Intraarticular glucocorticoid treatment reduces inflammation in synovial cell infiltrations more efficiently than in synovial blood vessels.

PubMed

af Klint, Erik; Grundtman, Cecilia; Engström, Marianne; Catrina, Anca Irinel; Makrygiannakis, Dimitrios; Klareskog, Lars; Andersson, Ulf; Ulfgren, Ann-Kristin

2005-12-01

To investigate whether intraarticular (IA) glucocorticoid (GC) therapy diminishes synovial cell infiltration, vascularity, expression of proinflammatory cytokines, and adhesion molecule levels in patients with chronic arthritides. Thirty-one patients with chronic arthritides received a single IA injection of triamcinolone hexacetonide to treat active large-joint inflammation. Synovial biopsy specimens were obtained with arthroscopic guidance before and 9-15 days after injection. The presence of T lymphocytes, macrophages, intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), the pan-endothelial marker CD31, and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor (TNF), and high mobility group box chromosomal protein 1 (HMGB-1) was studied by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction. IA GC treatment resulted in good clinical response in 29 of 31 joints. After therapeutic intervention, the number of synovial T lymphocytes declined, whereas the number of macrophages remained unchanged. Overall synovial protein expression of TNF, IL-1beta, extranuclear HMGB-1, VEGF, and ICAM-1 was reduced at followup tissue sampling, while no significant effects were observed regarding vascularity. In contrast, expression of IL-1alpha, VEGF, and cytoplasmic HMGB-1 protein in vascular endothelial cells was not affected. GC therapy down-regulated levels of messenger RNA encoding IL-1alpha and IL-1beta, but not TNF or HMGB-1. Synovial cell infiltration and proinflammatory cytokine expression were affected in a multifaceted manner by IA GC treatment. Marked reduction of synovial T lymphocytes, TNF, IL-1beta, extranuclear HMGB-1, ICAM-1, and VEGF occurred in association with beneficial clinical effects. Unexpectedly, macrophage infiltration and proinflammatory endothelial cytokine expression remained unchanged. These findings may reflect mechanisms controlling the transiency

Synovial sarcoma of nerve.

PubMed

Scheithauer, Bernd W; Amrami, Kimberly K; Folpe, Andrew L; Silva, Ana I; Edgar, Mark A; Woodruff, James M; Levi, Allan D; Spinner, Robert J

2011-04-01

Tumors of peripheral nerve are largely neuroectodermal in nature and derived from 2 elements of nerve, Schwann or perineurial cells. In contrast, mesenchymal tumors affecting peripheral nerve are rare and are derived mainly from epineurial connective tissue. The spectrum of the latter is broad and includes lipoma, vascular neoplasms, hematopoietic tumors, and even meningioma. Of malignant peripheral nerve neoplasms, the vast majority are primary peripheral nerve sheath tumors. Malignancies of mesenchymal type are much less common. To date, only 12 cases of synovial sarcoma of nerve have been described. Whereas in the past, parallels were drawn between synovial sarcoma and malignant glandular schwannoma, an uncommon form of malignant peripheral nerve sheath tumor, molecular genetics have since clarified the distinction. Herein, we report 10 additional examples of molecularly confirmed synovial sarcoma, all arising within minor or major nerves. Affecting 7 female and 3 male patients, 4 tumors occurred in pediatric patients. Clinically and radiologically, most lesions were initially thought to be benign nerve sheath tumors. On reinterpretation of imaging, they were considered indeterminate in nature with some features suspicious for malignancy. Synovial sarcoma of nerve, albeit rare, seems to behave in a manner similar to its more common, soft tissue counterpart. Those affecting nerve have a variable prognosis. Definitive recommendations regarding surgery and adjuvant therapies await additional reports and long-term follow-up. The literature is reviewed and a meta-analysis is performed with respect to clinicopathologic features versus outcome. Copyright © 2011. Published by Elsevier Inc.

Basic radiological assessment of synovial diseases: a pictorial essay

PubMed Central

Turan, Aynur; Çeltikçi, Pınar; Tufan, Abdurrahman; Öztürk, Mehmet Akif

2017-01-01

The synovium is a specialized tissue lining the synovial joints, bursae, and tendon sheaths of the body. It is affected by various localized or systemic disorders. Synovial diseases can be classified as inflammatory, infectious, degenerative, traumatic, hemorrhagic, and neoplastic. Damage in other intraarticular structures, particularly cartilages, generally occurs as a part of pathologic processes involving the synovium, leading to irreversible joint destruction. Imaging has an essential role in the early detection of synovial diseases prior to irreversible joint damage. Obtaining and understanding characteristic imaging findings of synovial diseases enables a proper diagnosis for early treatment. This article focuses on the recent literature that is related with the role of imaging in synovial disease. PMID:28638696

Osteoarthritis screening using Raman spectroscopy of dried human synovial fluid drops

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Mandair, Gurjit S.; Esmonde-White, Francis W. L.; Raaii, Farhang; Roessler, Blake J.; Morris, Michael D.

2009-02-01

We describe the use of Raman spectroscopy to investigate synovial fluid drops deposited onto fused silica microscope slides. This spectral information can be used to identify chemical changes in synovial fluid associated with osteoarthritis (OA) damage to knee joints. The chemical composition of synovial fluid is predominately proteins (enzymes, cytokines, or collagen fragments), glycosaminoglycans, and a mixture of minor components such as inorganic phosphate crystals. During osteoarthritis, the chemical, viscoelastic and biological properties of synovial fluid are altered. A pilot study was conducted to determine if Raman spectra of synovial fluid correlated with radiological scoring of knee joint damage. After informed consent, synovial fluid was drawn and x-rays were collected from the knee joints of 40 patients. Raman spectra and microscope images were obtained from the dried synovial fluid drops using a Raman microprobe and indicate a coarse separation of synovial fluid components. Individual protein signatures could not be identified; Raman spectra were useful as a general marker of overall protein content and secondary structure. Band intensity ratios used to describe protein and glycosaminoglycan structure were used in synovial fluid spectra. Band intensity ratios of Raman spectra indicate that there is less ordered protein secondary structure in synovial fluid from the damage group. Combination of drop deposition with Raman spectroscopy is a powerful approach to examining synovial fluid for the purposes of assessing osteoarthritis damage.

Synovial osteochondromatosis in hereditary arthro-ophthalmopathy (Wagner-Stickler syndrome).

PubMed

Tins, Bernhard; Cassar-Pullicino, Victor

2003-05-01

A case of bilateral synovial osteochondromatosis in a patient with hereditary arthro-ophthalmopathy is presented. The osteochondral lesions were largely calcified in one joint and largely chondromatous in the other. Typical features of hereditary arthro-ophthalmopathy are reviewed and it is hypothesised that the abnormal collagen in this syndrome is responsible for the development of synovial osteochondromatosis. Synovial manifestations of skeletal dysplasias have to our knowledge not been described previously but we suggest that synovial osteochondromatosis can be the manifestation of an underlying skeletal dysplasia.

The Rheological Properties of the Biopolymers in Synovial Fluid

NASA Astrophysics Data System (ADS)

Krause, Wendy E.; Klossner, Rebecca R.; Wetsch, Julie; Oates, Katherine M. N.; Colby, Ralph H.

2005-03-01

The polyelectrolyte hyaluronic acid (HA, hyaluronan), its interactions with anti-inflammatory drugs and other biopolymers, and its role in synovial fluid are being studied. We are investigating the rheological properties of sodium hyaluronate (NaHA) solutions and an experimental model of synovial fluid (comprised of NaHA, and the plasma proteins albumin and γ-globulins). Steady shear measurements on bovine synovial fluid and the synovial fluid model indicate that the fluids are highly viscoeleastic and rheopectic (stress increases with time under steady shear). In addition, the influence of anti-inflammatory agents on these solutions is being explored. Initial results indicate that D-penicillamine and hydroxychloroquine affect the rheology of the synovial fluid model and its components. The potential implications of these results will be discussed.

Primary pleuropulmonary synovial sarcoma with brain metastases in a paediatric patient: an unusual presentation.

PubMed

Chirmade, Pushpak Chandrakant; Parikh, Sonia; Anand, Asha; Panchal, Harsha; Patel, Apurva; Shah, Sandip

2017-01-01

Primary lung neoplasms are rare in children. The most common primary lung malignancies in children are pleuropulmonary blastoma and carcinoid tumour. Synovial sarcoma (SS) accounts for approximately 1% of all childhood malignancies. In absolute terms, the SS of the lungs and pleura are extremely rare and pose a diagnostic difficulty. Soft tissue sarcomas usually have a high potential for metastases, however, metastasis to the brain is rare, even in widely disseminated disease, and it has been described only in 3 case reports previously. Primary pleuropulmonary SS with brain metastases is even rarer. Here we present a case of an 11-year-old boy who presented with respiratory complaints, viz. fever and cough for 20 days. Initial impression was lung abscess, however, on histopathological, immunohistochemical and molecular study, the disorder was diagnosed as synovial sarcoma. After a week from the first consult, the child developed neurological symptoms, viz., an episode of convulsion and gradually worsening power of the lower limb. Computed tomography scan and Magnetic Resonance Spectroscopy was suggestive of brain metastases. Given the rarity of primary lung neoplasms in children, clinical detection remains a challenge. Delayed diagnoses are common as respiratory symptoms may be attributed to inflammatory or infective processes. Primary pleuropulmonary synovial sarcoma is a rare tumour and it is not known to commonly metastasise to the brain. Though rare, primary pleuropulmonary SS should be considered an important differential among peadiatric primary lung neoplasms due to its potential for curability if detected early, and more aggressive metastatic pattern, e.g. brain metastases making early detection imperative.

Magnetic particle translation as a surrogate measure for synovial fluid mechanics.

PubMed

Shah, Yash Y; Maldonado-Camargo, Lorena; Patel, Neal S; Biedrzycki, Adam H; Yarmola, Elena G; Dobson, Jon; Rinaldi, Carlos; Allen, Kyle D

2017-07-26

The mechanics of synovial fluid vary with disease progression, but are difficult to quantify quickly in a clinical setting due to small sample volumes. In this study, a novel technique to measure synovial fluid mechanics using magnetic nanoparticles is introduced. Briefly, microspheres embedded with superparamagnetic iron oxide nanoparticles, termed magnetic particles, are distributed through a 100μL synovial fluid sample. Then, a permanent magnet inside a protective sheath is inserted into the synovial fluid sample. Magnetic particles translate toward the permanent magnet and the percentage of magnetic particles collected by the magnet in a given time can be related to synovial fluid viscosity. To validate this relationship, magnetic particle translation was demonstrated in three phases. First, magnetic particle translation was assessed in glycerol solutions with known viscosities, demonstrating that as fluid viscosity increased, magnetic particle translation decreased. Next, the relationship between magnetic particle translation and synovial fluid viscosity was assessed using bovine synovial fluid that was progressively degenerated via ultrasonication. Here, particle collection in a given amount of time increased as fluid degenerated, demonstrating that the relationship between particle collection and fluid mechanics holds in non-Newtonian synovial fluid. Finally, magnetic particle translation was used to assess differences between healthy and OA affected joints in equine synovial fluid. Here, particle collection in a given time was higher in OA joints relative to healthy horses (p<0.001). Combined, these data demonstrate potential viability of magnetic particle translation in a clinical setting to evaluate synovial fluid mechanics in limited volumes of synovial fluid sample. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ultrasound-guided synovial Tru-cut biopsy: indications, technique, and outcome in 111 cases.

PubMed

Sitt, Jacqueline C M; Griffith, James F; Lai, Fernand M; Hui, Mamie; Chiu, K H; Lee, Ryan K L; Ng, Alex W H; Leung, Jason

2017-05-01

To investigate the diagnostic performance of ultrasound-guided synovial biopsy. Clinical notes, pathology and microbiology reports, ultrasound and other imaging studies of 100 patients who underwent 111 ultrasound-guided synovial biopsies were reviewed. Biopsies were compared with the final clinical diagnosis established after synovectomy (n = 43) or clinical/imaging follow-up (n = 57) (mean 30 months). Other than a single vasovagal episode, no complication of synovial biopsy was encountered. One hundred and seven (96 %) of the 111 biopsies yielded synovium histologically. Pathology ± microbiology findings for these 107 conclusive biopsies comprised synovial tumour (n = 30, 28 %), synovial infection (n = 18, 17 %), synovial inflammation (n = 45, 42 %), including gouty arthritis (n = 3), and no abnormality (n = 14, 13 %). The accuracy, sensitivity, and specificity of synovial biopsy was 99 %, 97 %, and 100 % for synovial tumour; 100 %, 100 %, and 100 % for native joint infection; and 78 %, 45 %, and 100 % for prosthetic joint infection. False-negative synovial biopsy did not seem to be related to antibiotic therapy. Ultrasound-guided Tru-cut synovial biopsy is a safe and reliable technique with a high diagnostic yield for diagnosing synovial tumour and also, most likely, for joint infection. Regarding joint infection, synovial biopsy of native joints seems to have a higher diagnostic yield than that for infected prosthetic joints. • Ultrasound-guided Tru-cut synovial biopsy has high accuracy (99 %) for diagnosing synovial tumour. • It has good accuracy, sensitivity, and high specificity for diagnosis of joint infection. • Synovial biopsy of native joints works better than biopsy of prosthetic joints. • A negative synovial biopsy culture from a native joint largely excludes septic arthritis. • Ultrasound-guided Tru-cut synovial biopsy is a safe and well-tolerated procedure.

Differences in synovial fluid cytokine levels but not in synovial tissue cell infiltrate between anti-citrullinated peptide/protein antibody-positive and –negative rheumatoid arthritis patients

PubMed Central

2013-01-01

Introduction Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum. Methods A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array. Results A total of 83 patients underwent arthroscopy, with a mean age of 55.9 ± 12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1β, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients. Conclusions In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology. PMID:24485167

Synovial sarcoma: a rare presentation of parapharyngeal mass.

PubMed

Shaariyah, Mohd Mokhtar; Mazita, Ami; Masaany, Mansor; Razif, Mohd Yunus; Isa, Mohamed Rose; Asma, Abdullah

2010-06-01

Synovial sarcoma is a rare soft tissue sarcoma of the head and neck region involving the parapharyngeal space. The diagnosis of synovial sarcoma can be very challenging to the pathologists. We present a rare case of parapharyngeal synovial sarcoma in a young female patient who had a two-month history of left cervical intumescent mass at level II. The fine needle aspiration cytology of the mass was proved inconclusive. Transcervical excision of the mass was performed and the first case of parapharyngeal sarcoma was identified in our center by fluorescence in situ hybridization (FISH) technique. Repeat imaging revealed residual tumor. The patient successfully underwent a second excision of the residual tumor and received adjuvant radiotherapy.

Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis.

PubMed

Takeba, Y; Suzuki, N; Takeno, M; Asai, T; Tsuboi, S; Hoshino, T; Sakane, T

1997-12-01

To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA. The effects of SOM on proinflammatory cytokine (interleukin-6 [IL-6] and IL-8) and collagenase production by RA synovial cells were estimated by enzyme-linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription-polymerase chain reaction (RT-PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT-PCR. Local production of SOM was estimated by RT-PCR and immunohistochemical staining. Physiologic concentrations (approximately 10(-10)M) of SOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast-like synovial cells, and the expression of SOMR-2 was up-regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast-like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA. SOM inhibited aberrant synovial cell function in patients with RA, suggesting possible clinical applications of this neuropeptide.

Analysis of synovial fluid of the Capybara's stifle joints.

PubMed

Brombini, Giovanna C; Rahal, Sheila C; Bergamini, Bruno C S; Lopes, Raimundo S; Santos, Ivan F C; Schimming, Bruno C

2017-03-01

Although normal synovial fluid has been well characterized in domestic animals such as dogs, cats, horses, and cows, the available information on larger rodents is scarce. The purpose of the study was to analyze the physical, chemical, and cytologic characteristics of the synovial fluid in stifle joints of Capybaras. Five free-ranging adult female Capybaras (Hydrochoerus hydrochaeris), weighing from 37 to 56 kg were used. Synovial fluid was obtained by aspiration of 10 stifle joints. Samples were analyzed for physical, chemical, and cytologic properties. Spontaneous clotting was negative in 9 samples. Most synovial fluids had pH 8, and protein concentrations ranged from 1.6 to 3.6 g/dL. The mucin clot test was good in all 6 samples that were tested. Nucleated cell counts ranged from 140 to 508 cells/μL. Relative differential leukocyte counts demonstrated a predominance of mononuclear cells (97.6%), including 76.2% undifferentiated mononuclear cells, 18.1% macrophages, and 3.66% lymphocytes. Polymorphonuclear cells included 1.83% neutrophils and 0.2% eosinophils. The synovial stifle joint fluid of healthy free-ranging adult Capybaras is clear, colorless, viscous, and with chemical features and cytologic findings similar to those seen in domestic animals. © 2017 American Society for Veterinary Clinical Pathology.

An investigation of the optical properties of cholesterol crystals in human synovial fluid

NASA Astrophysics Data System (ADS)

Zakharova, M. M.; Nasonova, V. A.; Konstantinova, A. F.; Chudakov, V. S.; Gaĭnutdinov, R. V.

2009-05-01

The synovial fluid of patients with rheumatoid diseases has been investigated. The presence of cholesterol crystals in the synovial fluid is revealed by polarization microscopy. A comparative analysis of the composition and properties of synovial fluid and the optical properties of cholesterol crystals is performed. It is established that the size, number, and growth of cholesterol crystals are interrelated to the synovial fluid composition. It is shown that rheumatoid diseases can be accompanied by the formation of cholesterol crystals in the synovial fluid from different joints and in rheumatic nodules. It is shown that all investigated crystals have a significant birefringence.

Mimicry of lyme arthritis by synovial hemangioma.

PubMed

Hospach, Toni; Langendörfer, M; Kalle, T V; Tewald, F; Wirth, T; Dannecker, G E

2011-12-01

To report on the differential diagnosis of lyme arthritis and synovial hemangioma due to similar clinical and radiological signs and symptoms. A 15-year-old boy presented at the age of 9 with recurrent rather painless swelling of the right knee. Altogether four episodes lasting for 1-2 weeks each occurred over a period of 18 months before medical advice was sought. Physical examination revealed only a slightly limited range of motion. Living in an endemic area of borreliosis, he reported a tick bite 6 months prior to onset of his symptoms with erythema migrans and was treated for 10 days with amoxicillin. Serology revealed two positive unspecific bands in IgG immunoblot (p41 and 66) with slight positivity for ELISA. Ultrasound revealed synovial thickening and increased fluid. Despite the weak positive serology a diagnosis of lyme arthritis could not be excluded and intravenous antibiotic treatment with ceftriaxone was started. After two further relapses antiinflammatory therapy including intraarticular steroids were introduced with no long lasting effect. A chronical disease developed with alternate periods of swelling and almost complete remission. Ultrasound as well as MRI demonstrated ongoing signs of synovitis, therefore after further progression, a diagnostic arthroscopy was performed showing an inconspicuous knee joint. A second MRI showed focal suprapatellar enhancement and was followed by open arthrotomy revealing a histopathological proven synovial cavernous juxtaarticular hemangioma. To our knowledge, the differential diagnosis of lyme arthritis and synovial hemangioma has not yet been reported despite obvious clinical similarities. In conclusion, in children and adolescents synovial hemangioma has to be considered in differential diagnosis of recurrent knee swelling. Early diagnosis is important to prevent prolonged suffering from chronic joint swelling with probable joint damages, unnecessary treatment procedures and as well school and sports

Characterisation of lubricin in synovial fluid from horses with osteoarthritis.

PubMed

Svala, E; Jin, C; Rüetschi, U; Ekman, S; Lindahl, A; Karlsson, N G; Skiöldebrand, E

2017-01-01

The glycoprotein lubricin contributes to the boundary lubrication of the articular cartilage surface. The early events of osteoarthritis involve the superficial layer where lubricin is synthesised. To characterise the glycosylation profile of lubricin in synovial fluid from horses with osteoarthritis and study secretion and degradation of lubricin in an in vitro inflammation cartilage model. In vitro study. Synovial fluid samples collected from horses with joints with normal articular cartilage and structural osteoarthritic lesions; with and without osteochondral fragments, were analysed for the lubricin glycosylation profiles. Articular cartilage explants were stimulated with or without interleukin-1β for 25 days. Media samples collected at 3-day intervals were analysed by quantitative proteomics, western blot and enzyme-linked immunosorbent assay. O-glycosylation profiles in synovial fluid revealed both Core 1 and 2 O-glycans, with Core 1 O-glycans predominating. Synovial fluid from normal joints (49.5 ± 1.9%) contained significantly lower amounts of monosialylated Core 1 O-glycans compared with joints with osteoarthritis (53.8 ± 7.8%, P = 0.03) or joints with osteochondral fragments (57.3 ± 8.8%, P = 0.001). Additionally, synovial fluid from normal joints (26.7 ± 6.7%) showed higher amounts of disialylated Core 1 O-glycan than from joints with osteochondral fragments (21.2 ± 4.9%, P = 0.03). A C-terminal proteolytic cleavage site in lubricin was found in synovial fluid from normal and osteochondral fragment joints and in media from interleukin-1β stimulated and unstimulated articular cartilage explants. This is the first demonstration of a change in the glycosylation profile of lubricin in synovial fluid from diseased equine joints compared with that from normal joints. We demonstrate an identical proteolytic cleavage site of lubricin both in vitro and in vivo. The reduced sialation of lubricin in synovial fluid from diseased joints may affect the

Ultrastructure of the synovial membrane in seronegative inflammatory arthropathies.

PubMed Central

Morris, C J; Farr, M; Hollywell, C A; Hawkins, C F; Scott, D L; Walton, K W

1983-01-01

The ultrastructure of the synovial membrane has been studied in 6 patients with seronegative inflammatory arthropathies: Reiter's (2), Crohn's (2), Whipple's (1) and Behçet's disease (1). The most striking changes were found in the synovial B cells, many containing abnormally large mitochondria with altered cristae surrounded by fibrillar material. Similar material was present in dilated endoplasmic reticulum which was the probable source of groups of extracellular fibrillar spheroidal bodies. The B cells also contained electron dense granular lysosomes of very variable size which, in common with the abnormal mitochondria, were often associated with bundles of orientated microfilaments and large golgi complexes. Light microscopy of the synovial membrane was consistent with an inflammatory arthritis, as were the high white cell counts in the synovial fluid. Systemic activity in the patients was indicated by raised ESR and C-reactive protein (CRP). Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. A Figure 5. B PMID:6186810

Ultrasound-guided synovial biopsy

PubMed Central

Sitt, Jacqueline C M; Wong, Priscilla

2016-01-01

Ultrasound-guided needle biopsy of synovium is an increasingly performed procedure with a high diagnostic yield. In this review, we discuss the normal synovium, as well as the indications, technique, tissue handling and clinical applications of ultrasound-guided synovial biopsy. PMID:26581578

[Primary breast synovial sarcoma].

PubMed

Alfaro-Cervelló, Clara; Burgués, Octavio

Primary synovial sarcoma of the breast is very rare. We report a case of a 33-year-old woman, who had previously undergone a radical mastectomy, having been diagnosed with fusocellular breast carcinoma. Histopathology revealed a hypercellular lesion formed by spindle cells with storiform and herringbone patterns. Immunohistochemistry showed strong expression of vimentin and CD99, and focal bcl2, EMA, CK AE1-AE3, actin and desmin, with negativity for S100, CD34, CK7, CK14, CK19, hormone receptors, caldesmon and myosin. Molecular biology revealed the expression of the fusion product of the SS18 and SSX genes, indicative of the translocation t(X;18)(p11.2;q11.2), which confirmed the diagnosis of synovial sarcoma. Copyright © 2017 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.

Multivariate analysis of prognostic factors in synovial sarcoma.

PubMed

Koh, Kyoung Hwan; Cho, Eun Yoon; Kim, Dong Wook; Seo, Sung Wook

2009-11-01

Many studies have described the diversity of synovial sarcoma in terms of its biological characteristics and clinical features. Moreover, much effort has been expended on the identification of prognostic factors because of unpredictable behaviors of synovial sarcomas. However, with the exception of tumor size, published results have been inconsistent. We attempted to identify independent risk factors using survival analysis. Forty-one consecutive patients with synovial sarcoma were prospectively followed from January 1997 to March 2008. Overall and progression-free survival for age, sex, tumor size, tumor location, metastasis at presentation, histologic subtype, chemotherapy, radiation therapy, and resection margin were analyzed, and standard multivariate Cox proportional hazard regression analysis was used to evaluate potential prognostic factors. Tumor size (>5 cm), nonlimb-based tumors, metastasis at presentation, and a monophasic subtype were associated with poorer overall survival. Multivariate analysis showed metastasis at presentation and monophasic tumor subtype affected overall survival. For the progression-free survival, monophasic subtype was found to be only 1 prognostic factor. The study confirmed that histologic subtype is the single most important independent prognostic factors of synovial sarcoma regardless of tumor stage.

Primary Synovial Sarcoma of External Auditory Canal: A Case Report

PubMed Central

Jayakumar, Krishnannair l L

2017-01-01

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression. PMID:28948118

Primary Synovial Sarcoma of External Auditory Canal: A Case Report.

PubMed

Devi, Aarani; Jayakumar, Krishnannair L L

2017-07-20

Synovial sarcoma is a rare malignant tumor of mesenchymal origin. Primary synovial sarcoma of the ear is extremely rare and to date only two cases have been published in English medical literature. Though the tumor is reported to have an aggressive nature, early diagnosis and treatment may improve the outcome. Here, we report a rare case of synovial sarcoma of the external auditory canal in an 18-year-old male who was managed by chemotherapy and referred for palliation due to tumor progression.

The influence of the acetabular labrum seal, intact articular superficial zone and synovial fluid thixotropy on squeeze-film lubrication of a spherical synovial joint.

PubMed

Hlavácek, M

2002-10-01

A model of synovial fluid (SF) filtration by articular cartilage (AC) in a step-loaded spherical synovial joint at rest is presented. The effects of joint pathology (such as a depleted acetabular labrum, a depleted cartilage superficial zone consistent with early osteoarthritis and an inflammatory SF) on the squeezed synovial film are also investigated. Biphasic mixture models for AC (ideal fluid and elastic porous transversely isotropic two-layer matrix) and for SF (ideal and thixotropic fluids) are applied and the following results are obtained. If the acetabular labrum is able to seal the pressurised SF between the articular surfaces (as in the normal hip joint), the fluid in the synovial film and in the cartilage within the labral ring is homogeneously pressurised. The articular surfaces remain separated by a fluid film for minutes. If the labrum is destroyed or absent and the SF can escape across the contact edge, the fluid pressure is non-homogeneous and with a small jump at the articular surface at the very moment of load application. The ensuing synovial film filtration by porous cartilage is lower for the normal cartilage (with the intact superficial zone) than if this zone is already depleted or rubbed off as in the early stage of primary osteoarthritis. Compared with the inflammatory (Newtonian) SF, the normal (thixotropic) fluid applies favourably in the squeezed film near the contact centre only, yielding a thicker SF film there, but not affecting the minimum thickness in the fluid film profile at a fixed time. For all that, in the unsealed case for both the normal and pathological joint, the macromolecular concentration of the hyaluronic acid-protein complex in the synovial film quickly increases due to the filtration in the greater part of the contact. A stable synovial gel film, thick on the order of 10(-7)m, protecting the articular surfaces from the intimate contact, is formed within a couple of seconds. Boundary lubrication by the synovial gel is

Synovial tumefactive extramedullary hematopoiesis associated to polycythemia vera.

PubMed

Alvarez-Argüelles Cabrera, Hugo; Carrasco Juan, José Luis; García Castro, María Candelaria; González Gaitano, Manuel; Bonilla Arjona, Alfonso; Díaz-Flores, Lucio

2007-01-01

The case of a 66-year-old male patient with a chronic myeloproliferative type polycythemia vera disorder, who after 2 years of evolution is developing a tumefactive extramedullary hematopoiesis (TEH) located in the synovial of the articulation in the right knee, is described. The tumor histologically consists of a relatively lax and edematous synovial structure diffusely infiltrated by mature and semimature hematopoietic cellular population. The simultaneous study of the bone marrow reveals medullar spaces full of hematopoietic cellularity, with a predominance of megakaryocytic and red series, and with the addition of severe reticulin fibrosis, facts that suggest a progression toward myelofibrosis. The TEH developed in tissues without a reticulum endothelial system is very uncommon. We provide data about the first case located in the synovial membrane and we review the literature regarding this pathologic entity.

Imatinib mesylate inhibits platelet derived growth factor stimulated proliferation of rheumatoid synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sandler, Charlotta; Joutsiniemi, Saima; Lindstedt, Ken A.

Synovial fibroblast is the key cell type in the growth of the pathological synovial tissue in arthritis. Here, we show that platelet-derived growth factor (PDGF) is a potent mitogen for synovial fibroblasts isolated from patients with rheumatoid arthritis. Inhibition of PDGF-receptor signalling by imatinib mesylate (1 {mu}M) completely abrogated the PDGF-stimulated proliferation and inhibited approximately 70% of serum-stimulated proliferation of synovial fibroblasts. Similar extent of inhibition was observed when PDGF was neutralized with anti-PDGF antibodies, suggesting that imatinib mesylate does not inhibit pathways other than those mediated by PDGF-receptors. No signs of apoptosis were detected in synovial fibroblasts cultured inmore » the presence of imatinib. These results suggest that imatinib mesylate specifically inhibits PDGF-stimulated proliferation of synovial fibroblasts, and that inhibition of PDGF-receptors could represent a feasible target for novel antirheumatic therapies.« less

Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.

PubMed

Carlson, Alyssa K; Rawle, Rachel A; Adams, Erik; Greenwood, Mark C; Bothner, Brian; June, Ronald K

2018-05-05

Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n = 5), rheumatoid arthritic (n = 3), and healthy (n = 5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve >0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease. Copyright © 2018 Elsevier Inc. All rights reserved.

Metastatic carcinoma presenting as hind-limb lameness: diagnosis by synovial fluid cytology.

PubMed

Meinkoth, J H; Rochat, M C; Cowell, R L

1997-01-01

A dog presented for evaluation of left hind-limb lameness and pain associated with manipulation of the tail. Synovial metastasis of a carcinoma was diagnosed by joint fluid examination. A primary bronchiolar-alveolar carcinoma with widespread (including synovial and skeletal) metastases was diagnosed on postmortem examination. Metastasis to synovial surfaces is uncommon, but when it occurs, the metastasis-induced arthritis may be the initial presenting complaint for which medical attention is sought. Although rarely reported, cytological examination of synovial fluid may be diagnostic. This paper presents an interesting clinical case and reviews the literature concerning metastatic disease of the synovium.

A Systems Biology Approach to Synovial Joint Lubrication in Health, Injury, and Disease

PubMed Central

Hui, Alexander Y.; McCarty, William J.; Masuda, Koichi; Firestein, Gary S.; Sah, Robert L.

2013-01-01

The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multi-faceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis. PMID:21826801

Biphasic synovial sarcoma in the cervical spine: Case report.

PubMed

Foreman, Stephen M; Stahl, Michael J

2011-05-23

Synovial sarcoma is a rare malignant neoplasm of soft tissue that typically arising near large joints of the upper and lower extremities in young adult males. Only 3% of these neoplasms have been found to arise in the head and neck region. To our knowledge, there are limited reports in the literature of this neoplasm in the cervical spine.A case of biphasic synovial sarcoma of the cervical spine is reviewed. A 29 year-old male presented with pain on the left side of the cervical spine. Physical examination revealed a global loss of cervical motion and large, palpable mass in the left paravertebral area. The long-delayed Magnetic Resonance (MR) scan revealed a soft tissue mass measuring 8.3 centimeters (cm) × 5.7 cm that was surgically removed. A malignant biphasic synovial sarcoma was diagnosed on pathologic examination.The clinical and imaging findings of an atypically located synovial sarcoma are reviewed. This case report emphasizes the consequences of a limited differential diagnosis, prolonged treatment and the failure to perform timely diagnostic imaging in the presence of a paraspinal mass.

Monophasic Synovial Sarcoma Presenting as Mitral Valve Obstruction

PubMed Central

Chokesuwattanaskul, Warangkana; Terrell, Jason; Jenkins, Leigh Ann

2010-01-01

We report the case of a 26-year-old man who experienced progressive left-sided chest pain and 2 episodes of near-syncope. Studies revealed a 15-cm mass in the upper left lung, a 10-cm mass in the medial base of the left lung, and a 5-cm left atrial mass that involved the left lung, infiltrated the left pulmonary vein, and prolapsed into the mitral valve, causing intermittent obstruction. The patient underwent surgical excision of the left atrial tumor. Pathologic evaluation confirmed the diagnosis of monophasic synovial sarcoma. To our knowledge, this is only the 3rd report of left atrial invasion and resultant mitral valve obstruction from a synovial sarcoma that infiltrated the pulmonary vein. We believe that this is the 1st documented case of a metastatic left atrial synovial sarcoma in monophasic form. PMID:20844626

Expression of Connexin 43 in Synovial Tissue of Patients With Rheumatoid Arthritis

PubMed Central

MATSUKI, Tomohiro; TSUCHIDA, Shinji; TERAUCHI, Ryu; ODA, Ryo; FUJIWARA, Hiroyoshi; MAZDA, Osam; KUBO, Toshikazu

2016-01-01

Objectives This study aims to identify the distribution and expression level of connexin 43 (Cx43) in synovial tissue in patients with rheumatoid arthritis (RA). Patients and methods The expression of Cx43 in synovial tissue from eight patients with RA (2 males, 6 females; mean age 59.5±2.7 years; range 52 to 71 years), five patients with osteoarthritis (2 males, 3 females; mean age 68.4±2.7 years; range 61 to 81 years), and one normal female subject (mean age 61 year) was analyzed by quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry of tissue sections. Induction of Cx43 following stimulation of human RA synovial fibroblasts with tumor necrosis factor-alpha (TNF-a) cultures was examined by quantitative reverse transcriptase polymerase chain reaction. The effect of small interfering ribonucleic acid targeting Cx43 (siCx43) on the expression of TNF-a and interleukin-6 was examined using quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assays. Results Connexin 43 was highly expressed in RA synovial tissue, which also expressed TNF-a, but was expressed lower in osteoarthritis and normal synovial tissue. Expression of Cx43 was markedly up-regulated in RA synovial fibroblasts after stimulation with TNF-a. The over-expression of pro- inflammatory cytokines was suppressed by transfection of siCx43. Conclusion This study shows that Cx43 is expressed in RA synovial tissue and that its expression is induced by stimulation with TNF-a. The expression of the pro-inflammatory cytokines was inhibited by transfection of siCx43. Cx43 may be a novel marker of inflammation in RA synovial tissue. PMID:29900991

Utility of percutaneous joint aspiration and synovial biopsy in identifying culture-positive infected hip arthroplasty.

PubMed

Cross, M Connor; Kransdorf, Mark J; Chivers, F Spencer; Lorans, Roxanne; Roberts, Catherine C; Schwartz, Adam J; Beauchamp, Christopher P

2014-02-01

Percutaneous synovial biopsy has recently been reported to have a high diagnostic value in the preoperative identification of periprosthetic infection of the hip. We report our experience with this technique in the evaluation of patients undergoing revision hip arthroplasty, comparing results of preoperative synovial biopsy with joint aspiration in identifying an infected hip arthroplasty by bacteriological analysis. We retrospectively reviewed the results of the 110 most recent revision hip arthroplasties in which preoperative synovial biopsy and joint aspiration were both performed. Revision surgery for these patients occurred during the period from September 2005 to March 2012. Using this study group, results from preoperative cultures were compared with preoperative laboratory studies and the results of intraoperative cultures. Synovial aspiration was done using an 18- or 20-gauge spinal needle. Synovial biopsy was done coaxially following aspiration using a 22-gauge Chiba needle or 21-gauge Sure-Cut needle. Standard microbiological analysis was performed on preoperative synovial fluid aspirate and synovial biopsy. Intraoperative tissue biopsy bacteriological analysis results at surgical revision were accepted as the "gold standard" for the presence or absence of infection. Seventeen of 110 (15 %) of patients had intraoperative culture-positive periprosthetic infection. Of these 17 cases, there were ten cases where either the synovial fluid aspiration and/or the synovial biopsy were true positive (sensitivity of 59 %, specificity of 100 %, positive predictive value of 100 % and accuracy of 94 %). There were seven cases where aspiration and biopsy results were both falsely negative, but no false-positive results. Similar results were found for synovial fluid aspiration alone. The results of synovial biopsy alone resulted in the identification of seven infected joints with no false-positive result (sensitivity of 41 %, specificity of 100 %, positive

Hip Synovial Fluid Cell Counts in Children From a Lyme Disease Endemic Area.

PubMed

Dart, Arianna H; Michelson, Kenneth A; Aronson, Paul L; Garro, Aris C; Lee, Thomas J; Glerum, Kimberly M; Nigrovic, Peter A; Kocher, Mininder S; Bachur, Richard G; Nigrovic, Lise E

2018-05-01

Patients with septic hip arthritis require surgical drainage, but they can be difficult to distinguish from patients with Lyme arthritis. The ability of synovial fluid white blood cell (WBC) counts to help discriminate between septic and Lyme arthritis of the hip has not been investigated. We assembled a retrospective cohort of patients ≤21 years of age with hip monoarticular arthritis and a synovial fluid culture obtained who presented to 1 of 3 emergency departments located in Lyme disease endemic areas. Septic arthritis was defined as a positive synovial fluid culture result or synovial fluid pleocytosis (WBC count ≥50 000 cells per µL) with a positive blood culture result. Lyme arthritis was defined as positive 2-tiered Lyme disease serology results and negative synovial fluid bacterial culture results. All other patients were classified as having other arthritis. We compared median synovial fluid WBC counts by arthritis type. Of the 238 eligible patients, 26 (11%) had septic arthritis, 32 (13%) had Lyme arthritis, and 180 (76%) had other arthritis. Patients with septic arthritis had a higher median synovial fluid WBC count (126 130 cells per µL; interquartile range 83 303-209 332 cells per µL) than patients with Lyme arthritis (53 955 cells per µL; interquartile range 33 789-73 375 cells per µL). Eighteen patients (56%) with Lyme arthritis had synovial fluid WBC counts ≥50 000 cells per µL. Of the 94 patients who underwent surgical drainage, 13 were later diagnosed with Lyme arthritis. In Lyme disease endemic areas, synovial fluid WBC counts cannot always help differentiate septic from Lyme arthritis. Rapid Lyme diagnostics could help avoid unnecessary operative procedures in patients with Lyme arthritis. Copyright © 2018 by the American Academy of Pediatrics.

Cervical myelopathy associated with extradural synovial cysts in 4 dogs.

PubMed

Levitski, R E; Chauvet, A E; Lipsitz, D

1999-01-01

Three Mastiffs and 1 Great Dane were presented to the University of Wisconsin Veterinary Medical Teaching Hospital for cervical myelopathy based on history and neurologic examination. All dogs were males and had progressive ataxia and tetraparesis. Degenerative arthritis of the articular facet joints was noted on survey spinal radiographs. Myelography disclosed lateral axial compression of the cervical spinal cord medial to the articular facets. Extradural compressive cystic structures adjacent to articular facets were identified on magnetic resonance imaging (1 dog). High protein concentration was the most important finding on cerebrospinal fluid analysis. Dorsal laminectomies were performed in all dogs for spinal cord decompression and cyst removal. Findings on cytologic examination of the cystic fluid were consistent with synovial fluid, and histopathologic results supported the diagnosis of synovial cysts. All dogs are ambulatory and 3 are asymptomatic after surgery with a follow-up time ranging from 1 to 8 months. This is the 1st report of extradural synovial cysts in dogs, and synovial cysts should be a differential diagnosis for young giant breed dogs with cervical myelopathy.

[Passage of nonsteroidal anti-inflammatory agents across the synovial membrane].

PubMed

Netter, P; Bannwarth, B; Monot, C; Royer, R J; Gaucher, A

1983-09-24

The therapeutic effectiveness of non-steroid anti-inflammatory (NSAI) drugs is partly determined by their passage across the synovial membrane. The synovium can be compared to a double barrier the permeability of which to NSAI drugs depends on the degree of inflammation of the joint and on the pharmacokinetic properties of the drugs (lipophilia, pka, protein-binding). A few hours after one single systemic dose, concentrations in the synovial fluid are higher than in serum. During chronic administration, concentrations of NSAI drugs with a short half-life vary less in synovial fluid than in serum. During steady state, free fractions of NSAI drugs with prolonged half-life may be similar in both compartments.

Can lumbar hemorrhagic synovial cyst cause acute radicular compression? Case report

PubMed Central

Timbó, Luciana Sátiro; Rosemberg, Laercio Alberto; Brandt, Reynaldo André; Peres, Ricardo Botticini; Nakamura, Olavo Kyosen; Guimarães, Juliana Frota

2014-01-01

Lumbar synovial cysts are an uncommon cause of back pain and radiculopathy, usually manifesting with gradual onset of symptoms, secondary to involvement of the spinal canal. Rarely, intracyst hemorrhage occurs, and may acutely present as radicular - or even spinal cord - compression syndrome. Synovial cysts are generally associated with degenerative facets, although the pathogenesis has not been entirely established. We report a case of bleeding complication in a synovial cyst at L2-L3, adjacent to the right interfacet joint, causing acute pain and radiculopathy in a patient on anticoagulation therapy who required surgical resection. PMID:25628207

Raman spectroscopy of synovial fluid as a tool for diagnosing osteoarthritis

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Mandair, Gurjit S.; Raaii, Farhang; Jacobson, Jon A.; Miller, Bruce S.; Urquhart, Andrew G.; Roessler, Blake J.; Morris, Michael D.

2009-05-01

For many years, viscosity has been the primary method used by researchers in rheumatology to assess the physiochemical properties of synovial fluid in both normal and osteoarthritic patients. However, progress has been limited by the lack of methods that provide multiple layers of information, use small sample volumes, and are rapid. Raman spectroscopy was used to assess the biochemical composition of synovial fluid collected from 40 patients with clinical evidence of knee osteoarthritis (OA) at the time of elective surgical treatment. Severity of knee osteoarthritis was assessed by a radiologist using Kellgren/Lawrence (K/L) scores from knee joint x rays, while light microscopy and Raman spectroscopy were used to examine synovial fluid (SF) aspirates (2 to 10 μL), deposited on fused silica slides. We show that Raman bands used to describe protein secondary structure and content can be used to detect changes in synovial fluid from osteoarthritic patients. Several Raman band intensity ratios increased significantly in spectra collected from synovial fluid in patients with radiological evidence of moderate-to-severe osteoarthritis damage. These ratios can be used to provide a ``yes/no'' damage assessment. These studies provide evidence that Raman spectroscopy would be a suitable candidate in the evaluation of joint damage in knee osteoarthritis patients.

Synovial sarcoma of the temporomandibular joint and infratemporal fossa.

PubMed

Nomura, Fuminori; Kishimoto, Seiji

2014-12-01

Synovial sarcoma in the head and neck region is rare, and is difficult to resect with adequate safety margins because of its anatomical complexity. We herein report our experiences with synovial sarcoma in this region, and review the literature regarding the management of such cases. We retrospectively examined four cases of synovial sarcoma arising from the temporomandibular joint (TMJ) area and infratemporal fossa. Only one patient remains alive without disease, while the other three patients have died. The local control of these tumors has improved because of the progress in the surgical operation methods, while it is expected that there is still a high rate of deaths due to distant metastasis increase. The development of strong chemotherapy is needed for the use after the initial treatment and surgery. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Ceramic debris in hip prosthesis: correlation between synovial fluid and joint capsule.

PubMed

De Pasquale, Dalila; Stea, Susanna; Beraudi, Alina; Montesi, Monica; Squarzoni, Stefano; Toni, Aldo

2013-05-01

Detection of ceramic particles in synovial fluids allows early diagnosis of ceramic damage, but there is no evidence of a relationship between ceramic debris in the articular space and in the joint capsule. The aim of the present study is to verify if the particles isolated in the synovial fluid are comparable with those stored in the capsular tissue. Twenty-one patients were enrolled. Both synovial fluid and capsular samples were collected during revision surgery and ceramic particles were isolated and analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis. It resulted a significant correlation between the samples couples (18 out of 21). This study confirms that the synovial fluid analysis can give a clear definition of the presence of particles in the joint capsule. Copyright © 2013 Elsevier Inc. All rights reserved.

Giant Solitary Synovial Osteochondroma of the Subtalar Joint.

PubMed

Lui, Tun Hing

2016-01-01

A rapidly progressing calcified mass was found in the left sinus tarsi in a 12-year-old female after a trivial ankle sprain. The lesion mimicked an aggressive lesion clinically and radiographically. Ultrasound-guided biopsy confirmed the diagnosis of a synovial chondroma. Excision of the tumor and partial synovectomy were performed. The histologic diagnosis was a solitary synovial osteochondroma. The condition had not recurred after a follow-up period of 12 months. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

[Articular cartilage regenerative therapy with synovial mesenchymal stem cells in a pig model].

PubMed

Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Kobayashi, Eiji

2013-12-01

Current therapies for cartilage injury remain some issues such as the quality of regenerated cartilage and its invasiveness. We have been trying to develop a low invasive treatment for cartilage regeneration with synovial mesenchymal stem cells (MSCs) . Here we introduce our preclinical study with miniature pigs whose knee joints are similar to those of humans in terms of size and cartilage metabolism. Cartilage defect was created at the weight bearing area of both porcine knee joints. Synovial MSCs were transplanted by delivering a synovial MSC suspension onto the cartilage defect of the one side and the knee was kept immobilized for 10 minutes. Sequential arthroscopic and histological observations showed the contribution of synovial MSCs after transplantation, and a better hyaline cartilaginous-tissue regeneration in the MSC-treated knees than in the non-treated control knees at 12 weeks. Based on this and other preclinical studies, we have started a clinical study for cartilage regeneration with autologous synovial MSCs.

Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation

PubMed Central

Takano, Shotaro; Miyagi, Masayuki; Inoue, Gen; Aikawa, Jun; Iwabuchi, Kazuya; Takaso, Masashi

2017-01-01

Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages. PMID:28299347

Synovial inflammation in patients with different stages of knee osteoarthritis.

PubMed

Ene, Răzvan; Sinescu, Ruxandra Diana; Ene, Patricia; Cîrstoiu, Monica Mihaela; Cîrstoiu, Florin Cătălin

2015-01-01

The synovium is an intra-articular mesenchymal tissue and essential for the normal joint function. It is involved in many pathological characteristic processes and sometimes specific for this distinctive tissue. In this study, we refer to synovial proliferative disorders according to the stage of osteoarthritis (OA) disease. Forty-three patients with knee OA were treated in the Department of Orthopedics and Traumatology, Emergency University Hospital of Bucharest, Romania, in the last two years. In all cases, we used at least five criteria for the knee OA: knee pain, knee joint tenderness, no palpable warmth over the knee, stiffness, erythrocyte sedimentation rate and C-reactive protein levels. In all the cases the synovial tissue was selected by the orthopedic surgeon. X-ray examination was taken in every case of the affected joint. Patients who were considered to have early OA underwent arthroscopic synovial biopsy of the symptomatic joint. Synovial tissue samples from patients with late OA were obtained at the time of knee joint arthroplasty. Microscopic examination in early osteoarthritis revealed for more than half of patients with synovial biopsy through arthroscopic technique having synovitis lesions with mononuclear infiltrates, diffuse fibrosis, thickening of the lining layer, macrophages appearance and neoformation vessels also. The synovitis seen in advanced OA knees tends to be diffuse and is not mandatory localized to areas of chondral defects, although an association has been reported between chondral defects and associated synovitis in the knee medial tibio-femoral compartment. The overexpression of mediators of inflammation and the increased mononuclear cell infiltration were seen in early OA, compared with late OA.

Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids

PubMed Central

Menzel, J.; Steffen, C.; Kolarz, G.; Eberl, R.; Frank, O.; Thumb, N.

1976-01-01

Menzel, J., Steffen, C., Kolarz, G., Eberl, R., Frank, O., and Thumb, N. (1976).Annals of the Rheumatic Diseases, 35, 446-450. Demonstration of antibodies to collagen and of collagen-anticollagen immune complexes in rheumatoid arthritis synovial fluids. Twenty-nine synovial fluids from patients with rheumatoid arthritis (RA) and 10 synovial fluids from patients with other joint diseases were investigated with regard to the presence of antibodies to denatured human collagen and of collagen-anticollagen immune complexes. 12 of the 29 RA synovial fluids showed anticollagen titres from 1: 16 to 1: 512 in passive haemagglutination. Only one patient in the group with no arthritis had a significant anticollagen titre of 1: 32. Digestion of the synovial fluids with bacterial collagenase resulted in an anticollagen titre increase from two to four dilution steps in 9 of the RA fluids, while 6 previously negative RA synovial fluids showed anticollagen titres from 1: 32 to 1: 128 after digestion with collagenase. These results indicate the existence of collagen-anticollagen immune complexes in 15 of the 29 RA synovial fluids investigated. PMID:185972

Use of vitamin B12 in joint lavage for determination of dilution factors of canine synovial fluid.

PubMed

de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Cox, Eric

2005-11-01

To test a modified saline (0.9% NaCl) solution joint washing (lavage) technique that includes the use of vitamin B12 as an internal marker for the evaluation of synovial fluid dilution in lavage samples from canine joints. 9 plasma samples obtained from blood samples of 9 healthy dogs and 9 synovial fluid samples aspirated from stifle joints of 9 cadaveric dogs. Photometric absorbances of 25% vitamin B12 solution, canine synovial fluid, and canine plasma were measured in a spectrophotometer to establish an optimal wavelength for analysis. Canine synovial fluid and plasma samples were mixed with the 25% vitamin B12 solution to obtain 1%, 3%, 5%, 10%, 20%, and 50% solutions of synovial fluid or plasma. Diluted synovial fluid and plasma samples were used to simulate joint lavage samples and to examine the possible interference of these substances (synovial fluid or plasma) with the absorbance of the 25% vitamin B12 solution in photometric analysis. The optimal wavelength was found to be at 550 nm. Canine synovial fluid and plasma samples did not interfere with the absorbance measurements of the 25% vitamin B12 solution up to a 50% dilution of plasma or synovial fluid. The modified saline solution joint lavage method with the use of a 25% vitamin B12 solution as an internal standard provides an accurate and reliable technique for the evaluation of synovial fluid dilution in lavage samples from canine joints.

Overexpression of decoy receptor 3 in synovial tissues of inflammatory arthritis.

PubMed

Chen, Ming-Han; Chen, Wei-Sheng; Tsai, Chang-Youh; Liao, Hsien-Tzung; Chen, Chun-Hsiung; Chou, Chung-Tei

2012-01-01

Decoy receptor 3 (DCR3) was a newly identified soluble receptor which was reported to modulate the function of T cells, dendritic cells and macrophages. The aim of this study was to investigate DCR3 expression on the synovial tissue in different types of arthritis. We obtained synovial tissues from 17 rheumatoid arthritis (RA), 17 ankylosing spondylitis (AS) and 17 osteoarthritis (OA) patients. Synovial specimens were stained with hematoxylin and eosin. The amount of lymphocytes and mononuclear cells infiltration and vascularity during light microscopic examination was scored from 0-4. The expression of CD3, CD4, CD8, CD68 and DCR3 in lining layer (LL) and sublining layer (SL) cells was stained using the immunohistochemical method and analysed by microscopic examination (score from 0-4, 0=absent, 1=slight, 2=moderate, 3=large, 4=extreme). OA patients were older than the RA and AS patients (65.9±10.3 years for OA, 58.4±17.7 for RA, and 43.2±16.4 for AS). Synovial tissues in RA patients had significantly increased mononuclear cells infiltration when compared to AS and OA patients (2.3±0.6, 1.9±0.5, 1.6±0.5, respectively, p<0.05). There was no striking difference in DCR3 expression in the synovial LL between RA, AS, and OA patients. CD4+ T cells and CD68+ monocytes/macrophages in the SL were more prominent in RA and AS than in OA (p<0.05). Similarly, DCR3 in the SL was more overexpressed in RA and AS than in OA (1.83±0.21, 1.71±0.36, 1.39±0.31, respectively, p<0.01). The increased synovial inflammatory cells infiltration in RA and AS was associated with the elevated DCR3 expression.

Synovial calprotectin: a potential biomarker to exclude a prosthetic joint infection.

PubMed

Wouthuyzen-Bakker, M; Ploegmakers, J J W; Kampinga, G A; Wagenmakers-Huizenga, L; Jutte, P C; Muller Kobold, A C

2017-05-01

Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. Cite this article: Bone Joint J 2017;99-B:660-5. ©2017 The British Editorial Society of Bone & Joint Surgery.

Simulation Of The Synovial Fluid In A Deformable Cavity

NASA Astrophysics Data System (ADS)

Martinez-Gutierrez, Nancy; Ibarra-Bracamontes, Laura A.

2016-11-01

The main components of a synovial joint are a cartilage and a biofluid known as the synovial fluid. The results were obtained using the FLUENT software to simulate the behavior of the synovial fluid within a deformable cavity with a simple geometry. The cartilage is represented as a porous region. By reducing the available region for the fluid, a fluid displacement into the cartilage is induced. The total pressure reached in the interface of the deformable cavity and the porous region is presented. The geometry and properties of the system are scaled to values found in a knee joint. The effect of deformation rate, fluid viscosity and properties of the porous medium on the total pressure reached are analyzed. The higher pressures are reached either for high deformation rate or when the fluid viscosity increases. This study was supported by the Mexican Council of Science and Technology (CONACyT) and by the Scientific Research Coordination of the University of Michoacan in Mexico.

Minimally Invasive Tubular Resection of Lumbar Synovial Cysts: Report of 40 Consecutive Cases.

PubMed

Birch, Barry D; Aoun, Rami James N; Elbert, Gregg A; Patel, Naresh P; Krishna, Chandan; Lyons, Mark K

2016-10-01

Lumbar synovial cysts are a relatively common clinical finding. Surgical treatment of symptomatic synovial cysts includes computed tomography-guided aspiration, open resection and minimally invasive tubular resection. We report our series of 40 consecutive minimally invasive microscopic tubular lumbar synovial cyst resections. Following Institutional Review Board approval, a retrospective analysis of 40 cases of minimally invasive microscopic tubular retractor synovial cyst resections at a single institution by a single surgeon (B.D.B.) was conducted. Gross total resection was performed in all cases. Patient characteristics, surgical operating time, complications, and outcomes were analyzed. Lumbar radiculopathy was the presenting symptoms in all but 1 patient, who presented with neurogenic claudication. The mean duration of symptoms was 6.5 months (range, 1-25 months), mean operating time was 58 minutes (range, 25-110 minutes), and mean blood loss was 20 mL (range, 5-50 mL). Seven patients required overnight observation. The median length of stay in the remaining 33 patients was 4 hours. There were 2 cerebrospinal fluid leaks repaired directly without sequelae. The mean follow-up duration was 80.7 months. Outcomes were good or excellent in 37 of the 40 patients, fair in 1 patient, and poor in 2 patients. Minimally invasive microscopic tubular retractor resection of lumbar synovial cysts can be done safely and with comparable outcomes and complication rates as open procedures with potentially reduced operative time, length of stay, and healthcare costs. Patient selection for microscopic tubular synovial cyst resection is based in part on the anatomy of the spine and synovial cyst and is critical when recommending minimally invasive vs. open resection to patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Outcome of Percutaneous Lumbar Synovial Cyst Rupture in Patients with Lumbar Radiculopathy.

PubMed

Eshraghi, Yashar; Desai, Vimal; Cajigal Cajigal, Calvin; Tabbaa, Kutaiba

2016-01-01

Lumbar synovial cysts can result from spondylosis of facet joints. These cysts can encroach on adjacent nerve roots, causing symptoms of radiculopathy. Currently the only definitive treatment for these symptoms is surgery, which may involve laminectomy or laminotomy, with or without spinal fusion. Surgery has been reported to successfully relieve radicular pain in 83.5% of patients by Zhenbo et al. Little information is available concerning the efficacy and outcome of percutaneous fluoroscopic synovial cyst rupture for treatment of facet joint synovial cysts. The goal of this investigation was to assess the efficacy of fluoroscopically guided lumbar synovial cyst rupture, in particular for its relief of radicular symptoms and its potential to reduce the need for surgical intervention. Retrospective evaluation of a case series. University hospital and urban public health care system. With approval from the Institutional Review Board of Case Western Reserve University/ MetroHealth Medical Center, we reviewed the medical charts of patients with lumbar radiculopathy who underwent percutaneous lumbar synovial cyst rupture. The 30 patients in the cohort were treated by one pain specialist between 2006 and 2013. These patients were diagnosed with moderate to severe lower back pain, radiculopathy, and ranged in age from 42 to 80 years. Patients were followed up for a minimum of 6 months and up to 24 months. Pre- and post-procedure pain assessments were reviewed by clinical chart review. In addition post-procedure pain assessments and duration of pain relief were obtained with telephone interviews. Pain had been reported by the patients using a numeric rating scale of 0 - 10 (0 = no pain; 10 = worst possible pain). Charts were reviewed to determine if surgery was eventually performed to correct radicular symptoms. More than 6 months of pain relief was achieved in 14/30 patients (46%) and between one and 6 months of pain relief was achieved in 7/30 patients (23.3%). Nine

The JAK inhibitor tofacitinib suppresses synovial JAK1-STAT signalling in rheumatoid arthritis

PubMed Central

Boyle, D L; Soma, K; Hodge, J; Kavanaugh, A; Mandel, D; Mease, P; Shurmur, R; Singhal, A K; Wei, N; Rosengren, S; Kaplan, I; Krishnaswami, S; Luo, Z; Bradley, J; Firestein, G S

2015-01-01

Objective Tofacitinib is an oral Janus kinase (JAK) inhibitor for the treatment of rheumatoid arthritis (RA). The pathways affected by tofacitinib and the effects on gene expression in situ are unknown. Therefore, tofacitinib effects on synovial pathobiology were investigated. Methods A randomised, double-blind, phase II serial synovial biopsy study (A3921073; NCT00976599) in patients with RA with an inadequate methotrexate response. Patients on background methotrexate received tofacitinib 10 mg twice daily or placebo for 28 days. Synovial biopsies were performed on Days -7 and 28 and analysed by immunoassay or quantitative PCR. Clinical response was determined by disease activity score and European League Against Rheumatism (EULAR) response on Day 28 in A3921073, and at Month 3 in a long-term extension study (A3921024; NCT00413699). Results Tofacitinib exposure led to EULAR moderate to good responses (11/14 patients), while placebo was ineffective (1/14 patients) on Day 28. Tofacitinib treatment significantly reduced synovial mRNA expression of matrix metalloproteinase (MMP)-1 and MMP-3 (p<0.05) and chemokines CCL2, CXCL10 and CXCL13 (p<0.05). No overall changes were observed in synovial inflammation score or the presence of T cells, B cells or macrophages. Changes in synovial phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT3 strongly correlated with 4-month clinical responses (p<0.002). Tofacitinib significantly decreased plasma CXCL10 (p<0.005) at Day 28 compared with placebo. Conclusions Tofacitinib reduces metalloproteinase and interferon-regulated gene expression in rheumatoid synovium, and clinical improvement correlates with reductions in STAT1 and STAT3 phosphorylation. JAK1-mediated interferon and interleukin-6 signalling likely play a key role in the synovial response. Trial registration number NCT00976599. PMID:25398374

Dynamic gadolinium-enhanced magnetic resonance imaging allows accurate assessment of the synovial inflammatory activity in rheumatoid arthritis knee joints: a comparison with synovial histology.

PubMed

Axelsen, M B; Stoltenberg, M; Poggenborg, R P; Kubassova, O; Boesen, M; Bliddal, H; Hørslev-Petersen, K; Hanson, L G; Østergaard, M

2012-03-01

To determine whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) evaluated using semi-automatic image processing software can accurately assess synovial inflammation in rheumatoid arthritis (RA) knee joints. In 17 RA patients undergoing knee surgery, the average grade of histological synovial inflammation was determined from four biopsies obtained during surgery. A preoperative series of T(1)-weighted dynamic fast low-angle shot (FLASH) MR images was obtained. Parameters characterizing contrast uptake dynamics, including the initial rate of enhancement (IRE), were generated by the software in three different areas: (I) the entire slice (Whole slice); (II) a manually outlined region of interest (ROI) drawn quickly around the joint, omitting large artefacts such as blood vessels (Quick ROI); and (III) a manually outlined ROI following the synovial capsule of the knee joint (Precise ROI). Intra- and inter-reader agreement was assessed using the intra-class correlation coefficient (ICC). The IRE from the Quick ROI and the Precise ROI revealed high correlations to the grade of histological inflammation (Spearman's correlation coefficient (rho) = 0.70, p = 0.001 and rho = 0.74, p = 0.001, respectively). Intra- and inter-reader ICCs were very high (0.93-1.00). No Whole slice parameters were correlated to histology. DCE-MRI provides fast and accurate assessment of synovial inflammation in RA patients. Manual outlining of the joint to omit large artefacts is necessary.

Editorial Commentary: Role of Synovial Biomarkers in Patient Outcomes After Knee Arthroscopy.

PubMed

Brand, Jefferson C

2016-03-01

Humans are notably poor at predicting event outcomes. In "Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy," Cuellar, Cuellar, Kirsch, and Strauss show that some synovial fluid biomarkers (20 were sampled for the investigation) may predict operative findings at the time of arthroscopy and patient-reported outcome measures at follow-up. Further research will clarify the role of synovial biomarkers in knee pathology and, hopefully, narrow the choices to one or two pertinent markers that can be used to improve our ability to predict outcomes from arthroscopic knee surgery. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Influence of Anti-inflammatory Drugs on the Rheological Properties of Synovial Fluid and Its Components

NASA Astrophysics Data System (ADS)

Krause, Wendy E.; Klossner, Rebecca R.; Liang, Jing; Colby, Ralph H.

2006-03-01

The polyelectrolyte hyaluronic acid (HA, hyaluronan), its interactions with anti-inflammatory drugs and other biopolymers, and its role in synovial fluid are being studied. We are investigating the rheological properties of sodium hyaluronate (NaHA) solutions and an experimental model of synovial fluid (comprised of NaHA, and the plasma proteins albumin and γ-globulins). Steady shear measurements on bovine synovial fluid, the synovial fluid model, and plasma protein solutions indicate that the fluids are rheopectic (stress increases with time under steady shear). In addition, the influence of anti-inflammatory agents on these solutions is being explored. Initial results indicate that D-penicillamine and hydroxychloroquine (HCQ) affect the rheology of the synovial fluid model and its components. While HCQ has no effect on the viscosity of NaHA solutions, it inhibits/suppresses the observed rheopexy of the synovial fluid model and plasma protein solutions. In contrast, D-penicillamine has a complex, time dependent effect on the viscosity of NaHA solutions,---reducing the zero shear rate viscosity of a 3 mg/mL NaHA (in phosphate buffered saline) by ca. 40% after 44 days. The potential implications of these results will be discussed.

Feasibility of a tetracycline-binding method for detecting synovial fluid basic calcium phosphate crystals.

PubMed

Rosenthal, Ann K; Fahey, Mark; Gohr, Claudia; Burner, Todd; Konon, Irina; Daft, Laureen; Mattson, Eric; Hirschmugl, Carol; Ryan, Lawrence M; Simkin, Peter

2008-10-01

Basic calcium phosphate (BCP) crystals are common components of osteoarthritis (OA) synovial fluid. Progress in understanding the role of these bioactive particles in clinical OA has been hampered by difficulties in their identification. Tetracyclines stain calcium phosphate mineral in bone. The aim of this study was to investigate whether tetracycline staining might be an additional or alternative method for identifying BCP crystals in synovial fluid. A drop of oxytetracycline was mixed with a drop of fluid containing synthetic or native BCP, calcium pyrophosphate dihydrate (CPPD), or monosodium urate (MSU) crystals and placed on a microscope slide. Stained and unstained crystals were examined by light microscopy, with and without a portable broad-spectrum ultraviolet (UV) pen light. A small set of characterized synovial fluid samples were compared by staining with alizarin red S and oxytetracycline. Synthetic BCP crystals in synovial fluid were quantified fluorimetrically using oxytetracycline. After oxytetracycline staining, synthetic and native BCP crystals appeared as fluorescent amorphous aggregates under UV light. Oxytetracycline did not stain CPPD or MSU crystals or other particulates. Oxytetracycline staining had fewer false-positive test results than did alizarin red S staining and could provide estimates of the quantities of synthetic BCP crystals in synovial fluid. With further validation, oxytetracycline staining may prove to be a useful adjunct or alternative to currently available methods for identifying BCP crystals in synovial fluid.

Synovial sarcoma in cerebellum: a case report and literature review.

PubMed

Xiao, Guan-ying; Pan, Bin-cai; Tian, Xiao-ying; Li, Yang; Li, Bin; Li, Zhi

2014-01-01

Synovial sarcoma is a tumor of unknown origin and is extremely rare in the central nervous system. We present a case involving an unusual cerebellar synovial sarcoma in a male infant. Neuroimaging revealed a large, solid, gadolinium-enhancing mass located in the parenchyma of the right cerebellar hemisphere and associated with multiple cyst formation. Histologically, the tumor was composed of uniform spindle cells with indistinct borders and numerous mitotic figures. The tumor cells were observed to form dense cellular sheets, but in some areas the tumor showed a hemangiopericytomatous vascular pattern consisting of tumor cells arranged around dilated, thin-walled blood vessels. Immunohistochemistry showed that vimentin, CD99 and Bcl-2 were diffusely positive in most cells, and focal reactivity for cytokeratin (AE1/AE3) and S-100 protein was also observed. The tumor cells were, however, negative for CK19, EMA, CD34, synaptophysin, GFAP, desmin, myogenin, and smooth muscle actin. Cytogenetic analysis using fluorescence in situ hybridization demonstrated the translocation t(X;18)(p11;q11). A diagnosis of primary cerebellar monophasic synovial sarcoma was made. To our knowledge, this is the first report of a synovial sarcoma in brain parenchyma. The present case indicates that it is essential to select the appropriate immunohistochemical panel and-especially-perform molecular analysis to accurately diagnose intracranial spindle cell tumors.

Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a murine model of rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Matsuo, Yusuke; Mizoguchi, Fumitaka; Saito, Tetsuya

Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP andmore » wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G{sub 2}/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. - Highlights: • We studied how synovial fibroblasts accumulate in joints in a murine model of RA. • Bone marrow-derived cells did not accumulate in arthritic joints. • Synovial fibroblasts did not accumulate in arthritic joints

Nerve growth factor concentrations in the synovial fluid from healthy dogs and dogs with secondary osteoarthritis.

PubMed

Isola, M; Ferrari, V; Miolo, A; Stabile, F; Bernardini, D; Carnier, P; Busetto, R

2011-01-01

To measure the concentrations of nerve growth factor (NGF) in the synovial fluid from normal dogs and dogs with osteoarthritis (OA) secondary to common joint disorders. Nerve growth factor synovial concentrations were measured by ELISA assay in 50 dogs divided into three groups: 12 healthy, 16 affected by acute lameness within seven days before enrolment, and 22 with chronic lameness persisting by more than one month before enrolment and accompanied by radiological signs of OA. Both acute and chronic lameness were secondary to orthopaedic diseases involving the shoulder, elbow and stifle joints. Nerve growth factor synovial concentrations were compared between means for healthy and acute groups and between the three groups using an F-test. Significance level was set at p <0.05. Nerve growth factor was detected in all canine synovial fluid samples. However, the mean synovial NGF concentration of healthy dogs (3.65 ± 2.18 pg/ml) was not significantly different from the mean value in dogs with acute lameness (6.45 ± 2.45 pg/ml) (p = 0.79). Conversely, the mean synovial NGF concentration in dogs with chronic lameness (20.19 ± 17.51 pg/ml) was found to be significantly higher than that found in healthy dogs (p <0.01). This study demonstrates for the first time the presence of NGF in canine synovial fluid and its increased concentrations in dogs with chronic lameness compared to healthy dogs and dogs with acute lameness. The association between chronic lameness and raised synovial concentrations may suggest an involvement of NGF in OA inflammation and chronic pain.

Synovial fluid response to extensional flow: effects of dilution and intermolecular interactions.

PubMed

Haward, Simon J

2014-01-01

In this study, a microfluidic cross-slot device is used to examine the extensional flow response of diluted porcine synovial fluid (PSF) samples using flow-induced birefringence (FIB) measurements. The PSF sample is diluted to 10× 20× and 30× its original mass in a phosphate-buffered saline and its FIB response measured as a function of the strain rate at the stagnation point of the cross-slots. Equivalent experiments are also carried out using trypsin-treated PSF (t-PSF) in which the protein content is digested away using an enzyme. The results show that, at the synovial fluid concentrations tested, the protein content plays a negligible role in either the fluid's bulk shear or extensional flow behaviour. This helps support the validity of the analysis of synovial fluid HA content, either by microfluidic or by other techniques where the synovial fluid is first diluted, and suggests that the HA and protein content in synovial fluid must be higher than a certain minimum threshold concentration before HA-protein or protein-protein interactions become significant. However a systematic shift in the FIB response as the PSF and t-PSF samples are progressively diluted indicates that HA-HA interactions remain significant at the concentrations tested. These interactions influence FIB-derived macromolecular parameters such as the relaxation time and the molecular weight distribution and therefore must be minimized for the best validity of this method as an analytical technique, in which non-interaction between molecules is assumed.

[LE cells in synovial fluid: prevalence and diagnostic usefulness in rheumatic diseases].

PubMed

Puszczewicz, Mariusz; Białkowska-Puszczewicz, Grazyna

2010-01-01

This study was undertaken to determine the prevalence of LE cells in synovial fluid and their importance for the diagnosis of rheumatic disease. Synovial fluid was obtained from 631 patients: 31 with systemic lupus erythematosus (SLE), 337 with rheumatoid arthritis (RA), 4 with Still's disease, 9 with systemic scleroderma (SS), 27 with the overlap syndrome (RA/SLE), 132 with ankylosing spondylitis (AS), 57 with Reiter's syndrome, and 34 with psoriatic arthritis (PA). The fluid was centrifuged, precipitate smears were done and were May-Grünwald-Giemsa stained for cytologic assessment. The supernatant was collected for antinuclear antibody (ANA) testing. Physicochemical and serologic properties of the synovial fluid were routinely determined. All synovial fluids demonstrated signs of inflammation. The presence of LE cells was ascertained in five patients with SLE and nine patients with the overlap syndrome. In these cases, LE cells were accompanied by ANA. In addition, hematoxylin bodies were revealed in SLE patients. LE cells were observed in 2.6% of patients with RA but were not accompanied by ANA. Patients with SS, Still's disease, AS, Reiter's syndrome, and PA tested negative for LE cells. It appears from these results that LE cells are rarely present in the synovial fluid of patients with rheumatic diseases. In contrast, they occur in more than 40% of patients with the overlap syndrome and may thus be regarded as important for the diagnosis of this condition.

