Manjarix attenuated pain and joint swelling in a rat model of monosodium iodoacetate-induced osteoarthritis.

Osteoarthritis (OA) is a joint disease characterized by degeneration of cartilage, intra-articular inflammation, remodeling of subchondral bone and joint pain. The present study was designed to assess the therapeutic effects and the possible underlying mechanism of action of Manjarix, a herbal combination composed of ginger and turmeric powder extracts, on chemically induced osteoarthritis in rats. An OA model was generated by intra-articular injection of 50 µL (40 mg mL-1) of monosodium iodoacetate (MIA) into the right knee joint of rats. After one week of osteoarthritis induction, a comparison of the anti-inflammatory efficacy of indomethacin at an oral dose of 2 mg kg-1 daily for 4 successive weeks versus five decremental dose levels of Manjarix (1000, 500, 250, 125, and 62.5 mg kg-1) was performed. Serum inflammatory cytokines, interleukin 6, interleukin 8, and tumor necrosis factor alpha; C-telopeptide of type II collagen (CTX-II) and hyaluronic acid (HA) were measured, along with weekly assessment of the knee joint swelling. Pain-like behavior was assessed and knee radiographic and histological examination were performed to understand the extent of pain due to cartilage degradation. Manjarix significantly reduced the knee joint swelling, decreased the serum levels of IL6, TNF-α, CTX-II and HA, and reduced the pathological injury in joints, with no evidence of osteo-reactivity in the radiographic examination. Manjarix also significantly prevented MIA-induced pain behavior. These results demonstrate that Manjarix exhibits chondroprotective effects and can inhibit the OA pain induced by MIA, and thus it can be used as a potential therapeutic product for OA.

Curcumin: hopeful treatment of hemophilic arthropathy via inhibition of inflammation and angiogenesis.

Introduction: Hemophilic arthropathy (HA) is a serious complication among hemophilic patients causing a wide range of morbidity due to the inflammatory reactions followed by repeated episodes of bleeding. This condition has recently been shown to be accompanied by angiogenesis. The cascade starts with iron accumulation leading to an increase in CD68+ and CD11b+ cells responsible for initiating the inflammation.Areas covered: During inflammation, different factors and cytokines such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor α (TNF-α) actively play parts in the pathogenesis of HA and also angiogenesis. It has been demonstrated that different pro-angiogenic and angiogenic factors such as hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), oxidative stress and matrix metalloproteinases (MMPs) are also important in the pathogenesis of HA. Curcumin is known for its strong anti-inflammatory and anti-angiogenic potentials. This agent is able to inhibit the mentioned inflammatory and angiogenic factors such as IL-1, IL-6, TNF-α, VEGF, MMPs, and HIF-1α. Also, as well as anti-angiogenic and anti-inflammatory activity, curcumin has a strong antioxidant potential and can decrease oxidative stress.Expert opinion: It seems that curcumin could be considered as a possible agent for the treatment of HA through inhibition of inflammation, oxidative stress, and angiogenesis.

Wrist Deformity in Children and Adolescents with b-thalassemia on Oral Iron Chelation Therapy.

OBJECTIVE: To describe a novel wrist deformity in b-thalassemia major patients, and their radiographic and magnetic resonance imaging findings. METHODS: 30 patients with b-thalassemia major who were noticed to have ulnar deviation at wrist joint were evaluated for previous history of medications, serum ferritin levels, presence of pain and swelling at the wrist joint, and the duration of iron chelation therapy. Radiographs of wrist and limited magnetic resonance imaging (MRI) sequences were obtained in 30 and 15 patients, respectively. RESULTS: Radiographs revealed varying severity of distal ulnar shortening, distal radial slanting and presence of soft tissue distal to the ulna. MRI showed similar deformities along with abnormal marrow signal at distal ulnar ends; in 8 patients, a soft tissue distal to the distal end of ulna was noted. CONCLUSIONS: Varying severity of radiological abnormalities, predominantly affecting the distal ulna, are present in children and adolescents with b-thalassemia receiving oral chelation therapy.

