Induction Of Synovitis Research Articles

Ultrassonografia da articulação femorotibiopatelar em ovinos submetidos à indução de sinovite por lipopolissacarídeos

Abstract Synovitis can be induced in animals through the application of bacterial wall lipopolysaccharide and has similar signs to naturally-occurring synovitis. Several studies have been using the sheep species as an experimental model to understand osteoarticular diseases of the femorotibiopatellar (FTP) joint in humans. There are echographic studies on the standardization of normality of the femorotibiopatellar joint in sheep. However, there is a gap in the literature for changes such as acute synovitis. The objective was to serially describe the sonographic aspects of the synovitis process induced by intra-articular infiltration of Escherichia coli (E. coli) lipopolysaccharide in the femorotibiopatellar joint of sheep. Twelve healthy crossbred sheep (Santa Inês x Dorper) were used. Induction of synovitis was performed only in the right FTP joints, which were serially evaluated using ultrasound examination at baseline moment (M0) and 12 (M12), 24 (M24), 48 (M48), 72 (M72), and 120 (M120) hours after lipopolysaccharide infiltration for synovitis induction. Intra-articular application of E. coli lipopolysaccharide resulted in one or more echographic signs of synovitis (increased synovial fluid volume, folding of the synovial membrane, and cellularity in the joint cavity), which were identified early, 12 hours after inoculation, and regressed over the evaluated times (p=0.0001) until disappearing after 120 hours of inoculation.

Acute pain in toll like receptor 2 induced synovitis is mediated by the toll like receptor 4 ligand S100A9

Purpose: Synovitis-associated pain is an important aspect of arthritis pathology. Several inflammatory mediators released by the synovium have been implicated in the regulation of pain, including S100A8 and S100A9 which may regulate pain either via direct stimulation of TLR4 on the nerve endings in the synovium or via stimulation of the dorsal root ganglia (DRG), thereby enabling an increased phagocyte infiltration, which may cause sensitization. We aimed to elucidate the role of S100A9 in the pain response after induction of synovitis using streptococcal cell walls (SCW), a known TLR2 ligand, as a trigger, comparing S100A9-/- mice and their WT controls.

TNIIIA2, The Peptide of Tenascin-C, as a Candidate for Preventing Articular Cartilage Degeneration.

TNIIIA2 is a peptide of the extracellular matrix glycoprotein tenascin-C. We evaluated whether intra-articular injection of TNIIIA2 could prevent articular cartilage degeneration without inducing synovitis in an osteoarthritis mice model. Ten micrograms per milliliter of TNIIIA2 were injected into the knee joint of mice (group II) to evaluate the induction of synovitis. The control group received an injection of phosphate buffered saline (group I). Synovitis was evaluated using synovitis score 2 and 4 weeks after injection. The ligaments of knee joints of mice were transected to make the osteoarthritis model. After transection, 10 µg/mL of TNIIIA2 was injected into the knee joint (group IV). The control group received an injection of phosphate buffered saline after transection (group III). Histologic examinations were made using hematoxylin and eosin and safranin-O staining at 2, 4, 8, and 12 weeks postoperatively. An in vitro study was also performed to determine the mechanism by which TNIIIA2 prevents cartilage degeneration. Human chondrocytes were isolated, cultured, and treated with TNIIIA2. The expressions of various mRNAs, including inflammatory cytokines, and anabolic and catabolic factors for cartilage were compared using real-time polymerase chain reaction. There were no differences between groups in the study of intra-articular injection of mice (group I vs. group II). In the osteoarthritis model, we found development of osteoarthritis was suppressed in group IV at 4 and 8 weeks. TNIIIA2 upregulated the expressions of tumor necrosis factor-α, matrix metalloproteinase 3, and basic fibroblast growth factor. We demonstrated that TNIIIA2 could prevent cartilage degeneration without synovitis.