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

PubMed Central

Fox, D A; Millard, J A; Kan, L; Zeldes, W S; Davis, W; Higgs, J; Emmrich, F; Kinne, R W

1990-01-01

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis. Images PMID:2212003

Plasma pharmacokinetics and synovial concentrations of S-flurbiprofen plaster in humans.

PubMed

Yataba, Ikuko; Otsuka, Noboru; Matsushita, Isao; Kamezawa, Miho; Yamada, Ichimaro; Sasaki, Sigeru; Uebaba, Kazuo; Matsumoto, Hideo; Hoshino, Yuichi

2016-01-01

The purpose of this study is to investigate the pharmacokinetics and deep tissue penetration capability of the newly developed S-flurbiprofen plaster (SFPP) in humans. Study 1: SFPP tape-type patch (2-60 mg) was applied to the lower back for 24 h in healthy adult volunteers. S-flurbiprofen (SFP) plasma concentration was measured over time to examine SFP pharmacokinetics. Study 2: SFPP (20 mg) was applied for 12 h to the affected knee of osteoarthritis (OA) patients who were scheduled for total knee arthroplasty. Deep tissues (synovial tissue and synovial fluid) were collected during surgery to compare SFP concentrations after application of SFPP or a commercially available flurbiprofen (FP) gel-type patch. Study 1: The plasma concentration of SFP was sustained during 24-h topical application of the SFPP, showing a high percutaneous absorption ratio of 51.4-72.2 %. Cmax and AUC0-∞ were dose-proportional. Study 2: After application of the SFPP for 12 h, SFP concentrations in the synovial tissue and synovial fluid were 14.8-fold (p = 0.002) and 32.7-fold (p < 0.001) higher, respectively, than those achieved by the FP patch. Sustained plasma concentration of SFP and high percutaneous absorption ratio was observed after 24-h topical application of the SFPP. Compared to the FP patch, the SFPP showed superior percutaneous absorption and greater tissue penetration of SFP into the synovial tissue. Greater tissue penetration of the SFPP seemed to be primarily due to its formulation. Thus, SFPP is expected to show higher efficacy for the treatment of knee OA.

Arthroscopic resection of humeroradial synovial plica for persistent lateral elbow pain.

PubMed

Rajeev, Aysha; Pooley, Joesph

2015-04-01

To review the outcome of 121 patients who underwent arthroscopic resection of a humeroradial synovial plica for persistent lateral elbow pain. 92 men and 29 women aged 24 to 56 (mean, 38) years with chronic lateral elbow pain underwent arthroscopic resection of a humeroradial synovial plica using a motorised soft tissue shaver, followed by intensive physiotherapy. The modified elbow score and range of motion were assessed, as were wound healing, infection, soft tissue swelling or effusion, tenderness, ligamentous instability, and motor strength. No patient had any ligamentous instability. 80 patients were pain-free at 3 months; only 3 patients were taking pain medication at 6 months. All patients had full pronation and supination; the mean range of motion was 3º to 135º of flexion. The mean modified elbow score at 12 months was 93.2 (range, 72-100). The percentages of patients with excellent, good, fair, and poor score were 70%, 17%, 8%, and 5% at 3 months, 74%, 20%, 3%, and 3% at 6 months, and 76%, 18%, 3%, and 3% at 12 months, respectively. A humeroradial synovial plica is one of the causes of chronic lateral elbow pain. Arthroscopic resection of the synovial plica followed by intensive physiotherapy achieved good outcome.

Synovial fibroblasts self-direct multicellular lining architecture and synthetic function in three-dimensional organ culture.

PubMed

Kiener, Hans P; Watts, Gerald F M; Cui, Yajun; Wright, John; Thornhill, Thomas S; Sköld, Markus; Behar, Samuel M; Niederreiter, Birgit; Lu, Jun; Cernadas, Manuela; Coyle, Anthony J; Sims, Gary P; Smolen, Josef; Warman, Matthew L; Brenner, Michael B; Lee, David M

2010-03-01

To define the intrinsic capacity of fibroblast-like synoviocytes (FLS) to establish a 3-dimensional (3-D) complex synovial lining architecture characterized by the multicellular organization of the compacted synovial lining and the elaboration of synovial fluid constituents. FLS were cultured in spherical extracellular matrix (ECM) micromasses for 3 weeks. The FLS micromass architecture was assessed histologically and compared with that of dermal fibroblast controls. Lubricin synthesis was measured via immunodetection. Basement membrane matrix and reticular fiber stains were performed to examine ECM organization. Primary human and mouse monocytes were prepared and cocultured with FLS in micromass to investigate cocompaction in the lining architecture. Cytokine stimuli were applied to determine the capacity for inflammatory architecture rearrangement. FLS, but not dermal fibroblasts, spontaneously formed a compacted lining architecture over 3 weeks in the 3-D ECM micromass organ cultures. These lining cells produced lubricin. FLS rearranged their surrounding ECM into a complex architecture resembling the synovial lining and supported the survival and cocompaction of monocyte/macrophages in the neo-lining structure. Furthermore, when stimulated by cytokines, FLS lining structures displayed features of the hyperplastic rheumatoid arthritis synovial lining. This 3-D micromass organ culture method demonstrates that many of the phenotypic characteristics of the normal and the hyperplastic synovial lining in vivo are intrinsic functions of FLS. Moreover, FLS promote survival and cocompaction of primary monocytes in a manner remarkably similar to that of synovial lining macrophages. These findings provide new insight into inherent functions of the FLS lineage and establish a powerful in vitro method for further investigation of this lineage.

Immunoglobulin heavy chain variable region gene utilization by B cell hybridomas derived from rheumatoid synovial tissue.

PubMed

Brown, C M; Longhurst, C; Haynes, G; Plater-Zyberk, C; Malcolm, A; Maini, R N

1992-08-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that primarily affects synovial joints. Activated B lymphocytes and plasma cells are present in the synovial tissue and are thought to contribute to the immunopathology of the rheumatoid joint. To investigate rheumatoid synovial B lymphocytes, we have generated B cell hybridomas from synovial tissue of an RA patient. Here we describe the immunoglobulin VH gene repertoire of eight IgM- and 10 IgG-secreting synovial-derived hybridomas. The VH4 gene family is highly represented (38.5%) in this panel of hybridomas compared with the frequency of VH4 gene expression in circulating B lymphocytes reported previously (19-22%) and with the VH4 gene frequency we observed in a panel of hybridomas derived in the same manner from the spleen and tonsil of normal individuals (19%). The increased frequency of VH4 gene expression was not due to the expansion of a single B cell clone in vivo as none of these hybridomas was clonally related. Two synovial-derived hybridomas secreted autoantibodies; one (VH3+) secreted an IgM-rheumatoid factor (RF) and the other (VH4+) secreted IgM with polyreactive binding to cytoskeletal proteins and cardiolipin. The antibodies secreted by the remaining synovial-derived hybridomas were not reactive with the autoantigens tested. The VH gene usage in a proportion (5/17) of synovial-derived hybridomas that expressed CD5 antigen provided preliminary evidence that CD5+ B cells in RA synovium have a similar increase of VH4 gene expression reported for CD5+ B cells from normal individuals and patients with chronic lymphocytic leukaemia.

Expression of proteins in serum, synovial fluid, synovial membrane, and articular cartilage samples obtained from dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament disease and dogs without stifle joint arthritis.

PubMed

Garner, Bridget C; Kuroki, Keiichi; Stoker, Aaron M; Cook, Cristi R; Cook, James L

2013-03-01

To identify proteins with differential expression between healthy dogs and dogs with stifle joint osteoarthritis secondary to cranial cruciate ligament (CCL) disease. Serum and synovial fluid samples obtained from dogs with stifle joint osteoarthritis before (n = 10) and after (8) surgery and control dogs without osteoarthritis (9) and archived synovial membrane and articular cartilage samples obtained from dogs with stifle joint osteoarthritis (5) and dogs without arthritis (5). Serum and synovial fluid samples were analyzed via liquid chromatography-tandem mass spectrometry; results were compared against a nonredundant protein database. Expression of complement component 3 in archived tissue samples was determined via immunohistochemical methods. No proteins had significantly different expression between serum samples of control dogs versus those of dogs with stifle joint osteoarthritis. Eleven proteins (complement component 3 precursor, complement factor I precursor, apolipoprotein B-100 precursor, serum paraoxonase and arylesterase 1, zinc-alpha-2-glycoprotein precursor, serum amyloid A, transthyretin precursor, retinol-binding protein 4 precursor, alpha-2-macroglobulin precursor, angiotensinogen precursor, and fibronectin 1 isoform 1 preproprotein) had significantly different expression (> 2.0-fold) between synovial fluid samples obtained before surgery from dogs with stifle joint osteoarthritis versus those obtained from control dogs. Complement component 3 was strongly expressed in all (5/5) synovial membrane samples of dogs with stifle joint osteoarthritis and weakly expressed in 3 of 5 synovial membrane samples of dogs without stifle joint arthritis. Findings suggested that the complement system and proteins involved in lipid and cholesterol metabolism may have a role in stifle joint osteoarthritis, CCL disease, or both.

Synovial deposition of wild-type transthyretin-derived amyloid in knee joint osteoarthritis patients.

PubMed

Takanashi, Tetsuo; Matsuda, Masayuki; Yazaki, Masahide; Yamazaki, Hideshi; Nawata, Masashi; Katagiri, Yoshiki; Ikeda, Shu-Ichi

2013-09-01

To investigate histological features of deposited amyloid in the synovial tissue and its clinical significance in knee joint osteoarthritis (OA) patients. We prospectively enrolled 232 consecutive patients who underwent arthroplasty or total replacement of the knee joint for treatment of OA. Congo red staining and immunohistochemistry were performed in the synovial tissue obtained at surgery. When transthyretin (TTR)-derived amyloid was positive, we analyzed all 4 exons of the TTR gene using the direct DNA sequencing method in order to detect mutations. We analyzed 322 specimens in this study. Twenty-six specimens (8.1%) obtained from 21 patients (5 men and 16 women; mean, 79.0 ± 4.6 years) showed deposition of amyloid, which was positively stained with the anti-TTR antibody. Eighteen patients showed inhomogeneous accumulations of amyloid in the loose connective tissue under the synovial epithelia sometimes with nodule formation, while in the remaining three, small vessels in the adipose tissue were involved. Medical records of these patients revealed nothing remarkable in the clinical course, laboratory data or macroscopic intraarticular findings at surgery. No mutations were detectable in the TTR gene analysis. Wild-type TTR-derived amyloid may affect the synovial tissue as a result of long-term mechanical stress or as a part of senile systemic amyloidosis in approximately 8% of knee joint OA patients. No obvious clinical significance was found in synovial deposition of amyloid.

Direct Detection and Identification of Prosthetic Joint Infection Pathogens in Synovial Fluid by Metagenomic Shotgun Sequencing.

PubMed

Ivy, Morgan I; Thoendel, Matthew J; Jeraldo, Patricio R; Greenwood-Quaintance, Kerryl E; Hanssen, Arlen D; Abdel, Matthew P; Chia, Nicholas; Yao, Janet Z; Tande, Aaron J; Mandrekar, Jayawant N; Patel, Robin

2018-05-30

Background: Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis, since synovial fluid cultures are not universally positive, and synovial fluid is easily obtained pre-operatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Results: Genus- and species-level analysis of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analysis yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analysis of the 60 culture-negative aseptic failure cases yielded 53 (88.3%) and 56 (93.3%) cases with insignificant findings, and 7 (11.7%) and 4 (6.7%) with potential clinically-significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Conclusion: Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases. Copyright © 2018 American Society for Microbiology.

Comparison of synovial fluid culture and 16S rRNA PCR in dogs with suspected septic arthritis.

PubMed

Scharf, V F; Lewis, D D; Wellehan, J F; Wamsley, H L; Richardson, R

2015-06-01

To prospectively compare the sensitivity and specificity of 16S rRNA PCR with culture for identifying the causative organism in synovial fluid obtained from dogs with suspected septic arthritis. Synovial fluid cytology, PCR analysis and aerobic, anaerobic and Mycoplasma culture of samples from the affected joints of 18 dogs presenting with suspected septic arthritis were performed. Synovial fluid samples from the corresponding contralateral joints of 7 dogs were also analysed as negative controls. There was no significant difference between the sensitivity of bacterial detection via culture (63.2%) versus PCR (73.7%) of synovial fluid (P=0.728) or between culture and combined PCR and culture (89.5%) of synovial fluid (P=0.124). The specificity of PCR (42.9%) was significantly lower than culture specificity (100%) (P=0.07). Although 16S PCR may hold potential as an ancillary diagnostic test for identifying the causative organism in dogs with septic arthritis, our study failed to demonstrate improved accuracy compared with traditional synovial fluid culture. © 2015 Australian Veterinary Association.

Synovial Fluid Response to Extensional Flow: Effects of Dilution and Intermolecular Interactions

PubMed Central

Haward, Simon J.

2014-01-01

In this study, a microfluidic cross-slot device is used to examine the extensional flow response of diluted porcine synovial fluid (PSF) samples using flow-induced birefringence (FIB) measurements. The PSF sample is diluted to 10× 20× and 30× its original mass in a phosphate-buffered saline and its FIB response measured as a function of the strain rate at the stagnation point of the cross-slots. Equivalent experiments are also carried out using trypsin-treated PSF (t-PSF) in which the protein content is digested away using an enzyme. The results show that, at the synovial fluid concentrations tested, the protein content plays a negligible role in either the fluid's bulk shear or extensional flow behaviour. This helps support the validity of the analysis of synovial fluid HA content, either by microfluidic or by other techniques where the synovial fluid is first diluted, and suggests that the HA and protein content in synovial fluid must be higher than a certain minimum threshold concentration before HA-protein or protein-protein interactions become significant. However a systematic shift in the FIB response as the PSF and t-PSF samples are progressively diluted indicates that HA-HA interactions remain significant at the concentrations tested. These interactions influence FIB-derived macromolecular parameters such as the relaxation time and the molecular weight distribution and therefore must be minimized for the best validity of this method as an analytical technique, in which non-interaction between molecules is assumed. PMID:24651529

The dual regulation of substance P-mediated inflammation via human synovial mast cells in rheumatoid arthritis.

PubMed

Okamura, Yuki; Mishima, Shintaro; Kashiwakura, Jun-Ichi; Sasaki-Sakamoto, Tomomi; Toyoshima, Shota; Kuroda, Kazumichi; Saito, Shu; Tokuhashi, Yasuaki; Okayama, Yoshimichi

2017-09-01

Neural pathways are thought to be directly involved in the pathogenesis of rheumatoid arthritis (RA). Although synovial mast cells (MCs) are activated by substance P (SP), the role of MCs in neural pathways in RA remains unknown. The aims of this study were to investigate 1) whether tachykinins are produced by synovial MCs and whether production differs in RA and osteoarthritis (OA) patients, and 2) what is the responsible receptor for SP in synovial MCs. Synovial tissues were obtained from patients with RA or OA undergoing joint replacement surgery. Cultured synovium-derived MCs were generated by culturing dispersed synovial cells with stem cell factor. SP expression was investigated using immunofluorescence and enzyme immunoassays. Mas-related gene X2 (MrgX2) expression was reduced in human MCs using a lentiviral shRNA silencing technique. SP expression was localized around the cell membrane in 41% (median) of the MCs in synovium from RA but in only 7% of that from OA, suggesting the activation of MCs. Synovial MCs expressed tachykinin (TAC) 1 mRNA, the expression of which was upregulated by the aggregation of FcɛRI or the addition of aggregated IgG. However, the released SP appeared to be rapidly degraded by MC chymase. Synovial MCs were activated with SP through MrgX2 to release histamine without producing proinflammatory cytokines. Activated synovial MCs may rapidly degrade SP, which may downregulate the SP-mediated activation of synoviocytes in RA. On the other hand, SP activates MCs to induce inflammatory mediators, suggesting the dual regulation of SP-mediated inflammation by MCs in RA. Copyright © 2017 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Concentration polarization of hyaluronan on the surface of the synovial lining of infused joints

PubMed Central

Lu, Y; Levick, JR; Wang, W

2004-01-01

Hyaluronan (HA) in joints conserves the lubricating synovial fluid by making trans-synovial fluid escape almost insensitive to pressure elevation (e.g. effusions, joint flexion). This phenomenon, ‘outflow buffering’, was discovered during HA infusion into the rabbit knee joint cavity. It was also found that HA is partially reflected by the joint lining (molecular sieving), and that the reflected fraction R decreases as trans-synovial filtration rate Q is increased. It was postulated therefore that outflow buffering is mediated by HA reflection. Reflection creates a HA concentration polarization layer, the osmotic pressure of which opposes fluid loss. A steady-state, cross-flow ultrafiltration model was previously used to explain the outflow buffering and negative R-vs.-Q relation. However, the steady-state, cross-perfusion assumptions restricted the model's applicability for an infused, dead-end cavity or a non-infused joint during cyclical motion. We therefore developed a new, non-steady-state model which describes the time course of dead-end, partial HA ultrafiltration. The model describes the progressive build-up of a HA concentration polarization layer at the synovial surface over time. Using experimental parameter values, the model successfully accounts for the observed negative R-vs.-Q relation and shows that the HA reflected fraction (R) also depends on HA diffusivity, membrane area expansion and the synovial HA reflection coefficient. The non-steady-state model thus explains existing experimental work, and it is a key stage in understanding synovial fluid turnover in intact, moving, human joints or osteoarthritic joints treated by HA injections. PMID:15579541

Mesenchymal Stem/Progenitor Cells Derived from Articular Cartilage, Synovial Membrane and Synovial Fluid for Cartilage Regeneration: Current Status and Future Perspectives.

PubMed

Huang, Yi-Zhou; Xie, Hui-Qi; Silini, Antonietta; Parolini, Ornella; Zhang, Yi; Deng, Li; Huang, Yong-Can

2017-10-01

Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.

Synovial sarcoma of the neck associated with previous head and neck radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mischler, N.E.; Chuprevich, T.; Tormey, D.C.

1978-08-01

Synovial sarcoma is a rare neoplasm that uncommonly arises in the neck. Fourteen years after facial and neck radiation therapy for acne, synovial sarcoma of the neck developed in a young man. Possible radiation-induced benign and malignant neoplasms that arise in the head and neck region, either of thyroid or extrathyroid origin, remain a continuing medical problem.

A rapid screen for four corticosteroids in equine synovial fluid.

PubMed

Agrawal, Karan; Ebel, Joseph G; Bischoff, Karyn

2014-06-01

Most antidoping method development in the equine industry has been for plasma and urine, though there has been recent interest in the analysis of synovial fluid for evidence of doping by intra-articular corticosteroid injection. Published methods for corticosteroid analysis in synovial fluid are primarily singleplex methods, do not screen for all corticosteroids of interest and are not adequately sensitive. The purpose of this study is to develop a rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) screening method for the detection of four of the most common intra-articularly administered corticosteroids--betamethasone, methylprednisolone, methylprednisolone acetate and triamcinolone acetonide. Sample preparation consisted of protein precipitation followed by a basified liquid-liquid extraction. LC-MS-MS experiments consisted of a six-min isocratic separation using a Phenomenex Polar-RP stationary phase and a mobile phase consisting of 35% acetonitrile, 5 mM ammonium acetate and 0.1% formic acid in nanopure water. The detection system used was a triple quadrupole mass analyzer with thermospray ionization, and compounds were identified using selective reaction monitoring. The method was validated to the ISO/IEC 17025 standard, and real synovial fluid samples were analyzed to demonstrate the application of the method in an antidoping context. The method was highly selective for the four corticosteroids with limits of detection of 1-3 ng/mL. The extraction efficiency was 50-101%, and the matrix effects were 14-31%. These results indicate that the method is a rapid and sensitive screen for the four corticosteroids in equine synovial fluid, fit for purpose for equine antidoping assays.

Retrospective evaluation of the efficacy of isolating bacteria from synovial fluid in dogs with suspected septic arthritis.

PubMed

Scharf, V F; Lewis, S T; Wellehan, J F; Wamsley, H L; Richardson, R; Sundstrom, D A; Lewis, D D

2015-06-01

To evaluate the efficacy of synovial fluid culture in obtaining the causative organism from dogs with suspected septic arthritis. In this retrospective evaluation, synovial fluid cytology and microbiology submissions from dogs with suspected septic arthritis from March 2007 to August 2011 were reviewed. Synovial fluid cytology consistent with joint sepsis was identified. Cultures of synovial fluid from dogs with clinical histories and abnormalities consistent with septic arthritis were used to evaluate the efficacy of bacterial isolation. In total, 36 dogs met the inclusion criteria. Initial aerobic cultures of joint fluid yielded bacterial growth in 44% of these dogs. All anaerobic cultures were negative. In 19% of the dogs with positive cultures, antibiotics had been administered prior to arthrocentesis compared with 10% of dogs with negative cultures. There was no association between culture efficacy and the administration of antimicrobial treatment prior to synovial fluid culture or recent surgery involving the affected joint (P=0.637 and P=0.106, respectively). Culture of synovial fluid from dogs with suspected septic arthritis has a low yield, necessitating a more effective means of identifying bacteria from suspected septic joints in dogs. © 2015 Australian Veterinary Association.

Tribological and Rheological Properties of a Synovial Fluid Model

NASA Astrophysics Data System (ADS)

Klossner, Rebecca; Liang, Jing; Krause, Wendy

2010-03-01

Hyaluronic acid (HA) and the plasma proteins, albumin and globulins, are the most abundant macromolecules in synovial fluid, the fluid that lubricates freely moving joints. In previous studies, bovine synovial fluid, a synovial fluid model (SFM) and albumin in phosphate buffered saline (PBS) were observed to be rheopectic---viscosity increases over time under constant shear. Additionally, steady shear experiments have a strong shear history dependence in protein-containing solutions, whereas samples of HA in PBS behaved as a ``typical'' polyelectrolyte. The observed rheopexy and shear history dependence are indicative of structure building in solution, which is most likely caused by protein aggregation. The tribology of the SFM was also investigated using nanoindenter-based scratch tests. The coefficient of frictions (μ) between the diamond nanoindenter tip and a polyethylene surface was measured in the presence of the SFM and solutions with varied protein and HA concentrations. The lowest μ is observed in the SFM, which most closely mimics a healthy joint. Finally, an anti-inflammatory drug, hydroxychloroquine, was shown to inhibit protein interactions in the SFM in rheological studies, and thus the tribological response was examined. We hypothesize that the rheopectic behavior is important in lubrication regimes and therefore, the rheological and tribological properties of these solutions will be correlated.

Analysis of synovial fluid components of hydrarthrosis in long-term hemodialysis patients.

PubMed

Shiota, E; Maekawa, M; Ohtani, M

1999-01-01

The synovial fluid components in long-term hemodialysis patients (HD; 43 knees in 43 patients) were investigated and compared with those in patients with osteoarthritis (OA; 21 knees in 21 patients) and rheumatoid arthritis (RA; 26 knees in 26 patients). The average ages in the three groups were, respectively, 60.7 years (range, 34-79 years), 63.2 years (range, 48-88 years), and 59.7 years (range, 37-76 years). The duration of hemodialysis in the HD group averaged 14.0 years (range, 4-24 years). The concentrations of hyaluronic acid, protein, and isomers of chondroitin sulfate (chondroitin 6-sulfate [C6S] and chondroitin 4-sulfate [C4S]) in the synovial fluid, and its viscosity were measured. Differences in each of the parameters were investigated according to disease clinical stage, roentgenological grade, and periods of dialysis in the HD group. The viscosity of the synovial fluid and the concentration of hyaluronic acid in HD patients were similar to those in OA patients; however, the C6S/C4S ratio in the synovial fluid of HD patients was similar to that in RA patients. The latter finding suggests that synovitis may be present in the hydrarthrosis of HD patients. The cause of this synovitis in HD patients remains to be elucidated.

Effect of repeated arthrocentesis on cytologic analysis of synovial fluid in dogs.

PubMed

Berg, R I M; Sykes, J E; Kass, P H; Vernau, W

2009-01-01

Serial arthrocentesis and synovial fluid examination can be used to monitor treatment efficacy in immune-mediated polyarthritis (IMPA), but whether this procedure induces inflammation that interferes with test result interpretation is unknown. The aim of this study was to determine the effect of repeated arthrocentesis on synovial fluid cytology in healthy dogs. Nine healthy client-owned dogs. Prospective study. Arthrocentesis was performed under sedation on 4 joints (both carpi, 1 tarsus, 1 stifle) on each dog every 3 weeks, a total of 4 times. Automated cell counts were done on stifle fluid, smears were made, and differential cell counts done on smears from all joints. Slides were evaluated microscopically for erythrocyte numbers, total nucleated cell count, differential cell count, and cell morphology. Data were analyzed by 2-way analysis of variance. A total of 144 synovial fluid samples were examined. Repeated arthrocentesis was not associated with increases in synovial fluid neutrophil numbers. Mild mononuclear inflammation was detected in 13 samples from 6 dogs. Serial arthrocentesis at 3-week intervals can rarely be associated with mild mononuclear joint inflammation, but does not appear to induce neutrophilic inflammation, at least in healthy dogs, and can be useful to monitor treatment response in canine IMPA.

Connexin43 Mediated Delivery of ADAMTS5 Targeting siRNAs from Mesenchymal Stem Cells to Synovial Fibroblasts.

PubMed

Liu, Shuo; Niger, Corinne; Koh, Eugene Y; Stains, Joseph P

2015-01-01

Osteoarthritis is a joint-destructive disease that has no effective cure. Human mesenchymal stem cells (hMSCs) could offer therapeutic benefit in the treatment of arthritic diseases by suppressing inflammation and permitting tissue regeneration, but first these cells must overcome the catabolic environment of the diseased joint. Likewise, gene therapy also offers therapeutic promise given its ability to directly modulate key catabolic factors that mediate joint deterioration, although it too has limitations. In the current study, we explore an approach that combines hMSCs and gene therapy. Specifically, we test the use of hMSC as a vehicle to deliver ADAMTS5 (an aggrecanase with a key role in osteoarthritis)-targeting siRNAs to SW982 synovial fibroblast-like cells via connexin43 containing gap junctions. Accordingly, we transduced hMSCs with ADAMTS5-targeting shRNA or non-targeted shRNA, and co-cultured them with synovial fibroblasts to allow delivery of siRNAs from hMSC to synovial fibroblasts. We found that co-culture of hMSCs-shRNA-ADAMTS5 and synovial fibroblasts reduced ADAMTS5 expression relative to co-culture of hMSCs-shRNA-control and synovial fibroblasts. Furthermore, ADAMTS5 was specifically reduced in the synovial fibroblasts populations as determined by fluorescence-activated cell sorting, suggesting transfer of the siRNA between cells. To test if Cx43-containing gap junctions are involved in the transfer of siRNA, we co-cultured hMSCs-shRNA-ADAMTS5 cells with synovial fibroblasts in which connexin43 was knocked down. Under these conditions, ADAMTS5 levels were not inhibited by co-culture, indicating that connexin43 mediates the delivery of siRNA from hMSCs to synovial fibroblasts. In total, our findings demonstrate that hMSCs can function as donor cells to host and deliver siRNAs to synovial fibroblasts via connexin43 gap junction in vitro. These data may have implications in the combination of hMSCs and gene therapy to treat diseases like

OSTEOCHONDROMA OF THE PROXIMAL HUMERUS WITH FRICTIONAL BURSITIS AND SECONDARY SYNOVIAL OSTEOCHONDROMATOSIS.

PubMed

De Groote, J; Geerts, B; Mermuys, K; Verstraete, K

2015-01-01

We report a case of multiple hereditary exostosis in a 33-year old patient with clinical symptoms of pain and impression of a growing mass of the left shoulder alerting potential risk of malignant transformation of an osteochondroma. Imaging studies illustrated perilesional bursitis surrounding an osteochondroma of the proximal humerus. Malignant transformation was excluded with MRI. Fragments of the osteochondroma were dislocated in the inflammatory synovial bursa illustrating a case of secondary synovial osteochondromatosis.

Btk inhibition suppresses agonist-induced human macrophage activation and inflammatory gene expression in RA synovial tissue explants.

PubMed

Hartkamp, Linda M; Fine, Jay S; van Es, Inge E; Tang, Man Wai; Smith, Michael; Woods, John; Narula, Satwant; DeMartino, Julie; Tak, Paul P; Reedquist, Kris A

2015-08-01

Bruton's tyrosine kinase (Btk) is required for B lymphocyte and myeloid cell contributions to pathology in murine models of arthritis. Here, we examined the potential contributions of synovial Btk expression and activation to inflammation in rheumatoid arthritis (RA). Btk was detected by immunohistochemistry and digital image analysis in synovial tissue from biologically naive RA (n=16) and psoriatic arthritis (PsA) (n=12) patients. Cell populations expressing Btk were identified by immunofluorescent double labelling confocal microscopy, quantitative (q-) PCR and immunoblotting. The effects of a Btk-specific inhibitor, RN486, on gene expression in human macrophages and RA synovial tissue explants (n=8) were assessed by qPCR, ELISA and single-plex assays. Btk was expressed at equivalent levels in RA and PsA synovial tissue, restricted to B lymphocytes, monocytes, macrophages and mast cells. RN486 significantly inhibited macrophage IL-6 production induced by Fc receptor and CD40 ligation. RN486 also reduced mRNA expression of overlapping gene sets induced by IgG, CD40 ligand (CD40L) and RA synovial fluid, and significantly suppressed macrophage production of CD40L-induced IL-8, TNF, MMP-1 and MMP-10, LPS-induced MMP-1, MMP-7 and MMP-10 production, and spontaneous production of IL-6, PDGF, CXCL-9 and MMP-1 by RA synovial explants. Btk is expressed equivalently in RA and PsA synovial tissue, primarily in macrophages. Btk activity is needed to drive macrophage activation in response to multiple agonists relevant to inflammatory arthritis, and promotes RA synovial tissue cytokine and MMP production. Pharmacological targeting of Btk may be of therapeutic benefit in the treatment of RA and other inflammatory diseases. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Examination of synovial fluid hyaluronan quantity and quality in stifle joints of dogs with osteoarthritis.

PubMed

Venable, Rachel O; Stoker, Aaron M; Cook, Cristi R; Cockrell, Mary K; Cook, James L

2008-12-01

To determine the quantity (concentration) and quality (molecular weight) of synovial fluid hyaluronan with respect to presence and severity of osteoarthritis in stifle joints of dogs. 21 purpose-bred dogs and 6 clinically affected large-breed dogs (cranial cruciate ligament [CrCL] disease with secondary osteoarthritis). Research dogs underwent arthroscopic surgery in 1 stifle joint to induce osteoarthritis via CrCL transection (CrCLt; n=5 stifle joints), femoral condylar articular cartilage groove creation (GR; 6), or meniscal release (MR; 5); 5 had sham surgery (SH) performed. Contralateral stifle joints (n=21) were used as unoperated control joints. Synovial fluid was obtained from research dogs at time 0 and 12 weeks after surgery and from clinically affected dogs prior to surgery. All dogs were assessed for lameness, radiographic signs of osteoarthritis, and pathologic findings on arthroscopy as well as for quantity and quality of hyaluronan. Clinically affected dogs had significantly greater degrees of pathologic findings, compared with dogs with surgically induced osteoarthritis (ie, those with CrCLt, GR, and MR stifle joints), and with respect to lameness scores, radiographic signs of osteoarthritis, pathologic findings on arthroscopy, and synovial fluid hyaluronan concentration. Synovial fluid from stifle joints of dogs with surgically induced osteoarthritis had hyaluronan bands at 35 kd on western blots that synovial fluid from SH and clinically affected stifle joints did not. Synovial fluid hyaluronan quantity and quality were altered in stifle joints of dogs with osteoarthritis, compared with control stifle joints. A specific hyaluronan protein fragment may be associated with early pathologic changes in affected joints.

MT1-MMP is a crucial promotor of synovial invasion in human rheumatoid arthritis

PubMed Central

Miller, Mary-Clare; Manning, Hugh B.; Jain, Abhilash; Troeberg, Linda; Dudhia, Jayesh; Essex, David; Sandison, Ann; Seiki, Motoharu; Nanchahal, Jagdeep; Nagase, Hideaki; Itoh, Yoshifumi

2010-01-01

Objective A hallmark of rheumatoid arthritis (RA) is invasion of the synovial pannus into cartilage and this step requires degradation of the collagen matrix. The aim of this study was to explore the role of one of the collagen-degrading matrix metalloproteinases (MMPs), membrane-type 1 MMP (MT1-MMP), in synovial pannus invasiveness. Methods Expression and localization of MT1-MMP in human RA pannus were investigated by Western blot analysis of primary synovial cells and immunohistochemistry of RA joints specimens. The functional role of MT1-MMP was analyzed by 3D collagen invasion assays and a cartilage invasion assay in the presence or absence of tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, or GM6001. The effect of adenoviral expression of a dominant negative MT1-MMP construct lacking a catalytic domain was also examined. Results MT1-MMP was highly expressed at the pannus-cartilage junction of RA joints. Freshly isolated rheumatoid synovial tissues and isolated RA synovial fibroblasts invaded into a 3D collagen matrix in an MT1-MMP-dependent manner. Invasion was blocked by TIMP-2 and GM6001, but not by TIMP-1. It was also inhibited by the over-expression of a dominant negative MT1-MMP which inhibits collagenolytic activity and proMMP-2 activation by MT1-MMP on the cell surface. Synovial fibroblasts also invaded into cartilage in an MT1-MMP-dependent manner. This process was further enhanced by removing aggrecan from the cartilage matrix. Conclusion MT1-MMP is an essential collagen-degrading proteinase during pannus invasion in human RA. Specific inhibition of MT1-MMP-dependent invasion may form a novel therapeutic strategy for RA. PMID:19248098

Size selectivity of hyaluronan molecular sieving by extracellular matrix in rabbit synovial joints

PubMed Central

Sabaratnam, S; Arunan, V; Coleman, PJ; Mason, RM; Levick, JR

2005-01-01

In joint fluid the polymer hyaluronan (HA) confers viscous lubrication and greatly attenuates trans-synovial fluid loss (outflow buffering). Outflow buffering arises from the molecular sieving (reflection) and concentration polarization of HA at the synovial membrane surface. Outflow buffering declines if HA chain length is reduced, as in arthritis, and this has been attributed to reduced HA reflection. This was tested directly in the present study. Infused solutions of HA of ∼2200 kDa (HA2000, 0.2 mg ml−1) or ∼500 kDa (HA500, 0.2 mg ml−1) or ∼140 kDa (HA140, 0.2–4.0 mg ml−1) were filtered across the synovial lining of the knee joint cavity of anaesthetized rabbits at a constant rate, along with a freely permeating reference solute, 20 kDa fluorescein–dextran (FD20). After a priming period the femoral lymph was sampled over 3 h. Mixed intra-articular (i.a.) fluid and subsynovial fluid were sampled at the end. Fluids were analysed by gel exclusion chromatography. The trans-synovial concentration profile was found to depend on polymer size. The i.a. concentration of HA2000 increased substantially relative to infusate and the subsynovial and lymph concentrations fell substantially. For HA500 and HA140 the trans-synovial concentration gradients were less pronounced, and absent for FD. The reflected fractions for HA2000, HA500 and HA140 across the cavity-to-lymph barrier were 0.65 ± 0.05 (n = 10), 0.43 ± 0.09 (n = 3) and 0.19 ± 0.05 (n = 7), respectively, at matched filtration rates (P < 0.0001, analysis of variance). Reflected fractions calculated from HA i.a. accumulation or subsynovial dilution showed the same trend. The results demonstrate size-selective molecular sieving by the synovial extracellular matrix, equivalent to steric exclusion from cylindrical pores of radius 33–59 nm. The findings underpin the concentration polarization-outflow buffering theory and indicate that reduced HA chain length in arthritis exacerbates lubricant loss from a

A guided tour of current research in synovial joints with reference to wavelet methodology

NASA Astrophysics Data System (ADS)

Agarwal, Ruchi; Salimath, C. S.; Alam, Khursheed

2017-10-01

Main aim of this article is to provide a comprehensive overview of biomechanical aspects of synovial joints of human body. This can be considered as a part of continued research work carried out by various authors over a period of time. Almost every person once in life time has suffered from joint disease; this has triggered intensive investigation into various biomechanical aspects of synovial joints. This has also resulted into an increase of arthroplasty with introduction to various clinical trials. From last few decades new improvements and ideas for new technologies have been introduced to decrease the incidence of joint problem. In this paper a literature survey of recent advances, developments and recognition of wear and tear of human joint is presented. Wavelet method in Computational fluid dynamics (CFD) is relatively a new research field. This review aims to provide a glimpse of wavelet methodology in CFD. Wavelets methodology has played a vital role in the solution of governing equation of synovial fluid flow in the synovial joints represented by Reynolds equation and its modified version.

Impact of synovial fluid flow on temperature regulation in knee cartilage.

PubMed

Moghadam, Mohamadreza Nassajian; Abdel-Sayed, Philippe; Camine, Valérie Malfroy; Pioletti, Dominique P

2015-01-21

Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Analysis of factors related to the number of mesenchymal stem cells derived from synovial fluid of the temporomandibular joint].

PubMed

Sun, Y P; Zheng, Y H; Zhang, Z G

2017-06-09

Objective: To analyze related factors on the number of mesenchymal stem cells in the synovial fluid of the temporomandibular joint (TMJ) and provide an research basis for understanding of the source and biological role of mesenchymal stem cells derived from synovial fluid in TMJ. Methods: One hundred and twenty-two synovial fluid samples from 91 temporomandibular disorders (TMD) patients who visited in Department of TMJ Center, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University from March 2013 to December 2013 were collected in this study, and 6 TMJ synovial fluid samples from 6 normal volunteers who were studying in the North Campus of Sun Yat-sen University were also collected, so did their clinical information. Then the relation between the number of mesenchymal stem cells derived from synovial fluid and the health status of the joints, age of donor, disc perforation, condylar bony destruction, blood containing and visual analogue scale score of pain were investigated using Mann-Whitney U test and Spearman rank correlation test. Results: The number of mesenchymal stem cells derived from synovial fluid had no significant relation with visual analogue scale score of pain ( r= 0.041, P= 0.672), blood containing ( P= 0.063), condylar bony destruction ( P= 0.371). Linear correlation between the number of mesenchymal stem cells derived from synovial fluid and age of donor was very week ( r= 0.186, P= 0.043). The number of mesenchymal stem cells up-regulated when the joint was in a disease state ( P= 0.001). The disc perforation group had more mesenchymal stem cells in synovial fluid than without disc perforation group ( P= 0.042). Conclusions: The number of mesenchymal stem cells derived from synovial fluid in TMJ has no correlation with peripheral blood circulation and condylar bony destruction, while has close relation with soft tissue structure damage of the joint.

Establishment and characterization of the NCC-SS1-C1 synovial sarcoma cell line.

PubMed

Kito, Fusako; Oyama, Rieko; Takai, Yoko; Sakumoto, Marimu; Shiozawa, Kumiko; Qiao, Zhiwei; Uehara, Takenori; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-04-01

Synovial sarcoma is an aggressive mesenchymal malignancy characterized by unique gene fusions. Tissue culture cells are essential tools for further understanding tumorigenesis and anti-cancer drug development; however, only a limited number of well-characterized synovial sarcoma cell lines exist. Thus, the objective of this study was to establish a patient-derived synovial sarcoma cell line. We established a synovial sarcoma cell line from tumor tissue isolated from a 72-year-old female patient. Prepared cells were analyzed for the presence of gene fusions by fluorescence in situ hybridization, RT-PCR, and karyotyping. In addition, the resulting cell line was characterized by viability, short tandem repeat, colony and spheroid formation, and invasion analyses. Differences in gene enrichment between the primary tumor and cell line were examined by mass spectrometric protein expression profiling and KEGG pathway analysis. Our analyses revealed that the primary tumor and NCC-SS1-C1 cell line harbored the SS18-SSX1 fusion gene typical of synovial sarcoma and similar proteomics profiles. In vitro analyses also confirmed that the established cell line harbored invasive, colony-forming, and spheroid-forming potentials. Moreover, drug screening with chemotherapeutic agents and tyrosine kinase inhibitors revealed that doxorubicin, a subset of tyrosine kinase inhibitors, and several molecular targeting drugs markedly decreased NCC-SS1-C1 cell viability. Results from the present study support that the NCC-SS1-C1 cell line will be an effective tool for sarcoma research.

Identification of the advanced glycation end products N -carboxymethyllysine in the synovial tissue of patients with rheumatoid arthritis

PubMed Central

Drinda, S; Franke, S; Canet, C; Petrow, P; Brauer, R; Huttich, C; Stein, G; Hein, G

2002-01-01

Background: Generation of advanced glycation end products (AGEs) is an inevitable process in vivo and can be accelerated under pathological conditions such as oxidative stress. In serum and synovial fluid of patients with rheumatoid arthritis (RA) raised AGE levels have been found. Objective: To determine the presence of N -carboxymethyllysine (CML; marker of oxidative stress) in RA synovial tissue by immunohistology. Methods: Frozen synovial tissue samples from 10 patients with RA and eight controls (four patients without joint disease and four patients with osteoarthritis (OA)) were treated with rabbit-anti-CML-IgG and goat-antirabbit-IgG. Immunostaining was visualised by streptavidine-alkaline phosphatase (chromogen fuchsin). Cell differentiation was performed with antibodies against CD68, CD45RO, and CD20. Results: CML was detected in the synovial lining, sublining, and endothelium in 10/10 RA and 4/4 OA synovial specimens. In RA some macrophages (CD68+) and T cells (CD45RO+) showed positive immunostaining for CML, whereas B cells were negative. Staining in OA synovial sublining was weak compared with RA. Conclusions: CML was detected for the first time in RA and OA synovial tissue. Different patterns of immunostaining in RA and OA and the presence of CML on macrophages and T cells, suggest a role for CML in the pathogenesis of RA. This might be due to presentation of new epitopes which can maintain or even trigger an autoimmune response. PMID:12006318

Synovial fluid multiplex PCR is superior to culture for detection of low-virulent pathogens causing periprosthetic joint infection.

PubMed

Morgenstern, Christian; Cabric, Sabrina; Perka, Carsten; Trampuz, Andrej; Renz, Nora

2018-02-01

Analysis of joint aspirate is the standard preoperative investigation for diagnosis of periprosthetic joint infection (PJI). We compared the diagnostic performance of culture and multiplex polymerase chain reaction (PCR) of synovial fluid for diagnosis of PJI. Patients in whom aspiration of the prosthetic hip or knee joint was performed before revision arthroplasty were prospectively included. The performance of synovial fluid culture and multiplex PCR was compared by McNemar's chi-squared test. A total of 142 patients were included, 82 with knee and 60 with hip prosthesis. PJI was diagnosed in 77 patients (54%) and aseptic failure in 65 patients (46%). The sensitivity of synovial fluid culture and PCR was 52% and 60%, respectively, showing concordant results in 116 patients (82%). In patients with PJI, PCR missed 6 high-virulent pathogens (S. aureus, streptococci, E. faecalis, E. coli) which grew in synovial fluid culture, whereas synovial fluid culture missed 12 pathogens detected by multiplex PCR, predominantly low-virulent pathogens (Cutibacterium acnes and coagulase-negative staphylococci). In patients with aseptic failure, PCR detected 6 low-virulent organisms (predominantly C. acnes). While the overall performance of synovial fluid PCR was comparable to culture, PCR was superior for detection of low-virulent bacteria such as Cutibacterium spp. and coagulase-negative staphylococci. In addition, synovial fluid culture required several days for growth, whereas multiplex PCR provided results within 5hours in an automated manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Synovial chemokine expression and relationship with knee symptoms in patients with meniscal tears

PubMed Central

Nair, Anjali; Gan, Justin; Bush-Joseph, Charles; Verma, Nikhil; Tetreault, Matthew W.; Saha, Kanta; Margulis, Arkady; Fogg, Louis; Scanzello, Carla R.

2015-01-01

Objective In patients with knee OA, synovitis is associated with knee pain and symptoms. We previously identified synovial mRNA expression of a set of chemokines (CCL19, IL-8, CCL5, XCL-1, CCR7) associated with synovitis in patients with meniscal tears but without radiographic OA. CCL19 and CCR7 were also associated with knee symptoms. This study sought to validate expression of these chemokines and association with knee symptoms in more typical patients presenting for meniscal arthroscopy, many who have pre-existing OA. Design Synovial biopsies and fluid (SF) were collected from patients undergoing meniscal arthroscopy. Synovial mRNA expression was measured using quantitative RT-PCR. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was administered preoperatively. Regression analyses determined if associations between chemokine mRNA levels and KOOS scores were independent of other factors including radiographic OA. CCL19 in SF was measured by ELISA, and compared to patients with advanced knee OA and asymptomatic organ donors. Results 90% of patients had intra-operative evidence of early cartilage degeneration. CCL19, IL-8, CCL5, XCL1, CCR7 transcripts were detected in all patients. Synovial CCL19 mRNA levels independently correlated with KOOS Activities of Daily Living scores (95% CI [-8.071, -0.331], p= 0.036), indicating higher expression was associated with more knee-related dysfunction. SF CCL19 was detected in 7 of 10 patients, compared to 4 of 10 asymptomatic donors. Conclusion In typical patients presenting for meniscal arthroscopy, synovial CCL19 mRNA expression was associated with knee-related difficulty with activities of daily living, independent of other factors including presence of radiographic knee OA. PMID:25724256

Bilateral symptomatic synovial cysts of the lumbar spine caused by calcium pyrophosphate deposition disease: a case report.

PubMed

Gadgil, Anirudh A; Eisenstein, Stephan M; Darby, Alan; Cassar Pullicino, Victor

2002-10-01

A case of bilateral symptomatic facet joint synovial cysts arising in association with calcium pyrophosphate deposition disease is reported. To present a previously unreported cause for symptomatic synovial cysts of the lumbar spine. Synovial cysts of the facet joints occur most commonly in association with degenerative disease of the spine in older individuals. The association of these cysts with trauma, rheumatoid arthritis, spondylolysis, and kissing spinous processes also has been reported. These cysts can cause symptoms and signs from direct compression of the dura. Chondrocalcinosis has not been previously reported to cause symptomatic synovial cysts. A 67-year-old woman presented with right lower limb sciatica caused by a right L4-L5 facet joint cyst, which resolved after surgical decompression. A year later, she presented with left lower limb sciatica caused by development of a new L4-L5 facet joint cyst, which also resolved after surgical decompression. Histopathologic examination of each cyst showed a cyst wall of fibrous tissue with synovial lining, inflammation, and granulation tissue. Examination of the tissue under polarized light showed positively birefringent, short blunt crystals of calcium pyrophosphate dihydrate. In patients with a history of gout or pseudogout, a rare possibility of a synovial cyst should be considered in the differential diagnosis during investigation for the cause of neural compression resulting in sciatic syndrome.

Monophasic Synovial Sarcoma of Prostatic Fascia: Case Report and Literature Review.

PubMed

Olivetti, Lucio; Benecchi, Luigi; Corti, Serena; Del Boca, Carlo; Ferrari, Matteo; Sergio, Pietro; Bercich, Luisa; Tanzi, Giulia

2015-01-01

Synovial sarcoma (SS) primarily occurs in the para-articular soft tissue of the lower extremities in young adults and it is extremely rare in the prostatic region. We report a case of a 46-year-old man who presented with urinary retention. Pelvic ultrasound (US) examination, computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated an 8.5 cm mass that appeared to originate in the prostatic fascia of the right lobe. Preoperative prostatic ultrasound transrectal needle biopsy revealed mesenchymal neoplastic tissue. Patient underwent surgery. The final pathologic findings were consistent with the diagnosis of monophasic synovial sarcoma.

Complete human serum maintains viability and chondrogenic potential of human synovial stem cells: suitable conditions for transplantation.

PubMed

Mizuno, Mitsuru; Katano, Hisako; Otabe, Koji; Komori, Keiichiro; Kohno, Yuji; Fujii, Shizuka; Ozeki, Nobutake; Horie, Masafumi; Tsuji, Kunikazu; Koga, Hideyuki; Muneta, Takeshi; Sekiya, Ichiro

2017-06-13

In our clinical practice, we perform transplantations of autologous synovial mesenchymal stem cells (MSCs) for cartilage and meniscus regenerative medicine. One of the most important issues to ensuring clinical efficacy involves the transport of synovial MSCs from the processing facility to the clinic. Complete human serum (100% human serum) is an attractive candidate material in which to suspend synovial MSCs for their preservation during transport. The purpose of this study was to investigate whether complete human serum maintained MSC viability and chondrogenic potential and to examine the optimal temperature conditions for the preservation of human synovial MSCs. Human synovium was harvested from the knees of 14 donors with osteoarthritis during total knee arthroplasty. Passage 2 synovial MSCs were suspended at 2 million cells/100 μL in Ringer's solution or complete human serum at 4, 13, and 37 °C for 48 h. These cells were analyzed for live cell rates, cell surface marker expression, metabolic activity, proliferation, and adipogenic, calcification, and chondrogenic differentiation potentials before and after preservation. After preservation, synovial MSCs maintained higher live cell rates in human serum than in Ringer's solution at 4 and 13 °C. Synovial MSCs preserved in human serum at 4 and 13 °C also maintained high ratios of propidium iodide - and annexin V - cells. MSC surface marker expression was not altered in cells preserved at 4 and 13 °C. The metabolic activities of cells preserved in human serum at 4 and 13 °C was maintained, while significantly reduced in other conditions. Replated MSCs retained their proliferation ability when preserved in human serum at 4 and 13 °C. Adipogenesis and calcification potential could be observed in cells preserved in each condition, whereas chondrogenic potential was retained only in cells preserved in human serum at 4 and 13 °C. The viability and chondrogenic potential of synovial MSCs were

Response to pazopanib in two pediatric patients with pretreated relapsing synovial sarcoma.

PubMed

Casanova, Michela; Basso, Eleonora; Magni, Chiara; Bergamaschi, Luca; Chiaravalli, Stefano; Carta, Roberto; Tirtei, Elisa; Massimino, Maura; Fagioli, Franca; Ferrari, Andrea

2017-01-21

Pazopanib is an oral multikinase inhibitor that has proved effective in adults treated for relapsing soft tissue sarcoma and synovial sarcoma in particular. Two cases are reported here of pediatric patients with pretreated relapsing synovial sarcoma whose tumors showed a prolonged response to pazopanib given on compassionate grounds. These results suggest that new agents found effective in adult patients might achieve similar results in adolescents with the same disease. Facilitating the availability of new drugs for children and adolescents is a major challenge for pediatric oncologists.

[Latent-disseminated tuberculosis revealed by atypical skin ulcerations].

PubMed

Ferrati-Fidelin, G; Pham-Ledard, A; Fauconneau, A; Chauvel, A; Houard, C; Doutre, M-S; Beylot-Barry, M

2016-10-01

Cutaneous tuberculosis (CT) is rare in industrialized countries. Given the clinicopathological polymorphism and the difficulty of isolating the pathogen, diagnosis can be difficult. The condition may be associated with other known locations of the disease or in rare cases, it may be a tell-tale sign, as in our case, in which leg ulcers revealed paucisymptomatic disseminated tuberculosis. A 67-year-old man was referred for rapidly extensive ulcers of the right leg contiguous to debilitating arthritis of the knee of unknown aetiology for 18 months. Earlier investigations revealed thymoma and a pulmonary nodule considered to be sarcoidosis. A skin biopsy showed a granulomatous eosinophilic-rich infiltrate and vasculitis of the small vessels. Screening of the skin sample and gastric aspirate for Koch Bacillus (BK) was negative. A diagnosis of sarcoidosis was made. A positive QuantiFERON test eventually led to the correct diagnosis. On further testing of bronchoalveolar fluid and a synovial biopsy, culture for Mycobacterium tuberculosis (MT) was positive. The PET scan showed high metabolism in the prostate, bone, spleen, liver, nodes and heart. The quad- and then dual-antibiotic antitubercular therapies produced a rapid improvement but treatment was continued over 12 months, given the persistence of high metabolism on PET-CT scan and the low blood rifampicin concentration. A CT should be considered in the presence of giant-cell granulomas, even in the absence of caseous necrosis, and where both direct examination and culture for the skin are negative. Our case also underlines the importance of an extensive workup to rule out disseminated disease even if the patient is not symptomatic. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Malignant inguinal monophasic synovial sarcoma: report of a case and review of the literature.

PubMed

Xu, Ji; Wang, Jia; Cui, Long; Wu, Xiangru

2010-11-21

A synovial sarcoma (SS) is an aggressive soft tissue tumor that classically occurs in the extremities near, but rarely within large joints, in young adults. Variable symptoms and clinical manifestations may be encountered and a definite diagnosis should depend on pathological results. This poses certain difficulties in arriving at a prompt diagnosis and appropriate treatment. We report the case of a 68-year-old woman patient who presented an inguinal mass with swelling and pain in the right lower limb. She underwent surgery, and later received systematic intravenous chemotherapy. The pathological studies, especially the specific chromosomal translocation of a t(X;18) (p11.2;q11.2), confirmed the diagnosis as a synovial sarcoma. To the best of our knowledge, this is the first report of a monophasic synovial sarcoma in the inguinal region. Besides making the readership aware of the rarity of location and age of this present case, this report distinctly highlights the great value of a molecular analysis of an SYT associated genetic alteration in the diagnosis of synovial sarcoma occurring at rare sites especially when immunochemical results are equivocal.

What drives osteoarthritis?-synovial versus subchondral bone pathology.

PubMed

Hügle, Thomas; Geurts, Jeroen

2017-09-01

Subchondral bone and the synovium play an important role in the initiation and progression of OA. MRI often permits an early detection of synovial hypertrophy and bone marrow lesions, both of which can precede cartilage damage. Newer imaging modalities including CT osteoabsorptiometry and hybrid SPECT-CT have underlined the importance of bone in OA pathogenesis. The subchondral bone in OA undergoes an uncoupled remodelling process, which is notably characterized by macrophage infiltration and osteoclast formation. Concomitant increased osteoblast activity leads to spatial remineralization and osteosclerosis in end-stage disease. A plethora of metabolic and mechanical factors can lead to synovitis in OA. Synovial tissue is highly vascularized and thus exposed to systemic influences such as hypercholesterolaemia or low grade inflammation. This review aims to describe the current understanding of synovitis and subchondral bone pathology and their connection in OA. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Disappearance kinetics of solutes from synovial fluid after intra-articular injection.

PubMed Central

Owen, S G; Francis, H W; Roberts, M S

1994-01-01

1. Five rheumatoid patients with a knee joint effusion participated in the study. An aqueous solution (0.1 to 0.2 ml) containing paracetamol, salicylate, diclofenac and [125I]-albumin was injected into a given joint to yield target concentrations of approximately 20 micrograms ml-1 for diclofenac, salicylate and paracetamol and 10(8) counts ml-1 for [125I]-albumin. 2. Paracetamol, salicylate and diclofenac were analysed in synovial fluid by h.p.l.c. [125I]-albumin was analysed using gamma counting. 3. The clearances (+/- s.d.) obtained for the solutes were [125I]-albumin (0.0053 +/- 0.0019 l h-1), diclofenac (0.0096 +/- 0.0061 l h-1), salicylate (0.024 +/- 0.022 l h-1) and paracetamol (0.055 +/- 0.041 l h-1). The corresponding fractions unbound of these solutes in synovial fluid were 0.0, < or = 0.01, 0.34 +/- 0.09 and 0.85 +/- 0.10, respectively. 4. Diffusion of unbound solute through the synovium is estimated to account for (+/- s.d.) 0.52 +/- 0.08, 0.87 +/- 0.06 and 0.99 +/- 0.01 of the total clearance of diclofenac, salicylate and paracetamol from the joint space, respectively. The remaining proportion of clearance is accounted for by efflux of solute bound to albumin. 5. An expression for the ratio of synovial fluid to total plasma concentrations after systemic administration was developed to include both diffusion of unbound solute and albumin flux. Most solutes appear to satisfy the conditions in which this expression reduces to the limiting case where the unbound concentration of the solute is identical in the synovial fluid and plasma under steady state conditions. PMID:7833225

Identification of Synovial Fluid Biomarkers for Knee Osteoarthritis and Correlation with Radiographic Assessment.

PubMed

Monibi, Farrah; Roller, Brandon L; Stoker, Aaron; Garner, Bridget; Bal, Sonny; Cook, James L

2016-04-01

Osteoarthritis (OA) is a costly and debilitating condition that is typically not diagnosed early enough to prevent progression of disease. The purpose of this study was to evaluate synovial fluid from knees with and without OA for potential markers of joint inflammation and degradation and to correlate these findings with radiographic severity of disease. With Institutional Review Board approval, synovial fluid samples were collected before the patient undergoing total knee arthroplasty. Control knees (n = 3) were patients younger than 30 years of age with no history of anterior cruciate ligament, posterior cruciate ligament, or meniscal injury, and no surgical history for either knee. Weight-bearing, anterior-posterior radiographic views were used to determine radiographic OA severity using the modified Kellgren and Lawrence scale. Synovial fluid samples from 18 patients (21 knees) were analyzed using a multiplex assay. Matrix metalloproteinase (MMP)-1 (p < 0.001), interleukin (IL)-6 (p < 0.013), IL-8 (p < 0.024), and Chemokine (C-C motif) ligand 5 (CCL5) (p < 0.006) were significantly higher in the synovial fluid of OA patients compared with normal patients. The radiographic score was significantly higher in patients with OA compared with normal knees (p < 0.002). MMP-1 had a moderate positive correlation with MMP-2, IL-6, IL-8, and CCL5. IL-6 had a strong positive correlation with IL-8 and a moderate positive correlation with MMP-2. Monocyte chemotactic protein 1 had a moderate positive correlation with IL-6 and a strong positive correlation with IL-8. Radiographic scores had a strong positive correlation with IL-6 and IL-8 and a moderate positive correlation with MCP-1. These data provide novel and clinically relevant information for the investigation of synovial fluid biomarkers for knee OA. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The use of native fluorescence analysis of synovial fluid in the diagnosis of medial compartment disease in medium- and large-breed dogs.

PubMed

Bilská, Kamila; Šteffeková, Zuzana; Birková, Anna; Mareková, Mária; Ledecký, Valent; Hluchý, Marián; Kisková, Terézia

2016-05-01

We assumed that proteins are most likely responsible for synovial fluid fluorescence and that changes detected in fluorescence intensity are most likely the result of changes in the concentration of fluorescent proteins. Synchronous fluorescent matrices from synovial fluid samples were measured in the excitation wavelength range of 200-350 nm using a luminescence spectrophotometer. The synchronous matrix of synovial fluid consists of 2 dominant fluorescent centers (F1 and F2) in the ultraviolet region. The fluorescence intensities of both centers were significantly higher in pathological samples, with p = 0.001 (a 59% increase of the median value) for the F1 center and p = 0.002 (a 52% increase of the median value) for the F2 center. Receiver operating characteristic analysis confirmed that synovial fluid autofluorescence is a significant predictor of medial compartment disease in dogs, with the area under the curve at 0.776 (F1) and 0.778 (F2). We did not detect any differences in the autofluorescence of synovial fluid between male and female, or any breed-based changes. No position changes of fluorescent centers were recorded in the synovial fluid in diseased dogs compared with healthy dogs. The synovial fluid metabolic fingerprint of canine patients with medial compartment disease differed from that of healthy dogs. Our study demonstrated the feasibility of synovial fluid fingerprinting to identify disease-specific profiles of synovial fluid metabolites. © 2016 The Author(s).

Serum and synovial fluid concentrations of keratan sulfate and hyaluronan in dogs with induced stifle joint osteoarthritis following cranial cruciate ligament transection.

PubMed

Budsberg, Steven C; Lenz, Mary Ellen; Thonar, Eugene J-M A

2006-03-01

To examine longitudinal changes in serum and synovial fluid concentrations of keratan sulfate (KS) and hyaluronan (HA) after cranial cruciate ligament (CCL) transection in dogs. 12 clinically normal adult mixed-breed dogs. Following CCL transection in the right stifle joint, KS and HA concentrations were determined in serum and neat (undiluted) synovial fluid prior to and 1, 2, 3, and 12 months after surgery. Postsurgical dilution of synovial fluid was corrected by use of urea as a passive marker. Synovial fluid KS and HA concentrations decreased at 1, 2, and 3 months after surgery in operated stifle joints, compared with baseline values. Synovial fluid KS concentration decreased in unoperated stifle joints at 1 month. A decrease in synovial fluid KS concentration was found in operated stifle joints, compared with unoperated stifle joints, at 2 and 3 months, and a decrease in synovial fluid HA concentrations was also found in operated stifle joints, compared with unoperated stifle joints, at 1, 2, and 3 months. Serum KS concentrations increased from baseline values at 3 months after surgery. Hyaluronan concentrations in operated stifle joints were lower than baseline values at 1, 2, and 3 months. Urea-adjusted synovial fluid concentrations revealed that dilution did not account for the decline in biomarker concentrations. The initial decrease and subsequent increase in synovial fluid concentrations of HA and KS may be caused by an acute inflammatory response to surgical intervention that negatively affects cartilage metabolism or an increase in production of immature proteoglycans.

Is posterior synovial plica excision necessary for refractory lateral epicondylitis of the elbow?

PubMed

Rhyou, In Hyeok; Kim, Kang Wook

2013-01-01

Arthroscopic treatments for lateral epicondylitis including débridement of the extensor carpi radialis brevis (ECRB) origin (Baker technique) or resection of the radiocapitellar synovial plica reportedly improve symptoms. However the etiology of the disease and the role of the plica remain unclear. We asked if posterior radiocapitellar synovial plica excision made any additional improvement in pain or function after arthroscopic ECRB release. We retrospectively reviewed 38 patients who had arthroscopic treatment for refractory lateral epicondylitis between November 2003 and October 2009. Twenty patients (Group A) underwent the Baker technique and 18 patients (Group B) underwent a combination of the Baker technique and posterior synovial plica excision. The minimum followup was 36 months (mean, 46 months; range, 36-72 months) for Group A and 25 months (mean, 30 months; range, 25-36 months) for Group B. Postoperatively we obtained VAS pain and DASH scores for each group. Two years postoperatively, we found no differences in the VAS pain score or DASH: the mean VAS pain scores were 0.3 points in Group A and 0.4 points in Group B, and the DASH scores were 5.1 points and 6.1 points respectively. The addition of débridement of the posterior synovial fold did not appear to enhance either pain relief or function compared with the classic Baker technique without decortication.

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

PubMed Central

Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

1998-01-01

OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

[Modified Cheng's Juanbi Decoction downregulates expression of prostaglandin E receptor 4 in synovial tissue in rats with adjuvant arthritis].

PubMed

Xu, Xia; Cheng, Hui; Cao, Jian; DU, Huan; Meng, Qingwei; Guo, Mengyuan

2017-06-01

Objective To investigate the effect of modified Cheng's Juanbi Decoction on the expression of prostaglandin E receptor 4 (PTGER4), the T cell receptor in the synovial tissues, in rats with adjuvant arthritis (AA). Methods A rat model of AA was established by subcutaneous injection of Freund's complete adjuvant at the vola pedis combined with ice-water bath and blowing. The degree of joint swelling and arthritis index were determined in each group. The quantitative real-time PCR was performed to assess the effect of modified Cheng's Juanbi Decoction on the mRNA expression of PTGER4in the synovial tissue. Results Cheng's Juanbi Decoction significantly alleviated the damage in the joints and synovial tissues in the AA rats. High-dose (the content of crude drug: 4 g/mL) Cheng's Juanbi Decoction significantly reduced the mRNA expression of PTGER4 in the synovial tissues. Conclusion Cheng's Juanbi Decoction can reduce the level of PTGER4 mRNA in the synovial tissue in AA rats.

Elevated synovial fluid concentration of adenosine triphosphate in dogs with osteoarthritis or sodium urate-induced synovitis of the stifle.

PubMed

Torres, Bryan T; Jimenez, David A; Budsberg, Steven C

2016-07-19

Adenosine triphosphate has been shown to stimulate nociceptive nerve terminals in joints. Elevated synovial fluid adenosine triphosphate concentrations as well as a correlation between synovial fluid adenosine triphosphate concentrations and osteoarthritic knee pain has been demonstrated in humans, but not yet in dogs. This study documented elevated synovial fluid adenosine triphosphate concentrations in the stifles of dogs with secondary osteoarthritis and urate-induced synovitis, as compared to normal stifles.

Synovial Sarcoma in the Foot of a 5-Year-Old ChildA Case Report.

PubMed

Lepow, Gary M; Grimmer, Daniel L; Lemar, Onya V; Bridges, Evan A

2016-07-01

The purpose of this case report is to present a rare finding of synovial sarcoma in a 5-year-old child. Most soft-tissue masses of the foot are too often presumed to be small and benign; therefore, compared with soft-tissue sarcomas, they are difficult to clinically differentiate and treat. A 5-year-old girl presented with a painful lesion that was diagnosed as synovial sarcoma after an excisional biopsy was performed. This was an unexpected finding of synovial sarcoma involving the tibialis posterior tendon of her right foot. The patient presented with an 8-month history of tenderness and an antalgic gait. We would like to encourage that all soft-tissue tumors of the foot be preoperatively evaluated with the aid of diagnostic imaging so that a well-planned biopsy assessment can be performed, with adequate margins excised.

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts

PubMed Central

Kaneko, M; Inoue, H; Nakazawa, R; Azuma, N; Suzuki, M; Yamauchi, S; Margolin, S B; Tsubota, K; Saito, I

1998-01-01

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1α in the presence or absence of pirfenidone (range 0–1000 μm), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1α-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts. PMID:9697986

Arthroscopic Transplantation of Synovial Stem Cells Improves Clinical Outcomes in Knees With Cartilage Defects.

PubMed

Sekiya, Ichiro; Muneta, Takeshi; Horie, Masafumi; Koga, Hideyuki

2015-07-01

Transplantation of mesenchymal stem cells (MSCs) is one possible strategy to achieve articular cartilage repair. We previously reported that synovial MSCs were highly proliferative and able to undergo chondrogenesis. We also found that placing a suspension of synovial MSCs on a cartilage defect for 10 minutes promoted cartilage repair in rabbit and pig models. However, the in vivo efficacy of this approach has not been tested clinically. We asked whether transplantation of synovial MSCs improves (1) MRI features, (2) histologic features, and (3) clinical evaluation scores in patients with cartilage defects in the knee? Patients with a symptomatic single cartilage lesion of the femoral condyle were indicated for inclusion in our study, and between April 2008 and April 2011, 10 patients were enrolled in this study. All patients completed followups of 3 years or more. The average followup period was 52 months (range, 37-80 months). Synovial MSCs were expanded with 10% autologous human serum for 14 days after digestion. For transplantation, the patient was positioned so that the cartilage defect was facing upward, and synovial MSC suspension was placed on the cartilage defect with a syringe under arthroscopic control. The defect with the applied suspension then was held in the upward position for 10 minutes. Five patients underwent concomitant ACL reconstructions, among whom two had meniscus suturing performed simultaneously. For MRI quantification, the cartilage defect was scored from 0 to 5. Second-look arthroscopy was performed for four patients and biopsy specimens were evaluated histologically. Clinical outcome was assessed using the Lysholm score and Tegner Activity Level Scale at final followup. Comparisons of MRI and Lysholm scores before and after treatment for each patient were analyzed using the Wilcoxon signed-rank test. MRI score (median ± 95% CI) was 1.0 ± 0.3 before and 5.0 ± 0.7 after, and increased after treatment in each patient (p = 0.005). Second

Synovial Mesenchymal Stem Cells Promote Meniscus Regeneration Augmented by an Autologous Achilles Tendon Graft in a Rat Partial Meniscus Defect Model

PubMed Central

Ozeki, Nobutake; Muneta, Takeshi; Matsuta, Seiya; Koga, Hideyuki; Nakagawa, Yusuke; Mizuno, Mitsuru; Tsuji, Kunikazu; Mabuchi, Yo; Akazawa, Chihiro; Kobayashi, Eiji; Saito, Tomoyuki; Sekiya, Ichiro

2015-01-01

Although meniscus defects and degeneration are strongly correlated with the later development of osteoarthritis, the promise of regenerative medicine strategies is to prevent and/or delay the disease's progression. Meniscal reconstruction has been shown in animal models with tendon grafting and transplantation of mesenchymal stem cells (MSCs); however, these procedures have not shown the same efficacy in clinical studies. Here, our aim was to investigate the ability of tendon grafts pretreated with exogenous synovial-derived MSCs to prevent cartilage degeneration in a rat partial meniscus defect model. We removed the anterior half of the medial meniscus and grafted autologous Achilles tendons with or without a 10-minute pretreatment of the tendon with synovial MSCs. The meniscus and surrounding cartilage were evaluated at 2, 4, and 8 weeks (n = 5). Tendon grafts increased meniscus size irrespective of synovial MSCs. Histological scores for regenerated menisci were better in the tendon + MSC group than in the other two groups at 4 and 8 weeks. Both macroscopic and histological scores for articular cartilage were significantly better in the tendon + MSC group at 8 weeks. Implanted synovial MSCs survived around the grafted tendon and native meniscus integration site by cell tracking assays with luciferase+, LacZ+, DiI+, and/or GFP+ synovial MSCs and/or GFP+ tendons. Flow cytometric analysis showed that transplanted synovial MSCs retained their MSC properties at 7 days and host synovial tissue also contained cells with MSC characteristics. Synovial MSCs promoted meniscus regeneration augmented by autologous Achilles tendon grafts and prevented cartilage degeneration in rats. Stem Cells 2015;33:1927–1938 PMID:25993981

Down-Regulation of Myeloid Cell Leukemia 1 by Epigallocatechin-3-Gallate Sensitizes Rheumatoid Arthritis Synovial Fibroblasts to Tumor Necrosis Factor α–Induced Apoptosis

PubMed Central

Ahmed, Salahuddin; Silverman, Matthew D.; Marotte, Hubert; Kwan, Kevin; Matuszczak, Natalie; Koch, Alisa E.