[Neurogenic paraosteopathy of the elbow: results of surgical arthrolysis (a retrospective study of 37 cases)]. / La para-ostéopathie neurogène du coude: résultat de l'arthrolyse chirurgicale (étude rétrospective de 37 cas).

Neurogenic paraosteoarthropathies are ectopic ossifications which develop near the joints. They are a process of neo-ectopic osteogenesis occurring after central or peripheral neurological lesions, in some types of comas (oxygen carbon intoxication, prolonged sedation) and following peripheral traumas including burns. They inolve almost exclusively the large proximal joints of the limbs. Elbow is the second area of involvment. The purpose of our study was to analyze the results of surgical arthrolysis in 37 patients with elbow stiffness due to neurogenic osteoarthropathy of the elbow. We conducted a retrospective study of 35 patients and 37 elbows over a 25-year period. Preoperative assessment included clinical and radiological examination. Since 2003 the patients had undergone systematic elbow arthroscopy. The gold standard surgical treatment was arthrolysis. All patients underwent functional rehabilitation protocol. Outcomes were analyzed after a mean 5-year follow-up period (6 months - 10 years). Neurogenic paraosteoarthropathy was caused by head injury with coma in 58.8% of cases. Preoperative assessment showed bending stiffness in the majority of cases (88%), severe or very severe in 64.7% of cases. Intraoperatively functional elbow range of motion from -30° to 130° was obtained in 61.7% of cases and in 41% of cases in the long term. Ulnar nerve liberation was satisfactory in 92% of cases. No postoperative instability of the elbow was reported. Two patients with definitive neurological lesions had osteoma recurrence. The results were equivalent regardless surgical delay. Surgical arthrolysis is an effective treatment for neurogenic osteomas of the elbow.

Extracellular Vesicles in Joint Disease and Therapy.

The use of extracellular vesicles (EVs) as a potential therapy is currently explored for different disease areas. When it comes to the treatment of joint diseases this approach is still in its infancy. As in joint diseases both inflammation and the associated articular tissue destruction are important factors, both the immune-suppressive and the regenerative properties of EVs are potentially advantageous characteristics for future therapy. There is, however, only limited knowledge on the basic features, such as numerical profile and function, of EVs in joint articular tissues in general and their linking medium, the synovial fluid, in particular. Further insight is urgently needed in order to appreciate the full potential of EVs and to exploit these in EV-mediated therapies. Physiologic joint homeostasis is a prerequisite for proper functioning of joints and we postulate that EVs play a key role in the regulation of joint homeostasis and hence can have an important function in re-establishing disturbed joint homeostasis, and, in parallel, in the regeneration of articular tissues. In this mini-review EVs in the joint are explained from a historical perspective in both health and disease, including the potential niche for EVs in articular tissue regeneration. Furthermore, the translational potential of equine models for human joint biology is discussed. Finally, the use of MSC-derived EVs that is recently gaining ground is highlighted and recommendations are given for further EV research in this field.

The role of scapular kinematics in patients with different shoulder musculoskeletal disorders: A systematic review approach.

This study aimed to identify the role of the scapula in shoulder musculoskeletal disorders (SMDs) and provided a systematic review of available studies in the field of scapular three-dimensional kinematics. We systematically searched 5 international databases, including Scopus, EMBASE, PubMed, CINAHL, PEDro, and Cochrane Library from June to September 2015. Twenty studies met the inclusion criteria and were retrieved in full paper. The selected studies were critically appraised independently by two researchers. The patients with shoulder impingement syndrome (SIS) and shoulder instability had an increased protraction, lesser upward rotation (UR), and increased internal rotation (IR) during scapular plane elevation, whereas the patients with frozen shoulders had lesser protraction. Moreover, the patients with SIS had a greater scapular posterior tilt (PT) and external rotation during shoulder abduction. Increased scapular UR and PT with decreased scapular IR was seen in patients with stiffness of Latissimus Dorsi and fibromyalgia without any changes in the scapular IR. The results of this systematic review help the clinicians to have an insight about scapular kinematics as a predictive index for SMDs.

