developing horses. ANIMALS: 43 Dutch Warmblood foals with varying severity of osteochondrosis. PROCEDURE: 24 foals were monitored for 5 months and 19 foals were monitored for 11 months. Monthly radiographs of femoropatellar-femorotibial and tibio-tarsal joints were graded for osteochondral abnormalities. Serial blood samples were assayed for 8 cartilage and bone biomarkers. At the end of the monitoring period, foals were examined for macroscopic osteochondrosis lesions. RESULTS: Temporal relationships were evident between certain serum biomarkers and osteochondrosis severity in foals during their first year. Biomarkers of collagen degradation (collagenase-generated neoepitopes of type-II collagen fragments, type-I and -II collagen fragments [COL2-3/4C(short)], and cross-linked telopeptide fragments of type-I collagen) and bone mineralization (osteocalcin) were positive indicators of osteochondrosis severity at 5 months of age. In foals with lesions at 11 months of age, osteochondrosis severity correlated negatively with COL2-3/4C(short) and osteocalcin and positively with C-propeptide of type-II procollagen (CPII), a collagen synthesis marker. Radiographic grading of osteochondrosis lesions significantly correlated with macroscopic osteochondrosis severity score at both ages and was strongest when combined with osteocalcin at 5 months and CPII at 11 months. CONCLUSIONS AND CLINICAL RELEVANCE: The ability of serum biomarkers to indicate osteochondrosis severity appears to depend on stage of disease and is strengthened with radiography. In older foals with more permanent lesions, osteochondrosis severity is significantly related to biomarker concentrations of decreased bone formation and increased cartilage synthesis.  相似文献   

6.
OBJECTIVE: To investigate interglobular domain (IGD) cleavage of aggrecan in dogs with naturally developing osteoarthritis (OA). SAMPLE POPULATION: Samples of synovial fluid (SF) obtained from 3 cubital (elbow) joints and 3 stifle joints of 4 clinically normal dogs, 24 elbow joints of 12 dogs with early-stage OA, 8 stifle joints of 5 dogs with early-stage OA, and 10 stifle joints of 9 dogs with late-stage OA. PROCEDURE: Fractions of SF were assayed for total glycosaminoglycan (GAG) content and also subjected to Western blot analysis by use of monoclonal antibodies against neoepitopes generated by cleavage of the IGD of the aggrecan protein core by matrix metalloproteinase (MMP; BC-14) and aggrecanase (BC-3). RESULTS: Total GAG content of SF from joints of clinically normal dogs did not differ from that of dogs with early-stage OA. The GAG content of SF from joints of dogs with late-stage OA was significantly lower, compared with GAG content for other SF samples. Aggrecanase-generated fragments were detected in SF from all groups but not in all samples. Matrix metalloproteinase-generated fragments were not detected in any SF samples. In early-stage OA, high-molecular-weight aggrecanase-generated aggrecan catabolites were evident. CONCLUSIONS AND CLINICAL RELEVANCE: GAG content of SF obtained from dogs with late-stage OA is significantly decreased, suggesting proteoglycan depletion of cartilage. Aggrecanases, but not MMPs, are the major proteolytic enzymes responsible for IGD cleavage of aggrecan in canine joints. Analyses of SF samples to detect aggrecanase-generated catabolites may provide an early biomarker for discriminating early- and late-stage OA in dogs.  相似文献   