Gene delivery of TIPE2 attenuates collagen-induced arthritis by modulating inflammation

Rheumatoid arthritis (RA) is an autoimmune disease that leads to severe disabilities through the induction of synovitis and subsequent cartilage and bone destruction. The development of a novel therapeutic strategy for suppressing inflammatory responses in RA will be of great benefit to patients. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is an important regulator of immune response in various diseases. However, the expression and function of TIPE2 in RA are still unclear. In the present study, the expression of TIPE2 during the development of collagen-induced arthritis (CIA) was determined. Lentivirus (LV) was utilized to deliver a TIPE2 overexpression system into the joints of CIA mice, and this was followed by pathological analysis, immune cell infiltration analysis, and inflammatory cytokine detection. TIPE2 was downregulated in CIA mice, which was inversely correlated with arthritis progression. The ectopic expression of TIPE2 from gene delivery prevented susceptibility and disease severity by inhibiting the infiltration of macrophages and myeloid-derived suppressor cells (MDSCs) in the joints of CIA mice. Furthermore, lower expression of proinflammatory cytokines was observed in LV-TIPE2-injected CIA mice, which was in part associated with the activation of STAT3 and NF-κB signaling pathways in the cartilage cells. These data support the suppressive function of TIPE2 in autoimmune diseases and identify the gene delivery of TIPE2 as an important therapeutic agent for the treatment of RA and perhaps other autoimmune diseases.

Induction of Synovitis Using Interleukin-1 Beta: Are There Differences in the Response of Middle Carpal Joint Compared to the Tibiotarsal Joint?

Background: The effects of recombinant interleukin-1β (rIL-1β) have been described for the middle carpal joint (MCJ). However, we are unaware of any studies that have described the cytological response of the tibiotarsal joint (TTJ) to rIL-1β or compared the clinical and cytological responses of the MCJ to the TTJ following the administration of intra-articular rIL-1β. Such information is critical for researchers planning to use rIL-1β to create acute synovitis models in horses.Objectives: To compare the clinical and cytological responses of the MCJ to the TTJ following administration of intra-articular rIL-1β.Methods: Twelve horses were used for the study. Eight horses received 75 ng of rIL-1β into the MCJ and four horses received 75 ng of rIL-1β into the TTJ. Clinical and cytological outcome parameters including lameness, joint circumference, joint effusion score, total nucleated cell count, cellular differentials, C-reactive protein, and prostaglandin-E2 concentrations were determined at baseline and multiple post-treatment time points over a 336 h period (2 weeks).Results: Recombinant IL-1β administered into the TTJ resulted in a significantly greater respiratory rate at 24 h and heart rate at 12 h when compared to rIL-1β administered into the MCJ. In addition, the TTJ had a significantly greater increase in joint circumference at 24 post-injection hour (PIH) and subjective effusion grade at 24 PIH and 336 PIH. The MCJ had significantly higher total protein concentration at 6 PIH, and a significantly higher NCC at 24 and 72 PIH when compared to the TTJ. Conversely, the TTJ had significantly higher neutrophilic infiltration than the MCJ at 6 PIH and 168 PIH.Conclusions: This study establishes that the same intra-articular dose of rIL-1 β elicits significantly different clinical and cytological responses in the MCJ compared to the TTJ in the equine model of intra-articular synovitis. In addition, clinical and cytological evidence of synovitis may persist up to or >1 week following intra-articular administration of rIL-1 β.

Effects of denervation of the hip joint on results of clinical observations and instrumented gait analysis in dogs with sodium urate crystal-induced synovitis.

