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Sample records for acute inflammatory arthritis

  1. Development of a new humanized mouse model to study acute inflammatory arthritis

    PubMed Central

    2012-01-01

    Background Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis. Methods One to two-day old irradiated NOD-scid IL2rγnull (NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically. Results Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils. Conclusions The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells. PMID:22974474

  2. Vasculitis and inflammatory arthritis.

    PubMed

    Watts, Richard A; Scott, David G I

    2016-10-01

    Vasculitis has been described in most types of inflammatory arthritis. The best described and most widely recognised form is rheumatoid vasculitis. The incidence of systemic rheumatoid vasculitis has declined significantly following the general early use of methotrexate in the 1990s, and it is now a rare form of vasculitis. Treatment of rheumatoid vasculitis is conventionally with glucocorticoids and cyclophosphamide, but there is an increasing role for rituximab similar to that in other types of vasculitis. Despite these developments the mortality of rheumatoid vasculitis remains high. Vasculitis in other types of inflammatory arthritis is less well described and the treatment remains empirical. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Acute phase protein haptoglobin as inflammatory marker in serum and synovial fluid in an equine model of arthritis.

    PubMed

    Barrachina, Laura; Remacha, Ana Rosa; Soler, Lourdes; García, Natalia; Romero, Antonio; Vázquez, Francisco José; Vitoria, Arantza; Álava, María Ángeles; Lamprave, Fermín; Rodellar, Clementina

    2016-12-01

    Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp) serum level is increased in horses undergoing different inflammatory processes, including arthritis. However, Hp concentration has not been assessed in inflammatory synovial fluid (SF). The aim of the present study was to investigate the Hp response in serum and SF in horses undergoing experimentally induced arthritis. For this purpose, serum and SF samples were collected from 12 animals before amphotericin B-induced arthritis was created (T0, healthy) and 15days after the lesion induction (T1, joint inflammation) and Hp was determined by single radial immunodiffusion. The Hp increase between T0 and T1 was significant in both serum and SF, and serum Hp concentration at T0 was significantly higher than in SF, but significant differences were not found at T1, indicating a higher Hp increase in SF. A significant positive correlation for Hp concentration between serum and SF samples was found. These results highlight the potential usefulness of Hp as inflammatory marker in horses, showing for the first time the increase of Hp in SF from joint inflammation in the horse. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Capillaroscopic pattern in inflammatory arthritis

    PubMed Central

    Lambova, Sevdalina Nikolova; Müller-Ladner, Ulf

    2012-01-01

    Background There are limited data about the role of nailfold capillaroscopy in inflammatory arthritis. Objectives To study the role of capillaroscopy in inflammatory arthritis — rheumatoid arthritis (RA), psoriatic arthritis (PsA) and early arthritis. Methods Patients from the following groups were included in the study: 62 patients with RA; 34 patients with PsA with involvement of the joints of the hands; 9 women with early arthritis. Nailfold capillaroscopy was performed with videocapillaroscope. Results Raynaud's phenomenon (RP) was found in 30.6% (19/62) of RA patients, in 32.4% (11/34) of PsA patients and 44.4%, (4/9) of cases with early arthritis. The most frequent found capillaroscopic changes in RA patients were presence of elongated capillaries in 58% of cases (36/62) and prominent subpapillary plexus in 69% (43/62). Dilated capillaries were found in 78.9% (15/19) of patients with secondary RP and in 62.8% (27/43) of those without RP. “Scleroderma-like” capillaroscopic pattern was observed with low frequency in RA patients (14.5%/9/62). “Scleroderma-like” capillaroscopic pattern was also found in 11.1% (1/9) in the group of patients with early arthritis. The low frequency of the last type of capillaroscopic pattern in RA requires patients with such changes to be observed during regular follow-up for the development of systemic rheumatic disease different from inflammatory arthritis. In patients with PsA capillaries with specific morphology (tight terminal convolutions) were found in 58.8% (20/34) of cases. Conclusions Results from the present study confirm the necessity for inclusion of the nailfold capillaroscopy in the diagnostic algorithm in patients with inflammatory arthritis. PMID:22426123

  5. Acute septic arthritis.

    PubMed

    Shirtliff, Mark E; Mader, Jon T

    2002-10-01

    Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.

  6. Colchicine-responsive protracted gouty arthritis with systemic inflammatory reactions.

    PubMed

    Nonaka, Fumiaki; Migita, Kiyoshi; Haramura, Tomoko; Sumiyoshi, Remi; Kawakami, Atsushi; Eguchi, Katsumi

    2014-05-01

    Acute gouty arthritis is a severe but self-limiting arthritis caused by inflammatory responses to urate crystals. Oral colchicines are effective for initial stages or prophylaxis, but generally, colchicines are ineffective for established gouty arthritis. We describe an unusual case of gouty arthritis with systemic inflammatory reactions, including high fever and polymyalgia. Refractory polyarthritis and high fever were eradicated by colchicine treatment. Genetic analysis revealed a heterozygous mutation in exon 2 of the MEFV gene (E148Q). This case underscores the possibility that MEFV gene mutations may modify the phenotype of gouty arthritis.

  7. Targeting pro-inflammatory cytokines following joint injury: acute intra-articular inhibition of interleukin-1 following knee injury prevents post-traumatic arthritis

    PubMed Central

    2014-01-01

    Introduction Post-traumatic arthritis (PTA) is a progressive, degenerative response to joint injury, such as articular fracture. The pro-inflammatory cytokines, interleukin 1(IL-1) and tumor necrosis factor alpha (TNF-α), are acutely elevated following joint injury and remain elevated for prolonged periods post-injury. To investigate the role of local and systemic inflammation in the development of post-traumatic arthritis, we targeted both the initial acute local inflammatory response and a prolonged 4 week systemic inflammatory response by inhibiting IL-1 or TNF-α following articular fracture in the mouse knee. Methods Anti-cytokine agents, IL-1 receptor antagonist (IL-1Ra) or soluble TNF receptor II (sTNFRII), were administered either locally via an acute intra-articular injection or systemically for a prolonged 4 week period following articular fracture of the knee in C57BL/6 mice. The severity of arthritis was then assessed at 8 weeks post-injury in joint tissues via histology and micro computed tomography, and systemic and local biomarkers were assessed in serum and synovial fluid. Results Intra-articular inhibition of IL-1 significantly reduced cartilage degeneration, synovial inflammation, and did not alter bone morphology following articular fracture. However, systemic inhibition of IL-1, and local or systemic inhibition of TNF provided no benefit or conversely led to increased arthritic changes in the joint tissues. Conclusion These results show that intra-articular IL-1, rather than TNF-α, plays a critical role in the acute inflammatory phase of joint injury and can be inhibited locally to reduce post-traumatic arthritis following a closed articular fracture. Targeted local inhibition of IL-1 following joint injury may represent a novel treatment option for PTA. PMID:24964765

  8. Inflammatory arthritis in children with osteochondrodysplasias

    PubMed Central

    Scuccimarri, R.; Azouz, E; Duffy, K.; Fassier, F.; Duffy, C.

    2000-01-01

    Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.

 PMID:11053062

  9. Inflammatory arthritis in children with osteochondrodysplasias.

    PubMed

    Scuccimarri, R; Azouz, E M; Duffy, K N; Fassier, F; Duffy, C M

    2000-11-01

    Osteochondrodysplasias are a heterogeneous group of genetic skeletal dysplasias. Patients with these diseases commonly develop an early degenerative arthritis or osteoarthritis. Occasional observations of inflammatory arthritis have been made in this population but such observations are based on clinical grounds alone without confirmatory imaging studies. Four patients followed up in a paediatric rheumatology clinic with three different skeletal dysplasias, who had both clinical and radiological evidence of an inflammatory arthritis and coexistent degenerative arthritis, are described.

  10. Reactive arthritis mimicking inflammatory bowel disease arthritis: a challenging diagnosis.

    PubMed

    Trabulo, D; Mangualde, J; Cremers, I; Oliveira, A P

    2014-01-01

    Reactive arthritis comprises a subgroup of infection-associated arthritis which occurs after genitourinary or gastrointestinal tract infection in genetically susceptible hosts. Studies have proposed Salmonella, Shigella or Yersinia infection as the microorganisms responsible for the post-dysenteric form. The human leukocyte antigen (HLA)-B27 is a well recognised best-known predisposing factor. We report a case of HLA-B27-associated reactive arthritis after Salmonella goldcoast enteritis, mimicking inflammatory bowel disease arthritis.

  11. Resveratrol lowers synovial hyperplasia, inflammatory markers and oxidative damage in an acute antigen-induced arthritis model.

    PubMed

    Riveiro-Naveira, Romina R; Valcárcel-Ares, Marta N; Almonte-Becerril, Maylin; Vaamonde-García, Carlos; Loureiro, Jesús; Hermida-Carballo, Laura; López-Peláez, Eduardo; Blanco, Francisco J; López-Armada, María J

    2016-10-01

    The present study aimed to determine the protective effects of dietary supplementation with resveratrol (RSV) in an acute antigen-induced arthritis (AIA) model. Rats were randomly divided into three groups: control, AIA and RSV-treated AIA group. RSV (12.5 mg/kg/day) was given orally for 8 weeks before induction of AIA and until the end of the experiment (48 h after intra-articular injection). The control and AIA animals were administered 100 μl of water. Results were evaluated by macroscopic observation, histopathology and immunohistochemistry for anti-PCNA, macrophages (CD68), T lymphocytes (CD3), monocyte chemoattractant protein-1 and 8-oxo-7,8-dihydro-2'-deoxyguanine (a marker of DNA damage). Cytokine-induced neutrophil chemoattractant-1 in serum and peroxidase activity in synovial tissue were measured using commercial kits. At the end of the study, RSV significantly reduced knee swelling. Likewise, the histological score of synovial tissue also reduced significantly. The arthritis-protective effects were associated with a significant decrease in PCNA, CD68, CD3 and monocyte chemoattractant protein-1 staining, as well as a reduction in serum concentrations of cytokine-induced neutrophil chemoattractant-1. RSV treatment also decreased the level of the marker of DNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanine. Accordingly, peroxidase activity in the synovial tissue was up-regulated. Dietary supplementation with RSV lowers the main pathological hallmarks of RA disease in an acute model of AIA. RSV may represent a promising strategy in controlling the severity of RA. © 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.

  12. Photoacoustic tomography to identify inflammatory arthritis

    NASA Astrophysics Data System (ADS)

    Rajian, Justin Rajesh; Girish, Gandikota; Wang, Xueding

    2012-09-01

    Identifying neovascularity (angiogenesis) as an early feature of inflammatory arthritis can help in early accurate diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT) is a hybrid imaging modality which relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. PAT is used to identify changes in the development of inflammatory arthritis in a rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, on rats revealed that there is a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histology images obtained from both the normal and the arthritis affected rats correlated well with the PAT findings. Results support the fact that the emerging PAT could become a new tool for clinical management of inflammatory arthritis.

  13. Acute-phase serum amyloid A regulates tumor necrosis factor α and matrix turnover and predicts disease progression in patients with inflammatory arthritis before and after biologic therapy.

    PubMed

    Connolly, Mary; Mullan, Ronan H; McCormick, Jennifer; Matthews, Clare; Sullivan, Owen; Kennedy, Aisling; FitzGerald, Oliver; Poole, A Robin; Bresnihan, Barry; Veale, Douglas J; Fearon, Ursula

    2012-04-01

    To investigate the relationship between acute-phase serum amyloid A (A-SAA) and joint destruction in inflammatory arthritis. Serum A-SAA and C-reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), and levels of matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinases 1 (TIMP-1), vascular endothelial growth factor (VEGF), and type I and type II collagen-generated biomarkers C2C and C1,2C were measured at 0-3 months in patients with inflammatory arthritis commencing anti-tumor necrosis factor α (anti-TNFα) therapy and were correlated with 1-year radiographic progression. The effects of A-SAA on MMP/TIMP expression on RA fibroblast-like synoviocytes (FLS), primary human chondrocytes, and RA/psoriatic arthritis synovial explant cultures were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, antibody protein arrays, and gelatin zymography. Serum A-SAA levels were significantly (P < 0.05) correlated with MMP-3, the MMP-3:TIMP-1 ratio, C1,2C, C2C, and VEGF. The baseline A-SAA level but not the ESR or the CRP level correlated with the 28-joint swollen joint count and was independently associated with 1-year radiographic progression (P = 0.038). A-SAA increased MMP-1, MMP-3, MMP-13, and MMP/TIMP expression in RA FLS and synovial explants (P < 0.05). In chondrocytes, A-SAA induced MMP-1, MMP-3, and MMP-13 messenger RNA and protein expression (all P < 0.01), resulting in a significant shift in MMP:TIMP ratios (P < 0.05). Gelatin zymography revealed that A-SAA induced MMP-2 and MMP-9 activity. Blockade of the A-SAA receptor SR-B1 (A-SAA receptor scavenger receptor-class B type 1) inhibited MMP-3, MMP-2, and MMP-9 expression in synovial explant cultures ex vivo. Importantly, we demonstrated that A-SAA has the ability to induce TNFα expression in RA synovial explant cultures (P < 0.05). A-SAA may be involved in joint destruction though MMP induction and collagen cleavage in

  14. Inhibition of inflammatory arthritis using fullerene nanomaterials.

    PubMed

    Dellinger, Anthony L; Cunin, Pierre; Lee, David; Kung, Andrew L; Brooks, D Bradford; Zhou, Zhiguo; Nigrovic, Peter A; Kepley, Christopher L

    2015-01-01

    Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis.

  15. Inhibition of Inflammatory Arthritis Using Fullerene Nanomaterials

    PubMed Central

    Dellinger, Anthony L.; Cunin, Pierre; Lee, David; Kung, Andrew L.; Brooks, D. Bradford; Zhou, Zhiguo; Nigrovic, Peter A.; Kepley, Christopher L.

    2015-01-01

    Inflammatory arthritis (e.g. rheumatoid arthritis; RA) is a complex disease driven by the interplay of multiple cellular lineages. Fullerene derivatives have previously been shown to have anti-inflammatory capabilities mediated, in part, by their ability to prevent inflammatory mediator release by mast cells (MC). Recognizing that MC can serve as a cellular link between autoantibodies, soluble mediators, and other effector populations in inflammatory arthritis, it was hypothesized that fullerene derivatives might be used to target this inflammatory disease. A panel of fullerene derivatives was tested for their ability to affect the function of human skin-derived MC as well as other lineages implicated in arthritis, synovial fibroblasts and osteoclasts. It is shown that certain fullerene derivatives blocked FcγR- and TNF-α-induced mediator release from MC; TNF-α-induced mediator release from RA synovial fibroblasts; and maturation of human osteoclasts. MC inhibition by fullerene derivatives was mediated through the reduction of mitochondrial membrane potential and FcγR-mediated increases in cellular reactive oxygen species and NF-κB activation. Based on these in vitro data, two fullerene derivatives (ALM and TGA) were selected for in vivo studies using K/BxN serum transfer arthritis in C57BL/6 mice and collagen-induced arthritis (CIA) in DBA/1 mice. Dye-conjugated fullerenes confirmed localization to affected joints in arthritic animals but not in healthy controls. In the K/BxN moldel, fullerenes attenuated arthritis, an effect accompanied by reduced histologic inflammation, cartilage/bone erosion, and serum levels of TNF-α. Fullerenes remained capable of attenuating K/BxN arthritis in mast cell-deficient mice Cre-Master mice, suggesting that lineages beyond the MC represent relevant targets in this system. These studies suggest that fullerene derivatives may hold promise both as an assessment tool and as anti-inflammatory therapy of arthritis. PMID:25879437

  16. [Differential diagnosis of acute arthritis].

    PubMed

    Eviltis, Egidijus

    2003-01-01

    Acute arthritis can first present as a symptom of dangerous and rapidly progressing disease. It is quite easy to differentiate between arthritis and periarthritis. More problematical is correct early differential diagnosis of the acute arthritis. Determining whether one, several or many joints are affected can narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing provide much information and should be done at initial evaluation if possible. The presence or absence of fever, rash, family history of joint disease and exposure to infective organisms can further direct diagnostic studies and treatment. In general, to avoid masking clues, drug therapy should be delayed for mild symptoms until diagnosis is complete. This article is designed mostly for primary care physicians, residents and includes author's original data and review of recommended reading.

  17. Interferon Regulatory Factor 5 Promotes Inflammatory Arthritis

    PubMed Central

    Duffau, Pierre; Menn-Josephy, Hanni; Cuda, Carla M.; Dominguez, Salina; Aprahamian, Tamar R.; Watkins, Amanda A.; Yasuda, Kei; Monach, Paul; Lafyatis, Robert; Rice, Lisa M.; Haines, G. Kenneth; Gravallese, Ellen M.; Baum, Rebecca; Richez, Christophe; Perlman, Harris; Bonegio, Ramon G.; Rifkin, Ian R.

    2015-01-01

    Objective Polymorphisms in the transcription factor IRF5 are associated with an increased risk of developing RA. This study was done to determine the role of IRF5 in arthritis development. Methods K/BxN serum transfer arthritis was induced in mice deficient in IRF5, or lacking IRF5 only in myeloid cells, and arthritis severity was evaluated. K/BxN arthritis was also induced in mice deficient in TRIF, TLR2, TLR3, TLR4 and TLR7 to determine pathways through which IRF5 might promote arthritis. In-vitro studies were performed to determine the role of IRF5 in IL-1 receptor and TLR signaling. Results Arthritis severity was reduced in IRF5-deficient, TRIF-deficient, TLR3-deficient and TLR7-deficient mice. The expression of multiple genes regulating neutrophil recruitment or function and bioactive IL-1β formation was reduced in the joints during active arthritis in IRF5-deficient mice. In vitro studies showed that TLR7 and the TRIF-dependent TLR3 pathway induce pro-inflammatory cytokine production in disease relevant cell types in an IRF5-dependent manner. Conclusion IRF5 contributes to disease pathogenesis in inflammatory arthritis. This is likely due at least in part to the role of IRF5 in mediating pro-inflammatory cytokine production downstream of TLR7 and TLR3. As TLR7 and TLR3 are both RNA-sensing TLRs, this suggests that endogenous RNA ligands present in the inflamed joint promote arthritis development. These findings may be relevant to human RA as RNA capable of activating TLR7 and TLR3 is present in synovial fluid and TLR7 and TLR3 are upregulated in the joints of RA patients. PMID:26315890

  18. Clinical approaches to early inflammatory arthritis.

    PubMed

    van Schaardenburg, Dirkjan; Dijkmans, Ben A C

    2009-11-01

    Several advances have been made in the understanding of the pathogenesis, as well as in the clinical evaluation and treatment, of early inflammatory arthritis. The presence of anti-citrullinated protein antibodies (ACPAs) has emerged as a major new biomarker for use in clinical practice. The presence of ACPAs can be used to divide patients with early arthritis into subsets that are phenotypically similar but have varying pathogenetic and prognostic features. Although the detection of ACPAs is a major development in the diagnosis and prognosis of rheumatoid arthritis (RA), prediction of the outcome of arthritis at the individual level can still be much improved. For patients diagnosed with RA, and who have active polyarthritis, treatment is not dependent on the assessment of prognostic factors, as these patients are best treated with combination therapy; over 40% of these patients achieve remission with such treatment. In patients who present with oligoarthritis, however, management should be based on the assessment of prognostic factors. The success of early treatment of inflammatory arthritis and the recognition of a measurable preclinical phase of RA offer hope that treating the disease before it becomes clinically active might be possible.

  19. S100A9 is not essential for disease expression in an acute (K/BxN) or chronic (CIA) model of inflammatory arthritis.

    PubMed

    Rampersad, R R; Esserman, D; McGinnis, M W; Lee, D M; Patel, D D; Tarrant, T K

    2009-01-01

    S100A8 (calgranulin A, MRP8) and S100A9 (calgranulin B, MRP14) are calcium-binding proteins highly expressed by activated myeloid cells and thought to be involved in the pathogenesis of inflammatory diseases. Circulating levels of S100A8/S100A9 are elevated in both human and experimental models of autoimmune disease, including rheumatoid arthritis (RA). Mice deficient in S100A9 (S100A9 - /-) and wild-type controls were immunized using standard techniques for the K/BxN serum transfer or the collagen-induced arthritis (CIA) model. S100A9 - /- animals, with defective expression of both S100A8 and S100A9 proteins, had similar arthritis and histopathology to that of wild-type controls in both mouse models. S100A8 and S100A9 are not essential for disease expression in either the K/BxN serum transfer or the CIA model of inflammatory arthritis.

  20. Effect and Treatment of Chronic Pain in Inflammatory Arthritis

    PubMed Central

    2013-01-01

    Pain is the most common reason patients with inflammatory arthritis see a rheumatologist. Patients consistently rate pain as one of their highest priorities, and pain is the single most important determinant of patient global assessment of disease activity. Although pain is commonly interpreted as a marker of inflammation, the correlation between pain intensity and measures of peripheral inflammation is imperfect. The prevalence of chronic, non-inflammatory pain syndromes such as fibromyalgia is higher among patients with inflammatory arthritis than in the general population. Inflammatory arthritis patients with fibromyalgia have higher measures of disease activity and lower quality of life than inflammatory patients who do not have fibromyalgia. This review article focuses on current literature involving the effects of pain on disease assessment and quality of life for patients with inflammatory arthritis. It also reviews non-pharmacologic and pharmacologic options for treatment of pain for patients with inflammatory arthritis, focusing on the implications of comorbidities and concurrent disease-modifying antirheumatic drug therapy. Although several studies have examined the effects of reducing inflammation for patients with inflammatory arthritis, very few clinical trials have examined the safety and efficacy of treatment directed specifically towards pain pathways. Most studies have been small, have focused on rheumatoid arthritis or mixed populations (e.g., rheumatoid arthritis plus osteoarthritis), and have been at high risk of bias. Larger, longitudinal studies are needed to examine the mechanisms of pain in inflammatory arthritis and to determine the safety and efficacy of analgesic medications in this specific patient population. PMID:23292816

  1. Treatment of acute septic arthritis.

    PubMed

    Pääkkönen, Markus; Peltola, Heikki

    2013-06-01

    Acute septic arthritis is a rare, but potentially devastating disease. The treatment is initiated intravenously, but can be safely switched to oral after 2-4 days providing large doses of a well-absorbing antibiotic and, for time-dependent antibiotics, 4 times-a-day administration are used. Empiric treatment should always cover Staphylococcus aureus and common respiratory pathogens, whereas Kingella kingae and Salmonella are important only regionally. Studies conducted by our group have shown that a total course of 10 days may suffice for previously healthy children in a Western setting. Treatment of neonates, patients with immunodeficiency or cases caused by methicillin-resistant S. aureus, may deserve a different approach.

  2. In Vitro TNF-α Inhibitory Activity of Brazilian Plants and Anti-Inflammatory Effect of Stryphnodendron adstringens in an Acute Arthritis Model

    PubMed Central

    Henriques, Bárbara O.; Corrêa, Olívia; Azevedo, Elaine Patrícia C.; Pádua, Rodrigo M.; de Oliveira, Vívian Louise S.; Oliveira, Thiago Henrique C.; Boff, Daiane; Dias, Ana Carolina F.; Amaral, Flávio A.; Castilho, Rachel O.

    2016-01-01

    Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity. PMID:27867403

  3. In Vitro TNF-α Inhibitory Activity of Brazilian Plants and Anti-Inflammatory Effect of Stryphnodendron adstringens in an Acute Arthritis Model.

    PubMed

    Henriques, Bárbara O; Corrêa, Olívia; Azevedo, Elaine Patrícia C; Pádua, Rodrigo M; de Oliveira, Vívian Louise S; Oliveira, Thiago Henrique C; Boff, Daiane; Dias, Ana Carolina F; de Souza, Danielle G; Amaral, Flávio A; Teixeira, Mauro M; Castilho, Rachel O; Braga, Fernão C

    2016-01-01

    Stryphnodendron species, popularly named "barbatimão," are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity.

  4. Managing cardiovascular risk in patients with inflammatory arthritis: practical considerations

    PubMed Central

    Tournadre, Anne; Mathieu, Sylvain; Soubrier, Martin

    2016-01-01

    Patients with inflammatory arthritis, such as rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis, have higher rates of cardiovascular mortality. While the increased cardiovascular risk is only explained to some extent, a lot of research is currently conducted to improve our understanding of its pathogenesis, risk stratification, and optimal cardiovascular risk management. This review sought to report epidemiological data pertaining to the cardiovascular disease burden in patients with inflammatory arthritis, underlying mechanisms accounting for excessive cardiovascular risk, along with recommendations regarding risk assessment and management in this patient population. PMID:27721904

  5. Th2 and eosinophil responses suppress inflammatory arthritis

    PubMed Central

    Chen, Zhu; Andreev, Darja; Oeser, Katharina; Krljanac, Branislav; Hueber, Axel; Kleyer, Arnd; Voehringer, David; Schett, Georg; Bozec, Aline

    2016-01-01

    Th2–eosinophil immune responses are well known for mediating host defence against helminths. Herein we describe a function of Th2–eosinophil responses in counteracting the development of arthritis. In two independent models of arthritis, Nippostrongylus brasiliensis infection leads to Th2 and eosinophil accumulation in the joints associated with robust inhibition of arthritis and protection from bone loss. Mechanistically, this protective effect is dependent on IL-4/IL-13-induced STAT6 pathway. Furthermore, we show that eosinophils play a central role in the modulation of arthritis probably through the increase of anti-inflammatory macrophages into arthritic joints. The presence of these pathways in human disease is confirmed by detection of GATA3-positive cells and eosinophils in the joints of rheumatoid arthritis patients. Taken together, these results demonstrate that eosinophils and helminth-induced activation of the Th2 pathway axis effectively mitigate the course of inflammatory arthritis. PMID:27273006

  6. Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators.

    PubMed

    Dhanasekar, Chitra; Rasool, Mahaboobkhan

    2016-09-05

    The anti-inflammatory effect of morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -α, interleukin (IL)-1β, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)), and nuclear factor-kappa B (NF-κB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in morin treated MSU crystal-induced rats. In addition, morin treatment reduced the protein expression of NF-κB p65, p-NF-κB p65, iNOS, COX-2, and TNF-α. The results clearly demonstrated that morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats.

  7. Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review

    PubMed Central

    Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

    2017-01-01

    Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated. PMID:28293455

  8. Viscosupplementation of the knee: Three cases of acute Pseudoseptic Arthritis with painful and irritating complications and a literature review.

    PubMed

    Aydın, Murat; Arıkan, Murat; Toğral, Güray; Varış, Onur; Aydın, Güle

    2017-03-01

    Acute pseudoseptic arthritis is a very rare complication that is associated with intra-articular hyaluronic acid injections, which normally involve minimal risk. The most common adverse events that are caused by hyaluronic acid injections are inflammatory reactions or flares at the injection site. In this study, we described three cases of acute pseudoseptic arthritis that was caused by hyaluronic acid; the symptoms in these cases were reminiscent of acute septic arthritis. Moreover, we performed a literature review on pseudoseptic arthritis following hyaluronic acid injections to determine the manner in which this condition can be described, diagnosed, and treated.

  9. Footwear characteristics in people with inflammatory arthritis in Singapore.

    PubMed

    Carter, K; Lahiri, M; Cheung, P P; Santosa, A; Rome, K

    2016-01-01

    Foot problems are common in people with inflammatory arthritis. Despite suitable footwear having the potential to alleviate pain, improve mobility and maintain independence, previous studies have found many people with inflammatory arthritis wearing poorly fitting and inappropriate footwear. Footwear styles and characteristics have not been reported in a Singapore inflammatory arthritis population. The objective of this study was to identify current footwear styles and characteristics of footwear worn by people with inflammatory arthritis in Singapore. One-hundred-and-one participants with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a large public hospital in Singapore. Disease and clinical characteristics were recorded. A patient-reported outcome included current foot pain. An objective footwear assessment of style, age of shoe, fit and construction was conducted. The majority of participants were Chinese women with a mean (SD) age was 52.0 (15.0) years old and a mean (SD) disease duration of 9.3 (0.3) years. We found 50 % of participants (n = 51) reported footwear problems. Sandals (n = 27, 26 %), flip-flops (n = 19, 19 %) and moccasin type (n = 19, 19 %) was the most common footwear choice. Evaluation of footwear characteristics found that there was a lack of motion control features. Only 32 (32 %) participants had correctly fitting footwear with regard to length, width and depth. No participant was wearing therapeutic footwear. This study provides the first insight into footwear preferences of people with inflammatory arthritis in Singapore. Use of slip-on and poorly fitting footwear was found to be common in people with inflammatory arthritis. Further research on footwear preferences in Southeast-Asian communities needs to take into account cultural habit and preference, socio-economic status, footwear options and affordability.

  10. Septic versus inflammatory arthritis: discriminating the ability of serum inflammatory markers.

    PubMed

    Talebi-Taher, Mahshid; Shirani, Fatemeh; Nikanjam, Najmeh; Shekarabi, Mehdi

    2013-02-01

    Early diagnosis of septic arthritis is very important. Few studies showed diagnostic accuracy of serum inflammatory markers in septic arthritis. The aim of our study was to compare the serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts and PMN percentage] in septic and inflammatory arthritis. Seventy-five patients, including 25 and 50 septic and non-septic arthritis, were enrolled in the study. The serum and synovial fluid markers [procalcitonin, serum IL-6, TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage] were compared in septic and inflammatory arthritis. Patients with septic arthritis had significantly elevated levels of procalcitonin, serum TNF-α, C-reactive protein, erythrocyte sedimentation rate, synovial fluid white blood cell counts, and PMN percentage in comparison with the inflammatory arthritis group (P < 0.00). Serum IL-6 level does not differ among the two groups. In a receiver operating characteristic curve analysis, synovial fluid WBC counts, PMN percentage, TNF-α, ESR, and serum PCT preformed best in distinguishing between septic and non-septic arthritis. Our study suggests that PCT can be used to diagnose the septic arthritis, but more studies warranted in order to determine the specificity and sensitivity of the test.

  11. Sirt2 suppresses inflammatory responses in collagen-induced arthritis

    SciTech Connect

    Lin, Jiangtao; Sun, Bing; Jiang, Chuanqiang; Hong, Huanyu; Zheng, Yanping

    2013-11-29

    Highlights: •Sirt2 expression decreases in collagen-induced arthritis (CIA). •Sirt2 knockout aggravates severity of arthritis in mice with CIA. •Sirt2 knockout increases levels of pro-inflammatory factors in the serum. •Sirt2 deacetylates p65 and inhibits pro-inflammatory factors expression. •Sirt2 rescue abates severity of arthritis in mice with CIA. -- Abstract: Arthritis is a common autoimmune disease that is associated with progressive disability, systemic complications and early death. However, the underling mechanisms of arthritis are still unclear. Sirtuins are a NAD{sup +}-dependent class III deacetylase family, and regulate cellular stress, inflammation, genomic stability, carcinogenesis, and energy metabolism. Among the sirtuin family members, Sirt1 and Sirt6 are critically involved in the development of arthritis. It remains unknown whether other sirtuin family members participate in arthritis. Here in this study, we demonstrate that Sirt2 inhibits collagen-induced arthritis (CIA) using in vivo and in vitro evidence. The protein and mRNA levels of Sirt2 significantly decreased in joint tissues of mice with CIA. When immunized with collagen, Sirt2-KO mice showed aggravated severity of arthritis based on clinical scores, hind paw thickness, and radiological and molecular findings. Mechanically, Sirt2 deacetylated p65 subunit of nuclear factor-kappa B (NF-κB) at lysine 310, resulting in reduced expression of NF-κB-dependent genes, including interleukin 1β (IL-1β), IL-6, monocyte chemoattractant protein 1(MCP-1), RANTES, matrix metalloproteinase 9 (MMP-9) and MMP-13. Importantly, our rescue experiment showed that Sirt2 re-expression abated the severity of arthritis in Sirt2-KO mice. Those findings strongly indicate Sirt2 as a considerably inhibitor of the development of arthritis.

  12. 78 FR 65450 - Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-31

    ... AFFAIRS Agency Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire) Activity... oira_submission@omb.eop.gov . Please refer to ``OMB Control No. 2900- NEW (Non-Degenerative Arthritis...

  13. 78 FR 36305 - Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-17

    ... AFFAIRS Proposed Information Collection (Non-Degenerative Arthritis (Including Inflammatory, Autoimmune, Crystalline and Infectious Arthritis) and Dysbaric Osteonecrosis Disability Benefits Questionnaire) Activity... disability benefits related to a claimant's diagnosis of a non-degenerative arthritis or osteonecrosis...

  14. Low-intensity laser therapy efficacy evaluation in FVB mice subjected to acute and chronic arthritis.

    PubMed

    Issa, João Paulo Mardegan; Trawitzki, Bianca Ferreira; Ervolino, Edilson; Macedo, Ana Paula; Lilge, Lothar

    2017-08-01

    Rheumatoid arthritis, an autoimmune inflammation, has a high prevalence in the population, and while therapy is available, it required often injection of drugs causing discomfort to patients. This study evaluates the clinical and histological effect of low-intensity laser therapy (LILT) as an alternative treatment, in a murine model of acute and chronic inflammation. FVB mice received either a Zymosan A injection into one knee joint inducing acute inflammation, followed after 15 min or 24 h by LILT or a collagen bovine type II injection emulsified in "Freund's Complete Adjuvant" to induce chronic arthritis, followed at 4 weeks with multiple LILT sessions. LILT mediated by either 660, 808, or 905 nm and tissue response was evaluated based on clinical symptoms and histological analysis of inflammatory infiltrate and damage to the articular surfaces. LILT can be effective in elevating clinical symptoms, so Kruskal-Wallis testing indicated no significant differences between knees affected by acute arthritis and treated once with LILT and an injured knee without treatment (p > 0.05) for 660 and 808 nm with some improvements for the 905-nm LILT. Mice receiving two treatments for acute arthritis showed exacerbation of inflammation and articular resorption following therapy with a 660-nm continuous laser (p < 0.05). For chronic inflammation, differences were not noted between LILT treated and untreated injured knee joints (p > 0.05). Among the lasers, the 905 nm tends to show better results for anti-inflammatory effect in acute arthritis, and the 660 nm showed better results in chronic arthritis. In conclusion, LILT wavelength selection depends on the arthritis condition and can demonstrate anti-inflammatory effects for chronic arthritis and reduced resorption area in this murine model.

  15. Venipuncture Induced Complex Regional Pain Syndrome Presenting as Inflammatory Arthritis

    PubMed Central

    Arora, Pramod; Mittal, Manoj; Nair, Anugrah; Sultana, Waqia

    2016-01-01

    Venipuncture is one of the most commonly done medical procedures. We report a unique case of a 23-year-old young male who presented with features suggestive of inflammatory arthritis. The symptoms, which initially started on the right side, also involved the other side after a few weeks. Although the patient's symptoms and signs were simulating inflammatory arthritis, he had atypical features like poor response to anti-inflammatory medicines and normal laboratory parameters. His musculoskeletal ultrasonography was also not suggestive of arthritis. His history was reviewed and on direct questioning he revealed a history of venipuncture for blood sample withdrawal, done from right antecubital region for routine health check on the day prior to the onset of symptoms. Complex regional pain syndrome was suspected and triple-phase radioisotope bone scan was done which was highly suggestive of this diagnosis. The patient was managed with multidimensional approach and responded very well to the treatment. Complex regional pain syndrome is usually not thought of in the initial differential diagnosis of inflammatory arthritis. In this report we highlight the need to elicit the often overlooked history of trivial trauma like venipuncture, especially in atypical cases of arthritis. Also the role of newer diagnostic modalities in such cases is emphasized. PMID:27891152

  16. Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups

    PubMed Central

    Siebert, Stefan; Porter, Duncan; Paterson, Caron; Hampson, Rosie; Gaya, Daniel; Latosinska, Agnieszka; Mischak, Harald; Schanstra, Joost; Mullen, William; McInnes, Iain

    2017-01-01

    Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis. PMID:28091549

  17. In vivo inhibition of human neutrophil collagenase (MMP-8) activity during long-term combination therapy of doxycycline and non-steroidal anti-inflammatory drugs (NSAID) in acute reactive arthritis.

    PubMed Central

    Lauhio, A; Salo, T; Ding, Y; Konttinen, Y T; Nordström, D; Tschesche, H; Lähdevirta, J; Golub, L M; Sorsa, T

    1994-01-01

    We studied the in vivo effect of long-term doxycycline treatment combined with NSAID on human interstitial collagenases, other matrix metalloproteinases, serine proteinases, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and lactoferrin from saliva and serum during the course of acute reactive arthritis (ReA). Collagenase activity and serine proteases (elastase-like, cathepsin G-like and trypsin-like activities) of saliva (n = 10) and gelatinase, lactoferrin and TIMP-1 of saliva (n = 10) and serum (n = 10) samples before and after 2 months doxycycline treatment, combined with NSAID, were studied by quantitative SDS-PAGE assay, ELISA assay and by spectrophotometric assay. The cellular source and molecular forms of salivary collagenase were characterized by immunoblotting using specific antisera. We found that activities of total and endogenously active interstitial collagenase reduced significantly. The salivary collagenase was found to originate from neutrophils. No fragmentation of either pro 75-kD and active 65-kD MMP-8 was detected after 2 months doxycycline treatment. However, during 2 months doxycycline and NSAID treatment no reduction of salivary and serum gelatinase, lactoferrin and TIMP-1-levels and salivary serine protease activities were detected. The in vivo inhibition of collagenase (MMP-8) activity during long-term doxycycline therapy in human saliva containing inflammatory exudate of ReA patients may contribute to the reduced tissue destruction observed in recent clinical and animal model studies in arthritides during long-term doxycycline/tetracycline treatment. Images Fig. 2 Fig. 3 PMID:7923879

  18. Photoacoustic and ultrasound dual-modality imaging for inflammatory arthritis

    NASA Astrophysics Data System (ADS)

    Xu, Guan; Chamberland, David; Girish, Gandikota; Wang, Xueding

    2014-03-01

    Arthritis is a leading cause of disability, affecting 46 million of the population in the U.S. Rendering new optical contrast in articular tissues at high spatial and temporal resolution, emerging photoacoustic imaging (PAI) combined with more established ultrasound (US) imaging technologies provides unique opportunities for diagnosis and treatment monitoring of inflammatory arthritis. In addition to capturing peripheral bone and soft tissue images, PAI has the capability to quantify hemodynamic properties including regional blood oxygenation and blood volume, both abnormal in synovial tissues affected by arthritis. Therefore, PAI, especially when performed together with US, should be of considerable help for further understanding the pathophysiology of arthritis as well as assisting in therapeutic decisions, including assessing the efficacy of new pharmacological therapies. In this paper, we will review our recent work on the development of PAI for application to the diagnostic imaging and therapeutic monitoring of inflammatory arthritis. We will present the imaging results from a home-built imaging system and another one based on a commercial US. The performance of PAI in evaluating pharmacological therapy on animal model of arthritis will be shown. Moreover, our resent work on PAI and US dual-modality imaging of human peripheral joints in vivo will also be presented.

  19. Agmatine ameliorates adjuvant induced arthritis and inflammatory cachexia in rats.

    PubMed

    Taksande, Brijesh G; Gawande, Dinesh Y; Chopde, Chandrabhan T; Umekar, Milind J; Kotagale, Nandkishor R

    2017-02-01

    The present study investigated the pharmacological effect of agmatine in Complete Freud Adjuvant (CFA) induced arthritis and cachexia in rats. The rats were injected with CFA (0.1ml/rat) to induced symptoms of arthritis. Day 8 onwards of CFA administration, rats were injected daily with agmatine for next 7days, and arthritis score, body weights and food intake were monitored daily (g). Since cachexia is known to produce severe inflammation, malnutrition and inhibition of albumin gene expression, we have also monitored the total proteins, albumin, TNF-α and IL-6 levels in arthritic rats and its modulation by agmatine. In the present study, CFA treated rats showed a progressive reduction in both food intake and body weight. In addition analysis of blood serum of arthritis animals showed a significant reduction in proteins and albumin and significant elevation in tumor necrosis factor (TNF)-α and Interleukins (IL)-6. Chronic agmatine (20-40mg/kg, ip) treatment not only attenuated the signs of arthritis but also reverses anorexia and body weight loss in CFA treated rats. In addition, agmatine restored total protein and albumin and reduces TNF-α and IL-6 levels in arthritis rats. These results suggest that agmatine administration can prevent the body weights loss and symptoms of arthritis via inhibition of inflammatory cytokines.

  20. Heat shock proteins and their immunomodulatory role in inflammatory arthritis.

    PubMed

    Spierings, Julia; van Eden, Willem

    2017-02-01

    Autoimmune diseases, including inflammatory arthritis, are characterized by a loss of self-tolerance, leading to an excessive immune responses and subsequent ongoing inflammation. Current therapies are focused on dampening this inflammation, but a permanent state of tolerance is seldom achieved. Therefore, novel therapies that restore and maintain tolerance are needed. Tregs could be a potential target to achieve permanent immunotolerance. Activation of Tregs can be accomplished when they recognize and bind their specific antigens. HSPs are proteins present in all cells and are upregulated during inflammation. These proteins are immunogenic and can be recognized by Tregs. Several studies in animal models and in human clinical trials have shown the immunoregulatory effects of HSPs and their protective effects in inflammatory arthritis. In this review, an overview is presented of the immunomodulatory effects of several members of the HSP family in general and in inflammatory arthritis. These effects can be attributed to the activation of Tregs through cellular interactions within the immune system. The effect of HSP-specific therapies in patients with inflammatory arthritis should be explored further, especially with regard to long-term efficacy and safety and their use in combination with current therapeutic approaches. © 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.

  1. Inflammatory Arthritis, Sacroiliitis, and Morphea: Evidence of a Systemic Inflammatory Disease

    PubMed Central

    Omair, Mohammed A.