2010-01-01

Objective Overexpression of the antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) in rheumatoid arthritis (RA) synovial fibroblasts is a major cause of their resistance to tumor necrosis factor α (TNFα)–induced apoptosis. This study was undertaken to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) in down-regulating Mcl-1 expression and its mechanism of RA synovial fibroblast sensitization to TNFα-induced apoptosis. Methods EGCG effects on cultured RA synovial fibroblast cell morphology, proliferation, and viability over 72 hours were determined by microscopy and a fluorescent cell enumeration assay. Caspase 3 activity was determined by a colorimetric assay. Western blotting was used to evaluate the apoptosis mediators poly(ADP-ribose) polymerase (PARP), Mcl-1, Bcl-2, Akt, and nuclear translocation of NF-κB. Results In RA synovial fibroblasts, EGCG (5–50 μM) inhibited constitutive and TNFα-induced Mcl-1 protein expression in a concentration- and time-dependent manner (P < 0.05). Importantly, EGCG specifically abrogated Mcl-1 expression in RA synovial fibroblasts and affected Mcl-1 expression to a lesser extent in osteoarthritis and normal synovial fibroblasts or endothelial cells. Inhibition of Mcl-1 by EGCG triggered caspase 3 activity in RA synovial fibroblasts, which was mediated via down-regulation of the TNFα-induced Akt and NF-κB pathways. Caspase 3 activation by EGCG also suppressed RA synovial fibroblast growth, and this effect was mimicked by Akt and NF-κB inhibitors. Interestingly, Mcl-1 degradation by EGCG sensitized RA synovial fibroblasts to TNFα-induced PARP cleavage and apoptotic cell death. Conclusion Our findings indicate that EGCG itself induces apoptosis and further sensitizes RA synovial fibroblasts to TNFα-induced apoptosis by specifically blocking Mcl-1 expression and, hence, may be of promising adjunct therapeutic value in regulating the invasive growth of synovial fibroblasts in RA. PMID:19404960

Synovial Calprotectin: An Inexpensive Biomarker to Exclude a Chronic Prosthetic Joint Infection.

PubMed

Wouthuyzen-Bakker, Marjan; Ploegmakers, Joris J W; Ottink, Karsten; Kampinga, Greetje A; Wagenmakers-Huizenga, Lucie; Jutte, Paul C; Kobold, Anneke C M

2018-04-01

To diagnose or exclude a chronic prosthetic joint infection (PJI) can be a clinical challenge. Therefore, sensitive and specific biomarkers are needed in the diagnostic work-up. Calprotectin is a protein with antimicrobial properties and is released by activated neutrophils, making it a specific marker for infection. Because of its low costs and ability to obtain a quantitative value as a point of care test, it is an attractive marker to use in clinical practice. In addition, the test is already used in routine care in most hospitals for other indications and therefore easy to implement. Between June 2015 and June 2017 we collected synovial fluid of all consecutive patients who underwent revision surgery of a prosthetic joint because of chronic pain with or without prosthetic loosening. Synovial calprotectin was measured using a lateral flow immunoassay. A PJI was defined by the diagnostic criteria described by the Musculoskeletal Infection Society. Fifty-two patients with chronic pain were included. A PJI was diagnosed in 15 of 52 (29%) patients. The median calprotectin in the PJI group was 859 mg/L (interquartile range 86-1707) vs 7 mg/L (interquartile range 3-25) in the control group (P < .001). With a cut-off value of 50 mg/L, synovial calprotectin showed a sensitivity, specificity, positive predictive value, and negative predictive value of 86.7%, 91.7%, 81.3%, and 94.4%, respectively. Synovial calprotectin is a useful and cheap biomarker to use in the diagnostic work-up of patients with chronic pain, especially to exclude a PJI prior to revision surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature

PubMed Central

Gerlag, Danielle M; Borges, Eric; Tak, Paul P; Ellerby, H Michael; Bredesen, Dale E; Pasqualini, Renata; Ruoslahti, Erkki; Firestein, Gary S

2001-01-01

Because angiogenesis plays a major role in the perpetuation of inflammatory arthritis, we explored a method for selectively targeting and destroying new synovial blood vessels. Mice with collagen-induced arthritis were injected intravenously with phage expressing an RGD motif. In addition, the RGD peptide (RGD-4C) was covalently linked to a proapoptotic heptapeptide dimer, D(KLAKLAK)2, and was systemically administered to mice with collagen-induced arthritis. A phage displaying an RGD-containing cyclic peptide (RGD-4C) that binds selectively to the αvβ3 and αvβ5 integrins accumulated in inflamed synovium but not in normal synovium. Homing of RGD-4C phage to inflamed synovium was inhibited by co-administration of soluble RGD-4C. Intravenous injections of the RGD-4C–D(KLAKLAK)2 chimeric peptide significantly decreased clinical arthritis and increased apoptosis of synovial blood vessels, whereas treatment with vehicle or uncoupled mixture of the RGD-4C and the untargeted proapoptotic peptide had no effect. Targeted apoptosis of synovial neovasculature can induce apoptosis and suppress clinical arthritis. This form of therapy has potential utility in the treatment of inflammatory arthritis. PMID:11714389

Canine adipose-derived stromal cell viability following exposure to synovial fluid from osteoarthritic joints.

PubMed

Kiefer, Kristina M; O'Brien, Timothy D; Pluhar, Elizabeth G; Conzemius, Michael

2015-01-01

Stem cell therapy used in clinical application of osteoarthritis in veterinary medicine typically involves intra-articular injection of the cells, however the effect of an osteoarthritic environment on the fate of the cells has not been investigated. Assess the viability of adipose derived stromal cells following exposure to osteoarthritic joint fluid. Adipose derived stromal cells (ASCs) were derived from falciform adipose tissue of five adult dogs, and osteoarthritic synovial fluid (SF) was obtained from ten patients undergoing surgical intervention on orthopedic diseases with secondary osteoarthritis. Normal synovial fluid was obtained from seven adult dogs from an unrelated study. ASCs were exposed to the following treatment conditions: culture medium, normal SF, osteoarthritic SF, or serial dilutions of 1:1 to 1:10 of osteoarthritic SF with media. Cells were then harvested and assessed for viability using trypan blue dye exclusion. There was no significant difference in the viability of cells in culture medium or normal SF. Significant differences were found between cells exposed to any concentration of osteoarthritic SF and normal SF and between cells exposed to undiluted osteoarthritic SF and all serial dilutions. Subsequent dilutions reduced cytotoxicity. Osteoarthritic synovial fluid in this ex vivo experiment is cytotoxic to ASCs, when compared with normal synovial fluid. Current practice of direct injection of ASCs into osteoarthritic joints should be re-evaluated to determine if alternative means of administration may be more effective.

Raman spectroscopy of dried synovial fluid droplets as a rapid diagnostic for knee joint damage

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Mandair, Gurjit S.; Raaii, Farhang; Roessler, Blake J.; Morris, Michael D.

2008-02-01

Human synovial fluid droplets were investigated using drop deposition in combination with Raman spectroscopy. Following informed consent, synovial fluid was obtained from forty human patients with various severities of knee pain and/or osteoarthritis at the time of knee arthroscopy or total joint replacement. Synovial fluid was aspirated from the knee joint of each patient and stored at -80°C until examination by near-infrared Raman spectroscopy. Synovial fluid aspirates from the knee joint of each patient were deposited onto a clean fused silica microscope slide and the droplet dried under ambient laboratory conditions. Each droplet was illuminated by a line-focused or a ring-focused 785 nm laser. As the droplet dries, biofluid components segregated based on solubility differences and a deposit that is spatially heterogeneous was made. Spectra taken from the droplet edges and center were dominated by protein bands and showed the presence of at least two protein moieties in the droplet. Band area and band height ratios (1410 cm -1/1450 cm -1) showed the greatest change between specimens from patients with mild/early osteoarthritis compared to those with severe/late stage osteoarthritis. The greatest differences were found in the center of the droplet, which contains more soluble protein components than the edges.

Matrix metalloproteinase and tissue inhibitor of metalloproteinase in serum and synovial fluid of osteoarthritic dogs.

PubMed

Salinardi, B J; Roush, J K; Schermerhorn, T; Mitchell, K E

2006-01-01

To better understand the mechanisms responsible for the pathological processes of osteoarthritis (OA) and to potentially identify a profile of changes that could be predictive of early OA, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of matrix metalloproteinase-2 (TIMP-2) in the synovial fluid and serum of normal and osteoarthritic dogs were examined. The concentration of MMP-1 in the synovial fluid of osteoarthritic dogs (0.62 +/- 0.16), as measured by densitometry, was significantly higher than that found in control dogs (0.42 +/- 0.19) (P = 0.03). The concentration of MMP-1 in the serum of osteoarthritic dogs (0.74 +/- 0.16) was significantly less than that found in control dogs (0.87 +/- 0.08) (P = 0.05). The concentration of TIMP-2 in the synovial fluid of osteoarthritic dogs (46.2 +/- 21.9 ng/ml) was significantly less than that of control dogs (122.0 +/- 66.5 ng/ml) (P = 0.009). The concentration of TIMP-2 in the serum of osteoarthritic dogs (116.2 +/- 43.1 ng/ml) was not significantly different than that of control dogs (95.1 +/- 94.4 ng/ml) (P = 0.554). In addition, a phospho-tyrosine immunoprecipitation and mass spectrometry were used to isolate and identify interferon-alpha in canine synovial fluid.

Ablation of synovial pannus using microbubble-mediated ultrasonic cavitation in antigen-induced arthritis in rabbits.

PubMed

Qiu, Li; Jiang, Yong; Zhang, Lingyan; Wang, Lei; Luo, Yan

2012-12-01

To investigate the ablative effectiveness of microbubble-mediated ultrasonic cavitation for treating synovial pannus and to determine a potential mechanism using the antigen-induced arthritis model (AIA). Ultrasonic ablation was performed on the knee joints of AIA rabbits using optimal ultrasonic ablative parameters. Rabbits with antigen-induced arthritis were randomly assigned to 4 groups: (1) the ultrasound (US) + microbubble group; (2) the US only group; (3) the microbubble only group, and (4) the control group. At 1 h and 14 days after the first ablation, contrast-enhanced ultrasonography (CEUS) monitoring and pathology synovitis score were used to evaluate the therapeutic effects. Synovial necrosis and microvascular changes were also measured. After the ablation treatment, the thickness of synovium and parameters of time intensity curve including derived peak intensity and area under curve were measured using CEUS, and the pathology synovitis score in the ultrasound + microbubble group was significantly lower than that found in the remaining groups. No damage was observed in the surrounding normal tissues. The mechanism underlying the ultrasonic ablation was related to microthrombosis and microvascular rupture that resulted in synovial necrosis. The results suggest that microbubble-mediated ultrasonic cavitation should be applied as a non-invasive strategy for the treatment of synovial pannus in arthritis under optimal conditions.

On the matter of synovial fluid lubrication: implications for Metal-on-Metal hip tribology.

PubMed

Myant, Connor; Cann, Philippa

2014-06-01

Artificial articular joints present an interesting, and difficult, tribological problem. These bearing contacts undergo complex transient loading and multi axes kinematic cycles, over extremely long periods of time (>10 years). Despite extensive research, wear of the bearing surfaces, particularly metal-metal hips, remains a major problem. Comparatively little is known about the prevailing lubrication mechanism in artificial joints which is a serious gap in our knowledge as this determines film formation and hence wear. In this paper we review the accepted lubrication models for artificial hips and present a new concept to explain film formation with synovial fluid. This model, recently proposed by the authors, suggests that interfacial film formation is determined by rheological changes local to the contact and is driven by aggregation of synovial fluid proteins. The implications of this new mechanism for the tribological performance of new implant designs and the effect of patient synovial fluid properties are discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

A citrus flavonoid, nobiletin, suppresses production and gene expression of matrix metalloproteinase 9/gelatinase B in rabbit synovial fibroblasts.

PubMed

Ishiwa, J; Sato, T; Mimaki, Y; Sashida, Y; Yano, M; Ito, A

2000-01-01

Flavonoids including nobiletin are known to exert many biological actions in vitro. We investigated the chondroprotective effect of citrus flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts and articular chondrocytes. We examined the effects of citrus flavonoids on the production and gene expression of matrix metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit synovial fibroblasts. Six flavonoids isolated from Citrus depressa Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin, 5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin most effectively suppressed proMMP-9 production along with the decrease in its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the synovial cells, but did not modify the synthesis of total protein. These suppressive effects of nobiletin were also observed in rabbit articular chondrocytes. Nobiletin inhibited proliferation of rabbit synovial fibroblasts in the growth phase. These results suggest nobiletin is a novel antiinflammatory candidate that has the potential to inhibit PGE2 production, matrix degradation of the articular cartilage, and pannus formation in osteoarthritis and rheumatoid arthritis.

Complement activating properties of complexes containing rheumatoid factor in synovial fluids and sera from patients with rheumatoid arthritis.

PubMed Central

Elson, C J; Carter, S D; Cottrell, B J; Scott, D G; Bacon, P A; Wallington, T B

1985-01-01

The relationship between complexes containing rheumatoid factor and complexes activating complement was examined in synovial fluids and sera from patients with rheumatoid arthritis (RA). In each case this was performed by quantifying the amount of rheumatoid factor bound by solid phase Fab'2 anti-C3 and/or solid phase conglutinin. Both anti-C3 coated and conglutinin coated microtitre plates bound high levels of complexes containing rheumatoid factor from sera of RA patients with vasculitis. Unexpectedly, these complexes were detected in synovial fluids from only a minority of RA patients with synovitis. However, RA synovial fluids did contain other complexes as shown by the presence of complement consuming activity, C1q binding material and immunoglobulin attaching to conglutinin. It is considered that in RA synovial fluids the complexes containing RF and those activating complement are not necessarily the same whilst in vasculitic sera the complexes containing rheumatoid factor also activate complement. PMID:3978872

Establishment and proteomic characterization of a novel synovial sarcoma cell line, NCC-SS2-C1.

PubMed

Oyama, Rieko; Kito, Fusako; Sakumoto, Marimu; Shiozawa, Kumiko; Toki, Shunichi; Endo, Makoto; Yoshida, Akihiko; Kawai, Akira; Kondo, Tadashi

2018-05-01

Synovial sarcoma is an aggressive mesenchymal tumor, characterized by the presence of unique transfusion gene, SS18-SSX. Cell lines enable researchers to investigate the molecular backgrounds of disease and the significance of SS18-SSX in relevant cellular contexts. We report the establishment and proteomic characterization of a novel synovial sarcoma cell line. Primary tissue culture was performed using tumor tissue of synovial sarcoma. The established cell line was authenticated by assessing its DNA microsatellite short tandem repeat analysis and characterized by in vitro assay. Proteomic study was achieved by mass spectrometry, and the results were analyzed by treemap. The cell line NCC-SS2-C1 was established from a primary tumor tissue of a synovial sarcoma patient. The cell line has grown well for 11 mo and has been subcultured more than 15 times. The established cells were authenticated by assessing their short tandem repeat pattern comparing with that of original tumor tissue. The cells showed polygonal in shape and formed spheroid when seeded on the low-attachment dish. Proteomic analysis revealed the molecular pathways which are unique to the original tumor tissue or the established cell line. In conclusion, a novel synovial sarcoma cell line NCC-SS2-C1 was successfully established from the primary tumor tissue. The cell line has characteristic transfusion SS18-SSX and poses aggressive in vitro growth and capability of spheroid formation. Thus, NCC-SS2-C1 cell line will be a useful tool for investigation of the mechanisms of disease and the biological role of fusion gene.

Implantation of Allogenic Synovial Stem Cells Promotes Meniscal Regeneration in a Rabbit Meniscal Defect Model

PubMed Central

Horie, Masafumi; Driscoll, Matthew D.; Sampson, H. Wayne; Sekiya, Ichiro; Caroom, Cyrus T.; Prockop, Darwin J.; Thomas, Darryl B.

2012-01-01

Update This article was updated on May 16, 2012, because of a previous error. The legend for Figures 7-A and 7-B that had previously read “Representative macroscopic appearance (Fig. 7-A) and histological sections (Fig. 7-B) of the meniscal defect one day to twelve weeks after the implantation of GFP-positive green fluorescent protein under fluorescence” now reads “Representative macroscopic appearance (Fig. 7-A) and histological sections (Fig. 7-B) of the meniscal defect one day to twelve weeks after the implantation of GFP-positive synovial mesenchymal stem cells under fluorescence.” Background: Indications for surgical meniscal repair are limited, and failure rates remain high. Thus, new ways to augment repair and stimulate meniscal regeneration are needed. Mesenchymal stem cells are multipotent cells present in mature individuals and accessible from peripheral connective tissue sites, including synovium. The purpose of this study was to quantitatively evaluate the effect of implantation of synovial tissue-derived mesenchymal stem cells on meniscal regeneration in a rabbit model of partial meniscectomy. Methods: Synovial mesenchymal stem cells were harvested from the knee of one New Zealand White rabbit, expanded in culture, and labeled with a fluorescent marker. A reproducible 1.5-mm cylindrical defect was created in the avascular portion of the anterior horn of the medial meniscus bilaterally in fifteen additional rabbits. Allogenic synovial mesenchymal stem cells suspended in phosphate-buffered saline solution were implanted into the right knees, and phosphate-buffered saline solution alone was placed in the left knees. Meniscal regeneration was evaluated histologically at four, twelve, and twenty-four weeks for (1) quantity and (2) quality (with use of an established three-component scoring system). A similar procedure was performed in four additional rabbits with use of green fluorescent protein-positive synovial mesenchymal stem cells for the

PPAR-δ Agonist With Mesenchymal Stem Cells Induces Type II Collagen-Producing Chondrocytes in Human Arthritic Synovial Fluid.

PubMed

Heck, Bruce E; Park, Joshua J; Makani, Vishruti; Kim, Eun-Cheol; Kim, Dong Hyun

2017-08-01

Osteoarthritis (OA) is an inflammatory joint disease characterized by degeneration of articular cartilage within synovial joints. An estimated 27 million Americans suffer from OA, and the population is expected to reach 67 million in the United States by 2030. Thus, it is urgent to find an effective treatment for OA. Traditional OA treatments have no disease-modifying effect, while regenerative OA therapies such as autologous chondrocyte implantation show some promise. Nonetheless, current regenerative therapies do not overcome synovial inflammation that suppresses the differentiation of mesenchymal stem cells (MSCs) to chondrocytes and the expression of type II collagen, the major constituent of functional cartilage. We discovered a synergistic combination that overcame synovial inflammation to form type II collagen-producing chondrocytes. The combination consists of peroxisome proliferator-activated receptor (PPAR) δ agonist, human bone marrow (hBM)-derived MSCs, and hyaluronic acid (HA) gel. Interestingly, those individual components showed their own strong enhancing effects on chondrogenesis. GW0742, a PPAR-δ agonist, greatly enhanced MSC chondrogenesis and the expression of type II collagen and glycosaminoglycan (GAG) in hBM-MSC-derived chondrocytes. GW0742 also increased the expression of transforming growth factor β that enhances chondrogenesis and suppresses cartilage fibrillation, ossification, and inflammation. HA gel also increased MSC chondrogenesis and GAG production. However, neither GW0742 nor HA gel could enhance the formation of type II collagen-producing chondrocytes from hBM-MSCs within human OA synovial fluid. Our data demonstrated that the combination of hBM-MSCs, PPAR-δ agonist, and HA gel significantly enhanced the formation of type II collagen-producing chondrocytes within OA synovial fluid from 3 different donors. In other words, the novel combination of PPAR-δ agonist, hBM-MSCs, and HA gel can overcome synovial inflammation to form

MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs.

PubMed

Boland, L; Danger, R; Cabon, Q; Rabillard, M; Brouard, S; Bouvy, B; Gauthier, O

2014-01-01

To measure the activity of matrix metalloproteinases (MMP)-2 and -9 in synovial fluid from the stifle joints of dogs with cranial cruciate ligament (CrCL) rupture and to compare that to values from contralateral stifle joints and dogs with clinically normal stifle joints. Additionally, the C-reactive protein (CRP) levels were also measured. Fourteen large breed dogs with unilateral CrCL rupture and 11 large breed normal dogs were included in this prospective clinical study. Synovial fluid was collected from CrCL-ruptured stifle joints, contralateral clinically normal stifle joints of the same dogs, and stifle joints of normal dogs. Serum was also collected. Synovial fluid activities of MMP-2 and MMP-9 and serum CRP level were measured. The MMP-2 activity in synovial fluid was significantly higher in CrCL-ruptured joints compared to contralateral joints and to stifles from normal dogs. There was no significant difference in activity of MMP-2 in contralateral joints of CrCL-ruptured dogs compared to normal dogs. Both serum CRP level and MMP-9 activity did not differ significantly between the studied conditions. It was confirmed that MMP-2 activity is significantly related to CrCL rupture, but there was a failure to demonstrate any significant increase in the contralateral joints compared to the stifle joints of normal dogs. The MMP-2 involvement in progressing CrCL disease still has to be defined.

Incidental synovial myxoma with extensive intermuscular infiltration in a dog.

PubMed

Izawa, Takeshi; Tanaka, Miyuu; Aoki, Mika; Ohashi, Fumihito; Yamate, Jyoji; Kuwamura, Mitsuru

2012-12-01

A 16-year-old male mixed-breed dog was euthanized due to progression of renal failure caused by renal adenocarcinoma in the left kidney. Apart from main symptomatic lesion, accumulation of transparent jelly-like fluid was observed between the right femoral muscles. Gross examination of the right hindlimb revealed multiple nodules in the articular surface and capsule of the stifle joints, which extended into the crural muscles. Histopathologically, the joint and intermuscular masses were characterized by variously-sized hypocellular nodules consisting of spindle to stellate cells suspended in an abundant myxoid matrix. There were cystic structures within the intermuscular masses, lined by synoviocyte-like cells. Based on the gross and histopathologic findings, the case was diagnosed as synovial myxoma with extensive intermuscular infiltration. Synovial myxoma should be considered in the differential diagnosis of dogs with myxomatous tumor between skeletal muscles, even in absence of joint or muscle symptoms.

Combined measurement of synovial fluid α-Defensin and C-reactive protein levels: highly accurate for diagnosing periprosthetic joint infection.

PubMed

Deirmengian, Carl; Kardos, Keith; Kilmartin, Patrick; Cameron, Alexander; Schiller, Kevin; Parvizi, Javad

2014-09-03

The diagnosis of periprosthetic joint infection remains a challenge. The purpose of this study was to evaluate the combined measurement of the levels of two synovial fluid biomarkers, α-defensin and C-reactive protein (CRP), for the diagnosis of periprosthetic joint infection. One hundred and forty-nine synovial fluid aspirates, including 112 from patients with an aseptic diagnosis and thirty-seven from patients with periprosthetic joint infection, met the inclusion criteria for this prospective study. Synovial fluid aspirates were tested for α-defensin and CRP levels with use of enzyme-linked immunosorbent assay (ELISA). The Musculoskeletal Infection Society (MSIS) definition of periprosthetic joint infection was utilized for the classification of cases as aseptic or infected. Comorbidities, such as inflammatory conditions, that could confound a test for periprosthetic joint infection were documented, but the patients with such comorbidities were included in the study. The combination of synovial fluid α-defensin and CRP tests demonstrated a sensitivity of 97% and a specificity of 100% for the diagnosis of periprosthetic joint infection. Synovial fluid α-defensin tests alone demonstrated a sensitivity of 97% and a specificity of 96% for the diagnosis of periprosthetic joint infection. Synovial fluid CRP tests, with a low threshold of 3 mg/L, reversed all-false positive α-defensin results without affecting the sensitivity of the test. The diagnostic characteristics of these assays were achieved in a population of patients demonstrating a 23% rate of systemic inflammatory diseases (in the series as a whole) and a 27% rate of concurrent antibiotic treatment (in the infection group). The synovial fluid levels of α-defensin in the setting of periprosthetic joint infection were unchanged during concurrent antibiotic treatment. The combined measurement of synovial fluid α-defensin and CRP levels correctly diagnosed 99% of the cases in this study as aseptic or

Synovial sarcoma of the jaw in a dog.

PubMed

Griffith, J W; Frey, R A; Sharkey, F E

1987-05-01

A case of synovial sarcoma of the jaw with pulmonary metastasis is described in a dog. It appears to be a rare or underdiagnosed neoplasm in animals and not previously reported in the jaw. Its diagnostic microscopic features are the biphasic cellular pattern and cleft formations. It may otherwise resemble haemangiopericytoma, malignant fibrous histiocytoma, reticulum cell sarcoma, fibrosarcoma, or giant-cell tumour of soft tissue.

Disseminated sporotrichosis

PubMed Central

Romero-Cabello, Raúl; Bonifaz, Alexandro; Romero-Feregrino, Raúl; Sánchez, Carlos Javier; Linares, Yancy; Zavala, Jorge Tay; Romero, Leticia Calderón; Romero-Feregrino, Rodrigo; Vega, José T Sánchez

2011-01-01

Sporotrichosis is a subacute or chronic infection caused by Sporothrix schenckii. It is a primary cutaneous infection and it has different clinical forms: disseminated by lymphatic vessels (75%), localised cutaneous form (20%), disseminated cutaneous and extracuteus rarely. The systemic disseminated sporotrichosis is considered a severe opportunistic infection. The best diagnostic test is the culture. The authors report a case of a 36-year-old man, originally from Puebla, Mexico, with a diagnosis of disseminated sporotrichosis. Differential diagnosis with other pathologies includes leishmaniasis, chromoblastomycosis, tuberculosis verrucose and lymphangitis. The development of unusual presentations in immunocompromised patients has been reported. PMID:22700076

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis

PubMed Central

Yarmola, Elena G.; Shah, Yash; Arnold, David P.; Dobson, Jon; Allen, Kyle D.

2015-01-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker - the c-terminus telopeptide of type II collagen (CTXII) - magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 µL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed 10 fold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat. PMID:26136062

Magnetic Capture of a Molecular Biomarker from Synovial Fluid in a Rat Model of Knee Osteoarthritis.

PubMed

Yarmola, Elena G; Shah, Yash; Arnold, David P; Dobson, Jon; Allen, Kyle D

2016-04-01

Biomarker development for osteoarthritis (OA) often begins in rodent models, but can be limited by an inability to aspirate synovial fluid from a rodent stifle (similar to the human knee). To address this limitation, we have developed a magnetic nanoparticle-based technology to collect biomarkers from a rodent stifle, termed magnetic capture. Using a common OA biomarker--the c-terminus telopeptide of type II collagen (CTXII)--magnetic capture was optimized in vitro using bovine synovial fluid and then tested in a rat model of knee OA. Anti-CTXII antibodies were conjugated to the surface of superparamagnetic iron oxide-containing polymeric particles. Using these anti-CTXII particles, magnetic capture was able to estimate the level of CTXII in 25 μL aliquots of bovine synovial fluid; and under controlled conditions, this estimate was unaffected by synovial fluid viscosity. Following in vitro testing, anti-CTXII particles were tested in a rat monoiodoacetate model of knee OA. CTXII could be magnetically captured from a rodent stifle without the need to aspirate fluid and showed tenfold changes in CTXII levels from OA-affected joints relative to contralateral control joints. Combined, these data demonstrate the ability and sensitivity of magnetic capture for post-mortem analysis of OA biomarkers in the rat.

Relationship between synovial inflammatory cytokines and progression of osteoarthritis after hip arthroscopy: Experimental assessment.

PubMed

Fukushima, Kensuke; Inoue, Gen; Uchida, Kentaro; Fujimaki, Hisako; Miyagi, Masayuki; Nagura, Naoshige; Uchiyama, Katsufumi; Takahira, Naonobu; Takaso, Masashi

2018-01-01

Synovial membrane inflammation is the most commonly presenting finding during hip arthroscopy and may have a role in the pathomechanism of hip osteoarthritis (OA). The aim of this study was to determine the relationship between synovial cytokine levels and progression of OA after hip arthroscopy. We prospectively examined 20 patients (20 hips) who underwent arthroscopic hip surgery. For all patients, radiographs and severity of pain were evaluated preoperatively. During arthroscopy, we harvested a sample of the synovial membrane and determined the levels of six typical inflammatory cytokines with real-time polymerase chain reaction. We compared the levels of these cytokines in patients who showed OA progression and non-progression after hip arthroscopy. Although the average age of patients who showed OA progression postoperatively tended to be higher, there were no significant differences in characteristics involving clinical assessment between patients who showed OA progression and those who showed non-progression. Intraoperative tumour necrosis factor α (TNFα) expression was significantly higher in patients who showed OA progression postoperatively ( p = 0.042). Elevation of TNFα level might be a predictor of OA progression after hip arthroscopy.

Vascular perfusion kinetics by contrast-enhanced ultrasound are related to synovial microvascularity in the joints of psoriatic arthritis.

PubMed

Fiocco, Ugo; Stramare, Roberto; Coran, Alessandro; Grisan, Enrico; Scagliori, Elena; Caso, Francesco; Costa, Luisa; Lunardi, Francesca; Oliviero, Francesca; Bianchi, Fulvia Chieco; Scanu, Anna; Martini, Veronica; Boso, Daniele; Beltrame, Valeria; Vezzù, Maristella; Cozzi, Luisella; Scarpa, Raffaele; Sacerdoti, David; Punzi, Leonardo; Doria, Andrea; Calabrese, Fiorella; Rubaltelli, Leopoldo

2015-11-01

The purpose of the study was to assess the relationship of the continuous mode contrast-enhanced harmonic ultrasound (CEUS) imaging with the histopathological and immunohistochemical (IHC) quantitative estimation of microvascular proliferation on synovial samples of patients affected by sustained psoriatic arthritis (PsA). A dedicated linear transducer was used in conjunction with a specific continuous mode contrast enhanced harmonic imaging technology with a second-generation sulfur hexafluoride-filled microbubbles C-agent. The examination was carried out within 1 week before arthroscopic biopsies in 32 active joints. Perfusional parameters were analyzed including regional blood flow (RBF); peak (PEAK) of the C-signal intensity, proportional to the regional blood volume (RBV); beta (β) perfusion frequency; slope (S), representing the inclination of the tangent in the origin; and the refilling time (RT), the reverse of beta. Arthroscopic synovial biopsies were targeted in the hypervascularity areas, as in the same knee recesses assessed by CEUS; the synovial cell infiltrate and vascularity (vessel density) was evaluated by IHC staining of CD45 (mononuclear cell) and CD31, CD105 (endothelial cell) markers, measured by computer-assisted morphometric analysis. In the CEUS area examined, the corresponding time-intensity curves demonstrated a slow rise time. Synovial histology showed slight increased layer lining thickness, perivascular lymphomonocyte cell infiltration, and microvascular remodeling, with marked vessel wall thickening with reduction of the vascular lumen. A significant correlation was found between RT and CD31+ as PEAK and CD105+ vessel density; RT was inversely correlated to RBF, PEAK, S, and β. The study demonstrated the association of the CEUS perfusion kinetics with the histopathological quantitative and morphologic estimation of synovial microvascular proliferation, suggesting that a CEUS imaging represents a reliable tool for the estimate of the

Prevalence and relevance of antibodies to type-I and -II collagen in synovial fluid of dogs with cranial cruciate ligament damage.

PubMed

de Rooster, H; Cox, E; van Bree, H

2000-11-01

To measure and compare synovial fluid antibody titers to type-I and -II collagen in stifle joints with instability caused by complete or partial cranial cruciate ligament (CCL) rupture and joints with osteoarthrosis secondary to other pathologic changes in dogs. 82 dogs with diseased stifle joints. Synovial fluid samples were collected from 7 dogs with clinically normal stifles (control group) and 82 dogs with diseased joints (50 stifle joints with complete rupture of the CCL, 20 with partial damage of the CCL, and 12 joints with radiographic signs of osteoarthritis secondary to other arthropathies). Synovial fluid samples were tested for autoantibodies to type-I and -II collagen by an ELISA. In dogs with complete and partial CCL rupture, synovial fluid antibody titers to type-I and -II collagen were significantly increased, compared with control dogs. Forty-eight percent (24/50) of samples from dogs with complete CCL rupture and 35% (7/20) of samples from dogs with partial CCL rupture had antibody titers to type-I collagen that were greater than the mean plus 2 standard deviations of the control group titers. Synovial fluid antibody titers to type-II collagen were high in 40% of the dogs with partial or (8/20) complete (20/50) CCL rupture. Dogs with osteoarthrosis secondary to other pathologic changes had significantly increased synovial fluid antibodies to type-I and -II collagen, compared with control dogs. Increases in autoantibodies to collagen in synovial fluid are not specific for the type of joint disorder. It is unlikely that the anticollagen antibodies play an active role in the initiation of weakening of the CCL.

Characterization of the effect of high molecular weight hyaluronan on trans-synovial flow in rabbit knees.

PubMed

Coleman, P J; Scott, D; Mason, R M; Levick, J R

1999-01-01

1. The effect of a rooster comb hyaluronan (3.6-4.0 g l-1) of similar chain length to rabbit synovial fluid hyaluronan, on the trans-synovial escape of fluid from the joint cavity in the steady state ( 8d s) was studied in 29 rabbit knees at controlled intra-articular pressures (Pj). 2. Rooster hyaluronan caused the pressure-flow relation to flatten out as pressure was raised. At 10-20 cmH2O the slope of the quasi-plateau, 0.05 +/- 0.01 microliter min-1 cmH2O-1 (mean +/- s.e.m.), was 1/39th that for Ringer solution (1.94 +/- 0.01 microliter 2O-1 ). 3. Bovine synovial fluid had a similar effect to hyaluronan in Ringer solution. 4. The quasi-plateau was caused by increasing opposition to outflow; the pressure required to drive unit outflow increased 4.4-fold between 5 and 20 cmH2O. The increased opposition to outflow at 20 cmH2O was equivalent to an effective osmotic pressure of 13-17 cmH2O at the interface. Since the infusate's osmotic pressure was only 0.9 cmH2O, this implied concentration polarization to 15-18 g l-1 hyaluronan at the interface. 5. Mechanical perforation of the lining, or enzymatic degradation of the interstitial matrix by chymopapain, abolished the quasi-plateau. Hydrational expansion of the matrix by approximately 2-fold did not. The increased opposition to outflow was reversible by washing out the hyaluronan, or by reducing Pj. It was unaffected by interruption of tissue blood flow or synoviocyte oxidative metabolism. These properties are compatible with a concentration polarization mechanism, i.e. flow-induced concentration of hyaluronan at the synovial interface due to molecular reflection. 6. A concentration polarization theory was developed for a partially reflected solute. Numerical solutions supported the feasibility of this osmotic explanation of the quasi-plateau. Additional mechanisms may also be involved. 7. It is concluded that native-size hyaluronan helps to retain synovial fluid in the joint cavity when pressure is raised and acts

Characterization of the effect of high molecular weight hyaluronan on trans-synovial flow in rabbit knees

PubMed Central

Coleman, P J; Scott, D; Mason, R M; Levick, J R

1999-01-01

The effect of a rooster comb hyaluronan (3.6–4.0 g l−1) of similar chain length to rabbit synovial fluid hyaluronan, on the trans-synovial escape of fluid from the joint cavity in the steady state (Q̇s) was studied in 29 rabbit knees at controlled intra-articular pressures (Pj).Rooster hyaluronan caused the pressure-flow relation to flatten out as pressure was raised. At 10–20 cmH2O the slope of the quasi-plateau, 0.05 ± 0.01 μl min−1 cmH2O−1 (mean ±s.e.m.), was 1/39th that for Ringer solution (1.94 ± 0.01 μl min−1 cmH2O−1).Bovine synovial fluid had a similar effect to hyaluronan in Ringer solution.The quasi-plateau was caused by increasing opposition to outflow; the pressure required to drive unit outflow increased 4.4-fold between 5 and 20 cmH2O. The increased opposition to outflow at 20 cmH2O was equivalent to an effective osmotic pressure of 13–17 cmH2O at the interface. Since the infusate's osmotic pressure was only 0.9 cmH2O, this implied concentration polarization to 15–18 g l−1 hyaluronan at the interface.Mechanical perforation of the lining, or enzymatic degradation of the interstitial matrix by chymopapain, abolished the quasi-plateau. Hydrational expansion of the matrix by /2-fold did not. The increased opposition to outflow was reversible by washing out the hyaluronan, or by reducing Pj. It was unaffected by interruption of tissue blood flow or synoviocyte oxidative metabolism. These properties are compatible with a concentration polarization mechanism, i.e. flow-induced concentration of hyaluronan at the synovial interface due to molecular reflection.A concentration polarization theory was developed for a partially reflected solute. Numerical solutions supported the feasibility of this osmotic explanation of the quasi-plateau. Additional mechanisms may also be involved.It is concluded that native-size hyaluronan helps to retain synovial fluid in the joint cavity when pressure is raised and acts, at least in part, by exerting

Synovial perlecan is required for osteophyte formation in knee osteoarthritis

PubMed Central

Kaneko, Haruka; Ishijima, Muneaki; Futami, Ippei; Tomikawa-Ichikawa, Naoki; Kosaki, Keisuke; Sadatsuki, Ryo; Yamada, Yoshihiko; Kurosawa, Hisashi; Kaneko, Kazuo; Arikawa-Hirasawa, Eri

2013-01-01

The osteophyte associated with osteoarthritis (OA) is a bony outgrowth formed at the margins of the affected joint through endochondral ossification-like processes. However, the mechanism of osteophyte formation and its pathogenesis are unclear. Perlecan (Hspg2), a heparan sulfate proteoglycan, is expressed in many extracellular tissues and plays critical roles in skeletal development and diseases. The aim of the present study is to identify the role of synovial perlecan in osteophyte formation using perinatal lethality rescued perlecan-knockout mice (Hspg2−/−-Tg) wherein perlecan expression is lacking in the synovial and other tissues, except for cartilage. We analyzed the development of osteophytes in joints of Hspg2−/−-Tg mice in two different animal models: the surgical OA model, in which the medial collateral ligament was transected and the medial meniscus was resected, and the TGF-β-induced osteophyte formation model. In the surgical OA model, the osteophyte size and maturation were significantly reduced in the OA joints of Hspg2−/−-Tg mice compared with control mice, while OA developed on the medial side of the knee joints with no differences in the cartilage degradation score or synovitis score between control and Hspg2−/−-Tgmice. The reduced osteophyte formation in Hspg2−/−-Tg mice was associated with reduced cell proliferation and chondrogenesis. In the TGF-β model, the osteophyte size and maturation were also significantly reduced in Hspg2−/−-Tg mice compared with control mice. Our findings suggest that synovial perlecan plays an important role in osteophyte development in OA, and they provide insights that may facilitate the development of OA therapy. PMID:23339896

Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles.

PubMed

Giangarra, Jenna E; Barry, Sabrina L; Dahlgren, Linda A; Lanz, Otto I; Benitez, Marian E; Werre, Stephen R

2018-04-25

To identify if synovial fluid prostaglandin E 2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle. There were no significant differences in synovial fluid prostaglandin E 2 (PGE 2 ) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE 2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE 2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE 2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.

Molecular pathways involved in synovial cell inflammation and tumoral proliferation in diffuse pigmented villonodular synovitis.

PubMed

Fiocco, U; Sfriso, P; Lunardi, F; Pagnin, E; Oliviero, F; Scagliori, E; Cozzi, L; Vezzù, M; Molena, B; Scanu, A; Panziera, C; Nardacchione, R; Rubaltelli, L; Dayer, J M; Calabrese, F; Punzi, L

2010-09-01

Diffuse-type tenosynovial giant cell tumors, also known as pigmented villonodular synovitis, are unique mesenchymal lesions that arise from the synovial tissue of the joints. They are predominantly intraarticular, aggressive, infiltrative processes, characterized by both inflammatory or neoplastic properties and local destructive progression. The pattern of synovial gene and protein expressions in pigmented villonodular synovitis, similar to those in activated macrophages in rheumatoid arthritis, and the phenotype of multinucleated giant cells, characteristic of osteoclasts, suggest that there is a common autocrine mechanism in osteoclast differentiation in both diseases and indicate the potential utility of tumor necrosis factor (TNF)-alpha blockade. High synovial colony stimulating factor 1 (CSF1) messenger RNA (m RNA) expression in pigmented villonodular synovitis, unrelated to a chromosomal translocation involving CSF1 locus, may indicate that there is a synergic paracrine loop mediated by TNF-alpha and CSF1, as shown in both inflammatory and neoplastic conditions. The effects of a new therapeutic approach consisting in intraarticular TNF-alpha blockade were studied in four pigmented villonodular synovitis knees. Knee injections produced a rapid reduction in clinical and sonographic indexes and immunohistological alterations, confirmed by arthroscopic synovectomy. A delayed relapse in one of the four knees and unaltered synovial CSF1 expression were other important findings. In the light of these observations, CSF1/CSF1R interaction probably represents a more sensible therapeutic target than TNF-alpha blockade in the diffuse form of pigmented villonodular synovitis. Copyright 2010 Elsevier B.V. All rights reserved.

Transplantation of autologous synovial mesenchymal stem cells promotes meniscus regeneration in aged primates.

PubMed

Kondo, Shimpei; Muneta, Takeshi; Nakagawa, Yusuke; Koga, Hideyuki; Watanabe, Toshifumi; Tsuji, Kunikazu; Sotome, Shinichi; Okawa, Atsushi; Kiuchi, Shinji; Ono, Hideo; Mizuno, Mitsuru; Sekiya, Ichiro

2017-06-01

Transplantation of aggregates of synovial mesenchymal stem cells (MSCs) enhanced meniscus regeneration in rats. Anatomy and biological properties of the meniscus depend on animal species. To apply this technique clinically, it is valuable to investigate the use of animals genetically close to humans. We investigated whether transplantation of aggregates of autologous synovial MSCs promoted meniscal regeneration in aged primates. Chynomolgus primates between 12 and 13 years old were used. After the anterior halves of the medial menisci in both knees were removed, an average of 14 aggregates consisting of 250,000 synovial MSCs were transplanted onto the meniscus defect. No aggregates were transplanted to the opposite knee for the control. Meniscus and articular cartilage were analyzed macroscopically, histologically, and by MRI T1rho mapping at 8 (n = 3) and 16 weeks (n = 4). The medial meniscus was larger and the modified Pauli's histological score for the regenerated meniscus was better in the MSC group than in the control group in each primate at 8 and 16 weeks. Mankin's score for the medial femoral condyle cartilage was better in the MSC group than in the control group in all primates at 16 weeks. T1rho value for both the regenerated meniscus and adjacent articular cartilage in the MSC group was closer to the normal meniscus than in the control group in all primates at 16 weeks. Transplantation of aggregates of autologous synovial MSCs promoted meniscus regeneration and delayed progression of degeneration of articular cartilage in aged primates. This is the first report dealing with meniscus regeneration in primates. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1274-1282, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

The influence of skeletal maturity on allogenic synovial mesenchymal stem cell-based repair of cartilage in a large animal model.

PubMed

Shimomura, Kazunori; Ando, Wataru; Tateishi, Kosuke; Nansai, Ryosuke; Fujie, Hiromichi; Hart, David A; Kohda, Hideyuki; Kita, Keisuke; Kanamoto, Takashi; Mae, Tatsuo; Nakata, Ken; Shino, Konsei; Yoshikawa, Hideki; Nakamura, Norimasa

2010-11-01

One of the potential factors that may affect the results of mesenchymal stem cell (MSC)-based therapy is the age of donors and recipients. However, there have been no controlled studies to investigate the influence of skeletal maturity on the MSC-based repair of cartilage. The purpose of this study was to compare the repair quality of damaged articular cartilage treated by a scaffold-free three-dimensional tissue-engineered construct (TEC) derived from synovial MSCs between immature and mature pigs. Synovial MSCs were isolated from immature and mature pigs and the proliferation and chondrogenic differentiation capacities were compared. The TEC derived from the synovial MSCs were then implanted into equivalent chondral defects in the medial femoral condyle of both immature and mature pigs, respectively. The implanted defects were morphologically and biomechanically evaluated at 6 months postoperatively. There was no skeletal maturity-dependent difference in proliferation or chondrogenic differentiation capacity of the porcine synovial MSCs. The TEC derived from synovial MSCs promoted the repair of chondral lesion in both immature and mature pigs without the evidence of immune reaction. The repaired tissue by the TEC also exhibited similar viscoelastic properties to normal cartilage regardless of the skeletal maturity. The results of the present study not only suggest the feasibility of allogenic MSC-based cartilage repair over generations but also may validate the use of immature porcine model as clinically relevant to test the feasibility of synovial MSC-based therapies in chondral lesions. Copyright 2010 Elsevier Ltd. All rights reserved.

Descriptions of therapeutic arthrocenthesis and of synovial fluid in a Nahuatl text from prehispanic Mexico.

PubMed Central

Alarcon-Segovia, D

1980-01-01

Paracelsus is considered to have been the first to record the viscid quality of the synovial fluid. However, his contemporary Bernardino de Sahagún, a Franciscan friar who came to Mexico shortly after the Spanish conquest, obtained from elderly Aztec Indians who spoke only Nahuatl the descriptions of therapeutic arthrocentesis and of the viscid nature of the synovial fluid. They compared the fluid from the knee joint to the viscid fluid from the leaves of the nopal cactus (Opuntia sp.). We here record their description and confirm the accuracy of their comparison. Images PMID:7416821

Descriptions of therapeutic arthrocenthesis and of synovial fluid in a Nahuatl text from prehispanic Mexico.

PubMed

Alarcon-Segovia, D

1980-06-01

Paracelsus is considered to have been the first to record the viscid quality of the synovial fluid. However, his contemporary Bernardino de Sahagún, a Franciscan friar who came to Mexico shortly after the Spanish conquest, obtained from elderly Aztec Indians who spoke only Nahuatl the descriptions of therapeutic arthrocentesis and of the viscid nature of the synovial fluid. They compared the fluid from the knee joint to the viscid fluid from the leaves of the nopal cactus (Opuntia sp.). We here record their description and confirm the accuracy of their comparison.

Curcumin induces apoptosis and inhibits prostaglandin E(2) production in synovial fibroblasts of patients with rheumatoid arthritis.

PubMed

Park, Cheol; Moon, Dong-Oh; Choi, Il-Whan; Choi, Byung Tae; Nam, Taek-Jeong; Rhu, Chung-Ho; Kwon, Taeg Kyu; Lee, Won Ho; Kim, Gi-Young; Choi, Yung Hyun

2007-09-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease that is characterized by hyperplasia of the synovial fibroblasts, which is partly the result of decreased apoptosis. This study investigated the mechanisms through which curcumin, a polyphenolic compound from the rhizome of Curcuma longa, exerts its anti-proliferative action in the synovial fibroblasts obtained from patients with RA. Exposure of the synovial fibroblasts to curcumin resulted in growth inhibition and the induction of apoptosis, as measured by MTT assay, fluorescent microscopy and Annexin-V-based assay. RT-PCR and immunoblotting showed that treating the cells with curcumin resulted in the down-regulation of anti-apoptotic Bcl-2 and the X-linked inhibitor of the apoptosis protein as well as the up-regulation of pro-apoptotic Bax expression in a concentration-dependent manner. Curcumin-induced apoptosis was also associated with the proteolytic activation of caspase-3 and caspase-9, and the concomitant degradation of poly(ADP-ribose) polymerase protein. Furthermore, curcumin decreased the expression levels of the cyclooxygenase (COX)-2 mRNA and protein without causing significant changes in the COX-1 levels, which was correlated with the inhibition of prostaglandin E(2) synthesis. These results show that curcumin might help identify a new therapeutic pathway against hyperplasia of the synovial fibroblasts in RA.

Predictive value of synovial fluid analysis in estimating the efficacy of intra-articular corticosteroid injections in patients with rheumatoid arthritis.

PubMed Central

Luukkainen, R; Hakala, M; Sajanti, E; Huhtala, H; Yli-Kerttula, U; Hämeenkorpi, R

1992-01-01

The predictive relevance of synovial fluid analysis and some other variables for the efficacy of intra-articular corticosteroid injections in 30 patients with rheumatoid arthritis and hydropsy in a knee joint was evaluated in a prospective study. At the onset of the study, the knee joints were aspirated and 30 mg triamcinolone hexacetonide injected intra-articularly. The circumferences and the tenderness scores of the knee joints were measured at onset, after two months, and at the end of the six months' follow up. Of the variables studied, synovial fluid C4, percentage of synovial fluid polymorphonuclear leucocytes, blood haemoglobin, and serum C3 correlated significantly with the decrease in knee joint circumference after two months, whereas only the percentage of synovial fluid polymorphonuclear leucocytes correlated significantly after six months. Between the patients with and without improvement in the tenderness scores of the knee joints, only serum IgM differed at the examination after two months; this was higher in patients whose scores showed no improvement. PMID:1632661

Proinflammatory cytokine activities, matrix metalloproteinase-3 activity, and sulfated glycosaminoglycan content in synovial fluid of dogs with naturally acquired cranial cruciate ligament rupture.

PubMed

Fujita, Yukihiro; Hara, Yasushi; Nezu, Yoshinori; Schulz, Kurt S; Tagawa, Masahiro

2006-06-01

To measure and compare activities of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and matrix metalloproteinase-3 (MMP-3); as well as sulfated glycosaminoglycan (S-GAG) content in synovial fluid from dogs with cranial cruciate ligament rupture (CCLR) and dogs with clinically normal stifles. To determine whether correlations exist between demographic and disease-related variables and these synovial markers. Prospective clinical study. Dogs with CCLR (n=23) and Beagles with normal stifle joints (n=21). Synovial fluid activities of proinflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) were determined by bioassay. MMP-3 activity was measured using fluorogenic substrate. S-GAG contents were determined by dimethylmethylene blue dye-binding assay. Mann-Whitney U-test was used to compare results from CCLR joints with normal controls. Spearman's rank correlation test was used to evaluate associations between demographic and disease-related markers and synovial markers. Mean values for synovial markers were significantly higher in CCLR joints compared with controls. IL-1beta and MMP-3 were positively correlated with lameness duration. Activities of proinflammatory cytokines, MMP-3 activity and S-GAG contents were significantly elevated in synovial fluid from canine stifle joints with naturally acquired CCLR. These results indicate that there is joint inflammation and increased release of GAGs into synovial fluid, suggesting that these inflammatory changes are associated with depletion of proteoglycan from articular cartilage. Medical and surgical treatments designed to decrease joint inflammation and breakdown of proteoglycans may be of value in the management of CCLR in the dog.

Proteomic Analysis of Synovial Fluid Obtained From a Dog Diagnosed With Idiopathic Immune-Mediated Polyarthritis.

PubMed

Tan, Wei Miao; Lau, Seng Fong; Ajat, Mokrish; Mansor, Rozaihan; Abd Rani, Puteri Azaziah Megat; Rahmad, Norasfaliza Binti

2017-03-01

This case study is to report the proteins detected by proteomic analysis of synovial fluid from a dog diagnosed with idiopathic immune-mediated polyarthritis, and to compare it with healthy dogs. Synovial fluid was collected via arthrocentesis from a dog diagnosed with immune-mediated polyarthritis. Protein precipitation was performed on the synovial fluid, followed by isoelectric focusing and 2-dimensional gel electrophoresis. The spots on the 2-dimensional gels were analyzed using MALDI-TOF/MS. The results were then analyzed against the MASCOT database. The results from the proteomic analysis revealed an abundance of several types of immunoglobulins together with the presence of complement C4b-binding protein alpha chain. Actin and keratin were also among the proteins detected. Proteomic studies, facilitate a better understanding of the different levels of proteins expressed during disease activity. Potential disease biomarkers can aid in the diagnosis of disease, as well as help in monitoring treatment efficacy and providing prognosis for the patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Bone marrow mesenchymal stem cells do not enhance intra-synovial tendon healing despite engraftment and homing to niches within the synovium.

PubMed

Khan, Mohammad R; Dudhia, Jayesh; David, Frederic H; De Godoy, Roberta; Mehra, Vedika; Hughes, Gillian; Dakin, Stephanie G; Carr, Andrew J; Goodship, Allen E; Smith, Roger K W

2018-06-19

Intra-synovial tendon injuries display poor healing, which often results in reduced functionality and pain. A lack of effective therapeutic options has led to experimental approaches to augment natural tendon repair with autologous mesenchymal stem cells (MSCs) although the effects of the intra-synovial environment on the distribution, engraftment and functionality of implanted MSCs is not known. This study utilised a novel sheep model which, although in an anatomically different location, more accurately mimics the mechanical and synovial environment of the human rotator cuff, to determine the effects of intra-synovial implantation of MSCs. A lesion was made in the lateral border of the lateral branch of the ovine deep digital flexor tendon within the digital sheath and 2 weeks later 5 million autologous bone marrow MSCs were injected under ultrasound guidance into the digital sheath. Tendons were recovered post mortem at 1 day, and 1-2, 4, 12 and 24 weeks after MSC injection. For the 1-day and 1-2-week groups, MSCs labelled with fluorescent-conjugated magnetic iron-oxide nanoparticles (MIONs) were tracked with MRI, histology and flow cytometry. The 4, 12 and 24-week groups were implanted with non-labelled cells and compared with saline-injected controls for healing. The MSCs displayed no reduced viability in vitro to an uptake of 20.0 ± 4.6 pg MIONs per cell, which was detectable by MRI at minimal density of ~ 3 × 10 4 cells. Treated limbs indicated cellular distribution throughout the tendon synovial sheath but restricted to the synovial tissues, with no MSCs detected in the tendon or surgical lesion. The lesion was associated with negligible morbidity with minimal inflammation post surgery. Evaluation of both treated and control lesions showed no evidence of healing of the lesion at 4, 12 and 24 weeks on gross and histological examination. Unlike other laboratory animal models of tendon injury, this novel model mimics the failed tendon healing

[Postoperative evaluation of surgically treated cases with temporary silicone implant in temporomandibular joint].

PubMed

Aoyama, Shigeru; Kino, Koji; Shibuya, Toshihisa; Sato, Fumiaki; Kobayashi, Akiko; Yoshitake, Hiroyuki; Haketa, Tadasu; Amamori, Yoko; Ishikawa, Takayuki; Yoshida, Nahoko; Amagasa, Teruo

2003-09-01

We have carried out temporary silicone implants after diskectomies or arthroplasties in temporomandibular joint surgeries to avoid postoperative adhesion and to maintain articular space. We evaluated 19 joints in 15 patients who had received dacron-reinforced silicone implant after silicone sheet removal through follow-up for at least 6 months. The cases included temporomandibular joint disorder (10 joints in 9 patients), psoriatic arthritis (2 joints in 1 patient), ankylosis (4 joints in 3 patients) and synovial chondromatosis (2 joints in 2 patients). On the basis of the criteria of temporomandibular dysfunction for the results, they were classified as bad (4 patients). It is thought that factors other than the implant are related to the bad results in the postoperative evaluation. In this study, lymphadenopathy induced by exfoliated silicone debris could not be confirmed. The temporary silicone implant in the temporomandibular joint was thought to be useful.

The limitations of Gram-stain microscopy of synovial fluid in concomitant septic and crystal arthritis.

PubMed

Stirling, Paul; Tahir, Mohammed; Atkinson, Henry Dushan

2017-03-29

Rapid diagnosis of septic arthritis from Gram-stain microscopy is limited by an inherent false-negative rate of 25-78%. The presence of concomitant crystal arthritis in 5% of cases represents a particular diagnostic challenge. This study aims to investigate the effects that a concomitant crystal arthropathy have on the ability of Gram-stain microscopy of synovial fluid to diagnose a septic arthritis. This is a 12-year retrospective cohort study. Inclusion criteria were a positive synovial fluid culture result with a positive clinical diagnosis of septic arthritis. Results were correlated with presence or absence of urate and calcium pyrophosphate crystals, and Gram-stain result. During this time our collection and analysis methods remained unchanged. All samples were collected in Lithium Heparin containers. Chi-squared test with a p value < 0.05 was considered significant. 602 synovial fluid samples were included. 162 cases of concomitant crystal arthritis were identified (27%). Of these, 16 (10%) had an initial negative Gram-stain. Of the 440 samples with no crystals detected, 18 (4%) had an initial negative Gram-stain microscopy result (p < 0.05). The incidence of concurrent septic and crystal arthritis may be higher than previously thought. Synovial fluid samples in concomitant septic and crystal arthritis are significantly less likely to have a positive Gram-stain at microscopy than in cases of an isolated septic arthritis. We would advise the clinician to maintain a high index of suspicion for septic arthritis in these patients. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Importance of synovial fluid aspiration when injecting intra-articular corticosteroids

PubMed Central

Weitoft, T.; Uddenfeldt, P.

2000-01-01

OBJECTIVE—The aim of this prospective study was to find if a complete synovial fluid aspiration before injecting intra-articular corticosteroids influences the treatment result.
METHODS—The study was performed in 147 patients with rheumatoid arthritis (RA). One hundred and ninety one knees with synovitis were randomised to arthrocentesis (n=95) or no arthrocentesis (n=96) before 20 mg triamcinolone hexacetonide was injected. The duration of effect was followed up for a period of six months. All patients were instructed to contact the rheumatology department if signs and symptoms from the treated knee recurred. If arthritis could be confirmed by a clinical examination a relapse was noted.
RESULTS—There was a significant reduction of relapse in the arthrocentesis group (p=0.001).
CONCLUSION—The study shows that aspiration of synovial fluid can reduce the risk for arthritis relapse when treating RA patients with intra-articular corticosteroids. It is concluded that arthrocentesis shall be included in the intra-articular corticosteroid injection procedure.

 PMID:10700435

Correlation of Synovial Fluid Biomarkers With Cartilage Pathology and Associated Outcomes in Knee Arthroscopy.

PubMed

Cuéllar, Vanessa G; Cuéllar, Jason M; Kirsch, Thorsten; Strauss, Eric J

2016-03-01

To correlate the intraoperative concentrations of 20 synovial fluid biomarkers with preoperative symptoms, intraoperative findings, and postoperative outcomes in patients undergoing knee arthroscopy, with comparisons made to samples obtained from asymptomatic knees. Synovial fluid samples were obtained from 81 patients undergoing knee arthroscopy meeting the inclusion criteria, which included 70 samples from operative knees and 32 samples from contralateral knees. Preoperatively, baseline data obtained from clinical questionnaires including a visual analog scale (VAS) score, the Lysholm score, and the Knee Injury and Osteoarthritis Outcome Score-Physical Function Short Form were recorded. Synovial fluid was collected from both the operative knee and asymptomatic contralateral knee. Synovial fluid was stored with a protease inhibitor at -80°C until analysis. Intraoperative findings, procedures performed, and International Cartilage Repair Society (ICRS) cartilage status scores in all operative knees were documented. The concentrations of the following 20 biomarkers were measured using a multiplex magnetic bead immunoassay: matrix metalloproteinase (MMP) 3; MMP-13; tissue inhibitor of metalloproteinase (TIMP) 1; TIMP-2; TIMP-3; TIMP-4; fibroblast growth factor 2; eotaxin; interferon γ; interleukin (IL) 10; platelet-derived growth factor BB; IL-1 receptor antagonist; IL-1β; IL-6; monocyte chemotactic protein 1 (MCP-1); macrophage inflammatory protein 1α; macrophage inflammatory protein 1β; RANTES (regulated upon activation, normal T cell expressed and secreted); tumor necrosis factor α; and vascular endothelial growth factor. Clinical outcome scores were obtained in 83% of patients at a mean of 17 months' follow-up postoperatively. Analysis of variance and Pearson correlation analysis were performed to determine statistical significance between preoperative data, intraoperative findings, postoperative outcomes, and synovial fluid biomarker concentrations

Role of tumor necrosis factor-alpha and platelet-activating factor in neoangiogenesis induced by synovial fluids of patients with rheumatoid arthritis.

PubMed

Lupia, E; Montrucchio, G; Battaglia, E; Modena, V; Camussi, G

1996-08-01

The aim of the present study was to investigate in vivo in a mouse model the stimulation of neoangiogenesis by synovial fluids of patients with rheumatoid arthritis (RA) and to determine the role of tumor necrosis factor (TNF)-alpha and platelet-activating factor (PAF) in the formation of new vessels. Angiogenesis was studied in a mouse model in which Matrigel, injected subcutaneously, was used as a vehicle for the delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangiogenesis. Since synovial fluid of patients with RA contained significantly higher levels of TNF-alpha-like bioactivity and of PAF than that of patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF receptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mAb and particularly WEB 2170 significantly reduced neoangiogenesis induced by synovial fluids of RA patients. Moreover, PAF extracted and purified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alpha and PAF.

Knee Locking in Osteoarthritis due to Synovial Lipoma: A Case Report

PubMed Central

S. Amarjit, Kataria; Budhiraja, Shivali; Chandramouleeswari, K.; Anita, S.

2013-01-01

Intra–articular synovial lipomas are very rare and only few cases have been reported till now. We are reporting a rare case of a unilateral intra–articular lipoma of osteoarthritic knee joint in a 62 years old male. Patient had two episodes of sudden locking of knee joint, which resolved spontaneously. A plain X-ray showed changes which were suggestive of osteoarthritis. Clinically, patient was diagnosed as a case of loose bodies in left knee joint. An arthrotomy was performed. After a Histopathological Examination (HPE) of loose bodies, a diagnosis of an intra–articular synovial lipoma was made. Due to wide differentials and varied clinical behaviour of loose bodies, lipoma should be included in differential diagnosis of osteroarthritic patients who complain of episodic locking of knees. Intraarticular lipomas, on arthroscopic guided excision, get cured permanently, with no recurrence. The differentiation of an intra-articular lipoma from a relatively more common entity, Lipoma arborescens, has also been discussed. PMID:24086885

Activated fibrinolytic enzymes in the synovial fluid during acute arthritis induced by urate crystal injection in dogs.

PubMed

Morimoto, N; Sumi, H; Tsushima, H; Etou, Y; Yoshida, E; Mihara, H

1991-10-01

To identify the relationship of the severity of inflammation and fibrinolytic activity in arthritis, the fibrinolytic activity of synovial fluid was studied in acute experimental arthritis induced by injecting monosodium urate crystals into dogs' knee joints. The maximum activity in the synovial fluid was observed 6 h after crystal injection. It was inferred that the fibrinolytic activity was mainly due to plasminogen activator based on fibrin plate assays, substrate specificity, inhibitor effects and zymography. On the other hand, the activity of lysosomal enzymes (beta-glucuronidase and cathepsin G) reached a peak in the synovia after 12 h. Histological examination of the synovial membrane after 12 h also showed greater inflammation than at 6 h. The peak in fibrinolytic activity preceded the peak of lysosomal enzymes and histological changes. These results suggest that an increase in fibrinolytic activity by plasminogen activator may contribute to the development of an acute inflammatory response.

High expression of SDF-1 and VEGF is associated with poor prognosis in patients with synovial sarcomas.

PubMed

Feng, Qi; Guo, Peng; Wang, Jin; Zhang, Xiaoyu; Yang, Hui-Chai; Feng, Jian-Gang

2018-03-01

Stromal cell-derived factor-1 (SDF-1) predicts poor clinical outcomes of certain types of cancer. Furthermore, vascular endothelial growth factor (VEGF) promotes the growth and metastasis of solid tumors. The aim of the present study was to examine the expression of SDF-1 and VEGF in patients with synovial sarcoma and to determine their expression is correlated with unfavorable outcomes. Levels of SDF-1 and VEGF proteins were evaluated in 54 patients with synovial sarcoma using immunohistochemical and immunofluorescence staining. Potential associations between the expression of SDF-1 and VEGF and various clinical parameters were analyzed using Pearson's χ 2 test and the Spearman-rho test. Additionally, univariate and multivariate Cox regression analyses were used to identify potential prognostic factors, and the Kaplan-Meier method was used to analyze the overall survival rates of patients. Low SDF-1 and VEGF expression was detected in 20.4% (11/54) and 22.2% (12/54) of patients with synovial sarcoma; moderate expression was detected in 35.2% (19/54) and 37.0% (20/54) of patients and high expression was detected in 44.4% (24 of 54) and 40.7% (22 of 54) of patients, respectively. Levels of SDF-1 and VEGF proteins were significantly associated with histological grade (P<0.05), metastasis (P<0.05) and American Joint Committee on Cancer staging (P<0.05). In addition, levels of SDF-1 and VEGF expression were positively correlated with each other (P<0.001). Univariate analysis also indicated that VEGF expression was associated with shorter overall survival rates in (P<0.05), whereas multivariate analysis demonstrated that SDF-1 expression was associated with shorter patient survival rates (P<0.05). Finally, both SDF-1 and VEGF expression were associated with various characteristics of synovial sarcoma. Therefore, SDF-1 expression may be a potential independent prognostic indicator in patients with synovial sarcomas.

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs

PubMed Central

Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Hatsushika, Daisuke; Horie, Masafumi; Tsuji, Kunikazu; Kawarasaki, Tatsuo; Watanabe, Atsuya; Hishikawa, Shuji; Fujimoto, Yasuhiro; Tanaka, Hozumi; Kobayashi, Eiji

2012-01-01

Background aims Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. Methods The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Results Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Conclusions Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs. PMID:22309371

Arthroscopic, histological and MRI analyses of cartilage repair after a minimally invasive method of transplantation of allogeneic synovial mesenchymal stromal cells into cartilage defects in pigs.

PubMed

Nakamura, Tomomasa; Sekiya, Ichiro; Muneta, Takeshi; Hatsushika, Daisuke; Horie, Masafumi; Tsuji, Kunikazu; Kawarasaki, Tatsuo; Watanabe, Atsuya; Hishikawa, Shuji; Fujimoto, Yasuhiro; Tanaka, Hozumi; Kobayashi, Eiji

2012-03-01

Transplantation of synovial mesenchymal stromal cells (MSCs) may induce repair of cartilage defects. We transplanted synovial MSCs into cartilage defects using a simple method and investigated its usefulness and repair process in a pig model. The chondrogenic potential of the porcine MSCs was compared in vitro. Cartilage defects were created in both knees of seven pigs, and divided into MSCs treated and non-treated control knees. Synovial MSCs were injected into the defect, and the knee was kept immobilized for 10 min before wound closure. To visualize the actual delivery and adhesion of the cells, fluorescence-labeled synovial MSCs from transgenic green fluorescent protein (GFP) pig were injected into the defect in a subgroup of two pigs. In these two animals, the wounds were closed before MSCs were injected and observed for 10 min under arthroscopic control. The defects were analyzed sequentially arthroscopically, histologically and by magnetic resonance imaging (MRI) for 3 months. Synovial MSCs had a higher chondrogenic potential in vitro than the other MSCs examined. Arthroscopic observations showed adhesion of synovial MSCs and membrane formation on the cartilage defects before cartilage repair. Quantification analyses for arthroscopy, histology and MRI revealed a better outcome in the MSC-treated knees than in the non-treated control knees. Leaving a synovial MSC suspension in cartilage defects for 10 min made it possible for cells to adhere in the defect in a porcine cartilage defect model. The cartilage defect was first covered with membrane, then the cartilage matrix emerged after transplantation of synovial MSCs.

The tumour-associated glycoprotein podoplanin is expressed in fibroblast-like synoviocytes of the hyperplastic synovial lining layer in rheumatoid arthritis

PubMed Central

2011-01-01

Introduction Activated fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) share many characteristics with tumour cells and are key mediators of synovial tissue transformation and joint destruction. The glycoprotein podoplanin is upregulated in the invasive front of several human cancers and has been associated with epithelial-mesenchymal transition, increased cell migration and tissue invasion. The aim of this study was to investigate whether podoplanin is expressed in areas of synovial transformation in RA and especially in promigratory RA-FLS. Methods Podoplanin expression in human synovial tissue from 18 RA patients and nine osteoarthritis (OA) patients was assessed by immunohistochemistry and confirmed by Western blot analysis. The expression was related to markers of synoviocytes and myofibroblasts detected by using confocal immunofluoresence microscopy. Expression of podoplanin, with or without the addition of proinflammatory cytokines and growth factors, in primary human FLS was evaluated by using flow cytometry. Results Podoplanin was highly expressed in cadherin-11-positive cells throughout the synovial lining layer in RA. The expression was most pronounced in areas with lining layer hyperplasia and high matrix metalloproteinase 9 expression, where it coincided with upregulation of α-smooth muscle actin (α-sma). The synovium in OA was predominantly podoplanin-negative. Podoplanin was expressed in 50% of cultured primary FLSs, and the expression was increased by interleukin 1β, tumour necrosis factor α and transforming growth factor β receptor 1. Conclusions Here we show that podoplanin is highly expressed in FLSs of the invading synovial tissue in RA. The concomitant upregulation of α-sma and podoplanin in a subpopulation of FLSs indicates a myofibroblast phenotype. Proinflammatory mediators increased the podoplanin expression in cultured RA-FLS. We conclude that podoplanin might be involved in the synovial tissue transformation and

[Destruction of synovial pannus of antigen-induced arthritis by ultrasonic cavitation in rabbits].

PubMed

Zhang, Ling-yan; Qiu, Li; Wang, Lei; Lin, Ling; Wen, Xiao-rong

2011-11-01

To optimize the conditions of ultrasonic irradiation and microbubble of ultrasound cavitation on destruction of synovial pannus of antigen-induced arthritis (AIA) in rabbits. Antigen-induced arthritis was successfully induced on bilateral knee joints of 85 rabbits. Each 10 AIA rabbits were divided into two groups to compare various peak negative pressures, different ultrasonic pulse durations, various pulse repetition frequencies, different irradiance duration, different dosages of microbubble contrast agents, different ultrasonic irradiance times. With intravenous infusion of Sonovue to the rabbits, ultrasonic irradiance was performed on the right knee joint using the above condition of ultrasound cavitation. At the day 1 after ultrasonic irradiance, MRI and pathological examination were employed to evaluate the optimal conditions. The optimal parameters and conditions for ultrasonic irradiance included intermittent ultrasonic application (in 6 s intervals), 0.6 mL/kg of microbubble contrast agent, 4.6 MPa of ultrasonic peak negative pressure, 100 cycles of pulse duration, 50 Hz of pulse repetition frequency, 5 min of ultrasonic duration, 0.6 mL/kg of dosages of microbubble contrast agents and multi-sessional ultrasonic irradiance. After the ultrasonic irradiance, the thickness of right knee synovium measured by MRI was thinner than that of left knee and synovial necrosis was confirmed by the pathological finding. Under optimal ultrasonic irradiation and microbubble conditions, ultrasonic cavitation could destroy synovial pannus of AIA in rabbits.

Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis

PubMed Central

Yeo, L; Adlard, N; Juarez, M; Smallie, T; Snow, M; Buckley, C D; Raza, K; Filer, A; Scheel-Toellner, D

2016-01-01

Background and objectives For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Methods Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. Results A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68+ macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Conclusions Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. PMID:25858640

Examination of synovial fluid and serum following intravenous injections of hyaluronan for the treatment of osteoarthritis in dogs.