OBJECTIVE To evaluate the effects of selective hip joint denervation on gait abnormalities and signs of hip joint pain in dogs. ANIMALS 6 healthy adult hound-type dogs. PROCEDURES Minimally invasive denervation was performed on the right hip joint of each dog. Two weeks later, sodium urate was injected into the right hip joint to induce synovitis. Dogs were evaluated clinically and by use of instrumented gait analysis before and 2 weeks after minimally invasive denervation and 4, 8, and 24 hours after induction of synovitis. Dogs were euthanized, and necropsy and histologic examination were performed. RESULTS No kinetic or kinematic gait modifications were detected 2 weeks after minimally invasive denervation. Denervation did not eliminate signs of pain and lameness associated with sodium urate-induced synovitis. Results of histologic examination confirmed that denervation was an effective method for transecting the innervation of the craniolateral and caudolateral aspects of the hip joint capsule. CONCLUSIONS AND CLINICAL RELEVANCE In this study, minimally invasive denervation did not result in gait modifications in dogs. Denervation did not abolish the signs of pain and lameness associated with generalized induced synovitis of the hip joint. Further studies are required before conclusions can be drawn regarding the clinical usefulness of hip joint denervation for dogs with hip dysplasia.

The preventive effects of two nutraceuticals on experimentally induced acute synovitis.

SummaryBackgroundNutraceuticals are often used in the management of equine osteoarthritis, but scientific evidence of their efficacy is lacking.ObjectivesTo study the preventive effects of two new nutraceuticals after the experimental induction of synovitis in comparison with positive and negative control treatments.Study designBlinded, controlled, randomised experiment.MethodsTwenty‐four healthy Standardbred horses were randomly allocated to supplement AT (multi‐ingredient, 28 days), supplement HP (collagen hydrolysate, 60 days), meloxicam (4 days) or placebo (60 days). Synovitis was induced in the right intercarpal joint by intra‐articular injection of 0.5 ng lipopolysaccharide (LPS) of Escherichia coli while treatments were continued. Blood and synovial fluid were sampled before treatment, immediately prior to LPS injection, and at 8, 24 and 48 h post‐injection. Synovial fluid samples were analysed for total nucleated cell count (TNCC), total protein (TP) and selected biomarkers (prostaglandin E2 [PGE 2], interleukin‐6 [IL‐6], glycosaminoglycans [GAGs], type II collagen synthesis [CPII], matrix metalloproteinase [MMP]). Lameness was scored by visual examination and pressure plate analysis immediately prior to LPS injection, and at 8, 24 and 48 h post‐injection. Clinical examinations were performed before treatment, immediately prior to LPS injection, at 2, 4 and 6 h post‐injection, and then twice per day during the test period.ResultsBefore treatment and intra‐articular challenge, there were no statistically significant differences among the treatment groups for any of the parameters. After intra‐articular challenge, the placebo group showed significantly higher synovial fluid TP, TNCC and PGE 2 compared with the meloxicam group, although the model did not induce a relevant amount of lameness. Both nutraceuticals resulted in significantly lower synovial fluid TP, TNCC and PGE 2 compared with placebo. No statistical differences in IL‐6, GAGs, CPII or MMPs were observed among treatment groups. No adverse effects were observed.Main limitationsDespite evidence of synovitis, lameness was too mild to detect.ConclusionsThe preventive administration of these nutraceuticals showed anti‐inflammatory effects in this validated synovitis model. Therefore, further studies of their clinical applicability are warranted.

The novel cytokine interleukin-36α is expressed in psoriatic and rheumatoid arthritis synovium

BackgroundInterleukin (IL)-36α is a recently described member of the IL-1 cytokine family with pro-inflammatory and clearly pathogenic properties in psoriasis.ObjectiveTo determine the IL-36α expression in psoriatic arthritis (PsA) compared to...

Serum cortisol concentration and force plate analysis in the assessment of pain associated with sodium urate–induced acute synovitis in dogs