7.
Osteoarthritis (OA) of the metacarpophalangeal joint is the most common articular disease in polo ponies leading to early retirement. A biomarker that would discriminate between pathological and physiological changes secondary to exercise could be helpful in OA prevention. The aim of this study was to investigate the effects of polo training on synovial fluid biomarkers of inflammation and cartilage turnover in polo ponies of different skill levels. Synovial fluid samples were collected from metacarpophalangeal joints of polo ponies before and during the polo season (320 d). Nucleated cells, soluble protein, prostaglandin E2 (PGE2), glycosaminoglycans (GAG), and urea were measured. The main synovial fluid GAG are chondroitin sulphate (CS, ~25 μg/mL) and hyaluronic acid (HA, ~400 μg/mL). After a polo match, a transitory increase in protein and PGE2, but not CS and HA, occurred (expressed as urea ratio), returning to basal levels in 24 h. During the polo season, the number of synovial fluid nucleated cells was always in the normal range. Increases in protein and HA occurred during the initial 40 to 80 d, returning to basal levels afterwards. In contrast, in polo prospects the concentration of CS steadily increased during the season. Long-term follow-up revealed that the synovial fluid CS was significantly higher in polo ponies that developed joint diseases within 24 months following our study. In conclusion, CS seems to be an early marker of articular cartilage damage.  相似文献   

8.
REASONS FOR PERFORMING STUDY: The importance of osteoarthritis (OA) in the horse and the difficulty in its early diagnosis have led to a search for potential biomarkers of joint disease. If the levels of such markers are to be interpreted accurately, clinicians and researchers need to know whether they are influenced by environmental factors and/or interventions such as exercise and repeated arthrocentesis. OBJECTIVE: To investigate the influence of repeated arthrocentesis and exercise on nitric oxide (NO), prostaglandin E2 (PGE2) and glycosaminoglycan (GAG) concentrations in synovial fluid (SF) from normal equine joints. METHODS: SF was collected from the left metacarpophalangeal (MCP), radiocarpal and tarsocrural joints of 16 horses. Half of the horses were exercised and arthrocentesis was repeated 14, 14.5, 17 and 24 days after the start of the exercise programme, in both exercised and control horses. Nitric oxide was determined in SF from the MCP joint only and PGE2 and GAG concentrations were determined in SF from all joints. RESULTS: Repeated arthrocentesis caused an increase in NO concentration in the MCP joint on Day 145, in PGE2 concentrations in the radiocarpal and tarsocrural joints on Day 145 and the release of GAGs into SF of the MCP and radiocarpal joints on Day 17. Exercise resulted in an increase in PGE2 levels in all joints but did not influence the other parameters measured. POTENTIAL RELEVANCE: Repeated arthrocentesis is a potential confounding factor for the use of synovial NO, PGE2 and GAG concentrations as markers of joint disease. Based on this study, such a confounding effect can be avoided if one week or more separates arthrocentesis procedures. Moderate exercise causes a transient rise in PGE2 in SF.  相似文献   

9.
REASONS FOR PERFORMING STUDY: Osteoarthritis (OA) is one of the most prevalent and disabling chronic conditions affecting horses and leads to degeneration of articular cartilage. Diagnosis is based on clinical signs in combination with radiography, which is relatively insensitive and provides only an indication of accumulated damage. Alternative methods, such as molecular markers, are therefore needed that can quantitatively, reliably and sensitively detect osteoarthritic changes in the joints at an early stage of the disease. If such markers are to be used reliably, it is important to know the relationship between marker concentration and cartilage composition. OBJECTIVES: To study the relationship between cartilage composition, synovial fluid levels of glycosaminoglycans (GAGs), hydroxyproline (Hyp) and general matrix metalloproteinase (MMP) activity, and the presence and severity of articular cartilage damage on the articular surface of P1. METHODS: Synovial fluid (SF) was collected from the metacarpophalangeal joints of 60 mature horses, and levels of GAGs, Hyp and general MMP activity were determined. Further, GAG and denatured collagen content of the articular cartilage were determined at the dorsal articular margin of P1 (site 1) and central cavity (site 2). The presence and severity of cartilage change was quantified using the cartilage degeneration index (CDI), measured at the same 2 sites. Correlations between SF parameters, cartilage composition and degree of cartilage degeneration were sought using correlation analysis. RESULTS: There was no correlation between GAG or Hyp content of SF and the amount of GAGs or denatured collagen, respectively, in cartilage. In joints with moderate to severe cartilage damage, the GAG content of site 1 was significantly lower than in joints with no to minimal cartilage change (P = 0.005) and there was a negative correlation between the amount of denatured collagen and GAG content at site 1 in all joints (r = -039, P = 0.002). Further, in joints with moderate to severe cartilage damage, there was a significant positive correlation between MMP activity in SF and Hyp levels in SF (r = 0.72, P < 0.001) and CDI at sites 1 (r = 0.46, P = 0.03) and 2 (r = 0.43, P = 0.04). CONCLUSIONS: General MMP activity in joints with moderate to severe cartilage damage is related to the severity of those cartilage changes and to Hyp levels in SF. Glycosaminoglycan levels in SF are not directly related to MMP activity, GAG content of articular cartilage or severity of cartilage change. POTENTIAL RELEVANCE: Glycosaminoglycan levels in SF are not helpful for the early detection of cartilage lesions. In damaged joints, Hyp levels may give an indication of the severity of cartilage change as they are strongly related to MMP activity, but do not qualify as markers for the presence or absence of cartilage lesions.  相似文献   