PubMed

Canapp, S O; Cross, A R; Brown, M P; Lewis, D D; Hernandez, J; Merritt, K A; Tran-Son-Tay, R

2005-01-01

A randomized, blinded, prospective clinical trial was performed to determine the effects of intravenous (i.v.) administration of hyaluronan sodium (HA) on serum glycosaminoglycans (GAG) concentrations, synovial fluid (SF) hyaluronan concentrations and viscosity in dogs treated for unilateral rupture of the cranial cruciate ligament. Twenty-two dogs undergoing tibial plateau leveling osteotomy were used in this study. Synovial fluid from both stifles and serum were collected prior to surgery and at 2, 4, and 8 weeks following surgery. Dogs received either 1.0 ml (10 mg) of sodium hyaluronate (treatment group 1; n = 10) or equal volume of 0.9% NaCl (treatment group 2; n = 12), i.v. immediately, 2 and 4 weeks following surgery. Synovial fluid viscosity was evaluated using a magnetically driven, acoustically tracked, translating-ball rheometer. Synovial fluid HA disaccharide content was measured by fluorophore-assisted carbohydrate electrophoresis. Serum GAG concentrations were measured by alcian blue spectrophotometric assay. Data were analyzed using a Wilcoxon sign rank test (p < 0.05). Mean +/- SD viscosity (cP) was significantly higher (p = 0.011) in SF obtained from the intact stifle (450 +/- 604.1) than injured (54.8 +/- 60.8) prior to surgery. Mean +/- SD HA concentrations (ug/ml) were significantly higher (p = 0.02) in synovial fluid obtained from the injured stifles (281.4 +/- 145.9) than intact stifles (141.6 +/- 132.5). No significant difference was noted within or between treatment groups in SF viscosity, HA concentrations, or serum GAG concentrations at any time following surgery. Stifles with cranial cruciate ligament insufficiency had significant alterations in SF viscosity and HA concentrations.

The effect of robenacoxib on the concentration of C-reactive protein in synovial fluid from dogs with osteoarthritis.

PubMed

Bennett, David; Eckersall, Peter David; Waterston, Mary; Marchetti, Veronica; Rota, Alessandra; McCulloch, Eilidh; Sbrana, Silvia

2013-03-01

Robenacoxib is a novel and highly selective inhibitor of COX-2 in dogs and cats and because of its acidic nature is regarded as being tissue-selective. Thirty four dogs with stifle osteoarthritis secondary to failure of the cranial cruciate ligament were recruited into this study. Lameness, radiographic features, synovial cytology and C-reactive protein concentrations in serum and synovial fluid were assessed before and 28 days after commencing a course of Robenacoxib at a dose of 1 mg/kg SID. There was a significant reduction in the lameness score (P < 0.01) and an increase in the radiographic score (P < 0.05) between pre- and post-treatment assessments. There was no difference between pre- (median 1.49 mg/l; Q1-Q3 0.56-4.24 mg/L) and post - (1.10 mg/L; 0.31-1.78 mg/L) treatment serum C-reactive protein levels although synovial fluid levels were significantly reduced (pre- : 0.44 mg/L; 0.23-1.62 mg/L; post- : 0.17 mg/L; 0.05-0.49 mg/L) (P < 0.05). There was no correlation between C-reactive protein concentrations in serum and matched synovial fluid samples. Robenacoxib proved effective in reducing lameness in dogs with failure of the cranial cruciate ligament and osteoarthritis of the stifle joint. The drug also reduced levels of C-reactive protein in the synovial fluid taken from the affected stifle joint. Robenacoxib appears to reduce articular inflammation as assessed by C-reactive protein which supports the concept that Robenacoxib is a tissue-selective non-steroidal anti-inflammatory drug.

Relationship between automated total nucleated cell count and enumeration of cells on direct smears of canine synovial fluid.

PubMed

Dusick, Allison; Young, Karen M; Muir, Peter

2014-12-01

Canine osteoarthritis is a common disorder seen in veterinary clinical practice and causes considerable morbidity in dogs as they age. Synovial fluid analysis is an important tool for diagnosis and treatment of canine joint disease and obtaining a total nucleated cell count (TNCC) is particularly important. However, the low sample volumes obtained during arthrocentesis are often insufficient for performing an automated TNCC, thereby limiting diagnostic interpretation. The aim of the present study was to investigate whether estimation of TNCC in canine synovial fluid could be achieved by performing manual cell counts on direct smears of fluid. Fifty-eight synovial fluid samples, taken by arthrocentesis from 48 dogs, were included in the study. Direct smears of synovial fluid were prepared, and hyaluronidase added before cell counts were obtained using a commercial laser-based instrument. A protocol was established to count nucleated cells in a specific region of the smear, using a serpentine counting pattern; the mean number of nucleated cells per 400 × field was then calculated. There was a positive correlation between the automated TNCC and mean manual cell count, with more variability at higher TNCC. Regression analysis was performed to estimate TNCC from manual counts. By this method, 78% of the samples were correctly predicted to fall into one of three categories (within the reference interval, mildly to moderately increased, or markedly increased) relative to the automated TNCC. Intra-observer and inter-observer agreement was good to excellent. The results of the study suggest that interpretation of canine synovial fluid samples of low volume can be aided by methodical manual counting of cells on direct smears. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dissemination Activities Report

ERIC Educational Resources Information Center

Barclay, Hanna; Batatia, Hudj; Bauters, Merja; Ben Ami, Zvi; Drachman, Raul; Flouris, Giorgos; Jadin, Tanja; Jalonen, Satu; Karlgren, Klas; Karpati, Andrea; Kotzinos, Dimitris; Lakkala, Minna; Lallimo, Jiri; Moen, Anne; Nygard, Kathrine; Paavola, Sami; Padiglia, Sheila; Scapolla, Marina; Sins, Patrick; Vasileva, Tania

2008-01-01

In the first 24 months of the project, KP-Lab members were highly dedicated to dissemination and were engaged in various dissemination activities that contributed to the prime objective of the KP-Lab dissemination efforts which is "to make the project widely known to a variety of prospective users and, at a later stage, to promote the…

Differential roles of SS18-SSX fusion gene and insulin-like growth factor-1 receptor in synovial sarcoma cell growth

DOE Office of Scientific and Technical Information (OSTI.GOV)

Toernkvist, Maria; Natalishvili, Natalia; Xie Yuntao

2008-04-11

Recently we demonstrated that the synovial sarcoma specific fusion gene SS18-SSX is crucial for cyclin D1 expression and is linked to cell proliferation. In this report we explore the role of SS18-SSX and IGF-1R for their potential functions in cellular proliferation and survival in cultured synovial sarcoma cells. We found that targeting of SS18-SSX mRNA by antisense oligonucleotide treatment drastically and rapidly decreased cell proliferation but caused only a slight increase of apoptosis. The synovial sarcoma cells were confirmed to express IGF-1R, and treatment with an IGF-1R inhibitor resulted in substantially reduced cell viability by inducing apoptosis in these cells.more » Conversely, inhibition of the IGF-1R resulted only in a slight to moderate decrease in DNA synthesis. In conclusion, SS18-SSX and IGF-1R seem to play important but different roles in maintaining malignant growth of synovial sarcoma cells. Whereas SS18-SSX maintains cyclin D1 and cell proliferation, IGF-1R protects from apoptosis.« less

Identification of cytotoxic agents disrupting synovial sarcoma oncoprotein interactions by proximity ligation assay.

PubMed

Laporte, Aimée N; Ji, Jennifer X; Ma, Limin; Nielsen, Torsten O; Brodin, Bertha A

2016-06-07

Conventional cytotoxic therapies for synovial sarcoma provide limited benefit. Drugs specifically targeting the product of its driver translocation are currently unavailable, in part because the SS18-SSX oncoprotein functions via aberrant interactions within multiprotein complexes. Proximity ligation assay is a recently-developed method that assesses protein-protein interactions in situ. Here we report use of the proximity ligation assay to confirm the oncogenic association of SS18-SSX with its co-factor TLE1 in multiple human synovial sarcoma cell lines and in surgically-excised human tumor tissue. SS18-SSX/TLE1 interactions are disrupted by class I HDAC inhibitors and novel small molecule inhibitors. This assay can be applied in a high-throughput format for drug discovery in fusion-oncoprotein associated cancers where key effector partners are known.

Retrospective review of percutaneous synovial cyst ruptures: increased thickness of the T2 hypointense rim on post-rupture MRI may be associated with need for subsequent surgery.

PubMed

Kwan, Benjamin Y M; Salehi, Fateme; Jia, Sang; McGregor, Stuart; Duggal, Neil; Pelz, David; Sharma, Manas

2017-08-01

To analyze MRI characteristics of lumbar facet synovial cysts and distinguish those requiring subsequent surgical management for recurrence, after percutaneous synovial cyst rupture. Retrospective chart review conducted in patients undergoing percutaneous synovial cyst rupture between February 2012 and April 2015. Pre- and post-percutaneous rupture procedure MRI spine studies were serially reviewed. Synovial cyst sizes, T1 and T2 signal characteristics and changes therein, T2 hypointense (or 'dark rim') thickness and change, and changes in the complexity of cyst signals were compared. Operative notes for patients who underwent subsequent surgical removal of recurrent synovial cysts were reviewed. 24 patients received 41 percutaneous synovial cyst rupture procedures, with a technical success rate of 82.9%. There was a significant difference in the mean increased thickness of the T2 hypointense rim on the first post-rupture MRI scan (p=0.0411) between patients requiring subsequent surgery and those who did not. There was a significant difference in the average sizes of synovial cysts before the procedure (p=0.0483) in those requiring subsequent surgery and those who did not. Five complications were noted (12.2%), mostly involving leg pain or weakness. Of the nine patients who underwent subsequent surgery post-synovial cyst rupture, six of the surgeries had recorded difficulty pertaining to scarring and/or adherence of the cyst to dura. A larger increase in thickness of the T2 hypointense rim on the first post-rupture MRI scan and a larger synovial cyst size were associated with the need for subsequent surgical resection. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Synovial fluid progenitors expressing CD90+ from normal but not osteoarthritic joints undergo chondrogenic differentiation without micro-mass culture.

PubMed

Krawetz, Roman J; Wu, Yiru Elizabeth; Martin, Liam; Rattner, Jerome B; Matyas, John R; Hart, David A

2012-01-01

Mesenchymal progenitor cells (MPCs) can differentiate into osteoblasts, adipocytes, and chondrocytes, and are in part responsible for maintaining tissue integrity. Recently, a progenitor cell population has been found within the synovial fluid that shares many similarities with bone marrow MPCs. These synovial fluid MPCs (sfMPCs) share the ability to differentiate into bone and fat, with a bias for cartilage differentiation. In this study, sfMPCs were isolated from human and canine synovial fluid collected from normal individuals and those with osteoarthritis (human: clinician-diagnosed, canine: experimental) to compare the differentiation potential of CD90+ vs. CD90- sfMPCs, and to determine if CD90 (Thy-1) is a predictive marker of synovial fluid progenitors with chondrogenic capacity in vitro. sfMPCs were derived from synovial fluid from normal and OA knee joints. These cells were induced to differentiate into chondrocytes and analyzed using quantitative PCR, immunofluorescence, and electron microscopy. The CD90+ subpopulation of sfMPCs had increased chondrogenic potential compared to the CD90- population. Furthermore, sfMPCs derived from healthy joints did not require a micro-mass step for efficient chondrogenesis. Whereas sfMPCs from OA synovial fluid retain the ability to undergo chondrogenic differentiation, they require micro-mass culture conditions. Overall, this study has demonstrated an increased chondrogenic potential within the CD90+ fraction of human and canine sfMPCs and that this population of cells derived from healthy normal joints do not require a micro-mass step for efficient chondrogenesis, while sfMPCs obtained from OA knee joints do not differentiate efficiently into chondrocytes without the micro-mass procedure. These results reveal a fundamental shift in the chondrogenic ability of cells isolated from arthritic joint fluids, and we speculate that the mechanism behind this change of cell behavior is exposure to the altered milieu of the OA

MicroRNA221-3p modulates Ets-1 expression in synovial fibroblasts from patients with osteoarthritis of temporomandibular joint.

PubMed

Xu, J; Liu, Y; Deng, M; Li, J; Cai, H; Meng, Q; Fang, W; Long, X; Ke, J

2016-11-01

This study aimed to screen differential expression of microRNAs (miRNAs), and investigate function of the specifically selected miRNA in synovial fibroblasts from patients suffering osteoarthritis of temporomandibular joint (TMJOA). MiRNA microarray was used to select differentially expressed miRNAs between TMJOA and normal synovial fibroblasts. The expression of screened miRNA221-3p was quantified using real-time PCR, and its specific target gene was predicted by bioinformatics. After transfection of miRNA221-3p mimics or inhibitor into synovial fibroblasts, the expression of v-Ets avian erythroblastosis virus E26 oncogene homolog 1 (Ets-1) was detected by immunohistochemistry, real-time PCR and Western blot, respectively. Dual luciferase activity was performed to identify the direct regulation of miRNA221-3p on Ets-1. Interlukin-1β (IL-1β) mimics an inflammatory situation. In TMJOA synovial fibroblasts, eight miRNAs were up-regulated and six miRNAs were down-regulated. MiRNA221-3p was the most down-expressed. A sequence in the 3'-untranslated (3'-UTR) of Ets-1 complementary to the seed sequence of miRNA221-3p. Elevated expression of Ets-1 associated with attenuation of miRNA221-3p. Over-expression of miRNA221-3p suppressed the activity of a reporter construct containing the 3'-UTR of Ets-1 transcript and inhibited the expression of Ets-1 as well as its downstream molecules, matrix metalloproteinase 1 (MMP1) and MMP9 in TMJOA synovial fibroblasts. IL-1β suppressed the expression of miRNA221-3p in both a dose-dependent and time-dependent manner. The reduction of miRNA221-3p in synovial fibroblasts, attributed from abundance of IL-1β in inflamed circumstance, induces Ets-1 up-regulation and then, initiates MMP1 and MMP9 secretion, thereby leading to continuously pathological development in TMJOA. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Chiropractic management of a patient with lumbar spine pain due to synovial cyst: a case report

PubMed Central

Cox, James M.

2012-01-01

Introduction The purpose of this study is to report the findings resulting from chiropractic care using flexion distraction spinal manipulation for a patient with low back and radicular pain due to spinal stenosis caused by a synovial cyst. Case Report A 75-year-old man presented with low back pain radiating to the right anterior thigh and down the left posterior leg of 3 years' duration. Physical and imaging examinations showed a synovial cyst–induced spinal stenosis at the right L3-L4 level and bilateral L4-L5 spinal stenosis. Intervention and Outcomes Flexion distraction spinal manipulation and physiological therapeutics were applied at the levels of stenosis. After 4 visits, the patient noted total absence of the right and left lower extremity pain and no adverse reaction to treatment. After 3 months of treatment and 16 visits, his low back and buttock pain were minimal; and he had no leg pain. Conclusion Lumbar synovial cyst and stenosis–generated low back and radicular pain was 80% relieved in a 75-year-old man following Cox flexion distraction spinal manipulation. PMID:22942836

Introduction to the special section on dissemination: dissemination research and research dissemination: how can we close the gap?

PubMed

Kerner, Jon; Rimer, Barbara; Emmons, Karen

2005-09-01

One of the greatest challenges facing health promotion and disease prevention is translating research findings into evidence-based public health and clinical practices that are actively disseminated and widely adopted. Despite the tremendous strides made in developing effective disease prevention and control programs, there has been little study of effective dissemination of evidence-based programs to and adoption by community, public health, and clinical practice settings. This special section provides a venue in which to highlight exemplary dissemination research efforts while also identifying limitations in research to date and framing important future research questions. This issue establishes a resource for investigators interested in dissemination research, with relevance to health psychology. In this sense, it can serve as a benchmark by which to examine subsequent progress. The 6 articles reflect the state of the science in dissemination research for the promotion and adoption of health behavior change interventions. (c) 2005 APA, all rights reserved

Expression of interleukin-8 and intercellular cell adhesion molecule-1 in the synovial membrane and cranial cruciate ligament of dogs after rupture of the ligament

PubMed Central

El-Hadi, Mustafa; Charavaryamath, Chandarshekhar; Aebischer, Andrea; Smith, C. Wayne; Shmon, Cindy; Singh, Baljit

2012-01-01

This cross-sectional clinical study compared inflammation, including expression of the chemokine interleukin (IL)-8 and intercellular cell adhesion molecule-1 (ICAM-1), in the stifle joints of 4 control dogs and 23 dogs with cranial cruciate ligament rupture (CCLR). The CCL, synovial membrane, meniscus, cartilage, and synovial fluid from the affected stifle joints of all the dogs were examined. Inflammatory cell counts were performed on the synovial fluid, and the tissues were processed for histologic study and immunohistochemical detection of IL-8 and ICAM-1. The synovial fluid from the stifle joints of the dogs with CCLR had an increased percentage of neutrophils (P = 0.054) and a decreased percentage of lymphocytes (P = 0.004) but not macrophages compared with the fluid from the control dogs. There was accumulation of inflammatory cells and increased expression of IL-8 and ICAM-1 in the vascular endothelium of the synovial membrane and the CCL of the dogs with CCLR. The increase in inflammatory cells in the stifle joints of dogs with CCLR may therefore be due to increased expression of IL-8 and ICAM-1 in the synovial membrane and the CCL after the injury. These data may help in understanding the mechanisms of inflammation associated with CCLR. PMID:22754089

Expression of interleukin-8 and intercellular cell adhesion molecule-1 in the synovial membrane and cranial cruciate ligament of dogs after rupture of the ligament.

PubMed

El-Hadi, Mustafa; Charavaryamath, Chandarshekhar; Aebischer, Andrea; Smith, C Wayne; Shmon, Cindy; Singh, Baljit

2012-01-01

This cross-sectional clinical study compared inflammation, including expression of the chemokine interleukin (IL)-8 and intercellular cell adhesion molecule-1 (ICAM-1), in the stifle joints of 4 control dogs and 23 dogs with cranial cruciate ligament rupture (CCLR). The CCL, synovial membrane, meniscus, cartilage, and synovial fluid from the affected stifle joints of all the dogs were examined. Inflammatory cell counts were performed on the synovial fluid, and the tissues were processed for histologic study and immunohistochemical detection of IL-8 and ICAM-1. The synovial fluid from the stifle joints of the dogs with CCLR had an increased percentage of neutrophils (P = 0.054) and a decreased percentage of lymphocytes (P = 0.004) but not macrophages compared with the fluid from the control dogs. There was accumulation of inflammatory cells and increased expression of IL-8 and ICAM-1 in the vascular endothelium of the synovial membrane and the CCL of the dogs with CCLR. The increase in inflammatory cells in the stifle joints of dogs with CCLR may therefore be due to increased expression of IL-8 and ICAM-1 in the synovial membrane and the CCL after the injury. These data may help in understanding the mechanisms of inflammation associated with CCLR.

Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion

PubMed Central

de Matos, Cristina Teixeira; Berg, Louise; Michaëlsson, Jakob; Felländer-Tsai, Li; Kärre, Klas; Söderström, Kalle

2007-01-01

Natural killer (NK) cells are activated early during inflammatory events and contribute to the shaping of the ensuing adaptive immune response. To further understand the role for NK cells in inflammation, we investigated the phenotype and function of synovial fluid (SF) NK cells from patients with chronic joint inflammation, as well as from patients with transient inflammation of the knee following trauma. We confirm that synovial NK cells are similar to the well-characterized CD56bright peripheral blood (PB) NK-cell subset present in healthy individuals. However, compared to this PB subset the synovial NK cells express a higher degree of activation markers including CD69 and NKp44, the latter being up-regulated also on CD56bright NK cells in the PB of patients. Activated synovial NK cells produced interferon-γ and tumour necrosis factor, and the production was further up-regulated by antibody masking of CD94/NKG2A, and down-regulated by target cells expressing human leucocyte antigen-E in complex with peptides known to engage CD94/NKG2A. We conclude that synovial NK cells have an activated phenotype and that CD94/NKG2A is a key regulator of synovial NK-cell cytokine synthesis. PMID:17521371

Exposure of a tendon extracellular matrix to synovial fluid triggers endogenous and engrafted cell death: A mechanism for failed healing of intrathecal tendon injuries.

PubMed

Garvican, Elaine R; Salavati, Mazdak; Smith, Roger K W; Dudhia, Jayesh

2017-09-01

The purpose of this study was to investigate the effect of normal synovial fluid (SF) on exposed endogenous tendon-derived cells (TDCs) and engrafted mesenchymal stem cells (MSCs) within the tendon extracellular matrix. Explants from equine superficial digital flexor (extra-synovial) and deep digital flexor tendons (DDFTs) from the compressed, intra-synovial and the tensile, extra-synovial regions were cultured in allogeneic or autologous SF-media. Human hamstring explants were cultured in allogeneic SF. Explant viability was assessed by staining. Proliferation of equine monolayer MSCs and TDCs in SF-media and co-culture with DDFT explants was determined by alamarblue®. Non-viable Native Tendon matrices (NNTs) were re-populated with MSCs or TDCs and cultured in SF-media. Immunohistochemical staining of tendon sections for the apoptotic proteins caspase-3, -8, and -9 was performed. Contact with autologous or allogeneic SF resulted in rapid death of resident tenocytes in equine and human tendon. SF did not affect the viability of equine epitenon cells, or of MSCs and TDCs in the monolayer or indirect explant co-culture. MSCs and TDCs, engrafted into NNTs, died when cultured in SF. Caspase-3, -8, and -9 expression was the greatest in SDFT explants exposed to allogeneic SF. The efficacy of cells administered intra-synovially for tendon lesion repair is likely to be limited, since once incorporated into the matrix, cells become vlnerable to the adverse effects of SF. These observations could account for the poor success rate of intra-synovial tendon healing following damage to the epitenon and contact with SF, common with most soft tissue intra-synovial pathologies.

Targeted gene delivery to the synovial pannus in antigen-induced arthritis by ultrasound-targeted microbubble destruction in vivo.

PubMed

Xiang, Xi; Tang, Yuanjiao; Leng, Qianying; Zhang, Lingyan; Qiu, Li

2016-02-01

The purpose of this study was to optimize an ultrasound-targeted microbubble destruction (UTMD) technique to improve the in vivo transfection efficiency of the gene encoding enhanced green fluorescent protein (EGFP) in the synovial pannus in an antigen-induced arthritis rabbit model. A mixture of microbubbles and plasmids was locally injected into the knee joints of an antigen-induced arthritis (AIA) rabbits. The plasmid concentrations and ultrasound conditions were varied in the experiments. We also tested local articular and intravenous injections. The rabbits were divided into five groups: (1) ultrasound+microbubbles+plasmid; (2) ultrasound+plasmid; (3) microbubble+plasmid; (4) plasmid only; (5) untreated controls. EGFP expression was observed by fluorescent microscope and immunohistochemical staining in the synovial pannus of each group. The optimal plasmid dosage and ultrasound parameter were determined based on the results of EGFP expression and the present and absent of tissue damage under light microscopy. The irradiation procedure was performed to observe the duration of the EGFP expression in the synovial pannus and other tissues and organs, as well as the damage to the normal cells. The optimal condition was determined to be a 1-MHz ultrasound pulse applied for 5 min with a power output of 2 W/cm(2) and a 20% duty cycle along with 300 μg of plasmid. Under these conditions, the synovial pannus showed significant EGFP expression without significant damage to the surrounding normal tissue. The EGFP expression induced by the local intra-articular injection was significantly more increased than that induced by the intravenous injection. The EGFP expression in the synovial pannus of the ultrasound+microbubbles+plasmid group was significantly higher than that of the other four groups (P<0.05). The expression peaked on day 5, remained detectable on day 40 and disappeared on day 60. No EGFP expression was detected in the other tissues and organs. The UTMD

Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis.

PubMed

Yeo, L; Adlard, N; Biehl, M; Juarez, M; Smallie, T; Snow, M; Buckley, C D; Raza, K; Filer, A; Scheel-Toellner, D

2016-04-01

For our understanding of the pathogenesis of rheumatoid arthritis (RA), it is important to elucidate the mechanisms underlying early stages of synovitis. Here, synovial cytokine production was investigated in patients with very early arthritis. Synovial biopsies were obtained from patients with at least one clinically swollen joint within 12 weeks of symptom onset. At an 18-month follow-up visit, patients who went on to develop RA, or whose arthritis spontaneously resolved, were identified. Biopsies were also obtained from patients with RA with longer symptom duration (>12 weeks) and individuals with no clinically apparent inflammation. Synovial mRNA expression of 117 cytokines was quantified using PCR techniques and analysed using standard and novel methods of data analysis. Synovial tissue sections were stained for CXCL4, CXCL7, CD41, CD68 and von Willebrand factor. A machine learning approach identified expression of mRNA for CXCL4 and CXCL7 as potentially important in the classification of early RA versus resolving arthritis. mRNA levels for these chemokines were significantly elevated in patients with early RA compared with uninflamed controls. Significantly increased CXCL4 and CXCL7 protein expression was observed in patients with early RA compared with those with resolving arthritis or longer established disease. CXCL4 and CXCL7 co-localised with blood vessels, platelets and CD68(+) macrophages. Extravascular CXCL7 expression was significantly higher in patients with very early RA compared with longer duration RA or resolving arthritis Taken together, these observations suggest a transient increase in synovial CXCL4 and CXCL7 levels in early RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The effect of robenacoxib on the concentration of C-reactive protein in synovial fluid from dogs with osteoarthritis

PubMed Central

2013-01-01

Background Robenacoxib is a novel and highly selective inhibitor of COX-2 in dogs and cats and because of its acidic nature is regarded as being tissue-selective. Thirty four dogs with stifle osteoarthritis secondary to failure of the cranial cruciate ligament were recruited into this study. Lameness, radiographic features, synovial cytology and C-reactive protein concentrations in serum and synovial fluid were assessed before and 28 days after commencing a course of Robenacoxib at a dose of 1 mg/kg SID. Results There was a significant reduction in the lameness score (P < 0.01) and an increase in the radiographic score (P < 0.05) between pre- and post-treatment assessments. There was no difference between pre- (median 1.49 mg/l; Q1-Q3 0.56-4.24 mg/L) and post – (1.10 mg/L; 0.31-1.78 mg/L) treatment serum C-reactive protein levels although synovial fluid levels were significantly reduced (pre- : 0.44 mg/L; 0.23-1.62 mg/L; post- : 0.17 mg/L; 0.05-0.49 mg/L) (P < 0.05). There was no correlation between C-reactive protein concentrations in serum and matched synovial fluid samples. Conclusions Robenacoxib proved effective in reducing lameness in dogs with failure of the cranial cruciate ligament and osteoarthritis of the stifle joint. The drug also reduced levels of C-reactive protein in the synovial fluid taken from the affected stifle joint. Robenacoxib appears to reduce articular inflammation as assessed by C-reactive protein which supports the concept that Robenacoxib is a tissue-selective non-steroidal anti-inflammatory drug. PMID:23452411

Hip Arthroscopy Update

PubMed Central

Buly, Robert L.

2005-01-01

The management of hip injuries in the athlete has evolved significantly in the past few years with theadvancement of arthroscopic techniques. The application of minimally invasive surgical techniques has facilitated relatively rapid returns to sporting activity in recreational and elite athletes alike. Recent advancements in both hip arthroscopy and magnetic resonance imaging have elucidated several sources of intraarticular pathology that result in chronic and disabling hip symptoms. Many of these conditions were previously unrecognized and thus, left untreated. Current indications for hip arthroscopy include management of labral tears, osteoplasty for femoroacetabular impingement, thermal capsulorrhaphy and capsular plication for subtle rotational instability and capsular laxity, lateral impact injury and chondral lesions, osteochondritis dissecans, ligamentum teres injuries, internal and external snapping hip, removal of loose bodies, synovial biopsy, subtotal synovectomy, synovial chondromatosis, infection, and certain cases of mild to moderate osteoarthritis with associated mechanical symptoms. In addition, patients with long-standing, unresolved hip joint pain and positive physical findings may benefit from arthroscopic evaluation. Patients with reproducible symptoms and physical findings that reveal limited functioning, and who have failed an adequate trial of conservative treatment will have the greatest likelihood of success after surgical intervention. Strict attention to thorough diagnostic examination, detailed imaging, and adherence to safe and reproducible surgical techniques, as described in this review, are essential for the success of this procedure. PMID:18751808

The role of synovial fluid analysis in the detection of periprosthetic hip and knee infections: a systematic review and meta-analysis.

PubMed

De Fine, Marcello; Giavaresi, Gianluca; Fini, Milena; Illuminati, Andrea; Terrando, Silvio; Pignatti, Giovanni

2018-05-01

This study tried to ascertain (1) the accuracy of synovial fluid white blood cell count and polymorphonucleate percentage in the diagnosis of periprosthetic hip and knee infections, (2) which test yielded superior test performance, and (3) the influence on diagnostic accuracy of study characteristics such as patient number, study design, study level, anatomic site, and threshold value. A systematic search was conducted including papers assessing more effective cutoffs for synovial fluid tests, having comparative design, evaluating an exclusive cohort of hip or knee prostheses, including a clear definition of infected cases, and reporting sufficient data for the calculation of true-positive, false-positive, false-negative, and true-negative. A total of 375 articles were collected and, given the inclusion criteria, ten manuscripts were included. These studies assessed 1155 hip prostheses (276 infected cases) and 1235 knee prostheses (401 infected cases). The specificity of synovial fluid white blood cell count was significantly increased by using the threshold value ≥ 3000 cell/μL (p = 0.006); the sensitivity of polymorphonucleate percentage was significantly higher in detecting knee infections (p = 0.034). Both tests had a high specificity and sensitivity in detecting periprosthetic joint infections, and no clear superiority of one over the other existed. Furthermore, cutoff and anatomic site significantly influenced synovial fluid white blood cell count and polymorphonucleate percentage, respectively. Synovial fluid analysis is adequate in differentiating patients with periprosthetic hip and knee infections. Our data confirms international guidelines suggesting the use of 3000 cell/μL as cutoff threshold for synovial fluid white blood cell count. Since an anatomic site effect has been demonstrated, the goal of future studies will be to identify different cutoffs for hip and knee prostheses.

Longitudinal Assessment of Synovial, Lymph Node, and Bone Volumes in Inflammatory Arthritis in Mice using in vivo MRI and micro-CT

PubMed Central

Proulx, Steven T.; Kwok, Edmund; You, Zhigang; Papuga, M. Owen; Beck, Christopher A.; Shealy, David J.; Ritchlin, Christopher T.; Awad, Hani A.; Boyce, Brendan F.; Xing, Lianping; Schwarz, Edward M.

2009-01-01

Objective Development of longitudinal 3D outcomes of inflammation and bone erosion in murine arthritis using contrast enhanced (CE) MRI and in vivo micro-CT; and in a pilot study, to determine the value of entrance criteria by age versus synovial volume in therapeutic intervention studies. Methods CE-MRI and in vivo micro-CT was performed on TNF-Tg and WT littermates to quantify the synovial and popliteal lymph node (LN) volumes and patella and talus bone volumes, respectively, which were validated with histology. These longitudinal outcome measures were used to assess the natural history of inflammatory-erosive arthritis. We also performed anti-TNF versus placebo efficacy studies in TNF-Tg mice in which treatment was initiated either by age (4–5 months) or synovial volume (3mm3 as detected by CE-MRI). Linear regression was performed to analyze the correlation between synovitis and focal erosion. Results CE-MRI demonstrated the highly variable nature of TNF-induced joint inflammation. Initiation of treatment by synovial volume produced significantly larger treatment effects on synovial volume (p=0.04) and lymph node volume (p<0.01) than initiation by age. By correlating the MRI and microCT data we were able to demonstrate a significant relationship between changes in synovial and patellar volumes (R2 =0.75; p<0.01). Conclusion In vivo CE-MRI and micro-CT 3D outcome measures are powerful tools that accurately demonstrate the progression of inflammatory-erosive arthritis in mice. These methods can be used to identify mice with arthritis of similar severity before intervention studies are initiated and thus minimize heterogeneity in outcome studies of chronic arthritis seen between genetically identical littermates. PMID:18050199

Tribological performance of the biological components of synovial fluid in artificial joint implants

NASA Astrophysics Data System (ADS)

Ghosh, Subir; Choudhury, Dipankar; Roy, Taposh; Moradi, Ali; Masjuki, H. H.; Pingguan-Murphy, Belinda

2015-08-01

The concentration of biological components of synovial fluid (such as albumin, globulin, hyaluronic acid, and lubricin) varies between healthy persons and osteoarthritis (OA) patients. The aim of the present study is to compare the effects of such variation on tribological performance in a simulated hip joint model. The study was carried out experimentally by utilizing a pin-on-disk simulator on ceramic-on-ceramic (CoC) and ceramic-on-polyethylene (CoP) hip joint implants. The experimental results show that both friction and wear of artificial joints fluctuate with the concentration level of biological components. Moreover, the performance also varies between material combinations. Wear debris sizes and shapes produced by ceramic and polyethylene were diverse. We conclude that the biological components of synovial fluid and their concentrations should be considered in order to select an artificial hip joint to best suit that patient.

Largazole, a class I histone deacetylase inhibitor, enhances TNF-α-induced ICAM-1 and VCAM-1 expression in rheumatoid arthritis synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmed, Salahuddin, E-mail: Salah.Ahmed@utoledo.edu; Riegsecker, Sharayah; Beamer, Maria

In the present study, we evaluated the effect of largazole (LAR), a marine-derived class I HDAC inhibitor, on tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and matrix metalloproteinase-2 (MMP-2) activity. LAR (1–5 μM) had no adverse effect on the viability of RA synovial fibroblasts. Among the different class I HDACs screened, LAR (0.5–5 μM) inhibited the constitutive expression of HDAC1 (0–30%). Surprisingly, LAR increased class II HDAC [HDAC6] by ∼ 220% with a concomitant decrease in HDAC5 [30–58%] expression in RA synovial fibroblasts. SAHA (5 μM), a pan-HDAC inhibitor, also inducedmore » HDAC6 expression in RA synovial fibroblasts. Pretreatment of RA synovial fibroblasts with LAR further enhanced TNF-α-induced ICAM-1 and VCAM-1 expression. However, LAR inhibited TNF-α-induced MMP-2 activity in RA synovial fibroblasts by 35% when compared to the TNF-α-treated group. Further, the addition of HDAC6 specific inhibitor Tubastatin A with LAR suppressed TNF-α + LAR-induced ICAM-1 and VCAM-1 expression and completely blocked MMP-2 activity, suggesting a role of HDAC6 in LAR-induced ICAM-1 and VCAM-1 expression. LAR also enhanced TNF-α-induced phospho-p38 and phospho-AKT expression, but inhibited the expression of phospho-JNK and nuclear translocation of NF-κBp65 in RA synovial fibroblasts. These results suggest that LAR activates p38 and Akt pathways and influences class II HDACs, in particular HDAC6, to enhance some of the detrimental effects of TNF-α in RA synovial fibroblasts. Understanding the exact role of different HDAC isoenzymes in RA pathogenesis is extremely important in order to develop highly effective HDAC inhibitors for the treatment of RA. - Highlights: • Largazole enhances TNF-α-induced ICAM-1 and VCAM-1. • Largazole upregulates class II HDAC (HDAC6) in RA synovial fibroblasts. • Largazole also induces the expression of

Synovial haemangioma of the knee joint: an unusual cause of knee pain in a 14-month old girl.

PubMed

Wen, D W; Tan, T J; Rasheed, S

2016-06-01

We report a histologically proven case of synovial haemangioma of the knee in a 14-month old girl who presented to the emergency department with an acute 1-day history of refusing to weight-bear on the right leg and a preceding 3-week history of a right knee lump. Physical examination revealed a non-tender, soft lump over the lateral infrapatellar region. Radiographs revealed a poorly defined soft tissue density over the infrapatellar fat pad and a suprapatellar joint effusion. Ultrasound was used to confirm the presence of a vascular soft tissue mass compatible with a synovial haemangioma within the infrapatellar fat pad which showed both intra-articular and extra-articular extension. There was good correlation of the ultrasound findings with magnetic resonance imaging (MRI), highlighting the potential clinical utility of ultrasound as an alternative imaging modality in establishing the pre-operative diagnosis and extent of a synovial haemangioma about the knee joint.

Synovial angiostatic non-ELR CXC chemokines in inflammatory arthritides: does CXCL4 designate chronicity of synovitis?

PubMed

Erdem, Hakan; Pay, Salih; Musabak, Ugur; Simsek, Ismail; Dinc, Ayhan; Pekel, Aysel; Sengul, Ali

2007-08-01

In our previous studies, we found higher synovial fluid (SF) levels of angiogenic ELR(+) CXC chemokines such as CXCL1, CXCL5, CXCL6 and CXCL8, which play an important role in neutrophil migration and angiogenesis, and more abundant synovial CXCR2 chemokine receptor expression in patients with rheumatoid arthritis (RA) than those with Behçet's disease (BD), familial Mediterranean fever and osteoarthritis (OA). As a continuation of our previous studies, we investigated synovial levels of angiostatic non-ELR CXC chemokines (CXCL4, CXCL9 and CXCL10) in patients with RA, BD, spondyloarthritis (SpA), and OA. Seventy (17 RA, 15 BD, 19 SpA, and 19 OA) patients were enrolled in the study. The levels of CXCL4, CXCL9, and CXCL10 were measured by ELISA. The SF levels of CXCL4 in patients with RA were higher than those of the patients with BD, SpA, and OA (P = 0.007, P = 0.022, and P = 0.017, respectively). No difference was found with respect to CXCL4 levels among the BD, SpA, and OA patients. The synovial CXCL9 levels of patients with RA and SpA were found to be higher than those of the patients with OA (P = 0.002 and P = 0.005, respectively), while no statistically significant difference was detected among the other groups. With regard to SF CXCL10 levels, patients with RA had higher levels as compared to patients with OA (P = 0.002), but no significant difference was found among the other groups. CXCL9 correlated with CXCL4 and CXCL10 (P < 0.05 for both) in patients with RA. No correlation was found in other parameters. The angiostatic non-ELR CXC chemokines were expressed in synovial inflammation. We proposed that angiostatic non-ELR CXC chemokines may increase to balance angiogenic ELR (+) CXC chemokines in which increased levels were shown in patients with inflammatory arthritides and CXCL4 may contribute to designate the chronicity of synovitis in patients with RA. In addition, as CXCL-9 and CXCL-10 play crucial role in inflammation characterized by Th1 polarization

Reverse transcriptase polymerase chain reaction on fine needle aspirates for rapid detection of translocations in synovial sarcoma.

PubMed

Nilsson, G; Wang, M; Wejde, J; Kanter, L; Karlén, J; Tani, E; Kreicbergs, A; Larsson, O

1998-01-01

To evaluate the utilization of fine needle aspiration (FNA) biopsy to obtain material for reverse-transcriptase polymerase chain reaction (RT-PCR) in the detection of the t(X;18)(p11.2;q11.2) translocation in synovial sarcomas. We applied RT-PCR to detection of synovial sarcoma fusion gene transcripts on fine needle aspirates. Five clinical samples were first analyzed: one was a tumor previously diagnosed as malignant hemangiopericytoma, one was a poorly defined tumor, and three were suspected synovial sarcomas. FNA material was transferred directly to the RT-PCR reaction tube without RNA extraction. The t(X;18) translocation could be detected on the limited amount of material that FNA provides. In each of the cases studied the representivity of the tumor samples was confirmed microscopically. Our protocol permits analysis directly on representative samples without extraction of RNA. The results imply that RT-PCR offers reliable detection of sarcoma fusion gene transcripts on fine needle aspirates. The procedure, apart from being applicable to outpatients, is rapid and sensitive.

Discrimination of osteoarthritic and rheumatoid human synovial cells in culture by nuclear image analysis.

PubMed

Delage, B; Giroud, F; Monet, J D; Ekindjian, O G; Cals, M J

1999-06-01

Rheumatoid arthritic (RA) and osteoarthritic (OA) synovial cells in culture differ in their metabolic and proliferative behaviour. To assess links between these properties and nuclear changes, we used image analysis to study chromatin texture, together with nuclear morphometry and densitometry of OA and RA cells in primary culture. Chromatin pattern at the third day (D3) was heterogeneous and granular with chromatin clumps whereas at the final stage (D11) of culture a homogeneous and finely granular chromatin texture was observed. This evolution indicates global chromatin decondensation. These characteristics were more marked for RA than for OA nuclei. At each culture time, RA nuclei could be discriminated with high confidence from OA ones from parameters evaluating the organization of the chromatine texture. Nuclear image analysis is thus a useful tool for investigating synovial cell biology.

Hyaluronic acid concentrations in synovial fluid of dogs with different stages of osteoarthritis.

PubMed

Plickert, H D; Bondzio, A; Einspanier, R; Tichy, A; Brunnberg, L

2013-06-01

To compare hyaluronic acid (HA) concentrations measured in synovial fluid (SF) of joints with different stages of canine secondary osteoarthritis (OA), clinical-orthopedic, radiographic, macroscopic intra-operative and SF findings of 49 joints were assessed. The sum of single findings was correlated to HA concentrations measured by a commercially available ELISA. Joints were categorized into three OA-groups: non-osteoarthritic, mildly osteoarthritic, and severely osteoarthritic. A significant negative correlation was found between severity of OA and HA concentrations (r=-0.696; P<0.001). Median values of HA concentrations decreased with increasing severity of the disease. Statistically significant differences in HA concentrations were observed between the OA-groups (P<0.001). Due to overlapping values between groups, it was concluded that synovial HA concentrations may only indicate a trend of osteoarthritic disease activity, but is not suitable for staging the disease. Copyright © 2012 Elsevier Ltd. All rights reserved.

Use of proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture.

PubMed

Shahid, Muhammad; Manchi, George; Brunnberg, Leo; Raila, Jens

2018-04-01

OBJECTIVE To use proteomic analysis to determine the protein constituents of synovial fluid samples from the stifle joints of dogs with and without osteoarthritis secondary to cranial cruciate ligament rupture (CCLR). ANIMALS 12 dogs with clinically normal stifle joints (controls) and 16 dogs with osteoarthritis secondary to CCLR. PROCEDURES A synovial fluid sample was obtained from all dogs. Synovial fluid total protein concentration was determined by the Bradford assay. Proteins were separated by use of a 1-D SDS-PAGE to detect protein bands that differed between dogs with and without osteoarthritis. Those protein bands then underwent trypsin digestion and were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry, the results of which were compared with a curated protein sequence database for protein identification. One of the most frequently identified proteins, apoprotein (apo) A-I, was then quantified in all synovial fluid samples by use of a competitive-inhibition ELISA. Results were compared between dogs with and without osteoarthritis. RESULTS Median synovial fluid total protein and apo A-I concentrations for dogs with osteoarthritis were significantly greater than those for control dogs. The most abundant proteins identified in the synovial fluid were albumin and apo A-I. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that quantification of synovial fluid total protein and apo A-I concentrations might facilitate diagnosis of osteoarthritis secondary to CCLR in dogs. Further research and validation of synovial fluid apo A-I concentration as a biomarker for osteoarthritis in dogs are necessary before it can be recommended for clinical use.

Measurements of C-reactive protein in serum and lactate dehydrogenase in serum and synovial fluid of patients with osteoarthritis.

PubMed

Hurter, K; Spreng, D; Rytz, U; Schawalder, P; Ott-Knüsel, F; Schmökel, H

2005-03-01

Diagnosis of osteoarthritis (OA) is based upon the clinical orthopaedic examination and the radiographic assessment, both of which can be non-specific and insensitive in early joint disease. The aim of our study was to investigate if there is an increase in serum levels of C-reactive protein (CRP) in degenerative joint disease (DJD) and if CRP could be used to help diagnose OA. We also wished to investigate whether it was possible to distinguish a joint with clinically and radiographically confirmed OA from a healthy joint by comparing lactate dehydrogenase (LDH) levels within the synovial fluid and the serum. We have shown a difference in synovial LDH levels between diseased and healthy joints (P<0.0001). There was also a significant difference between LDH in arthritic synovial fluid and serum, with no correlation between the values. Despite the fact that the values of our clinical patients tended to be higher than the values of our control group (P=0.05) all measured values were within the normal limits of previous publications. From these data, we conclude that single measurements of serum CRP do not permit detection of OA in clinical patients and that serum LDH is not a reliable marker for osteoarthritis. LDH levels in the synovial fluid could be of diagnostic value for identifying osteoarthritis.

Correlation of dickkopf-1 concentrations in plasma and synovial fluid to the severity of radiographic signs of equine osteoarthritis.

PubMed

Mills, Jillian S; Kinsley, Marc A; Peters, Duncan F; Weber, Patty S D; Shearer, Tara R; Pease, Anthony P

2017-09-12

The purpose of this study was to determine whether there was a correlation between circulating and intra-synovial Dkk-1 and radiographic signs of equine osteoarthritis. Circulating and intra-synovial Dkk-1 levels were measured in clinical cases using a commercially available human Dkk-1 ELISA. Radiographs were performed of the joints from which fluid was collected and these were assessed and scored by a boarded radiologist for joint narrowing, subchondral bone sclerosis, subchondral bone lysis, and periarticular modelling. Comparisons were made between radiographic scores and the concentrations of Dkk-1 using a Kruskal-Wallis one-way ANOVA. Correlations were calculated using Kendall's statistic. A total of 42 synovial fluid samples from 21 horses were collected and used in the analysis. No significant correlation was identified between Dkk-1 concentrations and radiographic signs of osteoarthritis. Intra-synovial Dkk-1 concentrations were significantly greater (p <0.001) in low motion joints (mean concentration, 232.68 pg/mL; range, 109.07-317.17) when compared to high-motion joints (28.78 pg/mL; 0.05-186.44 pg/mL) (p <0.001). Low motion joints have significantly higher concentrations of Dkk-1 compared to high motion joints. Further research is needed to establish the importance of this finding and whether potential diagnostic or therapeutic applications of Dkk-1 exist in the horse.

Monophasic synovial sarcoma of posterior pharyngeal wall: a rare case report with unique reconstruction using lateral trapezius flap.

PubMed

Agarwal, Mudit; Singh, Abhishek; Abrari, Adleeb; Singh, Naveen

2017-04-01

Synovial sarcoma is a rare entity to be encountered in the head and neck region and is always a challenge in terms of diagnosis, treatment planning and reconstruction of the surgical defect. In our case, we faced a similar challenge for diagnosis and also have ventured for lateral trapezius flap as a new reconstructive option for such bulky tumour defects. We hereby present a 25-year old male patient with monophasic synovial sarcoma of posterior pharyngeal wall. The radiological and clinicopathological features along with various diagnostic tests and treatment options are discussed.

Laboratory evaluation and interpretation of synovial fluid.

PubMed

MacWilliams, Peter S; Friedrichs, Kristen R

2003-01-01

Canine and feline joint disease can be a primary disorder limited to joints or a manifestation of multisystemic disease. Collection and analysis of joint fluid provides valuable information for the diagnosis, prognosis, and treatment of diseases that affect the joint space. The cytologic recognition of the cellular components and infectious agents in synovial fluid categorizes the cell response and differentiates inflammatory and noninflammatory joint disorders. This information is supported by the cell counts, protein content, mucin clot test, bacterial culture, and serologic tests for infectious or immune-mediated disease. These results are integrated with the clinical history, physical examination, radiographic findings, and ancillary test results to arrive at a diagnosis and treatment plan.

Clonal analysis of synovial fluid stem cells to characterize and identify stable mesenchymal stromal cell/mesenchymal progenitor cell phenotypes in a porcine model: a cell source with enhanced commitment to the chondrogenic lineage.

PubMed

Ando, Wataru; Kutcher, Josh J; Krawetz, Roman; Sen, Arindom; Nakamura, Norimasa; Frank, Cyril B; Hart, David A

2014-06-01

Previous studies have demonstrated that porcine synovial membrane stem cells can adhere to a cartilage defect in vivo through the use of a tissue-engineered construct approach. To optimize this model, we wanted to compare effectiveness of tissue sources to determine whether porcine synovial fluid, synovial membrane, bone marrow and skin sources replicate our understanding of synovial fluid mesenchymal stromal cells or mesenchymal progenitor cells from humans both at the population level and the single-cell level. Synovial fluid clones were subsequently isolated and characterized to identify cells with a highly characterized optimal phenotype. The chondrogenic, osteogenic and adipogenic potentials were assessed in vitro for skin, bone marrow, adipose, synovial fluid and synovial membrane-derived stem cells. Synovial fluid cells then underwent limiting dilution analysis to isolate single clonal populations. These clonal populations were assessed for proliferative and differentiation potential by use of standardized protocols. Porcine-derived cells demonstrated the same relationship between cell sources as that demonstrated previously for humans, suggesting that the pig may be an ideal preclinical animal model. Synovial fluid cells demonstrated the highest chondrogenic potential that was further characterized, demonstrating the existence of a unique clonal phenotype with enhanced chondrogenic potential. Porcine stem cells demonstrate characteristics similar to those in human-derived mesenchymal stromal cells from the same sources. Synovial fluid-derived stem cells contain an inherent phenotype that may be optimal for cartilage repair. This must be more fully investigated for future use in the in vivo tissue-engineered construct approach in this physiologically relevant preclinical porcine model. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Properties and usefulness of aggregates of synovial mesenchymal stem cells as a source for cartilage regeneration

PubMed Central

2012-01-01

Introduction Transplantation of mesenchymal stem cells (MSCs) derived from synovium is a promising therapy for cartilage regeneration. For clinical application, improvement of handling operation, enhancement of chondrogenic potential, and increase of MSCs adhesion efficiency are needed to achieve a more successful cartilage regeneration with a limited number of MSCs without scaffold. The use of aggregated MSCs may be one of the solutions. Here, we investigated the handling, properties and effectiveness of aggregated MSCs for cartilage regeneration. Methods Human and rabbit synovial MSCs were aggregated using the hanging drop technique. The gene expression changes after aggregation of synovial MSCs were analyzed by microarray and real time RT-PCR analyses. In vitro and in vivo chondrogenic potential of aggregates of synovial MSCs was examined. Results Aggregates of MSCs cultured for three days became visible, approximately 1 mm in diameter and solid and durable by manipulation; most of the cells were viable. Microarray analysis revealed up-regulation of chondrogenesis-related, anti-inflammatory and anti-apoptotic genes in aggregates of MSCs. In vitro studies showed higher amounts of cartilage matrix synthesis in pellets derived from aggregates of MSCs compared to pellets derived from MSCs cultured in a monolayer. In in vivo studies in rabbits, aggregates of MSCs could adhere promptly on the osteochondral defects by surface tension, and stay without any loss. Transplantation of aggregates of MSCs at relatively low density achieved successful cartilage regeneration. Contrary to our expectation, transplantation of aggregates of MSCs at high density failed to regenerate cartilage due to cell death and nutrient deprivation of aggregates of MSCs. Conclusions Aggregated synovial MSCs were a useful source for cartilage regeneration considering such factors as easy preparation, higher chondrogenic potential and efficient attachment. PMID:22676383

Synovial fluid cytology in experimental acute canine monocytic ehrlichiosis (Ehrlichia canis).

PubMed

Theodorou, Konstantina; Leontides, Leonidas; Siarkou, Victoria I; Petanides, Theodoros; Tsafas, Konstantinos; Harrus, Shimon; Mylonakis, Mathios E

2015-05-15

Evidence-based information of a cause-and-effect relationship between Ehrlichia canis infection and polyarthritis in naturally- or experimentally-infected dogs is currently lacking. The aim of this prospective study was to investigate whether synovial fluid cytological evidence of arthritis could be documented in dogs with acute monocytic ehrlichiosis. Direct synovial fluid cytology smears from eight Beagle dogs experimentally infected with E. canis were examined prior to, and on 21, 35 and 63 days post-inoculation. The cytological variables assessed included cellularity, percentages of mononuclear cells and neutrophils, macrophage reactivity and evidence of E. canis morulae. The median cellularity and percentages of mononuclear cells and neutrophils prior to inoculation did not differ when compared to post-inoculation cytological evaluation. Increased cellularity, E. canis morulae or cytological evidence of arthritis or macrophage reactivity were not observed throughout the course of the study. In the present study, no cytological evidence of arthritis was found in dogs with experimental acute canine monocytic ehrlichiosis, suggesting that E. canis infection should be considered a rather uncommon cause of arthritis in dogs. Copyright © 2015 Elsevier B.V. All rights reserved.

The proinflammatory cytokines IL-1beta and TNF-alpha induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway.

PubMed

Gao, Beixue; Calhoun, Karen; Fang, Deyu

2006-01-01

The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1beta and tumor necrosis factor-alpha (TNF-alpha) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1beta activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1beta-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1beta-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1beta and TNF-alpha induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA.

The proinflammatory cytokines IL-1β and TNF-α induce the expression of Synoviolin, an E3 ubiquitin ligase, in mouse synovial fibroblasts via the Erk1/2-ETS1 pathway

PubMed Central

Gao, Beixue; Calhoun, Karen; Fang, Deyu

2006-01-01

The overgrowth of synovial tissues is critical in the pathogenesis of rheumatoid arthritis (RA). The expression of Synoviolin (SYN), an E3 ubiquitin ligase, is upregulated in arthritic synovial fibroblasts and is involved in the overgrowth of synovial cells during RA. However, the molecular mechanisms involved in the elevated SYN expression are not known. Here, we found that SYN expression is elevated in the synovial fibroblasts from mice with collagen-induced arthritis (CIA). The proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) induce SYN expression in mouse synovial fibroblasts. Cultivation of mouse synovial fibroblasts with IL-1β activates mitogen-activated protein kinases, including extra-cellular signal-regulated kinase (Erk), JNK (c-Jun N-terminal kinase), and p38, while only Erk-specific inhibitor blocks IL-1β-induced SYN expression. Expression of transcription factor ETS1 further enhances IL-1β-induced SYN expression. The dominant negative ETS1 mutant lacking the transcription activation domain inhibits SYN expression in a dose-dependent manner. The activation of both Erk1/2 and ETS1 is increased in the CIA synovial fibroblasts. Inhibition of Erk activation reduces ETS1 phosphorylation and SYN expression. Our data indicate that the proinflammatory cytokines IL-1β and TNF-α induce the overgrowth of synovial cells by upregulating SYN expression via the Erk1/-ETS1 pathway. These molecules or pathways could therefore be potential targets for the treatment of RA. PMID:17105652

Differences in the morphology of distal border synovial invaginations of the distal sesamoid bone in the horse as evaluated by computed tomography compared with radiography.

PubMed

Claerhoudt, S; Bergman, H J; Van Der Veen, H; Duchateau, L; Raes, E V; Saunders, J H

2012-11-01

Distal border synovial invaginations of the distal sesamoid bone are radiographically assessed during the selection process of horses admitted as breeding stallions or in purchase examinations. Nowadays, many moderately or some deeply penetrating proximally enlarged synovial invaginations are considered as moderate or severe radiographic findings. To measure the difference between and agreement of the morphology of distal border synovial invaginations on radiography vs. computed tomography (CT). It was hypothesised that the morphology of distal border synovial invaginations would be better evaluable on CT compared with radiography. Computed tomography scans and 3 dorsoproximal-palmarodistal oblique (DPr-PaDiO) radiographs were obtained on 50 cadaver forefeet from 25 Warmblood horses. Computed tomography was assumed to be the gold standard. The number, shape and depth of penetration of distal border synovial invaginations into the distal sesamoid bone were evaluated with both methods, and the comparison of their measurements was statistically described. A statistically significant mean difference for number of distal synovial invaginations between CT and all 3 DPr-PaDiO projections was found and was approximately equal to 2, meaning that CT permits visualisation of an average of 2 more invaginations than radiography. In none of the cases did radiography have a higher number observed than CT. A large variation in the difference of measurements for depth of penetration against their mean difference between CT and the 3 radiographic projections was seen. Radiography underestimated the depth of invaginations, and more so when these were deeper. There was no statistically significant mean difference found between the techniques for depth. A moderate to good agreement between measurements on CT and the three DPr-PaDiO projections for shape was seen, in which the D55°Pr-PaDiO projection showed the best agreement. A high specificity (90-99%) and low sensitivity (65%) for

HMGB1-mediated autophagy decreases sensitivity to oxymatrine in SW982 human synovial sarcoma cells

PubMed Central

Cai, Yongsong; Xu, Peng; Yang, Le; Xu, Ke; Zhu, Jialin; Wu, Xiaoqing; Jiang, Congshan; Yuan, Qiling; Wang, Bo; Li, Yuanbo; Qiu, Yusheng

2016-01-01

Oxymatrine (OMT) is a type of alkaloid extracted from a traditional Chinese medicinal herb, Sophora flavescens. Although the antitumor activities of OMT have been observed in various cancers, there are no reports regarding the effects of OMT on human synovial sarcoma. In the present study, we analyzed the antitumor activities of OMT in SW982 human synovial sarcoma cells and determine whether high mobility group box protein 1 (HMGB1)-mediated autophagy was associated with its therapeutic effects. We found that OMT exhibited antitumor activity in SW982 cells and facilitated increases in autophagy. Inhibition of autophagy by 3-MA or ATG7 siRNA increased the level of apoptosis, which indicated that OMT-induced autophagy protected cells from the cytotoxicity of OMT. Administration of OMT to SW982 cells increased the expression of HMGB1. When HMGB1 was inhibited via HMGB1-siRNA, OMT-induced autophagy was decreased, and apoptosis was increased. Furthermore, we found that HMGB1-siRNA significantly increased the expression of p-Akt and p-mTOR. OMT-induced autophagy may be mediated by the Akt/mTOR pathway, and HMGB1 plays a vital role in the regulation of autophagy. Therefore, we believe that combining OMT with an inhibitor of autophagy or HMGB1 may make OMT more effective in the treatment of human synovial sarcoma. PMID:27897164

TLR3 Ligand Poly(I:C) Exerts Distinct Actions in Synovial Fibroblasts When Delivered by Extracellular Vesicles

PubMed Central

Frank-Bertoncelj, Mojca; Pisetsky, David S.; Kolling, Christoph; Michel, Beat A.; Gay, Renate E.; Jüngel, Astrid; Gay, Steffen

2018-01-01

Extracellular vesicles (EV) can modulate the responses of cells to toll-like receptor (TLR) ligation; conversely, TLR ligands such as double-stranded RNA (dsRNA) can enhance the release of EV and influence of the composition and functions of EV cargos. Inflamed synovial joints in rheumatoid arthritis (RA) are rich in EV and extracellular RNA; besides, RNA released from necrotic synovial fluid cells can activate the TLR3 signaling in synovial fibroblasts (SFs) from patients with RA. Since EV occur prominently in synovial joints in RA and may contribute to the pathogenesis, we questioned whether EV can interact with dsRNA, a TLR3 ligand, and modify its actions in arthritis. We have used as model the effects on RA SFs, of EV released from monocyte U937 cells and peripheral blood mononuclear cells upon stimulation with Poly(I:C), a synthetic analog of dsRNA. We show that EV released from unstimulated cells and Poly(I:C)-stimulated U937 cells [Poly(I:C) EV] differ in size but bind similar amounts of Annexin V and express comparable levels of MAC-1, the receptor for dsRNA, on the vesicular membranes. Specifically, Poly(I:C) EV contain or associate with Poly(I:C) and at least partially protect Poly(I:C) from RNAse III degradation. Poly(I:C) EV shuttle Poly(I:C) to SFs and reproduce the proinflammatory and antiviral gene responses of SFs to direct stimulation with Poly(I:C). Poly(I:C) EV, however, halt the death receptor-induced apoptosis in SFs, thereby inverting the proapoptotic nature of Poly(I:C). These prosurvival effects sharply contrast with the high toxicity of cationic liposome-delivered Poly(I:C) and may reflect the route of Poly(I:C) delivery via EV or the fine-tuning of Poly(I:C) actions by molecular cargo in EV. The demonstration that EV may safeguard extracellular dsRNA and allow dsRNA to exert antiapoptotic effects on SFs highlights the potential of EV to amplify the pathogenicity of dsRNA in arthritis beyond inflammation (by concurrently enhancing the

Serum and synovial fluid cytokine profiling in hip osteoarthritis: distinct from knee osteoarthritis and correlated with pain.

PubMed

Ren, Guomin; Lutz, Ian; Railton, Pamela; Wiley, J Preston; McAllister, Jenelle; Powell, James; Krawetz, Roman J

2018-02-05

Inflammation is associated with the onset and progression of osteoarthritis in multiple joints. It is well known that mechanical properties differ between different joints, however, it remains unknown if the inflammatory process is similar/distinct in patients with hip vs. knee OA. Without complete understanding of the role of any specific cytokine in the inflammatory process, understanding the 'profile' of inflammation in a given patient population is an essential starting point. The aim of this study was to identify serum cytokine profiles in hip Osteoarthritis (OA), and investigate the association between cytokine concentrations and clinical measurements within this patient population and compare these findings to knee OA and healthy control cohorts. In total, 250 serum samples (100 knee OA, 50 hip OA and 100 control) and 37 synovial fluid samples (8 knee OA, 14 hip OA and 15 control) were analyzed using a multiplex ELISA based approach. Synovial biopsies were also obtained and examined for specific cytokines. Pain, physical function and activity within the hip OA cohort were examined using the HOOS, SF-36, HHS and UCLA outcome measures. The three cohorts showed distinct serum cytokine profiles. EGF, FGF2, MCP3, MIP1α, and IL8 were differentially expressed between hip and knee OA cohorts; while FGF2, GRO, IL8, MCP1, and VEGF were differentially expressed between hip OA and control cohorts. Eotaxin, GRO, MCP1, MIP1β, VEGF were differentially expressed between knee OA and control cohorts. EGF, IL8, MCP1, MIP1β were differentially expressed in synovial fluid from a sub-set of patients from each cohort. Specifically within the hip OA cohort, IL-6, MDC and IP10 were associated with pain and were also found to be present in synovial fluid and synovial membrane (except IL-6) of patients with hip OA. OA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. IL6, MDC and IP10 are

Involvement of synovial matrix degradation and angiogenesis in oxidative stress-exposed degenerative rotator cuff tears with osteoarthritis.

PubMed

Noh, Kyu-Cheol; Park, Sin-Hye; Yang, Cheol Jung; Lee, Geun Woo; Kim, Min Ki; Kang, Young-Hee

2018-01-01

Shoulder osteoarthritis is a gradual wearing of the articular cartilage concomitant with degenerative rotator cuff tears (RCTs). This pathologic disorder is related to inflammation, oxidative stress, and angiogenesis. Degenerative alterations may prompt production of cytokines and angiogenesis-related proteins, evoking rotator cuff diseases. This study tested the hypothesis that oxidative stress-responsive mediators can influence joint inflammation of patients with RCT. Twelve healthy RCT patients not suffering shoulder osteoarthritis were categorized as the control group, and 24 patients were allocated to 2 RCT groups (RCTP1 and RCTP2), according to severity of RCT and glenohumeral arthritis. Cytokines, growth factors, and angiogenic biomarkers in synovial fluids, blood, platelet-rich plasma (PRP), and tendon tissues were analyzed with enzyme-linked immunosorbent assay, immunoblotting, and collagen zymography. Induction of interleukin 8, tumor necrosis factor α, and interleukin 1β was considerably elevated in synovial fluids of RCTP groups (P = .0398, P = .0428, P = .0828, respectively). The joint inflammation highly enhanced insulin-like growth factor 1 and transforming growth factor β1 (TGF-β1) in the synovial fluids and serum. Angiogenesis-related angiopoietin (Ang) 1 and 2, Tie-2, and hypoxia-inducible factor 1α were upregulated in reactive oxygen species-exposed RCTP synovium (P < .05). The production of matrix metalloproteinase 1 markedly increased in synovial fluids of the RCTP group (P = .043), whereas tissue collagen type I expression diminished with reduction of connective tissue growth factor expression (P = .032). Although the secretion of platelet-derived growth factor AB and vascular endothelial growth factor was marginal in the circulation (P = .714, P = .335), platelet-derived growth factor AB, TGF-β1, Ang-1, and matrix metalloproteinase 1 were enriched in PRP of the RCTP group (P < .001, P = .002, P�

Involvement of the MAPK pathway in the pressure-induced synovial metaplasia procedure for the temporomandibular joint.

PubMed

Wu, M J; Lu, H P; Gu, Z Y; Zhou, Y Q

2016-06-20

Abnormal pressure is an important factor that contributes to bone adaptation in the temporomandibular joint (TMJ). We determined the effect of the mitogen-activated protein kinases (MAPK) pathway on the pressure-induced synovial metaplasia procedure for the TMJ, both in vitro and in vivo. Synovial fibroblasts (SFs) were exacted from rat TMJs and exposed to different hydrostatic pressures. The protein extracts were analyzed to determine the activation of ERK1/2, JNK, and p38. Surgical anterior disc displacement (ADD) was also performed on Japanese rabbits, and the proteins of TMJ were isolated to analyze pressure-induced MAPK activation after 1, 2, 4, and 8 weeks. The results showed that the activation of ERK1/2 and JNK in SFs significantly changed with increasing hydrostatic pressure, whereas p38 activation did not change. Moreover, p38 was activated in animals 1 week after surgical ADD. The levels of p38 gradually increased after 2 and 4 weeks, and then slightly decreased but remained higher than in the control 8 weeks after surgical ADD. Nevertheless, JNK was rarely activated after the ADD treatment. Our findings suggest the involvement of MAPK activation in the pressure-induced synovial metaplasia procedure with pressure loading in TMJ.

Evaluation of the anti-inflammatory actions of various functional food materials including glucosamine on synovial cells.

PubMed

Yamagishi, Yoshie; Someya, Akimasa; Imai, Kensuke; Nagao, Junji; Nagaoka, Isao

2017-08-01

The anti-inflammatory actions of glucosamine (GlcN) on arthritic disorders involve the suppression of inflammatory mediator production from synovial cells. GlcN has also been reported to inhibit the activation of the p38 mitogen-activated protein kinase (MAPK) pathway. The present study aimed to determine the cooperative and anti‑inflammatory actions of functional food materials and evaluated the production of interleukin (IL)‑8 and phosphorylation of p38 MAPK in IL-1β-activated synovial cells, incubated with the combination of GlcN and various functional food materials containing L‑methionine (Met), undenatured type II collagen (UC‑II), chondroitin sulfate (CS), methylsulfonylmethane (MSM) and agaro-oligosaccharide (AO). The results indicated that Met, UC‑II, CS, MSM and AO slightly or moderately suppressed the IL-1β-stimulated IL‑8 production by human synovial MH7A cells. The same compounds further decreased the IL‑8 level lowered by GlcN. Similarly, they slightly suppressed the phosphorylation level of p38 MAPK and further reduced the phosphorylation level lowered by GlcN. These observations suggest a possibility that these functional food materials exert an anti‑inflammatory action (inhibition of IL‑8 production) in combination with GlcN by cooperatively suppressing the p38 MAPK signaling (phosphorylation).

Primary orbital synovial sarcoma: A clinicopathologic review with a differential diagnosis and discussion of molecular genetics.

PubMed

Stagner, Anna M; Jakobiec, Frederick A; Fay, Aaron

Synovial sarcoma is a soft-tissue sarcoma of the extremities developing in young adults that has rarely been reported in the orbit. Synovial sarcoma is associated with a unique translocation, resulting in an SYT-SSX fusion gene. We analyze 7 published periocular cases, together with the current one, to gain a better appreciation of the features of the tumor in this location and to compare the findings with those derived from nonophthalmic studies. An inferior orbital mass developed in a 31-year-old woman after experiencing periorbital and hemifacial pain for more than a decade. Radiographically, the mass was circumscribed and displayed coarse internal calcifications. A large but subtotal excision with histopathologic examination disclosed a primitive tumor composed of spindled and ovoid cells. Immunohistochemistry demonstrated positivity for nuclear transducin-like enhancer of split 1 and membranous CD99, typical for synovial sarcoma. Fluorescence in situ hybridization identified a (X,18) translocation in the tumor cells. The patient underwent postoperative adjuvant proton beam radiotherapy with a good response that has been maintained during 1 year of follow-up. Orbital soft-tissue tumors of all types are increasingly identified by their distinctive genetic signatures that offer more specificity than standard immunohistochemical tests. Copyright © 2016 Elsevier Inc. All rights reserved.

Rheumatoid arthritis antigens homocitrulline and citrulline are generated by local myeloperoxidase and peptidyl arginine deiminases 2, 3 and 4 in rheumatoid nodule and synovial tissue.

PubMed

Turunen, Sanna; Huhtakangas, Johanna; Nousiainen, Tomi; Valkealahti, Maarit; Melkko, Jukka; Risteli, Juha; Lehenkari, Petri

2016-10-20

Seropositive rheumatoid arthritis (RA) is characterized by autoantibodies binding to citrullinated and homocitrullinated proteins. We wanted to study the expression patterns of these disease-associated protein forms and if the rheumatoid nodule and synovial tissue itself contain biologically active levels of citrullinating peptidyl arginine deiminases 2, 3 and 4 and homocitrullination-facilitating neutrophil enzyme myeloperoxidase. Total of 195 synovial samples from metatarsal joints from five ACPA/RF-positive RA patients (n = 77), synovial samples from knees of eight seropositive RA (n = 60), seven seronegative RA (n = 33) and five osteoarthritis (n = 25) patients were analyzed for citrulline and homocitrulline contents using HPLC. The location of citrulline- and homocitrulline-containing proteins, PAD 2, 3, 4 and myeloperoxidase were shown by immunostaining. Myeloperoxidase and citrulline- or homocitrulline-containing proteins were stained on Western blot. Overall, necrosis was frequent in metatarsals of seropositive RA and absent in seronegative RA and osteoarthritis patients. In histological analysis, there was a significant local patterning and variation in the citrulline and homocitrulline content and it was highest in metatarsal synovial tissues of seropositive RA patients. We found peptidyl arginine deiminase 2, 3 and 4 in the lining and sublining layers of intact synovial tissue. Myeloperoxidase was found locally around necrotic areas. The tissues with necrosis contained the highest levels of citrulline and homocitrulline. Rheumatoid nodules and synovia contain significant amount of PAD2, 3 and 4 and myeloperoxidase enzymes. These enzymes could explain the levels of citrulline and homocitrulline in seropositive RA synovial and rheumatoid nodule tissues especially around necrotic tissue.

Indonesia knowledge dissemination: a snapshot

NASA Astrophysics Data System (ADS)

Nasution, M. K. M.

2018-03-01

The educational progress of a country or educational institution is measured through the implementation of knowledge dissemination. Evidence of knowledge dissemination has carried out be in form of the type of published document, which is based on the databases of the index of scientific publications: Scopus. This paper expresses a simple form of knowledge dissemination based on document type. Although the growth of knowledge dissemination does not have the same pattern based on the appearance of document types, the general implementation is almost the same. However, maximum effort needs to be done by PTN-bh to support Indonesia knowledge dissemination.

Elevation of a collagenase generated type II collagen neoepitope and proteoglycan epitopes in synovial fluid following induction of joint instability in the dog

PubMed Central

Chu, Q.; Lopez, M.; Hayashi, K.; lonescu, M.; Billinghurst, R. C.; Johnson, K. A.; Poole, A. R.; Markel, M. D.

2007-01-01

Summary Clinical relevance Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations. Objective The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA. Design A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 ± 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(–) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed. Results Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(–) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture. Conclusions Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(–) epitope

Elevation of a collagenase generated type II collagen neoepitope and proteoglycan epitopes in synovial fluid following induction of joint instability in the dog.