[Diagnosis and therapy of benign intraarticular tumors]. / Diagnostik und Therapie benigner intraartikulärer Tumoren.

Intraarticular benign tumors are rare lesions in many cases seen as incidental findings. One of the typical lesions is the diffuse or nodular form of pigmented villonodular synovitis, which needs a complete surgical removal. Magnetic Resonance Imaging (MRI) is diagnostic in most of the cases because of the intracellular iron content which shows an at least in some parts dark T2-sequence. Adjuvant therapies as radiosynoviorthesis should be considered in diffuse or recurrent lesions. Synovial Chondromatosis represents a metaplastic disorder of the synovial membrane resulting in the production of loose cartilage bodies. Also in this dissease synovectomy or, in late cases, removal of the loose bodies only, is recommended. Synovial hemangiomas are hamartomas which may lead to pain or restriction of movement. In these cases total or partial resection is justified. Alternative treatment options such as laserablation may be possible. Lipoma arborescens represents a proliferative lipoid lesion of the subsynovial region leading to villonodular synovial proliferation. If clinically symptomatic, resection by arthroscopic or open synovectomy is recommented.

Grading Osteoarthritic Changes of the Zygapophyseal Joints from Radiographs: A Reliability Study.

OBJECTIVE: This study tested the reliability of a 5-point ordinal scale used to grade the severity of degenerative changes of zygapophyseal (Z) joints on standard radiographs. METHODS: Modifications were made to a Kellgren grading system to improve agreement for grading the severity of osteoarthritic changes in lumbar Z joints. These included adding 1 grade of no degeneration, multiple radiographic views, and structured examiner training. Thirty packets of radiographic files were obtained, which included representation of all 5 grades including no degeneration (0) and Kellgren's 4-point (1-4) joint degeneration classification criteria. Radiographs were digitized to create a radiographic atlas that was given to examiners for individual study and blinded evaluation sessions. Intrarater and interrater agreement was determined by weighted κ (κw) from the examination of 79 Z joints (25 packets). RESULTS: Using the modified scale and after training, examiners demonstrated a moderate-to-substantial level of interrater agreement (κw = 0.57, 0.60, and 0.68). Intrarater agreement was moderate (κw = 0.42 and 0.54). CONCLUSIONS: The modified Kellgren 5-point grading system provides acceptable intrarater and interrater reliability when examiners are adequately trained. This grading system may be a useful method for future investigations assessing radiographic osteoarthritis of the Z joints.

[Lead toxicity in its joint administration with the aluminium oxide nanoparticles to rats].