10.
Dietary intervention may be a valuable strategy to optimize the intra-articular environment in young horses to prolong their performance career. To test the hypothesis that dietary supplementation of a Saccharomyces cerevisiae fermentation product would reduce markers of joint inflammation and increase markers of cartilage metabolism following a single inflammatory insult, Quarter Horse yearlings (mean ± SD; 9 ± 1.0 mo) were balanced by age, sex, body weight (BW), and farm of origin and randomly assigned to the following treatment groups: 1.25% BW/d (dry matter basis) custom-formulated concentrate only (CON; n = 9) or concentrate top-dressed with 21 g/d S. cerevisiae fermentation product (SCFP; n = 10) for 98 d. Horses had ad libitum access to Coastal bermudagrass hay. On day 84, one randomly selected radial carpal joint from each horse was injected with 0.5 ng lipopolysaccharide (LPS) solution. The remaining carpal joint was injected with sterile lactated Ringer’s solution as a contralateral control. Synovial fluid obtained before supplementation (day 0) and on day 84 at preinjection hour 0 and 6, 12, 24, 168, and 336 h postinjection was analyzed for prostaglandin E2 (PGE2), carboxypropeptide of type II collagen (CPII), and collagenase cleavage neopeptide (C2C) by commercial assays. Rectal temperature, heart rate, respiration rate, carpal surface temperature, and carpal circumference were recorded prior to each sample collection and for 24 h postinjection. Data were analyzed using linear models with repeated measures. From day 0 to 84, synovial C2C declined (P ≤ 0.01) and the CPII:C2C ratio increased (P ≤ 0.01) in all horses with no effect of diet. In response to intra-articular LPS, synovial PGE2 increased by hour 6 (P ≤ 0.01) and returned to baseline by hour 336; CPII increased by hour 12, remained elevated through hour 168 (P ≤ 0.01), and returned to baseline by hour 336; and C2C increased by hour 6 (P ≤ 0.01) but did not return to baseline through hour 336 (P ≤ 0.01). Post-intra-articular injection, PGE2 levels were lower in SCFP than CON horses (P = 0.01) regardless of injection type. Synovial CPII and the CPII:C2C ratio demonstrated stability during the LPS challenge in SCFP compared with CON horses (P ≤ 0.01). Clinical parameters were not influenced by diet but increased in response to repeated arthrocentesis (P ≤ 0.01). Dietary SCFP may favorably modulate intra-articular inflammation following an acute stressor and influence cartilage turnover in young horses.  相似文献   