    2013-01-01

    Morphea is a skin disease characterized by local skin inflammation and fibrosis. Extracutaneous manifestations have been described with this disease including inflammatory arthritis. We describe a case of morphea who developed inflammatory polyarthritis and sacroiliitis coincident with new skin lesions. PMID:23997976

  2. Inflammatory arthritis in HIV positive patients: A practical guide.

    PubMed

    Adizie, T; Moots, R J; Hodkinson, B; French, N; Adebajo, A O

    2016-03-01

    Musculoskeletal manifestations of the human immunodeficiency virus (HIV) have been described since the outset of the global HIV epidemic. Articular syndromes that have been described in association with HIV include HIV-associated arthropathy, seronegative spondyloarthropathies (SPA) (reactive arthritis, psoriatic arthritis (PsA) and undifferentiated SPA), rheumatoid arthritis (RA) and painful articular syndrome. We carried out a computer-assisted search of PubMed for the medical literature from January 1981 to January 2015 using the keywords HIV, acquired immune-deficiency syndrome, rheumatic manifestations, arthritis, spondyloarthropathy, anti-TNF and disease modifying antirheumatic drugs. Only English language literature was included and only studies involving adult human subjects were assessed. There are challenges in the management of inflammatory arthritis in patients who are HIV-positive, including difficulties in the assessment of disease activity and limited information on the safety of immunosuppressive drugs in these individuals. This review focuses on the clinical characteristics of the inflammatory articular syndromes that have been described in association with HIV infection and discusses the therapeutic options for these patients.

  3. Divergent T-Cell Cytokine Patterns in Inflammatory Arthritis

    NASA Astrophysics Data System (ADS)

    Simon, A. K.; Seipelt, E.; Sieper, J.

    1994-08-01

    A major immunoregulatory mechanism in inflammatory infections and allergic diseases is the control of the balance of cytokines secreted by Th1/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseases; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune diseases. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Th1-like pattern whereas in reactive arthritis interferon γ expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confirmed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.

  4. [Pregnancy in patients with rheumatoid arthritis and inflammatory spondylarthropathies].

    PubMed

    Gromnica-Ihle, E; Ostensen, M

    2006-05-01

    The activity of a rheumatic disease can be influenced by pregnancy and puerperium. Prospective studies have shown an improvement in joint involvement in rheumatoid arthritis in two thirds to three quarters of pregnancies. After birth, an exacerbation is common. In spondylarthropathies there is no relevant change in disease activity. The fetal outcome is not impaired in patients with rheumatoid arthritis and inflammatory spondylarthropathies. Every pregnancy in women with a rheumatic disease should be considered as high-risk, and such pregnancies require close collaboration between rheumatologists and obstetricians.

  5. Predicting persistent inflammatory arthritis amongst early arthritis clinic patients in the UK: is musculoskeletal ultrasound required?

    PubMed Central

    2013-01-01

    Introduction Analyses of large clinical datasets from early arthritis cohorts permit the development of algorithms that may be used for outcome prediction in individual patients. The value added by routine use of musculoskeletal ultrasound (MSUS) in an early arthritis setting, as a component of such predictive algorithms, remains to be determined. Methods The authors undertook a retrospective analysis of a large, true-to-life, observational inception cohort of early arthritis patients in Newcastle upon Tyne, UK, which included patients with inflammatory arthralgia but no clinically swollen joints. A pragmatic, 10-minute MSUS assessment protocol was developed, and applied to each of these patients at baseline. Logistic regression was used to develop two "risk metrics" that predicted the development of a persistent inflammatory arthritis (PIA), with or without the inclusion of MSUS parameters. Results A total of 379 enrolled patients were assigned definitive diagnoses after ≥12 months follow-up (median 28 months), of whom 162 (42%) developed a persistent inflammatory arthritis. A risk metric derived from 12 baseline clinical and serological parameters alone had an excellent discriminatory utility with respect to an outcome of PIA (area under receiver operator characteristic (ROC) curve 0.91; 95% CI 0.88 to 0.94). The discriminatory utility of a similar metric, which incorporated MSUS parameters, was not significantly superior (area under ROC curve 0.91; 95% CI 0.89 to 0.94). Neither did this approach identify an added value of MSUS over the use of routine clinical parameters in an algorithm for discriminating PIA patients whose outcome diagnosis was rheumatoid arthritis (RA). Conclusions MSUS use as a routine component of assessment in an early arthritis clinic did not add substantial discriminatory value to a risk metric for predicting PIA. PMID:24028567

  6. The Discovery of Novel Experimental Therapies for Inflammatory Arthritis

    PubMed Central

    Malemud, Charles J.

    2009-01-01

    Conventional and biologic disease-modifying antirheumatic drugs have revolutionized the medical therapy of inflammatory arthritis. However, it remains unclear as to what can be done to treat immune-mediated chronic inflammation after patients become refractory to these therapies or develop serious side-effects and/or infections forcing drug withdrawal. Because of these concerns it is imperative that novel targets be continuously identified and experimental strategies designed to test potential arthritis interventions in vitro, but more importantly, in well-validated animal models of inflammatory arthritis. Over the past few years, sphingosine-1-phosphate, interleukin-7 receptor, spleen tyrosine kinase, extracellular signal-regulated kinase, mitogen-activated protein kinase 5/p38 kinase regulated/activated protein kinase, micro-RNAs, tumor necrosis factor-related apoptosis inducing ligand and the polyubiquitin-proteasome pathway were identified as promising novel targets for potential antiarthritis drug development. Indeed several experimental compounds alter the biological activity of these targets and have shown clinical efficacy in animal models of arthritis. A few of them have even entered the first phase of human clinical trials. PMID:20339519

  7. Photoacoustic evaluation of human inflammatory arthritis in human joints

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Xu, Guan; Marquardt, April; Girish, Gandikota; Wang, Xueding

    2017-03-01

    Photoacoustic (PA) imaging combined with ultrasonography (US) holds promise to offer a novel and powerful tool for clinical management of inflammatory arthritis, including early detection and treatment monitoring. As a complement to US, PA imaging can assess additional hemodynamic changes in inflammatory synovium, including hyperemia and hypoxia, both important and early physiological biomarkers of synovitis reflecting the increased metabolic demand and the relatively inadequate oxygen delivery of the inflammatory synovial tissue. In this study on arthritis patients and normal volunteers, the targeted metacarpophalangeal (MCP) joints were imaged using our real-time US-PA dual-modality imaging system. The blood volume and the blood oxygenation in the segmented synovium were quantified, and the results from the arthritis patients were compared to those from the normal volunteers. This initial study on human subjects demonstrated that PA imaging, by working at the optical wavelengths that are sensitive to oxygenated and deoxygenated hemoglobin, is capable of identifying and characterizing inflammation in joints based on the detection of hemodynamic changes.

  8. Distinguishing inflammatory from noninflammatory arthritis, enthesitis, and dactylitis in psoriatic arthritis: a report from the GRAPPA 2010 annual meeting.

    PubMed

    Mease, Philip J

    2012-02-01

    The most widely applied criteria for classifying psoriatic arthritis (PsA) are the CASPAR (ClASsification of Psoriatic ARthritis) criteria. A patient who fulfills the CASPAR criteria must have evidence of inflammatory arthritis, enthesitis, or spondylitis, and may have an inflammatory musculoskeletal component, dactylitis. Although the criteria were developed by rheumatologists, not all patients with PsA are seen by rheumatologists. Thus, it is important for clinicians such as dermatologists, primary care providers, physiatrists, and orthopedists, and patients themselves, to be able to recognize the presence of inflammatory musculoskeletal disease and distinguish it from degenerative or traumatic musculoskeletal disease. At their 2010 annual meeting, members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) discussed the steps they are taking to define the key variables that must be present to distinguish inflammatory arthritis, enthesitis, and dactylitis from degenerative, traumatic, mechanical, or infectious forms of these conditions.

  9. Autoimmune/Inflammatory Arthritis Associated Lymphomas: Who Is at Risk?

    PubMed Central

    2016-01-01

    Specific autoimmune and inflammatory rheumatic diseases have been associated with an increased risk of malignant lymphomas. Conditions such as rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE), dermatomyositis, and celiac disease have been consistently linked to malignant lymphomas. Isolated cases of lymphomas associated with spondyloarthropathies and autoinflammatory diseases have also been reported. Direct association between autoimmunity and lymphomagenesis has been reinforced by large epidemiological studies. It is still uncertain whether disease specific determinants or phenotypic or treatment related characteristics increase likelihood of lymphomagenesis in these patients. For example, recent literature has indicated a positive correlation between severity of inflammation and risk of lymphomas among RA and Sjögren's syndrome patients. It is also debated whether specific lymphoma variants are more commonly seen in accordance with certain chronic autoimmune arthritis. Previous studies have revealed a higher incidence of diffuse large B-cell lymphomas in RA and SLE patients, whereas pSS has been linked with increased risk of mucosa-associated lymphoid tissue lymphoma. This review summarizes recent literature evaluating risk of lymphomas in arthritis patients and disease specific risk determinants. We also elaborate on the association of autoimmune arthritis with specific lymphoma variants along with genetic, environmental, and therapeutic risk factors. PMID:27429984

  10. Photoacoustic imaging of inflammatory arthritis in human joints

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Xu, Guan; Marquardt, April; Francis, Sheeja; Yuan, Jie; Girish, Dhanuj; Girish, Gandikota; Wang, Xueding

    2016-02-01

    The ducal imaging with photoacoustic imaging (PAI) that is an emerging technology and clinical ultrasound imaging that is an established modality is developed for the imaging of early inflammatory arthritis. PAI is sensitive to blood volume, not limited by flow like ultrasound, holding great promise for the earliest detection of increase in blood volume and angiogenesis - a key early finding inflammation PAI has the capability of assessing inflammation in superficial human soft tissues, offering potential benefits in diagnosis, treatment and monitoring of inflammatory arthritis. PAI combined with ultrasonography (US), is a real time dual-modality system developed and tested to identify active synovitis in metacarpophalangeal (MCP) joints of 10 arthritis patients and 10 normal volunteers. Photoacoustic images of the joints were acquired at 580-nm laser wavelength, which provided the desired balance between the optical contrast of hemoglobin over bone cortex and the imaging depth. Confirmed by US Doppler imaging, the results from ten patients and ten normal volunteers demonstrated satisfactory sensitivity of PAI in assessing enhanced blood flow due to active synovitis. This preliminary study suggests that photoacoustic imaging, by identifying early increase in blood volume, related to increased vascularity, a hallmark of joint inflammation, could be a valuable supplement to musculoskeletal US.

  11. Arthritis

    MedlinePlus

    ... joints Infection, most often by bacteria or virus Crystals such as uric acid or calcium pyrophosphate dihydrate ... common types of inflammatory arthritis include: Ankylosing ... calcium pyrophosphate deposition disease Juvenile rheumatoid ...

  12. K/BxN Serum-Transfer Arthritis as a Model for Human Inflammatory Arthritis

    PubMed Central

    Christensen, Anne D.; Haase, Claus; Cook, Andrew D.; Hamilton, John A.

    2016-01-01

    The K/BxN serum-transfer arthritis (STA) model is a murine model in which the immunological mechanisms occurring in rheumatoid arthritis (RA) and other arthritides can be studied. To induce K/BxN STA, serum from arthritic transgenic K/BxN mice is transferred to naive mice and manifestations of arthritis occur a few days later. The inflammatory response in the model is driven by autoantibodies against the ubiquitously expressed self-antigen, glucose-6-phosphate isomerase (G6PI), leading to the formation of immune complexes that drive the activation of different innate immune cells such as neutrophils, macrophages, and possibly mast cells. The pathogenesis further involves a range of immune mediators including cytokines, chemokines, complement factors, Toll-like receptors, Fc receptors, and integrins, as well as factors involved in pain and bone erosion. Hence, even though the K/BxN STA model mimics only the effector phase of RA, it still involves a wide range of relevant disease mediators. Additionally, as a murine model for arthritis, the K/BxN STA model has some obvious advantages. First, it has a rapid and robust onset of arthritis with 100% incidence in genetically identical animals. Second, it can be induced in a wide range of strain backgrounds and can therefore also be induced in gene-deficient strains to study the specific importance of disease mediators. Even though G6PI might not be an essential autoantigen, for example, in RA, the K/BxN STA model is a useful tool to understand how autoantibodies, in general, drive the progression of arthritis by interacting with downstream components of the innate immune system. Finally, the model has also proven useful as a model wherein arthritic pain can be studied. Taken together, these features make the K/BxN STA model a relevant one for RA, and it is a potentially valuable tool, especially for the preclinical screening of new therapeutic targets for RA and perhaps other forms of inflammatory arthritis. Here, we

  13. K/BxN Serum-Transfer Arthritis as a Model for Human Inflammatory Arthritis.

    PubMed

    Christensen, Anne D; Haase, Claus; Cook, Andrew D; Hamilton, John A

    2016-01-01

    The K/BxN serum-transfer arthritis (STA) model is a murine model in which the immunological mechanisms occurring in rheumatoid arthritis (RA) and other arthritides can be studied. To induce K/BxN STA, serum from arthritic transgenic K/BxN mice is transferred to naive mice and manifestations of arthritis occur a few days later. The inflammatory response in the model is driven by autoantibodies against the ubiquitously expressed self-antigen, glucose-6-phosphate isomerase (G6PI), leading to the formation of immune complexes that drive the activation of different innate immune cells such as neutrophils, macrophages, and possibly mast cells. The pathogenesis further involves a range of immune mediators including cytokines, chemokines, complement factors, Toll-like receptors, Fc receptors, and integrins, as well as factors involved in pain and bone erosion. Hence, even though the K/BxN STA model mimics only the effector phase of RA, it still involves a wide range of relevant disease mediators. Additionally, as a murine model for arthritis, the K/BxN STA model has some obvious advantages. First, it has a rapid and robust onset of arthritis with 100% incidence in genetically identical animals. Second, it can be induced in a wide range of strain backgrounds and can therefore also be induced in gene-deficient strains to study the specific importance of disease mediators. Even though G6PI might not be an essential autoantigen, for example, in RA, the K/BxN STA model is a useful tool to understand how autoantibodies, in general, drive the progression of arthritis by interacting with downstream components of the innate immune system. Finally, the model has also proven useful as a model wherein arthritic pain can be studied. Taken together, these features make the K/BxN STA model a relevant one for RA, and it is a potentially valuable tool, especially for the preclinical screening of new therapeutic targets for RA and perhaps other forms of inflammatory arthritis. Here, we

  14. Gram staining in the diagnosis of acute septic arthritis.

    PubMed

    Faraj, A A; Omonbude, O D; Godwin, P

    2002-10-01

    This study aimed at determining the sensitivity and specificity of Gram staining of synovial fluid as a diagnostic tool in acute septic arthritis. A retrospective study was made of 22 patients who had arthroscopic lavage following a provisional diagnosis of acute septic arthritis of the knee joint. Gram stains and cultures of the knee aspirates were compared with the clinical and laboratory parameters, to evaluate their usefulness in diagnosing acute arthritis. All patients who had septic arthritis had pain, swelling and limitation of movement. CRP was elevated in 90% of patients. The incidence of elevated white blood cell count was higher in the group of patients with a positive Gram stain study (60%) as compared to patients with a negative Gram stain study (33%). Gram staining sensitivity was 45%. Its specificity was however 100%. Gram staining is an unreliable tool in early decision making in patients requiring urgent surgical drainage and washout.

  15. Specialised pro-resolving mediators of inflammation in inflammatory arthritis.

    PubMed

    Barden, Anne E; Moghaddami, Mahin; Mas, Emilie; Phillips, Michael; Cleland, Leslie G; Mori, Trevor A

    2016-04-01

    Specialised pro-resolving mediators (SPM) are derived from n-3 long chain polyunsaturated fatty acids (n-3FA). They promote resolution of inflammation and may contribute to the beneficial effects of n-3FA in patients with arthritis. This study compared SPM in knee effusions and plasma of patients with arthritis taking n-3FA, and plasma of healthy volunteers taking n-3FA. Thirty six patients taking n-3FA undergoing arthrocentesis for an inflammatory knee effusion and 36 healthy volunteers who had taken n-3FA (2.4g/day) for 4 weeks were studied. SPM in synovial fluid and plasma were measured by liquid chromatography-tandem mass spectrometry included 18-hydroxyeicosapentaenoic acid (18-HEPE), the precursor of the E-series SPM (RvE1, RvE2, RvE3, 18R-RvE3), and 17-hydroxydocosahexaenoic acid (17-HDHA), the precursor of the D-series SPM (RvD1, 17R-RvD1, RvD2). Other SPM included protectin D1 (PD1), 10S,17S-dihydroxydocosahexaenoic acid (10,17S-DHDHA), maresin-1 (MaR-1) and 14-hydroxydocosahexaenoic acid (14-HDHA) derived from docosahexaenoic acid (DHA). E- and D-series SPM and the precursors 18-HEPE and 17-HDHA were present in synovial fluid and plasma of the patients with inflammatory arthritis. Plasma SPM were negatively related to erythrocyte sedimentation rate in arthritis patients (P<0.01) and synovial fluid RvE2 was negatively associated with pain score (P=0.02). Conversion from 18-HEPE and 17-HDHA to E- and D-series SPM was greater in synovial fluid (P<0.01). Most plasma SPM in arthritis patients were elevated (P<0.05) compared with healthy volunteers, and conversion to E- and D-series SPM was greater (P<0.01). SPM are present in chronic knee effusions and although the levels are lower than in plasma, the association between synovial fluid RvE2 and reduced pain scores suggests that synthesis of SPM at the site of inflammation is a relevant mechanism by which n-3FA alleviate the symptoms of arthritis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Inflammatory arthritis in patients with myelodysplastic syndromes: a multicenter retrospective study and literature review of 68 cases.

    PubMed

    Mekinian, Arsène; Braun, Thorsten; Decaux, Olivier; Falgarone, Géraldine; Toussirot, Eric; Raffray, Loic; Omouri, Mohamed; Gombert, Bruno; De Wazieres, Benoit; Buchdaul, Anne-Laure; Ziza, Jean-Marc; Launay, David; Denis, Guillaume; Madaule, Serge; Rose, Christian; Grignano, Eric; Fenaux, Pierre; Fain, Olivier

    2014-01-01

    We describe the characteristics and outcome of inflammatory arthritis in patients with myelodysplastic syndrome (MDS) in a French multicenter retrospective study. Twenty-two patients with MDS (median age, 77.5 yr [interquartile range, 69-81]; 10 women) were included. Inflammatory arthritis presented as polyarthritis in 17 cases (77%) and with symmetric involvement in 15 cases (68%). At diagnosis, the median disease activity score 28 based on C-reactive protein (DAS28-CRP) was 4.5 [2-6.5]. Two patients had anti-citrullinated protein antibodies (ACPAs), and 1 had radiologic erosions. The median time between the diagnoses of arthritis and MDS was 10 months [6-42], with a median articular symptom duration of 3 months [2-8]. The diagnosis of both diseases was concomitant in 6 cases (27%); arthritis preceded MDS in 12 cases (55%), and occurred after MDS in 4 (18%). While the number of swollen and tender joints significantly decreased during follow-up, as did the median DAS28-CRP (from 4.3 [3.8-4.6] at baseline to 2.9 [1.75-3.3]; p < 0.05), CRP remained elevated (CRP >20 mg/L) in 8 patients (42%). Nevertheless, radiographic progression and new ACPA positivity were not observed during a median follow-up of 29 months [9-76]. While most of the patients were treated with steroids (n = 16) for arthritis, additional treatment was administered in only 4 patients (hydroxychloroquine, n = 2; sulfasalazine [Salazopyrin] and etanercept, n = 1, respectively). Eleven patients died during follow-up from acute myeloid leukemia (n = 5); infections (n = 3); or cerebral bleeding, cardiorespiratory failure, or undetermined cause (n = 1, respectively). Inflammatory arthritis associated with MDS can have various presentations and is often seronegative and nonerosive. Steroids alone are the most common treatment in MDS-associated arthritis, but that treatment is insufficient to control arthritis. Steroid-sparing strategies need to be identified.

  17. Nutraceuticals of anti-inflammatory activity as complementary therapy for rheumatoid arthritis.

    PubMed

    Al-Okbi, Sahar Y

    2014-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by elevated oxidative stress and inflammatory biomarkers. The severe side effects of drug used during such disease necessitate the search for new and safe approaches. Food is a rich source of antioxidants and anti-inflammatory bioactive constituents including phenolic compounds, polyunsaturated fatty acids, phytosterols, toccopherols, and carotenoids. We have a series of publications dealing with the anti-inflammatory activity of different food extracts (as nutraceuticals) in experimental animals (acute and chronic inflammation model) and in clinical study (RA patients). Fish oil, primrose oil, extracts of black cumin, fenugreek, liquorice, coriander, tomato, carrot, sweet potato, broccoli, green tea, rosemary, hazelnut, walnut, wheat germ, and date in addition to the probiotic Bifidobacterium bifidum were the nutraceuticals studied. During these studies, changes in inflammatory biomarkers (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), seromucoids, fibrinogen, tumor necrosis factor-α (TNF-α), prostaglandin E2), oxidative stress (malondialdehyde), antioxidant status (total antioxidant capacity, vitamin C, vitamin E, retinol, β-carotene), the level of copper (Cu) and zinc (Zn) and colonic microflora in response to the administration of nutraceuticals have been assessed. Results of these studies showed that the majority of nutraceuticals studied possess beneficial effect toward chronic inflammatory diseases, which might be due to the presence of one or more of the above-mentioned phytochemicals. Anti-inflammatory and antioxidant nutraceuticals may serve as complementary medicine for the management of RA. © The Author(s) 2012.

  18. DEK-targeting DNA aptamers as therapeutics for inflammatory arthritis

    PubMed Central

    Mor-Vaknin, Nirit; Saha, Anjan; Legendre, Maureen; Carmona-Rivera, Carmelo; Amin, M Asif; Rabquer, Bradley J.; Gonzales-Hernandez, Marta J.; Jorns, Julie; Mohan, Smriti; Yalavarthi, Srilakshmi; Pai, Dave A.; Angevine, Kristine; Almburg, Shelley J.; Knight, Jason S.; Adams, Barbara S.; Koch, Alisa E.; Fox, David A.; Engelke, David R.; Kaplan, Mariana J.; Markovitz, David M.

    2017-01-01

    Novel therapeutics are required for improving the management of chronic inflammatory diseases. Aptamers are single-stranded RNA or DNA molecules that have recently shown utility in a clinical setting, as they can specifically neutralize biomedically relevant proteins, particularly cell surface and extracellular proteins. The nuclear chromatin protein DEK is a secreted chemoattractant that is abundant in the synovia of patients with juvenile idiopathic arthritis (JIA). Here, we show that DEK is crucial to the development of arthritis in mouse models, thus making it an appropriate target for aptamer-based therapy. Genetic depletion of DEK or treatment with DEK-targeted aptamers significantly reduces joint inflammation in vivo and greatly impairs the ability of neutrophils to form neutrophil extracellular traps (NETs). DEK is detected in spontaneously forming NETs from JIA patient synovial neutrophils, and DEK-targeted aptamers reduce NET formation. DEK is thus key to joint inflammation, and anti-DEK aptamers hold promise for the treatment of JIA and other types of arthritis. PMID:28165452

  19. Inflammatory Cell Migration in Rheumatoid Arthritis: A Comprehensive Review.

    PubMed

    Nevius, Erin; Gomes, Ana Cordeiro; Pereira, João P

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects the joints. Self-reactive B and T lymphocytes cooperate to promote antibody responses against self proteins and are major drivers of disease. T lymphocytes also promote RA independently of B lymphocytes mainly through the production of key inflammatory cytokines, such as IL-17, that promote pathology. While the innate signals that initiate self-reactive adaptive immune responses are poorly understood, the disease is predominantly caused by inflammatory cellular infiltration and accumulation in articular tissues, and by bone erosions driven by bone-resorbing osteoclasts. Osteoclasts are giant multinucleated cells formed by the fusion of multiple myeloid cells that require short-range signals, such as the cytokines MCSF and RANKL, for undergoing differentiation. The recruitment and positioning of osteoclast precursors to sites of osteoclast differentiation by chemoattractants is an important point of control for osteoclastogenesis and bone resorption. Recently, the GPCR EBI2 and its oxysterol ligand 7a, 25 dihydroxycholesterol, were identified as important regulators of osteoclast precursor positioning in proximity to bone surfaces and of osteoclast differentiation under homeostasis. In chronic inflammatory diseases like RA, osteoclast differentiation is also driven by inflammatory cytokines such as TNFa and IL-1, and can occur independently of RANKL. Finally, there is growing evidence that the chemotactic signals guiding osteoclast precursors to inflamed articular sites contribute to disease and are of great interest. Furthering our understanding of the complex osteoimmune cell interactions should provide new avenues of therapeutic intervention for RA.

  20. The evidence for microbiome manipulation in inflammatory arthritis.

    PubMed

    Jethwa, Hannah; Abraham, Sonya

    2017-09-01

    The human body consists of millions of commensal bacteria (the microbiome), with the intestinal tract being the most prevalent site of colonization. This colonization process begins at birth, and despite numerous factors such as ageing, diet and drug use affecting the microbiome make-up, by adulthood the composition of the gut bacteria is relatively consistent across local populations. The recent advent of new scientific techniques has enabled us to explore how the microbiome affects health and, in particular, has shed light on the involvement of the microbiome in the pathogenesis of inflammatory disease. In this review we highlight the current evidence for microbiome manipulation in inflammatory arthritis in animal and human models and discuss potential therapeutics targeting the microbiome as treatment for these diseases. © 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.

  1. Hypercalcemia and Lytic Bone Lesions Masquerading Inflammatory Arthritis Treated as Rheumatoid Arthritis.

    PubMed

    Salari, Masoumeh; Aboutorabi, Robab Bigom; Rezaieyazdi, Zahra

    2015-10-01

    Hyperparathyroidism is a complex clinical syndrome characterized by dysfunction in the metabolism of bone, calcium and phosphorus. Rheumatologic manifestations are common amongst patients with hyperparathyroidism. We report a 50-year-old woman with hypercalcemia, lytic bone lesions and inflammatory arthritis of both hands that were not resolved after parathyroidectomy. Laboratory evidence of elevated erythrocyte sedimentation rate, positive C-reactive protein (CRP) and high titers of anti-CCP and rheumatoid factor was diagnostic of rheumatoid arthritis (RA) according to European League Against Rheumatism criteria. Eventually, with the concomitant diagnoses of hyperparathyroidism and RA, she was treated with methotrexate and hydroxychloroquin. Hyperparathyroidism may present with rheumatologic manifestations, leading to an initial misdiagnosis. Furthermore, attention to this fact that hypercalcemia is not commonly associated with RA, and rather suggestive of a concomitant disorder, is crucial to the diagnosis of hyperparathyroidism in RA patients with hypercalcemia.

  2. Prolactin promotes cartilage survival and attenuates inflammation in inflammatory arthritis

    PubMed Central

    Adán, Norma; Guzmán-Morales, Jessica; Ledesma-Colunga, Maria G.; Perales-Canales, Sonia I.; Quintanar-Stéphano, Andrés; López-Barrera, Fernando; Méndez, Isabel; Moreno-Carranza, Bibiana; Triebel, Jakob; Binart, Nadine; Martínez de la Escalera, Gonzalo; Thebault, Stéphanie; Clapp, Carmen

    2013-01-01

    Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3–dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor–null (Prlr–/–) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA. PMID:23908112

  3. Buprenorphine Alters Inflammatory and Oxidative Stress Molecular Markers in Arthritis

    PubMed Central

    Hitchon, Carol

    2017-01-01

    Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-γ, IL-6, and MMP-3, and oxidative markers, for example, iNOS, superoxide dismutase (SOD1), and catalase (CAT), in the CIA mice. As buprenorphine is an analgesic, we further monitored the association of expression of these biomarkers with pain scores in a human cohort of early rheumatoid arthritis (RA). Serum MMP-3 levels and blood mRNA expression of antioxidants sod1 and cat correlated with pain scores in the RA cohort. We have demonstrated that administration of buprenorphine alters the expression of inflammatory and oxidative stress-related molecular markers in a murine model of CIA. This caveat needs to be considered in animal experiments using buprenorphine as an analgesic, as it can be a confounding factor in murine studies used for prediction of response to therapy. Furthermore, the antioxidant enzymes that showed an association with pain scores in the human cohort may be explored as biomarkers for pain in future studies. PMID:28572711

  4. Mitochondrial mutagenesis correlates with the local inflammatory environment in arthritis.

    PubMed

    Harty, Leonard C; Biniecka, Monika; O'Sullivan, Jacintha; Fox, Edward; Mulhall, Kevin; Veale, Douglas J; Fearon, Ursula

    2012-04-01

    To examine the association between mitochondrial mutagenesis and the proinflammatory microenvironment in patients with inflammatory arthritis. Fifty patients with inflammatory arthritis underwent arthroscopy and synovial tissue biopsies, synovial fluid and clinical assessment were obtained. Fifteen patients pre/post-TNFi therapy were also recruited. Normal synovial biopsies were obtained from 10 subjects undergoing interventional arthroscopy. Macroscopic synovitis/vascularity was measured by visual analogue scale. Cell-specific markers CD3 (T cells) and CD68 (macrophages) were quantified by immunohistology. TNFα, IL-6, IFNγ and IL-1β were measured in synovial fluids by MSD multiplex assays. Synovial tissue mitochondrial mutagenesis was quantified using a mitochondrial random mutation capture assay (RMCA). The direct effect of TNFα on oxidative stress and mitochondrial function was assessed in primary cultures of rheumatoid arthritis synovial fibroblast cells (RASFCs). Mitochondrial mutagenesis, reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and mitochondrial mass (MM) were quantified using the RMCA and specific cell fluorescent probes. A significant increase in mtDNA mutation frequency was demonstrated in inflamed synovial tissue compared with control (p<0.05), an effect that was independent of age. mtDNA mutations positively correlated with macroscopic synovitis (r=0.52, p<0.016), vascularity (r=0.54, p<0.01) and with synovial fluid cytokine levels of TNFα (r=0.74, p<0.024) and IFNγ (r=0.72, p<0.039). mtDNA mutation frequency post-TNFi therapy was significantly lower in patients with a DAS<3.2 (p<0.05) and associated with clinical and microscopic measures of disease (p<0.05). In vitro TNFα significantly induced mtDNA mutations, ROS, MM and MMP in RASFCs (all p<0.05). High mitochondrial mutations are strongly associated with synovial inflammation showing a direct link between mitochondrial mutations and key proinflammatory pathways.

  5. Osteoarthritis-like damage of cartilage in the temporomandibular joints in mice with autoimmune inflammatory arthritis

    PubMed Central

    Ghassemi-Nejad, S.; Kobezda, T.; Rauch, T.A.; Matesz, C.; Glant, T.T.; Mikecz, K.

    2011-01-01

    Summary Objective To study temporomandibular joint (TMJ) involvement in an autoimmune murine model of rheumatoid arthritis (RA), a disease characterized by inflammatory destruction of the synovial joints. Although TMJ dysfunction is frequently found in RA, TMJ involvement in RA remains unclear, and TMJ pathology has not been studied in systemic autoimmune animal models of RA. Methods Proteoglycan (PG) aggrecan-induced arthritis (PGIA) was generated in genetically susceptible BALB/c mice. TMJs and joint tissues/cartilage were harvested for histological and immunohistochemical analyses and RNA isolation for quantitative polymerase chain reaction. Serum cytokine levels were measured in mice with acute or chronic arthritis, and in non-arthritic control animals. Results Despite the development of destructive synovitis in the limbs, little or no synovial inflammation was found in the TMJs of mice with PGIA. However, the TMJs of arthritic mice showed evidence of aggrecanase- and matrix metalloproteinase-mediated loss of glycosaminoglycan-containing aggrecan, and in the most severe cases, structural damage of cartilage. Serum levels of pro-inflammatory cytokines, including interleukin (IL)-1β, were elevated in arthritic animals. Expression of the IL-1β gene was also high in the inflamed limbs, but essentially normal in the TMJs. Local expression of genes encoding matrix-degrading enzymes (aggrecanases and stromelysin) was upregulated to a similar degree in both the limbs and the TMJs. Conclusion We propose that constantly elevated levels of catabolic cytokines, such as IL-1β, in the circulation (released from inflamed joints) create a pro-inflammatory milieu within the TMJ, causing local upregulation of proteolytic enzymes and subsequent loss of aggrecan from cartilage. PMID:21262368

  6. Canakinumab: a guide to its use in acute gouty arthritis flares.

    PubMed

    Lyseng-Williamson, Katherine A

    2013-08-01

    Canakinumab (Ilaris®), an anti-interleukin-1β monoclonal antibody, is a novel approach to treat acute gouty arthritis flares in a targeted population of patients in whom treatment options are limited. Relative to on-demand treatment with intramuscular triamcinolone acetonide 40 mg, on-demand treatment with subcutaneous canakinumab 150 mg significantly relieved the pain and inflammation of a new gout flare, and reduced the risk of new flares in patients with acute gouty arthritis flares in whom standard treatment with non-steroidal anti-inflammatories and/or colchicine was inappropriate. Canakinumab has an acceptable tolerability profile in this difficult-to-treat population. The increased risk of infections and neutropenia associated with canakinumab treatment can be minimized by following the recommended precautions.

  7. Gouty Arthritis: A Review of Acute Management and Prevention.

    PubMed

    Wilson, Liza; Saseen, Joseph J

    2016-08-01

    Gouty arthritis is one of the most common rheumatic diseases. The clinical burden of gouty arthritis has historically been well recognized; however, gout is often misdiagnosed and mismanaged. The prevalence of gout is rising and is likely attributed to several factors including increased incidence of comorbidities, lifestyle factors, and increased use of causative medications. With the increasing prevalence, there have been several innovations and evidence-based updates related to the diagnosis and management of gout. Acute gouty arthritis should be treated with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids, or a combination of two agents. Xanthine oxidase inhibitor therapy remains the consensus first-line treatment option for the prevention of recurrent gout. Add-on therapies that reduce serum urate concentration include traditional uricosuric agents and a novel uric acid reabsorption inhibitor. Prophylaxis of acute gout with NSAIDs, colchicine, or corticosteroids is universally recommended when initiating any urate-lowering therapy in order to prevent acute gouty arthritis for a period of at least 6 months. In this review, we discuss the epidemiology and risk factors for gouty arthritis and evaluate diagnostic strategies and therapeutic regimens for the management of gout, including a new drug approval.

  8. Seasonal trend of acute pelvic inflammatory disease.

    PubMed

    Xholli, Anjeza; Cannoletta, Marianna; Cagnacci, Angelo

    2014-05-01

    Many infections follow a seasonal trend. Aim of our study was to check whether acute pelvic inflammatory disease (PID) follows a seasonal progress. In a retrospective study on 12,152 hospital records, 158 cases of acute pelvic inflammatory disease were identified. Periodogram analysis was applied to the date of pelvic inflammatory disease admission and to related environmental factors, such as temperature and photoperiod. Pelvic inflammatory disease follows a seasonal rhythm with mean to peak variation of 23 % and maximal values in September (±37.2 days). The rhythm, more evident in married women, is related to the rhythm of temperature advanced by 2 months and of photoperiod advanced by 3 months. Cases of pelvic inflammatory disease are more frequent than expected in unmarried (36 vs. 17.3/34,626, p = 0.015), particularly divorced women 30-40 years of age. Our study evidences a seasonal trend and confirms unmarried, particularly divorced status, as important risk factor for acute pelvic inflammatory disease.

  9. Anti-Inflammatory Effects of Vitis thunbergii var. taiwaniana on Knee Damage Associated with Arthritis

    PubMed Central

    Tsai, Ching-Fent; Wang, Kun-Teng; Chen, Lih-Geeng; Lee, Chia-Jung; Tseng, Sung-Hui

    2014-01-01

    Abstract Vitis thunbergii Sieb. et Zucc. var. taiwaniana Lu (VT) is an indigenous plant in Taiwan that is traditionally used for promoting joint health. In this study, we used in vitro primary human chondrocytes (PHCs) and two in vivo animal models to evaluate the anti-inflammatory effects of VT on arthritis. Results showed that the water extract of the stems and roots from VT (VT-SR) was rich in flavones and phenols with 1.1 mg/g of resveratrol, 6.7 mg/g of hopeaphenol, and 5.1 mg/g of (+)-ɛ-viniferin. VT-SR significantly scavenged DPPH radicals and inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-induced PHCs without exhibiting significant cytotoxicity. In in vivo models, the VT-SR (500 mg/kg) significantly decreased serum PGE2 and knee 2-18F-fluoro-2-deoxy-D-glucose (18F-FDG) levels in LPS-induced acute inflammatory arthritis in rabbits. In addition, dietary supplementation with VT-SR for 28 days significantly alleviated type II collagenase-induced rat osteoarthritis with improvements in weight bearing and range of motion tests. In conclusion, our results suggest that the VT-SR is a good candidate for developing dietary supplements to prevent joint deterioration and inhibit inflammation. PMID:24720858

  10. Anti-inflammatory effects of Vitis thunbergii var. taiwaniana on knee damage associated with arthritis.

    PubMed

    Tsai, Ching-Fent; Wang, Kun-Teng; Chen, Lih-Geeng; Lee, Chia-Jung; Tseng, Sung-Hui; Wang, Ching-Chiung

    2014-04-01

    Vitis thunbergii Sieb. et Zucc. var. taiwaniana Lu (VT) is an indigenous plant in Taiwan that is traditionally used for promoting joint health. In this study, we used in vitro primary human chondrocytes (PHCs) and two in vivo animal models to evaluate the anti-inflammatory effects of VT on arthritis. Results showed that the water extract of the stems and roots from VT (VT-SR) was rich in flavones and phenols with 1.1 mg/g of resveratrol, 6.7 mg/g of hopeaphenol, and 5.1 mg/g of (+)-ɛ-viniferin. VT-SR significantly scavenged DPPH radicals and inhibited prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-induced PHCs without exhibiting significant cytotoxicity. In in vivo models, the VT-SR (500 mg/kg) significantly decreased serum PGE2 and knee 2-(18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG) levels in LPS-induced acute inflammatory arthritis in rabbits. In addition, dietary supplementation with VT-SR for 28 days significantly alleviated type II collagenase-induced rat osteoarthritis with improvements in weight bearing and range of motion tests. In conclusion, our results suggest that the VT-SR is a good candidate for developing dietary supplements to prevent joint deterioration and inhibit inflammation.

  11. Cissus quadrangularis attenuates the adjuvant induced arthritis by down regulating pro-inflammatory cytokine and inhibiting angiogenesis.

    PubMed

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender; Arunraja, S

    2015-12-04

    In traditional medicine, Cissus quadrangularis has been used as a chief ingredient of many formulation for the treatment of inflammatory and bone disorders.. The study was carried out to investigate the anti-arthritic activity of C. quadrangularis hydroalcoholic extract (CQHE) and to explore the plausible mechanism of action. Arthritis was induced by sub plantar administration of formaldehyde (2% v/v) and 0.1ml of complete Freund's adjuvant. Joint swelling was measured on days 8, 9 and 10 in formaldehyde-induced arthritis and on 3, 7, 14 and 21 days in adjuvant induced arthritis (AIA) respectively. Serum and ankle joints of AIA rats were used for estimation of serum TNF-α level, oxidative stress markers and synovial expression of proinflammatory cytokines/cytokine receptor (IL-1β, IL-6, TNF-R1), angiogenesis marker (VEGF) and matrix metalloproteinases (MMP-3& 9). An acute and 28-day oral toxicity was carried out to evaluate the safety of the test drug. CQHE produced a dose dependent inhibition of joint swelling in both formaldehyde-induced and adjuvant induced arthritis. CQHE treatment also reduced serum TNF-α level, oxidative stress and synovial expression of inflammatory and angiogenesis marker. In sub acute toxicity study of CQHE, chronic administration of CQHE did not produce any physiological and pathological changes as compared to normal rats. Our study demonstrated the anti-arthritic potential of C. quadrangularis and it validates its traditional use for the treatment of arthritis and other inflammatory disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Is it easy to clinically distinguish inflammatory arthritis of bacterial origin from monoarthritis attacks of gout disease?

    PubMed

    Atik, O Şahap; Ergişi, Yılmaz; Ayanoğlu, Tacettin; Tokgöz, Mehmet Ali; Sezgin, Erdem Aras; Göçün, Pınar Uyar

    2016-12-01

    Acute monoarthritis is a common situation in orthopedic emergency where the patient presents with typical inflamed joint. It is hard to clinically distinguish inflammatory arthritis of bacterial origin from monoarthritis attacks of gout disease. If these two situations, which are the most common causes of acute monoarthritis, are misdiagnosed, outcomes might be catastrophic and costly. Synovial fluid analysis is the most reliable method for confirming the diagnosis although it might not always lead to definitive diagnosis. If there is clinical suspicion for crystal arthropathy, repeated examinations may provide benefits for confirming the diagnosis.

  13. Mechanistic aspects of inflammation and clinical management of inflammation in acute gouty arthritis.

    PubMed

    Cronstein, Bruce N; Sunkureddi, Prashanth

    2013-01-01

    It has been recently demonstrated that interleukin 1β (IL-1β) plays a central role in monosodium urate crystal-induced inflammation and that the NALP3 inflammasome plays a major role in IL-1β production. These discoveries have offered new insights into the pathogenesis of acute gouty arthritis. In this review, we discuss the molecular mechanisms by which monosodium urate crystals induce acute inflammation and examine the mechanisms of action (MOAs) of traditional anti-inflammatory drugs (e.g., nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids) and biologic agents (e.g., the IL-1β antagonists anakinra, rilonacept, and canakinumab) to understand how their MOAs contribute to their safety profiles. Traditional anti-inflammatory agents may act on the IL-1β pathway at some level; however, their MOAs are broad-ranging, unspecific, and biologically complex. This lack of specificity may explain the range of systemic adverse effects associated with them. The therapeutic margins of nonsteroidal anti-inflammatory drugs, colchicine, and glucocorticoids are particularly low in elderly patients and in patients with cardiovascular, metabolic, or renal comorbidities that are frequently associated with gouty arthritis. In contrast, the IL-1β antagonists act on very specific targets of inflammation, which may decrease the potential for systemic adverse effects, although infrequent but serious adverse events (including infection and administration reactions) have been reported. Because these IL-1β antagonists target an early event immediately downstream from NALP3 inflammasome activation, they may provide effective alternatives to traditional agents with minimal systemic adverse effects. Results of ongoing trials of IL-1β antagonists will likely provide clarification of their potential role in the management of acute gouty arthritis.