In this paper we studied the effect of aluminum oxide (Al2O3) nanoparticles (NPs) on the accumulation and biomarkers of toxic action of lead (Pb) when co-administered to rats in subacute experiment. 36 Wistar rats with initial body weight 120-140 g were divided into 4 groups. Animal of group 1 (control group) were given distilled water by gavage. Rats in group 2 received Pb acetate solution in a dose of 20 mg/kg body weight (based on Pb), animal in the 3rd and 4th groups additionally to this received suspension of Al2O3 NPs in doses of 1 and 100 mg/kg body weight, respectively. The experiment lasted 22 days. Body and organ weight, standard haematologic parameters, protein, creatinine, uric acid level, aminotransferase activity (ALT and AST) in serum, urinary 5-aminolevulinic acid (5-ALA) concentration were measured. Apoptosis of hepatocytes was studied by flow cytometry. Pb content was determined by atomic absorption spectrometry. It has been shown that the administration of Al2O3 NPs together with Pb resulted in a significant dose-dependent increase in the relative weight of the kidneys (0.88 ± 0.03% and 0.94 ± 0.06% vs. 0.74 ± 0.02% and 0.85 ± 0.01% in control and group 1). The excretion of 5-ALA in the urine of animals treated with lead acetate significantly (p < 0.001) increased compared to the animals of group 1 (0.80 ± 0.08/µmol/l); while any dependence of this parameter on the dose of Al2O3 NPs was absent (p > 0.05) (group 2: 4.54 ± 0.56 µmol/l; group 3: 7.34 ± 1.35 µmol/l; group 4: 5.71 ± 1.74 µmol/l). The hemoglobin content was significantly reduced in animals of groups 2-4 (134.0 ± 2.9; 133.6 ± 1.8 and 129.9 ± 2.9 g/l) compared to the animals of the control group (144.6 ± 1.5 g/l), the dependence of this parameter on the dose of Al2O3 NPs was also absent. A marked and significant increase of the level of glucose has been noticed on the background of the Al2O3 and NPs (7.46 ± 0.49 u 8.24 ± 0.80 vs. 6.28 ± 0.34 mmol/l in group 2), and its level went beyond physiological norms in the 4th group and ANOVA indicated the influence of Al2O3 NPs administration. The toxic effects of lead on hematological parameters of blood on the background of the Al2O3 and NPs weren't weakened, and in the case of hematocrit even enhanced, as evidenced by one-way analysis of variance (p < 0.05). When administered together with the Al2O3 Pd accumulated in increased amounts in the liver [up to 1.96 ± 0.25 (group 3) and 2.16 ± 0.23 (group 4) vs. 1.17 ± 0.19 (group 2) mg/kg] (p < 0.05). Thus, Al2O3 NPs possibly presented as a contaminant in food can enhance the bioavailability of lead and some indices of its toxic action.

Ustekinumab associated with flares of psoriatic arthritis.

IMPORTANCE: Ustekinumab is a human monoclonal antibody that binds to the shared p40 subunit of interleukin (IL) 12 and IL-23. It is approved in the United States for adults (>18 years) with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. In 1 phase 2 trial of ustekinumab for treatment of psoriatic arthritis, joint disease improved. OBSERVATION: We report 4 cases of ustekinumab monotherapy for plaque psoriasis that resulted in disabling flares of known psoriatic arthritis or unmasked previously occult joint disease. In all of our cases, psoriasis improved dramatically with ustekinumab therapy while psoriatic arthritis flared. CONCLUSIONS AND RELEVANCE: Despite early results of a phase 2 ustekinumab trial suggesting efficacy for both plaque psoriasis and psoriatic arthritis, our case series raises concern that ustekinumab may unmask or aggravate joint disease in selected patients. These data underscore the need for further investigation of ustekinumab's effects on psoriatic arthritis.

Evaluation of serum trace mineral, vitamin D, and sex steroid hormone concentration, and survey data in llamas and alpacas with metacarpophalangeal and metatarsophalangeal hyperextension.

OBJECTIVE: To characterize serum trace mineral, sex steroid hormone, and vitamin D concentrations and identify factors associated with metacarpophalangeal and metatarsophalangeal hyperextension in llamas and alpacas. SAMPLES: Serum samples from 79 llamas and 15 alpacas and owner survey data for 573 llamas and 399 alpacas. PROCEDURES: Serum samples were stored at -20°C until analysis and were evaluated for trace mineral, vitamin D, estradiol, progesterone, and testosterone concentrations. Information regarding age of onset, number of affected animals in herd, feed and supplements given, type of housing, and management practices was obtained in an owner survey. RESULTS: Higher serum zinc and iron concentrations were associated with metacarpophalangeal and metatarsophalangeal hyperextension in camelids, compared with controls. In summer and fall months, vitamin D concentrations were significantly higher in affected camelids than controls. Overall prevalence was 13.3% in llamas, compared with 0.7% in alpacas. No management factors were found to be predictive of this condition. No other factors examined were associated with metacarpophalangeal and metatarsophalangeal hyperextension. CONCLUSIONS AND CLINICAL RELEVANCE: Despite similar supplementation practices and environmental conditions between affected and unaffected animals, an association of high serum zinc, iron, and vitamin D concentrations in affected camelids, compared with controls, may indicate differences of intake or absorption of dietary supplements.

