Triptolide inhibits inflammatory response and migration of fibroblast like synovial cells in rheumatoid arthritis through the circRNA 0003353/JAK2/STAT3 signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of triptolide (TPL) on inflammatory response and migration of fibroblast like synovial cells (FLS) in rheumatoid arthritis (RA-FLS) and the mechanism of circular noncoding RNA (circRNA) 0003353 for mediating this effect.@*METHODS@#We collected peripheral blood mononuclear cells (PBMCs) and serum samples from 50 hospitalized RA patients and 30 healthy individuals for detecting the expression of circRNA 0003353, immune and inflammatory indexes (ESR, CRP, RF, anti-CCP, IgA, IgG, IgM, C3, and C4) and DAS28 score. Cultured RA-FLS was treated with 10 ng/mL TPL and transfected with a circRNA 0003353 overexpression plasmid, and cell counting kit-8 (CCK-8) assay and Transwell assay were used to detect the changes in the viability and migration of the cells. Enzyme-linked immunosorbent assay (ELISA) was used to examine the cytokines IL-4, IL-6, and IL-17, and real-time fluorescence quantitative PCR (RT-qPCR) was performed to detect the expression of circRNA 003353; Western blotting was used to detect the expressions of p-JAK2, pSTAT3, JAK2 and STAT3 proteins in the treated cells.@*RESULTS@#The expression of circRNA 0003353 was significantly increased in PBMCs from RA patients and showed a good performance in assisting the diagnosis of RA (AUC=90.5%, P < 0.001, 95% CI: 0.83-0.98). CircRNA 0003353 expression was positively correlated with ESR, RF and DAS28 (P < 0.05). Treatment with TPL significantly decreased the expression of circRNA 0003353, suppressed the viability and migration ability, decreased the expressions of IL-6 and IL-17, and increased the expression IL-4 in cultured RA-FLS in a time-dependent manner (P < 0.01). TNF-α stimulation of RA-FLS significantly increased the ratios of p-JAK2/JAK2 and p-STAT3/STAT3, which were obviously lowered by TPL treatment (P < 0.01). TPL-treated RA-FLS overexpressing circRNA 0003353 showed significantly increased cell viability and migration ability with decreased IL-4 expression and increased IL-6 and IL-17 expressions and ratios of p-JAK2/ JAK2 and p-STAT3/STAT3 (P < 0.01).@*CONCLUSION@#The expression of circRNA 0003353 is increased in PBMCs in RA patients and in RA-FLS. TPL treatment can regulate JAK2/STAT3 signal pathway and inhibit the inflammatory response and migration of RA-FLS through circRNA 0003353.

Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee

ABSTRACT PURPOSE: To evaluate the usefulness of a knee osteoarthritis model through functional, radiological and microscopic changes of the synovial membrane. METHODS: Forty eight rats were divided randomly into two groups. The first received 0.9% saline in the joint and corresponded to the control group. The second was submitted to experimental osteoarthritis of the right knee induced by monosodium iodoacetate and corresponded to the osteoarthritis group. All animals were subjected to comparative tests of forced ambulation and joint movements, inability to articulate and tactile allodynia on day 1 post-experiment by forced ambulation (Roto-rod test), joint assessment of disability (weight bearing test) and assessment of tactile allodynia (Von Frey test). After inflammatory induction they were divided into four sub-groups corresponding to the scheduled death in 7, 14, 21 and 28 days when they were submitted to radiographic examination of the knee, arthrotomy and collection of the synovial membrane. RESULTS: The osteoarthritis group showed significant differences compared to control group on days 7 and 14 in Roto-rod, in weight bearing and Von Frey tests in all days, and in radiological evaluation. Microscopic examination of the synovial membrane showed abnormalities of inflammatory character at all stages. CONCLUSION: The osteoarthritis induced by intra-articular monosodium iodoacetate in rats knee is a good model to be used in related research, because it provides mensurable changes on joint movements, tactile allodynia, progressive radiological degeneration and microscopic inflammation of the synovial membrane, that represent markers for osteoarthritis evaluation

Intra-Articular Pigmentation of Synovium: An Unusual Cause

An unusual grayish brown discoloration of the synovium was found during a knee arthroscopy of a 72-year-old man. He also had similar pigmentation affecting the skin on the legs, arms, hands, and face. It was found he had been taking 400 mg of amiodarone hydrochloride daily for last 7 years. Amiodarone is known to cause a slate grey pigmentation of skin and cornea, but we believe this is the first report of amiodarone-induced pigmentation of the synovium. The arthroscopist should be aware of the possibility of drug-related synovial pigmentation and include this in differential diagnosis.