  14. Cutaneous abnormalities in rheumatoid arthritis compared with non‐inflammatory rheumatic conditions

    PubMed Central

    Douglas, K M J; Ladoyanni, E; Treharne, G J; Hale, E D; Erb, N; Kitas, G D

    2006-01-01

    Background Cutaneous abnormalities are common in rheumatoid arthritis, but exact prevalence estimates are yet to be established. Some abnormalities may be independent and coincidental, whereas others may relate to rheumatoid arthritis or its treatment. Objectives To determine the exact nature and point prevalence of cutaneous abnormalities in patients with rheumatoid arthritis compared with those in patients with non‐inflammatory rheumatic disease. Methods 349 consecutive outpatients for rheumatology (205 with rheumatoid arthritis and 144 with non‐inflammatory rheumatic conditions) were examined for skin and nail signs by a dermatologist. Histories of rheumatology, dermatology, drugs and allergy were noted in detail. Results Skin abnormalities were reported by more patients with rheumatoid arthritis (61%) than non‐inflammatory controls (47%). More patients with rheumatoid arthritis (39%) than controls (10%) attributed their skin abnormality to drugs. Cutaneous abnormalities observed by the dermatologist were also more common in patients with rheumatoid arthritis (76%) than in the group with non‐inflammatory disease (60%). Specifically, bruising, athlete's foot, scars, rheumatoid nodules and vasculitic lesions were more common in patients with rheumatoid arthritis than in controls. The presence of bruising was predicted only by current steroid use. The presence of any other specific cutaneous abnormalities was not predicted by any of the variables assessed. In the whole group, current steroid use and having rheumatoid arthritis were the only important predictors of having any cutaneous abnormality. Conclusions Self‐reported and observed cutaneous abnormalities are more common in patients with rheumatoid arthritis than in controls with non‐inflammatory disease. These include cutaneous abnormalities related to side effects of drugs or to rheumatoid arthritis itself and other abnormalities previously believed to be independent but which may be of clinical

  15. Anti-Inflammatory Effects of the Essential Oils of Ginger (Zingiber officinale Roscoe) in Experimental Rheumatoid Arthritis.

    PubMed

    Funk, Janet L; Frye, Jennifer B; Oyarzo, Janice N; Chen, Jianling; Zhang, Huaping; Timmermann, Barbara N

    2016-07-01

    Ginger and its extracts have been used traditionally as anti-inflammatory remedies, with a particular focus on the medicinal properties of its phenolic secondary metabolites, the gingerols. Consistent with these uses, potent anti-arthritic effects of gingerol-containing extracts were previously demonstrated by our laboratory using an experimental model of rheumatoid arthritis, streptococcal cell wall (SCW)-induced arthritis. In this study, anti-inflammatory effects of ginger's other secondary metabolites, the essential oils (GEO), which contain terpenes with reported phytoestrogenic activity, were assessed in female Lewis rats with SCW-induced arthritis. GEO (28 mg/kg/d ip) prevented chronic joint inflammation, but altered neither the initial acute phase of joint swelling nor granuloma formation at sites of SCW deposition in liver. Pharmacologic doses of 17-β estradiol (200 or 600 μg/kg/d sc) elicited the same pattern of anti-inflammatory activity, suggesting that GEO could be acting as a phytoestrogen. However, contrary to this hypothesis, GEO had no in vivo effect on classic estrogen target organs, such as uterus or bone. En toto, these results suggest that ginger's anti-inflammatory properties are not limited to the frequently studied phenolics, but may be attributable to the combined effects of both secondary metabolites, the pungent-tasting gingerols and as well as its aromatic essential oils.

  16. Effect of sodium alginate addition to resveratrol on acute gouty arthritis.

    PubMed

    Wang, Peng; Ren, Dunlin; Chen, Ying; Jiang, Meiju; Wang, Robin; Wang, Yan-Gang

    2015-01-01

    Resveratrol has been shown to exert anti-inflammatory and antioxidant effects, while sodium alginate is a common pharmaceutic adjuvant with antioxidative and immunomodulatory properties. We performed an animal study to investigate the effect of sodium alginate addition to resveratrol on acute gouty arthritis. Twenty-four SPF Wistar mice were randomized to four groups receiving the combination of sodium alginate and resveratrol, resveratrol alone, colchicine, and placebo, respectively. Acute gouty arthritis was induced by injection of 0.05 ml monosodium urate (MSU) solution (25g/mL) into ankle joint cavity. IL-1β, CCR5, and CXCL10 levels in both serum and synovial fluid were measured using ELISA. NLRP3 expression in the synovial tissues was measured using western plot. The combination of sodium alginate and resveratrol significantly reduced synovial levels of IL-1β, CCR5, and CXCL10 when compared with colchicines, and all P values were less than 0.0001. The combination of sodium alginate and resveratrol was also superior to resveratrol in terms of both serum levels and synovial levels of IL-1β, CCR5, and CXCL10. In addition, resveratrol, with or without sodium alginate, could reduce NLRP3 expression obviously in the synovial tissues. The combination of sodium alginate and resveratrol has better effect over colchicines in treating MSU-induced acute gouty arthritis.

  17. Shoulder arthroplasty for the treatment of inflammatory arthritis.

    PubMed

    Collins, David N; Harryman, Douglas T; Wirth, Michael A

    2004-11-01

    Prosthetic replacement of the glenohumeral joint can relieve pain and improve shoulder function for patients with end-stage inflammatory arthritis. The purpose of this study was to prospectively analyze the clinical, functional, and radiographic outcomes of shoulder reconstruction with hemiarthroplasty or total shoulder arthroplasty. In this multicenter prospective study, clinical history, physical examination, and self-assessment tools including a visual analogue scale, the Simple Shoulder Test, and an activities questionnaire were used to measure comfort, quality of life, and function. Radiographic outcome was determined by assessing the severity of the disease, the adaptation of the prosthesis to the anatomy, the implant position and relationships, and the restoration of glenohumeral alignment. At the time of follow-up, at a minimum of twenty-four months (mean, thirty-nine months), the thirty-six shoulders treated with a hemiarthroplasty and the twenty-five treated with a total shoulder arthroplasty showed significant improvement (p < 0.0001) as demonstrated by the visual analogue scale and the Simple Shoulder Test as well as improvements in the components of the activities questionnaire. Active forward elevation was significantly better (p < 0.004) after the total shoulder arthroplasties than after the hemiarthroplasties. The presence of extremely severe disease did not affect the clinical outcome. Prosthetic adaptation to the anatomy and restoration of glenohumeral alignment resulted in significant improvement in certain motion parameters and were associated with one another (p < 0.001). Restoration of glenohumeral alignment resulted in significant improvements in overall quality of life (p = 0.038), use of the arm for work and play (p = 0.014), and range of motion (p = 0.0004) compared with those parameters when alignment had not been restored. Glenoid erosion occurred in four of the shoulders treated with hemiarthroplasty. Two of the glenoid components used

  18. Symptomatic acute reactive arthritis after an outbreak of salmonella.

    PubMed

    Rohekar, Sherry; Tsui, Florence W L; Tsui, Hing Wo; Xi, Nancy; Riarh, Reena; Bilotta, Rose; Inman, Robert D

    2008-08-01

    In 2005, 592 individuals in Ontario developed acute gastroenteritis, predominantly after consuming bean sprouts contaminated with Salmonella enteritidis. Salmonella is a known trigger of reactive arthritis (ReA). We describe the population affected by the Salmonella outbreak in terms of clinical presentation of self-reported arthritic symptoms and HLA-B27 genotyping. Subjects were mailed a questionnaire, which assessed symptoms consistent with ReA. Subsequently, subjects were asked to submit saliva samples, which were analyzed for HLA-B27. Simple descriptive statistics were performed for analysis of survey responses, and the genetic component was analyzed by chi-square or Fisher's exact tests. Most respondents were female (71.3%), with a mean age of 46.0 years. The mean duration of diarrhea symptoms was 16.5 days. 62.5% of respondents reported extraintestinal symptoms that were consistent with ReA. The most commonly reported features were joint pain, swelling or stiffness (46.2%), stiffness > 30 min (35.6%), ocular symptoms (24.0%), and visibly swollen joints (19.2%). Subjects with Salmonella infection had a similar incidence of HLA-B27, regardless of whether they developed symptoms consistent with ReA or not. Notably, HLA-B27 was present more frequently in those who developed Salmonella infection than in healthy controls (OR 3.0). The study, one of the largest for a dysenteric outbreak, revealed a high event rate of self-reported symptoms consistent with ReA in those infected with Salmonella. Our results showed that HLA-B27 may have rendered individuals more susceptible to Salmonella infection, but did not contribute to the development of symptoms consistent with ReA after infection. We note that the methods used in this study, including self-report, are not ideal for diagnosis of inflammatory arthritis. However, given the rarity of large outbreaks of Salmonella, the study adds valuable knowledge about the course of ReA.

  19. Effects of TGFbeta1 and extracts from Cervus korean TEMMINCK var. mantchuricus Swinhoe on acute and chronic arthritis in rats.

    PubMed

    Kim, Kyung-Woon; Song, Kwon-Ho; Lee, Ji-Min; Kim, Kap-Sung; Kim, Sung-Il; Moon, Sung-Kwon; Kang, Bong-Seok; Kim, Dong-Soo; Chung, Kang-Hyun; Chang, Young-Chae; Kim, Cheorl-Ho

    2008-07-23

    To elucidate the pharmacological activities of deer antler acupuncture and TGF61538;1 on the acute and chronic phases of rheumatoid arthritis diseases. Polyarthritis rats were administered with TGF61538;1 and water extract of deer antler acupunture (DAA), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe. TGF61538; (0.1 to 2 61549;g/animal) and DAA (5-100 61549;g/kg animal) were initiated 1 day before an arthritogenic dose of streptococcal cell wall fragments to see the effects on the joint swelling and distortion during the acute phase and the chronic phase of the disease. Arthritic index suppression of rat arthritis model was examined by TGF61538; and DAA administrations. TGF61538;1 and DAA diminished the polyarthritis development in rats. TGF61538; and DAA eliminated the joint swelling and distortion observed during the acute phase and the chronic phase of the disease. The TGF61538; and DAA suppressed the arthritis progress when administration was begun after acute phase of arthritis. Consistent with the inhibition of inflammatory cell recruitment into the synovium, TGF61538;1 and DAA reversed the leukocytosis associated with the chronic phase of the arthritis, respectively.

  20. Protective effects of a blueberry extract in acute inflammation and collagen-induced arthritis in the rat.

    PubMed

    Figueira, Maria-Eduardo; Oliveira, Mónica; Direito, Rosa; Rocha, João; Alves, Paula; Serra, Ana-Teresa; Duarte, Catarina; Bronze, Rosário; Fernandes, Adelaide; Brites, Dora; Freitas, Marisa; Fernandes, Eduarda; Sepodes, Bruno

    2016-10-01

    Here we investigated the anti-inflammatory effect of a blueberry extract in the carrageenan-induced paw edema model and collagen-induced arthritis model, both in rats. Along with the chemical characterization of the phenolic content of the fruits and extract, the antioxidant potential of the extract, the cellular antioxidant activity and the effects over neutrophils' oxidative burst, were studied in order to provide a mechanistic insight for the anti-inflammatory effects observed. The extract significantly inhibited paw edema formation in an acute model the rat. Our results also demonstrate that the standardized extract had pharmacological activity when administered orally in the collagen-induced arthritis model in the rat and was able to significantly reduce the development of clinical signs of arthritis and the degree of bone resorption, soft tissue swelling and osteophyte formation, consequently improving articular function in treated animals.

  1. The Degree of CD4+ T Cell Autoreactivity Determines Cellular Pathways Underlying Inflammatory Arthritis

    PubMed Central

    Perng, Olivia A.; Aitken, Malinda; Rankin, Andrew L.; Garcia, Victoria; Kropf, Elizabeth; Erikson, Jan; Garlick, David S.; Caton, Andrew J.

    2014-01-01

    Although therapies targeting distinct cellular pathways (e.g. anti-cytokine versus anti-B cell therapy) have been found to be an effective strategy for at least some patients with inflammatory arthritis, the mechanisms that determine which pathways promote arthritis development are poorly understood. We have used a transgenic mouse model to examine how variations in the CD4+ T cell response to a surrogate self-peptide can affect the cellular pathways that are required for arthritis development. CD4+ T cells that are highly reactive with the self-peptide induce inflammatory arthritis that affects male and female mice equally. Arthritis develops by a B cell-independent mechanism, although it can be suppressed by an anti-TNF treatment, which prevented the accumulation of effector CD4+ Th17 cells in the joints of treated mice. By contrast, arthritis develops with a significant female bias in the context of a more weakly autoreactive CD4+ T cell response, and B cells play a prominent role in disease pathogenesis. In this setting of lower CD4+ T cell autoreactivity, B cells promote the formation of autoreactive CD4+ effector T cells (including Th17 cells), and IL-17 is required for arthritis development. These studies show that the degree of CD4+ T cell reactivity for a self-peptide can play a prominent role in determining whether distinct cellular pathways can be targeted to prevent the development of inflammatory arthritis. PMID:24591372

  2. [Vaccines and preventive activities in patients with inflammatory arthritis].

    PubMed

    Casals-Sánchez, J L; Casals Vázquez, C; Vázquez Sánchez, M Á; Giménez Basallote, S

    2013-10-01

    Patients with inflammatory arthritis and eligible for immunosuppressive therapy account for more than 1% of general population, and represents a significant workload on family doctors. They are prone to other comorbidities, with an increased cardiovascular risk and a higher incidence of infections than the general population, especially skin infections and pneumonitis. This comorbidity can be considered vulnerable to a prevention program-prevention of cardiovascular risk, cancer screening, vaccination schedule for adults. As for prevention through vaccination, importance should be given to pneumococcal infection - significant in adults aged 50 or over, especially amongst immunosuppressed patients. The 13-valent conjugate vaccine, which has been recently approved for adults, must be considered. An attempt has been made to write a simple, applicable document on preventive measures that should be implemented both at primary and secondary care level for those adults. Copyright © 2012 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España. All rights reserved.

  3. Peptidylarginine Deiminase 4 Contributes to Tumor Necrosis Factor α–Induced Inflammatory Arthritis

    PubMed Central

    Shelef, Miriam A.; Sokolove, Jeremy; Lahey, Lauren J.; Wagner, Catriona A.; Sackmann, Eric K.; Warner, Thomas F.; Wang, Yanming; Beebe, David J.; Robinson, William H.; Huttenlocher, Anna

    2014-01-01

    Objective Peptidylarginine deiminase 4 (PAD4) is a citrullinating enzyme that has multiple associations with inflammation. In rheumatoid arthritis, PAD4 and protein citrullination are increased in inflamed joints, and anti–citrullinated protein antibodies (ACPAs) form against citrullinated antigens are formed. ACPA immune complexes can deposit in the joint and induce the production of tumor necrosis factor α (TNFα), a critical inflammatory cytokine in the pathogenesis of rheumatoid arthritis. Further, in other settings, TNFα has been shown to induce PAD4 activity and modulate antibody formation. We undertook this study to investigate whether TNFα and PAD4 may synergistically exacerbate autoantibody production and inflammatory arthritis. Methods To determine whether TNFα and PAD4 augment autoantibody production and inflammatory arthritis, we first used a multiplex assay to determine whether mice with chronic inflammatory arthritis due to overexpression of TNFα develop autoantibodies against native and citrullinated antigens. With TNF+ PAD4+/+ and TNF+PAD4−/− mice, we then compared serum autoantibody levels by multiplex array, lymphocyte activation by flow cytometry, total serum IgG levels by enzyme-linked immunosorbent assay, arthritis by clinical and histologic scoring, and systemic inflammation using microfluidic devices. Results TNFα-overexpressing mice had increased levels of autoantibodies reactive against native and citrullinated antigens. PAD4−/− mice with TNFα-induced arthritis had lower levels of autoantibodies reactive against native and citrullinated antigens, decreased T cell activation and total IgG levels, and reduced inflammation and arthritis compared to PAD4+/+ TNFα-overexpressing mice. Conclusion PAD4 mediates autoantibody production and inflammatory arthritis downstream of TNFα. PMID:24497204

  4. Characterization and treatment monitoring of inflammatory arthritis by photoacoustic imaging: a study on adjuvant-induced arthritis rat model

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Rajian, Justin; Shao, Xia; Chamberland, David L.; Girish, Gandikota

    2014-03-01

    Neovascularity also known as angiogenesis is an early feature of inflammatory arthritis disease. Therefore, identifying the development of neovascularity is one way to potentially detect and characterize arthritis. Laser-based photoacoustic imaging (PAI) is an emerging biomedical imaging modality which may aid in detection of both early and continued development of neovascularity. In this work, we investigated the feasibility of PAI to measure angiogenesis, for the purpose of evaluating and monitoring inflammatory arthritis after treatment. The imaging results on an arthritis rat model demonstrate that 1) there is noticeable enhancement in image intensity in the arthritic ankle joints when compared to the normal joints, and 2) there is noticeable decrease in image intensity in the arthritic ankle joints after treatment when compared to the untreated arthritic joints. In order to validate the findings from PAI, we performed positron emission tomography (PET) and histology on the same joints. The diameters of the ankle joints, as a clinical score of the arthritis, were also measured at each time point.

  5. Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice.

    PubMed

    Miossec, Pierre

    2017-01-01

    Interleukin-17 (IL-17A) is a cytokine critical for the acute defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. The present review describes the key molecules of the IL-17 pathway, which are or could be targeted for treatment. Since targeting of IL-17A may affect defence mechanisms, the pathogenesis of such possible adverse events is analysed. Then the contributions of IL-17 to bone changes in various forms of arthritis are discussed. Finally, the results of current inhibitors of the IL-17 pathway in clinical trials are detailed. IL-17A inhibition has been first registered for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. Other therapeutic options are now tested in a long list of diseases.

  6. Update on interleukin-17: a role in the pathogenesis of inflammatory arthritis and implication for clinical practice

    PubMed Central

    Miossec, Pierre

    2017-01-01

    Interleukin-17 (IL-17A) is a cytokine critical for the acute defence against extracellular bacterial and fungal infections. Excess production during chronic inflammation has been associated with many inflammatory and autoimmune disorders. The present review describes the key molecules of the IL-17 pathway, which are or could be targeted for treatment. Since targeting of IL-17A may affect defence mechanisms, the pathogenesis of such possible adverse events is analysed. Then the contributions of IL-17 to bone changes in various forms of arthritis are discussed. Finally, the results of current inhibitors of the IL-17 pathway in clinical trials are detailed. IL-17A inhibition has been first registered for the treatment of psoriasis, psoriatic arthritis and ankylosing spondylitis. Other therapeutic options are now tested in a long list of diseases. PMID:28243466

  7. Anti-inflammatory and immunomodulatory effect of an extract of Coccidioides posadasii in experimental arthritis.

    PubMed

    Pinto, Ana Carolina Matias Dinelly; Cordeiro, Rossana de Aguiar; Sidrim, José Julio Costa; Leite, Ana Karine Rocha de Melo; Leite, Ana Caroline Rocha de Melo; Girão, Virgínia Cláudia Carneiro; Brilhante, Raimunda Sâmia Nogueira; Rocha, Marcos Fábio Gadelha; Cunha, Fernando de Queiroz; Rocha, Francisco Airton Castro

    2013-04-01

    Trying to surpass host defenses, fungal infections alter the immune response. Components from nonpathogenic fungi present therapeutic anti-inflammatory and immunomodulating activities. This study reveals that proteins present in a Coccidioides posadasii extract provide anti-inflammatory benefit in experimental arthritis. Zymosan was given intra-articularly to rats and mice, and groups were pretreated with C. posadasii extract either per os or intraperitoneally. Controls received the vehicle. Acute hypernociception was evaluated using articular incapacitation and von Frey methods. Cell influx and cytokine levels were assessed in joint exudates. Joint damage was evaluated by histopathology and determination of glycosaminoglycan content of the cartilage. Synovia was evaluated for cell death and inducible nitric oxide synthase (iNOS) expression using TUNEL and immunohistochemistry, respectively. Pretreatment with C. posadasii extract significantly inhibited acute and chronic cell influx, hypernociception, and provoked reduction of glycosaminoglycan loss while reducing chronic synovitis, cell death, and iNOS expression. Reduction/alkylation of C. posadasii extract abrogated these effects. C. posadasii administration did not alter TNF-α, IL-1β, IL-17, and γ-interferon levels, whereas IL-10 levels were significantly reduced. Data reveal that a C. posadasii extract reduces iNOS expression that is associated with inhibition of synovial apoptosis and decrease in IL-10 levels released into zymosan-inflamed joints. Characterization of active components excluded charged carbohydrates while pointing to a protein as responsible for these effects. In summary, systemic administration of components from a pathogenic fungus provides anti-inflammatory effects, being species-independent and orally active. Besides adding to understand host response against fungi, the results may lead to therapeutic implications.

  8. Lest we forget Hansen's disease (leprosy): an unusual presentation with an acute onset of inflammatory polyarthritis and the rheumatology experience.

    PubMed

    Sheetal, Salvi; Arvind, Chopra

    2009-04-01

    Several forms of arthritis and rheumatism can sometimes complicate leprosy. However, its presentation as an acute onset arthritis is unusual. We report two adult male naïve patients who presented to our rheumatology outpatient clinic with acute onset inflammatory polyarthritis, skin rash and mild sensory neurodeficit. Borderline lepromatous leprosy (in type I lepra reaction) was diagnosed. We also refer to 19 case records of Hansen arthritis in the clinic database (1998-2007) from approximately 35,000 patients and a community study to highlight the missed diagnosis of Hansen's disease and its unusual association with rheumatoid arthritis. In countries like India where leprosy is endemic, this disease also merits attention in rheumatology clinics.

  9. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis

    PubMed Central

    Bell, G M; Anderson, A E; Diboll, J; Reece, R; Eltherington, O; Harry, R A; Fouweather, T; MacDonald, C; Chadwick, T; McColl, E; Dunn, J; Dickinson, A M; Hilkens, C M U; Isaacs, John D

    2017-01-01

    Objectives To assess the safety of intra-articular (IA) autologous tolerogenic dendritic cells (tolDC) in patients with inflammatory arthritis and an inflamed knee; to assess the feasibility and acceptability of the approach and to assess potential effects on local and systemic disease activities. Methods An unblinded, randomised, controlled, dose escalation Phase I trial. TolDC were differentiated from CD14+ monocytes and loaded with autologous synovial fluid as a source of autoantigens. Cohorts of three participants received 1×106, 3×106 or 10×106 tolDC arthroscopically following saline irrigation of an inflamed (target) knee. Control participants received saline irrigation only. Primary outcome was flare of disease in the target knee within 5 days of treatment. Feasibility was assessed by successful tolDC manufacture and acceptability via patient questionnaire. Potential effects on disease activity were assessed by arthroscopic synovitis score, disease activity score (DAS)28 and Health Assessment Questionnaire (HAQ). Immunomodulatory effects were sought in peripheral blood. Results There were no target knee flares within 5 days of treatment. At day 14, arthroscopic synovitis was present in all participants except for one who received 10×106 tolDC; a further participant in this cohort declined day 14 arthroscopy because symptoms had remitted; both remained stable throughout 91 days of observation. There were no trends in DAS28 or HAQ score or consistent immunomodulatory effects in peripheral blood. 9 of 10 manufactured products met quality control release criteria; acceptability of the protocol by participants was high. Conclusion IA tolDC therapy appears safe, feasible and acceptable. Knee symptoms stabilised in two patients who received 10×106 tolDC but no systemic clinical or immunomodulatory effects were detectable. Trial registration number NCT01352858. PMID:27117700

  10. A review of current knowledge of the complement system and the therapeutic opportunities in inflammatory arthritis.

    PubMed

    Mizuno, M

    2006-01-01

    The complement activation system, a key component of the innate immune system, protects the host from microorganisms such as bacteria, and other foreign threats including abnormal cells. However, it is also double-edged in that it can have negative effects in the host; excessive complement activation damages the host and can even kill in anaphylactic shock and septic shock. Regulation of the complement system is a useful strategy to control inflammatory diseases, including inflammatory arthritis. Rheumatoid arthritis is a common inflammatory disease worldwide. Many medicines are developed to control inflammation, including recently developed biological response modifiers such as anti-TNF and IL-6 agents. Nevertheless, in some patients disease remains difficult to control because of complications, side effects and tolerance of medicines. In inflammatory arthritis, including rheumatoid arthritis, there is abundant evidence implicating complement activation in humans and animal models. Therefore, anti-complement agents might be beneficial as part of clinical treatment. However, at present, there are still no applicable agents for therapeutic regulation of excessive complement activation in chronic disease. Novel agents in development might be useful as a strategy to control complement activation. Here I describe recent knowledge of the complement system in inflammatory arthritis, the recent developments in anti-complement agents and their considerable potential for the future.

  11. Achievement of NICE quality standards for patients with new presentation of inflammatory arthritis: observations from the National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis.

    PubMed

    Ledingham, Joanna M; Snowden, Neil; Rivett, Ali; Galloway, James; Ide, Zoe; Firth, Jill; MacPhie, Elizabeth; Kandala, Ngianga; Dennison, Elaine M; Rowe, Ian

    2017-02-01

    A national audit was performed assessing the early management of suspected inflammatory arthritis by English and Welsh rheumatology units. The aim of this audit was to measure the performance of rheumatology services against National Institute for Health and Care Excellence (NICE) quality standards (QSs) for the management of early inflammatory arthritis benchmarked to regional and national comparators for the first time in the UK. All individuals >16 years of age presenting to rheumatology services in England and Wales with suspected new-onset inflammatory arthritis were included in the audit. Information was collected against six NICE QSs that pertain to early inflammatory arthritis management. We present national data for the 6354 patients recruited from 1 February 2014 to 31 January 2015; 97% of trusts and health boards in England and Wales participated in this audit. Only 17% of patients were referred by their general practitioner within 3 days of first presentation. Specialist rheumatology assessment occurred within 3 weeks of referral in 38% of patients. The target of DMARD initiation within 6 weeks of referral was achieved in 53% of RA patients; 36% were treated with combination DMARDs and 82% with steroids within the first 3 months of specialist care. Fifty-nine per cent of patients received structured education on their arthritis within 1 month of diagnosis. In total, 91% of patients had a treatment target set; the agreed target was achieved within 3 months of specialist review in only 27% of patients. Access to urgent advice via a telephone helpline was reported to be available in 96% of trusts. The audit has highlighted gaps between NICE standards and delivery of care, as well as substantial geographic variability. © 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.

  12. Application of a Novel Diagnostic Rule in the Differential Diagnosis between Acute Gouty Arthritis and Septic Arthritis.

    PubMed

    Lee, Kwang-Hoon; Choi, Sang-Tae; Lee, Soo-Kyung; Lee, Joo-Hyun; Yoon, Bo-Young

    2015-06-01

    Septic arthritis and gout are major diseases that should be suspected in patients with acute monoarthritis. These two diseases are clinically similar and often indistinguishable without the help of synovial fluid analysis. Recently, a novel diagnostic rule for gout without synovial fluid analysis was developed and showed relevant performances. This study aimed to determine whether this diagnostic rule could perform well in distinguishing gout from septic arthritis. The diagnostic rule comprises 7 clinical and laboratory variables, each of which is given a specified score. The probability of gout is classified into 3 groups according to the sum of the scores: high (≥ 8), intermediate (> 4 to < 8) and low probability (≤ 4). In this retrospective study, we applied this diagnostic rule to 136 patients who presented as acute monoarthritis and were subsequently diagnosed as acute gout (n = 82) and septic arthritis (n = 54) based on synovial fluid analysis. The mean sum of scores of acute gout patients was significantly higher than that of those with septic arthritis (8.6 ± 0.2 vs. 3.6 ± 0.32, P < 0.001). Patients with acute gout had significantly more 'high', and less 'low' probabilities compared to those with septic arthritis (Eta[η]: 0.776). The prevalence of acute gouty arthritis, as confirmed by the presence of monosodium crystal, was 95.5% (61/64), 57.5% (19/33), and 5.1% (2/39) in high, intermediate and low probability group, respectively. The recently introduced diagnostic rule properly discriminates acute gout from septic arthritis. It may help physicians diagnose gout in cases difficult to be differentiated from septic arthritis.

  13. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis

    PubMed Central

    Oliveira, Marina C.; Tavares, Luciana P.; Vago, Juliana P.; Batista, Nathália V.; Queiroz-Junior, Celso M.; Vieira, Angelica T.; Menezes, Gustavo B.; Sousa, Lirlândia P.; van de Loo, Fons A. J.; Teixeira, Mauro M.; Amaral, Flávio A.; Ferreira, Adaliene V. M.

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. PMID:26742100

  14. Tumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.

    PubMed

    Oliveira, Marina C; Tavares, Luciana P; Vago, Juliana P; Batista, Nathália V; Queiroz-Junior, Celso M; Vieira, Angelica T; Menezes, Gustavo B; Sousa, Lirlândia P; van de Loo, Fons A J; Teixeira, Mauro M; Amaral, Flávio A; Ferreira, Adaliene V M

    2016-01-01

    Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.

  15. Elbow septic arthritis associated with pediatric acute leukemia: a case report and literature review.

    PubMed

    Uemura, Takuya; Yagi, Hirohisa; Okada, Mitsuhiro; Yokoi, Takuya; Shintani, Kosuke; Nakamura, Hiroaki

    2015-01-01

    Acute leukemia in children presents with various clinical manifestations that mimic orthopaedic conditions. The association of septic arthritis of the elbow with acute leukemia is very rare, and the correct diagnosis of acute leukemia is often established only after treatment of the septic arthritis. In this article, we present a three-year-old child patient with elbow septic arthritis related to acute leukemia, diagnosed promptly by bone marrow aspiration on the same day as emergency surgical debridement of the septic elbow joint due to the maintenance of a high index of suspicion, and treated with chemotherapy as soon as possible. The emergency physician and orthopaedist must recognize unusual patterns of presentation like this. Since delay in initiating treatment of septic arthritis may result in growth disturbance, elbow septic arthritis associated with pediatric acute leukemia must be treated promptly and appropriately. Early diagnosis is a good prognostic feature of childhood acute leukemia.

  16. Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice.

    PubMed

    Huang, Qi-Quan; Hossain, M Moazzem; Sun, Wen; Xing, Lianping; Pope, Richard M; Jin, J-P

    2016-10-01

    Calponin is an actin cytoskeleton-associated protein that regulates motility-based cellular functions. Three isoforms of calponin are present in vertebrates, among which calponin 2 encoded by the Cnn2 gene is expressed in multiple types of cells, including blood cells from the myeloid lineage. Our previous studies demonstrated that macrophages from Cnn2 knockout (KO) mice exhibit increased migration and phagocytosis. Intrigued by an observation that monocytes and macrophages from patients with rheumatoid arthritis had increased calponin 2, we investigated anti-glucose-6-phosphate isomerase serum-induced arthritis in Cnn2-KO mice for the effect of calponin 2 deletion on the pathogenesis and pathology of inflammatory arthritis. The results showed that the development of arthritis was attenuated in systemic Cnn2-KO mice with significantly reduced inflammation and bone erosion than that in age- and stain background-matched C57BL/6 wild-type mice. In vitro differentiation of calponin 2-null mouse bone marrow cells produced fewer osteoclasts with decreased bone resorption. The attenuation of inflammatory arthritis was confirmed in conditional myeloid cell-specific Cnn2-KO mice. The increased phagocytotic activity of calponin 2-null macrophages may facilitate the clearance of autoimmune complexes and the resolution of inflammation, whereas the decreased substrate adhesion may reduce osteoclastogenesis and bone resorption. The data suggest that calponin 2 regulation of cytoskeleton function plays a novel role in the pathogenesis of inflammatory arthritis, implicating a potentially therapeutic target. Copyright © 2016 the American Physiological Society.

  17. Bruton's Tyrosine Kinase Deficiency Inhibits Autoimmune Arthritis in Mice but Fails to Block Immune Complex-Mediated Inflammatory Arthritis.

    PubMed

    Nyhoff, Lindsay E; Barron, Bridgette L; Johnson, Elizabeth M; Bonami, Rachel H; Maseda, Damian; Fensterheim, Benjamin A; Han, Wei; Blackwell, Timothy S; Crofford, Leslie J; Kendall, Peggy L

    2016-08-01

    Bruton's tyrosine kinase (BTK) is a B cell signaling protein that also contributes to innate immunity. BTK inhibitors prevent autoimmune arthritis but have off-target effects, and the mechanisms of protection remain unknown. We undertook these studies using genetic deletion to investigate the role of BTK in adaptive and innate immune responses that drive inflammatory arthritis. BTK-deficient K/BxN mice were generated to study the role of BTK in a spontaneous model that requires both adaptive and innate immunity. The K/BxN serum-transfer model was used to bypass the adaptive system and elucidate the role of BTK in innate immune contributions to arthritis. BTK deficiency conferred disease protection to K/BxN mice, confirming outcomes of BTK inhibitors. B lymphocytes were profoundly reduced, more than in other models of BTK deficiency. Subset analysis revealed loss of B cells at all developmental stages. Germinal center B cells were also decreased, with downstream effects on numbers of follicular helper T cells and greatly reduced autoantibodies. In contrast, total IgG was only mildly decreased. Strikingly, and in contrast to small molecule inhibitors, BTK deficiency had no effect in the serum-transfer model of arthritis. BTK contributes to autoimmune arthritis primarily through its role in B cell signaling and not through innate immune components. © 2016, American College of Rheumatology.

  18. Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression.

    PubMed

    Ross, E A; Naylor, A J; O'Neil, J D; Crowley, T; Ridley, M L; Crowe, J; Smallie, T; Tang, T J; Turner, J D; Norling, L V; Dominguez, S; Perlman, H; Verrills, N M; Kollias, G; Vitek, M P; Filer, A; Buckley, C D; Dean, J L; Clark, A R

    2017-03-01

    Tristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP. The expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP. TTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation. The phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments. 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/.

  19. Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools.

    PubMed

    van Riel, Piet; Alten, Rieke; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo

    2016-01-01

    Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists.

  20. Improving inflammatory arthritis management through tighter monitoring of patients and the use of innovative electronic tools

    PubMed Central

    van Riel, Piet; Combe, Bernard; Abdulganieva, Diana; Bousquet, Paola; Courtenay, Molly; Curiale, Cinzia; Gómez-Centeno, Antonio; Haugeberg, Glenn; Leeb, Burkhard; Puolakka, Kari; Ravelli, Angelo; Rintelen, Bernhard; Sarzi-Puttini, Piercarlo

    2016-01-01

    Treating to target by monitoring disease activity and adjusting therapy to attain remission or low disease activity has been shown to lead to improved outcomes in chronic rheumatic diseases such as rheumatoid arthritis and spondyloarthritis. Patient-reported outcomes, used in conjunction with clinical measures, add an important perspective of disease activity as perceived by the patient. Several validated PROs are available for inflammatory arthritis, and advances in electronic patient monitoring tools are helping patients with chronic diseases to self-monitor and assess their symptoms and health. Frequent patient monitoring could potentially lead to the early identification of disease flares or adverse events, early intervention for patients who may require treatment adaptation, and possibly reduced appointment frequency for those with stable disease. A literature search was conducted to evaluate the potential role of patient self-monitoring and innovative monitoring of tools in optimising disease control in inflammatory arthritis. Experience from the treatment of congestive heart failure, diabetes and hypertension shows improved outcomes with remote electronic self-monitoring by patients. In inflammatory arthritis, electronic self-monitoring has been shown to be feasible in patients despite manual disability and to be acceptable to older patients. Patients' self-assessment of disease activity using such methods correlates well with disease activity assessed by rheumatologists. This review also describes several remote monitoring tools that are being developed and used in inflammatory arthritis, offering the potential to improve disease management and reduce pressure on specialists. PMID:27933206

  1. Prevalence of foot problems in people with inflammatory arthritis in Singapore.

    PubMed

    Carter, K; Lahiri, M; Cheung, P P; Santosa, A; Rome, K

    2016-01-01

    Foot problems are highly prevalent in people with inflammatory arthritis reported from studies in the UK, Europe and New Zealand, but there is limited evidence from Southeast Asia. The study aim was to evaluate the prevalence of foot problems in people with inflammatory arthritis in Singapore. People with inflammatory arthritis were recruited from the rheumatology outpatient clinic of a tertiary hospital in Singapore. Disease and clinical characteristics included age, sex, disease duration, current blood tests and medications. The Leeds Foot Impact Scale was used to evaluate foot impairment/disability and the Modified Health Assessment Questionnaire was used to assess global function. We recruited 101 people with inflammatory arthritis, of which 50 % were female. The majority of participants were Chinese (70 %). The mean (SD) age was 52 (15) years, and the mean (SD) disease duration was 9.3 (0.3) years. The most commonly reported inflammatory arthritic conditions were rheumatoid arthritis (46), gout (31) and spondyloarthritis (15 %). The mean (SD) of the total Leeds Foot Impact Scale was 17 (13) indicating moderate to severe levels of foot impairment and activity limitation. Over 80 of participants reported foot pain during the course of their condition, and 48 % reported current foot pain. Despite the high prevalence of foot pain, only 21 participants (21 %) had been referred to a podiatrist. This is the first study to investigate the prevalence of foot problems in people with inflammatory arthritis from Singapore. The majority of the participants reported foot problems, but had not been referred to a podiatry service.

  2. Acute Painful Stress and Inflammatory Mediator Production

    PubMed Central

    Griffis, Charles A.; Breen, Elizabeth Crabb; Compton, Peggy; Goldberg, Alyssa; Witarama, Tuff; Kotlerman, Jenny; Irwin, Michael R.

    2014-01-01

    Pro-inflammatory pathways may be activated under conditions of painful stress, which is hypothesized to worsen the pain experience and place medically-vulnerable populations at risk for increased morbidity. Objectives To evaluate the effects of pain and subjective pain-related stress on pro-inflammatory activity. Methods A total of 19 healthy control subjects underwent a single standard cold-pressor pain test (CPT) and a no-pain control condition. Indicators of pain and stress were measured and related to inflammatory immune responses (CD811a, IL-1RA, and IL-6) immediately following the painful stimulus, and compared to responses under non-pain conditions. Heart rate and mean arterial pressure were measured as indicators of sympathetic stimulation. Results CPT was clearly painful and generated an activation of the sympathetic nervous system. CD811a increased in both conditions, but with no statistically significant greater increase following CPT (p < .06). IL-1RA demonstrated a non-statistically significant increase following CPT (p < .07). The change in IL-6 following CPT differed significantly from the response seen in the control condition (p < .02). Conclusions These findings suggest that CP acute pain may affect proinflammatory pathways, possibly through mechanisms related to adrenergic activation. PMID:23407214

  3. Therapeutic Effects of Acetone Extract of Saraca asoca Seeds on Rats with Adjuvant-Induced Arthritis via Attenuating Inflammatory Responses

    PubMed Central

    Gupta, Mradu; Sasmal, Saumyakanti; Mukherjee, Arup

    2014-01-01

    Saraca asoca has been traditionally used in Indian system for treatment of uterine, genital, and other reproductive disorders in women, fever, pain, and inflammation. The hypothesis of this study is that acetone extract of Saraca asoca seeds is an effective anti-inflammatory treatment for arthritis in animal experiments. The antiarthritic effect of its oral administration on Freund's adjuvant-induced arthritis has been studied in Wistar albino rats after acute and subacute toxicities. Phytochemical analysis revealed presence of high concentrations of phenolic compounds such as flavonoids and tannins, while no mortality or morbidity was observed up to 1000 mg/kg dose during acute and subacute toxicity assessments. Regular treatment up to 21 days of adjuvant-induced arthritic rats with Saraca asoca acetone extract (at 300 and 500 mg/kg doses) increases RBC and Hb, decreases WBC, ESR, and prostaglandin levels in blood, and restores body weight when compared with control (normal saline) and standard (Indomethacin) groups. Significant (P < 0.05) inhibitory effect was observed especially at higher dose on paw edema, ankle joint inflammation, and hydroxyproline and glucosamine concentrations in urine. Normal radiological images of joint and histopathological analysis of joint, liver, stomach, and kidney also confirmed its significant nontoxic, antiarthritic, and anti-inflammatory effect. PMID:24729890

  4. Uveitis in spondyloarthritis including psoriatic arthritis, ankylosing spondylitis, and inflammatory bowel disease.

    PubMed

    Rosenbaum, James T

    2015-06-01

    Uveitis is a common complication of spondyloarthritis. The "phenotype" of the uveitis characteristic of ankylosing spondylitis (sudden onset, anterior, unilateral, recurrent, more often male) may differ from the phenotype often seen with either psoriatic arthritis or inflammatory bowel disease (insidious onset, anterior and intermediate, bilateral, chronic, and/or more often female). The frequency of uveitis is also much greater in association with ankylosing spondylitis than with either inflammatory bowel disease or psoriasis. Uveitis may affect the choice of therapy and can rarely be a complication of therapy. Uveitis and arthritis also co-exist in several animal models.