To determine the relationship between serum cortisol concentration and pain severity as measured by force platform gait analysis in dogs with experimentally induced synovitis of the stifle joint. 10 healthy hound-type dogs. Dogs underwent 2 study phases. In the first phase, serum cortisol concentration, systolic arterial blood pressure, heart rate, and gait data were obtained at 0 (first sample), 2.5, 5, 7.5, and 10 hours. In the second phase, the same data were gathered immediately before (0 hours) and 2.5, 5, 7.5, and 10 hours after induction of acute urate synovitis in the left stifle joint. Data were statistically evaluated to compare changes in variable values over time and to determine the accuracy of serum cortisol measurements for diagnosis of acute orthopedic pain. Following induction of synovitis, ground reaction forces were significantly decreased relative to preinduction values at 2.5, 5.0, 7.5, and 10.0 hours and serum cortisol concentration was significantly increased at 2.5 hours. A cortisol concentration of >or= 1.6 microg/dL indicated pain with a 91% sensitivity and 35% specificity. In this model, cortisol concentration may be useful for diagnosing pain in dogs. Although, with a cutoff of >or= 1.6 microg/dL, pain would be detected in most dogs with pain, some pain-free dogs would also be identified as having pain. Conversely, dogs with a serum cortisol of < 1.6 microg/dL would be unlikely to have pain. Validation of this diagnostic test in a large, heterogeneous group of clinical patients is necessary.

Intra‐articular opioid analgesia is effective in reducing pain and inflammation in an equine LPS induced synovitis model

Intra-articular administration of morphine as a local analgesic and anti-inflammatory drug is widely used in human medicine. In equids, little is known about its clinical analgesic and anti-inflammatory efficacy. To use an inflammatory orthopaedic pain model to investigate the analgesic and anti-inflammatory effects of intra-articularly administered morphine as a new treatment modality in horses with acute arthritis. In a crossover study design, synovitis was induced in the left or right talocrural joint by means of intra-articular injection of 0.5 ng lipopolyssacharide (LPS). The effect of 120 mg morphine, intra-articularly administered at 1 h after induction of synovitis, was evaluated using both physiological and behavioural pain variables. Synovial fluid was sampled at 0, 4, 8, 28 and 52 h after induction of synovitis and analysed for total protein concentration, leucocyte count and for prostaglandin E(2), bradykinin and substance P concentrations by ELISA. Ranges of motion of metatarsophalangeal and talocrural joints were measured as kinematic variables with the horses walking and trotting on a treadmill under sound and lame conditions. Clinical lameness scores and several behavioural variables related to the perception of pain were obtained. LPS injection caused marked transient synovitis, resulting in increased concentrations of inflammatory synovial fluid markers, clinical lameness, joint effusion and several behavioural changes, such as increased time spent recumbent, decreased limb loading at rest and decreased time spent eating silage. Intra-articular morphine resulted in a significant decrease in synovial white blood cell count, prostaglandin E(2) and bradykinin levels and improvement in clinical lameness, kinematic and behavioural parameters, compared to placebo treatment. Intra-articular morphine offers potent analgesic and anti-inflammatory effects in horses suffering from acute synovitis. Local administration of opioids may be useful for horses with acute inflammatory joint pain and offers possibilities for multimodal analgesic therapies without opioid-related systemic side effects.

Evaluation of analgesia provided by the administration of epidural ketamine in dogs with a chemically induced synovitis

Objective To determine if epidural ketamine provides analgesia in dogs with a chemically induced synovitis.Study design Prospective randomized experimental trial.Animals Thirty-two healthy, adult mongrel dogs (13–30 kg).Methods (Part I) Synovitis was induced in the right stifle of 16 dogs and allowed to develop for 12 hours. Epidural injection at the lumbosacral space of either ketamine (2 mg kg−1; n = 8) or placebo (n = 8) was performed. Limb use and pain were measured using a force platform and numerical rating scale (NRS). Assessments were performed before and at 12, 14, 16, 18, 20, and 24 hours after the induction of synovitis. (Part II) Epidural injection of either ketamine (n = 8) or placebo (n = 8) was performed immediately before the induction of synovitis. Analgesia was assessed as in Part I. Assessments occurred before and at 2, 4, 6, 8, and 12 hours after the induction of synovitis.Results (Part I) Vertical ground reaction forces (VGRF) significantly decreased and NRS scores of total pain significantly increased after the induction of synovitis in all dogs (p < 0.05). No significant differences in VGRF or NRS scores were measured between treatment groups at any assessment period. (Part II) Dogs that received ketamine had significantly lower NRS scores 2 hours after treatment (p < 0.05). NRS scores did not differ between groups at any other evaluation. VGRF did not differ significantly between treatment groups at any assessment period.Conclusion Epidural ketamine at a dose of 2 mg kg−1 administered after the development of synovitis does not provide significant levels of analgesia. Administration of ketamine before the induction of synovitis significantly decreased the NRS score 2 hours post-induction.Clinical relevance Administration of epidural ketamine before tissue injury may provide analgesia of short duration in dogs.