11.
OBJECTIVE: To assess the effects of supraphysiologic concentrations of insulin-like growth factor-1 (IGF-1) on morphologic and phenotypic responses of chondrocytes. SAMPLE POPULATION: Articular cartilage obtained from 2 young horses. PROCEDURE: Chondrocytes were suspended in fibrin cultures and supplemented with 25, 12.5, or 0 mg of IGF-1/ml of fibrin. Chondrocyte morphology and phenotypic expression were assessed histologically, using H&E and Alcian blue stains, immunoreaction to collagen type I and II, and in situ hybridization. Proteoglycan content, synthesis, and monomer size were analyzed. The DNA content was determined by bisbenzimide-fluorometric assay, and elution of IGF-1 into medium was determined by IGF-1 radioimmunoassay. RESULTS: Both 12.5 and 25 kg of IGF-1/ml enhanced phenotypic expression of chondrocytes without inducing detrimental cellular or metabolic effects. Highest concentration of IGF-1 (25 microg/ml) significantly increased total DNA content, glycosaminoglycan (GAG) content, GAG synthesis, and size of proteoglycan monomers produced, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. Histologic examination confirmed these biochemical effects. Matrix metachromasia, type-II collagen in situ hybridization and immunoreaction were increased in cultures treated with 25 microg of IGF-1/ml, compared with cultures supplemented with 12.5 microg of IGF-1/ml or untreated cultures. CONCLUSIONS AND CLINICAL RELEVANCE: Chondrocytes exposed to high concentrations of IGF-1 maintained differentiated chondrocyte morphology and had enhanced synthesis of matrix molecules without inducing apparent detrimental effects on chondrocyte metabolism. These results suggest that application of such composites for in vivo use during cartilage grafting procedures should provide an anabolic effect on the grafted cells.  相似文献   

12.
OBJECTIVES: To evaluate the effects of equine recombinant interleukin-1alpha (rEqIL-1alpha) and recombinant interleukin-1beta (rEqIL-1beta) on proteoglycan metabolism and prostaglandin E2 (PGE2) synthesis by equine articular chondrocytes in explant culture. SAMPLE POPULATION: Near full-thickness articular cartilage explants (approx 50 mg) harvested from stifle joints of a 3-year-old and a 5-year-old horse. PROCEDURE: Expression constructs containing cDNA sequences encoding EqIL-1alpha and EqIL-1beta were generated, prokaryotically expressed, and the recombinant protein purified. Near full-thickness articular cartilage explants (approx 50 mg) harvested from stifle joints of a 3-year-old and a 5-year-old horse were separately randomized to receive rEqIL-1alpha or rEqIL-1beta treatments 10 to 500 ng/ml). Proteoglycan release was evaluated by 1,9-dimethylmethylene blue spectrophotometric analysis of explant media glycosaminoglycan (GAG) concentration and release of 35S-sulfate-labeled GAG to explant media. Proteoglycan synthesis was assessed by quantification of 35S-sulfate incorporation into proteoglycan. Explant media PGE2 concentrations were evaluated using a PGE2-specific enzyme-linked immunoassay. Data were collected at 48-hour intervals and normalized by DNA content. RESULTS: Proteoglycan release was induced by rEqIL-1alpha and rEqIL-1beta at concentrations > or =0.1 ng/ml, with 38 to 76% and 88 to 98% of total GAG released by 4 and 6 days, respectively. Inhibition of proteoglycan synthesis (42 to 64%) was observed at IL-1 concentrations > or = 0.1 ng/ml at 2 and 4 days. Increased PGE2 concentrations were observed at IL-1 concentrations > or = 0.1 ng/ml at 2 and 4 days. CONCLUSIONS AND CLINICAL RELEVANCE: The rEqIL-1 induced potent concentration-dependent derangement of equine chondrocyte metabolism in vitro. These findings suggest this model may be suitable for the in vitro study of the pathogenesis and treatment of joint disease in horses.  相似文献   

13.
Glycosaminoglycans in horses with osteoarthritis   总被引：1，自引：0，他引：1  
Horse articular cartilage glycosaminoglycans (GAGs) were measured in synovial fluids from 48 joints affected with osteoarthritis (OA), 22 normal joints, four joints with osteochondritis, three joints with traumatic arthritis and seven joints infected with bacteria. Serum and urine from individual horses were also examined for the presence of GAGs. High levels of GAGs were found in synovial fluids (SF) from horses with OA. In each case, the level was higher in the synovial fluid than in the serum or urine from the same horse. Horses with OA showed high GAG levels in SF, serum and urine compared to horses with normal and infected joints. High levels were also found in horses with osteochondritis and traumatic arthritis. Levels of synovial fluid GAG reflect cartilage destruction in arthritis and may be useful for monitoring disease progression in the equine species.  相似文献   