  5. CT findings of acute pelvic inflammatory disease.

    PubMed

    Lee, Mi Hee; Moon, Min Hoan; Sung, Chang Kyu; Woo, Hyunsik; Oh, Sohee

    2014-12-01

    To determine the computed tomographic (CT) findings of acute pelvic inflammatory disease (PID). This retrospective, single-institution case-control study was approved by our institutional review board, and the informed consent was waived owing to the retrospective nature of the study. CT images of 32 women with clinically proven acute PID and 32 control subjects with other conditions of similar presentation were retrospectively reviewed. Analysis of CT findings included hepatic capsular enhancement, pelvic fat haziness, complicated ascites, uterine serosal enhancement, tubal thickening, endometritis, and oophoritis. Comparison of CT findings was performed with the Chi square test or the Fisher exact test and logistic regression analysis was used to determine significant CT findings in predicting PID. The CT findings that showed a statistically significant difference were hepatic capsular enhancement on late arterial phase (p = 0.003), pelvic fat haziness (p = 0.045), and tubal thickening (p = 0.001). Subsequent multivariate logistic regression analysis revealed that the presence of hepatic capsular enhancement on late arterial phase and tubal thickening were significant predictors of PID (hepatic capsular enhancement on late arterial phase, p = 0.015, odds ratio [OR] = 4.8; tubal thickening, p = 0.005, OR = 10.5). Diagnostic morphological CT findings in women with clinically proven PID and acute abdominal pain include hepatic capsular enhancement on late arterial phase and tubal thickening.

  6. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  7. The effect of rheumatoid arthritis-associated autoantibodies on the incidence of cardiovascular events in a large inception cohort of early inflammatory arthritis.

    PubMed

    Barra, Lillian J; Pope, Janet E; Hitchon, Carol; Boire, Gilles; Schieir, Orit; Lin, Daming; Thorne, Carter J; Tin, Diane; Keystone, Edward C; Haraoui, Boulos; Jamal, Shahin; Bykerk, Vivian P

    2017-05-01

    . RA is associated with an increased risk of cardiovascular events (CVEs). The objective was to estimate independent effects of RA autoantibodies on the incident CVEs in patients with early RA. Patients were enrolled in the Canadian Early Inflammatory Arthritis Cohort, a prospective multicentre inception cohort. Incident CVEs, including acute coronary syndromes and cerebrovascular events, were self-reported by the patient and partially validated by medical chart review. Seropositive status was defined as either RF or ACPA positive. Multivariable Cox proportional hazards survival analysis was used to estimate the effects of seropositive status on incident CVEs, controlling for RA clinical variables and traditional cardiovascular risk factors. . A total of 2626 patients were included: the mean symptom duration at diagnosis was 6.3 months ( s . d . 4.6), the mean age was 53 years ( s . d . 15), 72% were female and 86% met classification criteria for RA. Forty-six incident CVEs occurred over 6483 person-years [incidence rate 7.1/1000 person-years (95% confidence interval 5.3, 9.4)]. The CVE rate did not differ in seropositive vs seronegative subjects and seropositivity was not associated with incident CVEs in multivariable Cox regression models. Baseline covariates independently associated with incident CVEs were older age, a history of hypertension and a longer duration of RA symptoms prior to diagnosis. The rate of CVEs early in the course of inflammatory arthritis was low; however, delays in the diagnosis of arthritis increased the rate of CVEs. Hypertension was the strongest independent risk factor for CVEs. Results support early aggressive management of RA disease activity and co-morbidities to prevent severe complications.

  8. Septic Arthritis of an Atlantoaxial Facet Joint with Normal Inflammatory Markers: Case Report and Literature Review.

    PubMed

    Kuyumcu, Gokhan; Simpfendorfer, Claus S; Babic, Maja; Kalfas, Iain H; Teixeira-Johnson, Lucileia; Winalski, Carl S

    2017-02-01

    Septic arthritis of the atlantoaxial facet joint is extremely rare. Contiguous spread to the median atlantoaxial joints with subsequent dens erosion can lead to atlantoaxial instability. Misleading normal inflammatory markers can result in delayed diagnosis and catastrophic consequences. A 56-year-old man presented with right-sided neck pain that had lasted for 2 days. He did not have fever or chills, and his serum C-reactive protein and erythrocyte sedimentation rate were normal. The patient was diagnosed with acute neck strain and treated conservatively. The pain continued for the next 3 weeks; cervical spine radiographs demonstrated normal findings with the exception of degenerative changes. The patient was treated with physical rehabilitation for the presumed neck strain and degenerative changes of the cervical vertebrae. Worsening neck pain and stiffness prompted a magnetic resonance imaging study obtained 5 weeks after the initial presentation, which showed an epidural collection with septic arthritis of the right facet and median atlantoaxial joints. Computed tomography demonstrated severe dens erosion. Surgical evacuation of the abscess and occipitocervical fusion were performed. Pathologic evaluation of tissue obtained during surgery demonstrated the presence of an infection, and Streptococcus anginosus grew from cultures. Infection must be considered in the differential diagnosis for neck pain when imaging findings are suggestive of an infectious process, even in an afebrile patient with normal C-reactive protein and erythrocyte sedimentation rate levels. Magnetic resonance imaging and computed tomography can play a critical role in such cases, potentially leading to a more timely diagnosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice.

    PubMed

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-12-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice.

  10. Pro-apoptotic Bid is required for the resolution of the effector phase of inflammatory arthritis

    PubMed Central

    Scatizzi, John C; Hutcheson, Jack; Bickel, Emily; Haines, G Kenneth; Perlman, Harris

    2007-01-01

    Rheumatoid arthritis is an autoimmune disease characterized by hyperplasia of the synovial lining and destruction of cartilage and bone. Recent studies have suggested that a lack of apoptosis contributes to the hyperplasia of the synovial lining and to the failure in eliminating autoreactive cells. Mice lacking Fas or Bim, two pro-apoptotic proteins that mediate the extrinsic and intrinsic death cascades, respectively, develop enhanced K/BxN serum transfer-induced arthritis. Since the pro-apoptotic protein Bid functions as an intermediate between the extrinsic and intrinsic apoptotic pathways, we examined the role that it plays in inflammatory arthritis. Mice deficient in Bid (Bid-/-) show a delay in the resolution of K/BxN serum transfer-induced arthritis. Bid-/- mice display increased inflammation, bone destruction, and pannus formation compared to wild-type mice. Furthermore, Bid-/- mice have elevated levels of CXC chemokine and IL-1β in serum, which are associated with more inflammatory cells throughout the arthritic joint. In addition, there are fewer apoptotic cells in the synovium of Bid-/- compared to Wt mice. These data suggest that extrinsic and intrinsic apoptotic pathways cooperate through Bid to limit development of inflammatory arthritis. PMID:17509138

  11. Protective effect of taraxasterol against rheumatoid arthritis by the modulation of inflammatory responses in mice

    PubMed Central

    Jiang, Shu-Hua; Ping, Li-Feng; Sun, Feng-Yan; Wang, Xiao-Lei; Sun, Zhi-Juan

    2016-01-01

    Taraxasterol is an effective component of dandelion that has anti-inflammatory effects in vivo and in vitro. The present study was performed to explore whether taraxasterol exhibits a protective effect against rheumatoid arthritis through the modulation of inflammatory responses in mice. Eight-week-old CCR9-deficient mice were injected with a collagen II monoclonal antibody cocktail to create a rheumatoid arthritis model. In the experimental group, arthritic model mice were treated with 10 mg/kg taraxasterol once per day for 5 days. Treatment with taraxasterol significantly increased the pain thresholds and reduced the clinical arthritic scores of the mice in the experimental group compared with those of the model group. Furthermore, treatment with taraxasterol significantly suppressed tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and nuclear factor-κB protein expression levels compared with those in the rheumatoid arthritis model mice. Taraxasterol treatment also significantly reduced nitric oxide, prostaglandin E2 and cyclooxygenase-2 levels compared with those in the rheumatoid arthritis model group. These observations indicate that the protective effect of taraxasterol against rheumatoid arthritis is mediated via the modulation of inflammatory responses in mice. PMID:28101182

  12. Juvenile-onset inflammatory arthritis: a study of adolescents’ beliefs about underlying cause

    PubMed Central

    Cordingley, Lis; Vracas, Tiffany; Baildam, Eileen; Chieng, Alice; Davidson, Joyce; Foster, Helen E.; Gardner-Medwin, Janet; Wedderburn, Lucy R.; Thomson, Wendy

    2012-01-01

    Objective. Patients’ beliefs regarding the cause of illness may influence treatment adherence and long-term outcome. Little is known of adolescents’ beliefs regarding the cause of JIA. This study aims to identify adolescents’ beliefs about the underlying cause of their arthritis at first presentation to the paediatric rheumatology department. Methods. One hundred and twenty-two adolescents aged ≥11 years participating in the larger prospective Childhood Arthritis Prospective Study, an inception cohort of childhood-onset inflammatory arthritis, were asked to complete a questionnaire regarding underlying beliefs about their arthritis. The top-listed causes were identified, and associations between beliefs and characteristics of the adolescents and their arthritis were compared across the different causal beliefs. Results. The most common causal beliefs were genetics (27.1%), the immune system (21.3%), accident or injury (15.6%) and infection (13.1%). Association between causal beliefs and gender, disease duration, International League Against Rheumatism subtype and source of referral was observed, although small numbers prevented robust statistical comparisons. Conclusion. This first report on adolescents’ beliefs about the cause of their juvenile arthritis found the most common causal beliefs to be related to genes or the immune system. Brief assessments of adolescents’ beliefs at presentation will enable providers to modify or adapt potentially unhelpful beliefs and provide age-appropriate information regarding arthritis. PMID:22942401

  13. EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.

    PubMed

    Peters, M J L; Symmons, D P M; McCarey, D; Dijkmans, B A C; Nicola, P; Kvien, T K; McInnes, I B; Haentzschel, H; Gonzalez-Gay, M A; Provan, S; Semb, A; Sidiropoulos, P; Kitas, G; Smulders, Y M; Soubrier, M; Szekanecz, Z; Sattar, N; Nurmohamed, M T

    2010-02-01

    To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

  14. Lithothamnion muelleri Treatment Ameliorates Inflammatory and Hypernociceptive Responses in Antigen-Induced Arthritis in Mice

    PubMed Central

    Costa, Vivian V.; Amaral, Flavio A.; Coelho, Fernanda M.; Queiroz-Junior, Celso M.; Malagoli, Bruna G.; Gomes, Jose Hugo S.; Lopes, Fernando; Silveira, Kátia D.; Sachs, Daniela; Fagundes, Caio T.; Tavares, Lívia D.; Pinho, Vanessa; Silva, Tarcilia A.; Teixeira, Mauro M.; Braga, Fernão C.; Souza, Danielle G.

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment. PMID:25793994

  15. Lithothamnion muelleri treatment ameliorates inflammatory and hypernociceptive responses in antigen-induced arthritis in mice.

    PubMed

    Costa, Vivian V; Amaral, Flavio A; Coelho, Fernanda M; Queiroz-Junior, Celso M; Malagoli, Bruna G; Gomes, Jose Hugo S; Lopes, Fernando; Silveira, Kátia D; Sachs, Daniela; Fagundes, Caio T; Tavares, Lívia D; Pinho, Vanessa; Silva, Tarcilia A; Teixeira, Mauro M; Braga, Fernão C; Souza, Danielle G

    2015-01-01

    Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment.

  16. Photoacoustic tomography to identify angiogenesis for diagnosis and treatment monitoring of inflammatory arthritis

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Rajian, Justin; Girish, Gandikota; Chamberland, David

    2013-03-01

    Identifying neovascularity, i.e. angiogenesis, as a feature of inflammatory arthritis, can help in early diagnosis and treatment monitoring of this disease. Photoacoustic tomography (PAT), as a hybrid imaging modality, relies on intrinsic differences in the optical absorption among the tissues being imaged. Since blood has highly absorbing chromophores including both oxygenated and deoxygenated hemoglobin, PAT holds potential in identifying early angiogenesis associated with inflammatory joint diseases. In this study, we used PAT to identify the changes in the development of inflammatory arthritis, through the study on a well-established adjuvant-induced arthritis (AIA) rat model. Imaging at two different wavelengths, 1064 nm and 532 nm, revealed that there was a significant signal enhancement in the ankle joints of the arthritis affected rats when compared to the normal control group. Histological analysis of both the normal and the arthritic rats correlated well with the imaging findings. The results from this study suggest that the emerging PAT technology could become a new tool for clinical management of inflammatory joint diseases.

  17. Folate-targeted nanoparticles show efficacy in the treatment of inflammatory arthritis

    PubMed Central

    Thomas, Thommey P.; Goonewardena, Sascha N.; Majoros, Istvan; Kotlyar, Alina; Cao, Zhengyi; Leroueil, Pascale R.; Baker, James R.

    2011-01-01

    Objective To investigate the uptake of a poly(amidoamine) dendrimer (generation 5 (G5)) nanoparticle covalently conjugated to polyvalent folic acid (FA) as the targeting ligand into macrophages, and the activity of a FA- and methotrexate-conjugated dendrimer (G5-FA-MTX) as a therapeutic for the inflammatory disease of arthritis. Methods In vitro studies were performed in macrophage cell lines and in isolated mouse macrophages to check the cellular uptake of fluorescently tagged G5-FA nanoparticles, using flow cytometry and confocal microscopy. In vivo studies were conducted in a rat model of collagen-induced arthritis to evaluate the therapeutic potential of G5-FA-MTX. Results Folate targeted dendrimer bound and internalized in a receptor-specific manner into both folate receptor β-expressing macrophage cell lines and primary mouse macrophages. The G5-FA-MTX acts as a potent anti-inflammatory agent and reduces arthritis-induced inflammatory parameters such as ankle swelling, paw volume, cartilage damage, bone resorption and body weight decrease. Conclusion The use of folate-targeted nanoparticles to specifically target MTX into macrophages may provide an effective clinical approach for anti-inflammatory therapy in rheumatoid arthritis. PMID:21618461

  18. Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis.

    PubMed

    Umar, Sadiq; Umar, Khalid; Sarwar, Abu Hasnath Md Golam; Khan, Altaf; Ahmad, Niyaz; Ahmad, Sayeed; Katiyar, Chandra Kant; Husain, Syed Akhtar; Khan, Haider A

    2014-05-15

    Rheumatoid arthritis (RA) is a chronic inflammatory disease which leads to destruction of joints. Current treatment modalities for RA either produce symptomatic relief (NSAIDs) or modify the disease process (DMARDs). Though effective, their use is also limited by their side effects. As a result, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. Our aim was to evaluate the antioxidant and antiarthritic activity of Boswellia serrata gum resin extract (BSE) in collagen induced arthritis. Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. BSE was administered at doses of 100 and 200mg/kg body weight once daily for 21 days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, catalase, SOD and NO), inflammatory mediators (IL-1β, IL-6, TNF-α, IL-10, IFN-γ and PGE2), and histological studies in joints. BSE was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, catalase, SOD and NO) studied. Oral administration of BSE resulted in significantly reduced levels of inflammatory mediators (IL-1β, IL-6, TNF-α, IFN-γ and PGE2), and increased level of IL-10. The protective effects of BSE against RA were also evident from the decrease in arthritis scoring and bone histology. The abilities to inhibit proinflammatory cytokines and modulation of antioxidant status suggest that the protective effect of Boswellia serrata extract on arthritis in rats might be mediated via the modulation of immune system.

  19. Infections and arthritis.

    PubMed

    Mathew, Ashish Jacob; Ravindran, Vinod

    2014-12-01

    Bacteria, viruses, fungi, and parasites can all cause arthritis of either acute or chronic nature, which can be divided into infective/septic, reactive, or inflammatory. Considerable advances have occurred in diagnostic techniques in the recent decades resulting in better treatment outcomes in patients with infective arthritis. Detection of emerging arthritogenic viruses has changed the epidemiology of infection-related arthritis. The role of viruses in the pathogenesis of chronic inflammatory arthritides such as rheumatoid arthritis is increasingly being recognized. We discuss the various causative agents of infective arthritis and emphasize on the approach to each type of arthritis, highlighting the diagnostic tests, along with their statistical accuracy. Various investigations including newer methods such as nucleic acid amplification using polymerase chain reaction are discussed along with the pitfalls in interpreting the tests.

  20. MACROPHAGE MIGRATION INHIBITORY FACTOR REGULATES NEUTROPHIL CHEMOTACTIC RESPONSES IN INFLAMMATORY ARTHRITIS

    PubMed Central

    Santos, Leilani L.; Fan, Huapeng; Hall, Pam; Ngo, Devi; Mackay, Charles R.; Fingerle-Rowson, Gunter; Bucala, Richard; Hickey, Michael J.; Morand, Eric F.

    2010-01-01

    Objectives Macrophage migration inhibitory factor (MIF) facilitates multiple aspects of inflammatory arthritis, the pathogenesis of which is significantly contributed to by neutrophils. The effects of MIF on neutrophil recruitment are unknown. We investigated the contribution of MIF to the regulation of neutrophil chemotactic responses. Methods K/BxN serum transfer arthritis was induced in wild-type (WT), MIF -/-, and MCP1 (CCL2)-deficient mice, and in WT mice treated with anti-KC (CXCL1) mAb. In vivo leukocyte trafficking was examined using intravital microscopy, and in vitro neutrophil function was examined using migration chambers and MAP kinase activation. Results K/BxN serum transfer arthritis was markedly attenuated in MIF-/- mice, with reductions in clinical and histological severity as well as synovial expression of KC and IL-1. Arthritis was also reduced by anti-KC antibody treatment, but not in MCP-1-deficient mice. In vivo neutrophil recruitment responses to KC were reduced in MIF-/- mice. Similarly, MIF-/-neutrophils exhibited reduced in vitro chemotactic responses to KC, despite unaltered chemokine receptor expression. Reduced chemotactic responses in MIF-/- neutrophils were associated with reduced phosphorylation of p38 and ERK MAP kinases. Conclusion These data suggest MIF promotes neutrophil trafficking in inflammatory arthritis via facilitation of chemokine-induced migratory responses and MAP kinase activation. Therapeutic MIF inhibition could limit synovial neutrophil recruitment. PMID:21452319

  1. Thermal signature analysis as a novel method for evaluating inflammatory arthritis activity

    PubMed Central

    Brenner, M; Braun, C; Oster, M; Gulko, P S

    2006-01-01

    Objective To examine the potential usefulness of a novel thermal imaging technique to evaluate and monitor inflammatory arthritis activity in small joints using rat models, and to determine whether thermal changes can be used to detect preclinical stages of synovitis. Methods Three different rat strains were studied in a model of inflammatory arthritis of the ankle induced by an intra‐articular (IA) injection of complete Freund's adjuvant (CFA), compared with the contralateral ankle injected with normal saline. Arthritis activity and severity scores, ankle diameters, pain related posture scores, and thermal images were obtained at 10 different times between 0 h (before induction) and day 7. The pristane induced arthritis (PIA) model was used to study preclinical synovitis. Thermal images were obtained at each time point using the TSA ImagIR system and were digitally analysed. Results Rats developed similar ankle arthritis detected six hours after the IA injection of CFA, which persisted for seven days. All ankle clinical indices, including arthritis activity and severity scores, correlated significantly with ankle thermal imaging changes in the monoarthritis model (p<0.003). No thermal imaging changes were detected in preclinical stages of PIA. However, PIA onset coincided with increased ankle thermal signature. Conclusions Thermal measurements correlated significantly with arthritis activity and severity indices. The technique was highly sensitive and could measure directly two cardinal signs of inflammation (warmth and oedema, based on ankle diameter) in an area (ankle) that is less than half the size of a human interphalangeal joint, suggesting a potential use in drug trials or clinical practice. PMID:16150784

  2. CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis.

    PubMed

    Huang, Qi-Quan; Perlman, Harris; Birkett, Robert; Doyle, Renee; Fang, Deyu; Haines, G Kenneth; Robinson, William; Datta, Syamal; Huang, Zan; Li, Quan-Zhen; Phee, Hyewon; Pope, Richard M

    2015-05-12

    Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag(-/-) mice. The CD8α(+) DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4(+) T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4(+) T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α(+) DCs and other cells of the immune system.

  3. CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis

    PubMed Central

    Huang, Qi-Quan; Perlman, Harris; Birkett, Robert; Doyle, Renee; Fang, Deyu; Haines, G. Kenneth; Robinson, William; Datta, Syamal; Huang, Zan; Li, Quan-Zhen; Phee, Hyewon; Pope, Richard M.

    2015-01-01

    Dendritic cells (DCs) are critical for immune homeostasis. To target DCs, we generated a mouse line with Flip deficiency in cells that express cre under the CD11c promoter (CD11c-Flip-KO). CD11c-Flip-KO mice spontaneously develop erosive, inflammatory arthritis, resembling rheumatoid arthritis, which is dramatically reduced when these mice are crossed with Rag−/− mice. The CD8α+ DC subset is significantly reduced, along with alterations in NK cells and macrophages. Autoreactive CD4+ T cells and autoantibodies specific for joint tissue are present, and arthritis severity correlates with the number of autoreactive CD4+ T cells and plasmablasts in the joint-draining lymph nodes. Reduced T regulatory cells (Tregs) inversely correlate with arthritis severity, and the transfer of Tregs ameliorates arthritis. This KO line identifies a model that will permit in depth interrogation of the pathogenesis of rheumatoid arthritis, including the role of CD8α+ DCs and other cells of the immune system. PMID:25963626

  4. Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis.

    PubMed

    Silva, S; Sepodes, B; Rocha, J; Direito, R; Fernandes, A; Brites, D; Freitas, M; Fernandes, E; Bronze, M R; Figueira, M E

    2015-04-01

    Virgin olive oil is the primary source of fat in the Mediterranean diet, and its beneficial health effects have been related with oleic acid and phenolic compounds content. Hydroxytyrosol, a typical virgin olive oil phenolic compound, has beneficial antioxidant and anti-inflammatory properties as previously reported. The aim of this study was to evaluate the effect of hydroxytyrosol-supplemented refined olive oil at 0.5 and 5 mg/kg in a rodent model of rheumatoid arthritis. Rheumatoid arthritis was induced by intradermic administration, in male Wistar rats, of Freund's adjuvant with collagen type II on days 1 and 21. Hydroxytyrosol-supplemented refined olive oils were administrated by gavage from day 23 until day 35. The treatment at 5-mg/kg dose significantly decreased paw edema (P<.01), histological damage, cyclooxygenase-2 and inducible nitric oxide synthase expression, and markedly reduced the degree of bone resorption, soft tissue swelling and osteophyte formation, improving articular function in treated animals. Acute inflammation, induced by carrageenan, was also evaluated for hydroxytyrosol-supplemented refined olive oils at 0.5 and 5 mg/kg. Both doses significantly reduced paw edema (P<.001). Our results suggest that the supplementation of refined olive oil with hydroxytyrosol may be advantageous in rheumatoid arthritis with significant impact not only on chronic inflammation but also on acute inflammatory processes.

  5. Paracetamol for the management of pain in inflammatory arthritis: a systematic literature review.

    PubMed

    Hazlewood, Glen; van der Heijde, Désirée M; Bombardier, Claire

    2012-09-01

    To systematically review the literature on the efficacy and safety of paracetamol (acetaminophen) in the management of pain in inflammatory arthritis. A systematic search was performed in Medline, Embase, the Cochrane Library, and 2008/2009 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) conference abstracts for clinical trials and observational studies of paracetamol in patients with inflammatory arthritis. Included trials were appraised for risk of bias, and relevant study details were abstracted. Efficacy was assessed from clinical trials using improvement in pain as the outcome measure, and safety was assessed using total adverse events and withdrawals due to adverse events as outcome measures. Safety data from observational studies were assessed separately. Eleven articles containing 12 clinical trials and 1 observational study were identified, all in patients with rheumatoid arthritis. The trials were of short duration, used atypical doses of paracetamol, and all had a high risk of bias. Overall, there was weak evidence of a benefit of paracetamol over placebo and an additive benefit of paracetamol in combination with nonsteroidal antiinflammatory drugs (NSAID). The benefit of paracetamol to NSAID alone was uncertain. No significant differences in safety were seen in the limited clinical trial data. One cohort study showed an increased rate of serious gastrointestinal events with paracetamol over NSAID when used concurrently with corticosteroids and other analgesics, but had significant methodological limitations. There is weak evidence for the efficacy of paracetamol in patients with inflammatory arthritis, and insufficient disease-specific safety data to draw conclusions.

  6. Dynamics in serum of the inflammatory markers serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins during induced noninfectious arthritis in the horse.

    PubMed

    Hultén, C; Grönlund, U; Hirvonen, J; Tulamo, R-M; Suominen, M M; Marhaug, G; Forsberg, M

    2002-11-01

    Despite the importance of noninfectious joint diseases in equine medicine, little is known about the acute phase response which may be elicited if the local inflammatory process of noninfectious arthritis is sufficiently strong, Therefore the aim of this study was to monitor the systemic inflammatory response during experimentally-induced noninfectious arthritis by studying the dynamics in serum of the acute phase proteins serum amyloid A (SAA), haptoglobin, fibrinogen and alpha2-globulins. Twenty-four Standardbred horses, age 3-7 years, found healthy on thorough clinical, radiological, haematological and serum biochemical examination, were injected aseptically into the right midcarpal joint with amphotericin B. Blood samples were drawn before induction of arthritis (0 h), and at 8, 16, 24, 36 and 48 h postinduction and then on Days 3, 4, 5 and 15 postinduction. All horses developed lameness with joint effusion and joint heat as well as increased respiratory rate, heart rate and body temperature. The lameness started to decline after 24-36 h and, in most animals, systemic signs disappeared on Day 2 postinjection. The concentration of the acute phase proteins increased following induction of arthritis. The SAA concentrations were higher than baseline concentrations from 16 h postinduction and were maximal at 36-48 h (227 times baseline concentration). The haptoglobin concentrations were higher than baseline concentrations from 24 h and were maximal at 48-96 h (1.14 times baseline concentration). The maximal concentrations of fibrinogen were seen between 36-72 h postinjection and increased on average 0.87 times from baseline concentrations. The fibrinogen concentrations were higher than baseline concentrations from 24 h postinjection. Alpha2-globulins concentrations showed a minor increase and increased 0.55 times from baseline concentrations. The markers had returned to baseline concentrations by Day 15. Our results demonstrate that amphotericin B-induced arthritis

  7. CD44 Antibodies and Immune Thrombocytopenia in the Amelioration of Murine Inflammatory Arthritis

    PubMed Central

    Mott, Patrick J.; Lazarus, Alan H.

    2013-01-01

    Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP) that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7), also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics. PMID:23785450

  8. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis.

    PubMed

    Walker, Mary E; Souza, Patricia R; Colas, Romain A; Dalli, Jesmond

    2017-08-01

    Rheumatoid arthritis is an inflammatory condition characterized by overzealous inflammation that leads to joint damage and is associated with an increased incidence of cardiovascular disease. Statins are frontline therapeutics for patients with cardiovascular disease and exert beneficial actions in rheumatoid arthritis. The mechanism that mediates the beneficial actions of statins in rheumatoid arthritis remains of interest. In the present study, we found that the administration of 2 clinically relevant statins-atorvastatin (0.2 mg/kg) or pravastatin (0.2 mg/kg)-to mice during inflammatory arthritis up-regulated systemic and tissue amounts of a novel family of proresolving mediators, termed 13-series resolvins (RvTs), and significantly reduced joint disease. Of note, administration of simvastatin (0.2 mg/kg) did not significantly up-regulate RvTs or reduce joint inflammation. We also found that atorvastatin and pravastatin each reduced systemic leukocyte activation, including platelet-monocyte aggregates (∼25-60%). These statins decreased neutrophil trafficking to the joint as well as joint monocyte and macrophage numbers. Atorvastatin and pravastatin produced significant reductions (∼30-50%) in expression of CD11b and major histocompatibility complex class II on both monocytes and monocyte-derived macrophages in joints. Administration of an inhibitor to cyclooxygenase-2, the initiating enzyme in the RvT pathway, reversed the protective actions of these statins on both joint and systemic inflammation. Together, these findings provide evidence for the role of RvTs in mediating the protective actions of atorvastatin and pravastatin in reducing local and vascular inflammation, and suggest that RvTs may be useful in measuring the anti-inflammatory actions of statins.-Walker, M. E., Souza, P. R., Colas, R. A., Dalli, J. 13-Series resolvins mediate the leukocyte-platelet actions of atorvastatin and pravastatin in inflammatory arthritis. © The Author(s).

  9. VDIPEN, a metalloproteinase-generated neoepitope, is induced and immunolocalized in articular cartilage during inflammatory arthritis.

    PubMed Central

    Singer, I I; Kawka, D W; Bayne, E K; Donatelli, S A; Weidner, J R; Williams, H R; Ayala, J M; Mumford, R A; Lark, M W; Glant, T T

    1995-01-01

    The destruction of articular cartilage in immune inflammatory arthritic disease involves the proteolytic degradation of its extracellular matrix. The role of activated matrix metalloproteinases (MMPs) in the chondrodestructive process was studied by identifying a selective cleavage product of aggrecan in murine arthritis models initiated by immunization with either type II collagen or proteoglycan. We conducted semiquantitative immunocytochemical studies of VDIPEN341 using a monospecific polyclonal antibody requiring the free COOH group of the COOH-terminal Asn for epitope detection. This antibody recognizes the aggrecan G1 domain fragment generated by MMP [i.e., stromelysin (SLN) or gelatinase A] cleavage of aggrecan between Asn341-Phe342 but does not recognize intact aggrecan. VDIPEN was undetectable in normal mouse cartilage but was observed in the articular cartilage (AC) of mice with collagen-induced arthritis 10 d after immunization, without histological damage and clinical symptoms. This aggrecan neoepitope was colocalized with high levels of glycosaminoglycans (GAGs) in pericellular matrices of AC chondrocytes but was not seen at the articular surface at this early time. Digestion of normal (VDIPEN negative) mouse paw cryosections with SLN also produced heavy pericellular VDIPEN labeling. Computer-based image analysis showed that the amount of VDIPEN expression increased dramatically by 20 d (70% of the SLN maximum) and was correlated with GAG depletion. Both infiltration of inflammatory cells into the synovial cavity and early AC erosion were also very prominent at this time. Analysis of adjacent sections showed that both induction of VDIPEN and GAG depletion were strikingly codistributed within sites of articular cartilage damage. Similar results occurred in proteoglycan-induced arthritis, a more progressive and chronic model of inflammatory arthritis. These studies demonstrate for the first time the MMP-dependent catabolism of aggrecan at sites of

  10. Arthritis

    MedlinePlus

    ... or have trouble moving around, you might have arthritis. Most kinds of arthritis cause pain and swelling in your joints. Joints ... joint can become severely damaged. Some kinds of arthritis can also cause problems in your organs, such ...

  11. [The systemic inflammatory response syndrome correction in acute destructive pancreatitis].

    PubMed

    Agapov, M A; Khoreva, M V; Gorskiĭ, V A

    2011-01-01

    Acute pancreatitis is a disease of variable severity. In which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis. In our research we have estimated influence of not steroid anti-inflammatory preparation on synthesis pro-and anti-inflammatory Cytokines at healthy donors and at patients with Acute pancreatitis.

  12. Evaluation of Anti-Inflammatory Potential of the New Ganghwaljetongyeum on Adjuvant-Induced Inflammatory Arthritis in Rats

    PubMed Central

    Kim, Wangin; Park, Sangbin; Kim, Youg Ran; Shin, Wook; Lee, Yumi; Choi, Donghee; Kim, Mirae; Lee, Hyunju; Kim, Seonjong; Na, Changsu

    2016-01-01

    Ganghwaljetongyeum (GHJTY) has been used as a standard treatment for arthritis for approximately 15 years at the Korean Medicine Hospital of Dongshin University. GHJTY is composed of 18 medicinal herbs, of which five primary herbs were selected and named new Ganghwaljetongyeum (N-GHJTY). The purpose of the present study was to observe the effect of N-GHJTY on arthritis and to determine its mechanism of action. After confirming arthritis induction using complete Freund's adjuvant (CFA) in rats, N-GHJTY (62.5, 125, and 250 mg/kg/day) was administered once a day for 10 days. In order to determine pathological changes, edema of the paws and weight were measured before and for 10 days after N-GHJTY administration. Cytokine (TNF-α, IL-1β, and IL-6) levels and histopathological lesions in the knee joint were also examined. Edema in the paw and knee joint of N-GHJTY-treated rats was significantly decreased at 6, 8, and 10 days after administration, compared to that in the CFA-control group, while weight consistently increased. Rats in N-GHJTY-treated groups also recovered from the CFA-induced pathological changes and showed a significant decline in cytokine levels. Taken together, our results showed that N-GHJTY administration was effective in inhibiting CFA-induced arthritis via anti-inflammatory effects while promoting cartilage recovery by controlling cytokine levels. PMID:27382402

  13. Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

    PubMed

    Molín, Jéssica; Márquez, Mercedes; Raurell, Xavier; Matiasek, Kaspar; Ferrer, Isidre; Pumarola, Martí

    2011-09-01

    We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

  14. Cytokines as therapeutic targets in rheumatoid arthritis and other inflammatory diseases.

    PubMed

    Siebert, Stefan; Tsoukas, Alexander; Robertson, Jamie; McInnes, Iain

    2015-01-01

    The human immune system involves highly complex and coordinated processes in which small proteins named cytokines play a key role. Cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases. Cytokines are therefore attractive therapeutic targets in these conditions. Anticytokine therapy for inflammatory diseases became a clinical reality with the introduction of tumor necrosis factor (TNF) inhibitors for the treatment of severe rheumatoid arthritis. Although these therapies have transformed the treatment of patients with severe inflammatory arthritis, there remain significant limiting factors: treatment failure is commonly seen in the clinic; safety concerns remain; there is uncertainty regarding the relevance of immunogenicity; the absence of biomarkers to direct therapy decisions and high drug costs limit availability in some healthcare systems. In this article, we provide an overview of the key efficacy and safety trials for currently approved treatments in rheumatoid arthritis and review the major lessons learned from a decade of use in clinical practice, focusing mainly on anti-TNF and anti-interleukin (IL)-6 agents. We also describe the clinical application of anticytokine therapies for other inflammatory diseases, particularly within the spondyloarthritis spectrum, and highlight differential responses across diseases. Finally, we report on the current state of trials for newer therapeutic targets, focusing mainly on the IL-17 and IL-23 pathways. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. The impact of endogenous annexin A1 on glucocorticoid control of inflammatory arthritis

    PubMed Central

    Patel, Hetal B; Kornerup, Kristin N; Sampaio, Andre' LF; D'Acquisto, Fulvio; Seed, Michael P; Girol, Ana Paula; Gray, Mohini; Pitzalis, Costantino; Oliani, Sonia M; Perretti, Mauro

    2012-01-01

    Objectives To establish the role and effect of glucocorticoids and the endogenous annexin A1 (AnxA1) pathway in inflammatory arthritis. Methods Ankle joint mRNA and protein expression of AnxA1 and its receptors were analysed in naive and arthritic mice by real-time PCR and immunohistochemistry. Inflammatory arthritis was induced with the K/BxN arthritogenic serum in AnxA1+/+ and AnxA1−/− mice; in some experiments, animals were treated with dexamethasone (Dex) or with human recombinant AnxA1 or a protease-resistant mutant (termed SuperAnxA1). Readouts were arthritic score, disease incidence, paw oedema and histopathology, together with pro-inflammatory gene expression. Results All elements of the AnxA1 pathway could be detected in naive joints, with augmentation during ongoing disease, due to the infiltration of immune cells. No difference in arthritis intensity of profile could be observed between AnxA1+/+ and AnxA1−/− mice. Treatment of mice with Dex (10 µg intraperitoneally daily from day 2) afforded potent antiarthritic effects highly attenuated in the knockouts: macroscopic changes were mirrored by histopathological findings and pro-inflammatory gene (eg, Nos2) expression. Presence of proteinase 3 mRNA in the arthritic joints led the authors to test AnxA1 and the mutant SuperAnxA1 (1 µg intraperitoneally daily in both cases from day 2), with the latter one being able to accelerate the resolving phase of the disease. Conclusion AnxA1 is an endogenous determinant for the therapeutic efficacy of Dex in inflammatory arthritis. Such an effect can be partially mimicked by application of SuperAnxA1 which may represent the starting point for novel antiarthritic therapeutic strategies. PMID:22562975

  16. Patient- and clinician-reported outcomes for patients with new presentation of inflammatory arthritis: observations from the National Clinical Audit for Rheumatoid and Early Inflammatory Arthritis.

    PubMed

    Ledingham, Joanna M; Snowden, Neil; Rivett, Ali; Galloway, James; Ide, Zoe; Firth, Jill; MacPhie, Elizabeth; Kandala, Ngianga; Dennison, Elaine M; Rowe, Ian

    2017-02-01

    Our aim was to conduct a national audit assessing the impact and experience of early management of inflammatory arthritis by English and Welsh rheumatology units. The audit enables rheumatology services to measure for the first time their performance, patient outcomes and experience, benchmarked to regional and national comparators. All individuals >16 years of age presenting to English and Welsh rheumatology services with suspected new-onset inflammatory arthritis were included in the audit. Clinician- and patient-derived outcome and patient-reported experience measures were collected. Data are presented for the 6354 patients recruited from 1 February 2014 to 31 January 2015. Ninety-seven per cent of English and Welsh trusts participated. At the first specialist assessment, the 28-joint DAS (DAS28) was calculated for 2659 (91%) RA patients [mean DAS28 was 5.0 and mean Rheumatoid Arthritis Impact of Disease (RAID) score was 5.6]. After 3 months of specialist care, the mean DAS28 was 3.5 and slightly >60% achieved a meaningful DAS28 reduction. The average RAID score and reduction in RAID score were 3.6 and 2.4, respectively. Of the working patients ages 16-65 years providing data, 7, 5, 16 and 37% reported that they were unable to work, needed frequent time off work, occasionally and rarely needed time off work due to their arthritis, respectively; only 42% reported being asked about their work. Seventy-eight per cent of RA patients providing data agreed with the statement 'Overall in the last 3 months I have had a good experience of care for my arthritis'; <2% disagreed. This audit demonstrates that most RA patients have severe disease at the time of presentation to rheumatology services and that a significant number continue to have high disease activity after 3 months of specialist care. There is a clear need for the National Health Service to develop better systems for capturing, coding and integrating information from outpatient clinics, including measures of

  17. The role of T helper type 17 cells in inflammatory arthritis

    PubMed Central

    Sarkar, S; Cooney, L A; Fox, D A

    2010-01-01

    While T cells have been implicated in the pathogenesis of inflammatory arthritis for more than three decades, the focus on the T helper type 17 (Th17) subset of CD4 T cells and their secreted cytokines, such as interleukin (IL)-17, is much more recent. Proinflammatory actions of IL-17 were first identified in the 1990s, but the delineation of a distinct Th17 subset in late 2005 has sparked great interest in the role of these cells in a broad range of immune-mediated diseases. This review summarizes current understanding of the role of Th17 cells and their products in both animal models of inflammatory arthritis and human immune-driven arthritides. PMID:19758374

  18. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis.

    PubMed

    Headland, Sarah E; Jones, Hefin R; Norling, Lucy V; Kim, Andrew; Souza, Patricia R; Corsiero, Elisa; Gil, Cristiane D; Nerviani, Alessandra; Dell'Accio, Francesco; Pitzalis, Costantino; Oliani, Sonia M; Jan, Lily Y; Perretti, Mauro

    2015-11-25

    Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular lipid and protein components to target cells, yet their function in disease is only now being explored. We found that neutrophil-derived MVs were increased in concentration in synovial fluid from rheumatoid arthritis patients compared to paired plasma. Synovial MVs overexpressed the proresolving, anti-inflammatory protein annexin A1 (AnxA1). Mice deficient in TMEM16F, a lipid scramblase required for microvesiculation, exhibited exacerbated cartilage damage when subjected to inflammatory arthritis. To determine the function of MVs in inflammatory arthritis, toward the possibility of MV-based therapeutics, we examined the role of immune cell-derived MVs in rodent models and in human primary chondrocytes. In vitro, exogenous neutrophil-derived AnxA1(+) MVs activated anabolic gene expression in chondrocytes, leading to extracellular matrix accumulation and cartilage protection through the reduction in stress-adaptive homeostatic mediators interleukin-8 and prostaglandin E2. In vivo, intra-articular injection of AnxA1(+) MV lessened cartilage degradation caused by inflammatory arthritis. Arthritic mice receiving adoptive transfer of whole neutrophils displayed abundant MVs within cartilage matrix and revealed that MVs, but not neutrophils themselves, can penetrate cartilage. Mechanistic studies support a model whereby MV-associated AnxA1 interacts with its receptor FPR2 (formyl peptide receptor 2)/ALX, increasing transforming growth factor-β production by chondrocytes, ultimately leading to cartilage protection. We envisage that MVs, either directly or loaded with therapeutics, can be harnessed as a unique therapeutic strategy for protection in diseases associated with cartilage degeneration. Copyright © 2015, American Association for the Advancement of Science.

  19. A Survey of Psychological Support Provision for People with Inflammatory Arthritis in Secondary Care in England

    PubMed Central

    Dures, Emma; Almeida, Celia; Caesley, Judy; Peterson, Alice; Ambler, Nicholas; Morris, Marianne; Pollock, Jon; Hewlett, Sarah

    2014-01-01

    Objectives The consequences of inflammatory arthritis can include depression, anxiety and low mood, reducing patients’ quality of life and increasing pressure on the healthcare system. Treatment guidelines recommend psychological support, but data are lacking on the provision available. Methods A postal survey concerning psychological support provision was sent to rheumatology units in 143 acute trusts across England. Nurses from 73 rheumatology units (51%) responded. Results Overall, 73% rated their unit's psychological support provision as ‘inadequate’ and only 4% rated it as ‘good’. Few units believed that psychological support did not fall within their remit (12%), yet only 8% had a psychologist in the team. Most units (68%) did not routinely screen patients to identify psychological difficulties. Referral to other service providers was reported in 42% of units, with 3% very satisfied with this provision. Within units, services containing elements of psychological support ranged from occupational therapy (81%) to psychology/counselling (14%). Psychological approaches used by team members ranged from shared decision making (77%) to cognitive–behavioural approaches (26%). The current barriers to providing psychological support were lack of clinical time and available training (86% and 74%, respectively), and delivery costs (74%). Future facilitators included management support (74%) and availability of skills training (74%). Conclusions Rheumatology units viewed psychological support provision as part of their remit but rated their overall provision as inadequate, despite some team members using psychological skills. To improve provision, clinicians’ training needs must be addressed and organizational support generated, and further research needs to define adequate psychological support provision from the patient perspective. © 2014 The Authors. Musculoskeletal Care published by John Wiley & Sons Ltd. PMID:24753071

  20. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis

    PubMed Central

    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    Background: Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be

  1. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis.