Three‐dimensional kinematic analysis of horses with induced tarsal synovitis

Techniques for 3D analysis have recently been developed. This study applied 3D kinematic analysis to describe the effects of lameness in the distal intertarsal (DIT) and tarsometatarsal (TMT) joints; complex joints such as this may show measurable amounts of movement outside the sagittal plane that may change in response to pathological conditions. Three-dimensional motions of the tarsal joint change after the induction of synovitis at the DIT and TMT joints. Twelve retroreflective markers, attached on the skin over the right limb, were used to develop 3D coordinate systems for tibial and metatarsal segments. Data were collected at trot from 4 horses on 2 occasions, before (sound condition) and after (lame condition) induction of synovitis of the DIT and TMT joints. Ranges of 3D motions of the metatarsal segment relative to the tibial segment were compared between sound and lame conditions using t tests. There were significant decreases (P<0.05) in tarsal joint flexion and cranial translation of the metatarsus relative to the tibia during stance, and in proximal translation of the metatarsus during swing. In the lame condition, reduced cranial translation at the DIT and TMT joints may lead to a reduction in the motion of the articular cartilage surfaces relative to each other, which may have adverse effects on cartilage nutrition and function. Further studies of tarsal 3D kinematics in horses with bone spavin could allow quantification of the biomechanical effects of the special shoes used for conservative treatment.

Tempromandibular joint (TMJ) response to intra-articular dexamethasone injection following mechanical arthropathy: a histological study in rats

The purpose of this study was to evaluate as well as to compare the effect of intra-articular versus intra-peritoneal injection of dexamethasone on synovitis induced by trauma to the rat’s TMJ. Twenty-seven male Wister rats were included in the present study. Induced forced condylar hypermobility achieved through opening the rat’s mouth manually 10 times for 10 consecutive days. Rats were randomized into three groups (3 rats in the control group, and 24 rats in both experimental groups). Group I (control group): Rats of this group were left without any treatment after induction of synovitis. Group II: Rats were injected with a single dose of 1.2 mg/kg dexamethasone intra-articularly (after 10 days). Group III: Rats were injected with a single intra-peritoneal injection of 1.2 mg/kg dexamethasone (after 10 days). Control rats were sacrificed at 6 weeks, while rats in Groups II and III were sacrificed at 1 and 6 weeks after drug injection, then joints were dissected and processed for histological study. The condylar head of the rats injected with intra-articular dexamethasone showed resorption with active osteoclastic activity, although the drug was given only once. This might be an alarming sign of the severe adverse effect(s) of the local injection of dexamethasone.

The evaluation of analgesia provided by epidural ketamine in dogs with chemically induced synovitis

Ketamine, a noncompetitive NMDA receptor antagonist, has been shown to provide analgesia in some species. To target the NMDA receptor specifically and to potentially minimize some untoward side-effects, ketamine had been used epidurally. The objective of this study was to determine the analgesic effect of epidurally administered ketamine in dogs with chemically induced synovitis. Sixteen healthy dogs were used. Dogs were anesthetized with propofol (4 mg kg−1 IV). Synovitis was induced by injecting 1 mL of sodium urate crystal solution (10 mg mL−1) into the right stifle. Dogs were allowed to recover and the synovitis was allowed to develop for 12 hours. The dogs were then anesthetized again using propofol (4 mg kg−1 IV). Lumbosacral epidural injections were performed with each dog receiving either 2 mg kg−1 of ketamine (20 mg mL−1) or an equal volume of placebo (sterile water containing not more than 0.1 mg mL−1 benzethonium chloride). Analgesia was assessed at baseline and then at 12, 14, 16, 18, 20, and 24 hours after induction of synovitis. Ground reaction forces (peak vertical force and impulse area) and overall pain were measured using a force platform and a pain scoring system (numerical rating scale). Analysis of the data by Repeated Measures anova showed that the dogs developed a significant lameness between the baseline and 12 hours. However, no significant difference in ground reaction forces or total pain score was demonstrated between the treatment and control groups at any other time. In conclusion, ketamine administered epidurally at a dose of 2 mg kg−1 did not provide significant analgesia in dogs with chemically induced synovitis.