PubMed

Chu, Q; Lopez, M; Hayashi, K; Ionescu, M; Billinghurst, R C; Johnson, K A; Poole, A R; Markel, M D

2002-08-01

Measurement of markers of cartilage pathology in synovial fluid may provide clinical rheumatologists and osteoarthritis (OA) researchers important information for early diagnosis of OA as well as a method for monitoring disease progression and response to treatment. This study demonstrates the value of this approach in an established model of OA (cranial cruciate ligament rupture) at a point distant enough from the original surgical manipulation so as to have little to no effect on the marker concentrations. The objective of this study was to determine whether measurement of markers of cartilage collagen cleavage and proteoglycan turnover in synovial fluid from a canine model could be used to detect cartilage changes following the onset of joint instability during the development of OA. A model of joint instability that develops OA was created in 18 mature dogs using monopolar radiofrequency energy (MRFE). MRFE was arthroscopically applied to one cranial cruciate ligament (CCL) while the contralateral CCL was sham treated. The treated CCLs ruptured approximately 8 weeks (55 +/- 1.6 days) after MRFE treatment. Synovial fluid was collected at time zero prior to MRFE treatment, 4 weeks after MRFE treatment, and at 4, 8, and 16 weeks after CCL rupture. Synovial fluid concentrations of the neoepitope COL2-3/4C long (type II collagen cleavage by collagenase) and epitopes 3B3(-) (proteoglycan aggrecan sulfation) and 846 (associated with aggrecan synthesis) were analyzed. Compared to sham treated joints, the synovial fluid concentrations of COL2-3/4C long and 3B3(-) were significantly increased 2.2 fold and 2.9 fold, respectively, in joints with MRFE treated CCLs following CCL rupture. Concentrations of the 846 epitope in synovial fluid showed a trend toward an increase, which was not significant, after CCL rupture. Concentrations of the collagenase-cleaved type II collagen neoepitope and 3B3(-) epitope in synovial fluid were significantly increased by 4 weeks and remained

Decoy receptor 3 regulates the expression of tryptophan hydroxylase 1 in rheumatoid synovial fibroblasts.

PubMed

Maeda, Toshihisa; Miura, Yasushi; Fukuda, Koji; Hayashi, Shinya; Kurosaka, Masahiro

2015-10-01

Decoy receptor 3 (DcR3) is expressed in rheumatoid arthritis fibroblast‑like synoviocytes (RA‑FLS) and downregulates the expression of tryptophan hydroxylase 1 (TPH1), which is the rate‑limiting enzyme in serotonin synthesis. The aim of the present study was to determine the specificity of the effects of DcR3 on TPH1 in RA‑FLS, and therefore determine whether DcR3 had the potential to modulate the pathogenesis of RA. The present study also aimed to compare the effects of DcR3 and inflammatory cytokines on the expression of TPH1 in RA‑FLS and osteoarthritis (OA)‑FLS. Primary cultured RA‑ or OA‑FLS were incubated with 1.0 µg/ml DcR3‑Fc protein or 1.0 µg/ml control immunoglobulin G (IgG)1 for 12 h, or with 1.0 ng/ml tumor necrosis factor (TNF)α, 1.0 ng/ml interleukin (IL)‑1β or serum‑free Opti‑MEM only, for 24 h. The relative mRNA expression levels of TPH1 were subsequently quantified using reverse transcription‑polymerase chain reaction. The expression of serotonin in RA or OA synovial tissue was detected using immunohistochemistry. The mRNA expression of TPH1 was observed in both RA‑ and OA‑FLS and was significantly decreased following treatment with DcR3 in the RA‑FLS, however, not in the OA‑FLS. The mRNA expression of TPH1 was significantly decreased following treatment with TNFα or IL‑1β in both the RA‑ and OA‑FLS. The expression of serotonin in the multi‑layered lining synovial cells of RA and the outer layer lining synovial cells of OA was detected using immunohistochemistry. The present study is the first, to the best of our knowledge, to demonstrate that the expression of TPH1 in FLS is downregulated by inflammatory cytokines, and that DcR3 suppressed the expression of TPH1 in RA‑FLS in a disease‑specific manner. These results suggested that synovial serotonin may be involved in the pathogenesis of RA, and that TPH1 and DcR3 may be potential therapeutic targets for the treatment of RA.

Effects of corticosteroids and local anaesthetics applied directly to the synovial vascular bed.

PubMed Central

De Ceulaer, K; Balint, G; El-Ghobarey, A; Dick, W C

1979-01-01

The effects of intra-articular injection of triamcinolone hexacetonide on the rate of clearance of radioactive xenon (133Xe) was studied in 11 patients with rheumatoid arthritis. No effect of the corticosteroid injection was observed, which suggests that the drug has no immediate effect on synovial blood vessels. PMID:518144

In arthritis the Doppler based degree of hypervascularisation shows a positive correlation with synovial leukocyte count and distinguishes joints with leukocytes greater and less than 5/nL.

PubMed

Löffler, Christian; Sattler, Horst; Peters, Lena; Tuleweit, Anika; Löffler, Uta; Wadsack, Daniel; Uppenkamp, Michael; Bergner, Raoul

2016-10-01

Power Doppler ultrasound is used to assess joint vascularity in acute arthritis. PDUS signals have been correlated with synovial histology and bone deterioration. Little is known about the correlation between power Doppler signals and synovial white blood count. In our study, we analyzed power Doppler signals in inflammatory joint diseases including gout, calcium pyrophosphate deposition disease, rheumatoid arthritis, spondyloarthritis and others and correlated power Doppler signals with synovial white blood count and with serologic markers of inflammation. We retrospectively evaluated 194 patients with arthritis. All patients underwent joint sonography, power Doppler ultrasound, synovial fluid analysis and blood examination of C-reactive protein and erythrocyte sedimentation rate. Correlation analyses (Spearman and Pearson), Chi(2) test, t-tests, a unifactorial ANOVA and regression analyses were applied. Hypervascularisation in power Doppler was most prominent in gout and calcium pyrophosphate deposition disease. Spondyloarthritis and non-inflammatory joint diseases presented with low degrees of hypervascularisation. Mean synovial white blood count did not differ significantly between crystal-related arthritides, rheumatoid arthritis, spondyloarthritis or other inflammatory joint diseases. There was a positive but weak correlation between power Doppler signals and synovial white blood count (P<0.001, rs=0.283), erythrocyte sedimentation rate (P<0.001, rs=0.387) and C-reactive protein (P<0.001, rs=0.373) over all diagnoses. This was especially relevant in rheumatoid arthritis (P<0.01, rs=0.479). Power Doppler degrees 0 and 1 were able to predict synovial leukocytes<5/nL, degrees 2 and 3 predict leukocytes≥5/nL (P<0.001). Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

In vivo effects of meloxicam and aspirin on blood, gastric mucosal, and synovial fluid prostanoid synthesis in dogs.

PubMed

Jones, Christopher J; Streppa, Heather K; Harmon, Barry G; Budsberg, Steven C

2002-11-01

To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively. 12 male dogs with unilateral osteoarthritis of the stifle joint. Each dog was treated in a crossover design with aspirin or meloxicam for 21 days. Prostaglandin E2 (PGE2) concentrations were measured at days 0 (baseline), 7, and 21 of each treatment period in lipopolysaccharide (LPS)-stimulated blood, synovial fluid collected by arthrocentesis, and endoscopic gastric mucosal biopsy specimens. Thromboxane B2 (TXB2) was evaluated in blood on days 0, 7, and 21 of each treatment period. Aspirin administration significantly suppressed PGE2 concentrations in blood, gastric mucosa, synovial fluid, and suppressed TXB2 concentration in blood at days 7 and 21. Meloxicam administration significantly suppressed PGE2 concentrations in blood and synovial fluid at days 7 and 21, but had no effect on concentrations of TXB2 in blood or PGE2 in gastric mucosa. Suppression of LPS-stimulated PGE2 concentrations in blood and synovial fluid by aspirin and meloxicam administration is consistent with activity against the COX-2 isoenzyme. Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1. Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1. Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints.

Isolation and characterization of human mesenchymal stem cells derived from synovial fluid by magnetic-activated cell sorting (MACS).

PubMed

Jia, Zhaofeng; Liang, Yujie; Xu, Xiao; Li, Xingfu; Liu, Qisong; Ou, Yangkan; Duan, Li; Zhu, Weimin; Lu, Wei; Xiong, Jianyi; Wang, Daping

2018-03-01

Mesenchymal stem cells (MSCs) are the primary source of cells used for cell-based therapy in tissue engineering. MSCs are found in synovial fluid, a source that could be conveniently used for cartilage tissue engineering. However, the purification and characterization of SF-MSCs has been poorly documented in the literature. Here, we outline an easy-to-perform approach for the isolation and culture of MSCs derived from human synovial fluid (hSF-MSCs). We have successfully purified hSF-MSCs using magnetic-activated cell sorting (MACS) using the MSC surface marker, CD90. Purified SF-MSCs demonstrate significant renewal capacity following several passages in culture. Furthermore, we demonstrated that MACS-sorted CD90 + cells could differentiated into osteoblasts, adipocytes, and chondrocytes in vitro. In addition, we show that these cells can generate cartilage tissue in micromass culture as well. This study demonstrates that MACS is a useful tool that can be used for the purification of hSF-MSCs from synovial fluid. The proliferation properties and ability to differentiate into chondrocytes make these hSF-MSCs a promising source of stem cells for applications in cartilage repair. © 2017 International Federation for Cell Biology.

Antioxidant capacity of synovial fluid in the temporomandibular joint correlated with radiological morphology of temporomandibular disorders.

PubMed

Ishimaru, Kyoko; Ohba, Seigo; Yoshimura, Hitoshi; Matsuda, Shinpei; Ishimaru, Jun-Ichi; Sano, Kazuo

2015-02-01

We investigated the correlation between the antioxidant capacity of synovial fluid and radiological findings of intra-articular structures in patients with disorders of the temporomandibular joint (TMJ). We recruited 21 patients (9 men and 12 women, aged 18-84 years of age) with such disorders, excluding myofascial pain and dysfunction syndrome, or other muscular disorders. The clinical variables recorded included age, sex, interincisal distance, and visual analogue pain scores (VAS). Radiological findings were obtained from diagnostic arthrogram and cone-beam computed tomography (CT). The antioxidant capacity of the synovial fluid was measured by chemiluminescence. Eleven patients were radiologically diagnosed with closed lock, and the remaining 10 with no closed lock. An anchored intra-articular disc was most often seen on cone-beam CT (n=19) followed by perforated disc (n=7), osteoarthrosis (n=7), and anterior disc displacement without reduction (n=5). Although there were no significant differences between antioxidant capacity and age, sex, VAS, or any findings on cone-beam CT, antioxidant capacity was significantly decreased in the patients with closed lock compared with those who did not have closed lock (p=0.02). The results suggest an association between the oxidative stress of the synovial fluid and closed-lock in disorders of the TMJ. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Increased pentosidine, an advanced glycation end product, in serum and synovial fluid from patients with knee osteoarthritis and its relation with cartilage oligomeric matrix protein

PubMed Central

Senolt, L; Braun, M; Olejarova, M; Forejtova, S; Gatterova, J; Pavelka, K

2005-01-01

Background: Pentosidine, an advanced glycation end product, increasingly accumulates in articular cartilage with age, and contributes to the pathogenesis of osteoarthritis (OA). Increased pentosidine concentrations are associated with inflammatory disorders—for example, rheumatoid arthritis. Objective: To compare pentosidine serum concentrations in patients with knee OA and in healthy volunteers and to determine a relationship between pentosidine and cartilage oligomeric matrix protein (COMP)—a marker of articular cartilage destruction. Methods: Paired serum and synovial fluid samples were obtained by arthrocentesis from 38 patients with knee OA and from 38 healthy volunteers. Pentosidine concentration was measured by reverse phase high performance liquid chromatography with fluorescent detection and COMP was determined by sandwich ELISA. Results: Significantly increased serum pentosidine (p<0.01) and COMP (p<0.05) levels were detected in the patients with OA compared with the control group. Serum pentosidine correlated significantly with synovial fluid pentosidine (p<0.001). Pentosidine in synovial fluid (p<0.05) and in serum (p<0.05) correlated significantly with synovial fluid COMP. Pentosidine and COMP concentrations did not correlate significantly with the radiological stage of the disease. Conclusion: Increased pentosidine serum concentration in patients with OA and its correlation with the cartilage destruction marker COMP in synovial fluid suggests that pentosidine may be important in OA pathology and is a new potential OA marker. PMID:15897309

High-sensitivity virus and mycoplasma screening test reveals high prevalence of parvovirus B19 infection in human synovial tissues and bone marrow.

PubMed

Watanabe, Ken; Otabe, Koji; Shimizu, Norio; Komori, Keiichirou; Mizuno, Mitsuru; Katano, Hisako; Koga, Hideyuki; Sekiya, Ichiro

2018-03-27

Latent microorganism infection is a safety concern for the clinical application of mesenchymal stem cells (MSCs). The aim of this study is to investigate the frequencies and sensitivities of the latent virus and mycoplasma infections in synovium, bone marrow, peripheral blood cells, and blood plasma and cultured synovial MSCs. Total DNA and RNA of the synovium (n = 124), bone marrow (n = 123), peripheral blood cells (n = 121), plasma (n = 121), and 14-day cultured synovial MSCs (n = 63) were collected from patients who underwent total knee arthroplasty or anterior ligament reconstruction after written informed consents were obtained. The multiplex polymerase chain reaction (PCR) primers were designed to quantitatively measure the representative genomes of 13 DNA viruses, 6 RNA viruses, and 9 mycoplasmas. Multi-spliced mRNA detection and virus spike test were also performed to demonstrate the sensitivity of synovial MSCs to the candidate pathogens. In synovium and bone marrow, the positive rates of parvovirus B19 genome were significantly higher than in peripheral blood cells (18.7% and 22% vs. 0.8%, respectively). Multi-alignment analysis of amplified and sequenced viral target genes showed the proximity of the parvovirus B19 gene from different tissue in the same patients. Synovial MSCs cultured for 14 days were positive for virus infection only in two patients (2/62 = 3%). Parvovirus B19 multi-spliced mRNAs were not detected in these two samples. Virus spike test demonstrated the sensitivity of synovial MSCs to herpes simplex virus (HSV)1 and cytomegalovirus (CMV), but not to parvovirus B19. This study revealed a relatively high incidence of latent parvovirus B19 in synovium and bone marrow tissue.

Hypotonic stress promotes ATP release, reactive oxygen species production and cell proliferation via TRPV4 activation in rheumatoid arthritis rat synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Fen; Hui, Zhenhai; Wei, Wei

Rheumatoid arthritis (RA) is a chronic and systemic autoimmune-disease with complex and unclear etiology. Hypotonicity of synovial fluid is a typical characteristic of RA, which may play pivotal roles in RA pathogenesis. In this work, we studied the responses of RA synovial fibroblasts to hypotonic stress in vitro and further explored the underlying mechanisms. Data showed that hyposmotic solutions significantly triggered increases in cytosolic calcium concentration ([Ca{sup 2+}]{sub c}) of synoviocytes. Subsequently, it caused rapid release of ATP, as well as remarkable production of intracellular reactive oxygen species (ROS). Meanwhile, hypotonic stimulus promoted the proliferation of synovial fibroblasts. These effects weremore » almost abolished by calcium-free buffer and significantly inhibited by gadolinium (III) chloride (a mechanosensitive Ca{sup 2+} channel blocker) and ruthenium red (a transient receptor potential vanilloid 4 (TRPV4) blocker). 4α-phorbol 12,13-didecanoate, a specific agonist of TRPV4, also mimicked hypotonic shock-induced responses shown above. In contrast, voltage-gated channel inhibitors verapamil and nifedipine had little influences on these responses. Furthermore, RT-PCR and western blotting evidently detected TRPV4 expression at mRNA and protein level in isolated synoviocytes. Taken together, our results indicated that hypotonic stimulus resulted in ATP release, ROS production, and cell proliferation depending on Ca{sup 2+} entry through activation of TRPV4 channel in synoviocytes. - Highlights: • Hypotonic stress evokes Ca{sup 2+} entry in rheumatoid arthritis synovial fibroblasts. • Hypotonic stress induces rapid ATP release and ROS production in synoviocytes. • Hypotonic stimulation promotes the proliferation of synovial fibroblasts. • TRPV4 controls hypotonic-induced responses in synoviocytes.« less

Endoplasmic reticulum stress-dependent ROS production mediates synovial myofibroblastic differentiation in the immobilization-induced rat knee joint contracture model.

PubMed

Jiang, Shihai; He, Ronghan; Zhu, Lei; Liang, Tangzhao; Wang, Zhe; Lu, Yunxiang; Ren, Jianhua; Yi, Xiaoyou; Xiao, Dahai; Wang, Kun

2018-05-30

Joint contracture is a common complication for people with joint immobility that involves fibrosis structural alteration in the joint capsule. Considering that endoplasmic reticulum (ER) stress plays a prominent role in the promotion of tissue fibrosis, we investigated whether the unfolded protein response (UPR) contributes to the fibrotic development in immobilization-induced knee joint contractures. Using a non-traumatic rat knee joint contracture model, twelve female Sprague-Dawley rats received knee joint immobilization for a period of 8 weeks. We found that fibrosis protein markers (type I collagen, α-SMA) and UPR (GRP78, ATF6α, XBP1s) markers were parallelly upregulated in rat primary cultured synovial myofibroblasts. In the same cell types, pre-treatment with an ER stress inhibitor, 4-phenylbutyric acid (4-PBA), not only abrogated cytokine TGFβ1 stimulation but also reduced the protein level of UPR. Additionally, high reactive oxygen species (ROS) generation was detected in synovial myofibroblasts through flow cytometry, as expected. Notably, TGFβ1-induced UPR was significantly reduced through the inhibition of ROS with antioxidants. These data suggest that ER stress act as a pro-fibrotic stimulus through the overexpression of ROS in synovial fibroblasts. Interestingly, immunohistochemical results showed an increase in the UPR protein levels both in human acquired joint contractures capsule tissue and in animal knee joint contracture tissue. Together, our findings suggest that ER stress contributes to synovial myofibroblastic differentiation in joint capsule fibrosis and may also serve as a potential therapeutic target in joint contractures. Copyright © 2018 Elsevier Inc. All rights reserved.

[Viscosity determination of synovial fluids from the canine hip and elbow joint as well as the human knee joint].

PubMed

Helms, Gabriele; Rittmann, Pia; Wefstaedt, Patrick; Windhagen, Henning; Pressel, Thomas; Behrens, Bernd-Arno; Nolte, Ingo

2008-01-01

The development of pathological changes in both human and canine hip joints is mainly caused by a lack of synovial fluid lubrication. This results in an increased joint abrasion. Even after implantation of joint prosthesis, inadequate lubrication can lead to abrasion in the tribological pair. This can finally result in aseptic loosening of the prosthesis. In spite of the enormous number of studies that have been performed on human, only little knowledge about the tribological properties of the joints in dogs is available in the literature. For this reason the viscosities of synovial fluid, derived from physiological and pathologically changed canine elbow joints were measured. The viscosities were determined by the use of a cone-plate viscometer at different temperatures and shear rates. The obtained values were compared with the viscosity values of pathologically changed synovial fluids from human knee joints as well as with pathological samples from the canine hip joint. The results show that the viscosity values vary within a series of measurements and are inversely proportional to the temperature of the sample and the shear rate. The differences between the average viscosities of canine and human synovial fluids taken from pathologically changed joints are below 4% (22.5 s(-1) at theta1 = 25 degrees C). The findings of this study are being implemented in a FE-Model for the computation of actual forces in the hip joint during different movements. This would represent a contribution to an improved prosthetic treatment of canine and human hips.

Validity of SW982 synovial cell line for studying the drugs against rheumatoid arthritis in fluvastatin-induced apoptosis signaling model

PubMed Central

Chang, Jae-Ho; Lee, Kyu-Jae; Kim, Soo-Ki; Yoo, Dae-Hyun; Kang, Tae-Young

2014-01-01

Background & objectives: To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed. Results: Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected. Interpretation & conclusions: Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study. PMID:24604047

Petaloid recombinant peptide enhances in vitro cartilage formation by synovial mesenchymal stem cells.

PubMed

Naritomi, Mana; Mizuno, Mitsuru; Katano, Hisako; Ozeki, Nobutake; Otabe, Koji; Komori, Keiichiro; Fujii, Shizuka; Ichinose, Shizuko; Tsuji, Kunikazu; Koga, Hideyuki; Muneta, Takeshi; Sekiya, Ichiro

2018-05-07

In vitro chondrogenesis of mesenchymal stem cells (MSCs) mimics in vivo chondrogenesis of MSCs. However, the size of the cartilage pellets that can be attained in vitro is limited by current methods; therefore, some modifications are required to obtain larger pellets. Petaloid pieces of recombinant peptide (petaloid RCP) have the advantage of creating spaces between cells in culture. The RCP used here is based on the alpha-1 sequence of human collagen type I and contains 12 Arg-Gly-Asp motifs. We examined the effect and mechanisms of adding petaloid RCP on the in vitro chondrogenesis of human synovial MSCs by culturing 125k cells with or without 0.125 mg petaloid RCP in chondrogenic medium for 21 days. The cartilage pellets were sequentially analyzed by weight, sulfated glycosaminoglycan content, DNA retention, and histology. Petaloid RCP significantly increased the weight of the cartilage pellets: the petaloid RCP group weighed 7.7 ± 1.2 mg (n = 108), whereas the control group weighed 5.3 ± 1.6 mg. Sulfated glycosaminoglycan and DNA contents were significantly higher in the petaloid RCP group than in the control group. Light and transmission electron microscopy images showed that the petaloid RCP formed the framework of the pellet at day 1, the framework was broken by production of cartilage matrix by the synovial MSCs at day 7, and the cartilage pellet grew larger, with diffuse petaloid RCP remaining, at day 21. Therefore, petaloid RCP formed a framework for the pellet, maintained a higher cell number, and promoted in vitro cartilage formation of synovial MSCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitahara, Kanako; Department of Immunology, Toho University School of Medicine, Tokyo; Kusunoki, Natsuko

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

Federal Mechanisms to Support Intervention Dissemination.

PubMed

Diana, Augusto; Bennett, Nicole

2015-01-01

This paper examines federal mechanisms that support program developers and researchers in disseminating effective interventions for public benefit. The purpose of this paper is not to discuss the dissemination of intervention research (i.e., how to inform stakeholders about research findings), nor is it intended to discuss the research of intervention dissemination (i.e., what is the best approach to disseminate an intervention). Rather, the paper discusses the challenges specific to finding pathways to disseminate an intervention and describes federal opportunities to support intervention dissemination. Three specific mechanisms are discussed: Federal Registries of Evidence-Based Programs, the Tiered Evidence Grant Programs, and the Small Business Innovative Research (SBIR) and the Small Technology Transfer Research (STTR) programs. The article presents some limitations associated with federal mechanisms for dissemination of effective interventions, but is intended to highlight current and future opportunities they may offer. © 2015 Wiley Periodicals, Inc.

Genetic sphingosine kinase 1 deficiency significantly decreases synovial inflammation and joint erosions in murine TNF-alpha-induced arthritis.

PubMed

Baker, DeAnna A; Barth, Jeremy; Chang, Raymond; Obeid, Lina M; Gilkeson, Gary S

2010-08-15

Sphingosine kinase 1 (SphK1) is an enzyme that converts sphingosine to bioactive sphingosine-1-phosphate. Recent in vitro data suggest a potential role of SphK1 in TNF-alpha-mediated inflammation. Our aims in this study were to determine the in vivo significance of SphK1 in TNF-alpha-mediated chronic inflammation and to define which pathogenic mechanisms induced by TNF-alpha are SphK1 dependent. To pursue these aims, we studied the effect of SphK1 deficiency in an in vivo model of TNF-alpha-induced chronic inflammatory arthritis. Transgenic hTNF-alpha mice, which develop spontaneous inflammatory erosive arthritis beginning at 14-16 wk, were crossed with SphK1 null mice (SphK1(-/-)), on the C57BL6 genetic background. Beginning at 4 mo of age, hTNF/SphK1(-/-) mice had significantly less severe clinically evident paw swelling and deformity, less synovial and periarticular inflammation, and markedly decreased bone erosions as measured quantitatively through micro-CT images. Mechanistically, the mice lacking SphK1 had less articular cyclooxygenase 2 protein and fewer synovial Th17 cells than did hTNF/SphK1(+/+) littermates. Microarray analysis and real-time RT-PCR of the ankle synovial tissue demonstrated that hTNF/SphK1(-/-) mice had increased transcript levels of suppressor of cytokine signaling 3 compared with hTNF/SphK1(+/+) mice, likely also contributing to the decreased inflammation in the SphK1-deficient mice. Finally, significantly fewer mature osteoclasts were detected in the ankle joints of hTNF/SphK1(-/-) mice compared with hTNF/SphK1(+/+) mice. These data indicate that SphK1 plays a key role in hTNF-alpha-induced inflammatory arthritis via impacting synovial inflammation and osteoclast number.

[Correlation study between interleukin-17 and ESR and CRP in serum and the synovial fluid of rheumatoid arthritis patients of accumulated dampness-heat obstruction in joints syndrome].

PubMed

Liu, De-Fang; Yan, Jiao; Guo, Ming-Yang; Wang, Chao; Hu, Yong-He; Yang, Min; Yun, Ming-Dong; Luo, Yong; Zhang, Jun; Li, Hua

2014-03-01

To probe the function of interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients of accumulated dampness-heat obstruction in joints syndrome (ADOJS) by detecting levels of IL-17 in serum and the synovial fluid and analyzing its correlation with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP). From January 2011 to January 2013, recruited were 90 RA inpatients of ADOJS at Department of Integrative Medical Rheumatism, General Hospital of Chengdu Military Region, of which 28 patients had knee joint effusion. Besides, 30 healthy volunteers who received physical examination at our hospital were recruited as the normal control group, and 30 patients with osteoarthritis (OA) who had knee joint effusion were recruited as the synovial fluid control group. The expression levels of IL-17 in serum and the synovial fluid were detected by enzyme linked immunosorbent assay (ELISA), and contents of ESR and CRP were detected in RA patients. Then correlation analyses were performed between levels of IL-17 and contents of ESR and CRP. Compared with the normal serum control group, the expression levels of IL-17 in serum of RA patients significantly increased (P < 0.05). Compared with the serum of RA patients and the synovial fluid of OA patients, the expression levels of IL-17 in the synovial fluid of RA patients significantly increased (P < 0.05). The expression levels of IL-17 in serum of RA patients were not correlated with ESR or CRP (r = 0.092, -0.082; P > 0.05), and the expressional levels of IL-17 in the synovial fluid of RA patients were not correlated with ESR or CRP (r = 0.113, -0.034; P > 0.05). IL-17 was the main effector cytokine of Th17 cells. The expressional levels of IL-17 significantly increased in serum and the synovial fluid of RA patients of ADOJS, but with no correlation to ESR or CRP. It indicated that IL-17 participated in the occurrence and development of RA. Concrete mechanisms needed to be further proved in larger samples.

Orally incoculated Salmonella typhimurium is detected in the lymph nodes and synovial fluid of swine

USDA-ARS?s Scientific Manuscript database

Salmonella is a foodborne pathogen that has been associated with illnesses from the consumption of meat products. Traditional carcass sampling techniques fail to account for contamination via atypical carcass reservoirs such as lymph nodes and synovial fluid that may harbor Salmonella. In this two-p...

Changes of synovial fluid protein concentrations in supra-patellar bursitis patients after the injection of different molecular weights of hyaluronic acid.

PubMed

Chen, Carl P C; Hsu, Chih Chin; Pei, Yu-Cheng; Chen, Ruo Li; Zhou, Shaobo; Shen, Hsuan-Chen; Lin, Shih-Cherng; Tsai, Wen Chung

2014-04-01

Knee pain is commonly seen in orthopedic and rehabilitation outpatient clinical settings, and in the aging population. Bursitis of the knee joint, especially when the volume of the synovial fluid is large enough, can compress and distend the nearby soft tissues, causing pain in the knee joint. Out of all the bursae surrounding the knee joint, supra-patellar bursitis is most often associated with knee pain. Treatment strategies in managing supra-patellar bursitis include the aspiration of joint synovial fluid and then followed by steroid injection into the bursa. When supra-patellar bursitis is caused by degenerative disorders, the concept of viscosupplementation treatment may be effective by injecting hyaluronic acid into the bursa. However, the rheology or the changes in the concentrations of proteins (biomarkers) that are related to the development of bursitis in the synovial fluid is virtually unexplored. Therefore, this study aimed to identify the concentration changes in the synovial fluid total protein amount and individual proteins associated with supra-patellar bursitis using the Bradford protein assay and western immunoglobulin methods. A total of 20 patients were divided into two groups with 10 patients in each group. One group received the high molecular weight hyaluronic acid product of Synvisc Hylan G-F 20 and the other group received the low molecular weight hyaluronic acid product of Hya-Joint Synovial Fluid Supplement once per week injection into the bursa for a total of 3 weeks. Significant decreases in the synovial fluid total protein concentrations were observed after the second dosage of high molecular weight hyaluronic acid injections. Apolipoprotein A-I, interleukin 1 beta, alpha 1 antitrypsin, and matrix metalloproteinase 1 proteins revealed a trend of decreasing western immunoblotting band densities after hyaluronic acid injections. The decreases in apolipoprotein A-I and interleukin 1 beta protein band densities were significant in the high

Direct evidence for the partial reflection of hyaluronan molecules by the lining of rabbit knee joints during trans-synovial flow

PubMed Central

Scott, D; Coleman, P J; Mason, R M; Levick, J R

1998-01-01

In synovial joints hydraulic and turnover studies indicate that the synovial lining may partially reflect large macromolecules like hyaluronan, despite discontinuities in the lining cell layer. The reflection hypothesis was tested directly in the present study. Solutions of high molecular weight hyaluronan were infused at controlled pressures into the cavity of rabbit knees under anaesthesia, at concentrations of 0.2 g l−1 (n = 5), 2 g l−1 (n = 5) and 4 g l−1 (n = 6). Time-averaged trans-synovial flows were 9.6, 4.8 and 2.9 μl min−1, respectively. After 5 h infusion the intra-articular fluid was mixed and sampled. Hyaluronan concentration was determined by size-exclusion chromatography. In all sixteen experiments the hyaluronan concentration in the aspirate was greater than that in the infusate (P = 0.0001, Student's paired t test). The increases averaged 2.28 ± 0.04 times at high filtration rates (0.2 g l−1 infusates; mean ± s.e.m.), 1.60 ± 0.09 times at intermediate filtration rates (2 g l−1 infusates) and 1.26 ± 0.08 times at low filtration rates (4 g l−1 infusates). Between 48 and 95% of the hyaluronan in the filtrand was retained in the joint cavity. The greater retention at 2 g l−1, viz.95%, than at 0.2 g l−1, viz.48%, was attributed to interactions between overlapping molecular domains in the more concentrated solution. It is concluded that synovial interstitial matrix can partially reflect hyaluronan molecules, and thus conserve intra-articular lubricant. PMID:9508822

Decreased synovial fluid ghrelin levels are linked with disease severity in primary knee osteoarthritis patients and are increased following laser therapy.

PubMed

Zou, Yu-Cong; Deng, Hong-Yu; Mao, Zheng; Zhao, Chang; Huang, Ju; Liu, Gang

2017-07-01

Ghrelin has been proved to inhibit inflammation and promote cartilage growth. So far, its role in patients with primary knee osteoarthritis has not been investigated. The current study was performed to explore the serum and synovial ghrelin levels as well as the relationship between ghrelin levels and disease severity in primary knee OA patients. 52 primary knee OA patients were recruited in the study. 52 sex and age-matched patients visiting our hospital for regular body check were selected as controls. The serum and synovial fluid ghrelin levels were examined by enzyme linked immunosorbent assay (ELISA) before treatment, one week and four weeks after laser therapy, respectively. The inflammation markers IL-6 and TNF-α were also investigated. The radiographic progression was assessed by Kellgren-Lawrence (K-L) grade scale and the symptomatic severity was evaluated by visual analog scale (VAS), Lequesne index and Lysholm scores. The Receiver Operating Characteristic (ROC) analysis curve was conducted to test the diagnostic value of ghrelin, IL-6 and TNF-α for radiographic progression. No significant difference of serum ghrelin levels was found between knee OA patients and healthy controls. Synovial fluid ghrelin concentrations were significantly negatively correlated with K-L grading (r=-0.591, P<0.001).Attenuated synovial fluid ghrelin levels were also related to clinical severity determined by Lequesne index (r=-0.308, P=0.025),VAS scores (r=-0.591, P<0.001) and Lysholm scores (r=0.381, P=0.005).In addition, ghrelin levels were also negatively associated with TNF-α (r=-0.424, P=0.002) and IL-6 concentrations (r=-0.428, P=0.002). ROC curve analysis demonstrated that ghrelin exhibited more diagnostic value than IL-6 and TNF-α for assessing radiographic progression in medium-late stage. Decreased synovial fluid ghrelin levels are related to disease severity in patients with primary osteoarthritis and are increased following laser therapy. Local application of

[Imaging of the elbow joint with focus MRI. Part 2: muscles, nerves and synovial membranes].

PubMed

Rehm, J; Zeifang, F; Weber, M-A

2014-03-01

This review article discusses the magnetic resonance imaging (MRI) features and pathological changes of muscles, nerves and the synovial lining of the elbow joint. Typical imaging findings are illustrated and discussed. In addition, the cross-sectional anatomy and anatomical variants, such as accessory muscles and plicae are discussed. Injuries of the muscles surrounding the elbow joint, as well as chronic irritation are particularly common in athletes. Morphological changes in MRI, for example tennis or golfer's elbow are typical and often groundbreaking. By adapting the examination sequences, imaging planes and slices, complete and incomplete tendon ruptures can be reliably diagnosed. Although the clinical and electrophysiological examinations form the basis for the diagnosis of peripheral neuropathies, MRI provides useful additional information about the precise localization due to its high resolution and good soft tissue contrast and helps to rule out differential diagnoses. Synovial diseases, such as inflammatory arthritis, proliferative diseases and also impinging plicae must be considered in the MRI diagnostics of the elbow joint.

Interleukin-8 mRNA expression in synovial fluid of canine stifle joints with osteoarthritis.

PubMed

de Bruin, T; de Rooster, H; van Bree, H; Cox, E

2005-12-15

The objective of this study was to examine and compare the presence of interleukin (IL)-8 mRNA in canine stifle osteoarthritis (OA) differing in etiopathogenesis. Synovial fluid (SF) samples were collected from 24 clinically normal stifle joints and 46 diseased stifle joints (32 stifle joints with cranial cruciate ligament rupture (CCLR), 2 joints with CCLR and patella luxation (PL), 7 joints with medial PL and 5 joints with primary OA). The samples were centrifuged to collect synovial fluid cells for RNA extraction. Reverse transcription polymerase chain reaction (RT-PCR) was performed to obtain cDNA from all samples. Canine IL-8 mRNA expression was determined using real time PCR. Synovial fluid glass smears were made of all samples and coloured with H&E for differential cell counts. All stifle joints were radiographed and graded for the severity of OA. Sixty-one percent (28/46) of the samples from canine stifle OA had IL-8 mRNA expression in contrast to 4% (1/24) in the control stifle joints. This difference in prevalence is highly significant. There were no statistically significant pairwise differences among the mean ranks of the various OA groups for the absolute amount of IL-8 mRNA expression. Neither was there a link between the severity of OA (determined by radiographic evaluation) and the presence of IL-8 in the SF nor any significant difference in the absolute amount of IL-8 between the different OA grades. No statistical difference was found in differential cell counts between IL-8-positive and -negative SF samples. IL-8 cannot be used as a specific joint disease marker since IL-8 expression is found in OA differing in etiopathogenesis. It might, however, relate to the ongoing inflammation within the joint.

Effect of synovial fluid, phosphate-buffered saline solution, and water on the dissolution and corrosion properties of CoCrMo alloys as used in orthopedic implants.

PubMed

Lewis, A C; Kilburn, M R; Papageorgiou, I; Allen, G C; Case, C P

2005-06-15

The corrosion and dissolution of high- and low-carbon CoCrMo alloys, as used in orthopedic joint replacements, were studied by immersing samples in phosphate-buffered saline (PBS), water, and synovial fluid at 37 degrees C for up to 35 days. Bulk properties were analyzed with a fine ion beam microscope. Surface analyses by X-ray photoelectron spectroscopy and Auger electron spectroscopy showed surprisingly that synovial fluid produced a thin oxide/hydroxide layer. Release of ions into solution from the alloy also followed an unexpected pattern where synovial fluid, of all the samples, had the highest Cr concentration but the lowest Co concentration. The presence of carbide inclusions in the alloy did not affect the corrosion or the dissolution mechanisms, although the carbides were a significant feature on the metal surface. Only one mechanism was recognized as controlling the thickness of the oxide/hydroxide interface. The analysis of the dissolved metal showed two mechanisms at work: (1) a protein film caused ligand-induced dissolution, increasing the Cr concentration in synovial fluid, and was explained by the equilibrium constants; (2) corrosion at the interface increased the Co in PBS. The effect of prepassivating the samples (ASTM F-86-01) did not always have the desired effect of reducing dissolution. The release of Cr into PBS increased after prepassivation. The metal-synovial fluid interface did not contain calcium phosphate as a deposit, typically found where samples are exposed to calcium rich bodily fluids. (c) 2005 Wiley Periodicals, Inc.

Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity*

PubMed Central

Jin, Chunsheng; Ekwall, Anna-Karin Hultgård; Bylund, Johan; Björkman, Lena; Estrella, Ruby P.; Whitelock, John M.; Eisler, Thomas; Bokarewa, Maria; Karlsson, Niclas G.

2012-01-01

Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1–3(GlcNAcβ1–6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation. PMID:22930755

Microscopical analysis of synovial fluid wear debris from failing CoCr hip prostheses

NASA Astrophysics Data System (ADS)

Ward, M. B.; Brown, A. P.; Cox, A.; Curry, A.; Denton, J.

2010-07-01

Metal on metal hip joint prostheses are now commonly implanted in patients with hip problems. Although hip replacements largely go ahead problem free, some complications can arise such as infection immediately after surgery and aseptic necrosis caused by vascular complications due to surgery. A recent observation that has been made at Manchester is that some Cobalt Chromium (CoCr) implants are causing chronic pain, with the source being as yet unidentified. This form of replacement failure is independent of surgeon or hospital and so some underlying body/implant interface process is thought to be the problem. When the synovial fluid from a failed joint is examined particles of metal (wear debris) can be found. Transmission Electron Microscopy (TEM) has been used to look at fixed and sectioned samples of the synovial fluid and this has identified fine (< 100 nm) metal and metal oxide particles within the fluid. TEM EDX and Electron Energy Loss Spectroscopy (EELS) have been employed to examine the composition of the particles, showing them to be chromium rich. This gives rise to concern that the failure mechanism may be associated with the debris.

C5a and C5aR are elevated in joints of rheumatoid and psoriatic arthritis patients, and C5aR blockade attenuates leukocyte migration to synovial fluid.

PubMed

Hornum, Lars; Hansen, Anker Jon; Tornehave, Ditte; Fjording, Marianne Scheel; Colmenero, Paula; Wätjen, Inger Falbe; Søe Nielsen, Niels Henrik; Bliddal, Henning; Bartels, Else Marie

2017-01-01

Complement activation correlates to rheumatoid arthritis disease activity, and increased amounts of the complement split product C5a is observed in synovial fluids from rheumatoid arthritis patients. Blockade of C5a or its receptor (C5aR) is efficacious in several arthritis models. The aim of this study was to investigate the role of C5a and C5aR in human rheumatoid arthritis and psoriatic arthritis-both with respect to expression and function. Synovial fluid, blood and synovial samples were obtained from rheumatoid arthritis, psoriatic arthritis and osteoarthritis patients as a less inflammatory arthritis type, and blood from healthy subjects. Cells infiltrating synovial tissue were analysed by immunohistochemistry and flow cytometry. SF and blood were analysed for biomarkers by flow cytometry or ELISA. The effect of a blocking anti-human C5aR mAb on leukocyte migration was determined using a Boyden chamber. Appropriate statistical tests were applied for comparisons. C5aR+ cells were detected in most rheumatoid arthritis, in all psoriatic arthritis, but not in non-inflammatory control synovia. C5aR+ cells were primarily neutrophils and macrophages. C5aR+ macrophages were mainly found in lymphoid aggregates in close contact with T cells. C5a levels were increased in both rheumatoid arthritis and psoriatic arthritis synovial fluid compared to osteoarthritis, and in blood from rheumatoid arthritis compared to healthy subjects. Neutrophil and monocyte migration to rheumatoid arthritis synovial fluid was significantly inhibited by anti-C5aR. The data support that the C5a-C5aR axis may be driving the infiltration of inflammatory cells into the synovial fluid and synovium in both rheumatoid and psoriatic arthritis, and suggest that C5a or C5aR may be a promising treatment target in both diseases.

Plasma rich in growth factors (PRGF-Endoret) stimulates tendon and synovial fibroblasts migration and improves the biological properties of hyaluronic acid.

PubMed

Anitua, E; Sanchez, M; De la Fuente, M; Zalduendo, M M; Orive, G

2012-09-01

Cell migration plays an essential role in development, wound healing, and tissue regeneration. Plasma rich in growth factors (PRGF-Endoret) technology offers a potential source of growth factors involved in tissue regeneration. Here, we evaluate the potential of PRGF-Endoret over tendon cells and synovial fibroblasts migration and study whether the combination of this autologous technology with hyaluronic acid (HA) improves the effect and potential of the biomaterials over the motility of both types of fibroblasts. Migration of primary tendon cells and synovial fibroblasts after culturing with either PRGF or PPGF (plasma poor in growth factors) at different doses was evaluated. Furthermore, the migratory capacity induced by the combination of PPGF and PRGF with HA was tested. PPGF stimulated migration of both types of cells but this effect was significantly higher when PRGF was used. Tendon cells showed an increase of 212% in migratory ability when HA was combined with PPGF and of 335% in the case of HA + PRGF treatment compared with HA alone. PRGF-Endoret stimulates migration of tendon cells and synovial fibroblasts and improves the biological properties of HA.

Spinal case of the month with short perspective: How would you treat this L3-L4 synovial cyst?

PubMed

Epstein, Nancy E

2018-01-01

In this new section, Case of the Month with Short Perspective from Surgical Neurology International, we want to see how various spine surgeons would approach different spinal pathologies. In this first case, an elderly male presented with 3 years of lower back pain and progressive neurogenic claudication with bilateral radiculopathy that had exacerbated over the prior 6 months. An outside physician performed a magnetic resonance (MR) study of the lumbar spine that showed a massive synovial cyst filling the spinal canal (e.g., large bilateral cysts) at the L3-L4 level with grade I spondylolisthesis. The MR and CT studies also both demonstrated moderate L2-L3, and severe L3-L4 stenosis. Despite the massive synovial cyst filling the spinal canal at the L3-L4 level, pain management (anesthesia training) spent 3 months performing three successive epidural steroid injections accompanied by attempts at percutaneous synovial cyst aspiration/rupture. By the time the patient presented to neurosurgery, he had developed severe neurogenic claudication, radiculopathy, myelopathy, and a cauda equina syndrome. Dynamic X-rays revealed a mild grade I degenerative spondylolisthesis at the L3-L4 level without active motion, while both computed tomography (CT) and MR studies confirmed moderate stenosis stenosis/ossification of the yellow ligament at the L2-L3 level, severe stenosis at L3-L4 level with spondylolisthesis, and massive bilateral synovial cysts at the L3-L4 level filling the spinal canal. Following an L2-L4 decompressive laminectomy without fusion (note the absence of motion intraoperatively at the L3-L4 level), the patient's symptoms resolved, and he regained normal function. How would you have managed this patient?

PNET-like features of synovial sarcoma of the lung: a pitfall in the cytologic diagnosis of soft-tissue tumors.

PubMed

Hummel, P; Yang, G C; Kumar, A; Cohen, J M; Winkler, B; Melamed, J; Scholes, J V; Jagirdar, J

2001-04-01

Fine-needle aspiration (FNA) cytology of soft-tissue tumors is evolving. As more experience is gained, we are becoming aware of potential pitfalls. We describe 2 cases of synovial sarcoma of the lung, primary and metastatic, in patients who had FNA biopsy performed on a lung mass. The cytologic smears showed extremely cellular groups of malignant small round cells, intersected by small blood vessels, with numerous loose single cells, in a background of macrophages and mature lymphocytes. The tumors displayed monomorphic cells forming rosettes and displaying occasional mitoses. A diagnosis of neuroendocrine tumor/primitive neuroepithelial tumor (PNET) was suspected. Furthermore, this suspicion was supported by immunohistochemical stains, which showed positivity for a neuroendocrine marker, Leu 7 (case 1), and for a neural marker, CD 99 (O 13 or HBA 71) (both cases); and negativity for cytokeratins (case 1). The resection specimen of case 1 had mostly tightly packed small round cells, with occasional rosettes, similar to the FNA biopsy, and focal areas composed of spindle cells, organized in a focal fibrosarcoma-like and hemangiopericytoma-like pattern. A balanced translocation between chromosomes X and 18, demonstrated by both karyotyping and fluorescent in situ hybridization (FISH), enabled us to make a diagnosis of synovial sarcoma, which was histologically classified as poorly differentiated. Case 2 was a metastatic biphasic synovial sarcoma of the arm, with a prominent epithelial component. Synovial sarcoma, when composed mainly of small round cells on cytologic smears, is a great mimicker of neuroendocrine/PNET tumors, with light microscopic and immunohistochemical overlap. Awareness of this potential pitfall may aid in preventing a misdiagnosis. Its recognition is of major concern, especially for the poorly differentiated variant, because it is associated with a worse prognosis. Copyright 2001 Wiley-Liss, Inc.

Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays

PubMed Central

2012-01-01

Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of autoantibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, the nucleic acid programmable protein array (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from 10 JIA patients was screened for antibodies against 768 proteins on NAPPAs. Results Quantitative reproducibility of NAPPAs was demonstrated with > 0.95 intra-array and inter-array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r = 0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusion The NAPPAs provide a high-throughput quantitatively reproducible platform to screen for disease-specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPAs could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level. PMID:22510425

Selective killing of proinflammatory synovial fibroblasts via activation of transient receptor potential ankyrin (TRPA1).

PubMed

Lowin, Torsten; Bleck, Janna; Schneider, Matthias; Pongratz, Georg

2018-05-24

Studies in rheumatoid arthritis synovial fibroblasts (RASF) demonstrated the expression of several transient receptor potential channels (TRP) such as TRPV1, TRPV2, TRPV4, TRPA1 and TRPM8. Upon ligation, these receptors increase intracellular calcium but they have also been linked to modulation of inflammation in several cell types. TNF was shown to increase the expression of TRPA1, the receptor for mustard oil and environmental poisons in SF, but the functional consequences have not been investigated yet. TRPA1 was detected by immunocytochemistry, western blot and cell-based ELISA. Calcium measurements were conducted in a multimode reader. Cell viability was assessed by quantification of lactate dehydrogenase (LDH) in culture supernatants and "RealTime-Glo" luminescent assays. IL-6 and IL-8 production by SF was quantified by ELISA. Proliferation was determined by cell titer blue incorporation. After 72 h, mimicking proinflammatory conditions by the innate cytokine TNF up-regulated TRPA1 protein levels in RASF which was accompanied by increased sensitivity to TRPA1 agonists AITC and polygodial. Under unstimulated conditions, polygodial elicited calcium flux only in the highest concentrations used (50 µM and 25 µM). TNF preincubation substantially lowered the activation threshold for polygodial (from 25 µM to 1 µM). In the absence of TNF pre-stimulation, only polygodial in high concentrations was able to reduce viability of synovial fibroblasts as determined by a real-time viability assay. However, following TNF preincubation, stimulation of TRPA1 led to a fast (<30 min) viability loss by necrosis of synovial fibroblasts. TRPA1 activation was also associated with decreased proliferation of RASFs, an effect that was also substantially enhanced by TNF preincubation. On the functional level, IL-6 and IL-8 production was attenuated by the TRPA1 antagonist A967079 but also polygodial, although the latter mediated this effect by reducing cell viability

Synovial T-cell lymphoma of the stifle in a dog.

PubMed

Lahmers, Sunshine M; Mealey, Katrina L; Martinez, Steven A; Haldorson, Gary J; Sellon, Rance K; Cambridge, Anthony J

2002-01-01

A 6-year-old, 43-kg, spayed female rottweiler was presented for a 1-month history of progressive, left hind-limb lameness. Upon physical examination, a cranial drawer sign and joint distention were present in the left stifle. Radiographically, the stifle had evidence of effusion, remodeling of the patella, and an enlarged popliteal lymph node. Marked synovial thickening and an intact cranial cruciate ligament were noted during surgery. Despite finding a nonspecific, mixed inflammatory response on joint fluid cytopathology, histopathology demonstrated T-cell lymphoma of the synovium. Lameness may be the sole presenting clinical sign in canine lymphoma.

Disseminated sporotrichosis in an immunocompetent patient.

PubMed

Hassan, Kareem; Turker, Tolga; Zangeneh, Tirdad

2016-01-01

Sporothrix schenckii, the causative agent of sporotrichosis, is a relatively rare infection. Local infection usually occurs through direct inoculation of the organism through the skin; disseminated disease is rarely seen. This article describes a case of disseminated sporotrichosis in a middle-aged man without the commonly seen risk factors for dissemination.

Population pharmacokinetic analysis of blood and joint synovial fluid concentrations of robenacoxib from healthy dogs and dogs with osteoarthritis.

PubMed

Silber, Hanna E; Burgener, Claudia; Letellier, Ingrid M; Peyrou, Mathieu; Jung, Martin; King, Jonathan N; Gruet, Philippe; Giraudel, Jerome M

2010-12-01

The purpose of this population analysis was to characterize the pharmacokinetic properties of robenacoxib in blood and stifle joint synovial fluid of dogs. Data were obtained from two studies: 1) 8 healthy Beagle dogs in which an acute inflammation was induced by injection of urate crystals into one joint; 2) 95 dogs from various breeds diagnosed with osteoarthritis (OA). Robenacoxib concentrations in blood and synovial fluid were measured using a validated HPLC-UV and LC-MS method. Non-linear mixed effects modeling was performed using NONMEM6. A two-compartment pharmacokinetic model with linear elimination was developed to describe blood concentrations of robenacoxib. Blood clearance in healthy animals was found to be 75% higher than in OA dogs. Synovial fluid concentrations were modeled using an effect-compartment-type model predicting longer residence times in OA dogs compared to healthy Beagles (e.g. concentrations above the IC(50) for COX-2, respectively, 16 h vs. 10 h at 1.5 mg/kg). Robenacoxib was found to reside longer at the effect site (inflamed joint) compared to blood in both healthy and OA dogs. These results may explain the good efficacy observed with once-daily dosing in clinical trials and the high safety index of robenacoxib in dogs.

Characterization of endocannabinoids and related acylethanolamides in the synovial fluid of dogs with osteoarthritis: a pilot study.

PubMed

Valastro, Carmela; Campanile, Debora; Marinaro, Mariarosaria; Franchini, Delia; Piscitelli, Fabiana; Verde, Roberta; Di Marzo, Vincenzo; Di Bello, Antonio

2017-11-06

Cannabis-based drugs have been shown to be effective in inflammatory diseases. A number of endocannabinoids including N- arachidonoylethanolamide (anandamide, AEA) and 2-arachidonyl glycerol (2-AG) with activity at the cannabinoid receptors (CBR) CBR1 and CBR2, have been identified. Other structurally related endogenous fatty acid compounds such as oleoylethanolamide (OEA) and palmitoyl ethanolamide (PEA) have been identified in biological tissues. These compounds do not bind to CBR but might be involved in facilitating the actions of directly acting endocannabinoids and thus are commonly termed "entourage" compounds due to their ability to modulate the endocannabinoid system. The aim of this study was to evaluate the presence of endocannabinoids and entourage compounds in the synovial fluid of dogs with osteoarthritis subjected to arthrotomy of the knee joint. Cytokines and cytology were studied as well. AEA, 2-AG, OEA and PEA were all present in the synovial fluid of arthritic knees and in the contralateral joints; in addition, a significant increase of OEA and 2AG levels were noted in SF from OA knees when compared to the contralateral joints. The identification and quantification of endocannabinoids and entourage compounds levels in synovial fluids from dogs with OA of the knee is reported for the first time. Our data are instrumental for future studies involving a greater number of dogs. Cannabinoids represent an emerging and innovative pharmacological tool for the treatment of OA and further studies are warranted to evaluate the effectiveness of cannabinoids in veterinary medicine.

In Vitro Study of a Liposomal Curcumin Formulation (Lipocurc™): Toxicity and Biological Activity in Synovial Fibroblasts and Macrophages.

PubMed

Kloesch, Burkhard; Gober, Lukas; Loebsch, Silvia; Vcelar, Brigitta; Helson, Lawrence; Steiner, Guenter

2016-01-01

The polyphenol curcumin is produced in the rhizome of Curcuma longa and exhibits potent anti-inflammatory, antioxidant, and chemopreventive activities. Due to the fact that curcumin is poorly soluble in water, many delivery systems have been developed to improve its solubility and bioavailability achieving optimum therapeutic application. In this study, we evaluated the biological effects of a liposomal curcumin formulation (Lipocurc™) on human synovial fibroblasts (SW982) and mouse macrophages (RAW264). Cellular uptake of liposomes was studied using calcein-loaded liposomes. Effects of Lipocurc™ on cell viability and proliferation were determined with Celltox green cytotoxicity assay and 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay, respectively. To induce cytokine/chemokine expression, the cells were stimulated with interleukin (IL)1β or lipopolysaccharide (LPS). The release of IL6, IL8, and tumor necrosis factor-alpha (TNFα) was quantified by enzyme-linked immunosorbent assay (ELISA). Data showed that the liposomal curcumin formulation Lipocurc™ was significantly less toxic to synovial fibroblasts and macrophages compared to non-encapsulated, free curcumin. Furthermore, Lipocurc™ effectively reduced pro-inflammatory cytokine/chemokine expression in synovial fibroblasts as well as in macrophages without affecting cell viability, suggesting that this curcumin nanoformulation might be a promising tool for the treatment of inflammatory diseases. Copyright © 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Adenosine monophosphate-activated protein kinase activation and suppression of inflammatory response by cell stretching in rabbit synovial fibroblasts.

PubMed

Kunanusornchai, Wanlop; Muanprasat, Chatchai; Chatsudthipong, Varanuj

2016-12-01

Joint mobilization is known to be beneficial in osteoarthritis (OA) patients. This study aimed to investigate the effect of stretching on adenosine monophosphate-activated protein kinase (AMPK) activity and its role in modulating inflammation in rabbit synovial fibroblasts. Uniaxial stretching of isolated rabbit synovial fibroblasts for ten min was performed. Stretching-induced AMPK activation, its underlying mechanism, and its anti-inflammatory effect were investigated using Western blot. Static stretching at 20 % of initial length resulted in AMPK activation characterized by expression of phosphorylated AMPK and phosphorylated acetyl-Co A carboxylase. AMP-activated protein kinase phosphorylation peaked 1 h after stretching and declined toward resting activity. Using cell viability assays, static stretching did not appear to cause cellular damage. Activation of AMPK involves Ca 2+ influx via a mechanosensitive L-type Ca 2+ channel, which subsequently raises intracellular Ca 2+ and activates AMPK via Ca 2+ /calmodulin-dependent protein kinase kinase β (CaMKKβ). Interestingly, stretching suppressed TNFα-induced expression of COX-2, iNOS, and phosphorylated NF-κB. These effects were prevented by pretreatment with compound C, an AMPK inhibitor. These results suggest that mechanical stretching suppressed inflammatory responses in synovial fibroblasts via a L-type Ca 2+ -channel-CaMKKβ-AMPK-dependent pathway which may underlie joint mobilization's ability to alleviate OA symptoms.

Disseminated sporotrichosis in an immunocompetent patient

PubMed Central

Hassan, Kareem; Turker, Tolga; Zangeneh, Tirdad

2016-01-01

Abstract Sporothrix schenckii, the causative agent of sporotrichosis, is a relatively rare infection. Local infection usually occurs through direct inoculation of the organism through the skin; disseminated disease is rarely seen. This article describes a case of disseminated sporotrichosis in a middle-aged man without the commonly seen risk factors for dissemination. PMID:27583270

Pleiotrophin, the angiogenic and mitogenic growth factor: levels in serum and synovial fluid in rheumatoid arthritis and osteoarthritis : And correlation with clinical, laboratory and radiological indices.

PubMed

Fadda, S M H; Bassyouni, I H; Khalifa, R H; Elsaid, N Y

2018-05-01

Few studies have reported a possible involvement of pleiotrophin (PTN) in the pathophysiology of osteoarthritis (OA) and very little is known about its role in rheumatoid arthritis (RA). This study is to measure PTN in the sera and synovial fluids in RA and OA and to assess its relation to activity, functional class and radiological staging. Serum and synovial fluid samples were collected from 35 RA patients and 40 knee OA patients and serum samples were withdrawn from 20 healthy controls. Demographic, clinical and serological data were prospectively assessed. Functional and radiographic grades were also assessed. Serum and synovial fluid PTN levels were measured using enzyme-linked immunosorbent assay (ELISA). There was no statistical significant differences (p > 0.05) on comparing the mean PTN level in sera of RA, OA patients and healthy controls. However the mean synovial fluid level of PTN in both patient groups was significantly higher than mean serum level (p < 0.001). Significant correlations between the serum PTN level and both morning stiffness duration (p = 0.008) and mHAQ score (p = 0.039) were only observed in RA patients. Our results point to a possible important role of PTN in RA and OA. We firstly report a serological pattern of PTN in the sera and synovial fluids of RA patients. However its implementation as a disease marker or a potential target therapy in both diseases awaits larger studies and further investigations.

Interleukin-6 in serum and in synovial fluid enhances the differentiation between periprosthetic joint infection and aseptic loosening.

PubMed

Randau, Thomas M; Friedrich, Max J; Wimmer, Matthias D; Reichert, Ben; Kuberra, Dominik; Stoffel-Wagner, Birgit; Limmer, Andreas; Wirtz, Dieter C; Gravius, Sascha

2014-01-01

The preoperative differentiation between septic and aseptic loosening after total hip or knee arthroplasty is essential for successful therapy and relies in part on biomarkers. The objective of this study was to assess synovial and serum levels of inflammatory proteins as diagnostic tool for periprosthetic joint infection and compare their accuracy with standard tests. 120 patients presenting with a painful knee or hip endoprosthesis for surgical revision were included in this prospective trial. Blood samples and samples of intraoperatively acquired joint fluid aspirate were collected. White blood cell count, C-reactive protein, procalcitonin and interleukin-6 were determined. The joint aspirate was analyzed for total leukocyte count and IL-6. The definite diagnosis of PJI was determined on the basis of purulent synovial fluid, histopathology and microbiology. IL-6 in serum showed significantly higher values in the PJI group as compared to aseptic loosening and control, with specificity at 58.3% and a sensitivity of 79.5% at a cut-off value of 2.6 pg/ml. With a cut-off >6.6 pg/ml, the specificity increased to 88.3%. IL-6 in joint aspirate had, at a cut-off of >2100 pg/ml, a specificity of 85.7% and sensitivity of 59.4%. At levels >9000 pg/ml, specificity was almost at 100% with sensitivity just below 50%, so PJI could be considered proven with IL-6 levels above this threshold. Our data supports the published results on IL-6 as a biomarker in PJI. In our large prospective cohort of revision arthroplasty patients, the use of IL-6 in synovial fluid appears to be a more accurate marker than either the white blood cell count or the C-reactive protein level in serum for the detection of periprosthetic joint infection. On the basis of the results we recommend the use of the synovial fluid biomarker IL-6 for the diagnosis of periprosthetic joint infection following total hip and knee arthroplasty.

Tenascin-C levels in synovial fluid are elevated after injury to the human and canine joint and correlate with markers of inflammation and matrix degradation.

PubMed

Chockalingam, P S; Glasson, S S; Lohmander, L S

2013-02-01

We have previously shown the capacity of tenascin-C (TN-C) to induce inflammatory mediators and matrix degradation in vitro in human articular cartilage. The objective of the present study was to follow TN-C release into knee synovial fluid after acute joint injury or in joint disease, and to correlate TN-C levels with markers of cartilage matrix degradation and inflammation. Human knee synovial fluid samples (n = 164) were from a cross-sectional convenience cohort. Diagnostic groups were knee healthy reference, knee anterior cruciate ligament rupture, with or without concomitant meniscus lesions, isolated knee meniscus injury, acute inflammatory arthritis (AIA) and knee osteoarthritis (OA). TN-C was measured in synovial fluid samples using an enzyme-linked immunosorbent assay (ELISA) and results correlated to other cartilage markers. TN-C release was also monitored in joints of dogs that underwent knee instability surgery. Statistically significantly higher levels of TN-C compared to reference subjects were observed in the joint fluid of all human disease groups and in the dogs that underwent knee instability surgery. Statistically significant correlations were observed between the TN-C levels in the synovial fluid of the human patients and the levels of aggrecanase-dependent Ala-Arg-Gly-aggrecan (ARG-aggrecan) fragments and matrix metalloproteinases 1 and 3. We find highly elevated levels of TN-C in human knee joints after injury, AIA or OA that correlated with markers of cartilage degradation and inflammation. TN-C in synovial fluid may serve dual roles as a marker of joint damage and a stimulant of further joint degradation. Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Surgical reconstruction of ruptured anterior cruciate ligament prolongs trauma-induced increase of inflammatory cytokines in synovial fluid: an exploratory analysis in the KANON trial.

PubMed

Larsson, S; Struglics, A; Lohmander, L S; Frobell, R

2017-09-01

Prospectively monitor how treatment of acutely ruptured anterior cruciate ligament (ACL) affects biomarkers of inflammation and proteolytic degradation over 5 years. We studied 119 subjects with acute ACL injury from the randomized controlled knee anterior cruciate ligament, non-surgical versus surgical treatment (KANON)-trial (Clinical trial ISRCTN 84752559) who had synovial fluid, serum and urine samples available from at least two out of six visits over 5 years after acute ACL rupture. All subjects followed a similar rehabilitation protocol where, according to randomization, 60 also had early ACL reconstruction and 59 had the option to undergo a delayed ACL reconstruction if needed. Interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), tumor necrosis factor (TNF), amino acids alanine, arginine, glycine, serine (ARGS)-aggrecan, C-terminal crosslinking telopeptide type II collagen (CTX-II) and N-terminal crosslinking telopeptide type I collagen (NTX-I) were quantified by enzyme-linked immunosorbent assays (ELISA). Subjects randomized to early ACL reconstruction had higher cytokine concentrations in index knee synovial fluid at 4 months (IL-6, IL-8, IL-10, TNF), 8 months (IL-6 and TNF) and at 5 years (IFNγ) compared to those randomized to optional delayed reconstruction. Those that underwent delayed ACL reconstruction within 5 years (30 subjects), had higher synovial fluid concentrations of IL-6 at 5 years compared to those treated with rehabilitation alone. No differences between groups were noted for ARGS-aggrecan in synovial fluid and serum or CTX-II and NTX-I in urine over 5 years, neither as randomized nor as treated. Surgical ACL reconstruction constitutes a second trauma to the acutely injured joint resulting in a prolonged elevation of already high synovial fluid levels of inflammatory cytokines. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Zymographic analysis using gelatin-coated film of the effect of etanercept on the extracellular matrix-degrading activity in synovial fluids of rheumatoid arthritis patients.

PubMed

Kamataki, Akihisa; Ishida, Mutsuko; Komagamine, Masataka; Yoshida, Masaaki; Ando, Takanobu; Sawai, Takashi

2016-04-01

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Most RA patients develop cartilage and bone destruction, and various proteinases are involved in the destruction of extracellular matrix of cartilage and bone. The aim of this study is to evaluate the utility of our newly developed method to measure total gelatinolytic activity. We adopted this method for measurement in synovial fluid from RA patients treated by the anti-rheumatic drug etanercept (ETN), a recombinant human soluble tumor necrosis factor receptor fusion protein, and compared the findings with clinical and laboratory data. Enzymatic activity of synovial fluid was analyzed by zymography using gelatin-coated film, and compared with the index of Disease Activity Score of 28 joints - C-reactive protein (DAS28-CRP), CRP and matrix metalloproteinase (MMP)-3 level before and after ETN therapy. Synovial fluids of 19 patients were collected before and after administration of ETN therapy. In nine of 19 patients, who showed a decrease in gelatin-degrading activity in synovial fluid, the index of DAS28-CRP (4.85-2.85, ΔDAS = -2.00) and CRP (3.30-0.94 mg/dL, ΔCRP = -2.36) was alleviated after ETN therapy, while cases with no change or an increase in gelatin-degrading activity showed a modest improvement in clinical data: DAS28-CRP (4.23-3.38, ΔDAS = -0.85) and CRP (1.70-0.74 mg/dL, ΔCRP = -0.96). Our newly developed method for measurement of gelatin-degrading activity in synovial fluid from RA patients is highly practicable and useful for predicting the effect of ETN therapy. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Disseminated cutaneous sporotrichosis.

PubMed

Chang, Shurong; Hersh, Andrew M; Naughton, Greg; Mullins, Kevin; Fung, Maxwell A; Sharon, Victoria R

2013-11-15

The dimorphic fungus Sporothrix schenckii commonly causes localized cutaneous disease with lymphocutaneous distribution. However, disseminated sporotrichosis occurs predominantly in immunocompromised patients. We report a case of disseminated cutaneous sporotrichosis in a patient with newly diagnosed HIV with a CD4 count of 208. The patient presented with multiple cutaneous and subcutaneous nodules as well as fever and malaise. Tissue culture and skin biopsy confirmed the diagnosis of sporotrichosis. He was started on itraconazole 200mg twice a day with rapid resolution of fever along with cessation of the development of new lesions.

Distinct expression pattern of IFN-alpha and TNF-alpha in juvenile idiopathic arthritis synovial tissue.

PubMed

Gattorno, M; Chicha, L; Gregorio, A; Ferlito, F; Rossi, F; Jarrossay, D; Lanzavecchia, A; Martini, A; Manz, M G

2007-04-01

Recent laboratory and clinical data suggest that two prototype autoimmune diseases, systemic lupus erythematosus and rheumatoid arthritis are mainly driven by distinct cytokines, interferon (IFN)-alpha and tumour necrosis factor (TNF)-alpha, respectively. We here investigated the presence and characteristics of natural type I IFN-producing cells (IPCs), as well as IFN-alpha and TNF-alpha expression at sites of inflammation in juvenile idiopathic arthritis (JIA). Peripheral blood (PB) and synovial fluid (SF) mononuclear cells (MNCs) (n = 25 each) from JIA patients with active disease were studied. IPCs were identified as BCDA-2(+)CD123(+)HLA-DR(+)CD45RA(+) cells, and dendritic cells (DCs) as CD11c(+)CD14(-/low)lin(-) cells by flow cytometry. IPCs and DCs were analysed for Toll-like receptor-7 and -9 mRNA expression by real-time polymerase chain reaction. IFN-alpha was measured by enzyme-linked immunosorbent assay in serum, SF and in supernatants of influenza virus-infected, cultured IPCs. Synovial tissues of n = 6 additional JIA patients were analysed by immunohistochemistry using mAbs against CD123, IFN-alpha, TNF-alpha, CD3, CD19 and CD138. IPCs were enriched in SF MNCs compared with PB MNCs in all JIA patients. Influenza-induced, but no spontaneous IFN-alpha release was detected from SF IPCs, and serum and SF IFN-alpha levels were not elevated. Nonetheless, in synovial tissue IFN-alpha producing cells accumulated at inflammatory lymph-follicular-like structures, while TNF-alpha producing cells were mostly found at the lining and sublining layers. These data suggest that besides TNF-alpha-expressing cells, IFN-alpha-producing IPCs are involved in initiation, maintenance or regulation of the inflammatory response in JIA.

Potential protein targets of the peptidylarginine deiminase 2 and peptidylarginine deiminase 4 enzymes in rheumatoid synovial tissue and its possible meaning

PubMed Central

Badillo-Soto, Martha Adriana; Rodríguez-Rodríguez, Mayra; Pérez-Pérez, María Elena; Daza-Benitez, Leonel; Bollain-y-Goytia, Juan José; Carrillo-Jiménez, Miguel Angel; Avalos-Díaz, Esperanza; Herrera-Esparza, Rafael

2016-01-01

Objective The molecular mechanism of citrullination involves the calcium-dependent peptidylarginine deiminase (PAD) family of enzymes. These enzymes induce a stereochemical modification of normal proteins and transform them into autoantigens, which in rheumatoid arthritis trigger a complex cascade of joint inflammatory events followed by chronic synovitis, pannus formation, and finally, cartilage destruction. By hypothesizing that PAD2 and PAD4 enzymes produce autoantigens, we investigated five possible synovial protein targets of PAD enzymes. Material and Methods We measured PAD2, PAD4, and citrullinated proteins in 10 rheumatoid and 10 osteoarthritis synovial biopsies and then assessed the post-translational modifications of fibrinogen, cytokeratin, tubulin, IgG, and vimentin proteins using a double-fluorescence assay with specific antibodies and an affinity-purified anti-citrullinated peptide (CCP) antibody. The degree of co-localization was analyzed, and statistical significance was determined by ANOVA, Fisher’s exact test, and regression analysis. Results The principal results of this study demonstrated that citrullinated proteins, such as fibrinogen, IgG, and other probed proteins, were targets of PAD2 and PAD4 activity in rheumatoid synovial biopsies, whereas osteoarthritis biopsies were negative for this enzyme (p<0.0001). An analysis of citrullination sites using the UniProtKB/Swiss-Prot data bank predicts that the secondary structure of the analyzed proteins displays most of the sites for citrullination; a discussion regarding its possible meaning in terms of pathogenesis is made. Conclusion Our results support the conclusion that the synovial citrullination of proteins is PAD2 and PAD4 dependent. Furthermore, there is a collection of candidate proteins that can be citrullinated. PMID:27708970

45 CFR 1388.7 - Program criteria-dissemination.

Code of Federal Regulations, 2013 CFR

2013-10-01

... contributes to the development of new knowledge. Dissemination activities promote the independence... best practices. (c) Specific target audiences must be identified for dissemination activities and... Affiliated Programs, and State service systems to disseminate information to target audiences. (e) The...

45 CFR 1388.7 - Program criteria-dissemination.

Code of Federal Regulations, 2011 CFR

2011-10-01

... contributes to the development of new knowledge. Dissemination activities promote the independence... best practices. (c) Specific target audiences must be identified for dissemination activities and... Affiliated Programs, and State service systems to disseminate information to target audiences. (e) The...