    PubMed

    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    Anti-cyclic citrullinated peptides (CCPs) are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF), an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP), an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9]) were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%), followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was found to be statistically significant. Although anti-CCP, RF, and CRP levels are

  2. Alterations to adipose tissue morphology during inflammatory arthritis is indicative of vasculopathology in DBA/1 mice.

    PubMed

    Sime, Katie; Choy, Ernest H; Williams, Anwen S

    2017-04-03

    The physiologic function of adipose tissue is altered by the host's inflammatory response; the implications for maintaining human health and regulating inflammation-associated disease progression are ill defined. However, this cannot be investigated in humans, therefore the use of animal models is required. With the aim to determine morphological and molecular alterations to perivascular and organ-associated adipose tissues during inflammatory arthritis, collagen-induced arthritis (CIA) was established in male DBA/1 mice. Emerging evidence from this study signposts CIA in the DBA/1 mouse as a model that is relevant to study the development and treatment of early cardiovascular pathology associated with inflammatory arthritis. Here, we show global morphological changes in adipose tissue and the thoracic aorta in animals induced with CIA compared with the non-immunized controls. In CIA, we concluded that the increased cell count in PVAT was, at least in part, caused by an ingress and/or expansion of macrophages that had a mixed phenotype. A substantial increase of galectin-3 was expressed in PVAT from mice with CIA. Galectin-3 is elevated in the blood of patients with CVDs, however, it has never before been measured in PVAT in rodents or humans. Here, PVAT-associated galectin-3 is identified as a potential biomarker for detecting early vascular pathology in CIA and a promising candidate for translation to RA.

  3. Alterations to adipose tissue morphology during inflammatory arthritis is indicative of vasculopathology in DBA/1 mice

    PubMed Central

    Sime, Katie; Choy, Ernest H.; Williams, Anwen S.

    2017-01-01

    Abstract The physiologic function of adipose tissue is altered by the host's inflammatory response; the implications for maintaining human health and regulating inflammation-associated disease progression are ill defined. However, this cannot be investigated in humans, therefore the use of animal models is required. With the aim to determine morphological and molecular alterations to perivascular and organ-associated adipose tissues during inflammatory arthritis, collagen-induced arthritis (CIA) was established in male DBA/1 mice. Emerging evidence from this study signposts CIA in the DBA/1 mouse as a model that is relevant to study the development and treatment of early cardiovascular pathology associated with inflammatory arthritis. Here, we show global morphological changes in adipose tissue and the thoracic aorta in animals induced with CIA compared with the non-immunized controls. In CIA, we concluded that the increased cell count in PVAT was, at least in part, caused by an ingress and/or expansion of macrophages that had a mixed phenotype. A substantial increase of galectin-3 was expressed in PVAT from mice with CIA. Galectin-3 is elevated in the blood of patients with CVDs, however, it has never before been measured in PVAT in rodents or humans. Here, PVAT-associated galectin-3 is identified as a potential biomarker for detecting early vascular pathology in CIA and a promising candidate for translation to RA. PMID:28425846

  4. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis

    PubMed Central

    Bombardieri, Michele; Greenhill, Claire J.; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S.; Pitzalis, Costantino; Jenkins, Brendan J.

    2015-01-01

    Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R–deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. PMID:26417004

  5. Interleukin-27 inhibits ectopic lymphoid-like structure development in early inflammatory arthritis.

    PubMed

    Jones, Gareth W; Bombardieri, Michele; Greenhill, Claire J; McLeod, Louise; Nerviani, Alessandra; Rocher-Ros, Vidalba; Cardus, Anna; Williams, Anwen S; Pitzalis, Costantino; Jenkins, Brendan J; Jones, Simon A

    2015-10-19

    Ectopic lymphoid-like structures (ELSs) reminiscent of secondary lymphoid organs often develop at sites of chronic inflammation where they contribute to immune-mediated pathology. Through evaluation of synovial tissues from rheumatoid arthritis (RA) patients, we now show that low interleukin-27 (IL-27) expression corresponds with an increased incidence of ELS and gene signatures associated with their development and activity. The presence of synovial ELS was also noted in mice deficient in the IL-27 receptor (IL-27R) after the onset of inflammatory arthritis. Here, pathology was associated with increased synovial expression of pro-inflammatory cytokines, homeostatic chemokines, and transcriptional regulators linked with lymphoid neogenesis. In both clinical and experimental RA, synovial ELS coincided with the heightened local expression of cytokines and transcription factors of the Th17 and T follicular helper (Tfh) cell lineages, and included podoplanin-expressing T cells within lymphoid aggregates. IL-27 inhibited the differentiation of podoplanin-expressing Th17 cells, and an increased number of these cells were observed in IL-27R-deficient mice with inflammatory arthritis. Thus, IL-27 appears to negatively regulate ELS development in RA through control of effector T cells. These studies open new opportunities for patient stratification and treatment. © 2015 Jones et al.

  6. Arthritis induced by adjuvant in spontaneously hypertensive and normotensive rats: endogenous glucocorticoid effects on inflammatory response.

    PubMed

    Torres, Micheli G; Kwasniewski, Fabio H; Scaliante, Luís G; Ishii-Iwamoto, Emy L; Caparroz-Assef, Silvana M; Cuman, Roberto K N; Bersani-Amado, Ciomar A

    2009-02-01

    The present study investigated arthritis induced by complete Freund adjuvant (AIA) in spontaneously hypertensive and normotensive rats (respectively, SHR and NTR rats). The inflammatory reaction was studied for 28 days by evaluating paw edema and secondary lesions found 10 days after complete Freund adjuvant (CFA) administration. The body weight of the animals and macroscopic alterations of several organs, including spleen, thymus, adrenal glands, and lymph nodes, were also analyzed. The results showed that the AIA manifestations were decreased in SHRs compared with NTRs. Moreover, this altered inflammatory response was not modified by surgical adrenalectomy.

  7. An improved acute gouty arthritis rat model and therapeutic effect of rhizoma Dioscoreae nipponicae on acute gouty arthritis based on the protein-chip methods.

    PubMed

    Yao, Li; Dong, Wanru; Lu, Fang; Liu, Shumin

    2012-01-01

    Rhizoma Dioscoreae nipponicae (RDN) is an herbal medicine. In the theories of Traditional Chinese Medicine (TCM), the function of RDN is to expel wind and remove dampness. Inflammatory mechanisms play an important role in the pathological process and prognosis of acute gouty arthritis (AGA). The aim of this study was to determine the specially expressed proteins through testing the proteins of the synovium in rats with AGA. The animal model of AGA was set up by Monosodium urate crystal (MSU) combined with hypoxanthine (HX), which was ameliorated in our previous experiment. Blood samples for measurement of serum uric acid were collected prior to sacrifice. Outcomes were assessed (two days after injection) by histological stain and protein quantitation. Three chips of RayBio® Human Label-based Antibody Array I were applied to detect 90 proteins in the synovium tissue of AGA rats. 14 differently expressed proteins were found in the synovium of AGA rats, and nine of them were first found in this model. There were seven up-regulated and seven down-regulated proteins, both TRAIL and Neuropilin-2 could be identified as key contributors to the pathomechanism of AGA.

  8. [CT - diagnosis and differential diagnosis of inflammatory acute intestinal conditions].

    PubMed

    Wiesner, W

    2011-08-24

    Multidetector-row CT has shown over the past years that it is able to provide reliable diagnoses in various acute intestinal conditions. The presented article provides an overview of primary and secondary inflammatory acute intestinal pathologies and their differential diagnoses.

  9. Update on the Management of Pediatric Acute Osteomyelitis and Septic Arthritis

    PubMed Central

    Castellazzi, Luca; Mantero, Marco; Esposito, Susanna

    2016-01-01

    Acute osteomyelitis and septic arthritis are two infections whose frequencies are increasing in pediatric patients. Acute osteomyelitis and septic arthritis need to be carefully assessed, diagnosed, and treated to avoid devastating sequelae. Traditionally, the treatment of acute osteoarticular infection in pediatrics was based on prolonged intravenous anti-infective therapy. However, results from clinical trials have suggested that in uncomplicated cases, a short course of a few days of parenteral antibiotics followed by oral therapy is safe and effective. The aim of this review is to provide clinicians an update on recent controversies and advances regarding the management of acute osteomyelitis and septic arthritis in children. In recent years, the emergence of bacterial species resistant to commonly used antibiotics that are particularly aggressive highlights the necessity for further research to optimize treatment approaches and to develop new molecules able to fight the war against acute osteoarticular infection in pediatric patients. PMID:27258258

  10. Substance P ameliorates collagen II-induced arthritis in mice via suppression of the inflammatory response

    SciTech Connect

    Hong, Hyun Sook; Son, Youngsook

    2014-10-10

    Highlights: • SP can increase IL-10 levels and reduce TNF-α and IL-17 levels in RA. • SP causes the increase in T{sub reg}, M2 macrophage, and MSCs in RA. • SP-induced immune suppression leads to the blockade of RA progression. • SP can be used as the therapeutics for autoimmune-related inflammatory diseases. - Abstract: Current rheumatoid arthritis (RA) therapies such as biologics inhibiting pathogenic cytokines substantially delay RA progression. However, patient responses to these agents are not always complete and long lasting. This study explored whether substance P (SP), an 11 amino acids long endogenous neuropeptide with the novel ability to mobilize mesenchymal stem cells (MSC) and modulate injury-mediated inflammation, can inhibit RA progression. SP efficacy was evaluated by paw swelling, clinical arthritis scoring, radiological analysis, histological analysis of cartilage destruction, and blood levels of tumor necrosis factor-alpha (TNF-α) interleukin (IL)-10, and IL-17 in vivo. SP treatment significantly reduced local inflammatory signs, mean arthritis scores, degradation of joint cartilage, and invasion of inflammatory cells into the synovial tissues. Moreover, the SP treatment markedly reduced the size of spleens enlarged by excessive inflammation in CIA, increased IL-10 levels, and decreased TNF-α and IL-17 levels. Mobilization of stem cells and induction of T{sub reg} and M2 type macrophages in the circulation were also increased by the SP treatment. These effect of SP might be associated with the suppression of inflammatory responses in RA and, furthermore, blockade of RA progression. Our results propose SP as a potential therapeutic for autoimmune-related inflammatory diseases.

  11. Are bacterial load and synovitis related in dogs with inflammatory stifle arthritis?

    PubMed

    Schwartz, Zeev; Zitzer, Nina C; Racette, Molly A; Manley, Paul A; Schaefer, Susan L; Markel, Mark D; Hao, Zhengling; Holzman, Gerianne; Muir, Peter

    2011-03-24

    It has been proposed that small quantities of microbial material within synovial joints may act as a trigger for development of synovitis. We have previously identified an association between intra-articular bacteria and development of inflammatory stifle arthritis and cranial cruciate ligament rupture (CCLR) in dogs, and now wished to quantify bacterial load and markers of synovitis in dogs with and without stifle arthritis and CCLR. Joint tissues were collected from dogs with CCLR (n=51) and healthy dogs with normal stifles (n=9). Arthritis was assessed radiographically in CCLR dogs. Bacterial load was assessed using qPCR and broad-ranging 16S rRNA primers. qRT-PCR was used to estimate expression of the T lymphocyte antigen receptor (TCR Vβ), CD3ɛ, tartrate-resistant acid phosphatase (TRAP), IL-4, IL-17, and TNF-α genes. Severity of synovitis was assessed histologically. Bacterial load was increased in arthritic stifles, when compared with healthy stifles. Histologic synovitis in arthritic stifles was mononuclear and was significantly correlated with bacterial load (1 of 2 primer sets) (S(R)=0.49, p<0.001). In arthritic stifles, expression of TRAP in synovium was increased relative to healthy stifles. Expression of pro-inflammatory genes was not correlated with bacterial load, histologic inflammation, or radiographic arthritis. Translocation of bacterial material to the canine stifle is related to the presence of joint inflammation. The lack of a strong positive correlation suggests that bacterial load is unlikely to be a primary pro-inflammatory factor. However, dysregulation of immune responses within synovial tissues may be dependent upon an environmental microbial trigger.

  12. Anti-inflammatory and antiarthritic effects of piperine in human interleukin 1β-stimulated fibroblast-like synoviocytes and in rat arthritis models

    PubMed Central

    Bang, Jun Soo; Oh, Da Hee; Choi, Hyun Mi; Sur, Bong-Jun; Lim, Sung-Jig; Kim, Jung Yeon; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun; Kim, Kyoung Soo

    2009-01-01

    Introduction The objective of this study was to determine the anti-inflammatory, nociceptive, and antiarthritic effects of piperine, the active phenolic component in black pepper extract. Methods The in vitro anti-inflammatory activity of piperine was tested on interleukin 1β (IL1β)-stimulated fibroblast-like synoviocytes derived form patients with rheumatoid arthritis. The levels of IL6, matrix metalloproteinase (MMPs), cyclo-oxygenase 2 (COX-2), and prostaglandin E2 (PGE2) were investigated by ELISA and RT-PCR analysis. The analgesic and antiarthritic activities of piperine were investigated on rat models of carrageenan-induced acute paw pain and arthritis. The former were evaluated with a paw pressure test, and the latter by measuring the squeaking score, paw volume, and weight distribution ratio. Piperine was administrated orally to rats at 20 and 100 mg/kg/day for 8 days. Results Piperine inhibited the expression of IL6 and MMP13 and reduced the production of PGE2 in a dose dependant manner at concentrations of 10 to 100 μg/ml. In particular, the production of PGE2 was significantly inhibited even at 10 μg/ml of piperine. Piperine inhibited the migration of activator protein 1 (AP-1), but not nuclear factor (NF)κB, into the nucleus in IL1β-treated synoviocytes. In rats, piperine significantly reduced nociceptive and arthritic symptoms at days 8 and 4, respectively. Histological staining showed that piperine significantly reduced the inflammatory area in the ankle joints. Conclusions These results suggest that piperine has anti-inflammatory, antinociceptive, and antiarthritic effects in an arthritis animal model. Thus, piperine should be further studied with regard to use either as a pharmaceutical or as a dietary supplement for the treatment of arthritis. PMID:19327174

  13. Inhibition of CDK9 as a therapeutic strategy for inflammatory arthritis

    PubMed Central

    Hellvard, Annelie; Zeitlmann, Lutz; Heiser, Ulrich; Kehlen, Astrid; Niestroj, André; Demuth, Hans-Ulrich; Koziel, Joanna; Delaleu, Nicolas; Jan Potempa; Mydel, Piotr

    2016-01-01

    Rheumatoid arthritis is characterised by synovial inflammation and proliferation of fibroblast-like synoviocytes. The induction of apoptosis has long been proposed as a target for proliferative autoimmune diseases, and has further been shown to act as a successful treatment of experimental models of arthritis, such as collagen-induced arthritis. Here we examined the effects of specific oral small-molecule inhibitors of the transcription regulating cyclin-dependent kinase 9 on the development and progression of collagen-induced arthritis. DBA/1 mice were immunised with bovine collagen type II and treated orally with specific CDK9 inhibitors. The effects of CDK9 inhibition on RNA levels and protein expression, apoptosis induction, caspase activation and lymphocyte phenotype were further analysed. Mice showed a significant delay in disease onset and a reduction in disease severity following treatment with CDK9 inhibitors. Inhibiting CDK9 activity in peripheral blood mononuclear cells resulted in the loss of Mcl-1 expression at both the protein and RNA levels, along with a subsequent increase in apoptosis. CDK9 specific inhibitors may be a potential alternative treatment not only of cancer, but also for autoimmune- and inflammatory diseases. Taken together, these results show that transient inhibition of CDK9 induces apoptosis in leukocyte subsets and modulates the immune response. PMID:27511630

  14. Lactobacillus casei reduces the inflammatory joint damage associated with collagen-induced arthritis (CIA) by reducing the pro-inflammatory cytokines: Lactobacillus casei: COX-2 inhibitor.

    PubMed

    Amdekar, Sarika; Singh, Vinod; Singh, Rambir; Sharma, Poonam; Keshav, Poonam; Kumar, Avnish

    2011-04-01

    This study evaluated the therapeutic efficacy of Lactobacillus casei in treating rheumatoid arthritis using collagen-induced arthritis (CIA) animal model. Healthy female Wistar rats (weight-180-200 g) were included in this study. Oral administration of L. casei was started on the same day. Indomethacin was used as standard reference drug. Serum level of IL-6, α-TNF, and IL-10 were observed. Four-point arthritis indexes were also assessed at the end of week for 28th day. L. casei-treated rats had shown normal histopathology without any synovial infiltration, pannus formation, cartilage, and bone destruction. Arthritis score was also lower for the group treated with L. casei. Oral administration of L. casei significantly decreased the pro-inflammatory cytokines. Present study suggests that L. casei has potent antiarthritic effect in CIA model. Inhibition of COX-2 via inhibiting the pro-inflammatory cytokines is an understanding of the complex interactions involved in these pathways.

  15. Role of cytokines, acute-phase proteins, and chemokines in the progression of rheumatoid arthritis.

    PubMed

    Badolato, R; Oppenheim, J J

    1996-10-01

    Rheumatoid arthritis (RA) has no firm etiologic basis. It progresses as an autoimmune disease and evolves into a chronic inflammatory joint disease complicated by recurrent episodes of systemic acute-phase reactions, which sometimes result in amyloidosis. Cytokines play a pivotol role in inflammation and the immune response. Proinflammatory cytokines such as interleukin-1, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 are present at high levels in arthritic joints, and their blood concentration correlates with the severity of the RA. Some of the activities of the proinflammatory cytokines, such as stimulation of leukocyte infiltration and release of their proteolytic enzymes, may be mediated by acute phase proteins (APPs), such as C-reactive protein and serum amyloid A, and by chemokines such as interleukin-8. Cytokines, chemokines, and APPs reciprocally regulate each others' expression and activities, constituting a communication network between fibroblasts, macrophages, lymphocytes, and hepatocytes. Activation of the network results in inflammation and the progressive destruction of joints and systemic symptoms characteristic of RA.

  16. Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis

    PubMed Central

    FRIESE, M A; MANUELIAN, T; JUNNIKKALA, S; HELLWAGE, J; MERI, S; PETER, H H; GORDON, D L; EIBEL, H; ZIPFEL, P F

    2003-01-01

    Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-γ and dexamethasone, whilst the pro-inflammatory cytokine TNF-α had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins. PMID:12780697

  17. Release of endogenous anti-inflammatory complement regulators FHL-1 and factor H protects synovial fibroblasts during rheumatoid arthritis.

    PubMed

    Friese, M A; Manuelian, T; Junnikkala, S; Hellwage, J; Meri, S; Peter, H H; Gordon, D L; Eibel, H; Zipfel, P F

    2003-06-01

    Rheumatoid arthritis is a chronic inflammatory disease of unknown aetiology predominantly affecting cells and tissues of synovial joints. Here we show that the two important complement regulators FHL-1 and factor H play a protective anti-inflammatory role in rheumatoid arthritis. Expression analyses at the mRNA- and protein level show in vitro expression and secretion of both regulators by synovial fibroblasts derived from patients with rheumatoid arthritis. Similarly the two regulators are synthesized in vivo in diseased synovial tissue, and in particular synovial lining cells express high levels of FHL-1. The anti-inflammatory role of these regulators in rheumatoid arthritis is highlighted by their induction with IFN-gamma and dexamethasone, whilst the pro-inflammatory cytokine TNF-alpha had no effect. Transient transfection experiments with various FHL-1/factor H promoter-luciferase reporter constructs into cells of distinct origin show independent cell and tissue specific promoter regulated transcription of these two regulators. The inducible expression, specifically of FHL-1 has physiological consequences. By binding directly to surfaces the released proteins protect cells from inflammatory damage and complement-mediated cell lysis. This study shows a novel protective and anti-inflammatory role of the two important complement regulators FHL-1 and factor H in rheumatoid arthritis and suggests a disease controlling role of the two proteins.

  18. Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

    PubMed Central

    Norling, Lucy V.; Headland, Sarah E.; Arnardottir, Hildur H.; Haworth, Oliver; Jones, Hefin R.; Serhan, Charles N.

    2016-01-01

    Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3–/–. These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA. PMID:27158677

  19. Correlation of Periodontal Disease With Inflammatory Arthritis in the Time Before Modern Medical Intervention.

    PubMed

    Rothschild, Bruce

    2017-03-01

    Controversy exists regarding possible correlation of periodontal disease with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Confounding factors may relate to stringency of inflammatory disease diagnosis and the effect of therapeutic intervention for RA on periodontal disease. These factors are investigated in this study. Forty-five individuals with documented RA (n = 15), spondyloarthropathy (n = 15), and calcium pyrophosphate deposition disease (CPPD) (n = 15), from the Hamann-Todd collection of human skeletons compiled from 1912 to 1938, and 15 individuals contemporarily incorporated in the collection were examined for tooth loss, cavity occurrence, average and maximum lingual and buccal depth of space between tooth and bone, periosteal reaction, serpentine bone resorption, abscess formation, and root penetration of the bone surface and analyzed by analysis of variance. Tooth loss was common, but actual number of teeth lost, cavity occurrence, average and maximum lingual and buccal depth of space between tooth and bone, periosteal reaction, serpentine grooving surrounding teeth (considered a sign of inflammation), abscess formation, and root exposure (penetration of bone surface) were indistinguishable among controls and individuals with RA, spondyloarthropathy, and CPPD. Although many factors can affect periodontal disease, presence of inflammatory arthritis does not appear to be one of them. The implication is that dental disease was common in the general population and not necessarily associated with arthritis, at least before the advent of modern rheumatologic medications. As specific diagnosis did not affect prevalence, perhaps current prevalence controversy may relate to current intervention, a subject for further study.

  20. Post-streptococcal acute glomerulonephritis complicated by gouty arthritis: a case report.

    PubMed

    Kuniyoshi, Yasutaka; Kamura, Azusa; Yasuda, Sumie; Tashiro, Makoto

    2015-06-17

    Gouty arthritis is uncommon in childhood and adolescence. On the other hand, there has been no report of cases with development of gouty arthritis with post-streptococcal acute glomerulonephritis (PSAGN) in pediatric patients. Here we report the case of a mildly obese 12-year-old boy with PSAGN complicated by gouty arthritis of the left first metatarsophalangeal joint. On follow-up, it was confirmed that as serum C3 level returned to normal, urinary excretion of uric acid increased and serum uric acid level decreased, thereby resolving the burning pain of the left big toe. In this case, not only did renal insufficiency associate with PSAGN but also mild obesity may have led to hyperuricemia and gouty arthritis. In conclusion, clinicians should be aware that PSAGN may be complicated by gouty arthritis in obese pediatric patients.

  1. GPR91 senses extracellular succinate released from inflammatory macrophages and exacerbates rheumatoid arthritis

    PubMed Central

    Zhang, Juan; Kneuer, Rainer

    2016-01-01

    When SUCNR1/GPR91-expressing macrophages are activated by inflammatory signals, they change their metabolism and accumulate succinate. In this study, we show that during this activation, macrophages release succinate into the extracellular milieu. They simultaneously up-regulate GPR91, which functions as an autocrine and paracrine sensor for extracellular succinate to enhance IL-1β production. GPR91-deficient mice lack this metabolic sensor and show reduced macrophage activation and production of IL-1β during antigen-induced arthritis. Succinate is abundant in synovial fluids from rheumatoid arthritis (RA) patients, and these fluids elicit IL-1β release from macrophages in a GPR91-dependent manner. Together, we reveal a GPR91/succinate-dependent feed-forward loop of macrophage activation and propose GPR91 antagonists as novel therapeutic principles to treat RA. PMID:27481132

  2. DMSO Represses Inflammatory Cytokine Production from Human Blood Cells and Reduces Autoimmune Arthritis

    PubMed Central

    Elisia, Ingrid; Nakamura, Hisae; Lam, Vivian; Hofs, Elyse; Cederberg, Rachel; Cait, Jessica; Hughes, Michael R.; Lee, Leora; Jia, William; Adomat, Hans H.; Guns, Emma S.; McNagny, Kelly M.; Samudio, Ismael; Krystal, Gerald

    2016-01-01

    Dimethyl sulfoxide (DMSO) is currently used as an alternative treatment for various inflammatory conditions as well as for cancer. Despite its widespread use, there is a paucity of data regarding its safety and efficacy as well as its mechanism of action in human cells. Herein, we demonstrate that DMSO has ex-vivo anti-inflammatory activity using Escherichia coli- (E. coli) and herpes simplex virus-1 (HSV-1)-stimulated whole human blood. Specifically, we found that between 0.5%– 2%, DMSO significantly suppressed the expression of many pro-inflammatory cytokines/chemokines and prostaglandin E2 (PGE2). However, a significant reduction in monocyte viability was also observed at 2% DMSO, suggesting a narrow window of efficacy. Anti-inflammatory concentrations of DMSO suppressed E. coli-induced ERK1/2, p38, JNK and Akt phosphorylation, suggesting DMSO acts on these signaling pathways to suppress inflammatory cytokine/chemokine production. Although DMSO induces the differentiation of B16/F10 melanoma cells in vitro, topical administration of DMSO to mice subcutaneously implanted with B16 melanoma cells was ineffective at reducing tumor growth, DMSO was also found to block mouse macrophages from polarizing to either an M1- or an M2-phenotype, which may contribute to its inability to slow tumor growth. Topical administration of DMSO, however, significantly mitigated K/BxN serum-induced arthritis in mice, and this was associated with reduced levels of pro-inflammatory cytokines in the joints and white blood cell levels in the blood. Thus, while we cannot confirm the efficacy of DMSO as an anti-cancer agent, the use of DMSO in arthritis warrants further investigation to ascertain its therapeutic potential. PMID:27031833

  3. A prospective evaluation of ultrasound as a diagnostic tool in acute microcrystalline arthritis.

    PubMed

    Zufferey, Pascal; Pascal, Zufferey; Valcov, Roxana; Fabreguet, Isabelle; Dumusc, Alexandre; Omoumi, Patrick; So, Alexander

    2015-07-22

    The performance of ultrasound (US) in the diagnosis of acute gouty (MSU) arthritis and calcium pyrophosphate (CPP) arthritis is not yet well defined. Most studies evaluated US as the basis for diagnosing crystal arthritis in already diagnosed cases of gout and few prospective studies have been performed. One hundred nine consecutive patients who presented an acute arthritis of suspected microcrystalline arthritis were prospectively included. All underwent an US of the symptomatic joints(s) and of knees, ankles and 1(st) metatarsopalangeal (MTP) joints by a rheumatologist "blinded" to the clinical history. 92 also had standard X-rays. Crystal identification was the gold standard. Fifty-one patients had MSU, 28 CPP and 9 had both crystals by microscopic analysis. No crystals were detected in 21. One had septic arthritis. Based on US signs in the symptomatic joint, the sensitivity of US for both gout and CPP was low (60% for both). In gout, the presence of US signs in the symptomatic joint was highly predictive of the diagnosis (PPV = 92%). When US diagnosis was based on an examination of multiple joints, the sensitivity for both gout and CPP rose significantly but the specificity and the PPV decreased. In the absence of US signs in all the joints studied, CPP arthritis was unlikely (NPV = 87%) particularly in patients with no previous crisis (NPV = 94%). X-ray of the symptomatic joints was confirmed to be not useful in diagnosing gout and was equally sensitive or specific as US in CPP arthritis. Arthrocenthesis remains the key investigation for the diagnosis of microcrystalline acute arthritis. Although US can help in the diagnostic process, its diagnostic performance is only moderate. US should not be limited to the symptomatic joint. Examination of multiple joints gives a better diagnostic sensitivity but lower specificity.

  4. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy.

    PubMed

    Dionne, Annie; Nicolle, Michael W; Hahn, Angelika F

    2010-02-01

    Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A-CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up.

  5. Management of the temporomandibular joint in inflammatory arthritis: Involvement of surgical procedures

    PubMed Central

    O’Connor, Rory C; Fawthrop, Fiona; Salha, Rami; Sidebottom, Andrew J

    2017-01-01

    Many conditions may affect the temporomandibular joint (TMJ), but its incidence in individual joint diseases is low. However, inflammatory arthropathies, particularly rheumatoid and psoriatic arthritis and ankylosing spondylitis, appear to have a propensity for affecting the joint. Symptoms include pain, restriction in mouth opening, locking, and noises, which together can lead to significant impairment. Jaw rest, a soft diet, a bite splint, and medical therapy, including disease-modifying antirheumatic drugs (DMARDs) and simple analgesia, are the bedrock of initial treatment and will improve most symptoms in most patients. Symptom deterioration does not necessarily follow disease progression, but when it does, TMJ arthroscopy and arthrocentesis can help modulate pain, increase mouth opening, and relieve locking. These minimally invasive procedures have few complications and can be repeated. Operations to repair or remove a damaged intra-articular disc or to refine joint anatomy are used in select cases. Total TMJ replacement is reserved for patients where joint collapse or fusion has occurred or in whom other treatments have failed to provide adequate symptomatic control. It yields excellent outcomes and is approved by the National Institute of Health and Care Excellence (NICE), UK. Knowledge of the assessment and treatment of the TMJ, which differs from other joints affected by inflammatory arthritis due to its unique anatomy and function, is not widespread outside of the field of oral and maxillofacial surgery. The aim of this article is to highlight the peculiarities of TMJ disease secondary to rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and how to best manage these ailments, which should help guide when referral to a specialist TMJ surgeon is appropriate. PMID:28638693

  6. Mechanism by which peripheral galanin increases acute inflammatory pain.

    PubMed

    Jimenez-Andrade, Juan Miguel; Zhou, Shengtai; Yamani, Ammar; Valencia de Ita, Sandra; Castañeda-Hernandez, Gilberto; Carlton, Susan M

    2005-09-21

    Galanin (GAL) is a neuropeptide involved in pain transmission. Intraplantar GAL at low doses enhances capsaicin (CAP)-induced pain behaviors in rat, suggesting an excitatory role for GAL under acute inflammatory conditions. The mechanisms underlying this pro-nociceptive action have not yet been elucidated. Thus, the present study investigated the role of protein kinase C (PKC) in the GAL enhancement of CAP-induced inflammatory pain. Ipsilateral, but not contralateral, calphostin C, a PKC inhibitor, blocked GAL-induced potentiation of CAP-evoked inflammatory pain in a dose-dependent fashion. Peripheral activation of PKC using the phorbol ester phorbol-12-myristate-13-acetate (PMA) mimicked the pro-nociceptive effect of GAL. These results suggest that GAL enhances acute inflammatory pain through activation of PKC intracellular pathways.

  7. Inflammatory arthritis in caspase-1 gene deficient mice: Contribution of proteinase 3 for caspase-1-independent production of bioactive IL-1β

    PubMed Central

    Joosten, Leo A.B.; Netea, Mihai G.; Fantuzzi, Giamila; Koenders, Marije I.; Helsen, Monique M.A.; Sparrer, Helmut; Pham, Christine T.; van der Meer, Jos W.M.; Dinarello, Charles A.; van den Berg, Wim B.

    2010-01-01

    Objective Caspase-1 is a known cysteine proteases and is a critical component of the inflammasome. Caspase-1 and neutrophil serine proteases, such as proteinase 3 (PR3) can process pro-IL-1β a crucial cytokine linked to the pathogenesis of rheumatoid arthritis, but their relative importance is unknown. Methods To this end we induced acute and chronic arthritis in caspase-1−/− mice and investigated the lack of caspase-1 on joint swelling, cartilage metabolism and joint pathology. In addition, caspase-1 activity was inhibited in mice lacking active cysteine proteases and evaluated the effect of dual blockade of caspase-1 and serine proteinase on arthritis severity and joint pathology. Results Surprisingly, caspase-1−/− mice developed joint swelling similar to wild-type mice in models of neutrophil-dominated arthritis. Joint fluid concentrations of bioactive IL-1β were comparable in caspase-1−/− mice and controls. In contrast, induction of chronic arthritis with minimal numbers of neutrophils in caspase-1−/− mice lead to reduced joint inflammation and cartilage damage, implying caspase-1 dependence. In mice lacking neutrophil serine PR3, inhibition caspase-1 activity results in decreased bioactive IL-1β concentrations in synovial tissue and less suppression of chondrocyte anabolic function. In addition, dual blockade of both PR-3 and caspase-1 lead to protection against cartilage and bone destruction. Conclusions We conclude that caspase-1 deficiency does not affect neutrophil-dominated joint inflammation, whereas in chronic arthritis the lack of caspase-1 results in reduced joint pathology. This study implies that caspase-1 inhibitors are not able to interfere with the whole spectrum of IL-1β production and hence may be of therapeutic value only in inflammatory conditions where limited numbers of neutrophils are present. PMID:19950280

  8. 11β-Hydroxysteroid Dehydrogenase Type 1, But Not Type 2, Deficiency Worsens Acute Inflammation and Experimental Arthritis in Mice

    PubMed Central

    Coutinho, Agnes E.; Gray, Mohini; Brownstein, David G.; Salter, Donald M.; Sawatzky, Deborah A.; Clay, Spike; Gilmour, James S.; Seckl, Jonathan R.; Savill, John S.

    2012-01-01

    Glucocorticoids profoundly influence immune responses, and synthetic glucocorticoids are widely used clinically for their potent antiinflammatory effects. Endogenous glucocorticoid action is modulated by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). In vivo, 11β-HSD1 catalyzes the reduction of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, thereby increasing intracellular glucocorticoid levels. 11β-HSD2 catalyzes the reverse reaction, inactivating intracellular glucocorticoids. Both enzymes have been postulated to modulate inflammatory responses. In the K/BxN serum transfer model of arthritis, 11β-HSD1-deficient mice showed earlier onset and slower resolution of inflammation than wild-type controls, with greater exostoses in periarticular bone and, uniquely, ganglion cysts, consistent with greater inflammation. In contrast, K/BxN serum arthritis was unaffected by 11β-HSD2 deficiency. In a distinct model of inflammation, thioglycollate-induced sterile peritonitis, 11β-HSD1-deficient mice had more inflammatory cells in the peritoneum, but again 11β-HSD2-deficient mice did not differ from controls. Additionally, compared with control mice, 11β-HSD1-deficient mice showed greater numbers of inflammatory cells in pleural lavages in carrageenan-induced pleurisy with lung pathology consistent with slower resolution. These data suggest that 11β-HSD1 limits acute inflammation. In contrast, 11β-HSD2 plays no role in acute inflammatory responses in mice. Regulation of local 11β-HSD1 expression and/or delivery of substrate may afford a novel approach for antiinflammatory therapy. PMID:22067318

  9. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.

    PubMed

    Ryan, Sinéad M; McMorrow, Jason; Umerska, Anita; Patel, Hetal B; Kornerup, Kristin N; Tajber, Lidia; Murphy, Evelyn P; Perretti, Mauro; Corrigan, Owen I; Brayden, David J

    2013-04-28

    Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery.

  10. Pentadecapeptide BPC 157 positively affects both non-steroidal anti-inflammatory agent-induced gastrointestinal lesions and adjuvant arthritis in rats.

    PubMed

    Sikiric, P; Seiwerth, S; Grabarevic, Z; Rucman, R; Petek, M; Jagic, V; Turkovic, B; Rotkvic, I; Mise, S; Zoricic, I; Konjevoda, P; Perovic, D; Simicevic, V; Separovic, J; Hanzevacki, M; Ljubanovic, D; Artukovic, B; Bratulic, M; Tisljar, M; Rekic, B; Gjurasin, M; Miklic, P; Buljat, G

    1997-01-01

    Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect.

  11. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... Is Juvenile Idiopathic Arthritis the same as Juvenile Rheumatoid Arthritis? Yes, Juvenile Idiopathic Arthritis (JIA) is a new ... of chronic inflammatory diseases that affect children. Juvenile Rheumatoid Arthritis (JRA) is the older term that was used ...

  12. Fibrin(ogen) mediates acute inflammatory responses to biomaterials

    PubMed Central

    1993-01-01

    Although "biocompatible" polymeric elastomers are generally nontoxic, nonimmunogenic, and chemically inert, implants made of these materials may trigger acute and chronic inflammatory responses. Early interactions between implants and inflammatory cells are probably mediated by a layer of host proteins on the material surface. To evaluate the importance of this protein layer, we studied acute inflammatory responses of mice to samples of polyester terephthalate film (PET) that were implanted intraperitoneally for short periods. Material preincubated with albumin is "passivated," accumulating very few adherent neutrophils or macrophages, whereas uncoated or plasma- coated PET attracts large numbers of phagocytes. Neither IgG adsorption nor surface complement activation is necessary for this acute inflammation; phagocyte accumulation on uncoated implants is normal in hypogammaglobulinemic mice and in severely hypocomplementemic mice. Rather, spontaneous adsorption of fibrinogen appears to be critical: (a) PET coated with serum or hypofibrinogenemic plasma attracts as few phagocytes as does albumin-coated material; (b) in contrast, PET preincubated with serum or hypofibrinogenemic plasma containing physiologic amounts of fibrinogen elicits "normal" phagocyte recruitment; (c) most importantly, hypofibrinogenemic mice do not mount an inflammatory response to implanted PET unless the material is coated with fibrinogen or the animals are injected with fibrinogen before implantation. Thus, spontaneous adsorption of fibrinogen appears to initiate the acute inflammatory response to an implanted polymer, suggesting an interesting nexus between two major iatrogenic effects of biomaterials: clotting and inflammation. PMID:8245787

  13. Prednisolone reduces experimental arthritis, and inflammatory tissue destruction in SCID mice infected with Borrelia burgdorferi.

    PubMed

    Hurtenbach, U; Böggemeyer, E; Stehle, T; Museteanu, C; Del Pozo, E; Simon, M M

    1996-05-01

    Glucocorticosteroids (GC) are widely used as anti-inflammatory agents. The effects of Prednisolone on the development of Borrelia (B.) burgdorferi-induced clinical arthritis and organ inflammation was studied in severe combined immunodeficiency (SCID) mice. The drug was administered orally at a dose of 3, 10 and 30 mg/kg, starting shortly before experimental infection of the mice. A dose dependent inhibition of arthritic joint swelling was observed. Full protection was obtained with 30 mg/kg until 21 days after infection, subsequently, mild joint swelling developed but progression and severity of the disease was considerably less than in the other treated as well as in the untreated mice. Inhibition of clinical arthritis coincided with reduction of inflammatory cell infiltration in the joints, liver and muscle. Prednisolone was ineffective when application was initiated after arthritis was fully developed, i.e., 22 days after infection. Since the activated endothelium plays a critical role in development of inflammatory lesions, the expression of the cellular adhesion molecules (CAMs) E-selectin, P-selectin, ICAM-1 and VCAM-1 was determined in vitro using the bEnd3 endothelial cell line. Stimulation with a sonicated B. burgdorferi preparation in the presence of the water-soluble compound Prednisolone-21-hemisuccinate considerably reduced expression of ICAM-1, and marginally also of E-selectin, whereas the level of P-selectin and VCAM-1 remained unaltered. Thus, downregulation of ICAM-1 might be a critical factor in Prednisolone-mediated inhibition of B. burgdorferi-induced inflammation; the flare up of the disease after the initial protection indicates that additional therapy, e.g. with antibiotics, is necessary.

  14. [EULAR recommendations for patient education of people with inflammatory arthritis. Translation and evaluation in Germany].

    PubMed

    Patermann, J; Ehlebracht-König, I; Lind-Albrecht, G; Genth, E; Reusch, A; Küffner, R; Müller-Ladner, U; Braun, J

    2016-03-01

    In 2015 EULAR published recommendations for patient education of people with inflammatory arthritis. The recommendations included two superior principles and eight recommendations based on the level of evidence and expert knowledge. The German translation of the recommendations was evaluated by 15 German experts. Experts graded the strength of the recommendations (SOR) on an 11 point numerical rating scale (from 0 = no agreement to 10 = total agreement). The mean score was 8,8 ± 0,49.

  15. Appearance of acute gouty arthritis on indium-111-labeled leukocyte scintigraphy

    SciTech Connect

    Palestro, C.J.; Vega, A.; Kim, C.K.; Swyer, A.J.; Goldsmith, S.J. )

    1990-05-01

    Indium-111-labeled leukocyte scintigraphy was performed on a 66-yr-old male with polyarticular acute gouty arthritis. Images revealed intense labeled leukocyte accumulation in a pattern indistinguishable from septic arthritis, in both knees and ankles, and the metatarsophalangeal joint of both great toes, all of which were involved in the acute gouty attack. Joint aspirate as well as blood cultures were reported as no growth; the patient was treated with intravenous colchicine and ACTH for 10 days with dramatic improvement noted. Labeled leukocyte imaging, repeated 12 days after the initial study, revealed near total resolution of joint abnormalities, concordant with the patient's clinical improvement. This case demonstrates that while acute gouty arthritis is a potential pitfall in labeled leukocyte imaging, in the presence of known gout, it may provide a simple, objective, noninvasive method of evaluating patient response to therapy.