Placental immunomodulator ferritin, a novel immunoregulator, suppresses experimental arthritis.

To determine the effect of treatment with C48, the recombinant cytokine-like domain of the novel human placental immunomodulator ferritin (PLIF) immunoregulator, on zymosan-induced arthritis (ZIA) in mice and on adjuvant-induced arthritis (AIA) in rats. The in vitro effect of PLIF/C48 was tested in mixed lymphocyte cultures (MLCs) of allogeneic mouse splenocytes. Arthritis was induced by intraarticular injection of zymosan into naive mice and by subcutaneous injection of Mycobacterium tuberculosis into rats. C48 was injected intraperitoneally daily from day 3 to day 9 or from day 7 to day 13 after induction of synovitis by zymosan, and every other day from day 2 to day 14 after induction of AIA. Swelling of the joints and histologic features of the synovium were assessed. Th1 and Th2 cytokines were quantified by enzyme-linked immunosorbent assay. Both PLIF and C48 significantly inhibited the in vitro immunoreactivity of mouse splenocytes in MLCs. Treatment of ZIA mice and AIA rats with C48 effectively reduced joint swelling. C48 treatment reduced synovial lining thickening, numbers of mononuclear cells and histiocytes, as well as cartilage destruction and bone erosions. In vitro, activated splenocytes from C48-treated ZIA and AIA animals produced significantly higher levels of interleukin-10 (IL-10). In animals with ZIA, this was accompanied by lower levels of tumor necrosis factor and IL-2. Human PLIF and C48 were shown to exert cross-species immunosuppressive activity in vitro. The in vivo suppression of articular inflammation in the experimental models of ZIA and AIA was the result of treatment with the antiinflammatory human C48. These results suggest that treatment with C48 may offer an effective immunotherapeutic means of controlling inflammatory polyarthritis.

Concentrations of cartilage oligomeric matrix protein in dogs with naturally developing and experimentally induced arthropathy.

To assay concentrations of cartilage oligomeric matrix protein (COMP) in canine sera and synovial fluid (SF), to compare COMP concentrations in clinically normal dogs and dogs with joint disease, and to analyze changes in COMP concentrations in dogs with experimentally induced acute synovitis. 69 control dogs without joint disease, 23 dogs with naturally occurring aseptic arthropathy, and 6 dogs with experimentally induced synovitis. Serum (n = 69) and SF (36) were obtained from control dogs. Samples of serum (n = 23) and SF (13) were obtained from dogs with naturally occurring aseptic arthropathy with or without radiographic features of osteoarthritis (OA). Serum and SF were obtained before and 1, 2, 3, and 7 days after induction of synovitis. The COMP concentrations were determined by use of an inhibition ELISA that had canine cartilage COMP and monoclonal antibody against human COMP. Concentrations of COMP in serum and SF of control dogs were 31.3+/-15.3 and 298.7+/-124.7 microg/ml, respectively. In naturally occurring OA, COMP concentrations in serum (44.9+/-177 microg/ml) and SF (401.7+/-74.3 microg/ml) were significantly higher than corresponding concentrations in control dogs. The COMP concentration in SF peaked 24 and 48 hours after induction of synovitis, whereas concentration in serum peaked on day 3. These results supported the hypothesis that COMP concentration in serum and SF of dogs may be altered after cartilage degradation or synovitis. Measurement of COMP concentrations can be useful when differentiating arthropathies in dogs.