Palaeopathology of human remains from the Roman Imperial Age.

The increasing attention of archaeological and anthropological research towards palaeopathological studies has allowed to focus the examination of many skeletal samples on this aspect and to evaluate the presence of many diseases afflicting ancient populations. This paper describes the most interesting diseases observed in skeletal samples from five necropolises found in urban and suburban areas of Rome during archaeological excavations in the last decades, and dating back to the Imperial Age. The diseases observed were grouped into the following categories: articular diseases, traumas, infections, metabolic or nutritional diseases, congenital diseases and tumors, and some examples are reported for each group. Although extensive epidemiological investigation in ancient skeletal records is impossible, palaeopathology allowed highlighting the spread of numerous illnesses, many of which can be related to the life and health conditions of the Roman population.

Investigation of serum amino acid and serum amyloid A concentrations in chickens with amyloid arthropathy.

BACKGROUND: Increased proteolytic cleavage of serum amyloid A (SAA) may potentially contribute to the development of AA amyloid deposition. OBJECTIVE: To study the possible relationship between amyloid artropathy and expression of SAA and some serum amino acids. ANIMALS AND METHODS: Values of 15 serum amino acids and SAA were investigated in chickens with experimentally induced amyloid arthropathy. Thirty-four, 5-week-old chicks were allocated into two groups: one group was injected intra-articularly with 0.25 mL complete Freund's adjuvant at the left tibio-metatarsal joint to induce amyloid arthropathy, whereas the other group served as control. All pullets were necropsied 13 weeks after injection. Collected tissue samples were examined histopathologically. Blood samples were collected and SAA concentrations were measured with enzyme-linked immunosorbent assay. High-performance liquid chromatography was used to assess the amino acid concentrations in serum. RESULTS: Amyloid accumulation in joints occurred only in the experimental group (89%). SAA concentrations of 166 ± 17 and 423 ± 39 (SD) ng/mL were found in the control and experimental groups, respectively (p < 0.001). In the experimental group, an increase was observed in all examined amino acid concentrations except for citrulline. The most significant (p < 0.001) increases were noticed in serine (from 159 ± 15 to 360 ± 29 µmol/L), glycine (from 151 ± 20 to 279 ± 16 µmol/L), isoleucine (from 48 ± 2 to 80 ± 6 µmol/L), and phenylalanine (from 49 ± 2 to 90 ± 3 µmol/L). CONCLUSION: The results of this study suggest that there is a positive correlation between some serum amino acid values, especially serine, glycine, isoleucine, and phenylalanine, and the high concentrations of SAA in chickens with amyloid arthropathy.

Evaluation of intramuscularly administered sodium pentosan polysulfate for treatment of experimentally induced osteoarthritis in horses.

OBJECTIVE: To assess clinical, radiographic, histologic, and biochemical effects of sodium pentosan polysulfate (NaPPS) administered IM for treatment of experimentally induced osteoarthritis in horses. ANIMALS: 18 horses. PROCEDURES: Osteoarthritis was induced arthroscopically in 1 middle carpal joint of all horses. Nine horses received NaPPS (3 mg/kg, IM) on study days 15, 22, 29, and 36. Nine control horses received the same volume of saline (0.9% NaCl) solution IM on study days 15, 22, 29, and 36. Clinical, radiographic, gross, histologic, histochemical, and biochemical findings as well as findings of synovial fluid analysis were evaluated. RESULTS: No adverse treatment-related events were detected. Induced osteoarthritis caused a substantial increase in lameness, response to flexion, joint effusion, radiographic findings, synovial membrane inflammation, and articular cartilage fibrillation. Articular cartilage fibrillation was substantially reduced by NaPPS treatment, and concentrations of chondroitin sulfate 846 epitope were significantly increased in the synovial fluid of osteoarthritic and non-osteoarthritic joints of treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that NaPPS has some beneficial disease-modifying effects and may be a therapeutic option for osteoarthritis in horses.