Malformación vascular de bajo flujo sinovial de la rodilla (hemangiolinfangioma): Reporte de caso / Low-low synovial vascular malformation of the knee (hemangiolymphangioma): Case report

Introducción: La malformación vascular venosa de bajo lujo se desarrolla generalmente durante la primera infancia y puede ser una causa poco frecuente de derrame recurrente de larodilla. La clínica, las pruebas de laboratorio y las radiografías suelen ser inespecíficas. Objetivo: Describir una patología infrecuente en pediatría, para enfatizar en la correcta clasificación y sospecha. Caso Clínico: Paciente de 2 años con historia de episodios de derrame articular de la rodilla derecha que requirió múltiples hospitalizaciones y tratamientos antibióticos. Exámenes de laboratorio normales. La radiografía simple de la rodilla no mostró cambios óseos. La resonancia magnética reportó malformación vascular de bajo lujo. Se realizó resección quirúrgica que evidenció lesión vascular entre las fibras musculares del vasto lateral del cuádriceps con extensión hasta la cápsula de la rodilla y disección de las fibras hasta el vasto lateral de la pierna derecha. El estudio histológico fue compatible con malformación vascular de bajo lujo. Ante el hallazgo benigno y la evolución favorable, continuó con tratamiento ambulatorio. Conclusiones: Aunque la malformación vascular de bajo lujo sinovial es una patología poco frecuente en la población pediátrica, debería considerarse la realización de un diagnóstico diferencial en pacientes con aparición repetida de hemartrosis sin historia de coagulopatía ni hemofilia.

Introduction: Low-low vascular malformation, which usually develops during the first stage of infancy, is a rare cause of recurrent effusion of the knee. History, laboratory and X-rays are usually non-specific. Objective: To describe a rare disease in pediatrics, emphasizing the correct classification and suspicion. Case Report: A case is presented of a two-year-old patient with a history of effusion of the right knee who required multiple hospitalizations and antibiotic treatments. Laboratory work-up was normal. Plain X-rays of the knee revealed no bone changes. MR imaging reported low-low vascular malformation. Surgical resection was performed, evidencing vascular lesion among the muscle fibers of the vastus lateralis of quadriceps until the capsule of the knee, as well as dissection of the fibers until the vastus lateralis of the right leg. Histology was consistent with low-low vascular malformation. Due to the benign outcome and favorable evolution, an outpatient management was possible. Conclusions: Although low-low synovial vascular malformation is a rare disease among the pediatric population, it should be considered in the differential diagnosis of patients with repeated hemarthrosis and no history of either coagulopathy or hemophilia.

Effects of immobilization and remobilization on the ankle joint in Wistar rats

A sprained ankle is a common musculoskeletal sports injury and it is often treated by immobilization of the joint. Despite the beneficial effects of this therapeutic measure, the high prevalence of residual symptoms affects the quality of life, and remobilization of the joint can reverse this situation. The aim of this study was to analyze the effects of immobilization and remobilization on the ankle joint of Wistar rats. Eighteen male rats had their right hindlimb immobilized for 15 days, and were divided into the following groups: G1, immobilized; G2, remobilized freely for 14 days; and G3, remobilized by swimming and jumping in water for 14 days, performed on alternate days, with progression of time and a series of exercises. The contralateral limb was the control. After the experimental period, the ankle joints were processed for microscopic analysis. Histomorphometry did not show any significant differences between the control and immobilized/remobilized groups and members, in terms of number of chondrocytes and thickness of the articular cartilage of the tibia and talus. Morphological analysis of animals from G1 showed significant degenerative lesions in the talus, such as exposure of the subchondral bone, flocculation, and cracks between the anterior and mid-regions of the articular cartilage and the synovial membrane. Remobilization by therapeutic exercise in water led to recovery in the articular cartilage and synovial membrane of the ankle joint when compared with free remobilization, and it was shown to be an effective therapeutic measure in the recovery of the ankle joint.