14.
REASONS FOR PERFORMING STUDY: Previous in vitro pilot studies have defined a potentially beneficial effect of insulin-like growth factor-1 (IGF-1) and triamcinolone acetonide (TA) on interleukin-1 (IL-1)-conditioned equine cartilage. Furthermore, an optimal dose for IGF-1 treatment alone has been documented previously using the same test system as in the current project. OBJECTIVES: To perform a dose titration of TA on IL-1-conditioned equine articular cartilage explants in the presence of an optimised IGF-1 dose, in order to optimise a triamcinolone concentration for use in combination with IGF-1 for future investigations. METHODS: Cartilage explants were harvested from the distal femur of a normal horse. The effect of a clinically relevant TA dose range was evaluated in the presence of IL-1 and IGF-1 through measurement of proteoglycan (PG) matrix metabolism (synthesis and degradation). RESULTS: TA and IGF-1 in combination inhibited the IL-1-induced release of PG matrix components (glycosaminoglycan or GAG) from the articular cartilage, as well as producing a significant increase in GAG synthesis. CONCLUSIONS: This experiment provided proof of principle that a combination treatment appears to be able to combat the IL-1-induced matrix depletion, while enhancing anabolic metabolism within the articular cartilage. POTENTIAL RELEVANCE: The use of IGF-1 in conjunction with TA in vivo has the potential to provide beneficial anabolic effects not seen with TA alone.  相似文献   

15.
AIMS: To determine the influence of copper (Cu) supplementation by injection of mares in late gestation on the frequency and severity of osteochondrosis (OC) lesions in their foals at around 160 days of age. To determine if there was any influence of the concentration of Cu in the liver, growth rate, birthweight, weight at 160 days of age, fatness, sex, or year of birth of the foal on the frequency and severity of OC lesions. To determine the influence of dam's age, and sex and birthweight of the foal on the growth rate from birth to 160 days of age, and weight at 160 days of age.

METHODS: Thirty-three Thoroughbred foals, born in two consecutive years, were weighed every 2 weeks from birth. The dams had been supplemented with parenteral Cu or saline during late gestation, and the supplementation regimens were different in each year. Foals had liver biopsies harvested at birth for determination of Cu concentration. Pasture samples were collected every 4–8 weeks for analysis of concentration of Cu and zinc (Zn). At 160 days of age, articular cartilage of long bones was examined. Gross lesions were counted and scored, then sawn and radiographed, and processed for histopathology. Lesions were given radiographic scores and histopathological scores. Maximum scores for each lesion were combined to give a total OC score for each joint and each foal. The fatness of 20 foals (10 each from Years 1 and 2) at 160 days of age was determined chemically.

RESULTS: Supplementation of dams with Cu had no significant effect on the concentration of Cu in the liver of foals at birth, or on the frequency or severity of lesions in articular cartilage at 160 days of age. The Cu and Zn concentrations of pasture were similar in Years 1 and 2, and were lower than current recommendations. All foals in Year 2, and 9/10 foals in Year 1 had irregularities in cartilage that was confirmed histologically to be indicative of OC. The average number of lesions per foal was 4.7 (SD 1.1) and 5.7 (SD 1.1) in Years 1 and 2, respectively. However, the severity of the lesions was considered mild, and no foals showed any clinical evidence of OC while alive. The number of lesions in the tarsocrural (TC) joint and the TC OC score at 160 days were positively associated with average daily weight gain (ADG) in the previous 4 weeks (p=0.005 and p=0.001, respectively). There was no significant effect of sex, fatness, birth-weight, weight at 160 days of age, or year of birth of the foal on the frequency and severity of OC lesions.