Bilateral carpal valgus deformity in hand-reared cheetah cubs (Acinonyx jubatus).

Four hand-reared cheetah cubs (Acinonyx jubatus) exhibited progressively severe bilateral valgus deformity of the carpi (CV) during the weaning period. Radiographs of the thoracic limbs suggested normal bone ossification, and serum chemistry was unremarkable. All affected cubs developed CV shortly after the onset of gastroenteritis, which was treated medically, and included use of a prescription diet. A sudden decrease in growth rate was associated with gastrointestinal disease. Before gastroenteritis and CV, affected cubs had higher growth rates than unaffected cubs, despite similar mean daily energy intake. Return to normal thoracic limb conformation was consequent to dietary manipulation (including a reduction in energy intake and vitamin and mineral supplementation), as well as decreased growth rates and recovery from gastroenteritis. The cause of the CV is likely to have been multi-factorial with potentially complex physiological interactions involved.

Inflammatory role of ASC in antigen-induced arthritis is independent of caspase-1, NALP-3, and IPAF.

Because IL-1beta plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC(-/-) mice showed reduced severity of AIA, decreased levels of synovial IL-1beta, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-gamma, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC(-/-) T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC(-/-) mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.

GATA-3 protects against severe joint inflammation and bone erosion and reduces differentiation of Th17 cells during experimental arthritis.

OBJECTIVE: Rheumatoid arthritis is associated with the infiltration of T helper cells into the joints. It is unclear whether interferon-gamma (IFNgamma)-producing Th1 cells or the novel T helper subset, interleukin-17 (IL-17)-producing Th17 cells, are the pathogenic mediators of joint inflammation in chronic nonautoimmune arthritis. Therefore, this study was aimed at examining whether the Th2-specific transcription factor GATA-3 can regulate arthritis, in an experimental murine model, by modulating Th1 and/or Th17 cell polarization. METHODS: Arthritis was induced with methylated bovine serum albumin (mBSA) in both wild-type and CD2 T cell-specific GATA-3 (CD2-GATA-3)-transgenic mice. At days 1 and 7 after the induction of arthritis, knee joints were scored macroscopically for arthritis severity and for histologic changes. Single-cell suspensions were generated from the spleens, lymph nodes, and inflamed knee joints. Cytokine expression by CD4+ T cells was determined using flow cytometry, and IL-17 expression in the inflamed knee joints was determined by enzyme-linked immunosorbent assay. Analyses of gene expression were performed for Th17-associated factors. RESULTS: Wild-type mice developed severe joint inflammation, including massive inflammatory cell infiltration and bone erosion that increased significantly over time, reaching maximal arthritis scores at day 7. In contrast, only mild joint inflammation was observed in CD2-GATA-3-transgenic mice. This mild effect was further accompanied by systemic and local reductions in the numbers of IL-17+IFNgamma- and IL-17+IFNgamma+, but not IL-17-IFNgamma+, CD4+ T cells, and by induction of Th2 cytokine expression. Moreover, GATA-3 overexpression resulted in reduced gene expression of the Th17-associated transcription factor retinoic acid-related orphan receptor gammat. CONCLUSION: These results indicate that enforced GATA-3 expression protects against severe joint inflammation and bone erosion in mice, accompanied by reduced differentiation of Th17 cells, but not Th1 cells, during mBSA-induced arthritis.

Synovial metastasis: an unusual cause of pain after total knee arthroplasty.