Extra-pulmonary manifestations of paracoccidioidomycosis associated with acquired immunodeficiency syndrome: a case report

We present a patient with Paracoccidioidomycosis/HIV coinfection which has been investigated because of chronic monoarthritis and mucocutaneous lesions. A biopsy of the synovial membrane and skin revealed structures consistent with Paracoccidioides brasiliensis. At diagnosis, the count of CD4 + T cells was 44 cells/mm3. We emphasize the importance of clinical suspicion of Paracoccidioidomycosis in patients with HIV/AIDS who live in or are from risk areas.

study of serum levels of B cell-attracting chemokine-13 [CXCL 13] and rheumatologic manifestations of chronic hepatitis C virus infection in a cohort of Egyptian patients

Many rheumatologic manifestations have been associated with Hepatitis C virus [HCV] infection including; arthralgia, myalgia, fatigue, fibromyalgia, vasculitis, and sicca syndrome. The relationship between emergence and persistence of intrahepatic or circulating B cell clonotypes and HCV infection is still unknown. However accumulating evidences indicate that certain chemokines play a critical role in providing the appropriate environment for activation and expansion of naive lymphocytes, one of these chemokines is B cell-attracting chemokine-13 [CXCL13]. CXCL13 is a major regulator of B-cell trafficking. This study evaluates circulating levels of CXCL13 protein in chronically HCV-infected Egyptian patients compared with healthy controls and its association with articular synovial hypertrophy. Rheumatic manifestations were present in 85% of patients; included fatigue [20%], arthralgia [the commonest manifestation] [65%], fibromyalgia [22%], myalgia [37%], Rayunad's phenomenon [10%], peripheral neuropathy and arthritis [2.5%], and tendenitis [7.5]. Cryoglobulins recorded in this study were of type II and III mixed cryoglobulins [MC] positive in 25% all of which showed positive rheumatoid factor [RF]. Significant low levels of C3 and C4 were reported in the patient group. CXCL13 serum levels were significantly high in the patient group especially in the MC positive group compared to controls. The highest levels of CXCL13 were significantly associated with rheumatologic manifestations with or without mixed cryoglobulinemia and significantly associated with articular synovial hypertrophy

Over-expression of extracellular superoxide dismutase in mouse synovial tissue attenuates the inflammatory arthritis

Oxidative stress such as reactive oxygen species (ROS) within the inflamed joint have been indicated as being involved as inflammatory mediators in the induction of arthritis. Correlations between extracellular-superoxide dismutase (EC-SOD) and inflammatory arthritis have been shown in several animal models of RA. However, there is a question whether the over-expression of EC-SOD on arthritic joint also could suppress the progression of disease or not. In the present study, the effect on the synovial tissue of experimental arthritis was investigated using EC-SOD over-expressing transgenic mice. The over-expression of EC-SOD in joint tissue was confirmed by RT-PCR and immunohistochemistry. The degree of the inflammation in EC-SOD transgenic mice was suppressed in the collagen-induced arthritis model. In a cytokine assay, the production of pro-inflammatory cytokines such as, IL-1beta, TNFalpha, and matrix metalloproteinases (MMPs) was decreased in fibroblast-like synoviocyte (FLS) but not in peripheral blood. Histological examination also showed repressed cartilage destruction and bone in EC-SOD transgenic mice. In conclusion, these data suggest that the over-expression of EC-SOD in FLS contributes to the activation of FLS and protection from joint destruction by depressing the production of the pro-inflammatory cytokines and MMPs. These results provide EC-SOD transgenic mice with a useful animal model for inflammatory arthritis research.

Intra-articular lipoma arborescens of the knee joint

Intra-articular lipoma arborescens [LA] is a rare entity that can present with monoarticular or polyarticular involvement of joints such as knees, ankles, hips, shoulders, and elbows. We describe a case in a 26-year-old man who presented with intermittent pain and swelling of the left knee joint for the previous 2 years. Physical examination showed only tenderness over the medial line of the left knee joint. MRI found only joint effusion; therefore, the patient was referred to the orthopedic clinic where he underwent arthroscopy, which revealed a diffuse yellow soft tissue synovial papillary growth involving both medial and lateral gutters of the suprapatellar pouch. A biopsy reported intra-articular LA. This is the first case of LA reported in Saudi Arabia. LA should be included in the clinical and radiologic differential diagnosis of cases with persistent knee joint effusion

Regulation of B cell activating factor (BAFF) receptor expression by NF-kappaB signaling in rheumatoid arthritis B cells

B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-kappaB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-kappaB inhibitors. NF-kappaB p65, NF-kappaB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-kappaB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-kappaB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-kappaB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.