45 CFR 1388.7 - Program criteria-dissemination.

Code of Federal Regulations, 2014 CFR

2014-10-01

... contributes to the development of new knowledge. Dissemination activities promote the independence... best practices. (c) Specific target audiences must be identified for dissemination activities and... Affiliated Programs, and State service systems to disseminate information to target audiences. (e) The...

45 CFR 1388.7 - Program criteria-dissemination.

Code of Federal Regulations, 2012 CFR

2012-10-01

... contributes to the development of new knowledge. Dissemination activities promote the independence... best practices. (c) Specific target audiences must be identified for dissemination activities and... Affiliated Programs, and State service systems to disseminate information to target audiences. (e) The...

Intra-abdominal primary monophasic synovial sarcoma with hemangiopericytoma-like areas.

PubMed

Rao, Lakshmi; Jaiprakash, Padmapriya; Palankar, Nagaraj; Gowda, Vinay

2013-01-01

We report a case of retroperitoneal intra-abdominal primary monophasic synovial sarcoma (SS) with hemangiopericytomatous (HPC) pattern in a 25-year-old male arising from the triangular ligament on the superior surface of liver encasing the inferior vena cava (IVC) and masquerading as a hepatic tumor. A large heterogeneously enhancing, well defined, lobulated, exophytic lesion was seen involving segment VIII of the liver with foci of calcification in the periphery. A biopsy, followed by total resection of the tumor, showed a spindle cell sarcoma with HPC pattern, which was consistent with monophasic SS on histology and immunohistochemistry. The unusual clinical presentation, radiology, pathology, and differential diagnosis will be discussed in detail.

34 CFR 75.192 - Dissemination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... of the Secretary, Department of Education DIRECT GRANT PROGRAMS How To Apply for a Grant Development of Curricula Or Instructional Materials § 75.192 Dissemination. If an applicant proposes to publish and disseminate curricula or instructional materials under a grant, the applicant shall include an...

34 CFR 75.192 - Dissemination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... of the Secretary, Department of Education DIRECT GRANT PROGRAMS How To Apply for a Grant Development of Curricula Or Instructional Materials § 75.192 Dissemination. If an applicant proposes to publish and disseminate curricula or instructional materials under a grant, the applicant shall include an...

Synovial Hemangioma of the Knee Management and Excellent Outcome 2 Years after Arthroscopic Synovectomy in a 25-year-old Male with a 20-year History.

PubMed

Bawa, Akshdeep Singh; Garg, Rajnish; Bhatnagar, Kaneeka; Singal, Shekhar

2017-01-01

Synovial hemangioma is a rare condition with <200 published case reports in world literature and is frequently misdiagnosed, leading to diagnostic delay of many years. This delay is even more significant if the patient comes from a rural background with a dearth of medical facilities in the area. This case had a lag of nearly 20 years from the time of onset of symptoms and the required management which is the maximum reported for any synovial hemangioma since most of them have been found and treated in adolescents. We present a case of an atypical synovial hemangioma in a 25-year-old Indian male from a poor socioeconomic background with a delay of 20 years who had both recurrent knee effusions and long-standing knee pain but kept ignoring his symptoms. It was managed by arthroscopic synovectomy. The patient reported to us after 2 years after the surgery with a painless knee and full range of movement. Synovial hemangioma mostly affects the knee joint, showing recurrent bloody effusions without a history of trauma. If there are no intermittent effusions, the diagnosis will be even more difficult. In cases of non-specific symptoms and long-standing knee pain of many years, the diagnosis of a synovial hemangioma should also be considered. In this particular case, magnetic resonance imaging was used to evaluate the patient after the plain radiographs and showed characteristic lace-like or linear patterns. Diagnostic arthroscopy and surgical excision were done in the same sitting, and biopsy was sent to the histopathology laboratory which confirmed our diagnosis. Although this patient had the disease since 20 years and presented late, he had little degeneration of cartilage at the time of arthroscopy. The functional outcome at 2-year follow-up was excellent, and he had no disability, effusion and was pain free.

Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

PubMed

Knych, Heather K; Harrison, Linda M; White, Alexandria; McKemie, Daniel S

2016-01-01

The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse. Copyright © 2015 John Wiley & Sons, Ltd.

Factors influencing message dissemination through social media

NASA Astrophysics Data System (ADS)

Zheng, Zeyu; Yang, Huancheng; Fu, Yang; Fu, Dianzheng; Podobnik, Boris; Stanley, H. Eugene

2018-06-01

Online social networks strongly impact our daily lives. An internet user (a "Netizen") wants messages to be efficiently disseminated. The susceptible-infected-recovered (SIR) dissemination model is the traditional tool for exploring the spreading mechanism of information diffusion. We here test our SIR-based dissemination model on open and real-world data collected from Twitter. We locate and identify phase transitions in the message dissemination process. We find that message content is a stronger factor than the popularity of the sender. We also find that the probability that a message will be forwarded has a threshold that affects its ability to spread, and when the probability is above the threshold the message quickly achieves mass dissemination.

Creating new realities: program development and dissemination.

PubMed Central

Fixsen, D L; Blase, K A

1993-01-01

Program development and dissemination in human services present challenges and opportunities for social scientists. Over the past 27 years the Teaching-Family Model of group home treatment has moved from prototype development to widespread dissemination across North America. Reviewing concepts in industry related to product development and dissemination, the application of these concepts to a human services delivery system, and program replication and dissemination data offer information about how innovative human services can be widely adapted and adopted. PMID:8307838

34 CFR 75.192 - Dissemination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 34 Education 1 2014-07-01 2014-07-01 false Dissemination. 75.192 Section 75.192 Education Office... of Curricula Or Instructional Materials § 75.192 Dissemination. If an applicant proposes to publish... curricula or materials were developed. (Authority: 20 U.S.C. 1221e-3 and 3474) ...

Correlation of prostaglandin E2 concentrations in synovial fluid with ground reaction forces and clinical variables for pain or inflammation in dogs with osteoarthritis induced by transection of the cranial cruciate ligament.

PubMed

Trumble, Troy N; Billinghurst, R Clark; McIlwraith, C Wayne

2004-09-01

To evaluate the temporal pattern of prostaglandin (PG) E2 concentrations in synovial fluid after transection of the cranial cruciate ligament (CCL) in dogs and to correlate PGE2 concentrations with ground reaction forces and subjective clinical variables for lameness or pain. 19 purpose-bred adult male Walker Hounds. Force plate measurements, subjective clinical analysis of pain or lameness, and samples of synovial fluid were obtained before (baseline) and at various time points after arthroscopic transection of the right CCL. Concentrations of PGE2 were measured in synovial fluid samples, and the PGE2 concentrations were correlated with ground reaction forces and clinical variables. The PGE2 concentration increased significantly above the baseline value throughout the entire study, peaking 14 days after transection. Peak vertical force and vertical impulse significantly decreased by day 14 after transection, followed by an increase over time without returning to baseline values. All clinical variables (eg, lameness, degree of weight bearing, joint extension, cumulative pain score, effusion score, and total protein content of synovial fluid, except for WBC count in synovial fluid) increased significantly above baseline values. Significant negative correlations were detected between PGE2 concentrations and peak vertical force (r, -0.5720) and vertical impulse (r, -0.4618), and significant positive correlations were detected between PGE2 concentrations and the subjective lameness score (r, 0.5016) and effusion score (r, 0.6817). Assessment of the acute inflammatory process by measurement of PGE2 concentrations in synovial fluid may be correlated with the amount of pain or lameness in dogs.

10 CFR 470.20 - Dissemination of information.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 3 2010-01-01 2010-01-01 false Dissemination of information. 470.20 Section 470.20 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION APPROPRIATE TECHNOLOGY SMALL GRANTS PROGRAM § 470.20 Dissemination of information. DOE shall disseminate to the public, in an appropriate manner, information of the...

10 CFR 470.20 - Dissemination of information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 3 2013-01-01 2013-01-01 false Dissemination of information. 470.20 Section 470.20 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION APPROPRIATE TECHNOLOGY SMALL GRANTS PROGRAM § 470.20 Dissemination of information. DOE shall disseminate to the public, in an appropriate manner, information of the...

10 CFR 470.20 - Dissemination of information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 3 2011-01-01 2011-01-01 false Dissemination of information. 470.20 Section 470.20 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION APPROPRIATE TECHNOLOGY SMALL GRANTS PROGRAM § 470.20 Dissemination of information. DOE shall disseminate to the public, in an appropriate manner, information of the...

10 CFR 470.20 - Dissemination of information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 3 2012-01-01 2012-01-01 false Dissemination of information. 470.20 Section 470.20 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION APPROPRIATE TECHNOLOGY SMALL GRANTS PROGRAM § 470.20 Dissemination of information. DOE shall disseminate to the public, in an appropriate manner, information of the...

10 CFR 470.20 - Dissemination of information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 3 2014-01-01 2014-01-01 false Dissemination of information. 470.20 Section 470.20 Energy DEPARTMENT OF ENERGY ENERGY CONSERVATION APPROPRIATE TECHNOLOGY SMALL GRANTS PROGRAM § 470.20 Dissemination of information. DOE shall disseminate to the public, in an appropriate manner, information of the...

10 CFR 605.20 - Dissemination of results.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Dissemination of results. 605.20 Section 605.20 Energy... PROGRAM § 605.20 Dissemination of results. (a) Recipients are encouraged to disseminate project results..., the reports resulting from awards. (b) DOE may waive progress reporting requirements set forth in...

10 CFR 605.20 - Dissemination of results.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Dissemination of results. 605.20 Section 605.20 Energy... PROGRAM § 605.20 Dissemination of results. (a) Recipients are encouraged to disseminate project results..., the reports resulting from awards. (b) DOE may waive progress reporting requirements set forth in...

10 CFR 605.20 - Dissemination of results.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Dissemination of results. 605.20 Section 605.20 Energy... PROGRAM § 605.20 Dissemination of results. (a) Recipients are encouraged to disseminate project results..., the reports resulting from awards. (b) DOE may waive progress reporting requirements set forth in...

10 CFR 605.20 - Dissemination of results.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Dissemination of results. 605.20 Section 605.20 Energy... PROGRAM § 605.20 Dissemination of results. (a) Recipients are encouraged to disseminate project results..., the reports resulting from awards. (b) DOE may waive progress reporting requirements set forth in...

10 CFR 605.20 - Dissemination of results.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Dissemination of results. 605.20 Section 605.20 Energy... PROGRAM § 605.20 Dissemination of results. (a) Recipients are encouraged to disseminate project results..., the reports resulting from awards. (b) DOE may waive progress reporting requirements set forth in...

Analysis of the levels of endotoxin and β-d-glucan in the synovial fluid of hemodialysis patients.

PubMed

Shiota, E; Maekawa, M; Kono, T

2001-12-01

Abstract We analyzed the levels of endotoxin and β-d-glucan, which possibly induce cytokine production, in the synovial fluid of patients on long-term hemodialysis and compared the results to those in patients with osteoarthritis and rheumatoid arthritis. We studied 42 knees in 42 hemodialysis patients, 21 in 21 osteoarthritis patients, and 26 in 26 rheumatoid arthritis patients. The mean ages were 60.7, 63.2, and 59.7 years, respectively. The duration of hemodialysis in the long-term hemodialysis group averaged 14.0 years. The concentrations of endotoxin and β-d-glucan in the synovial fluid of these three groups were measured. The concentration of endotoxin was the same in the three groups. However, the concentration of β-d-glucan was significantly higher in long-term hemodialysis patients. This finding suggests that β-d-glucan may have some relation to the pathogenesis of the synovitis which exists in the hydrarthrosis of long-term hemodialysis patients.

10 CFR 602.18 - Dissemination of results.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Dissemination of results. 602.18 Section 602.18 Energy... ASSISTANCE PROGRAM § 602.18 Dissemination of results. (a) Recipients are encouraged to disseminate research results promptly. DOE reserves the right to utilize, and have others utilize to the extent it deems...

10 CFR 602.18 - Dissemination of results.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Dissemination of results. 602.18 Section 602.18 Energy... ASSISTANCE PROGRAM § 602.18 Dissemination of results. (a) Recipients are encouraged to disseminate research results promptly. DOE reserves the right to utilize, and have others utilize to the extent it deems...

10 CFR 602.18 - Dissemination of results.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Dissemination of results. 602.18 Section 602.18 Energy... ASSISTANCE PROGRAM § 602.18 Dissemination of results. (a) Recipients are encouraged to disseminate research results promptly. DOE reserves the right to utilize, and have others utilize to the extent it deems...

10 CFR 602.18 - Dissemination of results.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Dissemination of results. 602.18 Section 602.18 Energy... ASSISTANCE PROGRAM § 602.18 Dissemination of results. (a) Recipients are encouraged to disseminate research results promptly. DOE reserves the right to utilize, and have others utilize to the extent it deems...

10 CFR 602.18 - Dissemination of results.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Dissemination of results. 602.18 Section 602.18 Energy... ASSISTANCE PROGRAM § 602.18 Dissemination of results. (a) Recipients are encouraged to disseminate research results promptly. DOE reserves the right to utilize, and have others utilize to the extent it deems...

Dissemination of Information from Home Economics Research.

ERIC Educational Resources Information Center

Johnson, Janet M.

1984-01-01

Describes several methods for disseminating research results and makes the following recommendations: (1) study the effectiveness of various methods, (2) consider popular media as a vehicle, (3) plan dissemination at the beginning of the project, (4) define a network for dissemination in the proposal, and (5) follow effective communication models.…

Toward understanding the role of cartilage particulates in synovial inflammation.

PubMed

Silverstein, A M; Stefani, R M; Sobczak, E; Tong, E L; Attur, M G; Shah, R P; Bulinski, J C; Ateshian, G A; Hung, C T

2017-08-01

Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium. In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy. Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups. The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Tofacitinib regulates synovial inflammation in psoriatic arthritis, inhibiting STAT activation and induction of negative feedback inhibitors

PubMed Central

Gao, W; McGarry, T; Orr, C; McCormick, J; Veale, D J; Fearon, U

2016-01-01

Background Psoriatic arthritis (PsA) is a chronic inflammatory disease, characterised by synovitis and destruction of articular cartilage/bone. Janus-kinase and signal transducer and activator of transcription (JAK-STAT) signalling pathway is implicated in the pathogenesis of PsA. Objectives To examine the effect of tofacitinib (JAK inhibitor) on proinflammatory mechanisms in PsA. Methods Primary PsA synovial fibroblasts (PsAFLS) and ex vivo PsA synovial explants were cultured with tofacitinib (1 µM). PhosphoSTAT3 (pSTAT3), phosphoSTAT1 (pSTAT1), suppressor of cytokine signaling-3 (SOCS3), protein inhibitor of activated Stat3 (PIAS3) and nuclear factor kappa B cells (NFκBp65) were quantified by western blot. The effect of tofacitinib on PsAFLS migration, invasion, Matrigel network formation and matrix metallopeptidase (MMP)2/9 was quantified by invasion/migration assays and zymography. Interleukin (IL)-6, IL-8, IFN-gamma-inducible protein 10 (IP-10) monocyte chemoattractant protein (MCP)-1, IL-17, IL-10, MMP3 and tissue inhibitor of metalloproteinases 3 (TIMP3) were assessed by ELISA. Results Tofacitinib significantly decreased pSTAT3, pSTAT1, NFκBp65 and induced SOCS3 and PIAS3 expression in PsAFLS and synovial explant cultures (p<0.05). Functionally, PsAFLS invasion, network formation and migration were inhibited by tofacitinib (all p<0.05). In PsA explant, tofacitinib significantly decreased spontaneous secretion of IL-6, IL-8, MCP-1, MMP9/MMP2, MMP3 (all p<0.05) and decreased the MMP3/TIMP3 ratio (p<0.05), with no effect observed for IP-10 or IL-10. Conclusions This study further supports JAK-STAT inhibition as a therapeutic target for the treatment of PsA. PMID:26353790

Synovial fluid proteomics in the pursuit of arthritis mediators: An evolving field of novel biomarker discovery.

PubMed

Mahendran, Shalini M; Oikonomopoulou, Katerina; Diamandis, Eleftherios P; Chandran, Vinod

Synovial fluid (SF) is a protein-rich fluid produced into the joint cavity by cells of the synovial membrane. Due to its direct contact with articular cartilage, surfaces of the bone, and the synoviocytes of the inner membrane, it provides a promising reflection of the biochemical state of the joint under varying physiological and pathophysiological conditions. This property of SF has been exploited within numerous studies in search of unique biomarkers of joint pathologies with the ultimate goal of developing minimally invasive clinical assays to detect and/or monitor disease states. Several proteomic methodologies have been employed to mine the SF proteome. From elementary immunoassays to high-throughput analyses using mass spectrometry-based techniques, each has demonstrated distinct advantages and disadvantages in the identification and quantification of SF proteins. This review will explore the role of SF in the elucidation of the arthritis proteome and the extent to which high-throughput techniques have facilitated the discovery and validation of protein biomarkers from osteoarthritis (OA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) patients.

Histopathological Analysis of PEEK Wear Particle Effects on the Synovial Tissue of Patients

PubMed Central

Jansson, V.; Giurea, A.

2016-01-01

Introduction. Increasing interest developed in the use of carbon-fiber-reinforced-poly-ether-ether-ketones (CFR-PEEK) as an alternative bearing material in knee arthroplasty. The effects of CFR-PEEK wear in in vitro and animal studies are controversially discussed, as there are no data available concerning human tissue. The aim of this study was to analyze human tissue containing CFR-PEEK as well as UHMWPE wear debris. The authors hypothesized no difference between the used biomaterials. Methods and Materials. In 10 patients during knee revision surgery of a rotating-hinge-knee-implant-design, synovial tissue samples were achieved (tibial inserts: UHMWPE; bushings and flanges: CFR-PEEK). One additional patient received revision surgery without any PEEK components as a control. The tissue was paraffin-embedded, sliced into 2 μm thick sections, and stained with hematoxylin and eosin in a standard process. A modified panoptical staining was also done. Results. A “wear-type” reaction was seen in the testing and the control group. In all samples, the UHMWPE particles were scattered in the tissue or incorporated in giant cells. CFR-PEEK particles were seen as conglomerates and only could be found next to vessels. CFR-PEEK particles showed no giant-cell reactions. In conclusion, the hypothesis has to be rejected. UHMWPE and PEEK showed a different scatter-behavior in human synovial tissue. PMID:27766256

Fluorescence and UV-vis Spectroscopy of Synovial Fluids

NASA Astrophysics Data System (ADS)

Pinti, Marie J.; Stojilovic, Nenad; Kovacik, Mark W.

2009-10-01

Total joint arthroplasty involves replacing the worn cartilaginous surfaces of the joint with man-made materials that are designed to be biocompatible and to withstand mechanical stresses. Commonly these bearing materials consist of metallic alloys (TiAlV or CoCrMo) and UHMWPE. Following joint arthroplasty, the normal generation of micro-metallic wear debris particles that dislodge from the prosthesis has been shown to cause inflammatory aseptic osteolysis (bone loss) that ultimately results in the failure of the implant. Here we report our results on the novel use of Fluorescence and UV-vis spectroscopy to investigate the metallic content of synovial fluid specimens taken from postoperative total knee arthroplasties. Preliminary finding showed presence of alumina and chromium is some specimens. The ability to detect and monitor the wear rate of these implants could have far reaching implications in the prevention of metallic wear-debris induced osteolysis and impending implant failure.

The entrapment of corrosion products from CoCr implant alloys in the deposits of calcium phosphate: a comparison of serum, synovial fluid, albumin, EDTA, and water.

PubMed

Lewis, A C; Kilburn, M R; Heard, P J; Scott, T B; Hallam, K R; Allen, G C; Learmonth, I D

2006-08-01

Physical wear of orthopedic implants is inevitable. CoCr alloy samples, typically used in joint reconstruction, corrode rapidly after removal of the protective oxide layer. The behavior of CoCr pellets immersed in human serum, foetal bovine serum (FBS), synovial fluid, albumin in phosphate-buffered saline (PBS), EDTA in PBS, and water were studied using X-ray Photoelectron Spectroscopy (XPS) and Time-of-Flight Secondary Ion Mass Spectroscopy (ToF-SIMS). The difference in the corrosive nature of human serum, water, albumin in PBS and synovial fluid after 5 days of immersion was highlighted by the oxide layer, which was respectively 15, 3.5, 1.5, and 1.5 nm thick. The thickness of an additional calcium phosphate deposit from human serum and synovial fluid was 40 and 2 nm, respectively. Co and Cr ions migrated from the bulk metal surface and were trapped in this deposit by the phosphate anion. This may account for the composition of wear debris from CoCr orthopedic implants, which is known to consist predominantly of hydroxy-phosphate compounds. Known components of synovial fluid including proteoglycans, pyrophosphates, phospholipids, lubricin, and superficial zone protein (SZP), have been identified as possible causes for the lack of significant calcium phosphate deposition in this environment. Circulation of these compounds around the whole implant may inhibit calcium phosphate deposition.

Summary - National Dissemination and the Five Target States, Part 3, Final Report for Phase II--Dissemination, Rural Shared Services.

ERIC Educational Resources Information Center

Northern Montana Coll., Havre.

The dissemination phase (Phase II) of the Rural Shared Services Project is reported in this document. Efforts of the dissemination phase were concentrated in 5 target states: Vermont, Georgia, Wyoming, Montana, and New Mexico; national dissemination was limited to attendance at national conferences, the U. S. Office of Education PREP materials for…

Biodynamic Performance of Hyaluronic Acid versus Synovial fluid of the Knee for Osteoarthritic Therapy

PubMed Central

Corvelli, Michael; Che, Bernadette; Saeui, Christopher; Singh, Anirudha; Elisseeff, Jennifer

2015-01-01

Hyaluronic acid (HA), a natural biomaterial present in healthy joints but depleted in osteoarthritis (OA), has been employed clinically to provide symptomatic relief of joint pain. Joint movement combined with a reduced joint lubrication in osteoarthritic knees can result in increased wear and tear, chondrocyte apoptosis, and inflammation, leading to cascading cartilage deterioration. Therefore, development of an appropriate cartilage model and evaluation for its friction properties with potential lubricants in different conditions is necessary, which can closely resemble a mechanically induced OA cartilage. Additionally, the comparison of different models with and without endogenous lubricating surface zone proteins, such as PRG4 promotes a well-rounded understanding of cartilage lubrication. In this study, we present our findings on the lubricating effects of HA on different articular cartilage model surfaces in comparison to synovial fluid, a physiological lubricating biomaterial. The mechanical testings data demonstrated that HA reduced average static and kinetic friction coefficient values of the cartilage samples by 75% and 70%, respectively. Furthermore, HA mimicked the friction characteristics of freshly harvested natural synovial fluid throughout all tested and modeled OA conditions with no statistically significant difference. These characteristics led us to exclusively identify HA as an effective boundary layer lubricant in the technology that we develop to treat OA [Singh et al. 2104]. PMID:25858258

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways

PubMed Central

Wechalekar, Mihir D.; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M.; Smith, Malcolm D.; Nagpal, Sunil

2017-01-01

Objectives This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Methods Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Results Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. Conclusions We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission. PMID:28863153

Triple DMARD treatment in early rheumatoid arthritis modulates synovial T cell activation and plasmablast/plasma cell differentiation pathways.

PubMed

Walsh, Alice M; Wechalekar, Mihir D; Guo, Yanxia; Yin, Xuefeng; Weedon, Helen; Proudman, Susanna M; Smith, Malcolm D; Nagpal, Sunil

2017-01-01

This study sought to investigate the genome-wide transcriptional effects of a combination of disease modifying anti-rheumatic drugs (tDMARD; methotrexate, sulfasalazine and hydroxychloroquine) in synovial tissues obtained from early rheumatoid arthritis (RA) patients. While combination DMARD strategies have been investigated for clinical efficacy, very little data exists on the potential molecular mechanism of action. We hypothesized that tDMARD would impact multiple biological pathways, but the specific pathways were unknown. Paired synovial biopsy samples from early RA patients before and after 6 months of tDMARD therapy were collected by arthroscopy (n = 19). These biopsies as well as those from subjects with normal synovium (n = 28) were profiled by total RNA sequencing. Large differences in gene expression between RA and control biopsies (over 5000 genes) were identified. Despite clinical efficacy, the expression of a restricted set of less than 300 genes was reversed after 6 months of treatment. Many genes remained elevated, even in patients who achieved low disease activity. Interestingly, tDMARD downregulated genes included those involved in T cell activation and signaling and plasmablast/plasma cell differentiation and function. We have identified transcriptomic signatures that characterize synovial tissue from RA patients with early disease. Analysis after 6 months of tDMARD treatment highlight consistent alterations in expression of genes related to T cell activation and plasmablast/plasma cell differentiation. These results provide novel insight into the biology of early RA and the mechanism of tDMARD action and may help identify novel drug targets to improve rates of treatment-induced disease remission.

Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide

PubMed Central

Ríos, Diana L.; Pérez, Jorge E.

2017-01-01

Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over 96 h. Then, SMEs were harvested for RNA extraction and quantitative gene expression analysis by RT-qPCR for nuclear factor kappa B (NFκB), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25% and 50% Lc-PRG supernatants led to downregulation of NFκB, MMP-13, ADAMTS-4, COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50% concentration) induced downregulation of NFκB, MMP-13, ADAMTS-4, and COL1A1 and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the treatment of inflammatory arthropathies in horses because they have anti-inflammatory and anabolic effects in the synovial membrane. PMID:28761774

Proinflammatory and Anabolic Gene Expression Effects of Platelet-Rich Gel Supernatants on Equine Synovial Membrane Explants Challenged with Lipopolysaccharide.

PubMed

Carmona, Jorge U; Ríos, Diana L; López, Catalina; Álvarez, María E; Pérez, Jorge E

2017-01-01

Platelet-rich plasma (PRP) preparations are used in horses with osteoarthritis (OA). However, some controversies remain regarding the ideal concentration of platelets and leukocytes to produce an adequate anti-inflammatory and anabolic response in the synovial membrane. The aims of this study were to study the influence of leukoconcentrated platelet-rich gel (Lc-PRG) and leukoreduced platelet-rich gel (Lr-PRG) supernatants on the quantitative expression of some proinflammatory and anabolic genes in equine synovial membrane explants (SMEs) challenged with lipopolysaccharide (LPS). SMEs from six horses were cultured over 96 h. Then, SMEs were harvested for RNA extraction and quantitative gene expression analysis by RT-qPCR for nuclear factor kappa B (NF κ B), matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4), collagen type I alpha 1 (COL1A1), collagen type II alpha 1 (COL2A1), and cartilage oligomeric matrix protein (COMP). The 25% and 50% Lc-PRG supernatants led to downregulation of NF κ B, MMP-13, ADAMTS-4, COL1A1, COL2A1, and COMP in SMEs. Lr-PRG supernatants (particularly at the 50% concentration) induced downregulation of NF κ B, MMP-13, ADAMTS-4, and COL1A1 and upregulation of COL2A1 and COMP. Lr-PRG supernatants should be used for the treatment of inflammatory arthropathies in horses because they have anti-inflammatory and anabolic effects in the synovial membrane.

Myostatin Promotes Interleukin-1β Expression in Rheumatoid Arthritis Synovial Fibroblasts through Inhibition of miR-21-5p.

PubMed

Hu, Sung-Lin; Chang, An-Chen; Huang, Chien-Chung; Tsai, Chun-Hao; Lin, Cheng-Chieh; Tang, Chih-Hsin

2017-01-01

Rheumatoid arthritis (RA) is characterized by the infiltration of a number of pro-inflammatory cytokines into synovial fluid and patients with RA often develop joint destruction and deficits in muscle mass. The growth factor myostatin is a key regulator linking muscle mass and bone structure. We sought to determine whether myostatin regulates rheumatoid synovial fibroblast activity and inflammation in RA. We found that levels of myostatin and interleukin (IL)-1β (a key pro-inflammatory cytokine in RA) in synovial fluid from RA patients were overexpressed and positively correlated. In in vitro investigations, we found that myostatin dose-dependently regulated IL-1β expression through the ERK, JNK, and AP-1 signal-transduction pathways. Computational analysis confirmed that miR-21-5p directly targets the expression of the 3' untranslated region (3' UTR) of IL-1β. Treatment of cells with myostatin inhibited miR-21-5p expression and miR-21-5p mimic prevented myostatin-induced enhancement of IL-1β expression, showing an inverse correlation between miR-21-5p and IL-1β expression during myostatin treatment. We also found significantly increased paw swelling in an animal model of collagen-induced arthritis (CIA), compared with controls; immunohistochemistry staining revealed substantially higher levels of myostatin and IL-1β expression in CIA tissue. Our evidence indicates that myostatin regulates IL-1β production. Thus, targeting myostatin may represent a potential therapeutic target for RA.

Synovial CD4+ T-cell-derived GM-CSF supports the differentiation of an inflammatory dendritic cell population in rheumatoid arthritis

PubMed Central

Reynolds, G; Gibbon, J R; Pratt, A G; Wood, M J; Coady, D; Raftery, G; Lorenzi, A R; Gray, A; Filer, A; Buckley, C D; Haniffa, M A; Isaacs, J D; Hilkens, C M U

2016-01-01

Objective A population of synovial inflammatory dendritic cells (infDCs) has recently been identified in rheumatoid arthritis (RA) and is thought to be monocyte-derived. Here, we investigated the role and source of granulocyte macrophage-colony-stimulating factor (GM-CSF) in the differentiation of synovial infDC in RA. Methods Production of GM-CSF by peripheral blood (PB) and synovial fluid (SF) CD4+ T cells was assessed by ELISA and flow cytometry. In vitro CD4+ T-cell polarisation experiments were performed with T-cell activating CD2/CD3/CD28-coated beads in the absence or presence of pro-Th1 or pro-Th17 cytokines. CD1c+ DC and CD16+ macrophage subsets were flow-sorted and analysed morphologically and functionally (T-cell stimulatory/polarising capacity). Results RA-SF CD4+ T cells produced abundant GM-CSF upon stimulation and significantly more than RA-SF mononuclear cells depleted of CD4+ T cells. GM-CSF-producing T cells were significantly increased in RA-SF compared with non-RA inflammatory arthritis SF, active RA PB and healthy donor PB. GM-CSF-producing CD4+ T cells were expanded by Th1-promoting but not Th17-promoting conditions. Following coculture with RA-SF CD4+ T cells, but not healthy donor PB CD4+ T cells, a subpopulation of monocytes differentiated into CD1c+ infDC; a process dependent on GM-CSF. These infDC displayed potent alloproliferative capacity and enhanced GM-CSF, interleukin-17 and interferon-γ production by CD4+ T cells. InfDC with an identical phenotype to in vitro generated cells were significantly enriched in RA-SF compared with non-RA-SF/tissue/PB. Conclusions We demonstrate a therapeutically tractable feedback loop of GM-CSF secreted by RA synovial CD4+ T cells promoting the differentiation of infDC with potent capacity to induce GM-CSF-producing CD4+ T cells. PMID:25923217

Demonstration of the ability of a canine Lyme vaccine to reduce the incidence of histological synovial lesions following experimentally-induced canine Lyme borreliosis.

PubMed

Grosenbaugh, Deborah A; Rissi, Daniel R; Krimer, Paula M

2016-11-01

Lyme disease in dogs can be effectively prevented by vaccination against antigens expressed by the spirochete Borrelia burgdorferi during transmission by the tick vector Ixodes sp. Lyme vaccine efficacy has traditionally been based on indicators of infection following wild-caught tick challenge whereas most other types of vaccine are required to demonstrate protection from clinical signs of disease. In this vaccination-challenge study we sought to demonstrate the ability of a nonadjuvanted, outer surface protein A (OspA) vaccine to protect from infection and to prevent synovial lesions consistent with Borreliosis. Thirty, purpose-bred beagles were randomly divided into vaccinated and unvaccinated groups. The vaccinated group was administered two subcutaneous doses of a nonadjuvanted, purified, Borrelia burgdorferi OspA vaccine at a 21- day interval. Dogs were challenged by wild-caught, B. burgdorferi-infected ticks (Ixodes scapularis). Clinical signs, serology, Borrelia isolation and PCR evaluated antemortem vaccine efficacy. Postmortem histopathological analysis of synovial tissue was compared to antemortem infection status. Borreliosis was demonstrated by Borrelia isolation from skin biopsies in 13 out of 15 unvaccinated dogs. All unvaccinated dogs' Western blot profiles were consistent with infection. Two of 15 vaccinated dogs had at least one positive spirochete culture which cleared 91days post-challenge, and Western blot profiles were consistent with vaccination alone. No dogs, vaccinated or unvaccinated, exhibited clinical signs consistent with borreliosis. Based on a histopathological cumulative joint scoring system (CJS), all unvaccinated dogs had synovial lesions indicative of Lyme disease. Only one of the vaccinated dogs had a CJS that was greater than the statistical cut off score for the absence of synovial lesions. There was high correlation between clinical histopathology and spirochete isolation. Infection with B burgdorferi may produce inconsistent

Leptin enhances MMP-1, MMP-3 and MMP-13 production in human osteoarthritic cartilage and correlates with MMP-1 and MMP-3 in synovial fluid from OA patients.

PubMed

Koskinen, Anna; Vuolteenaho, Katriina; Nieminen, Riina; Moilanen, Teemu; Moilanen, Eeva

2011-01-01

In the present study, we investigated the role of adipocytokine leptin in the pathogenesis of osteoarthritis (OA) by measuring its effects on matrix metalloproteinase (MMP) production in human OA cartilage. In addition, the correlations between leptin and MMP concentrations in synovial fluid from OA patients were studied. Cartilage tissue obtained from leftover pieces of total knee replacement surgery from patients with OA was used in the experiments. Production of collagenases MMP-1, MMP-8 and MMP-13, and stromelysin-1 (MMP-3) in the cartilage was measured by immunoassay and the signalling pathways were explored by pharmacological means. In addition, synovial fluid samples were collected from 84 OA patients undergoing knee replacement surgery. The concentrations of leptin and MMPs in synovial fluid were measured by immunoassay. Leptin alone and in combination with IL-1β enhanced production of MMP-1, MMP-3, and MMP-13 in human OA cartilage, while MMP-8 concentrations remained undetectable. The effects of leptin on MMP-1, MMP-3 and MMP-13 production were mediated through transcription factor NF-κβ, and through protein kinase C and MAP kinase pathways. Interestingly, leptin concentrations in synovial fluid from OA patients correlated positively with MMP-3 (r=0.51, p<0.001) and MMP-1 (r=0.41, p<0.001) levels. To our knowledge, this is the first study to show that leptin up-regulates MMP-1 and MMP-3 production in human OA cartilage and correlates positively to MMP-1 and MMP-3 in synovial fluid from OA patients. The findings suggest that leptin has catabolic effects in OA joints by increasing MMP production in cartilage.

Effects of cranberry components on IL-1β-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

PubMed

Tipton, David A; Christian, James; Blumer, Adam

2016-08-01

Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1β (IL-1β) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1β-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1β (0.001-1nM)±NDM (25-250μg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. ANOVA and Scheffe's F procedure for post hoc comparisons. NDM did not affect cell viability but inhibited IL-1β stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-κB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1β+NDM. Cranberry NDM inhibition of IL-1β-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ. Copyright © 2016 Elsevier Ltd. All rights reserved.

48 CFR 2905.101 - Methods of disseminating information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information. 2905.101 Section 2905.101 Federal Acquisition Regulations System DEPARTMENT OF LABOR ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Dissemination of Information 2905.101 Methods of disseminating... dissemination of information concerning procurement actions. The Division of Acquisition Management Services...

Disseminated Geotrichum candidum infection.

PubMed Central

Kassamali, H; Anaissie, E; Ro, J; Rolston, K; Kantarjian, H; Fainstein, V; Bodey, G P

1987-01-01

The pathogenicity of the fungus Geotrichum candidum in humans has not been clearly defined. A patient with acute leukemia who developed a fatal disseminated G. candidum infection while neutropenic is described. At autopsy examination, this patient was misdiagnosed on the basis of histopathology as having disseminated candidiasis until G. candidum was isolated from postmortem culture specimens. The emergence of this organism as an occasional pathogen in leukemic patients is of interest and illustrates the importance of obtaining fungal cultures. There is a need for more effective drugs for antifungal prophylaxis and therapy. PMID:3477570

THE CATION CHANNEL TRPV2 IS A NEW SUPPRESSOR OF ARTHRITIS SEVERITY, JOINT DAMAGE AND SYNOVIAL FIBROBLAST INVASION

PubMed Central

Laragione, Teresina; Cheng, Kai F.; Tanner, Mark R.; He, Mingzhu; Beeton, Christine; Al-Abed, Yousef; Gulko, Pércio S.

2015-01-01

Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1β-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and synovial blood vessel numbers suggesting anti-angiogenic activity. In this first in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in arthritis. These new compounds have the potential to become new therapies for RA and other diseases associated with inflammation, invasion and angiogenesis. PMID:25869297

Kentucky Information Dissemination System. Fall Dissemination Conference Follow-Up.

ERIC Educational Resources Information Center

Kentucky State Dept. of Education, Frankfort. Office of Communication Services.

Describing a state conference on information dissemination held in November 1979 in Frankfort, Kentucky, this report contains conference materials and evaluations of the mini-seminars and awareness sessions conducted there. Materials include a final agenda, seminar and roundabout topics, a description of the Kentucky Department of Education…

48 CFR 2905.101 - Methods of disseminating information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 7 2012-10-01 2012-10-01 false Methods of disseminating information. 2905.101 Section 2905.101 Federal Acquisition Regulations System DEPARTMENT OF LABOR ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Dissemination of Information 2905.101 Methods of disseminating...

Cyclic movement stimulates hyaluronan secretion into the synovial cavity of rabbit joints

PubMed Central

Ingram, K R; Wann, A K T; Angel, C K; Coleman, P J; Levick, J R

2008-01-01

The novel hypothesis that the secretion of the joint lubricant hyaluronan (HA) is coupled to movement has implications for normal function and osteoarthritis, and was tested in the knee joints of anaesthetized rabbits. After washing out the endogenous synovial fluid HA (miscibility coefficient 0.4), secretion into the joint cavity was measured over 5 h in static joints and in passively cycled joints. The net static secretion rate (11.2 ± 0.7 μg h−1, mean ± s.e.m., n = 90) correlated with the variable endogenous HA mass (mean 367 ± 8 μg), with a normalized value of 3.4 ± 0.2 μg h−1 (100 μg)−1 . Cyclic joint movement approximately doubled the net HA secretion rate to 22.6 ± 1.2 μg h−1 (n = 77) and raised the normalized percentage to 5.9 ± 0.3 μg h−1 (100 μg)−1. Secretion was inhibited by 2-deoxyglucose and iodoacetate, confirming active secretion. The net accumulation rate underestimated true secretion rate due to some trans-synovial loss. HA turnover time (endogenous mass/secretion rate) was 17–30 h (static) to 8–15 h (moved) The results demonstrate for the first time that the active secretion of HA is coupled to joint usage. Movement–secretion coupling may protect joints against the damaging effects of repetitive joint use, replace HA lost during periods of immobility (overnight), and contribute to the clinical benefit of exercise therapy in moderate osteoarthritis. PMID:18202097

Optimal control of epidemic information dissemination over networks.

PubMed

Chen, Pin-Yu; Cheng, Shin-Ming; Chen, Kwang-Cheng

2014-12-01

Information dissemination control is of crucial importance to facilitate reliable and efficient data delivery, especially in networks consisting of time-varying links or heterogeneous links. Since the abstraction of information dissemination much resembles the spread of epidemics, epidemic models are utilized to characterize the collective dynamics of information dissemination over networks. From a systematic point of view, we aim to explore the optimal control policy for information dissemination given that the control capability is a function of its distribution time, which is a more realistic model in many applications. The main contributions of this paper are to provide an analytically tractable model for information dissemination over networks, to solve the optimal control signal distribution time for minimizing the accumulated network cost via dynamic programming, and to establish a parametric plug-in model for information dissemination control. In particular, we evaluate its performance in mobile and generalized social networks as typical examples.

Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial Joints

DTIC Science & Technology

2016-10-01

test whether the pathological accumulation of a specific substance found in joint fluid following an injury mediated altered synovial fluid...joint injury contributes to the development of post-traumatic OA and is due, in part, to the pathological accumulation of a...studies, SF samples will be analyzed for the suspected pathological substance as well as lubrication function. 3.b.ii. Aim 2b

Data dissemination using gossiping in wireless sensor networks

NASA Astrophysics Data System (ADS)

Medidi, Muralidhar; Ding, Jin; Medidi, Sirisha

2005-06-01

Disseminating data among sensors is a fundamental operation in energy-constrained wireless sensor networks. We present a gossip-based adaptive protocol for data dissemination to improve energy efficiency of this operation. To overcome the data implosion problems associated with dissemination operation, our protocol uses meta-data to name the data using high-level data descriptors and negotiation to eliminate redundant transmissions of duplicate data in the network. Further, we adapt the gossiping with data aggregation possibilities in sensor networks. We simulated our data dissemination protocol, and compared it to the SPIN protocol. We find that our protocol improves on the energy consumption by about 20% over others, while improving significantly over the data dissemination rate of gossiping.

The Effectiveness of Selected Dissemination Activities.

ERIC Educational Resources Information Center

Chapman, David W.; Johnson, Russell H.

1981-01-01

The dissemination activities through which college admissions officers heard about Project CHOICE, a three-year project to help colleges improve the information they provided to prospective students, were investigated. The study involved determining how well various dissemination methods (newsletter, journal articles, conference presentations,…

48 CFR 5.101 - Methods of disseminating information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Methods of disseminating... ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Dissemination of Information 5.101 Methods of disseminating... posted instead of a notice, the contracting officer may employ various methods of satisfying the...

Concentrations of tylvalosin and 3-O-acetyltylosin attained in the synovial fluid of swine after administration by oral gavage at 50 and 5 mg/kg.

PubMed

Canning, P; Bates, J; Hammen, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Karriker, L

2016-12-01

The objectives of this study were to determine the concentration of tylvalosin (TVN) and its metabolite, 3-O-acetyltylosin (3AT) in the synovial fluid of growing pigs when administered as a single bolus by oral gavage at target doses of 50 mg/kg (Trial 1) and 5 mg/kg (Trial 2). TVN is a water soluble macrolide antimicrobial used in swine production. The stability of the drug in synovial fluid samples stored at -70 °C up to 28 days was also evaluated in Trial 2. In Trial 1, eight pigs were randomly assigned to one of eight time points for euthanasia and synovial fluid collection: 0, 1, 2, 3, 4, 6, 9, 12 h postgavage. For Trial 2, 24 pigs were randomly allocated to one terminal collection time point at 0, 2, 4, 6, 8 or 10 h postgavage. Synovial fluid was analyzed to determine TVN and 3AT concentrations. TVN and 3AT were detected in Trial 1 at all time points, except 0 h. At 2 h postgavage for trial 2, the mean concentrations peaked at 31.17 ng/mL (95% CI: 18.62-52.16) for TVN and at 58.82 ng/mL (95% CI: 35.14-98.46) for 3AT. Storage duration did not impact TVN or 3AT concentrations (P-value 0.9732). © 2016 John Wiley & Sons Ltd.

Varus knee osteoarthritis: Elevated synovial CD15 counts correlate with inferior biomechanical properties of lateral-compartment cartilage.

PubMed

Koller, Ulrich; Waldstein, Wenzel; Krenn, Veit; Windhager, Reinhard; Boettner, Friedrich

2018-03-01

The study analyzed the influence of synovitis on the histological and biomechanical properties of lateral-compartment cartilage. In a prospective cohort study, 84 patients (100 knees) with varus deformity of the knee were included. Osteochondral samples from the distal lateral femur underwent biomechanical and histologic analysis. Synovial tissue was sampled for histological (chronic synovitis score) and immunohistochemical evaluation of the degree of synovitis. CD15 (neutrophils), Ki-67 (dividing cells), and CD68 (macrophages) were tested in all synovial samples. While the histological synovitis score did not correlate with the degree of cartilage degeneration (histological OARSI grades), both CD15 (r s  = 0.297, p = 0.006) and Ki-67 (r s  = 0.249, p = 0.023) correlated with histological OARSI grades. There was a weak negative correlation of CD15 with biomechanical properties of cartilage of the distal lateral femur (aggregate modulus (Ha): r s  = -0.125; p = 0.257; dynamic modulus (DM): r s  = -0.216; p = 0.048). No correlations were observed for Ki-67 and CD68. In addition, biomechanical properties were inferior in knees with a CD15 of >8/high power field compared to knees with a CD15 of ≤8/high power field (Ha: p = 0.031, d = 0.46; DM: p = 0.005, d = 0.68). The study demonstrates an association of increased inflammatory activity with advanced cartilage degeneration. Lateral-compartment cartilage in knees with elevated synovial CD15 counts has a reduced ability to withstand compressive loads. CD15 might serve as an indicator for inferior biomechanical cartilage properties. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:841-846, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Serum amyloid A isoforms in serum and synovial fluid from spontaneously diseased dogs with joint diseases or other conditions.

PubMed

Kjelgaard-Hansen, Mads; Christensen, Michelle B; Lee, Marcel H; Jensen, Asger L; Jacobsen, Stine

2007-06-15

Serum amyloid A (SAA) is a major acute phase protein in dogs. However, knowledge of qualitative properties of canine SAA and extent of its synthesis in extrahepatic tissues is limited. The aim of the study was to investigate expression of different SAA isoforms in serum and synovial fluid in samples obtained from dogs (n=16) suffering from different inflammatory or non-inflammatory conditions, which were either related or unrelated to joints. Expression of SAA isoforms was visualized by denaturing isoelectric focusing and Western blotting. Serum amyloid A was present in serum from all dogs with systemic inflammatory activity, and up to four major isoforms with apparent isoelectric points between 6.1 and 7.9 were identified. In synovial fluid from inflamed joints one or more highly alkaline SAA isoforms (with apparent isoelectric points above 9.3) were identified, with data suggesting local production of these isoforms in the canine inflamed joint.

Synovial hemangioma in an adult horse.

PubMed

Holzhausen, Lars; Nowak, Michael; Junginger, Johannes; Puff, Christina

2012-03-01

A 15-year-old gelding presented with a progressive lameness of the left forelimb of 2.5 months duration. Clinically, a dilation of the deep flexor tendon sheath with a firm elastic consistency and a pronounced tenderness was noted. Ultrasonically, a marked swelling of the flexor tendon sheath with an irregular density of the mesotendineum was observed. The white, firm material forming a nodular distension of the flexor tendon sheath with a diameter of approximately 1 cm was excised and sent for histopathological examination. Biopsies of the deep flexor tendon and corresponding tendon sheath were sent for histopathological evaluation. Histologically, the mass consisted of clefts and numerous anastomosing vascular channels extending between the collagen fibers of the deep flexor tendon. These capillary-like spaces were lined by neoplastic cells that were flattened to polygonal and contained few erythrocytes. There was 0 to 1 mitotic figure per 10 high power fields (400×). Immunohistochemically, the neoplastic cells stained positive for vimentin and factor VIII-related antigen. Adjacent to the neoplastic endothelial cells located pericytes expressed α-smooth muscle actin antigen. Based on the histopathological and immunohistochemical features, synovial hemangioma was diagnosed. One year after surgery, the horse has shown no lameness.

A spread willingness computing-based information dissemination model.

PubMed

Huang, Haojing; Cui, Zhiming; Zhang, Shukui

2014-01-01

This paper constructs a kind of spread willingness computing based on information dissemination model for social network. The model takes into account the impact of node degree and dissemination mechanism, combined with the complex network theory and dynamics of infectious diseases, and further establishes the dynamical evolution equations. Equations characterize the evolutionary relationship between different types of nodes with time. The spread willingness computing contains three factors which have impact on user's spread behavior: strength of the relationship between the nodes, views identity, and frequency of contact. Simulation results show that different degrees of nodes show the same trend in the network, and even if the degree of node is very small, there is likelihood of a large area of information dissemination. The weaker the relationship between nodes, the higher probability of views selection and the higher the frequency of contact with information so that information spreads rapidly and leads to a wide range of dissemination. As the dissemination probability and immune probability change, the speed of information dissemination is also changing accordingly. The studies meet social networking features and can help to master the behavior of users and understand and analyze characteristics of information dissemination in social network.

Massive subacromial-subdeltoid bursitis with rice bodies secondary to an orthopedic implant.

PubMed

Urruela, Adriana M; Rapp, Timothy B; Egol, Kenneth A

2012-09-01

Both early and late complications following open reduction and internal fixation of proximal humerus fractures have been reported extensively in the literature. Although orthopedic implants are known to cause irritation and inflammation, to our knowledge, this is the first case report to describe a patient with rice bodies secondary to an orthopedic implant. Although the etiology of rice bodies is unclear, histological studies reveal that they are composed of an inner amorphous core surrounded by collagen and fibrin. The differential diagnosis in this case included synovial chondromatosis, infection, and the formation of a malignant tumor. Additional imaging studies, such as magnetic resonance imaging, and more specific tests were necessary to differentiate the rice bodies due to bursitis versus neoplasm, prior to excision. The patient presented 5 years following open reduction and internal fixation of a displaced proximal humerus fracture, with swelling in the area of the previous surgical site. Examination revealed a large, painless tumor-like mass on the anterior aspect of the shoulder. The patient's chief concern was the unpleasant aesthetic of the mass; no pain was reported. Upon excision of the mass, the patient's full, painless range of motion returned.

48 CFR 5.101 - Methods of disseminating information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Methods of disseminating... ACQUISITION PLANNING PUBLICIZING CONTRACT ACTIONS Dissemination of Information 5.101 Methods of disseminating... various methods of satisfying the requirements of 5.207(c). For example, the contracting officer may meet...

Dissemination, redissemination and fiber life

NASA Technical Reports Server (NTRS)

Eiber, W.

1979-01-01

The technical background of dissemination of carbon fibers as well as the possibility of redissemination and fiber life are outlined. Plume spread and weather, measures of pollution and of damage potential, and parameters controlling dissemination patterns are among the topics discussed. It is shown that the redissemination rate off hard surfaces decreases with time and that fiber length decreases with time. Redissemination from vegetated land is shown to be insignificant.

Evaluation of Partial Transection versus Synovial Debridement of the ACL as Novel Canine Models for Management of ACL Injuries.

PubMed

Bozynski, Chantelle C; Kuroki, Keiichi; Stannard, James P; Smith, Patrick A; Stoker, Aaron M; Cook, Cristi R; Cook, James L

2015-10-01

A major hurdle in investigating important clinical questions in knee ligament treatment is a lack of valid translational animal models. This study characterizes the effects of partial transection versus synovial debridement of the anterior (cranial) cruciate ligament (ACL) in dogs. A total of 27 adult purpose-bred research hounds underwent surgery and were assessed over the following 8 weeks. Dogs were randomized into the following three ACL status groups: sham control (n = 9), intact ACL with synovial debridement (exposed ACL) (n = 9), and partial transection of the ACL (partial tear ACL) (n = 9). Dogs in the exposed ACL group and partial tear ACL group had significantly (p < 0.05) more severe lameness, pain, effusion, reduced function, and reduced comfortable range of motion compared with controls, with the partial tear ACL group being most severely affected. More severe ACL and whole-joint pathology, and radiographic scores for osteoarthritis were present in the partial tear ACL group compared with exposed and/or sham control group. On the basis of these findings, biologic components of ACL injury (exposed ACL) played a role in whole-joint inflammation, but the clinical and pathological effects were more severe when both biologic and biomechanical components were present (i.e., partial tear ACL). These novel canine models were successfully developed to evaluate partial transection versus synovial debridement of the ACL and these models will be used to evaluate treatment options for acute management of ACL injuries. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Identification of dendritic cells in the blood and synovial fluid of children with Juvenile Idiopathic Arthritis.

PubMed

Tabarkiewicz, Jacek; Postępski, Jacek; Olesińska, Edyta; Roliński, Jacek; Tuszkiewicz-Misztal, Ewa

2011-01-01

Childhood chronic arthritis of unknown etiology is known collectively as juvenile idiopathic arthritis (JIA) and consists of heterogeneous subtypes with unique clinical patterns of disease. JIA is the commonest rheumatic disease in children and may still result in significant disability, with joint deformity, growth impairment, and persistence of active arthritis into adulthood. Basic research is rather focused on rheumatoid arthritis, and this lead to small number of publications considering JIA. In this study we examine, by flow cytometry, the expression of dendritic cells (DCs) in the peripheral blood and synovial fluid of children with active JIA in a group of 220 patients. We reveal a significant decrease in the percentage of immature DCs in the blood of patients compared to control children. Surprisingly, we found higher percentages of mature circulating dendritic cells. Both populations of DCs, immature and mature, were accumulated in patients' synovial fluid. We also confirmed the presence of CD206+/CD209+ in JIA samples, which can represent a population of macrophages with dendritic cells morphology. Our results support the thesis that dendritic cells are crucial in the induction and maintenance of autoimmune response and local inflammation during juvenile idiopathic arthritis.

Increased levels of the 14-3-3 η and γ proteins in the synovial fluid of dogs with unilateral cranial cruciate ligament rupture.

PubMed

Sardari, Kamran; Chavez-Muñoz, Claudia; Kilani, Ruhangiz T; Schiller, Terri; Ghahary, Aziz

2011-10-01

The present study investigated whether the 14-3-3 η and γ proteins, which are potent matrix metalloprotease (MMP) stimulators, are detectable in the synovial fluid of dogs with cranial cruciate ligament rupture (CCLR). Synovial fluid samples from 7 dogs with unilateral CCLR and control samples from 4 dogs without a history of any joint inflammation or any other abnormalities underwent Western blot analysis for the 14-3-3 η, γ, and σ proteins as well as MMP-1 and MMP-3. Craniocaudal and lateral radiographic projections of the stifle joint were evaluated for the presence and severity of 13 specific radiographic markers of osteoarthritis and graded numerically. The Spearman method was used to detect any correlation between the 14-3-3-η level in the synovial fluid and the radiograph-based grade. The η isoform was present only in the samples from the dogs with CCLR. The levels of 14-3-3-γ, MMP-1, and MMP-3 were significantly higher in the samples from the dogs with CCLR than in the control samples (P < 0.05). However, there was no significant difference between the CCLR and control samples in the level of the σ isoform. The Spearman method showed a significant correlation between the 14-3-3-η level in the synovial fluid and the presence of either patellar osteophytes or lateral or medial (or both) condylar periarticular osteophytes (P < 0.05). The MMP stimulatory effect of the 14-3-3 η and γ isoforms may be the reason for the high levels of MMP-1 and MMP-3 observed. Thus, 14-3-3 proteins, especially the η isoform, may be important markers of osteoarthritis caused by CCLR.

Increased levels of the 14-3-3 η and γ proteins in the synovial fluid of dogs with unilateral cranial cruciate ligament rupture

PubMed Central

Sardari, Kamran; Chavez-Muñoz, Claudia; Kilani, Ruhangiz T.; Schiller, Terri; Ghahary, Aziz

2011-01-01

The present study investigated whether the 14-3-3 η and γ proteins, which are potent matrix metalloprotease (MMP) stimulators, are detectable in the synovial fluid of dogs with cranial cruciate ligament rupture (CCLR). Synovial fluid samples from 7 dogs with unilateral CCLR and control samples from 4 dogs without a history of any joint inflammation or any other abnormalities underwent Western blot analysis for the 14-3-3 η, γ, and σ proteins as well as MMP-1 and MMP-3. Craniocaudal and lateral radiographic projections of the stifle joint were evaluated for the presence and severity of 13 specific radiographic markers of osteoarthritis and graded numerically. The Spearman method was used to detect any correlation between the 14-3-3-η level in the synovial fluid and the radiograph-based grade. The η isoform was present only in the samples from the dogs with CCLR. The levels of 14-3-3-γ, MMP-1, and MMP-3 were significantly higher in the samples from the dogs with CCLR than in the control samples (P < 0.05). However, there was no significant difference between the CCLR and control samples in the level of the σ isoform. The Spearman method showed a significant correlation between the 14-3-3-η level in the synovial fluid and the presence of either patellar osteophytes or lateral or medial (or both) condylar periarticular osteophytes (P < 0.05). The MMP stimulatory effect of the 14-3-3 η and γ isoforms may be the reason for the high levels of MMP-1 and MMP-3 observed. Thus, 14-3-3 proteins, especially the η isoform, may be important markers of osteoarthritis caused by CCLR. PMID:22468024

Temperature-sensitive release of prostaglandin E₂ and diminished energy requirements in synovial tissue with postoperative cryotherapy: a prospective randomized study after knee arthroscopy.

PubMed

Stålman, Anders; Berglund, Lukas; Dungnerc, Elisabeth; Arner, Peter; Felländer-Tsai, Li

2011-11-02

Local external cooling of the surgical field after joint surgery is intended to enhance recovery and to facilitate the use of outpatient surgery by reducing pain and improving mobility. We hypothesized that the effects of postoperative cooling and compression after knee arthroscopy would be reflected in changes in the concentrations of metabolic and inflammatory markers in the synovial membrane. Forty otherwise healthy patients who were to undergo knee arthroscopy were included in the study, and half were randomized to receive postoperative cooling and compression. Microdialysis of the synovial membrane was performed postoperatively, and the concentrations of prostaglandin E₂ (PGE₂), glucose, lactate, glycerol, and glutamate as well as the ethanol exchange ratio (which indicates blood flow) were measured. The temperature of the knee was monitored, and postoperative pain was assessed by the patient with use of a visual analog scale, a numeric rating scale, and the need for rescue medication. Application of the cooling and compression device after knee arthroscopy significantly lowered the temperature in the operatively treated knee (as measured on the skin, within the joint capsule, and intra-articularly). The cooling and compression appeared to decrease inflammation, as indicated by a temperature-sensitive decrease in the PGE₂ concentration. The hypothermia also decreased the metabolic rate of the synovial tissue and thus decreased energy requirements, as shown by the stability of the lactate concentration over time despite the decreased blood flow that was indicated by the increasing ethanol exchange ratio. No effect of the compression and cooling on postoperative pain was detected. Local cryotherapy and compression after knee arthroscopy significantly lowered the temperature in the knee postoperatively, and the synovial PGE₂ concentration was correlated with the temperature. Since PGE₂ is a marker of pain and inflammation, the postoperative local

Effects of ACL Reconstructive Surgery on Temporal Variations of Cytokine Levels in Synovial Fluid

PubMed Central

Bigoni, Marco; Gandolla, Marta; Sacerdote, Paola; Piatti, Massimiliano; Castelnuovo, Alberto; Franchi, Silvia; Gorla, Massimo; Munegato, Daniele; Gaddi, Diego; Pedrocchi, Alessandra; Omeljaniuk, Robert J.; Locatelli, Vittorio; Torsello, Antonio

2016-01-01

Anterior cruciate ligament (ACL) reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24–72 hours of ACL rupture (acute), 1 month after injury immediately prior to surgery (presurgery), and 1 month thereafter (postsurgery). For comparison, a “control” group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β. PMID:27313403

Effects of ACL Reconstructive Surgery on Temporal Variations of Cytokine Levels in Synovial Fluid.

PubMed

Bigoni, Marco; Turati, Marco; Gandolla, Marta; Sacerdote, Paola; Piatti, Massimiliano; Castelnuovo, Alberto; Franchi, Silvia; Gorla, Massimo; Munegato, Daniele; Gaddi, Diego; Pedrocchi, Alessandra; Omeljaniuk, Robert J; Locatelli, Vittorio; Torsello, Antonio

2016-01-01

Anterior cruciate ligament (ACL) reconstruction restores knee stability but does not reduce the incidence of posttraumatic osteoarthritis induced by inflammatory cytokines. The aim of this research was to longitudinally measure IL-1β, IL-6, IL-8, IL-10, and TNF-α levels in patients subjected to ACL reconstruction using bone-patellar tendon-bone graft. Synovial fluid was collected within 24-72 hours of ACL rupture (acute), 1 month after injury immediately prior to surgery (presurgery), and 1 month thereafter (postsurgery). For comparison, a "control" group consisted of individuals presenting chronic ACL tears. Our results indicate that levels of IL-6, IL-8, and IL-10 vary significantly over time in reconstruction patients. In the acute phase, the levels of these cytokines in reconstruction patients were significantly greater than those in controls. In the presurgery phase, cytokine levels in reconstruction patients were reduced and comparable with those in controls. Finally, cytokine levels increased again with respect to control group in the postsurgery phase. The levels of IL-1β and TNF-α showed no temporal variation. Our data show that the history of an ACL injury, including trauma and reconstruction, has a significant impact on levels of IL-6, IL-8, and IL-10 in synovial fluid but does not affect levels of TNF-α and IL-1β.

Synovial fluid bupivacaine concentrations following single intra-articular injection in normal and osteoarthritic canine stifles.

PubMed

Barry, S L; Martinez, S A; Davies, N M; Remsberg, C M; Sayre, C L; Bachelez, A

2015-02-01

Intra-articular bupivacaine helps alleviate pain in animals receiving joint surgery, but its use has become controversial as ex vivo studies have illuminated the potential for chondrotoxicity. Such studies typically involve cell cultures incubated in solutions containing high bupivacaine concentrations for long durations. The aim of this study was to measure the actual synovial fluid bupivacaine concentrations after intra-articular injection. Eight healthy beagles with normal stifles and 22 large and giant-breed dogs with stifle osteoarthritis (OA) were treated with a single intra-articular injection of bupivacaine (1 mg/kg) into a stifle. Joint fluid samples were taken from the treated stifle immediately after injection and 30 min after injection and analyzed for bupivacaine concentrations. Immediately after injection, the median bupivacaine concentrations in normal and OA stifles were 3.6 and 2.5 mg/mL, respectively. Thirty minutes after injection, bupivacaine concentrations in normal and OA stifles were 0.4 and 0.6 mg/mL, respectively. These results provide insight into the pharmacokinetics of bupivacaine after injection into a joint. Given its immediate dilution and rapid drop in synovial fluid concentration, bupivacaine is unlikely to damage chondrocytes when administered as a single intra-articular injection. © 2014 John Wiley & Sons Ltd.

Improving the accuracy of synovial fluid analysis in the diagnosis of prosthetic joint infection with simple and inexpensive biomarkers: C-reactive protein and adenosine deaminase.

PubMed

Sousa, R; Serrano, P; Gomes Dias, J; Oliveira, J C; Oliveira, A

2017-03-01

The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). The total

Federal Mechanisms to Support Intervention Dissemination

ERIC Educational Resources Information Center

Diana, Augusto; Bennett, Nicole

2015-01-01

This paper examines federal mechanisms that support program developers and researchers in disseminating effective interventions for public benefit. The purpose of this paper is not to discuss the dissemination of intervention research (i.e., how to inform stakeholders about research findings), nor is it intended to discuss the research of…

A Spread Willingness Computing-Based Information Dissemination Model

PubMed Central

Cui, Zhiming; Zhang, Shukui

2014-01-01

This paper constructs a kind of spread willingness computing based on information dissemination model for social network. The model takes into account the impact of node degree and dissemination mechanism, combined with the complex network theory and dynamics of infectious diseases, and further establishes the dynamical evolution equations. Equations characterize the evolutionary relationship between different types of nodes with time. The spread willingness computing contains three factors which have impact on user's spread behavior: strength of the relationship between the nodes, views identity, and frequency of contact. Simulation results show that different degrees of nodes show the same trend in the network, and even if the degree of node is very small, there is likelihood of a large area of information dissemination. The weaker the relationship between nodes, the higher probability of views selection and the higher the frequency of contact with information so that information spreads rapidly and leads to a wide range of dissemination. As the dissemination probability and immune probability change, the speed of information dissemination is also changing accordingly. The studies meet social networking features and can help to master the behavior of users and understand and analyze characteristics of information dissemination in social network. PMID:25110738

Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial Joints

DTIC Science & Technology

2015-10-01

AD______________ AWARD NUMBER: W81XWH-14-1-0562 TITLE: Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Development of a Lubricant Therapy to Prevent Development of Osteoarthritis after Acute Injury of Synovial...early-onset osteoarthritis after traumatic joint injury remains a clinical challenge and may be associated with the poor lubricant quality of the

Study on Dissemination Patterns in Location-Aware Gossiping Networks

NASA Astrophysics Data System (ADS)

Kami, Nobuharu; Baba, Teruyuki; Yoshikawa, Takashi; Morikawa, Hiroyuki

We study the properties of information dissemination over location-aware gossiping networks leveraging location-based real-time communication applications. Gossiping is a promising method for quickly disseminating messages in a large-scale system, but in its application to information dissemination for location-aware applications, it is important to consider the network topology and patterns of spatial dissemination over the network in order to achieve effective delivery of messages to potentially interested users. To this end, we propose a continuous-space network model extended from Kleinberg's small-world model applicable to actual location-based applications. Analytical and simulation-based study shows that the proposed network achieves high dissemination efficiency resulting from geographically neutral dissemination patterns as well as selective dissemination to proximate users. We have designed a highly scalable location management method capable of promptly updating the network topology in response to node movement and have implemented a distributed simulator to perform dynamic target pursuit experiments as one example of applications that are the most sensitive to message forwarding delay. The experimental results show that the proposed network surpasses other types of networks in pursuit efficiency and achieves the desirable dissemination patterns.

Minimally invasive resection of lumbar intraspinal synovial cysts via a contralateral approach: review of 13 cases.

PubMed

Sukkarieh, Hamdi G; Hitchon, Patrick W; Awe, Olatilewa; Noeller, Jennifer

2015-10-01

The authors sought to determine patient-related outcomes after minimally invasive surgical (MIS) lumbar intraspinal synovial cyst excision via a tubular working channel and a contralateral facet-sparing approach. All the patients with a symptomatic lumbar intraspinal synovial cyst who underwent surgery at the University of Iowa Hospitals and Clinics with an MIS excision via a contralateral approach were treated between July 2010 and August 2014. There was a total of 13 cases. Each patient was evaluated with preoperative neurological examinations, lumbar spine radiography, MRI, and visual analog scale (VAS) scores. The patients were evaluated postoperatively with neurological examinations and VAS and Macnab scores. The primary outcomes were improvement in VAS and Macnab scores. Secondary outcomes were average blood loss, hospital stay duration, and operative times. There were 5 males and 8 females. The mean age was 66 years, and the mean body mass index was 28.5 kg/m(2). Sixty-nine percent (9 of 13) of the cysts were at L4-5. Most patients had low-back pain and radicular pain, and one-third of them had Grade 1 spondylolisthesis. The mean (± SD) follow-up duration was 20.8 ± 16.9 months. The mean Macnab score was 3.4 ± 1.0, and the VAS score decreased from 7.8 preoperatively to 2.9 postoperatively. The mean operative time was 123 ± 30 minutes, with a mean estimated blood loss of 44 ± 29 ml. Hospital stay averaged 1.5 ± 0.7 days. There were no complications noted in this series. The MIS excision of lumbar intraspinal synovial cysts via a contralateral approach offers excellent exposure to the cyst and spares the facet joint at the involved level, thus minimizing risk of instability, blood loss, operative time, and hospital stay. Prospective randomized trials with longer follow-up times and larger cohorts are needed to conclusively determine the superiority of the contralateral MIS approach over others, including open or ipsilateral minimally invasive surgery.

Curriculum Dissemination as Planned Cultural Diffusion.

ERIC Educational Resources Information Center

Rudduck, Jean

The author traces the change from the use of the term "diffusion" to the term "dissemination" with reference to curriculum projects in Britain and discusses implications of the change. Although at one time the two terms were used interchangeably, the term "dissemination" now emphasizes techniques of effective management rather than the educational…

Evolution of diffusion and dissemination theory.

PubMed

Dearing, James W

2008-01-01

The article provides a review and considers how the diffusion of innovations Research paradigm has changed, and offers suggestions for the further development of this theory of social change. Main emphases of diffusion Research studies are compared over time, with special attention to applications of diffusion theory-based concepts as types of dissemination science. A considerable degree of paradigmatic evolution is observed. The classical diffusion model focused on adopter innovativeness, individuals as the locus of decision, communication channels, and adoption as the primary outcome measures in post hoc observational study designs. The diffusion systems in question were centralized, with fidelity of implementation often assumed. Current dissemination Research and practice is better characterized by tests of interventions that operationalize one or more diffusion theory-based concepts and concepts from other change approaches, involve complex organizations as the units of adoption, and focus on implementation issues. Foment characterizes dissemination and implementation Research, Reflecting both its interdisciplinary Roots and the imperative of spreading evidence-based innovations as a basis for a new paradigm of translational studies of dissemination science.

Effects of glucosamine-chondroitin combination on synovial fluid IL-1β, IL-6, TNF-α and PGE2 levels in internal derangements of temporomandibular joint

PubMed Central

Esen, Emin; Tatli, Ufuk

2015-01-01

Background The aim of the present study was to evaluate the effects of glucosamine-chondroitin sulphate combination on internal derangements of temporomandibular joint in clinical and biochemical manners. Material and Methods This randomized clinical study included 31 cases reporting joint tenderness, in which disc displacement was detected on MR imaging. In all patients, synovial fluid sampling was performed under local anesthesia. In the study group, the patients were prescribed a combination of 1500 mg glucosamine and 1200 mg chondroitin sulphate, while patients in the control group were only prescribed 50 mg tramadol HCl (twice daily) for pain control. After 8 weeks, synovial fluid sampling was repeated in the same manner. The levels of pain, maximum mouth opening (MMO), synovial fluid IL-1ß, IL-6, TNF-α and PGE2 measured before and after pharmacological intervention were compared. Results The reduction in pain levels was significant in both groups. There was no significant difference between two groups in terms of pain reduction. The improvement in MMO was significant in the study group but it was not in the control group. The MMO improvement was significantly higher in the study group compared to the control group. In the study group, significant decrease was observed in PGE2 level, while the decreases in IL-1β, IL-6 and TNF-α levels were not significant. In the control group, no significant decrease was observed in any of the inflammatory cytokines after 8 weeks, moreover IL-1ß and IL-6 levels were increased. Alterations of IL-1ß and IL-6 levels were significant in study group while TNF-α and PGE2 levels were not, compared to control group. Conclusions In conclusion, these results might suggest that glucosamine-chondroitin combination significantly increases the MMO and decreases the synovial fluid IL1β and IL6 levels in internal derangements of TMJ compared to tramadol. The modifications of synovial fluid TNF-α and PGE2 levels do not reach

The FAIR-INNOVATION dissemination project.