CONCLUSIONS: Many of the lesions classified as OC, using classification systems described by other authors, were likely to be normal variations of the process of endochondral ossification. Despite the high frequency of such lesions, they were considered to be of minor significance and none were clinically evident. The distribution of lesions was not typical, and most probably reflected the subtlety of the lesions. These results support the hypothesis that Cu is an over-emphasised factor in the aetiopathogenesis of OC. The relationship between subtle macroscopic lesions and lesions resulting in clinical signs of disease requires further investigation.  相似文献   

16.
REASONS FOR PERFORMING STUDY: Recombinant equine growth hormone (reGH) has recently been evaluated for effects on body condition and wound healing. It has the potential to influence articular cartilage via stimulation of IGF-1. OBJECTIVES: To investigate effects of administration on synovial joint metabolism. METHODS: Six mature horses were given 20 microg/kg bwt reGH daily for 8 weeks by i.m. injection. Three control horses were injected with sterile water. Serum and synovial fluid samples were collected at 6, 8, 11 and 16 weeks for GH and IGF-1 assays. Articular cartilage harvested at week 16 was evaluated by Western analysis using monoclonal antibodies BC-13, BC-4, 8-A-4 and CH-3. RESULTS: Concentrations of IGF-1 in serum and synovial fluid were significantly elevated (P < 0.05) at 6 and 8 weeks in the reGH group. Glycosaminoglycan concentrations in synovial fluid were significantly less than controls at these time points, suggesting that reGH may modulate proteoglycan metabolism in articular cartilage. In the reGH group, there were not any alterations in synovial fluid content of 3B3(-) epitope or aggrecan metabolite, or in aggrecan or link protein catabolites retained within cartilage, that might be expected with development of osteoarthritis. CONCLUSIONS: Intramuscular administration of reGH may be a more efficient means of delivery of IGF-1 to joints for cartilage resurfacing initiatives. POTENTIAL RELEVANCE: We found no alterations in cartilage metabolism indicative of development of osteoarthritis.  相似文献   

17.
The measurement of biomarkers that reflect cartilage breakdown is a powerful tool for investigating joint damage caused by disease or injury. Particularly in cases of osteochondrosis, synovial concentrations of these biomarkers may reveal the presence of osteoarthritic changes. Coll2-1, Coll2-1 NO2 and myeloperoxidase have recently been introduced in equine osteoarticular research but comparison between the concentrations of these markers in OCD affected and healthy joints has not been made. Therefore, this study aimed at reporting the synovial concentrations of these biomarkers in joints affected with osteochondral fragments in the tarsocrural joint compared to unaffected joints. Myeloperoxidase and Coll2-1NO2 revealed to have similar levels between affected joints and controls. However, in contrast to previous studies using C2C the present study demonstrated that synovial levels of Coll2-1 were significantly elevated in tarsocrural joints affected with osteochondrosis. Thus, Coll2-1 may be an earlier marker of cartilage degeneration than other cartilage degradation markers that have been previously used in equine medicine.  相似文献   

18.
A biological extract of high-rosmarinic acid mint (HRAM) has previously demonstrated inhibitory effects on lipopolysaccharide (LPS)-induced prostaglandin E(2) (PGE(2)), nitric oxide (NO) and glycosaminoglycan (GAG) release in vitro. This study was undertaken to determine whether HRAM added to feed produces similar effects in horses challenged with intra-articular LPS. Eight horses received HRAM (0 or 28.1 ± 1.3 g/day; n = 4 per group) in their feed for 24 days in a blinded manner. On day 21, all horses received an intra-articular injection of LPS (0.3 ng) into their left or right intercarpal joint. Synovial fluid (SF) samples were taken on postinjection day (PID)-21 (i.e. prior to commencement of supplementation), PID0, PID0.25, PID0.5, PID1 and PID3 and analysed for PGE(2), GAG, NO, protein and total nucleated cells counts. Blood biochemistry and haematology screens were conducted at PID-21, PID0, PID1 and PID3. There was a significant reduction in LPS-induced PGE(2) and GAG in SF in horses supplemented with HRAM compared with controls and a tendency to increase complement recognition protein accumulation in synovial fluid of HRAM horses. Plasma from HRAM horses had reduced total white blood cells, segmented neutrophils (compared with baseline concentrations) and lymphocytes (compared with controls), and increased SF nucleated cell count (compared with baseline concentrations and controls). It is concluded that HRAM offered as part of the feed alter biomarkers of inflammation in SF of LPS-challenged horses. Larger studies that seek to clarify effects of HRAM on synovial fluid cell counts and possible role of HRAM-induced interference with complement signalling are warranted.  相似文献   