Sinovitis villonodular pigmentada de rodilla: resultado en el tratamiento artroscópico en 10 pacientes / Pigmented villonodular synovitis of the knee: arthroscopic treatment in 10 patients

Objective: To report our experience in the diagnosis, treatment and follow up of patients with clinical and histopathological diagnosis of knee pigmented villonodular synovitis (PVNS). We performed a descriptive retrospective study of a consecutive series of 10 patients treated by knee PVNS in a ten years period. The mean follow-up was 39 months. Clinical records and surgery protocols were reviewed; functional clinical results were documented using the Lysholm score. Results: Nine patients consulted by pain and one case corresponded a incidental finding. All patients were initially treated with an arthroscopic synovectomy. Two patients presented relapse and as a final treatment they underwent total knee arthroplasty. The mean post-operative Lysholm score at follow up was 95 (90-100) points. Conclusion: We documented low incidence of knee PVNS. The total recurrence in our series was of 20 percent.

Objetivo: Reportar nuestra experiencia en el diagnóstico, tratamiento y evolución de pacientes con diagnóstico clínico-histopatológico de sinovitis villonodular pigmentada (SVNP) de rodilla tratados en nuestro centro. Métodos: Estudio retrospectivo, descriptivo, de una serie consecutiva de diez pacientes tratados por SNVP de rodilla en un período 10 años con un seguimiento promedio de 39 meses. Se revisaron fichas clínicas, protocolos quirúrgicos y documentamos los resultados funcionales subjetivos mediante el puntaje de Lysholm. Resultados: Nueve pacientes consultaron por dolor y en un caso correspondió a un hallazgo. A todos los pacientes se les realizó inicialmente una sinovectomía artroscópica. Dos pacientes presentaron recidiva y como tratamiento final se les realizó una artrosplastía total de rodilla. El promedio del puntaje Lysholm postoperatorio consignado durante el seguimiento fue 95 (90-100). Conclusión: La SVNP de rodilla corresponde a una patología de baja frecuencia, que presenta una recidiva de un 20 por ciento tras un tratamiento artroscópico.

Lipoma Arborescens of the knee: report of a case with full range of motion

This report describes a rare intra-articular benign tumor, lipoma arborescens, of the knee joint in a 21 year-old female. The patient suffered from left knee joint swelling for five years with occasional pain. Swelling was soft and boggy in the suprapatellar area. Motion of joint was complete. No abnormality was detected in any laboratory tests. MRI showed a large soft tissue density in the suprapatellar area with high signal intensity on T[1] and T[2] weighted images. Operative arthroscopy revealed a creamy brown hypertrophied synovium with diffuse papillary processes characterized by villous proliferation of the synovium infiltrated by mature fat tissue, chronic inflammatory cells and vessels as seen in the pathologic slides. Lipoma arborescens or villous lipomatous proliferation of the synovial membrane should be distinguished from other similar lipomatoid conditions such as synovial lipoma and Hoffa disease. Lipoma arborescens should be considered in patients with painless, slowly progressive swelling of a joint, especially the knee

Expression of osteopontin in synovial tissue of rheumatoid arthritis: its relation to disease activity and severity

To demonstrate the expression of osteopontin in synovial tissue of patients with rheumatoid arthritis and to correlate it with disease activity and severity in order to find out its possible role in the pathogenesis of the disease. This study was conducted on 30 RA patients and 10 control subjects with post traumatic knee injury. All patients were subjected to full medical history taking, thorough clinical examination with special attention to articular manifestations [Modified disease activity score] [DAS], and spread severity index [SSI]. Laboratory investigations included: CBC, ESR, CRP and RF. Radiological investigations included: plain x-ray of the affected knee joint using Larsen's score for assessment of joint damage and expression of osteopontin [OPN] in synovial tissues of both patients and controls was determined by immunohistochemical staining of formalin fixed, paraffin embedded synovial tissues. We demonstrated by immunohistochemistry that OPN was detected as brown cytoplasmic staining expressed predominantly in the lining layer of rheumatoid synovium rather than the sublining layer and it was absent in the lymphoid aggregates. In contrast, synovial tissue of the control group showed weak scattered staining for OPN. We found a highly statistical significant difference between RA patients and controls regarding the synovial expression of OPN which was highly associated with the activity. Also, percentage of OPN positive cells was highly associated with the severity of RA assessed clinically by SSI and radiological [p<0.01]. Osteopontin is critically involved in the pathogenesis of both inflammatory and joint-destructive processes in rheumatoid arthritis. OPN may reflect disease activity and can be used as a marker of disease severity