  16. Inflammatory role of the acinar cells during acute pancreatitis

    PubMed Central

    Dios, Isabel De

    2010-01-01

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and finally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the final balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the first inflammatory signals which can mediate the activation and recruitment of circulating inflammatory cells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis. PMID:21577290

  17. Inflammatory role of the acinar cells during acute pancreatitis.

    PubMed

    Dios, Isabel De

    2010-02-06

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and finally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the final balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the first inflammatory signals which can mediate the activation and recruitment of circulating inflammatory cells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

  18. Reactive arthritis or post-infectious arthritis?

    PubMed

    Hannu, Timo; Inman, Robert; Granfors, Kaisa; Leirisalo-Repo, Marjatta

    2006-06-01

    The term 'reactive arthritis' was first used in 1969 to describe the development of sterile inflammatory arthritis as a sequel to remote infection, often in the gastrointestinal or urogenital tract. The demonstration of antigenic material (e.g. Salmonella and Yersinia lipopolysaccharide), DNA and RNA, and, in occasional cases, evidence of metabolically active Chlamydia spp. in the joints has blurred the boundary between reactive and post-infectious forms of arthritis. No validated and generally agreed diagnostic criteria exist, but the diagnosis of reactive arthritis is mainly clinical based on acute oligoarticular arthritis of larger joints that develops within 2-4 weeks of the preceding infection. In about 25% of patients, the infection can be asymptomatic. Diagnosis of the triggering infection is very helpful for the diagnosis of reactive arthritis. This is mainly achieved by isolating the triggering infection (stools, urogenital tract) by cultures (stool cultures for enteric microbes) or ligase reaction (Chlamydia trachomatis). However, after the onset of arthritis, this is less likely to be possible. Therefore, the diagnosis must rely on various serological tests to demonstrate evidence of previous infection, but, these serological tests are unfortunately not standardized. Treatment with antibiotics to cure Chlamydia infection is important, but the use of either short or prolonged courses of antibiotics in established arthritis has not been found to be effective for the cure of arthritis. The long-term outcome of reactive arthritis is usually good; however, about 25-50% of patients, depending on the triggering infections and possible new infections, subsequently develop acute arthritis. About 25% of patients proceed to chronic spondyloarthritis of varying activity.

  19. Non-classical Ly6C− monocytes drive the development of inflammatory arthritis in mice

    PubMed Central

    Misharin, Alexander V; Cuda, Carla M; Saber, Rana; Turner, Jason D; Gierut, Angelica K; Haines, G. Kenneth; Berdnikovs, Sergejs; Filer, Andrew; Clark, Andrew R; Buckley, Christopher D; Mutlu, Gökhan M; Budinger, G.R. Scott; Perlman, Harris

    2014-01-01

    Summary Different subsets and/or polarized phenotypes of monocytes and macrophages may play distinct roles during the development and resolution of inflammation. Here, we demonstrate in a murine model of rheumatoid arthritis that non-classical Ly6C− monocytes are required for the initiation and progression of sterile joint inflammation. Moreover, non-classical Ly6C− monocytes differentiate into inflammatory macrophages (M1), which drive disease pathogenesis and display plasticity during the resolution phase. During the development of arthritis, these cells polarize toward an alternatively activated phenotype (M2), promoting the resolution of joint inflammation. The influx of Ly6C− monocytes and their subsequent classical and then alternative activation occurs without changes in synovial tissue-resident macrophages, which express markers of M2 polarization throughout the course of the arthritis and attenuate joint inflammation during the initiation phase. These data suggest that circulating Ly6C− monocytes recruited to the joint upon injury orchestrate the development and resolution of autoimmune joint inflammation. PMID:25373902

  20. Inflammatory spinal disease in psoriatic arthritis: a report from the GRAPPA 2010 annual meeting.

    PubMed

    Gladman, Dafna D

    2012-02-01

    Diagnosing axial disease in patients with psoriatic arthritis (PsA) has been largely dependent on identifying inflammatory back pain (IBP), which itself has been difficult to define. We review the criteria used to identify IBP in patients with ankylosing spondylitis (AS) and other forms of spondyloarthritis. Recently, the Ankylosing SpondyloArthritis International Society (ASAS) developed a list of clinical and radiographic criteria for identifying IBP in patients with AS. However, it is more difficult to identify IBP in patients with PsA because generally they have less pain than patients with rheumatoid arthritis or AS. Further, PsA patients may have clinical symptoms of pain but negative radiographs. It may be more useful to identify sacroiliitis or syndesmophytes by magnetic resonance imaging (MRI), since MRI identifies lesions in the sacroiliac joints and the spine much earlier than can be detected on radiographs. In summary, all patients with PsA should be assessed for axial involvement with history, physical examination, and imaging. Patients with psoriasis whose history includes onset of back pain before age 40 years, the presence of night pain, and improvement with exercise but not with rest, or who have limited neck or back mobility, should be referred to a rheumatologist.

  1. Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-gamma.

    PubMed

    Kim, Eugene Y; Chi, Howard H; Bouziane, Mohammed; Gaur, Amitabh; Moudgil, Kamal D

    2008-04-01

    The pathogenesis of T cell-mediated diseases like rheumatoid arthritis (RA) has typically been explained in the context of the Th1-Th2 paradigm: the initiation/propagation by pro-inflammatory cytokines, and downregulation by Th2 cytokines. However, in our study based on the adjuvant-induced arthritis (AA) model of RA, we observed that Lewis (LEW) (RT.1(l)) rats at the recovery phase of AA showed the highest level of IFN-gamma in recall response to mycobacterial heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1(l)) rats secreted high levels of IFN-gamma much earlier following disease induction. However, no significant secretion of IL-10 or TGF-beta was observed in either strain. Furthermore, pre-treatment of LEW rats with a peptide of self (rat) hsp65 (R465), which induced T cells secreting predominantly IFN-gamma, afforded protection against AA and decreased IL-17 expression by the arthritogenic epitope-restimulated T cells. These results provide a novel perspective on the pathogenesis of autoimmune arthritis.

  2. Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologics.

    PubMed

    Barthel, Deborah; Ganser, Gerd; Kuester, Rolf-Michael; Onken, Nils; Minden, Kirsten; Girschick, Hermann Josef; Hospach, Anton; Horneff, Gerd

    2015-11-01

    Evolving inflammatory bowel disease (IBD) is a matter of interest in patients with juvenile idiopathic arthritis (JIA) and might be associated with JIA therapy. Data from the German biologics registry (Biologika in der Kinderrheumatologie; BiKeR) from 2001 to 2013 were analyzed. There were 3071 patients with 8389 patient-years (PY) of observation followed. IBD was diagnosed in 11 patients, 8 with Crohn disease and 3 with ulcerative colitis. IBD incidence in patients with JIA was 1.31/1000 PY and higher than published IBD incidences in pediatric populations. Compared with the total BiKeR cohort, patients with IBD more commonly had enthesitis-related arthritis, extended oligoarthritis, psoriatic arthritis, and also rheumatoid factor (RF)-negative polyarthritis. No IBD occurred in patients with systemic JIA or RF-positive polyarthritis. In patients treated with methotrexate (MTX), the IBD incidence was significantly lower compared with patients not treated with MTX. Etanercept (ETN) monotherapy, but not the combination of ETN and MTX, was associated with an increased incidence of IBD. Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN.

  3. Is the risk of cardiovascular disease altered with anti-inflammatory therapies? Insights from rheumatoid arthritis

    PubMed Central

    Kraakman, Michael J; Dragoljevic, Dragana; Kammoun, Helene L; Murphy, Andrew J

    2016-01-01

    Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Atherosclerosis is the most common form of CVD, which is complex and multifactorial with an elevated risk observed in people with either metabolic or inflammatory diseases. Accumulating evidence now links obesity with a state of chronic low-grade inflammation and has renewed our understanding of this condition and its associated comorbidities. An emerging theme linking disease states with atherosclerosis is the increased production of myeloid cells, which can initiate and exacerbate atherogenesis. Although anti-inflammatory drug treatments exist and have been successfully used to treat inflammatory conditions such as rheumatoid arthritis (RA), a commonly observed side effect is dyslipidemia, inadvertently, a major risk factor for the development of atherosclerosis. The mechanisms leading to dyslipidemia associated with anti-inflammatory drug use and whether CVD risk is actually increased by this dyslipidemia are of great therapeutic importance and currently remain poorly understood. Here we review recent data providing links between inflammation, hematopoiesis, dyslipidemia and CVD risk in the context of anti-inflammatory drug use. PMID:27350883

  4. [Immune mediated inflammatory pathogenesis and assessment of disease activity in rheumatoid arthritis].

    PubMed

    Yin, Geng; Wen, Fu-qiang

    2015-03-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease with synovitis and pannus formation as its basic pathologic features. Immune mediated inflammation is the core event in the occurrence and development of RA, but the inflammatory mechanism in RA pathogenesis remains unclear and needs more research to be illustrated. T cells, B cells, proinflammatory cytokine network and chemokines were confirmed to be involved in the process. In addition, the cells related to the structure of bone and joint, such as synovial cells, osteoblasts and osteoclasts, also participate in the inflammation progression of RA acting as the effector cells of immune regulation. The severity of inflammation of RA is closely related to disease activity. There are many kinds of tools for the assessment of disease activity of RA, The rationale use and optimization of these assessment tools will be helpful to make the treatment decision and improve the prognosis of RA.

  5. Imaging of inflammatory arthritis with technetium-99m-labeled IgG

    SciTech Connect

    Breedveld, F.C.; van Kroonenburgh, M.J.; Camps, J.A.; Feitsma, H.I.; Markusse, H.M.; Pauwels, E.K. )

    1989-12-01

    The accumulation of nonspecific polyclonal human immunoglobulin G (IgG) radiolabeled with 99mTc was compared to that of (99mTc)albumin and (99mTc)nanocolloid in rats with collagen induced arthritis. Serial scintigrams were acquired directly, 4 and 24 hr after injection. A clearly discernable image of the site of synovitis was seen with (99mTc)IgG as early as 4 hr postinjection. The relative intensity of the inflammatory lesion was maximal at 24 hr. Discrimination between arthritic and nonarthritic joints as well as correlations between the relative intensity of the arthritic joint and clinical indices of joint inflammation were superior with IgG compared to albumin or nanocolloid. These studies show that localization and severity of inflammatory joint disease can be detected with radiolabeled nonspecific IgG.

  6. Herbal medicinal products target defined biochemical and molecular mediators of inflammatory autoimmune arthritis

    PubMed Central

    Venkatesha, Shivaprasad H.; Berman, Brian M.; Moudgil, Kamal D.

    2010-01-01

    Rheumatoid arthritis (RA) is a chronic debilitating disease characterized by synovial inflammation, damage to cartilage and bone, and deformities of the joints. Several drugs possessing anti-inflammatory and immunomodulatory properties are being used in the conventional (allopathic) system of medicine to treat RA. However, the long-term use of these drugs is associated with harmful side effects. Therefore, newer drugs with low or no toxicity for the treatment of RA are actively being sought. Interestingly, several herbs demonstrate anti-inflammatory and anti-arthritic activity. In this review, we describe the role of the major biochemical and molecular mediators in the pathogenesis of RA, and highlight the sites of action of herbal medicinal products that have anti-arthritic activity. With the rapidly increasing use of CAM products by patients with RA and other inflammation-related disorders, our review presents timely information validating the scientific rationale for the use of natural therapeutic products. PMID:21115252

  7. Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis.

    PubMed

    Boyden, Sean D; Hossain, Imtiyaz N; Wohlfahrt, Alyssa; Lee, Yvonne C

    2016-06-01

    Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.

  8. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase•heparin complexes1

    PubMed Central

    Shin, Kichul; Nigrovic, Peter A.; Crish, James; Boilard, Eric; McNeil, H. Patrick; Larabee, Katherine S.; Adachi, Roberto; Gurish, Michael F.; Gobezie, Reuben; Stevens, Richard L.; Lee, David M.

    2008-01-01

    Although mast cells (MCs) often are abundant in the synovial tissues of patients with rheumatoid arthritis (RA), MC’s contribution to joint inflammation and cartilage loss remains poorly understood. MC-restricted tryptase•heparin complexes have pro-inflammatory activity, and significant amounts of hTryptase-β are present in RA synovial fluid. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-β, and this serine protease is abundant in the synovium of arthritic mice. We now report that C57BL/6 (B6) mice lacking their tryptase•heparin complexes have attenuated arthritic responses, with mMCP-6 as the dominant tryptase responsible for augmenting neutrophil infiltration in the K/B×N mouse serum-transfer arthritis model. While inflammation in this experimental arthritis model was not dependent on protease activated receptor-2, it was dependent on the chemokine receptor CXCR2. In support of the latter data, exposure of synovial fibroblasts to hTryptase-β•heparin or mMCP-6•heparin complexes resulted in expression of the neutrophil chemotactic factors CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8. Our proteomics, histochemistry, and immunohistochemistry data also revealed substantial loss of cartilage-derived aggrecan proteoglycans in the arthritic joints of wild-type B6 mice but not mMCP-6-null B6 mice. These observations demonstrate the functional contribution of MC-restricted tryptase•heparin complexes in the K/B×N mouse arthritis model and connect our mouse findings with RA pathophysiology. PMID:19109198

  9. Optimizing the optical wavelength for the photoacoustic imaging of inflammatory arthritis

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Xu, Guan; Hu, Jack; Francis, Sheeja; Marquardt, April; Yuan, Jie; Girish, Gandikota; Wang, Xueding

    2015-03-01

    With the capability of assessing high resolution optical information in soft tissues at imaging depth up to several centimeters, innovative biomedical photoacoustic imaging (PAI) offers benefits to diagnosis and treatment monitoring of inflammatory arthritis, particularly in combination with more established ultrasonography (US). In this work, a PAI and US dual-modality system facilitating both imaging functions in a real-time fashion was developed and initially tested for its clinical performance on patients with active inflammatory arthritis. Photoacoustic (PA) images of metacarpophalangeal (MCP) joints were acquired at 580-nm wavelength that provides a desired balance between optical absorption of blood and attenuation in background tissue. The results from six patients and six normal volunteers used as a control demonstrated the satisfactory sensitivity of PAI in assessing the physiological changes in the joints, specifically enhanced blood flow as a result of active synovitis. This preliminary study suggests that PAI, by revealing vascular features suggestive of joint inflammation, could be a valuable supplement to musculoskeletal US for rheumatology clinic.

  10. Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis.

    PubMed

    Verhoeven, Frank; Prati, Clément; Maguin-Gaté, Katy; Wendling, Daniel; Demougeot, Céline

    2016-11-05

    Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.

  11. Regulation of Early Cartilage Destruction in Inflammatory Arthritis by Death Receptor 3

    PubMed Central

    Wang, Eddie C Y; Newton, Zarabeth; Hayward, Olivia A; Clark, Stephen R; Collins, Fraser; Perks, William V; Singh, Ravinder K; Twohig, Jason P; Williams, Anwen S

    2014-01-01

    Objective To investigate the role of death receptor 3 (DR-3) and its ligand tumor necrosis factor–like molecule 1A (TL1A) in the early stages of inflammatory arthritis. Methods Antigen-induced arthritis (AIA) was generated in C57BL/6 mice deficient in the DR-3 gene (DR3−/−) and their DR3+/+ (wild-type) littermates by priming and intraarticular injection of methylated bovine serum albumin. The joints were sectioned and analyzed histochemically for damage to cartilage and expression of DR3, TL1A, Ly-6G (a marker for neutrophils), the gelatinase matrix metalloproteinase 9 (MMP-9), the aggrecanase ADAMTS-5, and the neutrophil chemoattractant CXCL1. In vitro production of MMP-9 was measured in cultures from fibroblasts, macrophages, and neutrophils following the addition of TL1A and other proinflammatory stimuli. Results DR3 expression was up-regulated in the joints of wild-type mice following generation of AIA. DR3−/− mice were protected against cartilage damage compared with wild-type mice, even at early time points prior to the main accumulation of Teff cells in the joint. Early protection against AIA in vivo correlated with reduced levels of MMP-9. In vitro, neutrophils were major producers of MMP-9, while neutrophil numbers were reduced in the joints of DR3−/− mice. However, TL1A neither induced MMP-9 release nor affected the survival of neutrophils. Instead, reduced levels of CXCL1 were observed in the joints of DR3−/− mice. Conclusion DR-3 drives early cartilage destruction in the AIA model of inflammatory arthritis through the release of CXCL1, maximizing neutrophil recruitment to the joint and leading to enhanced local production of cartilage-destroying enzymes. PMID:25044706

  12. Anti-inflammatory effects of intravenous methotrexate associated with lipid nanoemulsions on antigen-induced arthritis

    PubMed Central

    Mello, Suzana B V; Tavares, Elaine R; Guido, Maria Carolina; Bonfá, Eloisa; Maranhão, Raul C

    2016-01-01

    OBJECTIVE: To test the hypothesis that intravenous use of methotrexate associated with lipid nanoemulsions can achieve superior anti-inflammatory effects in the joints of rabbits with antigen-induced arthritis compared with commercial methotrexate. METHODS: Arthritis was induced in New Zealand rabbits sensitized with methylated bovine serum albumin and subsequently intra-articularly injected with the antigen. A nanoemulsion of methotrexate labeled with 3H-cholesteryl ether (4 mg/kg methotrexate) was then intravenously injected into four rabbits to determine the plasma decaying curves and the biodistribution of the methotrexate nanoemulsion by radioactive counting. Additionally, the pharmacokinetics of the methotrexate nanoemulsion were determined by high-pressure liquid chromatography. Twenty-four hours after arthritis induction, the animals were allocated into three groups, with intravenous injection with saline solution (n=9), methotrexate nanoemulsion (0.5 µmol/kg methotrexate, n=7), or commercial methotrexate (0.5 µmol/kg, n=4). The rabbits were sacrificed 24 h afterward. Synovial fluid was then collected for protein leakage and cell content analyses and synovial membranes were collected for histopathological analysis. RESULTS: The methotrexate nanoemulsion was taken up mainly by the liver and the uptake by arthritic joints was two-fold greater than that by control joints. The methotrexate nanoemulsion treatment reduced leukocyte influx into the synovial fluid by nearly 65%; in particular, mononuclear and polymorphonuclear cells were reduced by 47 and 72%, respectively. In contrast, cell influx was unaffected following treatment with commercial methotrexate. Protein leakage into the arthritic knees of the rabbits was also more limited following methotrexate nanoemulsion treatment than following commercial methotrexate treatment. CONCLUSIONS: The intravenous methotrexate nanoemulsion showed anti-inflammatory effects on the synovia of arthritic joints that were

  13. Focal bone involvement in inflammatory arthritis: the role of IL17.

    PubMed

    Rossini, Maurizio; Viapiana, Ombretta; Adami, Silvano; Idolazzi, Luca; Fracassi, Elena; Gatti, Davide

    2016-04-01

    Conditions such as rheumatoid arthritis (RA) and spondyloarthritis (SpA, such as psoriatic arthritis, PsA, and ankylosing spondylitis, AS) are characterized by an imbalance between osteoclast (OC) bone resorption and osteoblast (OB) bone formation. The two conditions present substantial differences in bone involvement, which is probably related to the different expression of IL17 and TNFα, two cytokines that strongly promote osteoclastogenesis and focal bone erosions. TNFα is the major inflammatory cytokine in RA. It acts by both triggering OC bone erosion via the RANK-RANKL system, and suppressing OB bone formation through the overexpression of DKK1, a powerful inhibitor of the WNT bone anabolic signaling pathway. Differing from TNFα, IL17 promotes also osteogenesis, particularly at inflamed sites undergoing mechanical stress, such as entheses. Therefore, in RA, where overexpression of TNFα is higher than IL17, OC bone resorption largely prevails upon bone formation. In PsA and AS, the prevailing inflammatory cytokine is IL17, which promotes also osteogenesis. Given the prevalent involvement of entheses poor of OC, excess bone formation may even prevail over excess bone resorption. The results of clinical trials support the different pathophysiology of bone involvement in chronic arthritis. Inflammation control through anti-TNFα agents has not resulted in incomparable effects on radiographic progression and excess bone formation in both AS and PsA. Clinical trials investigating IL17 inhibitors, such as secukinumab, in patients with psoriatic disease are underway. The preliminary results on inflammation and symptoms appear positive, while long-term studies are required to demonstrate an effect on excess bone formation.

  14. Betahistine attenuates murine collagen-induced arthritis by suppressing both inflammatory and Th17 cell responses.

    PubMed

    Tang, Kuo-Tung; Chao, Ya-Hsuan; Chen, Der-Yuan; Lim, Yun-Ping; Chen, Yi-Ming; Li, Yi-Rong; Yang, Deng-Ho; Lin, Chi-Chen

    2016-10-01

    The objective of this study was to evaluate the potential therapeutic effects of betahistine dihydrochloride (betahistine) in a collagen-induced arthritis (CIA) mouse model. CIA was induced in DBA/1 male mice by primary immunization with 100μl of emulsion containing 2mg/ml chicken type II collagen (CII) mixed with complete Freund's adjuvant (CFA) in an 1:1 ratio, and booster immunization with 100μl of emulsion containing 2mg/ml CII mixed with incomplete Freund's adjuvant (IFA) in an 1:1 ratio. Immunization was performed subcutaneously at the base of the tail. After being boosted on day 21, betahistine (1 and 5mg/kg) was orally administered daily for 2weeks. The severity of CIA was determined by arthritic scores and assessment of histopathological joint destruction. Expression of cytokines in the paw and anti-CII antibodies in the serum was evaluated by ELISA. The proliferative response against CII in the lymph node cells was measured by (3)H-thymidine incorporation assay. The frequencies of different CII specific CD4(+) T cell subsets in the lymph node were determined by flow-cytometric analysis. Betahistine treatment attenuated the severity of arthritis and reduced the levels of pro-inflammatory cytokines, including TNF-α, IL-6, IL-23 and IL-17A, in the paw tissues of CIA mice. Lymph node cells from betahistine-treated mice showed a decrease in proliferation, as well as a lower frequency of Th17 cells. In vitro, betahistine suppressed CD4(+) T cell differentiation into Th17 cells. These results indicate that betahistine is effective in suppressing both inflammatory and Th17 responses in mouse CIA and that it may have therapeutic value as an adjunct treatment for rheumatoid arthritis.

  15. Acute CD4+ T lymphocyte-dependent interleukin-1-driven arthritis selectively requires interleukin-2 and interleukin-4, joint macrophages, granulocyte-macrophage colony-stimulating factor, interleukin-6, and leukemia inhibitory factor.

    PubMed

    Lawlor, Kate E; Wong, Peter K K; Campbell, Ian K; van Rooijen, Nico; Wicks, Ian P

    2005-12-01

    To further investigate the effects of interleukin-1 (IL-1) in immune-mediated joint inflammation, we examined the role of IL-2, Th1 interferon-gamma (IFNgamma), and Th2 (IL-4) cytokines, joint macrophages, and macrophage-derived cytokines (IL-12 p40, IL-6, leukemia inhibitory factor [LIF], oncostatin M [OSM], and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in a CD4+ T lymphocyte-dependent model of acute arthritis. Methylated bovine serum albumin (mBSA)/IL-1-induced arthritis was elicited in wild-type, gene-knockout, and monoclonal antibody-treated mice. Synovial lining macrophages were selectively depleted by intraarticular injection of clodronate liposomes prior to disease induction. The severity of arthritis was assessed histologically. Mice deficient in IL-2 were almost completely protected from arthritis, and neutralization of IL-4 reduced the severity of disease. In contrast, arthritis severity and resolution appeared to be independent of IFNgamma. Synovial lining macrophage depletion markedly reduced arthritis severity. IL-6 or LIF deficiency was only modestly protective, although as previously reported, GM-CSF deficiency conferred profound disease resistance. IL-12 p40-deficient mice (which lack IL-12 and IL-23) and OSM receptor-deficient mice were susceptible to mBSA/IL-1-induced arthritis. Acute mBSA/IL-1-induced arthritis is dependent on IL-2 and IL-4, but not IFNgamma. In vivo, the Th1/Th2 paradigm may be distorted by the presence of macrophage-derived cytokines such as IL-1. Synovial lining macrophages are essential in mBSA/IL-1-induced arthritis. However, the requirement for macrophage-derived cytokines is selective; that is, IL-6, LIF, and especially GM-CSF are necessary, but IL-12, IL-23, and OSM are dispensable. IL-1 may therefore influence both adaptive and innate immune mechanisms in acute inflammatory arthritis.

  16. Inflammatory biomarkers, disease activity index, and self-reported disability may be predictors of chronic arthritis after chikungunya infection: brief report.

    PubMed

    Sepúlveda-Delgado, J; Vera-Lastra, O L; Trujillo-Murillo, K; Canseco-Ávila, L M; Sánchez-González, R A; Gómez-Cruz, O; Lugo-Trampe, A; Fernández-Salas, I; Danis-Lozano, R; Contreras-Contreras, A; Mendoza-Torres, A; Domínguez-Arrevillaga, S; Mena-Vela, B A; Ocaña-Sibilla, M; Ramirez-Valdespino, J C; Jara, L J

    2017-03-01

    The chikungunya virus (ChikV) is a reemerging mosquito-borne pathogen that causes disabling chronic arthritis. The relationship between clinical evolution and inflammatory biomarkers in patients with ChikV-induced arthritis has not been fully described. We performed a prospective case series to evaluate the association among joint involvement, self-reported disability, and inflammatory biomarkers. Patients with ChikV infection were followed for 1 year. Joint involvement and self-reported disability were evaluated with disease activity index 28 (DAS-28) and World Health Organization Disablement Assessment Schedule II (WHODAS-II). Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were used as biomarkers. Ten patients with mean age 48 ±15.04 years were included. Symptoms at diagnosis were fever, arthralgias, myalgias, rash, arthritis, nausea, vomiting, and back pain. Polyarticular involvement was present in seven cases. At diagnosis, measures were as follows: DAS-28, 5.08±1.11; WHODAS-II score, 72.3±10.3 %; CRP, 5.09±7.23 mg/dL; ESR, 33.5±17.5 mm/h; RF, 64±21.7 IU/mL; and IL-6, 17.6±10.3 pg/mL. Six patients developed subacute and chronic symptoms. During follow-up, DAS-28 index, WHODAS-II score, ESR, and IL-6 were statistically different in patients with subacute and chronic symptoms compared to those who resolved in the acute phase (p < 0.05). DAS-28 index, WHODAS-II score, and IL-6 were related to chronicity of articular symptoms and could be used as predictors of ChikV-induced arthritis.

  17. Anti-Inflammatory Effects of TRAF-Interacting Protein in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

    PubMed Central

    Yan, Shi

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammatory cell infiltration, synovial inflammation, and cartilage destruction. Proliferative fibroblast-like synoviocytes (FLS) play crucial roles in both propagation of inflammation and joint damage because of their production of great amount of proinflammatory cytokines and proteolytic enzymes. In this study, we investigate the role of TRAF-interacting protein (TRIP) in regulating inflammatory process in RA-FLS. TRIP expression was attenuated in RA-FLS compared with osteoarthritis- (OA-) FLS. Overexpression of TRIP significantly inhibited the activation of NF-κB signaling and decreased the production of proinflammatory cytokines and matrix metalloproteinases (MMPs) in TNFα-stimulated RA-FLS. Furthermore, TRIP was found to interact with transforming growth factor β-activated kinase 1 (TAK1) and promoting K48-linked polyubiquitination of TAK1 in RA-FLS. Our results demonstrate that TRIP has anti-inflammatory effects on RA-FLS and suggest TRIP as a potential therapeutic target for human RA. PMID:27847407

  18. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis

    PubMed Central

    Khandpur, Ritika; Carmona-Rivera, Carmelo; Vivekanandan-Giri, Anuradha; Gizinski, Alison; Yalavarthi, Srilakshmi; Knight, Jason S.; Friday, Sean; Li, Sam; Patel, Rajiv M.; Subramanian, Venkataraman; Thompson, Paul; Chen, Pojen; Fox, David A.; Pennathur, Subramaniam; Kaplan, Mariana J.

    2013-01-01

    The early events leading to the development of rheumatoid arthritis (RA) remain unclear but formation of autoantibodies to citrullinated antigens (ACPA) is considered a key pathogenic phenomenon. Neutrophils isolated from patients with various autoimmune diseases display enhanced extracellular trap formation (NETs), a phenomenon that externalizes autoantigens and immunostimulatory molecules. We investigated whether aberrant NETosis occurs in RA, determined its triggers and examined its deleterious inflammatory consequences. Enhanced NETosis was observed in circulating and synovial fluid RA neutrophils, compared to neutrophils from healthy controls and from patients with osteoarthritis. Further, netting neutrophils infiltrated RA synovial tissue, rheumatoid nodules and skin. NETosis correlated with ACPA presence and levels and with systemic inflammatory markers. RA sera and immunoglobulin fractions from RA patients with high levels of ACPA and/or rheumatoid factor significantly enhanced NETosis, and the NETs induced by these autoantibodies displayed distinct protein content. During NETosis, neutrophils externalized citrullinated autoantigens implicated in RA pathogenesis, whereas anti-citrullinated vimentin antibodies potently induced NET formation. The inflammatory cytokines IL-17A and TNF-α induced NETosis in RA neutrophils. In turn, NETs significantly augmented inflammatory responses in RA and OA synovial fibroblasts, including induction of IL-6, IL-8, chemokines and adhesion molecules. These observations implicate accelerated NETosis in RA pathogenesis, through externalization of citrullinated autoantigens and immunostimulatory molecules that may promote aberrant adaptive and innate immune responses in the joint and in the periphery, and perpetuate pathogenic mechanisms in this disease. PMID:23536012

  19. Multifocal inflammatory demyelination in a patient with rheumatoid arthritis and treatment complications.

    PubMed

    Lu, Jian-Qiang; Ringrose, Jennifer; Gross, Donald; Emery, Derek; Blevins, Gregg; Power, Christopher

    2016-08-15

    Rheumatoid arthritis (RA) and multiple sclerosis (MS) are both autoimmune diseases that share similar pathogenesis, but the development of MS in RA patients without the treatment of anti-tumor necrosis factor-alpha is rarely reported, which might be attributed to the use of other medications with potential immunosuppressive effects in the treatment of RA. Since MS can be clinically silent and autopsy examination of the central nervous system in RA patients is rarely described, the association of MS with RA may be possibly under-recognized. We report an autopsy case revealing multifocal inflammatory demyelination in a RA patient who had a prolonged use of methotrexate and hydroxychloroquine resulting in hydroxychloroquine-induced myopathies and heart failure. The neuropathological features of this case are consistent with MS, although there are some altered inflammatory demyelinating features such as relatively smaller lesions and less infiltration of inflammatory cells, particularly T-cells. Our present case, in combination with literature review, suggests that the RA treatment especially with hydroxychloroquine and methotrexate is likely to alter the characteristics of inflammatory demyelination and disease course. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Contribution of cyclophilin A to the regulation of inflammatory processes in rheumatoid arthritis.

    PubMed

    Wang, Li; Wang, Cong-hua; Jia, Jun-feng; Ma, Xiao-kui; Li, Yu; Zhu, Hong-bin; Tang, Hao; Chen, Zhi-nan; Zhu, Ping

    2010-01-01

    Previous studies show that cyclophilin A (CypA) acts as a strong chemotactic cytokine to neutrophils, eosinophils, and monocytes in rheumatoid arthritis (RA). In this study, monocytes were stimulated by purified CypA and the production of matrix metalloproteinase (MMPs), the cell invasion and the release of inflammatory cytokines were detected respectively by gelatin zymography, invasion assay, and cytometric bead array FCM. The elevated level of inflammatory cytokine IL-8 was also detected. Results showed that CypA significantly promoted the invasion of THP-1 cells and increased the production of MMP-2 and MMP-9, which displayed a biphasic concentration dependency. In vivo experiments found that the cartilage erosion scores in CypA injection group were significantly higher than those in control group (P < 0.05). Our findings suggest that CypA significantly enhances the secretion of MMP-2 and MMP-9, the cell invasion, and the inflammatory cytokines production of monocytes. Our findings may shed some new light on the inflammatory process and the degradation of cartilage and bone in RA.

  1. Anti-inflammatory activity of aqueous fruit pulp extract of Hunteria umbellata K. Schum in acute and chronic inflammation.

    PubMed

    Igbe, Ighodaro; Ching, Fidelis P; Eromon, Aigbe

    2010-01-01

    The anti-inflammatory effect of the aqueous fruit pulp extract of Hunteria umbellata K. Schum (Apocynaceae) was evaluated using the carrageenan- and dextran-induced rat paw edema, xylene-induced ear edema and formalin-induced arthritis inflammation tests. Oral administration of the extract produced significant (p < 0.05) antiedematogenic effect with a dose of 500 mg/kg throughout the period of the experiment in the dextran induced paw edema and at the 3 h in the carrageenan model. The extract (250 and 500 mg/kg) exhibited a dose-related and significant (p < 0.01) inhibition of xylene induced ear edema and the effect was similar to that produced by dexamethasone (1 mg/kg). In the chronic inflammation (formalin induced arthritis) the extract did not show any significant anti-inflammatory activity. Oral acute toxicity assays did not show any mortality at 15 g/kg of the plant extract. The results indicate that the aqueous extract of H. umbellata possesses acute inflammatory activity which may be mediated by either inhibition or by blocking the release of prostaglandins and histamine, thus supporting the usage of the plant in traditional medicine treatment of inflammation.

  2. A pilot evaluation of Arthritis Self-Management Program by lay leaders in patients with chronic inflammatory arthritis in Hong Kong.

    PubMed

    Leung, Ying-Ying; Kwan, Jackie; Chan, Patsy; Poon, Peter K K; Leung, Christine; Tam, Lai-Shan; Li, Edmund K; Kwok, Anna

    2016-04-01

    The objectives of this paper are to evaluate the efficacy of a community-based lay-led Arthritis Self-Management Program (ASMP) among patients with chronic inflammatory arthritis and evaluate the effectiveness of "shared care collaboration" between hospital and community. We trained 17 lay leaders and recruited patients with chronic inflammatory arthritis via a new shared-care model between hospital rheumatology centers and community organizations. Participants were allocated to interventional group or a wait list control group. Evaluations were completed before, after (6 weeks), and 3 months after ASMP. We performed analysis of covariance with adjustment with age, sex, marital status, education, employment, duration of illness, and disability at baseline. A total of 65 participants and 32 controls completed the study. The mean (SD) age and duration of illness were 52.0 (11.4) and 5.6 (7.3) years, 90.7 % were female, 80.4 % had rheumatoid arthritis; 25.8, 53.6, and 12.4 % referrals were from hospitals, community organizations, and patient self-help groups, respectively. The interventional group had significantly less pain (p = 0.049 at 6 weeks), used more cognitive coping methods (p = 0.008 at 6 weeks, p = 0.041 at 3 months) and practiced more aerobic exercise (p = 0.049 at 6 weeks, p = 0.008 at 3 months) after adjustment of covariance. The interventional group had a trend of improvement in self-efficacy, fatigue, self-rated health, and health distress. A community-based lay-led ASMP showed positive beneficial effects on participants with chronic inflammatory arthritis. Shared-care collaboration between hospitals, community organizations, and patient self-help groups was demonstrated.

  3. Marked QTc Prolongation and Torsades de pointes in Patients with Chronic Inflammatory Arthritis

    PubMed Central

    Lazzerini, Pietro Enea; Capecchi, Pier Leopoldo; Bertolozzi, Iacopo; Morozzi, Gabriella; Lorenzini, Sauro; Simpatico, Antonella; Selvi, Enrico; Bacarelli, Maria Romana; Acampa, Maurizio; Lazaro, Deana; El-Sherif, Nabil; Boutjdir, Mohamed; Laghi-Pasini, Franco

    2016-01-01

    Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about torsades de pointes (TdP) prevalence in CIA, and the few cases reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development. We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24 h from TdP/marked QTc prolongation occurrence, and levels of IL-6, TNFα, and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNFα and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other “classical” risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This fact should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required. PMID:27703966

  4. TRPM8 is the Principal Mediator of Menthol-induced Analgesia of Acute and Inflammatory Pain

    PubMed Central

    Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B.; Jordt, Sven-Eric

    2013-01-01

    Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, while other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol and WS-12 induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively with diminished side effects. PMID:23820004

  5. TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain.

    PubMed

    Liu, Boyi; Fan, Lu; Balakrishna, Shrilatha; Sui, Aiwei; Morris, John B; Jordt, Sven-Eric

    2013-10-01

    Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. It remains unclear which of these targets contribute to menthol-induced analgesia, or to the irritating side effects associated with menthol therapy. Here, we use genetic and pharmacological approaches in mice to probe the role of TRPM8 in analgesia induced by L-menthol, the predominant analgesic menthol isomer in medicinal preparations. L-menthol effectively diminished pain behavior elicited by chemical stimuli (capsaicin, acrolein, acetic acid), noxious heat, and inflammation (complete Freund's adjuvant). Genetic deletion of TRPM8 completely abolished analgesia by L-menthol in all these models, although other analgesics (acetaminophen) remained effective. Loss of L-menthol-induced analgesia was recapitulated in mice treated with a selective TRPM8 inhibitor, AMG2850. Selective activation of TRPM8 with WS-12, a menthol derivative that we characterized as a specific TRPM8 agonist in cultured sensory neurons and in vivo, also induced TRPM8-dependent analgesia of acute and inflammatory pain. L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.

  6. Acute disseminated encephalomyelitis and other inflammatory demyelinating variants.

    PubMed

    Scolding, Neil

    2014-01-01

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory central nervous system disorder characterized by acute or subacute onset of multifocal neurologic deficits with headache and impaired conscious level. Acute haemorrhagic leuoko-encephalitis (AHEM) is a more sever, often fatal variant. These disorders often follows a viral illness or vaccination, and are usually monophasic, though (probably more commonly in childhood) a multiphasic variant of ADEM is recognized. Because of the relative non-specificity of the clinical presentation (a sub-acute encephalopathy with focal signs), the differential diagnosis is wide; and distinction from the first episode of relapsing-remitting multiple sclerosis can occasionally be difficult. Here the clinical and investigational features of these disorders and their treatment are discussed.

  7. Inflammatory stimuli acutely modulate peripheral taste function.

    PubMed

    Kumarhia, Devaki; He, Lianying; McCluskey, Lynnette Phillips

    2016-06-01

    Inflammation-mediated changes in taste perception can affect health outcomes in patients, but little is known about the underlying mechanisms. In the present work, we hypothesized that proinflammatory cytokines directly modulate Na(+) transport in taste buds. To test this, we measured acute changes in Na(+) flux in polarized fungiform taste buds loaded with a Na(+) indicator dye. IL-1β elicited an amiloride-sensitive increase in Na(+) transport in taste buds. In contrast, TNF-α dramatically and reversibly decreased Na(+) flux in polarized taste buds via amiloride-sensitive and amiloride-insensitive Na(+) transport systems. The speed and partial amiloride sensitivity of these changes in Na(+) flux indicate that IL-1β and TNF-α modulate epithelial Na(+) channel (ENaC) function. A portion of the TNF-mediated decrease in Na(+) flux is also blocked by the TRPV1 antagonist capsazepine, although TNF-α further reduced Na(+) transport independently of both amiloride and capsazepine. We also assessed taste function in vivo in a model of infection and inflammation that elevates these and additional cytokines. In rats administered systemic lipopolysaccharide (LPS), CT responses to Na(+) were significantly elevated between 1 and 2 h after LPS treatment. Low, normally preferred concentrations of NaCl and sodium acetate elicited high response magnitudes. Consistent with this outcome, codelivery of IL-1β and TNF-α enhanced Na(+) flux in polarized taste buds. These results demonstrate that inflammation elicits swift changes in Na(+) taste function, which may limit salt consumption during illness. Copyright © 2016 the American Physiological Society.

  8. Inflammatory stimuli acutely modulate peripheral taste function

    PubMed Central

    Kumarhia, Devaki; He, Lianying

    2016-01-01

    Inflammation-mediated changes in taste perception can affect health outcomes in patients, but little is known about the underlying mechanisms. In the present work, we hypothesized that proinflammatory cytokines directly modulate Na+ transport in taste buds. To test this, we measured acute changes in Na+ flux in polarized fungiform taste buds loaded with a Na+ indicator dye. IL-1β elicited an amiloride-sensitive increase in Na+ transport in taste buds. In contrast, TNF-α dramatically and reversibly decreased Na+ flux in polarized taste buds via amiloride-sensitive and amiloride-insensitive Na+ transport systems. The speed and partial amiloride sensitivity of these changes in Na+ flux indicate that IL-1β and TNF-α modulate epithelial Na+ channel (ENaC) function. A portion of the TNF-mediated decrease in Na+ flux is also blocked by the TRPV1 antagonist capsazepine, although TNF-α further reduced Na+ transport independently of both amiloride and capsazepine. We also assessed taste function in vivo in a model of infection and inflammation that elevates these and additional cytokines. In rats administered systemic lipopolysaccharide (LPS), CT responses to Na+ were significantly elevated between 1 and 2 h after LPS treatment. Low, normally preferred concentrations of NaCl and sodium acetate elicited high response magnitudes. Consistent with this outcome, codelivery of IL-1β and TNF-α enhanced Na+ flux in polarized taste buds. These results demonstrate that inflammation elicits swift changes in Na+ taste function, which may limit salt consumption during illness. PMID:27009163

  9. Predictors of functional impairment and pain in erosive osteoarthritis of the interphalangeal joints: comparison with controlled inflammatory arthritis.