There is only 1 previous report of synovial metastasis to a joint that has been replaced. A 73-year-old man presented for investigation of continuing pain after a left total knee arthroplasty with normal plain radiographs. Synovial biopsy revealed metastatic adenocarcinoma of colorectal type. A barium enema and flexible sigmoidoscopy showed a suspicious lesion at the rectosigmoid junction. The knee is the most frequently affected joint, and the lung is the most common primary site for synovial metastasis. This phenomenon should be considered in the differential diagnosis of continuing pain and effusion postarthroplasty.

Cartilage-derived retinoic acid-sensitive protein in equine synovial fluid from healthy and diseased joints.

REASONS FOR PERFORMING STUDY: More sensitive and specific diagnostic methods for early detection of changes in the joint cartilage are needed. Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a potential marker of cartilage synthesis and regeneration. This is the first study on equine CD-RAP. OBJECTIVES: To evaluate the ability of a commercially available human sandwich ELISA assay to detect equine CD-RAP in synovial fluid from healthy and diseased joints. METHODS: Synovial fluid was collected from 28 horses with no signs of joint disease and from 5 with induced inflammatory arthritis. CD-RAP concentrations were measured using a human CD-RAP ELISA. Intra- and interassay imprecision of the assay were evaluated by multiple measurements on pools of equine synovial fluid. Assay inaccuracy was determined by linearity under dilution. RESULTS: The assay showed moderate to large intra- and interassay variation when applied to equine synovial fluid. Equine CD-RAP was detected in synovial fluid from healthy horses ranged at 8.2-52 ng/ml. Repeated arthrocentesis (after injection of isotonic saline), age, joint or gender did not significantly affect CD-RAP concentrations. Twelve hours after intra-articular injection of lipopolysaccharide, concentrations of CD-RAP were significantly lower than after injection of isotonic saline and remained significantly lower until the end of the study at 144 h. CONCLUSION AND POTENTIAL RELEVANCE: The assay is suitable for longitudinal monitoring of CD-RAP concentration in individual horses. Disease significantly influenced CD-RAP levels. Similar to previous results obtained in man, CD-RAP seems to be a marker of cartilage synthesis and/or regeneration in horses.

[Paharmacological mechanisms of cellular immunity of overall alkali of tongbiling for the treatment of joint destruction].

AIM: To investigate the effect of the overall alkali of Traditional Chinese Medicine tongbiling(TBL) which comprises brucine and strychnine alkaloids on collagen induced-arthritis(CIA) and study its paharmacological mechanisms of cellular immunity. METHODS: Bovine CII was emulsified in Freund's incomplete adjuvant. Wistar rats were injected with Type II collagen intradermally at the base of the tail. After swelling, CIA groups were, randomly divided into physiological saline group and treatment group. Then the swelling of the rats' hindlimbs was evaluated. The whole body of the rats treated on 35 th days was photographed by mammography X-Ray. 96 joints in erosion scoring system and 100 joints in joint spacing narrow(JSN) scoring system were used to observe the joint destruction of CIA from X-Ray comprehensively and objectively. After the rats were killed, the third proximal claw pad of the right hindlimb and left forelimb were stained by HE dying, Neutrophil, lymphocyte, plasmacyte infiltration and hyperplasia of synoviocytes were assessed. Then MTT and Western blot were used to determine the effect of the overall alkali of TBL on proliferation of Jurkat cells and ERK1/2 phosphorylation of Jurkat cells, respectively. RESULTS: Inflammation of CIA joints was aggravated quickly. The swelling of CIA rats treated by MTX and overall alkali of TBL for 35 days was relieved (P<0.05). MTX and overall alkali of TBL inhibited the hyperplasia of synoviocytes. Overall alkali of TBL inhibited the infiltration of lymphocyteS and plasmacytes. Overall alkali of TBL inhibited the proliferation and ERK1/2 phosphorylation of Jurkat cells. CONCLUSION: Overall alkali of TBL could relieve joint inflammation and destruction of CIA rats by blocking the MAPK cell signalling pathway to inhibit the activation and proliferation of T cells. Our study might provide an experimental basis for treatment of rheumatoid arthritis with overall alkali of TBL.