Correlation of synovium osteoprotegrin with magnetic resonance imaging in rheumatoid arthritis

To demonstrate the role of Osteoprote grin [OPG] expression in the synovium in the pathogenesis of rheumatoid arthritis [RA] joint damage, and correlate it with Magnetic Resonance Imaging [MRI] finding. Twenty RA patients and five controls were included. RA disease activity was assessed by disease activity score [DAS 28]. MRI examination of knee joint, including evaluation of inflammation using synovitis score and evaluation of destruction with an erosion score, were performed. Knee joint's synovial biopsy specimens were obtained, by arthroscopy, to demonstrate the degree of expression of OPG by using immunohistochemical staining with monoclonal antibodies, and to study the histopathological activity scores by histopathological examination. The OPG expression was deficient [grade 0, 1] in 70% of synovial cells and 85% of endothelial cells lining of the synovial blood vessels, and grade I and 2 in 70% of infiltrating cells in active RA synovium. There was no significant association between OPG expression score [synovial, endothelial, infiltrating cells] and disease duration, number of tender swollen joints, ESR and Larsen score. There was a significant inverse correlation between OPG expression [synovial, infiltrating] and MRI erosion score. There was a highly significant correlation between MRI synovitis score and ESR, CRP, pain score, histopathological synovium score [p<0.01] and significant negative correlation with erosion score. We concluded that decrease in OPG expression in synovium has a role in pathogenesis of joint damage in RA patients, and MRI is considered a sensitive test to detect pathological lesion in joint damage in RA patients

adiponectin have a role in the pathogenesis of rheumatoid arthritis?

To elucidate the involvement of adipocytokines "Adiponectin" in the pathogenesis of rheumatoid arthritis [RA] by measuring serum and synovial fluid levels of adiponectin in RA patients and also by evaluating its expression in RA synovial tissue to find out its possible role in disease activity and severity in order to throw light on possible new strategy in the management of RA. Twenty RA patients and ten subjects with acute post traumatic knee effusion - who served as a control group-were recruited for this study. Serum adiponectin levels were measured using enzyme linked immunosorbent [ELISA]. Synovial fluid [SF] levels of adiponectin, IL-6 and pro MMP-1 were measured by ELISA. Modified disease activity score [DAS] and Larsen score were assessed in RA patients. Synovial tissue [ST] specimens were obtained from control subjects and RA patients. These specimens were assessed immunohistochemically for adiponectin and graded in a semiquantitative scale. Serum adiponectin was significantly raised in RA patients compared to controls [p<0.05]. There was a highly statistically significant increase in SF adiponectin, SF Pro MMP-1, ST adiponectin expression in RA patients compared to controls [p<0.01], while there was a significant increase in SF IL-6 in RA patients compared to controls [p<0.05]. SF adiponectin correlated positively with each of ST adiponectin expression, SF IL-6, SF pro MMP-1 [p<0.01]. A highly significant positive correlation was found between SF levels of adiponectin and each of DAS and Larsen score [p<0.01]. Adiponectin is expressed in the RA synovium and it stimulates the production of key mediators of destructive arthritis, IL-6 and pro MMP-1, so targeting the proinflammatory cascade of adiponectin may represent an exciting new therapeutic tool in RA

Synovial hemangioma: a rare benign synovial lesion.

We report an unusual case of a 10-year-old female with complaints of pain and swelling of the right knee for the last 4 years along with the limitation of movement for last 1 year. Repeated fine needle aspirations yielded blood and a provisional diagnosis of hemarthrosis was suggested. Coagulation profile subsequently carried out was found to be within normal limits. Arthroscopic biopsy was performed and tissue was sent for histopathological examination. A diagnosis of synovial hemangioma was made. Subtotal synovectomy was performed and the lesion was completely excised. The patient is completely asymptomatic and shows no signs of recurrence at 1 year.