PubMed

Gormley, R

2001-08-01

The goal of the FAIR-INNOVATION dissemination project (FLAIR-FLOW 3) (1997-2000) was to disseminate R&D results from the EU FAIR programme to small and medium-sized food enterprises (SMEs), health professionals (HPs) and consumer groups (CGs) in 19 European countries. The dissemination routes were: (i) one-page technical documents on research results; (ii) their reproduction on the internet; (iii) their reproduction in journals Europe-wide; (iv) workshops on results from EU-supported food research programmes; and (v) lectures and poster presentations by FLAIR-FLOW network personnel. Of the 135 one-pagers produced, 62% were targeted at SMEs, 18% at HPs and 5% at CGs. The remaining 15% were on food safety and were common to the three target groups. There were 1047 publications arising from one-pages in trade journals, and over 8000 requests (paper route) were received for follow-up information. These were in addition to 240 k downloads from the FLAIR-FLOW 3 web site (www.flair-flow.com). Initiatives for HPs included specially collated versions of the one-pagers for major conferences, 20 focused workshops, and interaction with the European Federation of Associations of Dieticians. Currently, dissemination is continuing through FLAIR-FLOW 4 (2001-2003) in 24 countries. FLAIR-FLOW 4 is co-ordinated by M. Jean François Quillien from INRA-CRIAA (FR) at criaa@rennes.inra.fr.

Variation in water disappearance, daily dose, and synovial fluid concentrations of tylvalosin and 3-O-acetyltylosin in commerical pigs during five day water medication with tylvalosin under field conditions.

PubMed

Canning, P; Bates, J; Skoland, K; Coetzee, J; Wulf, L; Rajewski, S; Wang, C; Gauger, P; Ramirez, A; Karriker, L

2018-03-23

Tylvalosin (TVN) is a water soluble macrolide used in swine production to treat enteric, respiratory, and arthritic pathogens. There is limited data on its distribution to synovial fluid beyond gavage studies, which do not represent field conditions. This study measured water disappearance, TVN concentration in the medicated water, daily dose, and concentrations of TVN and 3-O-acetyltylosin (3AT) in the synovial fluid and plasma of treated pigs over the administration period. The study emphasized understanding variation in tissue TVN concentrations within the context of a field setting. Sixty finisher pigs were housed individually with individual waterers. Six pigs were randomly allocated to the following time points for sample collection: 0, 48, 60, 72, 84, 96, 102, 108, 114, and 120 hr on medication. TVN was administered daily in the water for 5 days. Water disappearance and medicated water concentration were measured daily. At each time point, six pigs were euthanized and plasma and synovial fluid were collected for analysis. Median TVN synovial fluid concentrations ranged between <1 ng/ml (hour 0) to 3.6 ng/ml (hour 84). There was substantial variation between individual pigs for water disappearance (mean 4.36L and range 0-7.84). Median TVN water concentration was 59 ppm (range 38-75 ppm). © 2018 John Wiley & Sons Ltd.

Change of synovial vascularity in a single finger joint assessed by power doppler sonography correlated with radiographic change in rheumatoid arthritis: comparative study of a novel quantitative score with a semiquantitative score.

PubMed

Fukae, Jun; Kon, Yujiro; Henmi, Mihoko; Sakamoto, Fumihiko; Narita, Akihiro; Shimizu, Masato; Tanimura, Kazuhide; Matsuhashi, Megumi; Kamishima, Tamotsu; Atsumi, Tatsuya; Koike, Takao

2010-05-01

To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA). We studied 190 metacarpophalangeal (MCP) joints and 190 proximal interphalangeal (PIP) joints of 19 patients with active RA who had initial treatment with disease-modifying antirheumatic drugs (DMARDs). Patients were examined by clinical and laboratory assessments throughout the study. Hand and foot radiography was performed at baseline and the twentieth week. Magnetic resonance imaging (MRI) was performed at baseline. PDS was performed at baseline and the eighth week. Synovial vascularity was evaluated according to both quantitative and semiquantitative methods. Quantitative PDS was significantly correlated with the enhancement rate of MRI in each single finger joint. Comparing quantitative synovial vascularity and radiographic change in single MCP or PIP joints, the level of vascularity at baseline showed a significant positive correlation with radiographic progression at the twentieth week. The change of vascularity in response to DMARDs, defined as the percentage change in vascularity by the eighth week from baseline, was inversely correlated with radiographic progression in each MCP joint. The quantitative PDS method was more useful than the semiquantitative method for the evaluation of synovial vascularity in a single finger joint. The change of synovial vascularity in a single finger joint determined by quantitative PDS could numerically predict its radiographic progression. Using vascularity as a guide to consider a therapeutic approach would have benefits for patients with active RA.

[Effects of electro-acupuncture on expression of triggering receptor expressed on myeloid cells 1 in ankle joint synovial tissue of acute gouty arthritis rats].

PubMed

Zhang, Chao-Nan; Huang, Xue-Kuan; Luo, Yan; Jiang, Juan; Wan, Lei; Wang, Ling

2015-01-01

To investigate the effects of electro-acupuncture (EA) on the expression of triggering receptor expressed on myeloid cell (TREM)l in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. Forty male SD rats were randomly divided into 4 groups: normal, AGA, medication and EA group, 10 rats in each group. AGA model was established by induced monosodium urate (MSU) method, except the normal group. Tow days before AGA model was established, normal and AGA groups were lavaged with normal saline (20 ml/kg), medication group was lavaged with colchicine solution (20 ml/kg), EA(1.5-2 Hz, D.-D.wave, 9v; 1-3 rnA) was applied to "Sanyinjiao" (SP6), "jiexi" (ST41) and "Kunlun" (BL60) for 20 min, once daily;continuously for 9 days. Then observed the changes in dysfunction, and the content of TNF-α and IL-lβ detected by ELISA, the expression of TREM-l detected by immunohistochemistry and western blot. Compared to the normal group, the AGA group of the dysfunction index increased significantly (P<0.01), the content of TNF-α and IL-lβ increased significantly (P<0.05), the expression of TREM-l in synovial tissue increased significantly (P<0.05); the medication and EA groups compared to the AGA group, the dysfunction index decreased significantly (P<0.01), the content of TNF-α and IL-lβ decreased significantly (P<0.05), the expression of TREM-l in synovial tissue decreased significantly (P<0.05); there were not statistically significant between the medication and EA group (P>0.05). EA treating AGA may be through down-regulating the expression of TREM -1 in synovial tissue.

The cation channel Trpv2 is a new suppressor of arthritis severity, joint damage, and synovial fibroblast invasion.

PubMed

Laragione, Teresina; Cheng, Kai F; Tanner, Mark R; He, Mingzhu; Beeton, Christine; Al-Abed, Yousef; Gulko, Pércio S

2015-06-01

Little is known about the regulation of arthritis severity and joint damage in rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLS) have a central role in joint damage and express increased levels of the cation channel Trpv2. We aimed at determining the role of Trpv2 in arthritis. Treatment with Trpv2-specific agonists decreased the in vitro invasiveness of FLS from RA patients and arthritic rats and mice. Trpv2 stimulation suppressed IL-1β-induced expression of MMP-2 and MMP-3. Trpv2 agonists, including the new and more potent LER13, significantly reduced disease severity in KRN serum- and collagen-induced arthritis, and reduced histologic joint damage, synovial inflammation, and synovial blood vessel numbers suggesting anti-angiogenic activity. In this first in vivo use of Trpv2 agonists we discovered a new central role for Trpv2 in arthritis. These new compounds have the potential to become new therapies for RA and other diseases associated with inflammation, invasion, and angiogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Comprehensive analysis of information dissemination in disasters

NASA Astrophysics Data System (ADS)

Zhang, N.; Huang, H.; Su, Boni

2016-11-01

China is a country that experiences a large number of disasters. The number of deaths caused by large-scale disasters and accidents in past 10 years is around 900,000. More than 92.8 percent of these deaths could be avoided if there were an effective pre-warning system deployed. Knowledge of the information dissemination characteristics of different information media taking into consideration governmental assistance (information published by a government) in disasters in urban areas, plays a critical role in increasing response time and reducing the number of deaths and economic losses. In this paper we have developed a comprehensive information dissemination model to optimize efficiency of pre-warning mechanics. This model also can be used for disseminating information for evacuees making real-time evacuation plans. We analyzed every single information dissemination models for pre-warning in disasters by considering 14 media: short message service (SMS), phone, television, radio, news portals, Wechat, microblogs, email, newspapers, loudspeaker vehicles, loudspeakers, oral communication, and passive information acquisition via visual and auditory senses. Since governmental assistance is very useful in a disaster, we calculated the sensitivity of governmental assistance ratio. The results provide useful references for information dissemination during disasters in urban areas.

Molecular mechanisms of peritoneal dissemination in gastric cancer.

PubMed

Kanda, Mitsuro; Kodera, Yasuhiro

2016-08-14

Peritoneal dissemination represents a devastating form of gastric cancer (GC) progression with a dismal prognosis. There is no effective therapy for this condition. The 5-year survival rate of patients with peritoneal dissemination is 2%, even including patients with only microscopic free cancer cells without macroscopic peritoneal nodules. The mechanism of peritoneal dissemination of GC involves several steps: detachment of cancer cells from the primary tumor, survival in the free abdominal cavity, attachment to the distant peritoneum, invasion into the subperitoneal space and proliferation with angiogenesis. These steps are not mutually exclusive, and combinations of different molecular mechanisms can occur in each process of peritoneal dissemination. A comprehensive understanding of the molecular events involved in peritoneal dissemination is important and should be systematically pursued. It is crucial to identify novel strategies for the prevention of this condition and for identification of markers of prognosis and the development of molecular-targeted therapies. In this review, we provide an overview of recently published articles addressing the molecular mechanisms of peritoneal dissemination of GC to provide an update on what is currently known in this field and to propose novel promising candidates for use in diagnosis and as therapeutic targets.

Macrophage inflammatory protein 1 alpha expression by synovial fluid neutrophils in rheumatoid arthritis

PubMed Central

Hatano, Y.; Kasama, T.; Iwabuchi, H.; Hanaoka, R.; Takeuchi, H.; Jing, L.; Mori, Y.; Kobayashi, K.; Negishi, M.; Ide, H.; Adachi, M.

1999-01-01

OBJECTIVE—To determine the contribution made by synovial fluid (SF) neutrophils to the augmented expression of macrophage inflammatory protein 1 α (MIP-1α) in rheumatoid arthritis (RA).
METHODS—Neutrophils were isolated from samples of SF from RA patients and peripheral blood (PB) samples from RA patients and healthy controls. Cell associated MIP-1α was visualised immunohistochemically, and cell associated MIP-1α as well as MIP-1α secreted into the SF was assayed by ELISA. Steady state expression of MIP-1α mRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR).
RESULTS—Freshly isolated SF neutrophils contained significantly higher concentrations of both MIP-1α protein and its transcript than PB neutrophils from either RA patients or healthy controls; incubation in the absence or presence of tumour necrosis factor α for 24 hours resulted in a significant increase in MIP-1α secretion by RA SF neutrophils compared with neutrophils obtained from either normal PB or RA PB; and expression of MIP-1α by SF neutrophils was well correlated with both RA disease activity and SF mononuclear cell (MNC) counts.
CONCLUSION—Expression and secretion of MIP-1α by SF neutrophils may be indicative of local and systemic inflammation in RA. Moreover, this C-C chemokine may contribute to the recruitment of MNCs from the bloodstream into synovial joints and tissues.

 PMID:10225815

44 CFR 19.140 - Dissemination of policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Introduction § 19.140 Dissemination of policy. (a... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Dissemination of policy. 19.140 Section 19.140 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY, DEPARTMENT...

The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

PubMed Central

Lewallen, Eric A.; Bonin, Carolina A.; Li, Xin; Smith, Jay; Karperien, Marcel; Larson, A. Noelle; Lewallen, David G.; Cool, Simon M.; Westendorf, Jennifer J.; Krych, Aaron J.; Leontovich, Alexey A.; Im, Hee-Jeong; van Wijnen, Andre J.

2018-01-01

Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain with limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from pristine knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analysis reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that sampling anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should they be used to generate a normal baseline for the molecular characterization of diseased joints. PMID:27378743

Quantitation of substance-P and its metabolites in plasma and synovial fluid from patients with arthritis.

PubMed

Joyce, T J; Yood, R A; Carraway, R E

1993-09-01

Substance-P (SP) and its metabolites, SP-(1-7) and SP-(5-11), were quantitated in arthritic synovial fluids and plasma using a validated procedure. This process involved collection into appropriate enzyme inhibitors, extraction with acid-acetone, high pressure liquid chromatography, and RIA using region-specific antisera. Our results demonstrate that the levels of authentic SP in these fluids are less than 3.5 pmol/L, which is 50- to 10,000-fold less than those previously reported by others. These discrepant findings were not attributable to degradation, because added SP was recovered in good yield, and the measured levels of the metabolites SP-(1-7) and SP-(5-11) were also extremely low. In search of an explanation, we noted that many of the earlier reports involved direct assay of these fluids (without extraction and chromatography). Further work indicated that proteolytic enzymes (e.g. protease 24.11) present in these unextracted fluids can give rise to artifactually high SP measurements. We conclude that if SP is released within the joint space and if it participates in the inflammatory reaction and/or healing process, it most likely does so in a local fashion, which would not involve its accumulation in synovial fluid or plasma.

Gelatinase activity in synovial fluid and synovium obtained from healthy and osteoarthritic joints of dogs.

PubMed

Volk, Susan W; Kapatkin, Amy S; Haskins, Mark E; Walton, Raquel M; D'Angelo, Marina

2003-10-01

To determine matrix metalloproteinase (MMP) activity in synovial fluid (SF) obtained from the joints of dogs with degenerative joint disease (DJD) secondary to various underlying conditions. 35 samples of SF obtained from 18 clinically normal (control) dogs and 34 samples of SF obtained from 17 dogs with DJD; dogs with DJD were from 2 populations (client-owned dogs and research dogs that had DJD secondary to the lysosomal storage disease mucopolysaccharidosis VII). MMP activity in samples of SF was semiquantitatively examined by use of gelatin or casein zymography. Western blot analysis was performed by use of antibodies for MMP-2 and MMP-9. In addition, in situ MMP activity was observed in sections of synovial membrane obtained from healthy and osteoarthritic joints. Samples of SF from osteoarthritic joints had higher MMP-2 activity and dramatically increased MMP-9 activity, compared with values for healthy joints. Substrate-overlay analyses indicated minimal gelatin-degrading activity in synoviocytes obtained from control dogs, whereas greater activity was seen in osteoarthritic synoviocytes, with additional activity in the underlying tissue. Higher MMP-2 activity and dramatic increases in MMP-9 activity were associated with the osteoarthritic state, even though MMP-2 activity was detected in healthy joints. This study expands information on MMP production in SF of osteoarthritic joints in other species and documents the similarity of MMP activity patterns regardless of the cause of DJD.

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

40 CFR 56.6 - Dissemination of policy and guidance.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) REGIONAL CONSISTENCY § 56.6 Dissemination of policy and guidance. The Assistant Administrators of... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Dissemination of policy and guidance... to disseminate policy and guidance. They shall distribute material under foregoing systems to the...

The importance of serological tests implementation in disseminated candidiasis diagnose.

PubMed

Gegić, Merima; Numanović, Fatima; Delibegović, Zineta; Tihić, Nijaz; Nurkić, Mahmut; Hukić, Mirsada

2013-03-01

Candidiasis is defined as an infection or disease caused by a fungus of the genus Candida. Rate of disseminated candidiasis increases with the growth of the number of immunocompromised patients. In the the last few decades the incidence of disseminated candidiasis is in growth as well as the mortality rate. The aim of this survey is to show the importance of serological tests implementation in disseminated candidiasis diagnose. This is a prospective study involving 60 patients with malign diseases with and without clinical signs of disseminated candidiasis and 30 healthy people who represent the control group. Apart from hemoculture, detection of circulating mannan antigen and adequate antibodies of Candida species applying comercial ELISA test was determined in each patient. This survey deals with relevant factors causing disseminated candidiasis. This survey showed that the group of patients with clinical signs of disseminated candidiasis had more patients with positive hemoculture to Candida species, then the group of patients without clinical signs of disseminated candidiasis. The number of patients being examined and positive to antigens and antibodies was higher (p < 0.01) in the group of patients with clinical signs of disseminated candidiasis (7/30; 23.3%), then in the group of patients without clinical signs of disseminated candidiasis (0/30; 0%): Average value of titra antigen was statistically higher (p < 0.001) in patients with Candida spp. positive hemocultures rather then in patients with Candida spp. negative hemocultures. In the group of patients with clinical signs of disseminated candidiasis 6/30 (20%) of patients had Candida spp.positive hemocultures while in the group of patients without clinical signs of disseminated candidiasis 1/30 (3.3%) of patients had Candida spp. positive hemocultures, which was considerably higher (p < 0.05). Correlation of results of hemoculture and mannan antigens and antibodies in patients with disseminated

Optimal teaching strategy in periodic impulsive knowledge dissemination system.

PubMed

Liu, Dan-Qing; Wu, Zhen-Qiang; Wang, Yu-Xin; Guo, Qiang; Liu, Jian-Guo

2017-01-01

Accurately describing the knowledge dissemination process is significant to enhance the performance of personalized education. In this study, considering the effect of periodic teaching activities on the learning process, we propose a periodic impulsive knowledge dissemination system to regenerate the knowledge dissemination process. Meanwhile, we put forward learning effectiveness which is an outcome of a trade-off between the benefits and costs raised by knowledge dissemination as objective function. Further, we investigate the optimal teaching strategy which can maximize learning effectiveness, to obtain the optimal effect of knowledge dissemination affected by the teaching activities. We solve this dynamic optimization problem by optimal control theory and get the optimization system. At last we numerically solve this system in several practical examples to make the conclusions intuitive and specific. The optimal teaching strategy proposed in this paper can be applied widely in the optimization problem of personal education and beneficial for enhancing the effect of knowledge dissemination.

Optimal teaching strategy in periodic impulsive knowledge dissemination system

PubMed Central

Liu, Dan-Qing; Wu, Zhen-Qiang; Wang, Yu-Xin; Guo, Qiang

2017-01-01

Accurately describing the knowledge dissemination process is significant to enhance the performance of personalized education. In this study, considering the effect of periodic teaching activities on the learning process, we propose a periodic impulsive knowledge dissemination system to regenerate the knowledge dissemination process. Meanwhile, we put forward learning effectiveness which is an outcome of a trade-off between the benefits and costs raised by knowledge dissemination as objective function. Further, we investigate the optimal teaching strategy which can maximize learning effectiveness, to obtain the optimal effect of knowledge dissemination affected by the teaching activities. We solve this dynamic optimization problem by optimal control theory and get the optimization system. At last we numerically solve this system in several practical examples to make the conclusions intuitive and specific. The optimal teaching strategy proposed in this paper can be applied widely in the optimization problem of personal education and beneficial for enhancing the effect of knowledge dissemination. PMID:28665961

Exploring Organizational Approaches to Dissemination and Training.

ERIC Educational Resources Information Center

Firestone, William A.; Rossman, Gretchen B.

1986-01-01

Discusses four case studies of regional educational service agencies in their role as disseminators of new knowledge. Three characteristic approaches to dissemination were identified, namely, laissez-faire, entrepreneurial, and authoritarian. These approaches were shaped by five factors in the agency's context: state policy initiatives; client…

22 CFR 229.140 - Dissemination of policy.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Dissemination of policy. 229.140 Section 229.140 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT NONDISCRIMINATION ON THE BASIS OF SEX IN EDUCATION PROGRAMS OR ACTIVITIES RECEIVING FEDERAL FINANCIAL ASSISTANCE Introduction § 229.140 Dissemination...

Antibodies against recombinant heat shock proteins of 60 kDa from enterobacteria in the sera and synovial fluid of HLA-B27 positive ankylosing spondylitis patients.

PubMed

Domínguez-López, M L; Ortega-Ortega, Y; Manríquez-Raya, J C; Burgos-Vargas, R; Vega-López, A; García-Latorre, E

2009-01-01

To study the association of HLA-B27 with IgG antibodies to different enterobacterial HSP60s in patients with ankylosing spondylitis (AS). IgG antibodies to 60 kDa enterobacterial HSPs were determined by ELISA in paired samples of sera and synovial fluid from 21 HLA-B27+ ankylosing spondylitis (AS) patients; and in sera from 32 HLA-B27+ AS patients, 35 HLA-B27+ healthy relatives of AS patients, and 60 HLA-B27- healthy individuals with no family members with AS. HLA-B27+ patients and healthy individuals showed significantly higher IgG antibody levels to recombinant enterobacterial HSP60s than HLA-B27- healthy controls. The levels of anti-HSP60Sf and anti-HSP60Ec antibodies correlated with disease activity and anti-HSP60Ec antibodies with male gender. No association between enterobacterial HSP60 antibody levels and disease duration was observed. All groups had lower levels of IgG antibodies to rHSP60 from Streptococcus pyogenes (rHSP60 Spy). In paired samples of sera and synovial fluid from B27+ patients, IgG antibodies to enterobacterial HSP60s were detected, but in significantly higher levels in sera than in synovial fluid. The anti-rHSPSpy IgG response in these samples was lower and similar in the three groups. A correlation was found between HLA-B27 and the response to recombinat enterobacterial HSP60s. This response could be associated with disease activitir and gender in some proteins and the presence eof IgG antibodies to these proteins in synovial fluid could be associated with the inflammatory process and initiation of AS.

High mobility group box protein 1 in complex with lipopolysaccharide or IL-1 promotes an increased inflammatory phenotype in synovial fibroblasts

PubMed Central

2011-01-01

Introduction In addition to its direct proinflammatory activity, extracellular high mobility group box protein 1 (HMGB1) can strongly enhance the cytokine response evoked by other proinflammatory molecules, such as lipopolysaccharide (LPS), CpG-DNA and IL-1β, through the formation of complexes. Extracellular HMGB1 is abundant in arthritic joint tissue where it is suggested to promote inflammation as intra-articular injections of HMGB1 induce synovitis in mice and HMGB1 neutralizing therapy suppresses development of experimental arthritis. The aim of this study was to determine whether HMGB1 in complex with LPS, interleukin (IL)-1α or IL-1β has enhancing effects on the production of proinflammatory mediators by rheumatoid arthritis synovial fibroblasts (RASF) and osteoarthritis synovial fibroblasts (OASF). Furthermore, we examined the toll-like receptor (TLR) 4 and IL-1RI requirement for the cytokine-enhancing effects of the investigated HMGB1-ligand complexes. Methods Synovial fibroblasts obtained from rheumatoid arthritis (RA) and osteoarthritis (OA) patients were stimulated with HMGB1 alone or in complex with LPS, IL-1α or IL-1β. Tumour necrosis factor (TNF) production was determined by enzyme-linked immunospot assay (ELISPOT) assessment. Levels of IL-10, IL-1-β, IL-6 and IL-8 were measured using Cytokine Bead Array and matrix metalloproteinase (MMP) 3 production was determined by ELISA. Results Stimulation with HMGB1 in complex with LPS, IL-1α or IL-1β enhanced production of TNF, IL-6 and IL-8. HMGB1 in complex with IL-1β increased MMP production from both RASF and OASF. The cytokine production was inhibited by specific receptor blockade using detoxified LPS or IL-1 receptor antagonist, indicating that the synergistic effects were mediated through the partner ligand-reciprocal receptors TLR4 and IL-1RI, respectively. Conclusions HMGB1 in complex with LPS, IL-1α or IL-1β boosted proinflammatory cytokine- and MMP production in synovial fibroblasts from

Clinical characteristics associated with the intracranial dissemination of gliomas.

PubMed

Cai, Xu; Qin, Jun-Jie; Hao, Shu-Yu; Li, Huan; Zeng, Chun; Sun, Sheng-Jun; Yu, Lan-Bing; Gao, Zhi-Xian; Xie, Jian

2018-03-01

Glioma is the most common malignant tumor of the brain and the intracranial dissemination of gliomas is the late stage of the development of the tumor. However, there is little research in literature on the occurrence of intracranial dissemination of gliomas. In order to provide a reference for clinical work, we carried out this study on intracranial dissemination of glioma. A total of 629 patients with gliomas received tumor resection by the same surgeon from August 2010 to September 2015 were included in this study. The authors performed a retrospective review of the patients and the information regarding clinical features, histopathological results, molecular pathologic results and clinical outcomes was collected and analyzed. In this retrospective study, we found that the intracranial dissemination phenomenon occurred in 53 patients (8.43%). We analyzed the clinical characteristics of patients and found that the age at diagnosis (P = 0.011), WHO grade of the tumor (P < 0.001), and involvement of the corpus callosum (P = 0.010) were associated with the occurrence of dissemination. The higher grade of the tumor, the more prone to disseminate. Deletion of 1p/19q had no significant correlation with the intracranial dissemination. MMP9, Ki-67, and EGFR were highly expressed in tumor cells that caused dissemination, and the level of Ki-67 expression had significance in statistics (P < 0.01). In our study, older age (>40 years), high pathological grade, invasion of the corpus callosum and high levels of Ki-67 expression were risk factors associated with the intracranial dissemination of gliomas. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of mud-bath therapy in psoriatic arthritis patients treated with TNF inhibitors. Clinical evaluation and assessment of synovial inflammation by contrast-enhanced ultrasound (CEUS).

PubMed

Cozzi, Franco; Raffeiner, Bernd; Beltrame, Valeria; Ciprian, Luca; Coran, Alessandro; Botsios, Constantin; Perissinotto, Egle; Grisan, Enrico; Ramonda, Roberta; Oliviero, Francesca; Stramare, Roberto; Punzi, Leonardo

2015-03-01

Despite the efficacy of TNF inhibitors, most patients with psoriatic arthritis maintain a residual synovial inflammation. The main aim of the study was to evaluate the effects of mud-bath therapy on clinical picture of PsA patients treated with TNF inhibitors. The secondary outcome was to assess synovial inflammation in hand joints detected by contrast-enhanced ultrasound. Other aims were to verify the risk of arthritis flare and to evaluate the effects of spa treatment on functional ability and on quality of life. Thirty-six patients with psoriatic arthritis, treated in the last 6 months with TNF inhibitors, were enrolled. After 1:1 randomisation, 18 patients (group A) underwent mud-bath therapy (12 mudpacks and 12 thermal baths), maintaining treatment with TNF inhibitors; 18 patients (group B) continued pharmacological therapy alone. CRP, PASI, DAS28, swollen and tender joint count, VAS pain, HAQ and SF-36 were evaluated at baseline (T0) and after 45 days (T1). Synovial inflammation detected by contrast-enhanced ultrasound, analysed by a software system, was also assessed. A significant improvement in PASI (P<0.005), DAS28 (P<0.05), swollen joint count and tender joint count (P<0.001), and HAQ (P<0.001) between T0 and T1 was observed in group A. No patient underwent a flare-up of arthritis. Ultrasound videos demonstrated a significant appearance delay (P<0.05) and faster washout (P<0.02) of contrast dye in group A patients with respect to group B. These data suggest a decrease of residual synovial inflammation and a beneficial clinical effect of spa therapy in psoriatic arthritis patients treated with TNF inhibitors. Copyright © 2014 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Transcriptomic analysis of synovial extracellular RNA following knee trauma: A pilot study.

PubMed

Griswold, Anthony J; Perez, Jose; Nuytemans, Karen; Strong, Thomas A; Wang, Liyong; Vance, Danica D; Ennis, Hayley; Smith, Marvin K; Best, Thomas M; Vance, Jeffery M; Pericak-Vance, Margaret A; Kaplan, Lee D

2018-06-01

Traumatic knee injuries often result in damage to articular cartilage and other joint structures. Such trauma is a strong risk factor for the future development and progression of osteoarthritis (OA). The molecular mechanisms and signaling pathways modulating response to knee joint trauma remain unclear. Moreover, investigations of biomarkers influencing responses have been targeted rather than broad, unbiased discovery studies. Herein, we characterize the complete complement of extracellular RNA (exRNA) in the synovial fluid of 14 subjects following knee injury. Fluid was collected during surgery from the injured knees, and from the contralateral knee in a subset, undergoing surgical repair of the ACL and/or meniscal repair/debridement. Arthroscopic grading of chondral damage in four knee compartments was performed using the Outerbridge classification. exRNA was extracted and subjected to massively parallel total RNA sequencing. Differential abundance of RNA was calculated between the subject cohorts of injured and non-injured knee, average Outerbridge score ≥0.5 and less, and chronic and acute injury duration defined as ≤4 months till surgery or longer. Overall, expression of several thousand genes was identified in the synovial fluid. Furthermore, differential expression analysis suggests a role of exRNA fragments of matrix metalloproteinases and skeletal muscle fiber genes in the response to traumatic injury. Together, these data suggest that high-throughput approaches can indicate exRNA molecular signatures following knee trauma. Future studies are required to more fully characterize the biological roles of these exRNA and the cadence of their respective release that may lead to translational treatment options for post-traumatic OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1659-1665, 2018. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

PubMed

Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-07-01

To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

PubMed Central

Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-01-01

Objective To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Methods Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.6synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. Results PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68+, CD20+, CD3+ cells and CD31+ vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68+, CD20+, CD3+, CD31+ cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68+ (p=0.02) and CD3+ cells (p=0.04) as well as CD31+ vessels (p<0.001) than PDUS-negative patients with RA in remission. Conclusions PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. PMID

45 CFR 618.140 - Dissemination of policy.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 45 Public Welfare 3 2014-10-01 2014-10-01 false Dissemination of policy. 618.140 Section 618.140 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION... Introduction § 618.140 Dissemination of policy. (a) Notification of policy. (1) Each recipient shall implement...

45 CFR 618.140 - Dissemination of policy.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 45 Public Welfare 3 2012-10-01 2012-10-01 false Dissemination of policy. 618.140 Section 618.140 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION... Introduction § 618.140 Dissemination of policy. (a) Notification of policy. (1) Each recipient shall implement...

45 CFR 618.140 - Dissemination of policy.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 45 Public Welfare 3 2013-10-01 2013-10-01 false Dissemination of policy. 618.140 Section 618.140 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION... Introduction § 618.140 Dissemination of policy. (a) Notification of policy. (1) Each recipient shall implement...

45 CFR 618.140 - Dissemination of policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 45 Public Welfare 3 2011-10-01 2011-10-01 false Dissemination of policy. 618.140 Section 618.140 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION... Introduction § 618.140 Dissemination of policy. (a) Notification of policy. (1) Each recipient shall implement...

[The effects of electro-acupuncture on the signaling pathway of TLR/MYD88 in ankle joint synovial tissue of acute gouty arthritis rats].

PubMed

Zhang, Chao-nan; Huang, Xue-kuan; Luo, Yan; Jiang, Juan; Wan, Lei; Wang, Ling

2014-11-01

To investigate the effects of electro-acupuncture ( EA) on the related protein expression of the signaling pathway of the toll-like receptor2 (TLR2)/myeloid differentiation factor (MYD) 88 in ankle joint synovial tissue of acute gouty arthritis (AGA) rats. Fifty male SD rats were randomly divided into 5 groups: normal group, SMD group, AGA model group, medication group and EA group, 10 rats in each group. SMD group established model by inducing SMD, other groups established AGA model by inducing monosodium urate, except the normal group. Two days before model was established, normal and SMD and AGA model groups were lavaged with normal saline (20 mL/kg), medication group was lavaged with colchicine solution (1 mg/kg), EA (1. 5-2 Hz, D.-D. wave, 9 V, 1-3 mA) was applied to"Sanyinjiao" (SP6),"Jiexi"(ST41) and "kunlun" (BL60) for 20 min, once daily, continuously for 9 days. Then the join sewlling index was observed periodically, the protein expression of TLR2 and MYD88 was determined by immunohistochemistry. Compared to the normal group, the join sewlling of the SMD group in test join increased significantly (P<0. 05) and the protein expression of TLR2 and MYD88 in synovial tissue has not statistically significant (P>0.05), the oin sewlling and protein expression of TLR2 and MYD88 in synovial tissue of model group increased significantly P<0. 05); The medication and EA group compared to the model group, the protein expression of TLR2 and MYD88 in synovial tissue decreased significantly (P <0. 05), the join sewlling in test join decreased significantly P<1. 05); There were not statistically significant between the EA group and the medication group (P>0.05). EA can alleviate the symptoms of AGA, which may be related to regulation of the protein expression Y TRI and MYD88 in the TLR/MYD88 signaling pathway.

Selective glucocorticoid receptor modulator compound A, in contrast to prednisolone, does not induce leptin or the leptin receptor in human osteoarthritis synovial fibroblasts.

PubMed

Malaise, Olivier; Relic, Biserka; Quesada-Calvo, Florence; Charlier, Edith; Zeddou, Mustapha; Neuville, Sophie; Gillet, Philippe; Louis, Edouard; de Seny, Dominique; Malaise, Michel G

2015-06-01

Glucocorticoids are powerful anti-inflammatory compounds that also induce the expression of leptin and leptin receptor (Ob-R) in synovial fibroblasts through TGF-βsignalling and Smad1/5 phosphorylation. Compound A (CpdA), a selective glucocorticoid receptor agonist, reduces inflammation in murine arthritis models and does not induce diabetes or osteoporosis, thus offering an improved risk:benefit ratio in comparison with glucocorticoids. Due to the detrimental role of leptin in OA pathogenesis, we sought to determine whether CpdA also induced leptin and Ob-R protein expression as observed with prednisolone. Human synovial fibroblasts and chondrocytes were isolated from the synovium and cartilage of OA patients after joint surgery. The cells were treated with prednisolone, TGF-β1, TNF-α and/or CpdA. Levels of leptin, IL-6, IL-8, MMP-1 and MMP-3 were measured by ELISA and expression levels of Ob-R phospho-Smad1/5, phospho-Smad2, α-tubulin and glyceraldehyde 3-phosphate dehydrogenase were analysed by western blotting. CpdA, unlike prednisolone, did not induce leptin secretion or Ob-R protein expression in OA synovial fibroblasts. Moreover, CpdA decreased endogenous Ob-R expression and down-regulated prednisolone-induced leptin secretion and Ob-R expression. Mechanistically, CpdA, unlike prednisolone, did not induce Smad1/5 phosphorylation. CpdA, similarly to prednisolone, down-regulated endogenous and TNF-α-induced IL-6, IL-8, MMP-1 and MMP-3 protein secretion. The dissociative effect of CpdA was confirmed using chondrocytes with no induction of leptin secretion, but with a significant decrease in IL-6, IL-8, MMP-1 and MMP-3 protein secretion. CpdA, unlike prednisolone, did not induce leptin or Ob-R in human OA synovial fibroblasts, thereby demonstrating an improved risk:benefit ratio. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gossip-Based Dissemination

NASA Astrophysics Data System (ADS)

Friedman, Roy; Kermarrec, Anne-Marie; Miranda, Hugo; Rodrigues, Luís

Gossip-based networking has emerged as a viable approach to disseminate information reliably and efficiently in large-scale systems. Initially introduced for database replication [222], the applicability of the approach extends much further now. For example, it has been applied for data aggregation [415], peer sampling [416] and publish/subscribe systems [845]. Gossip-based protocols rely on a periodic peer-wise exchange of information in wired systems. By changing the way each peer is selected for the gossip communication, and which data are exchanged and processed [451], gossip systems can be used to perform different distributed tasks, such as, among others: overlay maintenance, distributed computation, and information dissemination (a collection of papers on gossip can be found in [451]). In a wired setting, the peer sampling service, allowing for a random or specific peer selection, is often provided as an independent service, able to operate independently from other gossip-based services [416].

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

Light Absorptive Properties of Articular Cartilage, ECM Molecules, Synovial Fluid, and Photoinitiators as Potential Barriers to Light-Initiated Polymer Scaffolding Procedures.

PubMed

Finch, Anthony J; Benson, Jamie M; Donnelly, Patrick E; Torzilli, Peter A

2017-06-01

Objective Many in vivo procedures to repair chondral defects use ultraviolet (UV)-photoinitiated in situ polymerization within the cartilage matrix. Chemical species that absorb UV light might reduce the effectiveness of these procedures by acting as light absorption barriers. This study evaluated whether any of the individual native biochemical components in cartilage and synovial fluid interfered with the absorption of light by common scaffolding photosensitizers. Materials UV-visible spectroscopy was performed on each major component of cartilage in solution, on bovine synovial fluid, and on four photosensitizers, riboflavin, Irgacure 2959, quinine, and riboflavin-5'-phosphate. Molar extinction and absorption coefficients were calculated at wavelengths of maximum absorbance and 365 nm. Intact articular cartilage was also examined. Results The individual major biochemical components of cartilage, Irgacure 2959, and quinine did not exhibit a significant absorption at 365 nm. Riboflavin and riboflavin-5'-phosphate were more effectual light absorbers at 365 nm, compared with the individual native species. Intact cartilage absorbed a significantly greater amount of UV light in comparison with the native species. Conclusion Our results indicate that none of the individual native species in cartilage will interfere with the absorption of UV light at 365 nm by these commonly used photoinitiators. Intact cartilage slices exhibited significant light absorption at 365 nm, while also having distinct absorbance peaks at wavelengths less than 300 nm. Determining the UV absorptive properties of the biomolecules native to articular cartilage and synovial fluid will aid in optimizing scaffolding procedures to ensure sufficient scaffold polymerization at a minimum UV intensity.

Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1 beta production by synovial T cells.

PubMed Central

Robinson, E; Keystone, E C; Schall, T J; Gillett, N; Fish, E N

1995-01-01

Earlier studies from this laboratory provided evidence for restricted cytokine expression in the T cell population in RA tissues. Specifically, IL-2, IL-4, IL-6 and interferon-gamma (IFN-gamma) gene expression levels were low. The selective chemoattractant and activation effects of chemokines on leucocytes identify them as potentially ideal candidates in mediating selective inflammatory processes in RA. Accordingly, we undertook studies to examine constitutive chemokine gene expression in RA tissues. RANTES, monocyte chemotactic protein-1 (MCP-1) and MIP-1 beta gene expression was examined in both the T and non-T cell populations in RA peripheral blood (PB), synovial fluid (SF) and synovial tissues (ST). Our results identified elevated levels of both RANTES and MIP-1 beta gene expression in circulating RA PB and SF T cells. By contrast, MCP-1 expression was virtually absent in RA PB, yet elevated MCP-1 mRNA levels were detected primarily in the non-T cell populations of the SF and ST samples. Histological examination of affected rheumatoid joints revealed extensive RANTES and MIP-1 beta expression in sites of lymphocyte infiltration and cell proliferation, namely the synovial lining and sublining layers. Fractionation or RA ST patient samples revealed that RANTES expression was restricted to the T cells, whereas MIP-1 beta expression was detected in both T and non-T fractions. These data suggest that MCP-1, MIP-1 beta and RANTES may have a central role in the trafficking of reactive molecules involved in immunoregulation and in the inflammatory processes in RA. Images Fig. 4 PMID:7545093

Traditional Chinese medicine formula Bi-Qi capsule alleviates rheumatoid arthritis-induced inflammation, synovial hyperplasia, and cartilage destruction in rats.

PubMed

Wang, Kai; Zhang, Dongmei; Liu, Yan; Wang, Xuan; Zhao, Jiantong; Sun, Tingting; Jin, Tingting; Li, Baoli; Pathak, Janak L

2018-03-14

Traditional Chinese medicine (TCM) formula Bi-Qi capsule (Bi-Qi) is a commonly prescribed drug to treat rheumatoid arthritis (RA). However, the mechanism of Bi-Qi-mediated amelioration of RA pathogenesis is still a mystery. Collagen induced arthritis (CIA) in rats is an established model that shares many similarities with RA in humans. In this study we investigated the effect of Bi-Qi on the pathogenesis of CIA in rats. CIA was developed in Sprague-Dawley (S.D) rats (n = 60, female) and used as a model resembling RA in humans. Rats were treated with a high or moderate dose of Bi-Qi, or methotrexate (MTX). Effects of the treatment on local joint and systemic inflammation, synovial hyperplasia, cartilage destruction, and other main features in the pathogenesis of CIA were analyzed. Inflamed and swollen ankles and joints were observed in arthritic rats, while Bi-Qi or MTX treatment alleviated these symptoms. Only the Bi-Qi moderate dose decreased RA-induced serum levels of tumor necrosis factor-alpha (TNF-α). Both Bi-Qi and MTX reduced the interleukin (IL)-18 serum level. Protein levels of cartilage oligomeric matrix protein and osteopontin in serum, synovium, and cartilage were elevated in arthritic rats, while Bi-Qi alleviated these effects. Synovial hyperplasia, inflammatory cell infiltration in synovium and a high degree of cartilage degradation was observed in RA, and Bi-Qi or MTX alleviated this effect. Bi-Qi at the moderate dose was the most effective in mitigating CIA-related clinical complications. Our findings showed that Bi-Qi alleviates CIA-induced inflammation, synovial hyperplasia, cartilage destruction, and the other main features in the pathogenesis of CIA. This provides fundamental evidence for the anti-arthritic properties of Bi-Qi and corroborates the use of Bi-Qi TCM formula for the treatment of RA.

CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

PubMed

Zhai, Yue; Wu, Bo; Li, Jia; Yao, Xi-ying; Zhu, Ping; Chen, Zhi-nan

2016-01-01

TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region. CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147's extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.

Dissemination and Exploitation: Project Goals beyond Science

NASA Astrophysics Data System (ADS)

Hamann, Kristin; Reitz, Anja

2017-04-01

Dissemination and Exploitation are essential parts of public funded projects. In Horizon 2020 a plan for the exploitation and dissemination of results (PEDR) is a requirement. The plan should contain a clear vision on the objectives of the project in relation to actions for dissemination and potential exploitation of the project results. The actions follow the basic idea to spread the knowledge and results gathered within the project and face the challenge of how to bring the results into potentially relevant policy circle and how they impact the market. The plan follows the purpose to assess the impact of the project and to address various target groups who are interested in the project results. Simply put, dissemination concentrates on the transfer of knowledge and exploitation on the commercialization of the project. Beyond the question of the measurability of project`s impact, strategies within science marketing can serve purposes beyond internal and external communication. Accordingly, project managers are facing the challenge to implement a dissemination and exploitation strategy that ideally supports the identification of all partners with the project and matches the current discourse of the project`s content within the society, politics and economy. A consolidated plan might unite all projects partners under a central idea and supports the identification with the project beyond the individual research questions. Which applications, strategies and methods can be used to bring forward a PEDR that accompanies a project successfully and allows a comprehensive assessment of the project afterwards? Which hurdles might project managers experience in the dissemination process and which tasks should be fulfilled by the project manager?

Disseminated Mycobacterium chimaera Infection After Cardiothoracic Surgery.

PubMed

Tan, Nicholas; Sampath, Rahul; Abu Saleh, Omar M; Tweet, Marysia S; Jevremovic, Dragan; Alniemi, Saba; Wengenack, Nancy L; Sampathkumar, Priya; Badley, Andrew D

2016-09-01

Ten case reports of disseminated Mycobacterium chimaera infections associated with cardiovascular surgery were published from Europe. We report 3 cases of disseminated M chimaera infections with histories of aortic graft and/or valvular surgery within the United States. Two of 3 patients demonstrated ocular involvement, a potentially important clinical finding.

Magnetic resonance imaging diagnosis of disseminated necrotizing leukoencephalopathy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atlas, S.W.; Grossman, R.I.; Packer, R.J.

1987-01-01

Disseminated necrotizing leukoencephalopathy is a rare syndrome of progressive neurologic deterioration seen most often in patients who have received central nervous system irradiation combined with intrathecal or systemic chemotherapy in the treatment or prophylaxis of various malignancies. Magnetic resonance imaging was more sensitive than computed tomography in detecting white matter abnormalities in the case of disseminated necrotizing leukoencephalopathy reported here. Magnetic resonance imaging may be useful in diagnosing incipient white matter changes in disseminated necrotizing leukoencephalopathy, thus permitting early, appropriate therapeutic modifications.

Gene expression analysis of rheumatoid arthritis synovial lining regions by cDNA microarray combined with laser microdissection: up-regulation of inflammation-associated STAT1, IRF1, CXCL9, CXCL10, and CCL5

PubMed Central

Yoshida, S; Arakawa, F; Higuchi, F; Ishibashi, Y; Goto, M; Sugita, Y; Nomura, Y; Niino, D; Shimizu, K; Aoki, R; Hashikawa, K; Kimura, Y; Yasuda, K; Tashiro, K; Kuhara, S; Nagata, K; Ohshima, K

2012-01-01

Objectives The main histological change in rheumatoid arthritis (RA) is the villous proliferation of synovial lining cells, an important source of cytokines and chemokines, which are associated with inflammation. The aim of this study was to evaluate gene expression in the microdissected synovial lining cells of RA patients, using those of osteoarthritis (OA) patients as the control. Methods Samples were obtained during total joint replacement from 11 RA and five OA patients. Total RNA from the synovial lining cells was derived from selected specimens by laser microdissection (LMD) for subsequent cDNA microarray analysis. In addition, the expression of significant genes was confirmed immunohistochemically. Results The 14 519 genes detected by cDNA microarray were used to compare gene expression levels in synovial lining cells from RA with those from OA patients. Cluster analysis indicated that RA cells, including low- and high-expression subgroups, and OA cells were stored in two main clusters. The molecular activity of RA was statistically consistent with its clinical and histological activity. Expression levels of signal transducer and activator of transcription 1 (STAT1), interferon regulatory factor 1 (IRF1), and the chemokines CXCL9, CXCL10, and CCL5 were statistically significantly higher in the synovium of RA than in that of OA. Immunohistochemically, the lining synovium of RA, but not that of OA, clearly expressed STAT1, IRF1, and chemokines, as was seen in microarray analysis combined with LMD. Conclusions Our findings indicate an important role for lining synovial cells in the inflammatory and proliferative processes of RA. Further understanding of the local signalling in structural components is important in rheumatology. PMID:22401175

Inflammatory cytokine levels in synovial fluid 3, 4 days postoperatively and its correlation with early-phase functional recovery after anterior cruciate ligament reconstruction: a cohort study.

PubMed

Inoue, Makiko; Muneta, Takeshi; Ojima, Miyoko; Nakamura, Kaori; Koga, Hideyuki; Sekiya, Ichiro; Okazaki, Mutsumi; Tsuji, Kunikazu

2016-12-01

Synovial fluid was collected prior to and at 3 to 4 days after ACL reconstruction to investigate the correlation between inflammatory cytokine levels in the acute phase after surgery and physical functional recovery at 3 months postoperatively.  For this purpose, 79 patients with ACL reconstruction using semitendinosus tendons were included in the study. Median days from injury to surgery were 80 days (13-291 days). Synovial fluid was obtained just before surgery and at 3 to 4 days after surgery. Physical activity of each patient was evaluated at 3 months postoperatively, and scored from 0 (hard to walk) to 5 (run). Patients able to jog (score 4) or run (score 5) were considered as the "quick recovery" group and others (scores 1-3) as the "delayed recovery" group. Physical activity recovery scores in the early surgery group (preoperative period less than 60 days; Group I) were significantly better than those in the delayed surgery group (Group II). Among the cytokines tested, TNF-alpha and IL10 levels in synovial fluid were significantly higher in Group II at 3 to 4 days postoperatively, while levels of these cytokines were quite comparable preoperatively between the groups. Increased IL1-beta expression was noted in the delayed recovery group at 3 to 4 days postoperatively. In addition, levels of IL6, IL10 and IFN-gamma also tended to increase in patients with delayed recovery. Delayed ACL reconstruction increases levels of inflammatory cytokines in synovial fluid after surgery and correlates with a prolonged recovery of short-period physical activity of the patients.

Disseminated Mycobacterium chimaera Infection After Cardiothoracic Surgery

PubMed Central

Tan, Nicholas; Sampath, Rahul; Abu Saleh, Omar M.; Tweet, Marysia S.; Jevremovic, Dragan; Alniemi, Saba; Wengenack, Nancy L.; Sampathkumar, Priya; Badley, Andrew D.

2016-01-01

Ten case reports of disseminated Mycobacterium chimaera infections associated with cardiovascular surgery were published from Europe. We report 3 cases of disseminated M chimaera infections with histories of aortic graft and/or valvular surgery within the United States. Two of 3 patients demonstrated ocular involvement, a potentially important clinical finding. PMID:27703994

Action of polysaccharides of similar average mass but differing molecular volume and charge on fluid drainage through synovial interstitium in rabbit knees

PubMed Central

Scott, D; Coleman, P J; Mason, R M; Levick, J R

2000-01-01

Hyaluronan (HA), an anionic polysaccharide of synovial fluid, attenuates fluid loss from joints as joint pressure is raised (‘outflow buffering’). The buffering is thought to depend on the expanded molecular domain of the polymer, which causes reflection by synovial extracellular matrix, leading to flow-dependent concentration polarization. We therefore assessed the effects of polysaccharides of differing average molecular volume and charge. Trans-synovial fluid drainage(Q̇s) was measured at controlled joint fluid pressure (Pj) in knees of anaesthetized rabbits. The joints were infused with polydisperse HA of weight-average mass 2100 kDa (4 mg ml−1, n = 17), with polydisperse neutral dextran of similar average mass (2000 kDa; n = 7) or with Ringer solution vehicle (n = 2). The role of polymer charge was assessed by infusions of neutral or sulphated dextran of average molecular mass 500 kDa (n = 6). When HA was present, Q̇s increased little with pressure, forming a virtual plateau of ∼4 μl min−1 from 10 to 25 cmH2O. Neutral dextran 2000 failed to replicate this effect. Instead, Q̇s increased steeply with Pj, reaching eight times the HA value by 20 cmH2O (P = 0.0001, ANOVA). Dextran 2000 reduced flows in comparison with Ringer solution. Analysis of the aspirated joint fluid showed that 31 ± 0.07 % (s.e.m.) of dextran 2000 in the filtrand was reflected by synovium, compared with ≥ 79 % for HA. The viscometric molecular radius of the dextran, ∼31 nm, was smaller than that of HA (101–181 nm), as was its osmotic pressure. Anionic dextran 500 failed to buffer fluid drainage, but it reduced fluid escape and synovial conductance dQ̇s/dPj more than neutral dextran 500 (P < 0.0001, ANOVA). The anionic charge increased the molecular volume and viscosity of dextran 500. The results support the hypothesis that polymer molecular volume influences its reflection by interstitial matrix and outflow buffering. Polymer charge influences flow through an effect on

Fiber-optic particle plasmon resonance sensor for detection of interleukin-1β in synovial fluids.

PubMed

Chiang, Chang-Yue; Hsieh, Ming-Lung; Huang, Kuo-Wei; Chau, Lai-Kwan; Chang, Chia-Ming; Lyu, Shaw-Ruey

2010-11-15

A facile and label-free biosensing method has been developed for determining an osteoarthritis concerned cytokine, interleukin-1β (IL-1β), in synovial fluids. The biosensing technique, fiber-optic particle plasmon resonance (FOPPR), is based on gold nanoparticles-modified optical fiber where the gold nanoparticle surface has been modified by a mixed self-assembled monolayer for further conjugation of anti-IL-1β antibody and minimization of nonspecific adsorption. Upon binding of IL-1β to anti-IL-1β on the gold nanoparticle surface, the absorbance of the gold nanoparticle layer on the optical fiber changes and the signal change is enhanced through multiple total internal reflections along the optical fiber. Results show that the detection of IL-1β in synovial fluid by this sensor agrees quantitatively with the clinically accepted enzyme-linked immunosorbent assay (ELISA) method but a much shorter analysis time is required (<10 min). The sensor response versus log concentration of IL-1β was linear (r=0.9947) over the concentration range of 0.050-10 ng/mL and a limit of detection (LOD) of 21 pg/mL (1.2 pM) was achieved. Such a LOD for IL-1β (17 kDa) represents a major advancement in the field of real-time monitoring of low molecular weight proteins in complex biological fluids. Copyright © 2010 Elsevier B.V. All rights reserved.

Public information, dissemination, and behavior analysis

PubMed Central

Morris, Edward K.

1985-01-01

Behavior analysts have become increasingly concerned about inaccuracies and misconceptions in the public, educational, and professional information portraying their activities, but have done little to correct these views. The present paper has two purposes in this regard. First, the paper describes some of the conditions that have given rise to these concerns. Second, and more important, the paper surveys various procedures and programs for the dissemination of public information that may correct inaccuracies and misconceptions. Special consideration is also given to issues involving (a) the assessment of the problem, (b) the content and means of dissemination, (c) the possible contributions of behavior analysts to current misunderstandings, and (d) relationships between behavior analysts and the media. The dissemination of accurate and unbiased information constitutes an important new undertaking for behavior analysis. The future of the field may depend in part on such activity. PMID:22478623

Evaluation of a collagenase generated osteoarthritis biomarker in the synovial fluid from elbow joints of dogs with medial coronoid disease and unaffected dogs.

PubMed

Prink, Adam; Hayashi, Kei; Kim, Sun-Young; Kim, James; Kapatkin, Amy

2010-01-01

To evaluate whether synovial fluid concentrations of an osteoarthritis biomarker in dysplastic canine elbows with medial coronoid disease (MCD) are elevated compared with unaffected elbows and to determine if these concentrations correlate to the degree of articular cartilage damage. Cross sectional clinical study. Dogs (n=19; 35 elbows) with MCD and dogs (8; 16 elbows) with unaffected elbows. Concentrations of a collagenase-generated cleavage neoepitope of type II collagen (Col2-3/4C(long mono), or C2C) in joint fluid from elbows were analyzed and compared between dogs with MCD and unaffected dogs. Correlation of C2C concentration with subjective grading of articular cartilage surface damage was also evaluated. Mean (+/-SD) C2C concentration from MCD dogs was significantly higher (112.3+/-24.8 ng/mL) than in unaffected dogs (76.1+/-16.9 ng/mL; P<.05). There was a moderate correlation between cartilage damage grade and increasing C2C concentrations (P<.05, r=0.62) C2C concentrations are elevated in the synovial fluid of dogs with MCD compared with unaffected elbows, and a moderate, significant correlation was identified between these concentrations and subjective grading of articular cartilage damage. This preliminary data suggest that C2C concentrations in synovial fluid may have potential as a biomarker for diagnosis of articular cartilage damage associated with MCD and as a means of objectively determining the degree of articular cartilage damage.

Pressure ulcer guideline development and dissemination in Europe.

PubMed

Meesterberends, Esther; Halfens, Ruud; Lohrmann, Christa; de Wit, Rianne

2010-06-01

To explore the current state of pressure ulcer guideline development and dissemination, from national to local level (i.e. nursing homes) in six European countries: England, Germany, Italy, the Netherlands, Portugal and Sweden. Pressure ulcers are a persistent problem in healthcare institutions. Their prevalence is influenced by many factors, one of them being the development and dissemination of pressure ulcer guidelines. These are difficult and complex processes and it is not clear whether they differ between European countries. Literature review and semi-structured interviews. Interviews were conducted in six countries at national and nursing home level. Four countries had national pressure ulcer prevention and treatment guidelines. Portugal had no national guidelines and Sweden had shifted the responsibility to regional level. All participating nursing homes had pressure ulcer guidelines except those in Portugal. Control and monitoring of guideline dissemination was carried out only in Sweden and England. All countries studied have national or regional pressure ulcer prevention and treatment guidelines, except Portugal. Portugal is also the only country where none of the nursing homes included had pressure ulcer guidelines. Because the dissemination of such guidelines does not imply actual implementation, further research should focus on the implementation process. Clinical guidelines, like pressure ulcer guidelines, are important tools in guiding the care processes in healthcare institutions. Successful dissemination of guidelines from national level to individual healthcare institutions is a first and necessary step in actually applying them. Monitoring of the guideline dissemination process is therefore essential.

Detection of disseminated peritoneal tumors by fluorescein diacrylate in mice

NASA Astrophysics Data System (ADS)

Harada, Yoshinori; Furuta, Hirokazu; Murayama, Yasutoshi; Dai, Ping; Fujikawa, Yuta; Urano, Yasuteru; Nagano, Tetsuo; Morishita, Koki; Hasegawa, Akira; Takamatsu, Tetsuro

2009-02-01

Tumor invasion to the peritoneum is a poor prognostic factor in cancer patients. Accurate diagnosis of disseminated peritoneal tumors is essential to accurate cancer staging. To date, peritoneal washing cytology during laparotomy has been used for diagnosis of peritoneal dissemination of gastrointestinal cancer, but its sensitivity has not been satisfactory. Thus, a more direct approach is indispensable to detect peritoneal dissemination in vivo. Fluorescein diacrylate (FDAcr) is an esterase-sensitive fluorescent probe derived from fluorescein. In cancer cells, fluorescent fluorescein generated by exogenous application of FDAcr selectively deposits owing to its stronger hydrolytic enzyme activity and its lower leakage rate. We examined whether FDAcr can specifically detect disseminated peritoneal tumors in athymic nude mouse models. Intraperitoneally administered FDAcr revealed disseminated peritoneal microscopic tumors not readily recognized on white-light imaging. These results suggest that FDAcr is a useful probe for detecting disseminated peritoneal tumors.

Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducing SP1-mediated Noxa expression and proteasomal degradation of Mcl-1.

PubMed

Kim, Eugene Y; Sudini, Kuladeep; Singh, Anil K; Haque, Mahamudul; Leaman, Douglas; Khuder, Sadik; Ahmed, Salahuddin

2018-05-25

Rheumatoid arthritis (RA) is characterized by hyperplastic pannus formation mediated by activated synovial fibroblasts (RASFs) that cause joint destruction. We have shown earlier that RASFs exhibit resistance to apoptosis, primarily as a result of enhanced expression of myeloid cell leukemia-1 (Mcl-1). In this study, we discovered that ursolic acid (UA), a plant-derived pentacyclic triterpenoid, selectively induces B-cell lymphoma 2 homology 3-only protein Noxa in human RASFs. We observed that UA-induced Noxa expression was followed by a consequent decrease in Mcl-1 expression in a dose-dependent manner. Subsequent evaluation of the signaling pathways showed that UA-induced Noxa is primarily mediated by the JNK pathway in human RASFs. Chromatin immunoprecipitation (IP) studies into the promoter region of Noxa indicated the role of transcription factor specificity protein 1 in JNK-mediated Noxa expression. Furthermore, the results from IP studies and proximity ligation assays indicated that UA-induced Noxa colocalizes and associates with Mcl-1 to prime it for proteasomal degradation through K 48 -linked ubiquitination by the selective recruitment of Mcl-1 ubiquitin ligase E3, a homologous to E6-associated protein C terminus domain-containing E3 ubiquitin ligase. These findings unveil a novel mechanism of inducing apoptosis in RASFs and a potential adjunct therapeutic strategy of regulating synovial hyperplasia in RA.-Kim, E. Y., Sudini, K., Singh, A. K., Haque, M., Leaman, D., Khuder, S., Ahmed, S. Ursolic acid facilitates apoptosis in rheumatoid arthritis synovial fibroblasts by inducing SP1-mediated Noxa expression and proteasomal degradation of Mcl-1.

The effect of polymer size and charge of molecules on permeation through synovial membrane and accumulation in hyaline articular cartilage.

PubMed

Sterner, B; Harms, M; Wöll, S; Weigandt, M; Windbergs, M; Lehr, C M

2016-04-01

The treatment of joint related diseases often involves direct intra-articular injections. For rational development of novel delivery systems with extended residence time in the joint, detailed understanding of transport and retention phenomena within the joint is mandatory. This work presents a systematic study on the in vitro permeation, penetration and accumulation of model polymers with differing charges and molecular weights in bovine joint tissue. Permeation experiments with bovine synovial membrane were performed with PEG polymers (6-200 kDa) and methylene blue in customized diffusion chambers. For polyethylene glycol, 2-fold (PEG 6 kDa), 3-fold (PEG 10 kDa) and 13-fold (PEG 35 kDa) retention by the synovial membrane in reference to the small molecule methylene blue was demonstrated. No PEG 200 kDa was found in the acceptor in detectable amounts after 48 h. This showed the potential for a distinct extension of joint residence times by increasing molecular weights. In addition, experiments with bovine cartilage tissue were conducted. The ability for positively charged, high molecular weight chitosans and HEMA-Co-TMAP (HCT) polymers (up to 233 kDa) to distribute throughout the entire cartilage matrix was demonstrated. In contrast, a distribution into cartilage was not observed for neutral PEG polymers (6-200 kDa). Furthermore, the positive charge density of different compounds (chitosan, HEMA-Co-TMAP, methylene blue, MSC C1 (neutral NCE) and MSC D1 (positively charged NCE) was found to correlate with their accumulation in bovine cartilage tissue. In summary, the results offer pre-clinical in vitro data, indicating that the modification of molecular size and charge of a substance has the potential to decelerate its clearance through the synovial membrane and to promote accumulation inside the cartilage matrix. Copyright © 2016 Elsevier B.V. All rights reserved.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

PubMed

Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-24

To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.

Disseminated cryptococcosis in an immunocompetent patient.

PubMed

Mada, Pradeep; Nowack, Brad; Cady, Beth; Joel Chandranesan, Andrew Stevenson

2017-07-18

Cryptococcosis is a fungal infection which is commonly associated with immune-compromised state. Disseminated infection in immunocompetent individuals is extremely rare. We present a case of a 56-year-old African American patient who presented with unilateral knee pain and swelling and was subsequently diagnosed with cryptococcal bone mass with dissemination of infection. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Information Dissemination: Case Studies on Electronic Dissemination at Four Agencies.

DTIC Science & Technology

1992-07-01

MEDLARS to conduct searches for physicians, nurses , lab technicians, and administrators, often for the same reasons-patient care , preparation of articles...accreditation that apply to health care delivery. Citations are prepared by NLM and the American Hospital Association. This file contains citations covering...AVLINE Audio Visuals On-line BIOETHICSLINE Bioethics On-line Page 5 GAOIIMTEC-92-6FS Electronic Information Dissemination Contents CANCERLIT Cancer

Dissemination: Bringing Translational Research to Completion

PubMed Central

Park, Daniel J.; Burke, Janice P.

2013-01-01

Despite the availability of innovative health care research, a gap exists between research-generated knowledge and the utilization of that knowledge in real-world practice settings. This article examines the transition from research to implementation in the context of the dissemination of A. Jean Ayres’ sensory integration procedures and of the challenges currently facing the University of Southern California Well Elderly Studies research team. Drawing from the emerging field of implementation science, this article discusses how researchers can develop an implementation plan to more easily translate evidence into practice. Such plans should address the intervention’s reach (i.e., its capacity to penetrate into the intended target population), the settings for which it is applicable, the leaders who will encourage practitioner uptake, stakeholder groups, and challenges to dissemination. By taking action to ensure the more effective dissemination of research-generated knowledge, researchers can increase the likelihood that their interventions will lead to improvements in practice and more effective care for consumers. PMID:23433273

40 CFR 1400.10 - Limitation on public dissemination.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.10 Limitation on public dissemination. Except as... officials, and qualified researchers are prohibited from disseminating OCA information and OCA rankings to...

40 CFR 1400.10 - Limitation on public dissemination.

Code of Federal Regulations, 2012 CFR

2012-07-01

... SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.10 Limitation on public dissemination. Except as... officials, and qualified researchers are prohibited from disseminating OCA information and OCA rankings to...

40 CFR 1400.10 - Limitation on public dissemination.

Code of Federal Regulations, 2014 CFR

2014-07-01

... SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.10 Limitation on public dissemination. Except as... officials, and qualified researchers are prohibited from disseminating OCA information and OCA rankings to...

40 CFR 1400.10 - Limitation on public dissemination.

Code of Federal Regulations, 2013 CFR

2013-07-01

... SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.10 Limitation on public dissemination. Except as... officials, and qualified researchers are prohibited from disseminating OCA information and OCA rankings to...

Course of serum amyloid A (SAA) plasma concentrations in horses undergoing surgery for injuries penetrating synovial structures, an observational clinical study.

PubMed

Haltmayer, Eva; Schwendenwein, Ilse; Licka, Theresia F

2017-05-22

Injuries penetrating synovial structures are common in equine practice and often result in septic synovitis. Significantly increased plasma levels of serum amyloid A (SAA) have been found in various infectious conditions in horses including wounds and septic arthritis. Plasma SAA levels were found to decrease rapidly once the infectious stimulus was eliminated. The purpose of the current study was to investigate the usefulness of serial measurements of plasma SAA as a monitoring tool for the response to treatment of horses presented with injuries penetrating synovial structures. In the current study plasma SAA concentrations were measured every 48 hours (h) during the course of treatment. A total of 19 horses with a wound penetrating a synovial structure were included in the current study. Horses in Group 1 (n = 12) (injuries older than 24 h) only needed one surgical intervention. Patients in this group had significantly lower median plasma SAA levels (P = 0.001) between 48 h (median 776 mg/L) and 96 h (median 202 mg/L) after surgery. A significant decrease (P = 0.004) in plasma SAA levels was also observed between 96 h after surgery (median 270 mg/L) and 6 days (d) after surgery (median 3 mg/L). Four horses (Group 2) required more than one surgical intervention. In contrast to Group 1 patients in Group 2 had either very high initial plasma concentrations (3378 mg/L), an increase or persistently high concentrations of plasma SAA after the first surgery (median 2525 mg/L). A small group of patients (n = 3) (Group 3) were admitted less than 24 h after sustaining a wound. In this group low SAA values at admission (median 23 mg/L) and peak concentrations at 48 h after surgery (median 1016 mg/L) were observed followed by a decrease in plasma SAA concentration over time. A decrease in plasma SAA concentrations between two consecutive time points could be associated with positive response to treatment in the current study. Therefore, serial

Characterization of synovial fluid cytokine profiles in chronic meniscal tear of the knee.

PubMed

Bigoni, Marco; Turati, Marco; Sacerdote, Paola; Gaddi, Diego; Piatti, Massimiliano; Castelnuovo, Alberto; Franchi, Silvia; Gandolla, Marta; Pedrocchi, Alessandra; Omeljaniuk, Robert J; Bresciani, Elena; Locatelli, Vittorio; Torsello, Antonio

2017-02-01

Concentrations of pro- and anti-inflammatory cytokines in synovial fluid samples collected from patients with chronic meniscal tears were investigated. An acute inflammatory response is generally reported 24-48 h after knee injury, but the largest body of data available in literature concerns anterior cruciate ligament injury and very little information is available about the balance of soluble factors in the synovial fluid of knees with chronic meniscal tears. Sixty-nine patients (46 males and 23 females) with meniscal tear that occurred more than 3 months earlier were enrolled. According to cartilage integrity assessment by arthroscopic examination, patients were assigned to one of the following groups: (i) no chondral damage (n = 18); (ii) chondral damage graded from I to II (n = 15); and (iii) chondral damage graded from III to IV (n = 37). In all groups, levels of IL-10 and inflammatory cytokines IL-6, TNF-α, and IL-8 where greater compared with those reported in the intact population; by contrast, levels of IL-1ra and IL-1β were significantly lower. Interestingly, IL-6 levels were higher in female than male patients. Cytokine levels did not correlate with degree of chondral damage. IL-6 and IL-1ra levels positively correlated with IL-1β, and negatively correlated with TNF-α. Interestingly, levels of IL-1β and TNF-α were inversely correlated. Our data demonstrate increased levels of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α) in the chronic phase of meniscal trauma. This pro-inflammatory state is maintained in the joint from the time of initial injury to several months later and could be a key factor in hampering cartilage regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:340-346, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Information dissemination and use: critical components in occupational safety and health.

PubMed

Schulte, P A; Okun, A; Stephenson, C M; Colligan, M; Ahlers, H; Gjessing, C; Loos, G; Niemeier, R W; Sweeney, M H

2003-11-01

Information dissemination is a mandated, but understudied, requirement of occupational and environmental health laws and voluntary initiatives. Research is needed on the factors that enhance and limit the development, transfer, and use of occupational safety and health information (OSH). Contemporary changes in the workforce, workplaces, and the nature of work will require new emphasis on the dissemination of information to foster prevention. Legislative and regulatory requirements and voluntary initiatives for dissemination of OSH information were identified and assessed. Literature on information dissemination was reviewed to identify important issues and useful approaches. More than 20 sections of laws and regulations were identified that mandated dissemination of occupational and environmental safety and health information. A four-stage approach for tracking dissemination and considering the flow of information was delineated. Special areas of dissemination were identified: the information needs of the changing workforce, new and young workers; small businesses; and workers with difficulty in understanding or reading English. We offer a framework for dissemination of OSH information and underscore the need to focus on the extent to which decision-makers and others receive and use such information. More solid data are also needed on current investments in disseminating, diffusing and applying OSH information and on the utility of that information. Am. J. Ind. Med. 44:515-531, 2003. Published 2003 Wiley-Liss, Inc.

Cacades: A reliable dissemination protocol for data collection sensor network

USGS Publications Warehouse

Peng, Y.; Song, W.; Huang, R.; Xu, M.; Shirazi, B.; LaHusen, R.; Pei, G.

2009-01-01

In this paper, we propose a fast and reliable data dissemination protocol Cascades to disseminate data from the sink(base station) to all or a subset of nodes in a data collection sensor network. Cascades makes use of the parentmonitor-children analogy to ensure reliable dissemination. Each node monitors whether or not its children have received the broadcast messages through snooping children's rebroadcasts or waiting for explicit ACKs. If a node detects a gap in its message sequences, it can fetch the missing messages from its neighbours reactively. Cascades also considers many practical issues for field deployment, such as dynamic topology, link/node failure, etc.. It therefore guarantees that a disseminated message from the sink will reach all intended receivers and the dissemination is terminated in a short time period. Notice that, all existing dissemination protocols either do not guarantee reliability or do not terminate [1, 2], which does not meet the requirement of real-time command control. We conducted experiment evaluations in both TOSSIM simulator and a sensor network testbed to compare Cascades with those existing dissemination protocols in TinyOS sensor networks, which show that Cascades achieves a higher degree of reliability, lower communication cost, and less delivery delay. ??2009 IEEE.

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts.

PubMed

Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R; Sundström, Yvonne; Galsgaard, Elisabeth D; Ahern, David; Andersen, Martin; Baslund, Bo; Bartels, Else M; Bliddal, Henning; Feldmann, Marc; Malmström, Vivianne; Berg, Louise; Spee, Pieter; Söderström, Kalle

2014-08-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA. © 2014 John Wiley & Sons Ltd.

Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A receptors determine natural killer degranulation towards rheumatoid arthritis synovial fibroblasts

PubMed Central

Nielsen, Natasja; Pascal, Veronique; Fasth, Andreas E R; Sundström, Yvonne; Galsgaard, Elisabeth D; Ahern, David; Andersen, Martin; Baslund, Bo; Bartels, Else M; Bliddal, Henning; Feldmann, Marc; Malmström, Vivianne; Berg, Louise; Spee, Pieter; Söderström, Kalle

2014-01-01

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA. PMID:24673109

Synovial aspiration and serological testing in two-stage revision arthroplasty for prosthetic joint infection: evaluation before reconstruction with a mean follow-up of twenty seven months.