    PubMed

    Wittoek, Ruth; Cruyssen, Bert Vander; Verbruggen, Gust

    2012-05-01

    To compare levels of pain and functional limitation in patients with erosive osteoarthritis (OA) of the interphalangeal finger joints with those in patients with nonerosive OA and patients with controlled inflammatory arthritis affecting the hands, and to explore predictors of functional impairment in erosive OA. A cross-sectional study including 270 patients with OA of the hands who were referred to rheumatology clinics was performed. A group of patients with inflammatory arthritis (rheumatoid arthritis or psoriatic arthritis) with a low Disease Activity Score in 28 joints (<3.2; n = 79) was examined. Levels of functional impairment (measured by the Functional Index for Hand OA [FIHOA] and Australian/Canadian OA Hand Index [AUSCAN]) and pain were compared between the groups. Predictors of functional impairment in erosive OA were evaluated by generalized linear models. Of 270 patients with hand OA, 167 (61.9%) were classified as having erosive OA. Despite a higher percentage of patients taking analgesics (almost 60%), patients with erosive OA had worse functional outcome and pain scores than patients with controlled inflammatory arthritis or nonerosive OA. Pain scores remained significantly higher in patients with erosive OA after correction for potential confounders. FIHOA and AUSCAN function scores showed a trend toward more disability in patients with erosive OA. Female sex and the number of radiographic affected joints (consisting of joints in the erosive and remodeled radiographic phases) were the strongest predictors of functional impairment in erosive OA. Whether the carpometacarpal joints were affected did not influence functional status in patients with erosive OA. Our findings indicate that patients with erosive OA have more functional impairment and significantly more pain compared to patients with controlled inflammatory arthritis affecting the hands. This highlights the significant clinical burden of erosive OA and warrants the search for new treatment

  10. Urinalysis for interleukin-8 in the non-invasive diagnosis of acute and chronic inflammatory diseases

    PubMed Central

    Taha, A; Grant, V; Kelly, R

    2003-01-01

    Background and aims: Given its role in mediating inflammation, the use of urinary interleukin-8 (IL-8) was assessed in the non-invasive diagnosis of acute and chronic inflammatory diseases. Methods: IL-8 was measured by an enzyme linked immunosorbent assay in random urine samples (1 ml each) carrying code numbers and taken from 208 patients: 177 adults and 31 children presenting with a range of active or inactive inflammatory conditions. Results: In the appropriate controls and in patients with inactive inflammation, the median urinary IL-8 levels ranged from 7–12 pg/ml, compared with 104 pg/ml in active ulcerative colitis (p = 0.002), 54 in active Crohn's disease (p = 0.025), 93 in active rheumatoid arthritis (p = 0.001), 107 in acute cholecystitis (p<0.0001), 127 in acute appendicitis (p = 0.0001), and 548 pg/ml in urinary tract infection (p<0.0001). Children with non-viral inflammation/infection also had higher IL-8 values (median, 199 pg/ml; p = 0.0001) than those with viral infection (median, 7 pg/ml) or non-specific conditions (median, 10 pg/ml). In the study group as a whole urinary IL-8 values correlated positively with peripheral blood white cell count (r = 0.32; p < 0.001), erythrocyte sedimentation rate (r = 0.41; p<0.001), and C-reactive protein (r = 0.33; p<0.001). Conclusion: Taking the appropriate clinical situation into account, urinary IL-8 measurement helps in the non-invasive assessment of active inflammation in at least a number of common acute and chronic conditions. PMID:12697917

  11. The application of dual-energy computed tomography in the diagnosis of acute gouty arthritis.

    PubMed

    Wu, Huaxiang; Xue, Jing; Ye, Lu; Zhou, Qijing; Shi, Dan; Xu, Rongzhen

    2014-07-01

    The aim of the study was to investigate the sensitivity and specificity of dual-energy computed tomography in the diagnosis of acute gouty arthritis, and the related risk factors for urate crystal deposition. One hundred ninety-one patients (143 with acute gouty arthritis and 48 with other arthritic conditions) were studied. All patients had acute arthritic attack in the recent 15 days and underwent dual-energy computed tomography (DECT) scan with the affected joints. The urate volume was calculated by DECT and the basic information of these patients was recorded at the same time. Uric acid crystals were identified with DECT in 140 of 143 (97.9 %) gout patients and 6 of 48 (12.5 %) of nongout patients, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of DECT in the diagnosis of acute gouty arthritis were 97.9, 87.5, 95.9, and 93.3 %, respectively. The urate volumes were ranged from 0.57 to 54,543.27 mm(3) with a mean volume of 1,787.81 ± 7,181.54 mm(3). Interestingly, urate volume was correlated with the disease duration, serum uric acid levels, the presence of tophi, and bone erosion. Two-year follow-up data was available in one patient with recurrent gouty arthritis, whose urate volume was gradually reduced in size by DECT detection after urate-lowering therapies. DECT showed high sensitivity and specificity for the identification of urate crystals and diagnosis of acute gout. The risk factors for uric acid deposition include the disease duration, serum uric acid levels, the presence of tophi, and bone erosion. DECT has an important role in the differential diagnosis of arthritis, and also could be served as a follow-up tool.

  12. Insight into the Endocrine System and the Immune System: A Review of the Inflammatory Role of Prolactin in Rheumatoid Arthritis and Psoriatic Arthritis.

    PubMed

    Tang, Man W; Garcia, Samuel; Gerlag, Danielle M; Tak, Paul P; Reedquist, Kris A

    2017-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects females three times more frequently than males. A potential role for hormones, such as prolactin (PRL), may in part explain this phenomenon. The risk of developing RA is increased in women who are lactating after the first pregnancy, which might be related to breastfeeding and the release of PRL. Other studies found a protective effect of PRL on RA development. Some studies have reported that hyperprolactinemia is more common in RA and serum PRL levels are correlated with several disease parameters, although others could not confirm these findings. Overall the plasma PRL levels are on average not elevated in RA. Previously, a small number of open-label clinical trials using bromocriptine, which indirectly decreases PRL levels, were performed in RA patients and showed clinical benefit, although others found the opposite effect. Locally produced PRL at the site of inflammation may have a crucial role in RA as well, as it has been shown that PRL can be produced by synovial macrophages. Locally produced PRL has both pro-inflammatory and anti-inflammatory effects in arthritis. Psoriatic arthritis (PsA) is also an autoinflammatory disease, in which the prolactin receptor is also expressed in macrophages. The aim of this review is to provide an overview of the potential role of PRL signaling in inflammatory joint diseases (RA and PsA) and its potential as a therapeutic target.

  13. Trends of inflammatory markers and cytokines after one month of phototherapy in patients with rheumatoid arthritis.

    PubMed

    Meneses Calderón, José; González Sánchez, Irma; Aburto Huacuz, Guillermo; Alonso Barreto, Arely Sarai; Del Carmen Colín Ferreyra, María; Mendieta Zerón, Hugo

    2015-01-01

    to evaluate changes in the expression of tumor necrosis factor-α in patients with rheumatoid arthritis submitted to phototherapy. This was an open label study, enrolling ten patients. The phototherapy scheme within a range of 425 to 650 nm, 11.33 Joules/cm2, 30 cm above the chest was as follows: a) 45-min daily sessions from Monday to Friday for 2 to 3 months; b) three, 45- min weekly sessions for 1 to 2 months; c) twice weekly 45-min sessions for 1 to 2 months, and d) one weekly session for 1 to 2 months until completion. Erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor were measured in peripheral blood and tumor necrosis factor-α, interleukin-1β, and interleukin-10 in leukocytes by quantitative real-time Reverse transcriptase-Polymerase chain reaction. In all the patients the next indexes: Karnofsky scale, Rheumatoid Arthritis-specific quality of life instrument, Steinbrocker Functional Capacity Rating and the Visual Analog Scale were evaluated. Erythrocyte sedimentation rate, C-reactive protein, and rheumatoid factor declined notoriously after the indicated sessions. In gene expression, there was a tendency in tumor necrosis factor-α to decrease after 1 month, from 24.5±11.4 to 18±9.2 relative units, without reaching a significant statistical difference. The four tested indexes showed improvement. Phototherapy appears to be a plausible complementary option to reduce the inflammatory component in rheumatoid arthritis. Copyright © 2015 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  14. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes

    PubMed Central

    Lattuada, D.; Gualtierotti, R.; Crotta, K.; Seneci, P.; Ingegnoli, F.; Corradini, C.; Viganò, R.; Marelli, O.; Casnici, C.

    2016-01-01

    Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLSs) are apoptosis-resistant and contribute to the pathogenesis of RA by producing cytokines and proteolytic enzymes, which degrade the extracellular matrix. We evaluated the proapoptotic and anti-inflammatory activity of the small molecule Smac127 on RA-FLSs cultured in synovial fluid (SF), in order to reproduce the physiopathological environmental characteristic of RA joints. In this context, Smac127 induces apoptosis by inhibiting apoptosis proteins (IAPs). This inhibition activates caspase 3 and restores the apoptotic pathway. In addition, Smac127 induces a significant inhibition of the secretion of IL-15 and IL-6, stimulation of pannus formation, and damage of bone and cartilage in RA. Also the secretion of the anti-inflammatory cytokine IL-10 is dramatically increased in the presence of Smac127. The cartilage destruction in RA patients is partly mediated by metalloproteinases; here we show that the MMP-1 production by fibroblasts cultured in SF is significantly antagonized by Smac127. Conversely, this molecule has no significant effects on RANKL and OPG production. Our observations demonstrate that Smac127 has beneficial regulatory effects on inflammatory state of RA-FLSs and suggest a potential use of Smac127 for the control of inflammation and disease progression in RA. PMID:26989333

  15. Smac127 Has Proapoptotic and Anti-Inflammatory Effects on Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

    PubMed

    Lattuada, D; Gualtierotti, R; Crotta, K; Seneci, P; Ingegnoli, F; Corradini, C; Viganò, R; Marelli, O; Casnici, C

    2016-01-01

    Rheumatoid arthritis (RA) is characterized by synovial inflammation and hyperplasia. Fibroblast-like synoviocytes (FLSs) are apoptosis-resistant and contribute to the pathogenesis of RA by producing cytokines and proteolytic enzymes, which degrade the extracellular matrix. We evaluated the proapoptotic and anti-inflammatory activity of the small molecule Smac127 on RA-FLSs cultured in synovial fluid (SF), in order to reproduce the physiopathological environmental characteristic of RA joints. In this context, Smac127 induces apoptosis by inhibiting apoptosis proteins (IAPs). This inhibition activates caspase 3 and restores the apoptotic pathway. In addition, Smac127 induces a significant inhibition of the secretion of IL-15 and IL-6, stimulation of pannus formation, and damage of bone and cartilage in RA. Also the secretion of the anti-inflammatory cytokine IL-10 is dramatically increased in the presence of Smac127. The cartilage destruction in RA patients is partly mediated by metalloproteinases; here we show that the MMP-1 production by fibroblasts cultured in SF is significantly antagonized by Smac127. Conversely, this molecule has no significant effects on RANKL and OPG production. Our observations demonstrate that Smac127 has beneficial regulatory effects on inflammatory state of RA-FLSs and suggest a potential use of Smac127 for the control of inflammation and disease progression in RA.

  16. Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3

    PubMed Central

    Montero-Melendez, Trinidad; Madeira, Mila F.M.; Norling, Lucy V.; Alsam, Asil; Curtis, Michael A.; da Silva, Tarcília A.; Perretti, Mauro

    2015-01-01

    Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp8–γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r−/− compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics. PMID:24979595

  17. Association between periodontal disease and inflammatory arthritis reveals modulatory functions by melanocortin receptor type 3.

    PubMed

    Montero-Melendez, Trinidad; Madeira, Mila F M; Norling, Lucy V; Alsam, Asil; Curtis, Michael A; da Silva, Tarcília A; Perretti, Mauro

    2014-08-01

    Because there is clinical evidence for an association between periodontal disease and rheumatoid arthritis, it is important to develop suitable experimental models to explore pathogenic mechanisms and therapeutic opportunities. The K/BxN serum model of inflammatory arthritis was applied using distinct protocols, and modulation of joint disruption afforded by dexamethasone and calcitonin was established in comparison to the melanocortin (MC) receptor agonist DTrp(8)-γ-melanocyte stimulating hormone (MSH; DTrp). Wild-type and MC receptor type 3 (MC3)-null mice of different ages were also used. There was significant association between severity of joint disease, induced with distinct protocols and volumes of the arthritogenic K/BxN serum, and periodontal bone damage. Therapeutic treatment with 10 μg dexamethasone, 30 ng elcatonin, and 20 μg DTrp per mouse revealed unique and distinctive pharmacological properties, with only DTrp protecting both joint and periodontal tissue. Further analyses in nonarthritic animals revealed higher susceptibility to periodontal bone loss in Mc3r(-/-) compared with wild-type mice, with significant exacerbation at 14 weeks of age. These data reveal novel protective properties of endogenous MC3 on periodontal status in health and disease and indicate that MC3 activation could lead to the development of a new genus of anti-arthritic bone-sparing therapeutics. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  18. Diagnosis and treatment of heel pain in chronic inflammatory arthritis using ultrasound.

    PubMed

    Cunnane, G; Brophy, D P; Gibney, R G; FitzGerald, O

    1996-06-01

    The authors examined the role of ultrasound (US) in diagnosis and management of heel pain in chronic inflammatory arthritis. Nineteen patients underwent US examination. Eight patients (2 with previously unsuccessful nonguided injections), had 11 US-guided corticosteroid injections for treatment of retrocalcaneal bursitis (n = 6), plantar fasciitis (n = 3), and posterior tibial tenosynovitis (n = 2). US-demonstrated Achilles tendon rupture (n = 2), Achilles tendinitis (n = 8), posterior tibial tenosynovitis (n = 6), peroneus longus tenosynovitis (n = 2), retrocalcaneal bursitis (n = 13), and plantar fasciitis (n = 4). Loss of smooth bone contour (n = 13) correlated with bone erosions on plain radiographs in all but one case. Ten of 11 guided injections resulted in full resolution of heel pain. The diverse causes of heel pain are highlighted, and the ability of US to provide information with management implications is confirmed. US-guided corticosteroid injection is beneficial, especially after failure of nonguided injection.

  19. Development of a self-administered early inflammatory arthritis detection tool

    PubMed Central

    2010-01-01

    Background Barriers to care limit the potential benefits of pharmacological intervention for inflammatory arthritis. A self-administered questionnaire for early inflammatory arthritis (EIA) detection may complement contemporary triage interventions to further reduce delays to rheumatologic care. The objective of this study was to develop a self-administered EIA detection tool for implementation in pre-primary care settings. Methods A core set of dimensions and constructs for EIA detection were systematically derived from the literature and augmented by investigative team arbitration. Identified constructs were formulated into lay language questions suitable for self-administration. A three-round Delphi consensus panel of EIA experts and stakeholders evaluated the relevance of each question to EIA detection and suggested additional items. Questions accepted by less than 70% of respondents in rounds one or two were eliminated. In round three, questions accepted by at least 80% of the panel were selected for the tool. Results Of 584 citations identified, data were extracted from 47 eligible articles. Upon arbitration of the literature synthesis, 30 constructs encompassing 13 dimensions were formulated into lay language questions and posed to the Delphi panel. A total of 181 EIA experts and stakeholders participated on the Delphi panel: round one, 60; round two, 59; and, round three, 169; 48 participated in all three rounds. The panel evaluated the 30 questions derived from the literature synthesis, suggested five additional items, and eliminated a total of 24. The eleven-question instrument developed captured dimensions of articular pain, swelling, and stiffness, distribution of joint involvement, function, and diagnostic and family history. Conclusions An eleven-question, EIA detection tool suitable for self-administration was developed to screen subjects with six to 52 weeks of musculoskeletal complaints. Psychometric and performance property testing of the tool is

  20. Effects of cold mist shower on patients with inflammatory arthritis: a crossover controlled clinical trial.

    PubMed

    Hinkka, H; Väättänen, S; Ala-Peijari, S; Nummi, T

    2017-05-01

    To evaluate the safety and effects of a new home treatment method, a whole-body cold mist treatment, on patients with chronic inflammatory arthritis. Whole-body cold mist shower therapy was given to 121 voluntary patients with chronic inflammatory arthritis in this crossover study during 1-week rehabilitation periods. Pain and sleep quality were assessed by a 10-cm visual analogue scale (VAS). Mental status was assessed by the Depression Scale (DEPS). Body temperature, blood pressure, heart rate, use of occasional pain and sleep medication, and possible side-effects were recorded. The differences in pain (VAS) between treatment and control periods were significant (2.0 vs. 2.4, p = 0.006, paired t-test) in the last measurement, when assessing the pain of the past week as a whole. A trend could be seen of an increasing difference towards the end of the week. The treatment effect was statistically significant [likelihood ratio test (LRT), p < 0.0001] after controlling for period and sequence effects. There was an indication of better sleep quality (VAS) during the treatment period (2.3 vs. 2.7, p = 0.058 paired t-test) when assessing the past week as a whole. The mean DEPS scores showed no difference between the treatment periods (5.5 vs. 5.0, p = 0.1874 paired t-test, at start, and 4.5 vs. 4.1 p = 0.29 paired t-test, at the end). No significant side-effects were recorded. The new whole-body cold treatment method may offer a safe option for self-treatment of pain at home but further study is needed to determine the clinical significance of the effect after longer use.

  1. [Acute osteomyelitis and septic arthritis in children: one year experience].

    PubMed

    Timsit, S; Pannier, S; Glorion, C; Chéron, G

    2005-01-01

    To describe bacteriologic epidemiology of bone and joint infections, a total of 52 osteomyelitis, 52 arthritis and 20 osteoarthritis of children aged one month to 15 years during a one-year period (2001) were included in a retrospective unicentric review. The mean age was 3,9 +/-3,6 years. Fever and pain were the most common clinical symptoms. The site of infection was single in 95%, involving lower extremities in 80%. Bone scintigraphy was abnormal in 71% of osteomyelitis. Positive cultures was obtained in 29% of all cases (blood cultures: 20%, aspiration cultures: 29%), but in 42% of cases which have both blood and aspiration cultures. Thirty-six bacteria were identified: 19 Staphylococcus (14 aureus), ten Streptococcus (four pneumoniae), three Salmonella, three Kingella kingae, one Moraxella. All the isolates were susceptible to the empiric antibiotic therapy. Outcome was good in 100% of osteomyelitis and in 96% of arthritis.

  2. Characterization of a novel and spontaneous mouse model of inflammatory arthritis.

    PubMed

    Adipue, Iris A; Wilcox, Joel T; King, Cody; Rice, Carolyn A Y; Shaum, Katherine M; Suard, Cory M; Brink, Elri ten; Miller, Stephen D; McMahon, Eileen J

    2011-07-12

    (-)) CD3(+) TCRα/β(+) T cells in the lymphoid organs of arthritic IIJ mice suggested significant disruption in the T-cell compartment. Overall, these data identify the IIJ strain as a new murine model of inflammatory, possibly autoimmune, arthritis. The IIJ strain is similar, both histologically and serologically, to RA and other murine models of autoimmune arthritis. It may prove particularly useful for understanding the female bias in autoimmune diseases.

  3. Characterization of a novel and spontaneous mouse model of inflammatory arthritis

    PubMed Central

    2011-01-01

    double-negative (CD4-CD8-) CD3+ TCRα/β+ T cells in the lymphoid organs of arthritic IIJ mice suggested significant disruption in the T-cell compartment. Conclusions Overall, these data identify the IIJ strain as a new murine model of inflammatory, possibly autoimmune, arthritis. The IIJ strain is similar, both histologically and serologically, to RA and other murine models of autoimmune arthritis. It may prove particularly useful for understanding the female bias in autoimmune diseases. PMID:21749708

  4. Acute coronary syndromes as auto-inflammatory disorders.

    PubMed

    Suzuki, Makoto

    2012-01-01

    From the onset to the healing stage of acute coronary syndromes, an endless inflammation has been presented with complex, multiple cross-talk mechanisms at the molecular, cellular, and organ levels. Even though the early reperfusion treatment either by thrombolysis or percutaneous coronary intervention provides the excellent clinical benefits in patients with acute coronary syndromes, ischemia/ reperfusion injury may somewhat offset those great advantages. Inflammation, although potentially protective, has been deeply associated with those detrimental conditions. The hexagonal vascular inflammatory network which is composed of activated various leukocytes, vascular endothelial cells, vascular smooth muscle cells, platelets, excess reactive oxygen species, and cholesterol may contribute these vicious circles. To address these complex syndromes with more benefits regarding the prevention and treatment, this review comprehensively updates the pathogenesis of acute coronary syndromes from the view points of vascular inflammation.

  5. Immune regulation and anti-inflammatory effects of isogarcinol extracted from Garcinia mangostana L. against collagen-induced arthritis.

    PubMed

    Fu, Yanxia; Zhou, Hailing; Wang, Mengqi; Cen, Juren; Wei, Qun

    2014-05-07

    Isogarcinol is a natural compound that we extracted from Garcinia mangostana L., and we were the first to report that it is a new immunosuppressant. In the present study, we investigated the immune regulation and anti-inflammatory effects of isogarcinol on collagen-induced arthritis (CIA) and explored its potential mechanism in the treatment of rheumatoid arthritis. The oral administration of isogarcinol significantly reduced clinical scores, alleviated cartilage and bone erosion, and reduced the levels of serum inflammatory cytokines in CIA mice. Isogarcinol inhibited xylene-induced mouse ear edema in vivo. In vitro, isogarcinol decreased iNOS and COX-2 mRNA expression and NO content by inhibiting NF-κB expression. Furthermore, isogarcinol decreased the activity of NFAT and inhibited IL-2 expression. The mechanism of action of isogarcinol is associated with down-regulation of both autoimmune and inflammatory reactions.

  6. The pathogenesis of rheumatoid arthritis in radiological studies. Part I: Formation of inflammatory infiltrates within the synovial membrane.

    PubMed

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Maśliński, Włodzimierz; Prochorec-Sobieszek, Monika; Kwiatkowska, Brygida; Zaniewicz-Kaniewska, Katarzyna; Warczyńska, Agnieszka

    2012-06-01

    Rheumatoid arthritis is a chronic inflammatory disease with a multifactorial etiology and varied course, which in the majority of patients leads to partial disability or to permanent handicap. Its characteristic trait is a persistent inflammation of the synovial membrane and the formation of an invasive synovial tissue, called the pannus, which in time leads to destruction of the cartilage, subchondral bone tissue, and the soft tissue of the affected joint(s). The pathogenesis of rheumatoid arthritis is complex and involves cells of both innate and adaptive immunity, a network of various cytokines and an immunoregulatory dysfunction. An important role in the discovery of rheumatoid arthritis pathogenesis was played by magnetic resonance imaging, which showed the disease process to extend beyond the synovium into the bone marrow. Many studies have shown a strict correlation between the vascularity of the synovium (assessed through the power Doppler ultrasound and magnetic resonance examinations), bone marrow edema and the clinical, laboratory and histopathological parameters of rheumatoid arthritis. From the current understanding of rheumatoid arthritis, bone erosions could occur from two directions: from the joint cavity and from the bone marrow. With power Doppler ultrasound, as well as in magnetic resonance imaging, it is possible to visualize the well-vascularized pannus and its destructive effects on joint structures and ligaments. In addition, the magnetic resonance study shows inflammatory and destructive changes within the bone marrow (bone marrow edema, inflammatory cysts, and erosions). Bone marrow edema occurs in 68-75% of patients with early rheumatoid arthritis and is considered to be a predictor of rapid disease progression.

  7. A distinct multicytokine profile is associated with anti-cyclical citrullinated peptide antibodies in patients with early untreated inflammatory arthritis.

    PubMed

    Hitchon, Carol A; Alex, Philip; Erdile, Lawrence B; Frank, Mark B; Dozmorov, Igor; Tang, Yuhong; Wong, Keng; Centola, Michael; El-Gabalawy, Hani S

    2004-12-01

    Early inflammatory arthritis is clinically heterogenous and biologically-based indicators are needed to distinguish severe from self-limited disease. Anti-cyclical citrullinated peptides (CCP) have been identified as potential prognostic markers in early arthritis cohorts. Since cytokine networks are known to play a critical role in the pathogenesis of rheumatoid arthritis (RA) and other forms of inflammatory arthritis, a panel of pro- and antiinflammatory cytokines was measured to identify biologically-based subsets of early arthritis, relating cytokine profiles to clinical measures and to the presence of RA-associated autoantibodies. Plasma concentrations of cytokines [interleukin 1beta (IL-1beta), IL-2, IL-4, IL-5, IL-6, IL-7, CXCL8 (IL-8), IL-10, IL-12p70, IL-13, IL-17, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony stimulating factor (GM-CSF), interferon-g (IFN-g), CCL2 (monocyte chemoattractant protein-1, MCP-1), CCL4 (MIP-1beta), and tumor necrosis factor-a (TNF-a)] were measured in patients with early, untreated inflammatory arthritis [symptom duration < or = 12 months; > or = 1 swollen joint; RA, n = 41; undifferentiated arthritis (UA), n = 23]. Cytokine expression patterns were determined using cluster analysis. Both pro- and antiinflammatory cytokines were elevated in patients over controls (n = 21). RA clustered into subgroups based solely on cytokine profiles. The "mild" RA subgroup (n = 23) had higher CCL4 (MIP-1beta), CXCL8 (IL-8), IL-2, IL-12, IL-17, IL-5, and IL-10 levels, lower IL-6, IFN-g, GM-CSF, and IL-4 levels, less CCP positivity (52% vs 82%; p < 0.05), and lower CCP titers [71 (78) vs 153 (94); p < 0.01], but similar erythrocyte sedimentation rate, C-reactive protein, and joint counts compared to the "severe" RA groups. CCL4 (MIP-1beta), IL-13, IL-12, TNF-a, and IL-4 best distinguished the groups. Combining UA with RA samples preserved cytokine subgroups and strengthened the autoantibody associations. Fewer UA

  8. Safety of non-steroidal anti-inflammatory drugs, including aspirin and paracetamol (acetaminophen) in people receiving methotrexate for inflammatory arthritis (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, other spondyloarthritis).

    PubMed

    Colebatch, Alexandra N; Marks, Jonathan L; Edwards, Christopher J

    2011-11-09

    Methotrexate is routinely used in the treatment of inflammatory arthritis. There have been concerns regarding the safety of using concurrent non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, or paracetamol (acetaminophen), or both, in these people. To systematically appraise and summarise the scientific evidence on the safety of using NSAIDs, including aspirin, or paracetamol, or both, with methotrexate in inflammatory arthritis; and to identify gaps in the current evidence, assess the implications of those gaps and to make recommendations for future research to address these deficiencies. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, second quarter 2010); MEDLINE (from 1950); EMBASE (from 1980); the Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Effects (DARE). We also handsearched the conference proceedings for the American College of Rheumatology (ACR) and European League against Rheumatism (EULAR) (2008 to 2009) and checked the websites of regulatory agencies for reported adverse events, labels and warnings. Randomised controlled trials and non-randomised studies comparing the safety of methotrexate alone to methotrexate with concurrent NSAIDs, including aspirin, or paracetamol, or both, in people with inflammatory arthritis. Two authors independently assessed the search results, extracted data and assessed the risk of bias of the included studies. Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis using various NSAIDs, including aspirin. There were no identified studies for other forms of inflammatory arthritis.For NSAIDs, 13 studies were included that used concurrent NSAIDs, of which nine studies examined unspecified NSAIDs. The mean number of participants was 150.4 (range 19 to 315), mean duration 2182.9 (range 183 to 5490) days, although the study duration was

  9. The impact of inflammatory rheumatic diseases on the presentation, severity, and outcome of acute coronary syndrome.

    PubMed

    Ben-Zvi, Ilan; Goldenberg, Ilan; Matetzky, Shlomi; Grossman, Chagai; Elis, Avishay; Gavrielov-Yusim, Natalie; Livneh, Avi

    2016-01-01

    Patients with inflammatory rheumatic diseases (IRD) have a high burden of cardiovascular disease (CVD), leading to increased mortality and morbidity. However, it is not clear whether increased CVD mortality in IRD is due to a higher incidence or worse outcome of cardiovascular events (higher case fatality). In this observational case-control study, we assessed the outcome of acute coronary syndrome (ACS) in patients with IRDs compared to matched controls without IRD, using data from the Acute Coronary Syndrome Israeli Survey (ACSIS), a large, national, real-life registry detailing the extent, severity, and outcome of ACS. Of 2,193 subjects enrolled to the ACSIS, 20 (nine men) were identified with IRD, including 11 patients with rheumatoid arthritis, five patients with systemic lupus erythematosus (SLE), three patients with ankylosing spondylitis (AS), and one patient with psoriatic arthritis (PsA). The study patients were compared to 120 matched control patients (adjusted for age and risk factors for CVD) without IRD. Compared to controls, IRD patients had similar clinical presentation and similar type of ACS and received identical initial treatment at the ER. The two groups had comparable rates of complications including major adverse cardiovascular events (death, recurrent myocardial infarction, stroke, major bleeding, and definite stent thrombosis) (10 vs. 11.7% in the study and control group, respectively, p > 0.05), re-hospitalization (20 vs. 21.1%, respectively, p > 0.05), and severe congestive heart failure (7.7 vs. 6.9%, respectively, p > 0.05) within 30 days. The outcome and prognosis of ACS in patients with IRD is not worse than that of control, supporting the higher prevalence of CVD in this population as the cause for their excess mortality.

  10. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis

    PubMed Central

    Adkison, April M.; Raptis, Sofia Z.; Kelley, Diane G.; Pham, Christine T.N.

    2002-01-01

    Leukocyte recruitment in inflammation is critical for host defense, but excessive accumulation of inflammatory cells can lead to tissue damage. Neutrophil-derived serine proteases (cathepsin G [CG], neutrophil elastase [NE], and proteinase 3 [PR3]) are expressed specifically in mature neutrophils and are thought to play an important role in inflammation. To investigate the role of these proteases in inflammation, we generated a mouse deficient in dipeptidyl peptidase I (DPPI) and established that DPPI is required for the full activation of CG, NE, and PR3. Although DPPI–/– mice have normal in vitro neutrophil chemotaxis and in vivo neutrophil accumulation during sterile peritonitis, they are protected against acute arthritis induced by passive transfer of monoclonal antibodies against type II collagen. Specifically, there is no accumulation of neutrophils in the joints of DPPI–/– mice. This protective effect correlates with the inactivation of neutrophil-derived serine proteases, since NE–/– × CG–/– mice are equally resistant to arthritis induction by anti-collagen antibodies. In addition, protease-deficient mice have decreased response to zymosan- and immune complex–mediated inflammation in the subcutaneous air pouch. This defect is accompanied by a decrease in local production of TNF-α and IL-1β. These results implicate DPPI and polymorphonuclear neutrophil–derived serine proteases in the regulation of cytokine production at sites of inflammation. PMID:11827996

  11. Robust Therapeutic Efficacy of Matrix Metalloproteinase-2-Cleavable Fas-1-RGD Peptide Complex in Chronic Inflammatory Arthritis

    PubMed Central

    Sa, Keum Hee; Sung, Shijin; Park, Jae Yong; Jo, Dong-Gyu; Park, Jae Hyung; Kim, In San; Kang, Young Mo

    2016-01-01

    Objective Therapeutic agents that are transformable via introducing cleavable linkage by locally enriched MMP-2 within inflamed synovium would enhance therapeutic efficacy on chronic inflammatory arthritis. Transforming growth factor-β-inducible gene-h3 (βig-h3), which consists of four fas-1 domains and an Arg-Gly-Asp (RGD) motif, intensifies inflammatory processes by facilitating adhesion and migration of fibroblast-like synoviocyte in the pathogenesis of rheumatoid arthritis (RA). The aim of this study was to investigate whether a MMP-2-cleavable peptide complex consisting of a fas-1 domain and an RGD peptide blocks the interaction between βig-h3 and resident cells and leads to the amelioration of inflammatory arthritis. Methods We designed βig-h3-derivatives, including the fourth fas-1 domain truncated for H1 and H2 sequences of mouse (MFK00) and MMP-2-cleavable peptide complex (MFK902). MMP-2 selectivity was examined by treatment with a series of proteases. MFK902 efficacy was determined by the adhesion and migration assay with NIH3T3 cells in vitro and collagen-induced arthritis (CIA) model using male DBA/1J mice in vivo. The mice were treated intraperitoneally with MFK902 at different dosages. Results MFK902 was specifically cleaved by active MMP-2 in a concentration-dependent manner, and βig-h3-mediated adhesion and migration were more effectively inhibited by MFK902, compared with RGD or MFK00 peptides. The arthritis activity of murine CIA, measured by clinical arthritis index and incidence of arthritic paws, was significantly ameliorated after treatment with all dosages of MFK902 (1, 10, and 30 mg/kg). MFK902 ameliorated histopathologic deterioration and reduced the expression of inflammatory mediators simultaneously with improvement of clinical features. In addition, a favorable safety profile of MFK902 was demonstrated in vivo. Conclusion The present study revealed that MMP-2-cleavable peptide complex based on βig-h3 structure is a potent and safe

  12. Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis

    PubMed Central

    Chien, Ting-Yi; Huang, Steven Kuan-Hua; Lee, Chia-Jung; Tsai, Po-Wei; Wang, Ching-Chiung

    2016-01-01

    The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E2 (PGE2) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment. PMID:26901193

  13. Antinociceptive and Anti-Inflammatory Effects of Zerumbone against Mono-Iodoacetate-Induced Arthritis.

    PubMed

    Chien, Ting-Yi; Huang, Steven Kuan-Hua; Lee, Chia-Jung; Tsai, Po-Wei; Wang, Ching-Chiung

    2016-02-18

    The fresh rhizome of Zingiber zerumbet Smith (Zingiberaceae) is used as a food flavoring and also serves as a folk medicine as an antipyretic and for analgesics in Taiwan. Zerumbone, a monocyclic sesquiterpene was isolated from the rhizome of Z. zerumbet and is the major active compound. In this study, the anti-inflammatory and antinociceptive effects of zerumbone on arthritis were explored using in vitro and in vivo models. Results showed that zerumbone inhibited inducible nitric oxide (NO) synthase (iNOS), cyclooxygenase (COX)-2 expressions, and NO and prostaglandin E₂ (PGE₂) production, but induced heme oxygenase (HO)-1 expression in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. When zerumbone was co-treated with an HO-1 inhibitor (tin protoporphyrin (SnPP)), the NO inhibitory effects of zerumbone were recovered. The above results suggest that zerumbone inhibited iNOS and COX-2 through induction of the HO-1 pathway. Moreover, matrix metalloproteinase (MMP)-13 and COX-2 expressions of interleukin (IL)-1β-stimulated primary rat chondrocytes were inhibited by zerumbone. In an in vivo assay, an acetic acid-induced writhing response in mice was significantly reduced by treatment with zerumbone. Furthermore, zerumbone reduced paw edema and the pain response in a mono-iodoacetate (MIA)-induced rat osteoarthritis model. Therefore, we suggest that zerumbone possesses anti-inflammatory and antinociceptive effects which indicate zerumbone could be a potential candidate for osteoarthritis treatment.

  14. Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks: a cross-sectional study

    PubMed Central

    2014-01-01

    Introduction Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans. Methods RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model. Results Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman’s ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman’s ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman’s ρ = 0.50), BME score (P = 0.04, approximate Spearman’s ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman’s ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman’s ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance. Conclusions The association between

  15. The effects of arthritis gloves on people with Rheumatoid Arthritis or Inflammatory Arthritis with hand pain: a study protocol for a multi-centre randomised controlled trial (the A-GLOVES trial).

    PubMed

    Prior, Yeliz; Sutton, Chris; Cotterill, Sarah; Adams, Jo; Camacho, Elizabeth; Arafin, Nazina; Firth, Jill; O'Neill, Terence; Hough, Yvonne; Jones, Wendy; Hammond, Alison

    2017-05-30

    Arthritis gloves are regularly provided as part of the management of people with rheumatoid arthritis (RA) and undifferentiated (early) inflammatory arthritis (IA). Usually made of nylon and elastane (i.e. Lycra®), these arthritis gloves apply pressure with the aims of relieving hand pain, stiffness and improving hand function. However, a systematic review identified little evidence supporting their use. We therefore designed a trial to compare the effectiveness of the commonest type of arthritis glove provided in the United Kingdom (Isotoner gloves) (intervention) with placebo (control) gloves (i.e. larger arthritis gloves providing similar warmth to the intervention gloves but minimal pressure only) in people with these conditions. Participants aged 18 years and over with RA or IA and persistent hand pain will be recruited from National Health Service Trusts in the United Kingdom. Following consent, participants will complete a questionnaire booklet, then be randomly allocated to receive intervention or placebo arthritis gloves. Within three weeks, they will be fitted with the allocated gloves by clinical specialist rheumatology occupational therapists. Twelve weeks (i.e. the primary endpoint) after completing the baseline questionnaire, participants will complete a second questionnaire, including the same measures plus additional questions to explore adherence, benefits and problems with glove-wear. A sub-sample of participants from each group will be interviewed at the end of their participation to explore their views of the gloves received. The clinical effectiveness and cost-effectiveness of the intervention, compared to placebo gloves, will be evaluated over 12 weeks. The primary outcome measure is hand pain during activity. Qualitative interviews will be thematically analysed. This study will evaluate the commonest type of arthritis glove (Isotoner) provided in the NHS (i.e. the intervention) compared to a placebo glove. The results will help

  16. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    PubMed Central

    Zhu, Kou-Zhu; Liu, Yan-Li; Gu, Jin-Hua; Qin, Zheng-Hong

    2013-01-01

    To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV) in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg), the native NNAV (untreated with heat; 90 μg/kg), and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg) were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA) rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg) significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis. PMID:23634171

  17. Polyphenolics isolated from virgin coconut oil inhibits adjuvant induced arthritis in rats through antioxidant and anti-inflammatory action.

    PubMed

    Vysakh, A; Ratheesh, M; Rajmohanan, T P; Pramod, C; Premlal, S; Girish kumar, B; Sibi, P I

    2014-05-01

    We evaluated the protective efficacy of the polyphenolic fraction from virgin coconut oil (PV) against adjuvant induced arthritic rats. Arthritis was induced by intradermal injection of complete Freund's adjuvant. The activities of inflammatory, antioxidant enzymes and lipid peroxidation were estimated. PV showed high percentage of edema inhibition at a dose of 80mg/kg on 21st day of adjuvant arthritis and is non toxic. The expression of inflammatory genes such as COX-2, iNOS, TNF-α and IL-6 and the concentration of thiobarbituric acid reactive substance were decreased by treatment with PV. Antioxidant enzymes were increased and on treatment with PV. The increased level of total WBC count and C-reactive protein in the arthritic animals was reduced in PV treated rats. Synovial cytology showed that inflammatory cells and reactive mesothelial cells were suppressed by PV. Histopathology of paw tissue showed less edema formation and cellular infiltration on supplementation with PV. Thus the results demonstrated the potential beneficiary effect of PV on adjuvant induced arthritis in rats and the mechanism behind this action is due to its antioxidant and anti-inflammatory effects.

  18. Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies.

    PubMed

    Lim, Jia Pei; Devaux, Jérôme; Yuki, Nobuhiro

    2014-10-01

    Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.

  19. Carvedilol alleviates adjuvant-induced arthritis and subcutaneous air pouch edema: Modulation of oxidative stress and inflammatory mediators

    SciTech Connect

    Arab, Hany H.; El-Sawalhi, Maha M.

    2013-04-15

    Rheumatoid arthritis (RA) is a systemic inflammatory disease with cardiovascular complications as the leading cause of morbidity. Carvedilol is an adrenergic antagonist which has been safely used in treatment of several cardiovascular disorders. Given that carvedilol has powerful antioxidant/anti-inflammatory properties, we aimed to investigate its protective potential against arthritis that may add further benefits for its clinical usefulness especially in RA patients with concomitant cardiovascular disorders. Two models were studied in the same rat; adjuvant arthritis and subcutaneous air pouch edema. Carvedilol (10 mg/kg/day p.o. for 21 days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5 mg/kg/day p.o.). Notably, carvedilol inhibited paw edema and abrogated the leukocyte invasion to air pouch exudates. The latter observation was confirmed by the histopathological assessment of the pouch lining that revealed mitigation of immuno-inflammatory cell influx. Carvedilol reduced/normalized oxidative stress markers (lipid peroxides, nitric oxide and protein thiols) and lowered the release of inflammatory cytokines (TNF-α and IL-6), and eicosanoids (PGE{sub 2} and LTB{sub 4}) in sera and exudates of arthritic rats. Interestingly, carvedilol, per se, didn't present any effect on assessed biochemical parameters in normal rats. Together, the current study highlights evidences for the promising anti-arthritic effects of carvedilol that could be mediated through attenuation of leukocyte migration, alleviation of oxidative stress and suppression of proinflammatory cytokines and eicosanoids. - Highlights: ► Carvedilol possesses promising anti-arthritic properties. ► It markedly suppressed inflammation in adjuvant arthritis and air pouch edema. ► It abrogated the leukocyte invasion to air pouch exudates and linings. ► It reduced/normalized oxidative stress markers in sera and exudates of

  20. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature.

    PubMed

    Li, Xiangling; Wang, Yanqiang

    2016-07-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement.

  1. Systemic Lupus Erythematosus With Acute Inflammatory Demyelinating Polyneuropathy: A Case Report and Review of the Literature

    PubMed Central

    Li, Xiangling; Wang, Yanqiang

    2016-01-01

    We recently encountered a patient with acute inflammatory demyelinating polyneuropathy (AIDP) that was associated with systemic lupus erythematosus (SLE). A 34-year-old Chinese female with a 3-year history of SLE presented with acute bilateral leg weakness and paraparesis, and lost the ability to walk 1 day after noticing bilateral leg numbness and pain for 12 days. Physical examination revealed bilateral facial muscle paralysis, muscle strength in the legs with graded 1/5 proximally and 2/5 distally bilaterally and absence of deep tendon reflex in both knees and ankles. Paresthesia was observed in distal limbs with glove and stocking distribution. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation. Electrophysiologic survey also indicated sensory-motor demyelinating polyneuropathy. The diagnosis of SLE was established based on her initial symptoms including intermittent fevers, hair loss, oral ulcers, malar rash and arthritis affecting the elbow, wrist and hand joints; positive immunologic findings for antinuclear antibody (ANA), anti-DNA antibody, anti-Smith (anti-Sm) antibody, low serum complement levels, and the kidney biopsy specimen showed glomerular mesangial proliferation with focal endothelial cell proliferation (ISN/PPS 2004 classification lupus nephritis, class III). Treatment with intravenous immunoglobulin, methylprednisolone and cyclophosphamide resulted in clinical and electrophysiological improvement. PMID:27298667

  2. Ultrasonography and magnetic resonance imaging of heel fat pad inflammatory-oedematous lesions in rheumatoid arthritis.