Expression of CCR2A, an isoform of MCP-1 receptor, is increased by MCP-1, CD40 ligand and TGF-beta in fibroblast like synoviocytes of patients with RA

Cytokine and chemokine receptors play a key role in inflammation caused by rheumatoid arthritis (RA). Two isoforms of human CC chemokine receptor R2 (CCR2), the receptor of monocyte chemoattractant protein 1 (MCP-1), have been identified but their relative expression in fibroblast-like synoviocytes (FLS) and their contribution to inflammatory responses mediated by MCP-1 or inflammatory cytokines in patients with RA remain uncertain. We examined the pattern of expression of two CCR2 isoforms upon stimulation by proinflammatory cytokines and CD40 ligation. FLS were prepared from the synovial tissues of RA patients and cultured in the presence of MCP-1, soluble CD40 ligand (sCD40L), TGF-beta, IL-1beta, IL-18, IL-15, and LPS. CCR2A and CCR2B expression was examined by immunohistochemistry, RT-PCR and western blot analysis. IL-15, TNF-alpha and MCP-1 production was determined by ELISA. Immunohistochemistry showed that CCR2A is highly expressed in RA synovium compared with OA synovium. Transcripts of both CCR2A and CCR2B were detected in FLS. Exogenous MCP-1, CD40L, TGF-beta, and IL-15 significantly increased the expression of CCR2A but not CCR2B. Exposure of FLS to sCD40L caused strong upregulation of CCR2A but not of CCR2B protein expression. MCP-1 increased the proliferation of FLS and the production of IL-15, TNF-alpha, and IL-18. Because CCR2A is the main target of regulation by cytokines and CD40 ligation, the relatively higher expression of CCR2A on the cell surface suggests that this isoform of MCP-1 receptor functions as the principal mediator of inflammatory signals in RA FLS.

A descriptive clinical evaluation of arthroscopic synovectomy in rheumatoid knees: a prospective study.

OBJECTIVE: To evaluate the clinical outcome of arthroscopic synovectomy for persistent rheumatoid synovitis of the knee joints. DESIGN: Prospective clinical study. SETTING: Kasturba Medical College Hospital, Manipal. PATIENTS: Fifty two knee joints in 46 patients. MEASUREMENTS: The effect of the procedure and its influence in the progression of the disease process on knee joints were assessed in terms of reduction of pain, improvement in range of motion, improvement in functional activity and recurrence of synovitis with effusion. RESULTS: During the average follow up period of 5 years, the patients showed appreciable improvement (90% of knee joints) until 3 years of follow up. At the end of 5 years of follow up, it reduced to about 75%. CONCLUSIONS: Arthroscopic synovectomy along with medical treatment can control the disease process and preserve the knee joint function for up to 3 years.

Rheumatoid arthritis cytokines and hypoxia. What is the link?

Rheumatoid arthritis [RA] is a chronic systemic inflammatory disorder that affects approximately 1% of the population, in a female to male ratio of 3:1. The disease can occur at any age, but it is most common among those aged 40-70 years. Despite many years of study, the etiology of RA is still undefined. However, with increased understanding of the immune system the pathogenesis of RA has become clearer. A large bulk of data suggests that T lymphocytes and macrophages play a critical role in the initiation and perpetuation of synovial inflammation. Recently, the cytokine profile of T helper cells has been associated with the disease, the cytokine repertoire of inflamed synovia is categorized as that of T helper 1 response. Moreover, in RA elevated levels of pro-inflammatory or inflammatory cytokines such as Tumor Necrosis Factor - alpha [TNF-alpha] and Interleukin -1 beta [IL-1beta] have been detected. Hypoxia up-regulates TNF-alpha and IL-1beta; therefore, considerable research interest has been focused on the biological consequences of the hypoxic nature of the rheumatoid synovium. Hypoxia might underlie the functional polarization of the T cells and cytokine production, and thus may contribute to the progression and persistence of the disease. In this short review, we discuss our current knowledge of the link between cytokines and RA and the role of hypoxia in the pathogenesis of the disease

Histology of two rice bodies isolated from the stifle of an adult draught horse stallion

In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.