19.
Many foals develop diarrhoea within the first two weeks of life which has been suggested to coincide with postpartum oestrus in their dams. To analyse the pathogenesis of this diarrhoea we have determined faecal bacteria in foals and their dams (n=30 each), and serum IGF-1 and γ-globulins for 6 weeks after birth. In addition, effects of β-carotene supplementation to mares (group 1: 1000 mg/day, n=15, group 2: control, n=15) on diarrhoea in foals were studied. Diarrhoea occurred in 92 and 79% of foals in groups 1 and 2, respectively, but was not correlated with oestrus in mares. Beta-carotene supplementation was without effect on foal diarrhoea. In mares, bacterial flora remained stable. The percentage of foals with cultures positive for E. coli was low at birth but increased within one day, the percentage positive for Enterococcus sp. was low for 10 days and for Streptococcus sp. and Staphylococcus sp. was low for 2-4 weeks. By 4 weeks of age, bacterial flora in foals resembled an adult pattern. Concentration of serum IGF-1 was low at birth (group 1: 149 ± 11, group 2: 166 ± 17ng/ml), increased after day 1 (day 7 group 1: 384 ± 30, group 2: 372 ± 36) but at no time differed between groups. Serum γ-globulin concentration in foals was low before colostrum intake and highest on day 1 (p<0.001 over time). In conclusion, neonatal diarrhoea in foals does not coincide with postpartum oestrus in their dams but with changes in intestinal bacteria and is not influenced by β-carotene supplementation given to mares.  相似文献   

20.
OBJECTIVE: To determine response of interleukin-1alpha (IL-1alpha)-conditioned equine articular cartilage explants to insulin-like growth factor-1 (IGF-1). Sample Population-Cartilage from the trochlea and condyles of the femur of a clinically normal 4-year-old horse. PROCEDURE: Effects of IGF-1 (0 to 500 ng/ml) after addition of IL-1alpha were evaluated by assessing matrix responses, using a sulfated glycosaminoglycan (GAG) assay, matrix 35SO4 GAG incorporation, and release of GAG. Mitogenic response was assessed by 3H-thymidine incorporation into DNA and fluorometric assay of total DNA concentration. RESULTS: Human recombinant IL-1alpha (40 ng/ml) increased the amount of labeled GAG released and decreased labeled and total GAG remaining in explants, and IL-1alpha decreased mitogenic response. Addition of IGF-1 counteracted effects seen with IL-1alpha alone. In general, IGF-1 decreased total and labeled GAG released into the medium, compared with IL-1alpha-treated explants (positive-control sample). Values for these variables did not differ significantly from those for negative-control explants. A significant increase in total and newly synthesized GAG in the explants at termination of the experiment was observed with 500 ng of IGF-1/ml. Labeled GAG remaining in explants was greater with treatment at 50 ng of IGF-1/ml, compared with treatment with IL-1alpha alone. Concentrations of 200 ng of IGF-1/ml abolished actions of IL-1alpha and restored DNA synthesis to values similar to those of negative-control explants. CONCLUSIONS AND CLINICAL RELEVANCE: IGF-1 at 500 ng/ml was best at overcoming detrimental effects associated with IL-1alpha in in vitro explants. These beneficial effects may be useful in horses with osteoarthritis.  相似文献   

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