Scintigraphic evaluation of dogs with acute synovitis after treatment with glucosamine hydrochloride and chondroitin sulfate

Abstract Objective To evaluate the effects of orally administered glucosamine hydrochloride (GIAm)–chondroitin sulfate (sCS) and GIAM–CS–S-adenosyl-L-methionine (SAMe) on chemically induced synovitis in the radiocarpal joint of dogs. Animals 32 adult mixed-breed dogs. Procedure For 21 days, all dogs received a sham capsule (3 groups) or GIAm-CS (prior treatment group) in a double-blinded study. Unilateral carpal synovitis was induced by injecting the right radiocarpal joint with chymopapain and the left radiocarpal joint (control joint) with saline (0.9% NaCl) solution. Joints were injected on alternate days for 3 injections. After induction of synovitis, 2 groups receiving sham treatment were given GIAm-CS or GIAm-CS–SAMe. Another group continued to receive sham capsules (control group). Joint inflammation was quantified, using nuclear scintigraphy, before injection of joints and days 13, 20, 27, 34, 41, and 48 after injection. Lameness evaluations were performed daily. Results Dogs given GIAm-CS before induction of synovitis had significantly less scintigraphic activity in the soft-tissue phase 48 days after joint injection, significantly less uptake in the bone phase 41 and 48 days after joint injection, and significantly lower lameness scores on days 12 to 19, 23, and 24 after injection, compared with other groups. Conclusions and Clinical Relevance Analysis of results of this study suggest that prior treatment with GIAm-CS for 21 days had a protective effect against chemically induced synovitis and associated bone remodeling. Prior treatment with GIAm-CS also reduced lameness in dogs with induced synovitis. (Am J Vet Res 1999;60:1552–1557)

Effects of hylan on amphotericin-induced carpal lameness in equids

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.

A possible role of two hydrophobic amino acids in antigen recognition by synovial T cells in rheumatoid arthritis.

Synovial T cells play a crucial role in the pathogenesis of rheumatoid arthritis (RA) synovitis. We have quantitatively analyzed the T cell receptor (TcR) variable (V) region gene repertoire of freshly isolated synovial fluid (SF) T cells, comparing it with that of peripheral blood (PB) T cells in RA. The TcR V gene repertoire of PB and SF T cells in RA and osteoarthritis was heterogeneous. In contrast, V alpha 11 in SF was expressed to a greater degree in three of five RA patients, and increased levels of V beta 6, 1-3 were found in the SF of four of six RA, compared with paired PB. Of note, V beta 6, 1-3 was universally used in four RA patients with a disease duration of less than 10 years, irrespective of their HLA-DR types. This was in contrast to two other RA patients, suffering for more than 20 years, who showed different V alpha and V beta usages. beta-chain sequence analysis in RA patients with a preference for V beta 6, 1-3 has shown that a few clones dominated in SF, whereas polyclonality was observed in PB. These findings suggest oligoclonal expansion of T cells in response to specific antigen(s) in the SF of these patients with RA of relatively short duration. Concomitant use of two hydrophobic amino acids, leucine and valine in the D beta region was noticeable among the predominant SF clones. These two amino acids might directly contact a peptide specific for the induction of synovitis in RA patients. TcR-directed therapy may, therefore, be useful for the treatment of early RA synovitis.

Streptococcal antigen-induced dislocation and dysplasia of the hip in newborn rats. Radiologic and histologic evaluation of a model of congenital dislocation of the hip.

Dislocation of the hip developed in 62% of newborn rats with streptococcal antigen-induced synovitis. Age at the time of the induction of synovitis is critical since dislocation is not observed in older rats. Synovitis with distention and laxity of the joint capsule is most likely responsible for the hip dislocation. Although congenital dislocation of the hip in children is not mediated by an inflammatory process, the current model of dislocation of the hip in rats is similar in being critically age-dependent, and associated with ligamentous laxity. Our model may be helpful in studying this important clinical entity.