PubMed

Mühlhofer, Heinrich M L; Knebel, C; Pohlig, Florian; Feihl, Susanne; Harrasser, Norbert; Schauwecker, Johannes; von Eisenhart-Rothe, Rüdiger

2018-02-01

The two-stage revision protocol is the gold standard for controlling and treating low-grade prosthetic joint infections of total hip and total knee arthroplasty. The antibiotic pause for diagnostic reasons before reconstruction (stage two) is discussed in relation to the persistence of the infection and the development of resistant bacterial strains. Serological markers and a synovial analysis are commonly used to exclude the persistence of infection. Therefore, we asked (1) is the serological testing of C-reactive protein and leucocytes a valuable tool to predict a persistence of infection? and (2) what is the role of synovial aspiration of Plymethylmethacrylat (PMMA) spacers in hip and knee joints? One hundred twelve patients who were MSIS criteria-positive for a prosthetic joint infection were studied, including 45 total hip arthroplasties (THA) and 67 total knee artrhoplasties (TKA) patients. All patients were treated with a two-stage-protocol using a mobile PMMA spacer after a 14-day antibiotic-free interval, during which we measured serological markers (C-reactive protein and leucocytes) and performed synovial aspiration (white blood cell count, polymorphonuclear cell percentage, and microbiological culture) in these patients and compared the results with those of their long-term-follow-up (mean follow-up 27 months, range 24-36 months). Of the 112 patients, 89 patients (79.5%; 95% CI 72-86.9) exhibited infection control after a two-stage exchange, and we detected most methicillin-resistant, coagulase-negative Staphylococci (CoNS) in cases of a persistent infection. The mean sensitivity of serum C-reactive protein in the patients was 0.43 (range 0.23-0.64), and the mean specificity was 0.73 (range 0.64-0.82). For serum leucocytes, the mean sensitivity was 0.09 (range 0-0.29), and the mean specificity was 0.81 (range 0.7-0.92). The mean sensitivity for the WBC count in the synovial fluid (PMMA spacer aspiration) was 0.1 (range 0-0.29), and the mean

21 CFR 99.401 - Corrective actions and cessation of dissemination of information.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HEALTH AND HUMAN SERVICES GENERAL DISSEMINATION OF INFORMATION ON UNAPPROVED/NEW USES FOR MARKETED DRUGS... cessation of dissemination of information. (a) FDA actions based on post dissemination data. If FDA receives... requirements; or (2) Order the manufacturer to cease dissemination of information and to take corrective action...

In vivo effects of carprofen, deracoxib, and etodolac on prostanoid production in blood, gastric mucosa, and synovial fluid in dogs with chronic osteoarthritis.

PubMed

Sessions, John K; Reynolds, Lisa R; Budsberg, Steven C

2005-05-01

To evaluate in vivo activity of carprofen, deracoxib, and etodolac on prostanoid production in several target tissues in dogs with chronic osteoarthritis. 8 dogs with chronic unilateral osteoarthritis of the stifle joint. Each dog received carprofen, deracoxib, or etodolac for 10 days with a 30- to 60-day washout period between treatments. On days 0, 3, and 10, prostaglandin (PG) E2 concentrations were measured in lipopolysaccharide-stimulated blood, synovial fluid, and gastric mucosal biopsy specimens; PGE1 concentrations were measured in gastric mucosal biopsy specimens; and thromboxane B2 (TXB2) was evaluated in blood. Carprofen and deracoxib significantly suppressed PGE2 concentrations in blood at days 3 and 10, compared with baseline, whereas etodolac did not. None of the drugs significantly suppressed TXB2 concentrations in blood or gastric PGE1 synthesis at any time point. All 3 drugs significantly decreased gastric synthesis of PGE2 at day 3 but not day 10 of each treatment period. All 3 drugs decreased synovial fluid PGE2 concentrations in the affected and unaffected stifle joints at days 3 and 10. Results indicate that carprofen and deracoxib act in vivo on target tissues as COX-1-sparing drugs by sparing gastric PGE1 and PGE2 synthesis and production of TXB2 by platelets. Etodolac also appears to be COX-1 sparing but may have variable effects on COX-2 depending on the tissue. In gastric mucosa and synovial fluid, there were no significant differences in PG production between compounds at recommended concentrations.

A comparison of manual and electronic counting for total nucleated cell counts on synovial fluid from canine stifle joints.

PubMed

Atilola, M A; Lumsden, J H; Rooke, F

1986-04-01

Synovial fluids collected from the stifle joints of 20 physically normal adult dogs were subjected to cytological examination. A total nucleated cell count was performed on each sample using both an electronic cell counter and a hemocytometer. The mean of the total counts done with the electronic counter was significantly higher (1008 cells/microL) than that obtained manually with the hemocytometer (848 cells/microL).

Stromal cell markers are differentially expressed in the synovial tissue of patients with early arthritis.

PubMed

Choi, Ivy Y; Karpus, Olga N; Turner, Jason D; Hardie, Debbie; Marshall, Jennifer L; de Hair, Maria J H; Maijer, Karen I; Tak, Paul P; Raza, Karim; Hamann, Jörg; Buckley, Christopher D; Gerlag, Danielle M; Filer, Andrew

2017-01-01

Previous studies have shown increased expression of stromal markers in synovial tissue (ST) of patients with established rheumatoid arthritis (RA). Here, ST expression of stromal markers in early arthritis in relationship to diagnosis and prognostic outcome was studied. ST from 56 patients included in two different early arthritis cohorts and 7 non-inflammatory controls was analysed using immunofluorescence to detect stromal markers CD55, CD248, fibroblast activation protein (FAP) and podoplanin. Diagnostic classification (gout, psoriatic arthritis, unclassified arthritis (UA), parvovirus associated arthritis, reactive arthritis and RA), disease outcome (resolving vs persistent) and clinical variables were determined at baseline and after follow-up, and related to the expression of stromal markers. We observed expression of all stromal markers in ST of early arthritis patients, independent of diagnosis or prognostic outcome. Synovial expression of FAP was significantly higher in patients developing early RA compared to other diagnostic groups and non-inflammatory controls. In RA FAP protein was expressed in both lining and sublining layers. Podoplanin expression was higher in all early inflammatory arthritis patients than controls, but did not differentiate diagnostic outcomes. Stromal marker expression was not associated with prognostic outcomes of disease persistence or resolution. There was no association with clinical or sonographic variables. Stromal cell markers CD55, CD248, FAP and podoplanin are expressed in ST in the earliest stage of arthritis. Baseline expression of FAP is higher in early synovitis patients who fulfil classification criteria for RA over time. These results suggest that significant fibroblast activation occurs in RA in the early window of disease.

Decoy receptor 3 down-regulates centrosomal protein 70 kDa specifically in rheumatoid synovial fibroblasts.

PubMed

Fukuda, Koji; Miura, Yasushi; Maeda, Toshihisa; Hayashi, Shinya; Kuroda, Ryosuke

2018-03-01

Decoy receptor 3 (DcR3) competitively binds to Fas ligand, lymphotoxin-related inducible ligand that competes for glycoprotein D binding to herpes virus entry mediator on T cells (LIGHT) and TNF-like ligand 1A (TL1A), thereby preventing their effects. Using a microarray assay, we previously newly identified centrosomal protein 70 kDa (CEP70) as one of the genes whose expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis (RA-FLS) is reduced by DcR3. Here, we investigated the significance of DcR3 regulation of CEP70 for RA-FLS. Synovial samples were obtained from RA patients who had never been treated with biologics and from osteoarthritis (OA) patients. CEP70 mRNA expression was quantified using RT-qPCR analysis. CEP70 protein expression was assessed using immunohistochemical and western blot analyses. CEP70 was expressed predominantly in the superficial lining layer in RA synovial tissue. CEP70 expression was dose-dependently downregulated by DcR3-Fc in RA-FLS but was not downregulated in OA-FLS. TL1A antibody prevented the DcR3-Fc inhibitory effects on CEP70 expression in RA-FLS. These results indicated that DcR3 reduces CEP70 expression in RA-FLS by binding to membrane-bound TL1A and may suppress RA-FLS proliferation. The reduction in CEP70 expression by DcR3/TL1A signaling may control the hyperplasia of RA synovium.

Administration of PDE4 Inhibitors Suppressed the Pannus-Like Inflammation by Inhibition of Cytokine Production by Macrophages and Synovial Fibroblast Proliferation

PubMed Central

Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

2007-01-01

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1β, TNF-α, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-α and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation. PMID:18274640

Administration of PDE4 inhibitors suppressed the pannus-like inflammation by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

PubMed

Kobayashi, Katsuya; Suda, Toshio; Manabe, Haruhiko; Miki, Ichiro

2007-01-01

A marked proliferation of synovial fibroblasts in joints leads to pannus formation in rheumatoid arthritis (RA). Various kinds of cytokines are produced in the pannus. The purpose of this study is to elucidate the effects of phosphodiesterase 4 (PDE4) inhibitors in a new animal model for the evaluation of pannus formation and cytokine production in the pannus. Mice sensitized with methylated bovine serum albumin (mBSA) were challenged by subcutaneous implantation of a membrane filter soaked in mBSA solution in the back of the mice. Drugs were orally administered for 10 days. The granuloma formed around the filter was collected on day 11. It was chopped into pieces and cultured in vitro for 24 hr. The cytokines were measured in the supernatants. The type of cytokines produced in the granuloma was quite similar to those produced in pannus in RA. Both PDE4 inhibitors, KF66490 and SB207499, suppressed the production of IL-1beta, TNF-alpha, and IL-12, and the increase in myeloperoxidase activity, a marker enzyme for neutrophils and hydroxyproline content. Compared to leflunomide, PDE4 inhibitors more strongly suppressed IL-12 production and the increase in myeloperoxidase activity. PDE4 inhibitors also inhibited lipopolysaccharide-induced TNF-alpha and IL-12 production from thioglycolate-induced murine peritoneal macrophages and the proliferation of rat synovial fibroblasts. These results indicate this model makes it easy to evaluate the effect of drugs on various cytokine productions in a granuloma without any purification step and may be a relevant model for evaluating novel antirheumatic drugs on pannus formation in RA. PDE4 inhibitors could have therapeutic effects on pannus formation in RA by inhibition of cytokine production by macrophages and synovial fibroblast proliferation.

Modelling multiple sources of dissemination bias in meta-analysis.

PubMed

Bowden, Jack; Jackson, Dan; Thompson, Simon G

2010-03-30

Asymmetry in the funnel plot for a meta-analysis suggests the presence of dissemination bias. This may be caused by publication bias through the decisions of journal editors, by selective reporting of research results by authors or by a combination of both. Typically, study results that are statistically significant or have larger estimated effect sizes are more likely to appear in the published literature, hence giving a biased picture of the evidence-base. Previous statistical approaches for addressing dissemination bias have assumed only a single selection mechanism. Here we consider a more realistic scenario in which multiple dissemination processes, involving both the publishing authors and journals, are operating. In practical applications, the methods can be used to provide sensitivity analyses for the potential effects of multiple dissemination biases operating in meta-analysis.

Interleukin-1 alpha modulates collagen gene expression in cultured synovial cells.

PubMed Central

Mauviel, A; Teyton, L; Bhatnagar, R; Penfornis, H; Laurent, M; Hartmann, D; Bonaventure, J; Loyau, G; Saklatvala, J; Pujol, J P

1988-01-01

The effects of porcine interleukin-1 (IL-1) alpha on collagen production were studied in cultured human rheumatoid synovial cells. Addition of 0.05-5 ng of IL-1/ml into the cultures resulted in a dose-dependent decreased rate of collagen released into the medium over 24 h. To determine whether this inhibition was due to secondary action of prostaglandin E2 (PGE2) secreted in response to IL-1, cultures were incubated in presence of various inhibitors of arachidonate metabolism. Depending on the cell strains, these inhibitors were able to suppress or diminish the effect of IL-1, suggesting that PGE2 is involved in the mechanism. Depression of collagen production caused by IL-1 mainly affected type I collagen and therefore led to a change in the type I/type III collagen ratio in the extracellular medium. Steady-state levels of mRNA for types I and III procollagens were estimated by dot-blot hybridization and compared with the amounts of respective collagens produced in the same cultures. IL-1 generally increased procollagen type I mRNA, but to a variable extent, as did indomethacin (Indo). Depending on the cell strain, the combination of indo and IL-1 could elevate the mRNA level of type I procollagen compared with Indo alone. These results did not correlate with the production rate of collagen in the medium, which was diminished by exposure to IL-1. The level of mRNA for collagen type III was not greatly changed by incubation with IL-1, and a better correlation was generally observed with the amount of type III collagen found in the medium. These data suggest that an additional control mechanism at translational or post-translational level must exist, counterbalancing the stimulatory effect of IL-1 on collagen mRNA transcription. It is likely that IL-1 could modulate the production of collagen in synovial cells by an interplay of different mechanisms, some of them limiting the effect of primary elevation of the steady-state mRNA level. Images Fig. 3. Fig. 4. Fig. 5

Intrathecal chemotherapy for refractory disseminated medulloblastoma.

PubMed

Yoshimura, Junichi; Nishiyama, Kenichi; Mori, Hiroshi; Takahashi, Hideaki; Fujii, Yukihiko

2008-05-01

To analyze the effect of intrathecal (IT) chemotherapy for disseminated medulloblastoma. Twenty-one patients received IT chemotherapy using the chemotherapeutic agents of methotrexate (MTX) and nitrosoureas (ACNU, MCNU) including nine patients for residual leptomeningeal lesions after initial surgery and radiation, and 12 for a recurrence with leptomeningeal dissemination. Of these 21 patients, 12 received a lumbar and/or ventricular bolus injection of the chemotherapeutic agents, one received the ventriculolumbar perfusion of the agents, and eight received both the perfusion and bolus injection. The doses ranged from 6-7 mg/m(2) of ACNU for perfusion and 3-3.5 mg/m(2) of ACNU, MCNU, or MTX for the bolus injection, and the cycles were administered from 3 to 12 times for perfusion and from 5 to 54 times for the bolus injection. The effects of chemotherapy were assessed by both radiological and cytological examinations, and the clinical symptoms were also assessed. Radiological and/or cytological responses were observed in 10 of 21 patients (47.6%), including seven cases demonstrating a complete remission. The 5-year overall survival rate and 5-year survival rate after dissemination were 61.5 and 46.4%, respectively. Five patients who received a lumbar bolus injection of nitrosoureas experienced paraplegia and double incontinence. One patient who received a ventricular injection of nitrosoureas experienced truncal ataxia. IT chemotherapy was found to be effective in some cases with refractory disseminated medulloblastoma and it seems to be an appropriate treatment choice for leptomeningeal recurrence. However, the frequent bolus injections of nitrosoureas should be avoided to prevent the side effects.

32 CFR 552.153 - Dissemination.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Fort Jackson, South Carolina § 552.153 Dissemination. (a) Unit commanders and supervisors shall ensure... the beginning of each training cycle. (b) All permanent party personnel and civilian employees will be...

Lessons Learned From Dissemination of Evidence-Based Interventions for HIV Prevention.

PubMed

Collins, Charles B; Sapiano, Tobey N

2016-10-01

In 1999, IOM issued a report that recommended that the Centers for Disease Control and Prevention should disseminate evidence-based HIV prevention interventions (EBIs) to be implemented by health departments, community-based organizations, drug treatment centers, and clinics. Based on these recommendations, the Diffusion of Effective Behavioral Interventions Project was initiated in 2000 and began disseminating interventions into public health practice. For 15 years, the Centers for Disease Control and Prevention has disseminated 29 EBIs to more than 11,300 agencies. Lessons were identified during the 15 years of implementation regarding successful methods of dissemination of EBIs. Lessons around selecting interventions for dissemination, developing a dissemination infrastructure including a resource website (https://effectiveinterventions.cdc.gov), and engagement with stakeholders are discussed. A continuous development approach ensured that intervention implementation materials, instructions, and technical assistance were all tailored to the needs of end users, focus populations, and agency capacities. Six follow-up studies demonstrated that adopters of EBIs were able to obtain comparable outcomes to those of the original efficacy research. The Diffusion of Effective Behavioral Interventions Project may offer guidance for other large, national, evidence-based public health dissemination projects. Published by Elsevier Inc.

Dissemination activities: a critical new role for substance abuse treatment organizations.

PubMed

Fields, Dail; Blum, Terry C; Roman, Paul M

2014-10-01

The Affordable Care Act calls for integration of substance abuse treatment into medical care via medical homes and continuing specialty care. For this integration to occur in the substance abuse treatment field, substantial sharing and dissemination of information by treatment providers is required. This study explored the determinants of organizational activities directed at disseminating evidence-based practices (EBPs) undertaken by 193 community treatment programs who are members of the National Institute on Drug Abuse (NIDA) Clinical Trials Network. Using factor analysis, the research identified two generic categories reflecting different motivations for dissemination activities and explored both treatment center leadership and organizational characteristics as determinants of these different types of dissemination activities. Organizational characteristics predicting treatment center dissemination activities included size, previous involvement in research protocols, linkages with other providers, and having non-profit status. The treatment center leader's membership in professional organizations was also a significant determinant. Organization variables account for a larger portion of the variance in treatment center dissemination activities. The results suggest that the willingness of treatment providers to help disseminate EBPs within the industry may be heavily influenced through shared network connections with other treatment organizations.

Dissemination Activities: A Critical New Role for Substance Abuse Treatment Organizations

PubMed Central

Blum, Terry C.; Roman, Paul M.

2014-01-01

The Affordable Care Act calls for integration of substance abuse treatment into medical care via medical homes and continuing specialty care. For this integration to occur in the substance abuse treatment field, substantial sharing and dissemination of information by treatment providers is required. This study explored the determinants of organizational activities directed at disseminating evidence-based practices (EBP) undertaken by 193 community treatment programs who are members of the National Institute on Drug Abuse (NIDA) Clinical Trials Network. Using factor analysis, the research identified two generic categories reflecting different motivations for dissemination activities, and explored both treatment center leadership and organizational characteristics as determinants of these different types of dissemination activities. Organizational characteristics predicting treatment center dissemination activities included size, previous involvement in research protocols, linkages with other providers, and having non-profit status. The treatment center leader's membership in professional organizations was also a significant determinant. Organization variables account for a larger portion of the variance in treatment center dissemination activities. The results suggest that the willingness of treatment providers to help disseminate EBPs within the industry may be heavily influenced through shared network connections with other treatment organizations. PMID:24722825

Herpes zoster (shingles) disseminated (image)

MedlinePlus

Herpes zoster (shingles) normally occurs in a limited area that follows a dermatome (see the "dermatome" picture). In individuals with damaged immune systems, herpes zoster may be widespread (disseminated), causing serious illness. ...

Study of information dissemination by satellite, volume 1

NASA Astrophysics Data System (ADS)

Connell, S.; Champness, B. G.; Stapley, B.; Winsbury, R.

1985-05-01

Western European demand for satellite information dissemination in the late 1990's was assessed. The major market opportunity lies in intra-organizational video communications. Broadcast satellites could be used to facilitate dispersal of newspaper printing sites and the development of regionalized or local editions. Examples would include the publication of editions of north European newspapers in Mediterranean holiday resorts. Data broadcasting services could use VBI or full channel teletext or other formats. The most promising area for data dissemination by satellite is the aggregation of a number of services which are themselves small, but in total could generate substantial demand. Examples of such services include dissemination of private company data to dispersed branches (pricing, stock levels, etc.).

Precise time dissemination via portable atomic clocks

NASA Technical Reports Server (NTRS)

Putkovich, K.

1982-01-01

The most precise operational method of time dissemination over long distances presently available to the Precise Time and Time Interval (PTTI) community of users is by means of portable atomic clocks. The Global Positioning System (GPS), the latest system showing promise of replacing portable clocks for global PTTI dissemination, was evaluated. Although GPS has the technical capability of providing superior world-wide dissemination, the question of present cost and future accessibility may require a continued reliance on portable clocks for a number of years. For these reasons a study of portable clock operations as they are carried out today was made. The portable clock system that was utilized by the U.S. Naval Observatory (NAVOBSY) in the global synchronization of clocks over the past 17 years is described and the concepts on which it is based are explained. Some of its capabilities and limitations are also discussed.

Effects of extracorporeal shock wave therapy and polysulfated glycosaminoglycan treatment on subchondral bone, serum biomarkers, and synovial fluid biomarkers in horses with induced osteoarthritis.

PubMed

Kawcak, Chris E; Frisbie, David D; McIlwraith, C Wayne

2011-06-01

To evaluate effects of extracorporeal shock wave therapy (ESWT) and polysulfated glycosaminoglycan treatment (PSGAGT) on subchondral bone (SCB), serum biomarkers, and synovial fluid biomarkers in horses with induced osteoarthritis. 24 healthy 2- to 3-year-old horses. An osteochondral fragment was created on the distal aspect of the radial carpal bone in 1 middle carpal joint of each horse. Horses were randomly allocated to receive local application of ESWT (days 14 and 28; n = 8), PSGAGT (IM, q 4 d for 28 days; 8), or a sham ESWT probe (placebo; days 14 and 28; 8). Serum biomarkers were measured every 7 days, and synovial fluid biomarkers were measured every 14 days. Bone density was measured by use of computed tomography on days 0 and 70, and microdamage and bone formation variables were compared among groups at the end of the study (day 70). There was no significant effect of ESWT or PSGAGT on any bone variable. Serum osteocalcin concentration was significantly greater in horses that received ESWT, compared with placebo-treated horses, and serum concentration of the C-terminal telopeptide of type I collagen was significantly higher in horses that received ESWT, compared with placebo- and PSGAG-treated horses. Concentrations of the synovial fluid epitope CS846 were significantly higher in joints with osteoarthritis treated with ESWT CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of osteoarthritis with ESWT had no effect on SCB but did induce increases in serum biomarkers indicative of bone remodeling. Treatment of osteoarthritis with PSGAG had no effect on SCB or biomarkers.

Not the last word: dissemination strategies for patient-centred research in nursing.

PubMed

Hagan, Teresa L; Schmidt, Karen; Ackison, Guyanna R; Murphy, Megan; Jones, Jennifer R

2017-08-01

Research results hold value for many stakeholders including researchers, patient populations, advocacy organizations, and community groups. The aim of this study is to describe our research team's systematic process to designing a dissemination strategy for a completed research study. We organized a dissemination event to feed the results of our study to participants and stakeholders and collect feedback regarding our study. We applied the Agency for Healthcare Research and Quality's dissemination framework to guide the development of the event and collected participant feedback during the event. We describe our dissemination strategy along with attendees' feedback and suggestions for our research as an example of a way to design a patient- and community-focused dissemination. We explain the details of our dissemination strategy including (a) our process of reporting a large research study into a stakeholder event, (b) stakeholder feedback collected at the event, and (c) the translation of feedback into our research team's research. We also describe challenges encountered during the dissemination process and ways to handle issues such as logistics, funding, and staff. This analysis provides key insights and practical advice for researchers looking for innovative ways to disseminate their findings within the lay and scientific communities.

Time required to achieve maximum concentration of amikacin in synovial fluid of the distal interphalangeal joint after intravenous regional limb perfusion in horses.

PubMed

Kilcoyne, Isabelle; Nieto, Jorge E; Knych, Heather K; Dechant, Julie E

2018-03-01

OBJECTIVE To determine the maximum concentration (Cmax) of amikacin and time to Cmax (Tmax) in the distal interphalangeal (DIP) joint in horses after IV regional limb perfusion (IVRLP) by use of the cephalic vein. ANIMALS 9 adult horses. PROCEDURES Horses were sedated and restrained in a standing position and then subjected to IVRLP (2 g of amikacin sulfate diluted to 60 mL with saline [0.9% NaCl] solution) by use of the cephalic vein. A pneumatic tourniquet was placed 10 cm proximal to the accessory carpal bone. Perfusate was instilled with a peristaltic pump over a 3-minute period. Synovial fluid was collected from the DIP joint 5, 10, 15, 20, 25, and 30 minutes after IVRLP; the tourniquet was removed after the 20-minute sample was collected. Blood samples were collected from the jugular vein 5, 10, 15, 19, 21, 25, and 30 minutes after IVRLP. Amikacin was quantified with a fluorescence polarization immunoassay. Median Cmax of amikacin and Tmax in the DIP joint were determined. RESULTS 2 horses were excluded because an insufficient volume of synovial fluid was collected. Median Cmax for the DIP joint was 600 μg/mL (range, 37 to 2,420 μg/mL). Median Tmax for the DIP joint was 15 minutes. CONCLUSIONS AND CLINICAL RELEVANCE Tmax of amikacin was 15 minutes after IVRLP in horses and Cmax did not increase > 15 minutes after IVRLP despite maintenance of the tourniquet. Application of a tourniquet for 15 minutes should be sufficient for completion of IVRLP when attempting to achieve an adequate concentration of amikacin in the synovial fluid of the DIP joint.

IGF-1 Gene Transfer to Human Synovial MSCs Promotes Their Chondrogenic Differentiation Potential without Induction of the Hypertrophic Phenotype.

PubMed

Ikeda, Yasutoshi; Sakaue, Morito; Chijimatsu, Ryota; Hart, David A; Otsubo, Hidenori; Shimomura, Kazunori; Madry, Henning; Suzuki, Tomoyuki; Yoshikawa, Hideki; Yamashita, Toshihiko; Nakamura, Norimasa

2017-01-01

Mesenchymal stem cell- (MSC-) based therapy is a promising treatment for cartilage. However, repair tissue in general fails to regenerate an original hyaline-like tissue. In this study, we focused on increasing the expression levels for insulin-like growth factor-1 (IGF-1) to improve repair tissue quality. The IGF-1 gene was introduced into human synovial MSCs with a lentiviral vector and examined the levels of gene expression and morphological status of MSCs under chondrogenic differentiation condition using pellet cultures. The size of the pellets derived from IGF-1-MSCs were significantly larger than those of the control group. The abundance of glycosaminoglycan (GAG) was also significantly higher in the IGF-1-MSC group. The histology of the IGF-1-induced pellets demonstrated similarities to hyaline cartilage without exhibiting features of a hypertrophic chondrocyte phenotype. Expression levels for the Col2A1 gene and protein were significantly higher in the IGF-1 pellets than in the control pellets, but expression levels for Col10, MMP-13, ALP, and Osterix were not higher. Thus, IGF-1 gene transfer to human synovial MSCs led to an improved chondrogenic differentiation capacity without the detectable induction of a hypertrophic or osteogenic phenotype.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

PubMed Central

Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-01

Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

[Disseminated cryptococcosis in an immunocompetent patient].

PubMed

Elkhihal, B; Hasnaoui, A; Ghfir, I; Moustachi, A; Aoufi, S; Lyagoubi, M

2015-09-01

Disseminated cryptococcosis is a serious opportunistic fungal infection caused by a yeast-encapsulated fungus of the genus Cryptococcus neoformans. It occurs most often in patients with a significant deficit of cellular immunity and preferentially affects the central nervous system. The skin and the lungs are the most commonly affected sites outside the neuro-subarachnoid location. We report the case of a patient apparently immunocompetent who had a disseminated cryptococcosis. The disease started with the multiple purplish skin lesions, large umbilicated on the face, groin, forearm and leg with progressively increasing volume. This symptomatology had evolved in the context of weight loss and poor general condition. The diagnosis was established by the presence of cryptococcal at the skin biopsy and cerebrospinal fluid. Research of immunosuppression common pathologies were negative. Treatment was initiated based on amphotericin B for 40 days. The patient's condition deteriorates onset of paraplegia and swallowing disorders causing death in an array of cachexia. This observation points out that disseminated cryptococcosis can occur in an immunocompetent patient. The skin lesions may be the first sign of the disease. Copyright © 2015. Published by Elsevier Masson SAS.

Endogenous nitric oxide production in canine osteoarthritis: Detection in urine, serum, and synovial fluid specimens.

PubMed

Spreng, D; Sigrist, N; Schweighauser, A; Busato, A; Schawalder, P

2001-01-01

To measure nitric oxide (NO) concentrations in serum, urine, and synovial fluid (SF) of dogs with naturally occurring cranial cruciate ligament (CCL) rupture and normal dogs, and to compare these with clinical and histologic changes of osteoarthritis (OA). Prospective clinical study including 2 groups of animals selected from the hospital population. Forty-three dogs (CCL group) with OA secondary to CCL rupture; 30 healthy dogs (control group) without CCL rupture. Serum, urine, and SF were collected before and during surgery in the CCL group or immediately after euthanasia in the control group. Articular cartilage and synovial membrane tissue specimens were prepared for routine histologic examination. The stable end products of NO, total nitrite and nitrate (NOt) activity, were measured in body fluids and compared with macroscopic and histologic degrees of OA. Urinary NOt concentration was compared with urinary creatinine concentration and stated as urinary NOt:creatinine ratio (UNCR). RESULTS-SF NOt concentrations were not significantly different between the 2 groups. Serum NOt concentrations (45.6 vs 28.9 micromol/L; P =.042) and the UNCR (0.007 vs 0.004; P =.035) were significantly higher in dogs of the CCL group compared with the control population. An association between UNCR and histologic and macroscopical OA grades could be demonstrated. UNCR might be a useful indicator of nitrite and nitrate production and, therefore, osteoarthritic changes in joints. UNCR could be used as a tool to evaluate the NOt production by joint tissues over time and might therefore provide a method of evaluating the effects of drugs in the control of osteoarthritis. Copyright 2001 by The American College of Veterinary Surgeons.

Disseminated Mastocytosis in a Dog

PubMed Central

Pukay, B. P.

1984-01-01

A 13 year old neutered female crossbred Poodle with disseminated mastocytosis was treated with systemic glucocorticoids and antibiotics. The diagnosis was made postmortem, based on histopathological findings. ImagesFigure 1.Figure 2.Figure 3. PMID:17422452

Systematic Dissemination of Research and Development Program Improvement Efforts.

ERIC Educational Resources Information Center

Sanders, Carol S.

A systematic approach to disseminaton of vocational education research and development program improvement efforts is comprehensive, effective, and efficient. Systematic dissemination is a prerequisite link to assessing impact of research and development--for program improvement to occur, successful dissemination is crucial. A systematic approach…

Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8/A9 serum levels.

PubMed

Schelbergen, R F; van Dalen, S; ter Huurne, M; Roth, J; Vogl, T; Noël, D; Jorgensen, C; van den Berg, W B; van de Loo, F A; Blom, A B; van Lent, P L E M

2014-08-01

Synovitis is evident in a substantial subpopulation of patients with osteoarthritis (OA) and is associated with development of pathophysiology. Recently we have shown that adipose-derived stem cells (ASC) inhibit joint destruction in collagenase-induced experimental OA (CIOA). In the current study we explored the role of synovitis and alarmins S100A8/A9 in the immunomodulatory capacity of ASCs in experimental OA. CIOA, characterized by synovitis, and surgical DMM (destabilization of medial meniscus) OA were treated locally with ASCs. Synovial activation, cartilage damage and osteophyte size were measured on histological sections. Cytokines in synovial washouts and serum were determined using Luminex or enzyme-linked immunosorbent assay (S100A8/A9), mRNA levels with reverse-transcriptase (RT)-qPCR. Local administration of ASCs at various time-points (days 7 or 14) after DMM induction had no effect on OA pathology. At day 7 of CIOA, already 6 h after ASC injection mRNA expression of pro-inflammatory mediators S100A8/A9, interleukin-1beta (IL-1β) and KC was down-regulated in the synovium. IL-1β protein, although low, was down-regulated by ASC-treatment of CIOA. S100A8/A9 protein levels were very high at 6 and 48 h and were decreased by ASC-treatment. The protective action of ASC treatment in CIOA was only found when high synovial inflammation was present at the time of deposition which was reflected by high serum S100A8/A9 levels. Finally, successful treatment resulted in significantly lower levels of serum S100A8/A9. Our study indicates that synovial activation rapidly drives anti-inflammatory and protective effects of intra-articularly deposited ASCs in experimental OA which is reflected by decreased S100A8/A9 levels. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Dissemination of psychosocial treatments for anxiety: the importance of taking a broad perspective.

PubMed

Taylor, Steven; Abramowitz, Jonathan S

2013-12-01

Dissemination methods are used to increase the likelihood that a given treatment or form of clinical practice is implemented by clinicians in the community. Therapist training in treatment methods is an important component of dissemination. Successful dissemination also requires that roadblocks to treatment implementation are identified and circumvented, such as misconceptions that clinicians might hold about a given treatment. The present article offers a commentary on the papers included in the special issue on treatment dissemination for anxiety disorders. Most papers focus on issues concerning the training and education of clinicians with regard to exposure therapy. Training and education is an important step but should be part of a broad, multifaceted approach. There are several other important methods of treatment dissemination, including methods developed and implemented with success by the pharmaceutical industry, might also be used to disseminate psychosocial therapies. Optimal dissemination likely requires a broad perspective in which multiple dissemination methods are considered for implementation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Systematic dissemination of a preschool physical activity intervention to the control preschools

PubMed Central

Howie, Erin K.; Brewer, Alisa E.; Brown, William H.; Saunders, Ruth P.; Pate, Russell R.

2016-01-01

For public health interventions to have a meaningful impact on public health, they must be disseminated to the wider population. Systematic planning and evaluation of dissemination efforts can aid translation from experimental trials to larger dissemination programs. The Study of Health and Activity in Preschool Environments (SHAPES) was a group-randomized intervention trial conducted in 16 preschools that successfully increased the physical activity of preschool age children. Following the completion of the research study protocol, the intervention was abbreviated, modified and implemented in four preschools who participated as control preschools in the original research study. The purposes of the current study were to describe the process of refining the intervention for dissemination to the control preschools, and to assess the acceptability of the resulting abbreviated intervention delivery. Five overarching behavioral objectives, informed by process evaluation, data from the original trial and collaboration with intervention teachers, were used to guide the implementation. Teachers in the dissemination classrooms reported high levels of acceptability, potential for sustainability of the program, and positive results in knowledge, skills, and child outcomes. Researchers can include a systematic approach to dissemination of effective intervention elements to the control participants in experimental studies to inform future dissemination efforts and begin to bridge the dissemination gap. PMID:27107302

Not the last word: dissemination strategies for patient-centred research in nursing

PubMed Central

Hagan, Teresa L.; Schmidt, Karen; Ackison, Guyanna R.; Murphy, Megan; Jones, Jennifer R.

2017-01-01

Introduction Research results hold value for many stakeholders including researchers, patient populations, advocacy organizations, and community groups. The aim of this study is to describe our research team’s systematic process to designing a dissemination strategy for a completed research study. Methodology We organized a dissemination event to feed the results of our study to participants and stakeholders and collect feedback regarding our study. We applied the Agency for Healthcare Research and Quality’s dissemination framework to guide the development of the event and collected participant feedback during the event. Results We describe our dissemination strategy along with attendees’ feedback and suggestions for our research as an example of a way to design a patient- and community-focused dissemination. We explain the details of our dissemination strategy including (a) our process of reporting a large research study into a stakeholder event, (b) stakeholder feedback collected at the event, and (c) the translation of feedback into our research team’s research. We also describe challenges encountered during the dissemination process and ways to handle issues such as logistics, funding, and staff. Conclusions This analysis provides key insights and practical advice for researchers looking for innovative ways to disseminate their findings within the lay and scientific communities. PMID:29081824

Twist1-positive epithelial cells retain adhesive and proliferative capacity throughout dissemination

PubMed Central

Shamir, Eliah R.; Coutinho, Kester; Georgess, Dan; Auer, Manfred

2016-01-01

ABSTRACT Dissemination is the process by which cells detach and migrate away from a multicellular tissue. The epithelial-to-mesenchymal transition (EMT) conceptualizes dissemination in a stepwise fashion, with downregulation of E-cadherin leading to loss of intercellular junctions, induction of motility, and then escape from the epithelium. This gain of migratory activity is proposed to be mutually exclusive with proliferation. We previously developed a dissemination assay based on inducible expression of the transcription factor Twist1 and here utilize it to characterize the timing and dynamics of intercellular adhesion, proliferation and migration during dissemination. Surprisingly, Twist1+ epithelium displayed extensive intercellular junctions, and Twist1– luminal epithelial cells could still adhere to disseminating Twist1+ cells. Although proteolysis and proliferation were both observed throughout dissemination, neither was absolutely required. Finally, Twist1+ cells exhibited a hybrid migration mode; their morphology and nuclear deformation were characteristic of amoeboid cells, whereas their dynamic protrusive activity, pericellular proteolysis and migration speeds were more typical of mesenchymal cells. Our data reveal that epithelial cells can disseminate while retaining competence to adhere and proliferate. PMID:27402962

Fine needle aspiration (FNA) of synovial sarcoma--a comparative histological-cytological study of 15 cases, including immunohistochemical, electron microscopic and cytogenetic examination and DNA-ploidy analysis.

PubMed

Akerman, M; Willén, H; Carlén, B; Mandahl, N; Mertens, F

1996-06-01

A retrospective study of 25 FNAs (11 aspirates from primary tumours and 14 from recurrencies and metastases) from 15 synovial sarcomas was performed. The cytological findings were correlated with the histopathology and the value of immunohistochemical and electron microscopic examination as well as DNA-ploidy and cytogenetic analysis for diagnosis were assessed. A reproducible cellular pattern with a reliable diagnosis of spindle cell sarcoma was possible provided that the aspirates were cell rich. However, a true biphasic pattern indicative of synovial sarcoma was only seen in one of the 25 specimens. Electron microscopic examination of the aspirates was a valuable adjunctive diagnostic method, whereas immunocytochemistry and DNA-ploidy analysis were not. Immunohistochemical, electron microscopic and cytogenetic analysis were all valuable ancillary methods when performed on surgical specimens. Malignant haemangiopericytoma and fibrosarcoma were the most important differential diagnoses in the FNA specimens.

From innovation to standard practice: Developing and disseminating behavioral procedures

PubMed Central

Paine, Stan C.; Bellamy, G. Thomas

1982-01-01

This paper proposes a three-stage continuum for discussing the development and dissemination of behavioral technology. At the level of behavioral techniques, researchers need only establish a functional relationship between technologically defined intervention procedures and socially significant target behaviors. Dissemination is conducted for informational purposes only, and the purposes and details surrounding subsequent use of the technique are left to the discretion of the user. At the level of behavioral demonstration, a collection of socially acceptable intervention procedures is refined and standardized and must be shown to produce behavior changes across a number of subjects. Here dissemination is conducted, in large part, to generate support for provision of services. At the level of behavioral models, procedural descriptions must be useroriented. Additionally, model effects must be obtainable by agents not associated with their development and must compare favorably with other treatment or service alternatives. The purpose of dissemination at this level is to obtain adoptions and replications of the model. Details of development and dissemination of behavioral technology at each of these three levels are discussed. PMID:22478555

29 CFR 403.8 - Dissemination and verification of reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... LABOR-MANAGEMENT STANDARDS LABOR ORGANIZATION ANNUAL FINANCIAL REPORTS § 403.8 Dissemination and verification of reports. (a) Every labor organization required to submit a report under section 201(b) of the... 29 Labor 2 2010-07-01 2010-07-01 false Dissemination and verification of reports. 403.8 Section...

Dissemination and implementation: INQRI's potential impact.

PubMed

Titler, Marita G; Wilson, Deleise S; Resnick, Barbara; Shever, Leah L

2013-04-01

Application of research evidence in care delivery improves patient outcomes. Large gaps still exist, however, between recommended care and that used in practice. To increase the understanding of implementation studies, and dissemination of research findings, we present the perspective of investigators from seven Interdisciplinary Nursing Quality Research Initiative (INQRI)-funded studies. To describe implementation strategies, challenges, and lessons learned from conducting 5 INQRI-funded implementation studies, and present 2 case examples of other INQRI studies to illustrate dissemination strategies. Potential impact of study findings are set forth. Qualitative descriptive methods were used for the implementation studies. Case examples were set forth by investigators using reflection questions. Four of the 5 implementation studies focused on clinical topics and 1 on professional development of nurse managers, 4 were multisite studies. Common implementation strategies used across studies addressed education, ongoing interaction with sites, use of implementation tools, and visibility of the projects on the study units. Major challenges were the Institutional Review Board approval process and the short length of time allocated for implementation. Successes and lessons learned included creating excitement about research, packaging of study tools and resources for use by other organizations, and understanding the importance of context when conducting this type of research. Case examples revealed that study findings have been disseminated to study sites and to the health care community through publications and presentations. The potential impact of all 7 studies is far reaching. This study captures several nuanced perspectives from 5 Principal Investigators, who were completing INQRI-funded implementation studies. These nuanced perspectives are important lessons for other scientists embarking on implementation studies. The INQRI case examples illustrate important

Statistical Policy Working Paper 24. Electronic Dissemination of Statistical Data

DOT National Transportation Integrated Search

1995-11-01

The report, Statistical Policy Working Paper 24, Electronic Dissemination of Statistical Data, includes several topics, such as Options and Best Uses for Different Media Operation of Electronic Dissemination Service, Customer Service Programs, Cost a...

[Can acute disseminated encephalomyelitis progress in a deferred way?].

PubMed

Gener, B; Garaizar-Axpe, C; Ruiz Espinosa, C; Prats-Viñas, J M

To report on the heterogeneity with regard to the clinical course of the acute disseminated encephalomyelitis (ADEM). A 5 year old boy suffered of acute disseminated encephalomyelitis of unknown origin. This child suffered two episodes of different neurologic symptoms separated by several weeks. Based on the clinical manifestations and typical appearance of magnetic resonance imaging findings and the absence of oligoclonal bands in CSF immunoglobulins, multiple sclerosis (MS) was ruled out. We postulate that the recurrent symptoms in our patient could be explained as a multiphasic disseminated encephalomyelitis (MDEM). Favourable outcome after simultaneous treatment with methylprednisolone and intravenous immunoglobulin is emphasized in this report.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

PubMed

O'Neill, Terence W; Parkes, Matthew J; Maricar, Nasimah; Marjanovic, Elizabeth J; Hodgson, Richard; Gait, Andrew D; Cootes, Timothy F; Hutchinson, Charles E; Felson, David T

2016-01-01

Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention. Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy. At all time points they completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. They had a contrast-enhanced (CE) MRI immediately prior to an intra-articular steroid injection with a repeat scan within 20 days. Response status was assessed using the Osteoarthritis Research Society International (OARSI) response criteria. OARSI responders were followed until their pain relapsed either within 20% of baseline or 6 months, shortly after which a third MRI was performed. Synovial tissue volume (STV) was measured on postcontrast knee images. We looked at changes in the STV and in pain, and their association. 120 subjects with preinjection and postinjection CE MRI were followed. Their mean age was 62.3 years (SD=10.3) and 62 (52%) were women. The median time between injection and follow-up scan was 8 days (IQR 7-14 days). 85/120 (71%) were OARSI responders. Pain decreased (mean change in KOOS=+23.9; 95% CI 20.1 to 27.8, p<0.001) following steroid injection, as did mean STV (mean change=-1071 mm(3); 95% CI -1839 mm(3) to -303 mm(3), p=0.01). Of the 80 who returned for a third MRI, pain relapsed in 57, and in the 48 of those with MRI data, STV increased between follow-up and final visit (+1220 mm(3); 95% CI 25 mm(3) to 2414 mm(3), p=0.05). 23 were persistent responders at 6 months and, in these, STV did not increase (mean change=-202 mm(3); 95% CI -2008 mm(3) to 1604 mm(3), p=0.83). Controlling for variation over time, there was a significant association between synovitis volume and KOOS pain (b coefficient-change in KOOS pain score per 1000 mm(3) change in STV=-1.13; 95% CI -1.87 to -0.39, p=0.003), although STV accounted for only a small proportion of

Total nucleated cell and leukocyte differential counts in canine pleural and peritoneal fluid and equine synovial fluid samples: comparison of automated and manual methods.

PubMed

Brudvig, Jean M; Swenson, Cheryl L

2015-12-01

Rapid and precise measurement of total and differential nucleated cell counts is a crucial diagnostic component of cavitary and synovial fluid analyses. The objectives of this study included (1) evaluation of reliability and precision of canine and equine fluid total nucleated cell count (TNCC) determined by the benchtop Abaxis VetScan HM5, in comparison with the automated reference instruments ADVIA 120 and the scil Vet abc, respectively, and (2) comparison of automated with manual canine differential nucleated cell counts. The TNCC and differential counts in canine pleural and peritoneal, and equine synovial fluids were determined on the Abaxis VetScan HM5 and compared with the ADVIA 120 and Vet abc analyzer, respectively. Statistical analyses included correlation, least squares fit linear regression, Passing-Bablok regression, and Bland-Altman difference plots. In addition, precision of the total cell count generated by the VetScan HM5 was determined. Agreement was excellent without significant constant or proportional bias for canine cavitary fluid TNCC. Automated and manual differential counts had R(2)  < .5 for individual cell types (least squares fit linear regression). Equine synovial fluid TNCC agreed but with some bias due to the VetScan HM5 overestimating TNCC compared to the Vet abc. Intra-assay precision of the VetScan HM5 in 3 fluid samples was 2-31%. The Abaxis VetScan HM5 provided rapid, reliable TNCC for canine and equine fluid samples. The differential nucleated cell count should be verified microscopically as counts from the VetScan HM5 and also from the ADVIA 120 were often incorrect in canine fluid samples. © 2015 American Society for Veterinary Clinical Pathology.

Bulk Data Dissemination in Low Power Sensor Networks: Present and Future Directions

PubMed Central

Xu, Zhirong; Hu, Tianlei; Song, Qianshu

2017-01-01

Wireless sensor network-based (WSN-based) applications need an efficient and reliable data dissemination service to facilitate maintenance, management and data distribution tasks. As WSNs nowadays are becoming pervasive and data intensive, bulk data dissemination protocols have been extensively studied recently. This paper provides a comprehensive survey of the state-of-the-art bulk data dissemination protocols. The large number of papers available in the literature propose various techniques to optimize the dissemination protocols. Different from the existing survey works which separately explores the building blocks of dissemination, our work categorizes the literature according to the optimization purposes: Reliability, Scalability and Transmission/Energy efficiency. By summarizing and reviewing the key insights and techniques, we further discuss on the future directions for each category. Our survey helps unveil three key findings for future direction: (1) The recent advances in wireless communications (e.g., study on cross-technology interference, error estimating codes, constructive interference, capture effect) can be potentially exploited to support further optimization on the reliability and energy efficiency of dissemination protocols; (2) Dissemination in multi-channel, multi-task and opportunistic networks requires more efforts to fully exploit the spatial-temporal network resources to enhance the data propagation; (3) Since many designs incur changes on MAC layer protocols, the co-existence of dissemination with other network protocols is another problem left to be addressed. PMID:28098830

Information, Vol. 1, Number 4. Teacher Corps Dissemination Project Bulletin.

ERIC Educational Resources Information Center

Rosenau, Fred S., Ed.

Guidelines are provided for disseminating information on teacher corps projects. Information is given on experienced disseminators such as existing networks that are available to help in planning. Suggestions are made on targeting information and marketing. (JD)

Do Haphazard Reviews Provide Sound Directions for Dissemination Efforts?

ERIC Educational Resources Information Center

Gambrill, Eileen; Littell, Julia H.

2010-01-01

Comments on The dissemination and implementation of evidence-based psychological treatments: A review of current efforts by Kathryn R. McHugh and David H. Barlow. The lead article in the February-March issue by McHugh and Barlow (2010) emphasized the need for "dissemination and implementation of evidence-based psychological treatments."…

The bromodomain protein inhibitor I-BET151 suppresses expression of inflammatory genes and matrix degrading enzymes in rheumatoid arthritis synovial fibroblasts.

PubMed

Klein, Kerstin; Kabala, Pawel A; Grabiec, Aleksander M; Gay, Renate E; Kolling, Christoph; Lin, Lih-Ling; Gay, Steffen; Tak, Paul P; Prinjha, Rab K; Ospelt, Caroline; Reedquist, Kris A

2016-02-01

To investigate the effects of BET bromodomain protein inhibition on inflammatory activation and functional properties of rheumatoid arthritis synovial fibroblasts (RASF). The expression of the BET bromodomain proteins BRD2, BRD3 and BRD4 was analysed in synovial tissue by immunohistochemistry. RASF were stimulated with tumour necrosis factor (TNF)-α, interleukin (IL)-1β and toll-like receptor (TLR) ligands (Pam3, pIC and lipopolysaccharide (LPS)) in the presence or absence of the BET inhibitor I-BET151, or siRNA targeting BRD2, BRD3 and BRD4. RASF expression of inflammatory mediators, including MMP1, MMP3, IL-6 and IL-8, was measured by q-PCR, q-PCR array and ELISA. Cellular viability, apoptosis, proliferation and chemoattractive properties of RASF were investigated using MTT, cell apoptosis ELISA, BrdU-based proliferation and transwell migration assays. BRD2, BRD3 and BRD4 proteins were detected in rheumatoid arthritis (RA) synovial tissue, expressed in both RASF and macrophages. I-BET151 suppressed cytokine and TLR ligand-induced secretion of MMP1, MMP3, IL-6 and IL-8, and mRNA expression of more than 70% of genes induced by TNF-α and IL-1β. Combined silencing of BRD2, BRD3 and BRD4 significantly reduced cytokine and TLR ligand-induced expression of a subset of gene products targeted by I-BET151, including MMP1, CXCL10 and CXCL11. I-BET151 treatment of RASF reduced RASF proliferation, and the chemotactic potential for peripheral blood leucocytes of RASF conditioned medium. Inhibition of BET family proteins suppresses the inflammatory, matrix-degrading, proliferative and chemoattractive properties of RASF and suggests a therapeutic potential in the targeting of epigenetic reader proteins in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Disseminated cutaneous sporotrichosis in an immunocompetent individual.

PubMed

Yap, Felix Boon-Bin

2011-10-01

Sporotrichosis is a subacute or chronic fungal infection caused by the ubiquitous fungus Sporothrix schenckii. Disseminated cutaneous sporotrichosis is an uncommon entity and is usually present in the immunosuppressed. Here, a case of disseminated cutaneous sporotrichosis in an immunocompetent patient is reported. This 70-year-old healthy woman presented with multiple painful ulcerated nodules on her face and upper and lower extremities of 6-month duration, associated with low-grade fever, night sweats, loss of appetite, and loss of weight. Histopathological examination of the skin biopsy revealed epidermal hyperplasia and granulomatous inflammation in the dermis, with budding yeast. Fungal culture identified S. schenckii. She had total resolution of the lesions after 2 weeks of intravenous amphotericin B and 8 months of oral itraconazole. All investigations for underlying immunosuppression and internal organ involvement were negative. This case reiterates that disseminated cutaneous sporotrichosis, although common in the immunosuppressed, can also be seen in immunocompetent patients. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Information Dissemination Analysis of Different Media towards the Application for Disaster Pre-Warning

PubMed Central

Zhang, Nan; Huang, Hong; Su, Boni; Zhao, Jinlong; Zhang, Bo

2014-01-01

Knowing the information dissemination mechanisms of different media and having an efficient information dissemination plan for disaster pre-warning plays a very important role in reducing losses and ensuring the safety of human beings. In this paper we established models of information dissemination for six typical information media, including short message service (SMS), microblogs, news portals, cell phones, television, and oral communication. Then, the information dissemination capability of each medium concerning individuals of different ages, genders, and residential areas was simulated, and the dissemination characteristics were studied. Finally, radar graphs were used to illustrate comprehensive assessments of the six media; these graphs show directly the information dissemination characteristics of all media. The models and the results are essential for improving the efficiency of information dissemination for the purpose of disaster pre-warning and for formulating emergency plans which help to reduce the possibility of injuries, deaths and other losses in a disaster. PMID:24878739

Information dissemination analysis of different media towards the application for disaster pre-warning.

PubMed

Zhang, Nan; Huang, Hong; Su, Boni; Zhao, Jinlong; Zhang, Bo

2014-01-01

Knowing the information dissemination mechanisms of different media and having an efficient information dissemination plan for disaster pre-warning plays a very important role in reducing losses and ensuring the safety of human beings. In this paper we established models of information dissemination for six typical information media, including short message service (SMS), microblogs, news portals, cell phones, television, and oral communication. Then, the information dissemination capability of each medium concerning individuals of different ages, genders, and residential areas was simulated, and the dissemination characteristics were studied. Finally, radar graphs were used to illustrate comprehensive assessments of the six media; these graphs show directly the information dissemination characteristics of all media. The models and the results are essential for improving the efficiency of information dissemination for the purpose of disaster pre-warning and for formulating emergency plans which help to reduce the possibility of injuries, deaths and other losses in a disaster.

Further dissemination of medical education projects after presentation at a pediatric national meeting (1998-2008).

PubMed

Smith, Sherilyn; Kind, Terry; Beck, Gary; Schiller, Jocelyn; McLauchlan, Heather; Harris, Mitchell; Gigante, Joseph

2014-01-01

Further dissemination of medical education work presented at national meetings is limited. The purpose of this study was to explore dissemination outcomes of scholarly work in pediatric medical education. Council on Medical Student Education in Pediatrics (COMSEP) members who presented at COMSEP national meetings from 1998 to 2008 received a questionnaire about scholarly dissemination outcomes. Descriptive statistics and chi-square analysis explored variables related to dissemination. Qualitative analysis of free text comments explored barriers to dissemination. Outcomes were determined for 81% of presentations (138/171). The dissemination rate was 67% (92/138 presentations), with 47 publications (34%). Dissemination rates did not vary by presentation type (poster vs. oral) or project type. There was no relationship between presentation type, project type, and dissemination method. Barriers included perceived inadequate time, mentorship, and methodological skills for scholarly work. Most projects were further disseminated. Additional resources including mentoring and protected time for scholarly work are needed by educators to optimize dissemination.

Network influences on dissemination of evidence-based guidelines in state tobacco control programs.

PubMed

Luke, Douglas A; Wald, Lana M; Carothers, Bobbi J; Bach, Laura E; Harris, Jenine K

2013-10-01

Little is known regarding the social network relationships that influence dissemination of evidence-based public health practices and policies. In public health, it is critical that evidence-based guidelines, such as the Centers for Disease Control and Prevention's Best Practices for Comprehensive Tobacco Control Programs, are effectively and efficiently disseminated to intended stakeholders. To determine the organizational and network predictors of dissemination among state tobacco control programs, interviews with members of tobacco control networks across eight states were conducted between August 2009 and September 2010. Measures included partner attributes (e.g., agency type) and relationships among network members (frequency of contact, extent of collaboration, and dissemination of Best Practices). Exponential random graph modeling was used to examine attribute and structural predictors of collaboration and dissemination among partners in each network. Although density and centralization of dissemination ties varied across states, network analyses revealed a consistent prediction pattern across all eight states. State tobacco control dissemination networks were less dense but more centralized compared with organizational contact and collaboration networks. Tobacco control partners in each state were more likely to disseminate the Best Practices guidelines if they also had existing contact and collaboration relationships with one another. Evidence-based guidelines in public health need to be efficiently and broadly disseminated if we hope to translate science into practice. This study suggests that funders, advocacy groups, and public health agencies can take advantage of existing public health organizational relationships to support the communication and dissemination of evidence-based practices and policies.

Disseminating an Effective Educational Technology.

ERIC Educational Resources Information Center

Axelrod, Saul

1992-01-01

Reasons for the failure to adopt behavior-analytic teaching strategies include the perception that behavior analysis is coercive and controlling, difficulties in implementation, university factors, and marketing problems. The goal of dissemination of these strategies could be met through creating motivational conditions and devising marketing…

Evaluation of anticollagen type I antibody titers in synovial fluid of both stifle joints and the left shoulder joint of dogs with unilateral cranial cruciate disease.

PubMed

de Bruin, Tanya; de Rooster, Hilde; van Bree, Henri; Cox, Eric

2007-03-01

To evaluate anticollagen type I antibodies in synovial fluid of the affected stifle joint, the contralateral stifle joint, and the left shoulder joint of dogs with unilateral cranial cruciate ligament (CrCL) rupture during an extended period of 12 to 18 months. 13 client-owned dogs with CrCL rupture and 2 sham-operated dogs. All dogs were examined and arthrocentesis of all 3 joints was performed every 6 months after surgery. Synovial fluid samples were tested for anticollagen type I antibodies by use of an ELISA. Dogs with partial CrCL rupture had higher antibody titers than dogs with complete rupture. Six of 13 dogs ruptured the contralateral CrCL during the study, whereby higher antibody titers were found for the stifle joints than for the shoulder joint. Seronegative dogs or dogs with extremely low antibody titers and 2 dogs with high antibody titers did not sustain a CrCL rupture in the contralateral stifle joint. In most dogs that had a CrCL rupture of the contralateral stifle joint, a distinct antibody titer gradient toward the stifle joints was detected, suggesting that there was a local inflammatory process in these joints. However, only a small number of sham-operated dogs were used to calculate the cutoff values used to determine the anticollagen type I antibody titers in these patients. Synovial fluid antibodies against collagen type I alone do not initiate CrCL rupture because not all dogs with high antibody titers sustained a CrCL rupture in the contralateral stifle joint.

Disseminated cutaneous sporotrichosis in patient with alcoholism.

PubMed

Benvegnú, Ana Maria; Stramari, Juliana; Dallazem, Lia Natália Diehl; Chemello, Raíssa Massaia Londero; Beber, André Avelino Costa

2017-01-01

Sporotrichosis is the most prevalent subcutaneous mycosis and is characterized by a subacute or chronic development of a cutaneous or subcutaneous nodular lesion. It is caused by the dimorphic fungus Sporothrix spp, which may manifest in different clinical forms. The disseminated cutaneous form is uncommon and is more likely to occur in immunocompromised patients. We report a 47-year-old male patient with multiple cutaneous and subcutaneous nodules. The patient was diagnosed with disseminated cutaneous sporotrichosis based on the isolation and identification of Sporothrix spp. The patient was treated with potassium iodide, which resulted in clinical improvement of the lesions.

Research Note--Online Dissemination of Research: Are Professional Associations Making the Grade?

ERIC Educational Resources Information Center

Borah, Elisa Vinson; Aguiniga, Donna M.

2013-01-01

Efficient and practical means of disseminating research to social workers are needed. The authors examined how 10 social work and 10 other helping profession association websites used their sites to disseminate research to their members. A rubric was used to rate the websites in 4 domains: (1) promotion, (2) accessibility, (3) dissemination, and…

Developing a Framework for the Dissemination of Educational and R&D Products.

ERIC Educational Resources Information Center

Cresap, McCormick, and Paget, Inc., New York, NY.

An indepth study was performed to assess the present status of dissemination in the Education Division of the Department of Health, Education and Welfare, to develop a conceptual framework that would provide a rational base for a dissemination policy, and to recommend an organizational plan for the management of the dissemination activity within…

A new inhibitor of synovial phospholipase A2 from fermentations of Penicillium sp. 62-92.

PubMed

Witter, L; Anke, T; Sterner, O

1998-01-01

Penidiamide, a new tripetide containing dehydrotryptamine, glycine and anthranilic acid linked together by two amide bonds, and oxindole were isolated from submerged cultures of Penicillium sp. 62-92. Both compounds preferentially inhibited human synovial phospholipase A2, penidiamide with an IC50 of 30 microM and oxindole of 380 microM. With the exception of U 937 cells (leukemia, human), no cytotoxic activities were detected against HL-60- (leukemia, human), HeLa S3- (epitheloid carcinoma, human), BHK 21- (kidney fibroblasts, hamster), and L1210-cells (leukemia, mouse). No antimicrobial activity was detected for oxindole, and only weak antibacterial activity for penidiamide. The structure of penidiamide was elucidated by spectroscopic methods.

Arthroscopic approach and intra-articular anatomy of the dorsal and plantar synovial compartments of the bovine tarsocrural joint.

PubMed

Lardé, Hélène; Nichols, Sylvain; Babkine, Marie; Desrochers, André

2017-01-01

To determine arthroscopic approaches to the dorsal and plantar synovial compartments of the tarsocrural joint in adult cattle, and to describe the arthroscopic intra-articular anatomy from each approach. Ex vivo study. Fresh adult bovine cadavers (n = 7). Two tarsocrural joint were injected with latex to determine arthroscopic portal locations and arthroscopy of the tarsocrural joint of 12 tarsi was performed. The dorsolateral approach was made through the large pouch located between the long digital extensor and peroneus longus tendons. The dorsomedial approach was made just medial to the common synovial sheath of the tibialis cranialis, peroneus tertius, and long digital extensor tendons. The plantarolateral and plantaromedial approaches were made lateral and medial to the tarsal tendon sheath, respectively. Each approach allowed visualization of the distal tibia articulating with the proximal trochlea of the talus. Consistently observed structures included the distal intermediate ridge of the tibia, and the medial and lateral trochlear ridges and trochlear groove of the talus. Lateral and medial malleoli were best assessed from dorsal approaches. From the lateral approaches evaluation of the abaxial surface of the lateral trochlear ridge allowed visualization of the fibulocalcaneal joint. From the plantar approaches additional observed structures included the coracoid process of the calcaneus, plantar trochlea of the talus, and plantar talotibial and talofibular ligaments. In cattle, the dorsolateral and plantarolateral approaches allowed for the best evaluation of the dorsal and plantar aspects of the tarsocrural joint, respectively. © 2017 The American College of Veterinary Surgeons.

48 CFR 1252.242-70 - Dissemination of information-educational institutions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... information-educational institutions. 1252.242-70 Section 1252.242-70 Federal Acquisition Regulations System... Provisions and Clauses 1252.242-70 Dissemination of information—educational institutions. As prescribed in (TAR) 48 CFR 1242.7000(a), insert the following clause: Dissemination of Information—Educational...

48 CFR 1252.242-70 - Dissemination of information-educational institutions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... information-educational institutions. 1252.242-70 Section 1252.242-70 Federal Acquisition Regulations System... Provisions and Clauses 1252.242-70 Dissemination of information—educational institutions. As prescribed in (TAR) 48 CFR 1242.7000(a), insert the following clause: Dissemination of Information—Educational...

48 CFR 1252.242-70 - Dissemination of information-educational institutions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... information-educational institutions. 1252.242-70 Section 1252.242-70 Federal Acquisition Regulations System... Provisions and Clauses 1252.242-70 Dissemination of information—educational institutions. As prescribed in (TAR) 48 CFR 1242.7000(a), insert the following clause: Dissemination of Information—Educational...

48 CFR 1252.242-70 - Dissemination of information-educational institutions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... information-educational institutions. 1252.242-70 Section 1252.242-70 Federal Acquisition Regulations System... Provisions and Clauses 1252.242-70 Dissemination of information—educational institutions. As prescribed in (TAR) 48 CFR 1242.7000(a), insert the following clause: Dissemination of Information—Educational...

48 CFR 1252.242-70 - Dissemination of information-educational institutions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... information-educational institutions. 1252.242-70 Section 1252.242-70 Federal Acquisition Regulations System... Provisions and Clauses 1252.242-70 Dissemination of information—educational institutions. As prescribed in (TAR) 48 CFR 1242.7000(a), insert the following clause: Dissemination of Information—Educational...

PPAR-α Agonist WY-14643 Inhibits LPS-Induced Inflammation in Synovial Fibroblasts via NF-kB Pathway.

PubMed

Huang, Degang; Zhao, Quanlai; Liu, Hongfei; Guo, Yongjie; Xu, Hongguang

2016-08-01

Osteoarthritis (OA), the most prevalent form of arthritis that results from breakdown of joint cartilage and underlying bone, has been viewed as a chronic condition manifested by persistence of inflammatory responses and infiltration of lymphocytes. Regulation of the inflammatory responses in synovial fibroblasts might be useful to prevent the development and deterioration of osteoarthritis. WY-14643, a potent peroxisome proliferator activator receptor-α (PPAR-α) agonist, has been described to beneficially regulate inflammation in many mammalian cells. Here, we investigate the potential anti-inflammatory role of WY-14643 in lipopolysaccharide (LPS)-induced synovial fibroblasts. WY-14643 greatly inhibited the production of NO and PGE2 induced by LPS. In addition, the mRNA expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelin-1 (ET-1), and tissue factor (TF) was significantly suppressed by WY-14643, as well as the secretion of pro-inflammatory cytokines including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), and monocyte chemotactic protein-1 (MCP-1). Furthermore, the transcription activity and nuclear translocation of NF-kB were found to be markedly decreased by WY-14643, while the phosphorylation of IkB was enhanced, indicating that the anti-inflammatory role of WY-14643 was meditated by NF-kB-dependent pathway. The application of WY-14643 failed to carry out its anti-inflammatory function in PPAR-α silenced cells, suggesting the role of PPAR-α. These findings may facilitate further studies investigating the translation of pharmacological PPAR-α activation into clinical therapy of OA.

Molecular and Cellular Mechanisms of Shigella flexneri Dissemination

PubMed Central

Agaisse, Hervé

2016-01-01

The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S. flexneri dissemination. The dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout the cytosol of primary infected cells. Polar actin assembly is supported by polar expression of the bacterial autotransporter family member IcsA, which recruits the N-WASP/ARP2/3 actin assembly machinery. As motile bacteria encounter cell-cell contacts, they form plasma membrane protrusions that project into adjacent cells. In addition to the ARP2/3-dependent actin assembly machinery, protrusion formation relies on formins and myosins. The resolution of protrusions into vacuoles occurs through the collapse of the protrusion neck, leading to the formation of an intermediate membrane-bound compartment termed vacuole-like protrusions (VLPs). VLP formation requires tyrosine kinase and phosphoinositide signaling in protrusions, which relies on the integrity of the bacterial type 3 secretion system (T3SS). The T3SS is also required for escaping double membrane vacuoles through the activity of the T3SS translocases IpaB and IpaC, and the effector proteins VirA and IcsB. Numerous factors supporting envelope biogenesis contribute to IcsA exposure and maintenance at the bacterial pole, including LPS synthesis, membrane proteases, and periplasmic chaperones. Although less characterized, the assembly and function of the T3SS in the context of bacterial dissemination also relies on factors supporting envelope biogenesis. Finally, the dissemination process requires the adaptation of the pathogen to various cellular compartments through transcriptional and post-transcriptional mechanisms

Molecular and Cellular Mechanisms of Shigella flexneri Dissemination.

PubMed

Agaisse, Hervé

2016-01-01

The intracellular pathogen Shigella flexneri is the causative agent of bacillary dysentery in humans. The disease is characterized by bacterial invasion of intestinal cells, dissemination within the colonic epithelium through direct spread from cell to cell, and massive inflammation of the intestinal mucosa. Here, we review the mechanisms supporting S. flexneri dissemination. The dissemination process primarily relies on actin assembly at the bacterial pole, which propels the pathogen throughout the cytosol of primary infected cells. Polar actin assembly is supported by polar expression of the bacterial autotransporter family member IcsA, which recruits the N-WASP/ARP2/3 actin assembly machinery. As motile bacteria encounter cell-cell contacts, they form plasma membrane protrusions that project into adjacent cells. In addition to the ARP2/3-dependent actin assembly machinery, protrusion formation relies on formins and myosins. The resolution of protrusions into vacuoles occurs through the collapse of the protrusion neck, leading to the formation of an intermediate membrane-bound compartment termed vacuole-like protrusions (VLPs). VLP formation requires tyrosine kinase and phosphoinositide signaling in protrusions, which relies on the integrity of the bacterial type 3 secretion system (T3SS). The T3SS is also required for escaping double membrane vacuoles through the activity of the T3SS translocases IpaB and IpaC, and the effector proteins VirA and IcsB. Numerous factors supporting envelope biogenesis contribute to IcsA exposure and maintenance at the bacterial pole, including LPS synthesis, membrane proteases, and periplasmic chaperones. Although less characterized, the assembly and function of the T3SS in the context of bacterial dissemination also relies on factors supporting envelope biogenesis. Finally, the dissemination process requires the adaptation of the pathogen to various cellular compartments through transcriptional and post-transcriptional mechanisms.

MULTIFOCAL CHOROIDITIS IN DISSEMINATED SPOROTRICHOSIS IN PATIENTS WITH HIV/AIDS.

PubMed

Biancardi, Ana L; Freitas, Dayvison F S; Valviesse, Vitor R G de A; Andrade, Hugo B; de Oliveira, Manoel M E; do Valle, Antonio C F; Zancope-Oliveira, Rosely M; Galhardo, Maria C G; Curi, Andre L L

2017-01-01

In this article, the authors describe multifocal choroiditis related to disseminated sporotrichosis in patients with HIV/AIDS. We conducted a retrospective observational study of three patients infected with HIV who presented with disseminated sporotrichosis characterized by cutaneous lesions, multifocal choroiditis, and other manifestations, including osteomyelitis and involvement of the bone marrow, larynx, pharynx, and nasal and oral mucosa. Five eyes of three patients with HIV/AIDS showed multifocal choroiditis related to disseminated sporotrichosis. The CD4 counts ranged from 25 to 53 mm. All patients were asymptomatic visually. The ocular disease was bilateral in two patients. The lesion size ranged from 1/3 to 2 disc diameters. None of the patients had vitritis. Of the 12 lesions, 9 were localized in the posterior pole (Zone 1) and 3 were localized in the mild periphery (Zone 2). Multifocal choroiditis due to disseminated sporotrichosis can occur in profoundly immunosuppressed patients with HIV/AIDS.

What predicts dissemination efforts among public health researchers in the United States?

PubMed

Tabak, Rachel G; Stamatakis, Katherine A; Jacobs, Julie A; Brownson, Ross C

2014-01-01

We identified factors related to dissemination efforts by researchers to non-research audiences to reduce the gap between research generation and uptake in public health practice. We conducted a cross-sectional study of 266 researchers at universities, the National Institutes of Health (NIH), and CDC. We identified scientists using a search of public health journals and lists from government-sponsored research. The scientists completed a 35-item online survey in 2012. Using multivariable logistic regression, we compared self-rated effort to disseminate findings to non-research audiences (excellent/good vs. poor) across predictor variables in three categories: perceptions or reasons to disseminate, perceived expectation by employer/funders, and professional training and experience. One-third of researchers rated their dissemination efforts as poor. Many factors were significantly related to whether a researcher rated him/herself as excellent/good, including obligation to disseminate findings (odds ratio [OR] = 2.7, 95% confidence interval [CI] 1.1, 6.8), dissemination important for their department (OR=2.3, 95% CI 1.2, 4.5), dissemination expected by employer (OR=2.0, 95% CI 1.2, 3.2) or by funder (OR=2.1, 95% CI 1.3, 3.2), previous work in a practice/policy setting (OR=4.4, 95% CI 2.1, 9.3), and university researchers with Prevention Research Center affiliation vs. NIH researchers (OR=4.7, 95% CI 1.4, 15.7). With all variables in the model, dissemination expected by funder (OR=2.0, 95% CI 1.2, 3.1) and previous work in a practice/policy setting (OR=3.5, OR 1.7, 7.1) remained significant. These findings support the need for structural changes to the system, including funding agency priorities and participation of researchers in practice- and policy-based experiences, which may enhance efforts to disseminate by researchers.

28 CFR 20.33 - Dissemination of criminal history record information.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Dissemination of criminal history record... SYSTEMS Federal Systems and Exchange of Criminal History Record Information § 20.33 Dissemination of criminal history record information. (a) Criminal history record information contained in the III System...

28 CFR 20.33 - Dissemination of criminal history record information.