    PubMed

    Falsetti, P; Frediani, B; Acciai, C; Baldi, F; Filippou, G; Galeazzi, M; Marcolongo, R

    2006-01-01

    To study heel fat pad (HFP) inflammatory-oedematous lesions in selected patients with rheumatoid arthritis (RA) using ultrasonography (US) and power Doppler US (PDUS), to describe and compare US features of these lesions with those obtained with magnetic resonance imaging (MRI), and to describe changes in the lesions after a short-term follow-up with conventional or anti-tumour necrosis factor-alpha (TNFalpha) therapy. Twelve heels of eight RA outpatients with HFP inflammatory-oedematous lesions were studied by US, PDUS, and unenhanced MRI. All the patients were followed up and US was performed after 3 months. Five patients started on anti-TNFalpha therapy. HFP lesions appeared at US as a heterogeneous and hypoechoic subcalcaneal mass, with loss of normal lobular structure and increased thickness of HFP, because of focal rupture of fibrous septae with oedema and fluid. PDUS showed peripheral vascularization of HFP lesions in 9/12 heels. In 3/12 heels some vascular signals was also detectable inside the lesion, always along the residual echoic septa. No detectable flow was observed within the central fluid-filled spaces. MRI of the HFP lesions showed areas of mean intensity in T1-weighted sequences and high intensity in T2-weighted sequences, with poorly or well-defined margins. After 3 months, PDUS showed reduction in HFP lesion vascularity (associated with reduction in pain) in 10/12 heels, while poor regression of grey-scale US abnormalities was observed. Both US and MRI are capable of demonstrating structural abnormalities in the HFP. PDUS is useful to assess and monitor inflammatory vascularization of the HFP lesions.

  3. Articular inflammation is controlled by myeloid cell-derived interleukin 1 receptor antagonist during the acute phase of arthritis in mice.

    PubMed

    Lamacchia, Céline; Rodriguez, Emiliana; Palmer, Gaby; Vigne, Solenne; Martin, Praxedis; Talabot-Ayer, Dominique; Seemayer, Christian A; Gabay, Cem

    2012-02-01

    To define the cell type (myeloid vs other cells) specific effect of interleukin 1 (IL-1) receptor antagonist (IL-1Ra) deficiency on the acute inflammatory phase of arthritis. Arthritis was induced by K/BxN serum transfer in wild-type (WT), IL-1Ra-deficient (IL-1Ra(-/-)) and conditional knockout mice. In the latter, IL-1Ra production was specifically targeted in myeloid cells (IL-1Ra(ΔM)) or in both hepatocytes and myeloid cells (IL-1Ra(ΔH+M)). Arthritis severity was clinically evaluated and ankle sections were scored for synovial inflammation and cartilage erosion. Quantitative RT-PCR, western blot and immunohistochemical analyses measured expression, localisation and cellular sources of the different IL-1Ra isoforms in arthritic joints. Total and myeloid cell-specific IL-1Ra deficiency was associated with increased arthritis severity, although disease incidence was similar to that of WT mice. Increased clinical scores were associated with exacerbated synovial inflammation. All IL-1Ra isoforms, except for intracellular (ic)IL-1Ra2, were expressed in arthritic joints of WT mice. In contrast, production of secreted (s)IL-1Ra and icIL-1Ra3 isoforms was markedly decreased in arthritic joints of both IL-1Ra(ΔM) and IL-1Ra(ΔH+M) mice. Immunohistochemical and western blot analyses suggested that the icIL-1Ra1 isoform is produced primarily by synovial fibroblasts. Myeloid cell-derived IL-1Ra, including both sIL-1Ra and icIL-1Ra3 isoforms, controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis.

  4. Activation of the cholinergic anti-inflammatory system by nicotine attenuates arthritis via suppression of macrophage migration

    PubMed Central

    Li, Sha; Zhou, Bin; Liu, Ben; Zhou, Yaou; Zhang, Huali; Li, Tong; Zuo, Xiaoxia

    2016-01-01

    Activation of the cholinergic anti-inflammatory pathway (CAP), which relies on the alpha-7 nicotinic acetylcholine receptor, has been reported to reduce proinflammatory cytokine levels in experimental arthritis. To gain more insight regarding the role of the CAP in the pathogenesis of arthritis, the present study focused on the modulation of macrophage infiltration. In a mouse model of collagen-induced arthritis (CIA), nicotine and vagotomy were used to stimulate and inhibit the CAP, respectively. Subsequently, arthritic scores were measured and histopathological assessment of joint sections was conducted. Cluster of differentiation (CD)11b-positive macrophages in the synovium were studied by immunofluorescence histochemistry. The serum levels of chemokines, including macrophage inflammatory protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1 and MIP-2 were evaluated by ELISA. Furthermore, the expression levels of C-C chemokine receptor (CCR)2 and intercellular adhesion molecule (ICAM)-1 in the synovium were evaluated by immunohistochemical staining. The results indicated that treatment with nicotine significantly attenuated the clinical and histopathological changes associated with arthritis, reduced CD11b-positive macrophages in the synovium, and downregulated the serum expression levels of MIP-1α and MCP-1. Conversely, vagotomy aggravated arthritis and upregulated the expression levels of MCP-1. However, MIP-2 expression did not differ among the control, CIA, vagotomy and nicotine groups. In addition, the expression levels of CCR2 were reduced in the nicotine group; however, they were increased in the vagotomy group compared with in the untreated CIA group. The expression levels of ICAM-1 in the synovium were also influenced by activation of the CAP. Taken together, the present results indicated that nicotine-induced activation of the CAP in mice with CIA may reduce the number of macrophages in the synovium, which may serve a role in alleviating

  5. Identification of Undiagnosed Inflammatory Arthritis in a Community Health-Fair Screen

    PubMed Central

    Deane, Kevin D.; Striebich, Christopher C.; Goldstein, Barbara L.; Derber, Lezlie A.; Parish, Mark C.; Feser, Marie L.; Hamburger, Elaine M.; Brake, Stacey; Belz, Cindy; Goddard, James; Norris, Jill M.; Karlson, Elizabeth W.; Holers, V. Michael

    2010-01-01

    Purpose The primary goals of this study were: 1) to identify individuals with undiagnosed inflammatory arthritis (IA) and rheumatoid arthritis (RA) in a community health-fair screen, and 2) to establish in a health-fair setting the diagnostic accuracy of combinations of the Connective Tissue Disease Screening Questionnaire (CSQ) and autoantibody testing for IA. Methods Screening for IA/RA was performed at health-fair sites using a combination of CSQ, joint examination, rheumatoid factor (RF) and anti-cyclic citrullinated (anti-CCP) antibody testing. IA was defined as ≥1 swollen joint/s suggestive of synovitis on joint examination by a trained clinician. Results Six-hundred one subjects were screened; 51.0% participating because of joint symptoms (pain, stiffness, or swelling). Eighty-four subjects (14.0%) had ≥1 swollen joint/s designated as IA on joint examination. Of the 601 subjects screened, 9 (1.5%) had IA and met ≥4 of 7 American College of Rheumatology criteria for RA but had no prior diagnosis of RA, and 15 (2.5%) had IA and RF and/or anti-CCP positivity, suggesting early RA. The diagnostic accuracy of combinations of CSQ and autoantibody testing for the identification of IA yielded maximal sensitivity, specificity, positive and negative predictive values of 95.3%, 99.2%, 71.4%, and 97.7%, respectively. Conclusions Health-fair screening may be an effective approach for the identification of individuals with undiagnosed IA/RA. A combination of CSQ and autoantibody testing alone has clinically useful diagnostic accuracy for the detection of IA. Decisions regarding which methodology to use for future health-fair IA/RA screening will depend on goals of screening and funding. PMID:19950306

  6. Meaningful patient engagement in inflammatory arthritis: development of the Patient Motivation Questionnaire.

    PubMed

    El Miedany, Y; El Gaafary, Maha; Youssef, Sally; El Aroussy, Nadia

    2017-04-05

    The objective of this study is to develop a questionnaire for evaluating the patient's "motivation" and assess the psychometric properties of that measure in patients with chronic inflammatory arthritis. Using Rasch analysis and questions item pool, content analysis, and semi-structured group discussion, the questionnaire was developed including 10-item scale (0-10 on VAS scale). Construct validity was assessed by correlating the questionnaire score to parameters of disease activity (DAS-28, ASDAS, and DAPSA scores), functional disability, quality of life, patient self-helplessness measure, as well as the patients' compliance to therapy. Reliability and comprehensibility and sensitivity to change were also assessed. The questionnaire was assessed in 432 RA, 415 psoriatic arthritis patients, and 232 ankylosing spondylitis patients. Dimensionality analysis revealed a 1-factor solution, explaining 98% of the total variance. It showed acceptable validity as it correlated significantly with disease activity measures: DAS-28: r = -0.85, ASDAS: r = -0.86, and DAPSA: r = -0.89. It also correlated significantly with functional disability score: r = -0.91, QoL: r = -0.90, as well as patient self-helplessness: r = -0.88. The questionnaire was reliable (Cronbach's alpha 0.958) and had no misfitting items. In addition, it was comprehensible (9.4) and sensitive to change (p < 0.01). The patient motivation score showed significant (p < 0.01) variation with the medication compliance. The measure is a patient-reported tool that is valid, reliable, comprehensible, and unidimensional scale that reflects the patients' motivation and engagement. The measure has good psychometric properties indicating that it can be used at the individual patient level to tailor management and monitor changes.

  7. Success rates of first-line antibiotics for culture-negative sub-acute and chronic septic arthritis.

    PubMed

    Chuckpaiwong, Bavornrit; Phoompoung, Saravut

    2014-09-01

    A combination of surgical and medical treatment is normally required for patients with septic arthritis. Antibiotics selected for use on these patients are normally based on tissue culture results. However, in sub-acute and chronic septic arthritis cases, the results of the culture are usually negative as a result of prior treatment. The present study will investigate the incidence of culture-negative septic arthritis and the outcomes based on the use of first-line drug antibiotics for the treatment of sub-acute and chronic septic arthritis. For the present study, the authors retrospectively reviewed medical records of surgically treated septic arthritis cases over the past 10 years at Siriraj Hospital. The patient culture results, the antibiotics used, and the results of treatment were all recorded and analyzed. One hundredfifty-three septic arthritis patients were reviewed. Sixty-two patients were classified as having been diagnosed with either sub-acute or chronic septic arthritis. Thirty-six of 62 patients (58.1%) had a negative culture result. In the culture-positive patients, 42.3% had Streptococcus, 26.9% had Staphylococcus aureus, 11.5% had other gram positive bacteria, 15.4% had gram-negative bacteria, and 3.8% had tuberculus infection. In the culture-negative sub-acute and chronic group (36 of 62), 23 patients received Cefazolin, nine patients received Cloxacillin, and four patients received Clindamycin. Successful results were 69.9%, 66.7% and 75%, respectively. The present study reflects that the incidence ofculture-negative, sub-acute and chronic septic arthritis is approximately 58.1%. The first-line class of antibiotics remains the appropriate antibiotic choice for these patients because they are still effective for treatment of septic arthritis in up to 70% of all cases.

  8. Anti-Inflammatory Effects of Polyphenolic-Enriched Red Raspberry Extract in an Antigen Induced Arthritis Rat Model†

    PubMed Central

    Jean-Gilles, Dinorah; Li, Liya; Ma, Hang; Yuan, Tao; Chichester, Clinton O.; Seeram, Navindra P.

    2011-01-01

    The red raspberry (Rubus idaeus) fruit contains bioactive polyphenols including anthocyanins and ellagitannins with reported anti-inflammatory properties. Here we sought to investigate the cartilage protecting and anti-inflammatory effects of a polyphenolic-enriched red raspberry extract (RRE; standardized to total polyphenol, anthocyanin, and ellagitannin contents) using: 1) an in vitro bovine nasal explant cell culture model and, 2) an in vivo adjuvant-induced arthritis rat model. RRE contained 20% total polyphenols (as gallic acid equivalents), 5% anthocyanins (as cyanidin-3-glucoside equivalents) and 9.25% ellagitannins (as ellagic acid equivalents). In the in vitro studies, bovine nasal explants were stimulated with 10 ng/mL IL-1β to induce the release of proteoglycan and type II collagen. On treatment with RRE (50 μg/mL), there was a decrease in the rate of degradation of both proteoglycan and type II collagen. In the in vivo antigen-induced arthritis rat model, animals were gavaged daily with RRE (at doses of 30 and 120 mg/Kg, respectively) for 30 days after adjuvant injection (750 μg of Mycobacterium tuberculosis suspension in squalene). At the higher dose, animals treated with RRE had a lower incidence and severity of arthritis compared to control animals. Also, histological analyses revealed significant inhibition of inflammation, pannus formation, cartilage damage, and bone resorption by RRE. This study suggests that red raspberry polyphenols may afford cartilage protection and/or modulate the onset and severity of arthritis. PMID:22111586

  9. A prospective comparison of telemedicine versus in-person delivery of an interprofessional education program for adults with inflammatory arthritis.

    PubMed

    Kennedy, Carol A; Warmington, Kelly; Flewelling, Carol; Shupak, Rachel; Papachristos, Angelo; Jones, Caroline; Linton, Denise; Beaton, Dorcas E; Lineker, Sydney; Hogg-Johnson, Sheilah

    2017-02-01

    Introduction We evaluated two modes of delivery of an inflammatory arthritis education program ("Prescription for Education" (RxEd)) in improving arthritis self-efficacy and other secondary outcomes. Methods We used a non-randomized, pre-post design to compare videoconferencing (R, remote using telemedicine) versus local (I, in-person) delivery of the program. Data were collected at baseline (T1), immediately following RxEd (T2), and at six months (T3). Self-report questionnaires served as the data collection tool. Measures included demographics, disorder-related, Arthritis Self-Efficacy Scale (SE), previous knowledge (Arthritis Community Research and Evaluation Unit (ACREU) rheumatoid arthritis knowledge questionnaire), coping efficacy, Illness Intrusiveness, and Effective Consumer Scale. Analysis included: baseline comparisons and longitudinal trends (R vs I groups); direct between-group comparisons; and Generalized Estimating Equations (GEE) analysis. Results A total of 123 persons attended the program (I: n = 36; R: n = 87) and 111 completed the baseline questionnaire (T1), with follow-up completed by 95% ( n = 117) at T2 and 62% ( n = 76) at T3. No significant baseline differences were found across patient characteristics and outcome measures. Both groups (R and I) showed immediate effect (improved arthritis SE, mean change (95% confidence interval (CI)): R 1.07 (0.67, 1.48); I 1.48 (0.74, 2.23)) after the program that diminished over six months (mean change (95% CI): R 0.45 (-0.1, 0.1); I 0.73 (-0.25, 1.7)). For each of the secondary outcomes, both groups showed similar trends for improvement (mean change scores (95% CI)) over time. GEE analysis did not show any meaningful differences between groups (R vs I) over time. Discussion Improvements in arthritis self-efficacy and secondary outcomes displayed similar trends for I and R participant groups.

  10. Antinociceptive effects of AS1892802, a novel Rho kinase inhibitor, in rat models of inflammatory and noninflammatory arthritis.

    PubMed

    Yoshimi, Eiji; Kumakura, Fumiyo; Hatori, Chie; Hamachi, Emi; Iwashita, Akinori; Ishii, Noe; Terasawa, Takeshi; Shimizu, Yasuaki; Takeshita, Nobuaki

    2010-09-01

    Rho kinase (ROCK) is involved in various physiological functions, including cell motility, vasoconstriction, and neurite extension. Although a functional role of ROCK in nociception in the central nervous tissue has been reported in neuropathy, the peripheral function of this protein in hyperalgesia is not known. In this study, antinociceptive effects of AS1892802 [1-[(1S)-2-hydroxy-1-phenylethyl]-3-[4-(pyridin-4-yl)phenyl]urea], a novel and highly selective ROCK inhibitor, were investigated in two rat models of arthritis. Orally administered AS1892802 exhibited potent antinociceptive effect in both an adjuvant-induced arthritis (AIA) model (inflammatory arthritis model) and a monoiodoacetate-induced arthritis (MIA) model (noninflammatory arthritis model), with an ED(50) of 0.15 mg/kg (MIA model). Fasudil, a ROCK inhibitor, and tramadol were also effective in both models; however, diclofenac was effective only in the AIA model. The onset of antinociceptive effect of AS1892802 was as fast as those of tramadol and diclofenac. AS1892802 did not induce gastric irritation or abnormal behavior. Because AS1892802 rarely penetrates the central nervous tissue and is also effective by intra-articular administration, it seemed to function peripherally. These results suggest that AS1892802 has an attractive analgesic profile for the treatment of severe osteoarthritis pain.

  11. Development of System-level Performance Measures for Evaluation of Models of Care for Inflammatory Arthritis in Canada.

    PubMed

    Barber, Claire E H; Marshall, Deborah A; Mosher, Dianne P; Akhavan, Pooneh; Tucker, Lori; Houghton, Kristin; Batthish, Michelle; Levy, Deborah M; Schmeling, Heinrike; Ellsworth, Janet; Tibollo, Heidi; Grant, Sean; Khodyakov, Dmitry; Lacaille, Diane

    2016-03-01

    To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis. This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set. Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita. The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.

  12. [Incidence of acute pancreatitis in children with inflammatory bowel disease].

    PubMed

    Stawarski, Andrzej; Iwańczak, Franciszek

    2004-07-01

    The aim of our study was to estimate the frequency of acute pancreatitis and the frequency of increased activity of pancreatic enzymes in serum of children with inflammatory bowel disease (IBD). Analysis comprises 101 children aged from 3 to 18-years treated because of IBD in the period of 1998-2002: 79 children with ulcerative colitis (UC) and 22 children Crohn's disease (CD). The authors analyzed together 191 admissions because of UC and 51 because of CD. Acute pancreatitis was observed in 4.5% of children with CD and in 5.1% of children with UC. Significantly more often acute pancreatitis was recognized in children with moderate and severe stage of UC. Hyperamylasemia was observed in 27.3% of children with CD and in 12.7% of children with UC. Hyperlipasemia was observed only in children with UC (3.8%), elevated urinary amylase was observed in 4.5% of children with CD and in 8.86% children with UC. No correlations between the frequency of acute pancreatitis and medication were observed.

  13. Anti-inflammatory properties of prostaglandin E2: deletion of microsomal prostaglandin E synthase-1 exacerbates non-immune inflammatory arthritis in mice.

    PubMed

    Frolov, Andrey; Yang, Lihua; Dong, Hua; Hammock, Bruce D; Crofford, Leslie J

    2013-10-01

    Prostanoids and PGE2 in particular have been long viewed as one of the major mediators of inflammation in arthritis. However, experimental data indicate that PGE2 can serve both pro- and anti-inflammatory functions. We have previously shown (Kojima et al., J. Immunol. 180 (2008) 8361-8368) that microsomal prostaglandin E synthase-1 (mPGES-1) deletion, which regulates PGE2 production, resulted in the suppression of collagen-induced arthritis (CIA) in mice. This suppression was attributable, at least in part, to the impaired generation of type II collagen autoantibodies. In order to examine the function of mPGES-1 and PGE2 in a non-autoimmune form of arthritis, we used the collagen antibody-induced arthritis (CAIA) model in mice deficient in mPGES-1, thereby bypassing the engagement of the adaptive immune response in arthritis development. Here we report that mPGES-1 deletion significantly increased CAIA disease severity. The latter was associated with a significant (~3.6) upregulation of neutrophil, but not macrophage, recruitment to the inflamed joints. The lipidomic analysis of the arthritic mouse paws by quantitative liquid chromatography/tandem mass-spectrometry (LC/MS/MS) revealed a dramatic (~59-fold) reduction of PGE2 at the peak of arthritis. Altogether, this study highlights mPGES-1 and its product PGE2 as important negative regulators of neutrophil-mediated inflammation and suggests that specific mPGES-1 inhibitors may have differential effects on different types of inflammation. Furthermore, neutrophil-mediated diseases could be exacerbated by inhibition of mPGES-1. © 2013 Published by Elsevier Ltd.

  14. Power Doppler ultrasound phenotyping of expanding versus collapsed popliteal lymph nodes in murine inflammatory arthritis.

    PubMed

    Bouta, Echoe M; Ju, Yawen; Rahimi, Homaira; de Mesy-Bentley, Karen L; Wood, Ronald W; Xing, Lianping; Schwarz, Edward M

    2013-01-01

    Rheumatoid arthritis is a chronic inflammatory disease manifested by episodic flares in affected joints that are challenging to predict and treat. Longitudinal contrast enhanced-MRI (CE-MRI) of inflammatory arthritis in tumor necrosis factor-transgenic (TNF-Tg) mice has demonstrated that popliteal lymph nodes (PLN) increase in volume and contrast enhancement during the pre-arthritic "expanding" phase of the disease, and then suddenly "collapse" during knee flare. Given the potential of this biomarker of arthritic flare, we aimed to develop a more cost-effective means of phenotyping PLN using ultrasound (US) imaging. Initially we attempted to recapitulate CE-MRI of PLN with subcutaneous footpad injection of US microbubbles (DEFINITY®). While this approach allowed for phenotyping via quantification of lymphatic sinuses in PLN, which showed a dramatic decrease in collapsed PLN versus expanding or wild-type (WT) PLN, electron microscopy demonstrated that DEFINITY® injection also resulted in destruction of the lymphatic vessels afferent to the PLN. In contrast, Power Doppler (PD) US is innocuous to and efficiently quantifies blood flow within PLN of WT and TNF-Tg mice. PD-US demonstrated that expanding PLN have a significantly higher normalized PD volume (NPDV) versus collapsed PLN (0.553 ± 0.007 vs. 0.008 ± 0.003; p<0.05). Moreover, we define the upper (>0.030) and lower (<0.016) quartile NPDVs in this cohort of mice, which serve as conservative thresholds to phenotype PLN as expanding and collapsed, respectively. Interestingly, of the 12 PLN phenotyped by the two methods, there was disagreement in 4 cases in which they were determined to be expanding by CE-MRI and collapsed by PD-US. Since the adjacent knee had evidence of synovitis in all 4 cases, we concluded that the PD-US phenotyping was correct, and that this approach is currently the safest and most cost-effective in vivo approach to phenotype murine PLN as a biomarker of arthritic flare.

  15. Identification of relevant functional issues for the care of patients with acute arthritis by health professionals, using the ICF framework and a multi-disciplinary focus group approach.

    PubMed

    Zochling, J; Grill, E; Alten, R; Ernst, J; Stucki, G; Braun, J

    2007-01-01

    To identify the most relevant problems to be addressed in the multi-disciplinary care of patients with acute arthritis using focus groups of health professionals followed by a Delphi process. Focus group and Delphi methodology were applied. The focus groups were conducted at three specialist rheumatology hospital clinics in Germany, each group comprising rheumatologists, nurses, physiotherapists, occupational therapists, psychologists and social workers. The participants were asked to decide which categories of the International Classification of Functioning, Disability and Health (ICF) are relevant to the care of patients with acute inflammatory arthritis. The results from the focus groups were then followed by an anonymous Delphi process. Twenty-six health professionals participated in the 3 focus groups. 167 of the second-level ICF categories (63% of all second-level categories) were considered as relevant by the rheumatology health professionals. Items from all four components, Body Functions, Body Structures, Activities and Participation and Environmental Factors were represented. Agreement between focus groups and between different health professional groups was substantial for all components with the exception of Environmental Factors (Cohen's kappa 0.23). The involvement of experts from different health professions is a valuable tool to identify typical patient characteristics, expressed as distinct ICF categories, to aid in patient care in the acute rheumatology setting. Acute patient care cannot and should not be separated from ongoing long-term management.

  16. Pellegrini-Stieda syndrome mimicking acute septic arthritis.

    PubMed

    Scheib, J S; Quinet, R J

    1989-01-01

    This case illustrates the potential severity of an uncommon and generally benign condition of the knee--the Pellegrini-Stieda syndrome. The regional bone scan clearly showed the etiologic role of the inflamed ligamentous attachment site. Therapy should include joint rest, nonsteroidal anti-inflammatory agents, and possibly ice for symptomatic relief.

  17. Near-infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute versus chronic phases of arthritis in mice.

    PubMed

    Zhou, Quan; Wood, Ronald; Schwarz, Edward M; Wang, Yong-Jun; Xing, Lianping

    2010-07-01

    To develop an in vivo imaging method to assess lymphatic draining function in the K/BxN mouse model of inflammatory arthritis. Indocyanine green, a near-infrared fluorescent dye, was injected intradermally into the footpads of wild-type mice, mouse limbs were illuminated with an 806-nm near-infrared laser, and the movement of indocyanine green from the injection site to the draining popliteal lymph node (LN) was recorded with a CCD camera. Indocyanine green near-infrared images were analyzed to obtain 5 measures of lymphatic function across time. Images of K/BxN arthritic mice and control nonarthritic littermates were obtained at 1 month of age, when acute joint inflammation commenced, and again at 3 months of age, when joint inflammation became chronic. Lymphangiogenesis in popliteal LNs was assessed by immunochemistry. Indocyanine green and its transport within lymphatic vessels were readily visualized, and quantitative measures were derived. During the acute phase of arthritis, the lymphatic vessels were dilated, with increased indocyanine green signal intensity and lymphatic pulses, and popliteal LNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, the appearance of indocyanine green in lymphatic vessels was delayed. The size and area of popliteal LN lymphatic sinuses progressively increased in the K/BxN mice. Our findings indicate that indocyanine green near-infrared lymphatic imaging is a valuable method for assessing the lymphatic draining function in mice with inflammatory arthritis. Indocyanine green-near-infrared imaging of K/BxN mice identified 2 distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders.

  18. Near infrared lymphatic imaging demonstrates the dynamics of lymph flow and lymphangiogenesis during the acute vs. chronic phases of arthritis in mice

    PubMed Central

    Zhou, Quan; Wood, Ronald; Schwarz, Edward M.; Wang, Yong-Jun; Xing, Lianping

    2010-01-01

    Objective Development of an in vivo imaging method to assess lymphatic draining function in the K/B×N mouse model of inflammatory arthritis. Methods Indocyanine green (ICG), a near-infrared (NIR) fluorescent dye, was injected intradermally into the footpad of wild-type mice, the limb was illuminated with an 806 nm NIR laser, and the movement of ICG from the injection site to the draining popliteal lymph node (PLN) was recorded with a CCD camera. ICG-NIR images were analyzed to obtain 5 measures of lymphatic function across time. K/B×N arthritic mice and control non-arthritic littermates were imaged at one-month of age when acute joint inflammation commenced, and repeated at 3 months when joint inflammation became chronic. Lymphangiogenesis in PLNs was assessed by immunochemistry. Results ICG and its transport within lymphatic vessels were readily visualized and quantitative measures derived. During the acute phase of arthritis, the lymphatic vessels were dilated with increased ICG signal intensity and lymphatic pulses, and PLNs became fluorescent quickly. During the chronic phase, new lymphatic vessels were present near the foot. However, ICG appearance in lymphatic vessels was delayed. The size and area of PLN lymphatic sinuses progressively increased in the K/B×N mice. Conclusion ICG-NIR lymphatic imaging is a valuable method to assess the lymphatic draining function in mice with inflammatory arthritis. ICG-NIR imaging of K/B×N mice identified two distinct lymphatic phenotypes during the acute and chronic phase of inflammation. This technique can be used to assess new therapies for lymphatic disorders. PMID:20309866

  19. A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis

    PubMed Central

    Boilard, Eric; Lai, Ying; Larabee, Katherine; Balestrieri, Barbara; Ghomashchi, Farideh; Fujioka, Daisuke; Gobezie, Reuben; Coblyn, Jonathan S; Weinblatt, Michael E; Massarotti, Elena M; Thornhill, Thomas S; Divangahi, Maziar; Remold, Heinz; Lambeau, Gérard; Gelb, Michael H; Arm, Jonathan P; Lee, David M

    2010-01-01

    Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation. PMID:20432503

  20. Rutoside decreases human macrophage-derived inflammatory mediators and improves clinical signs in adjuvant-induced arthritis

    PubMed Central

    Kauss, Tina; Moynet, Daniel; Rambert, Jérôme; Al-Kharrat, Abir; Brajot, Stephane; Thiolat, Denis; Ennemany, Rachid; Fawaz, Fawaz; Mossalayi, M Djavad

    2008-01-01

    Background Dietary flavonols may play an important role in the adjunct therapy of chronic inflammation. The availability of therapeutic formulations of pentahydroxyflavone glycoside, rutoside (RU), led us to investigate the ability of this molecule to modulate the release of various proinflammatory mediators from human activated macrophages in vitro and to ameliorate arthritic markers in a rat model. Methods RU was added simultaneously to human macrophages during their activation. Cells were then analyzed for inflammation-related gene expression using a specific array, and cell supernatants were collected to measure inflammatory mediators. RU was also injected into adjuvant-induced arthritic rats, and disease progression and body weight were evaluated until 50 days after injection. Sera and peritoneal macrophages were also collected to quantify the RU effect on various inflammatory markers. Results RU inhibited inflammation-related gene expression in activated human macrophages and the release of nitric oxide, tumor necrosis factor-alpha, interleukin (IL)-1, and IL-6 from these cells. In a rat model, RU inhibited clinical signs of chronic arthritis, correlating with decreased levels of inflammatory cytokines detected in rat sera and macrophage supernatants. Conclusion Thus, RU may have clinical value in reducing inflammatory manifestations in human arthritis and other inflammatory diseases. PMID:18252009

  1. A novel anti-inflammatory role for secretory phospholipase A2 in immune complex-mediated arthritis.

    PubMed

    Boilard, Eric; Lai, Ying; Larabee, Katherine; Balestrieri, Barbara; Ghomashchi, Farideh; Fujioka, Daisuke; Gobezie, Reuben; Coblyn, Jonathan S; Weinblatt, Michael E; Massarotti, Elena M; Thornhill, Thomas S; Divangahi, Maziar; Remold, Heinz; Lambeau, Gérard; Gelb, Michael H; Arm, Jonathan P; Lee, David M

    2010-05-01

    Phospholipase A2 (PLA2) catalyses the release of arachidonic acid for generation of lipid mediators of inflammation and is crucial in diverse inflammatory processes. The functions of the secretory PLA2 enzymes (sPLA2), numbering nine members in humans, are poorly understood, though they have been shown to participate in lipid mediator generation and the associated inflammation. To further understand the roles of sPLA2 in disease, we quantified the expression of these enzymes in the synovial fluid in rheumatoid arthritis and used gene-deleted mice to examine their contribution in a mouse model of autoimmune erosive inflammatory arthritis. Contrary to expectation, we find that the group V sPLA2 isoform plays a novel anti-inflammatory role that opposes the pro-inflammatory activity of group IIA sPLA2. Mechanistically, group V sPLA2 counter-regulation includes promotion of immune complex clearance by regulating cysteinyl leukotriene synthesis. These observations identify a novel anti-inflammatory function for a PLA2 and identify group V sPLA2 as a potential biotherapeutic for treatment of immune-complex-mediated inflammation.

  2. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing.

  3. Rheumatoid arthritis and periodontitis – inflammatory and infectious connections. Review of the literature

    PubMed Central

    Rutger Persson, G.

    2012-01-01

    An association between oral disease/periodontitis and rheumatoid arthritis (RA) has been considered since the early 1820s. The early treatment was tooth eradication. Epidemiological studies suggest that the prevalence of RA and periodontitis may be similar and about 5% of the population are aged 50 years or older. RA is considered as an autoimmune disease whereas periodontitis has an infectious etiology with a complex inflammatory response. Both diseases are chronic and may present with bursts of disease activity. Association studies have suggested odds ratios of having RA and periodontitis varying from 1.8:1 (95% CI: 1.0–3.2, NS) to 8:1 (95% CI: 2.9–22.1, p<0.001). Genetic factors are driving the host responses in both RA and periodontitis. Tumor necrosis factor-α, a proinflammatory cytokine, regulates a cascade of inflammatory events in both RA and periodontitis. Porphyromonas gingivalis is a common pathogen in periodontal infection. P. gingivalis has also been identified in synovial fluid. The specific abilities of P. gingivalis to citrullinate host peptides by proteolytic cleavage at Arg-X peptide bonds by arginine gingipains can induce autoimmune responses in RA through development of anticyclic citrullinated peptide antibodies. In addition, P. gingivalis carries heat shock proteins (HSPs) that may also trigger autoimmune responses in subjects with RA. Data suggest that periodontal therapies combined with routine RA treatments further improve RA status. Conclusions Periodontal infection (P. gingivalis) carries a unique risk for development of autoimmune antibodies associated with RA. Patients with RA have either lost many teeth or usually have severe periodontitis. Additional research, both in regards to basic mechanisms as well as clinical studies, are necessary before it can be said that there are causative links between RA and periodontitis. Cross-disciplinary research in well-defined populations should be performed to further enhance knowledge and

  4. Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid arthritis.

    PubMed

    Pawlik, A; Kurzawski, M; Szczepanik, T; Dziedziejko, V; Safranow, K; Borowiec-Chłopek, Z; Giedrys-Kalemba, S; Drozdzik, M

    2008-08-01

    Human allograft inflammatory factor-1 (AIF-1) is a cytoplasmic protein primarily identified in human and rat allografts, and data from several studies suggest an important role for AIF-1 in inflammatory processes. The aim of this study was to examine the association between AIF1 rs2269475:C>T polymorphism and rheumatoid arthritis (RA). AIF1 genotype was determined by means of the polymerase chain reaction-restriction fragment length polymorphism method in 276 White patients with RA and 236 healthy subjects. The frequency of the AIF1 rs2269475 TT genotype was significantly higher in the patients with RA than in the controls (OR=5.59, 95% CI: 1.22-25.55). The frequency of T allele carriers in the patient group with RA was 31.9% vs 19.1% among controls (P=0.0003). Moreover, the frequency of individuals positive for anti-cyclic citrullinated peptide (anti-CCP) antibodies was significantly elevated in the T allele carriers (OR=8.82, 95% CI: 2.06-37.7). It is noteworthy that no significant linkage disequilibria between the AIF1 C/T and DRB1 alleles associated with RA development and anti-CCP antibody production [including the most frequent, i.e. *04 (32.7%) and *01 (23.5%)] (P>0.1) were found. Our results show that the AIF1 rs2269475 T allele is associated with increased risk of RA development. Moreover, the frequency of individuals positive for anti-CCP antibodies is significantly increased among T allele carriers.

  5. Hypercortisolemia in acute stroke is related to the inflammatory response.

    PubMed

    Slowik, Agnieszka; Turaj, Wojciech; Pankiewicz, Joanna; Dziedzic, Tomasz; Szermer, Paweł; Szczudlik, Andrzej

    2002-04-15

    Hypercortisolemia is thought to be a marker of the stress response following stroke. The aim of this study was to investigate the prevalence and prognostic significance of hypercortisolemia. The circadian variation of cortisol level and the relationship between serum cortisol levels and other stress, inflammatory, and haemostatic markers were also investigated. Seventy consecutive patients with their first ischemic stroke and 24 age- and sex-matched controls were included in the study. Serum cortisol levels (at 6:00 AM, 10:00 AM, 6:00 PM, and 10:00 PM), 24-h urine catecholamine excretion, beta-thromboglobulin levels, and other standard biochemical and haematological parameters were measured on the first day of hospitalisation and in control subjects. Outcome measures used the Barthel Index at Day 30, as well as 30- and 90-day mortality rates. Hypercortisolemia, defined as at least two of the four measurements above the normal range of serum cortisol levels (i.e. >618 nmol/l from the morning samples and >460 nmol/l from the evening samples) was found in 25 (35.7%) of the acute stroke patients and in 3 (12.5%) of the controls (p<0.05). Hypercortisolemia was associated with older age, greater severity of neurological deficit, larger ischemic lesions on CT, and worse prognoses (p<0.05). The study did not find a correlation between serum cortisol levels and other markers of the stress response such as catecholamines excretion and glucose levels. A significant correlation between serum cortisol levels and some markers of the inflammatory response, such as fever, fibrinogen level, white blood cell (WBC) count, and beta-thromboglobulin level, was established in stroke patients. Prognostic significance of hypercortisolemia in acute stroke patients seems to be related to the inflammatory response rather than to the stress response.

  6. The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

    PubMed Central

    Papanagnou, Panagiota; Stivarou, Theodora; Tsironi, Maria

    2016-01-01

    MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional level. They are implicated in various processes, including cell differentiation, metabolism, and inflammation. An expanding list of miRNAs is known to be involved in the pathogenesis of common, non-autoimmune inflammatory diseases. Interestingly, osteoarthritis (OA) is now being conceptualized as a metabolic disease, as there is a correlation among hyperuricemia and metabolic syndrome (MetS). Experimental evidence suggests that metabolic deregulation is a commonality between these different pathological entities, and that miRNAs are key players in the modulation of metabolic routes. In light of these findings, this review discusses the role of miRNAs in OA and gouty arthritis, as well as the possible therapeutic targetability of miRNAs in these diseases. PMID:27845712

  7. Genetic linkage of familial granulomatous inflammatory arthritis, skin rash, and uveitis to chromosome 16

    SciTech Connect

    Tromp, G.; Kuivaniemi, H.; Ala-Kokko, L.

    1996-11-01

    Blau syndrome (MIM 186580), first described in a large, three-generation kindred, is an autosomal, dominantly inherited disease characterized by multiorgan, tissue-specific inflammation. Its clinical phenotype includes granulomatous arthritis, skin rash, and uveitis and probably represents a subtype of a group of clinical entities referred to as {open_quotes}familial granulomatosis.{close_quotes} It is the sole human model with recognizably Mendelian inheritance for a variety of multisystem inflammatory diseases affecting a significant percentage of the population. A genomewide search for the Blau susceptibility locus was undertaken after karyotypic analysis revealed no abnormalities. Sixty-two of the 74-member pedigree were genotyped with dinucleotide-repeat markers. Linkage analysis was performed under dominant model of inheritance with reduced penetrance. The marker D16S298 gave a maximum LOD score of 3.75 at {theta} = .04, with two-point analysis. LOD scores for flanking markers were consistent and placed the Blau susceptibility locus within the 16p12-q21 interval. 46 refs., 3 figs., 3 tabs.

  8. Newer, safer nonsteroidal anti-inflammatory drugs. Rational NSAID selection for arthritis.

    PubMed Central

    Bensen, W.; Zizzo, A.

    1998-01-01

    OBJECTIVE: To summarize current evidence that three new additions to nonsteroidal anti-inflammatory drugs (NSAIDs) offer comparable efficacy with fewer adverse effects than established NSAIDs. QUALITY OF EVIDENCE: No large randomized controlled trials (RCTs) have compared all important NSAIDs. Several RCTs have shown that H2 antagonists do not protect against NSAID side effects, but some RCTs compared the protective effect of misoprostol (Cytotec) used with other NSAIDs; others have compared etodolac (Ultradol) or nabumetone (Relafen) with placebo and naproxen (eg, Naprosyn). Postmarketing surveys have been used to support claims that the new NSAIDs have few gastric or renal side effects. MAIN FINDINGS: Using misoprostol in conjunction with traditional NSAIDs reduces gastric and renal adverse effects. Misoprostol can be taken at the same time as NSAIDs or in a combination tablet. Two new NSAIDS, etodolac and nabumetone, do not inhibit cyclooxygenase 1 prostaglandins, which occur in the stomach and kidneys, but more selectively block cyclooxygenase 2 prostaglandins, which cause arthritic inflammation. These two NSAIDs have efficacy profiles comparable to older NSAIDs but have markedly fewer side effects. CONCLUSIONS: Safer treatment for arthritis can be achieved by combining misoprostol with traditional NSAIDs or by using one of two new agents, nabumetone or etodolac. PMID:9481468

  9. Detection of autoantibodies to citrullinated BiP in rheumatoid arthritis patients and pro-inflammatory role of citrullinated BiP in collagen-induced arthritis

    PubMed Central

    2011-01-01

    Introduction Anti-citrullinated protein/peptide antibodies (ACPAs) are highly specific to rheumatoid arthritis (RA) patients and are thought to have a close relationship with the pathogenesis of arthritis. Several proteins, including fibrinogen, vimentin, and alpha-enolase, were reported as ACPA-target antigens, and their importance in RA pathogenesis was widely proposed. We identified citrullinated immunoglobulin binding protein (citBiP) as another ACPA target in RA patients and examined its pro-inflammatory role in arthritis. Methods We measured the levels of anti-citBiP, anti-BiP, and anti-cyclic citrullinated peptide (CCP) antibodies in the serum of RA patients (n = 100), systemic lupus erythematosus (SLE) patients (n = 60), and healthy controls (n = 30) using ELISA and immunoblotting. Epitope mapping was performed using 27 citBiP-derived peptides. In the mouse study, after DBA/1J mice were immunized with BiP or citBiP, serum titers of ACPAs were measured by ELISA and immunohistochemistry. The development of collagen-induced arthritis (CIA) was observed in BiP- or citBiP-pre-immunized mice. Results The serum levels of anti-BiP and anti-citBiP antibodies were significantly increased in RA patients, although only anti-BiP antibodies were slightly increased in SLE patients. Interestingly, anti-citBiP antibody levels were higher than anti-BiP antibody levels in 72% of RA patients, whereas no significant increase in anti-citBiP antibody levels was detected in SLE patients and healthy controls. The serum levels of anti-CCP antibodies were correlated with those of anti-citBiP antibodies in RA patients (R2 = 0.41). Several citrulline residues of citBiP were determined to be major epitopes of anti-citBiP antibodies, one of which showed cross-reactivity with CCP. Immunization of DBA/1J mice with citBiP induced several kinds of ACPAs, including anti-CCP and anti-citrullinated fibrinogen antibodies. Pre-immunization with citBiP exacerbated CIA, and anti-CCP antibody levels

  10. Chronic inflammatory appendiceal conditions that mimic acute appendicitis on helical CT.

    PubMed

    Checkoff, Jaime L; Wechsler, Richard J; Nazarian, Levon N

    2002-09-01

    Acute appendicitis is commonly diagnosed on CT, but chronic appendiceal processes can mimic acute appendicitis. The purpose of this study was to identify the frequency of these alternative conditions and their findings on helical CT. Chronic inflammatory conditions other than acute appendicitis were found in 9% of patients who underwent surgery after CT findings were interpreted as suspicious for appendicitis. These inflammatory conditions were indistinguishable from acute appendicitis when we used either primary or secondary CT signs.

  11. Are inflammatory parameters predictors of amputation in acute arterial occlusions?

    PubMed

    Saskin, Huseyin; Ozcan, Kazim S; Duzyol, Cagri; Baris, Ozgur; Koçoğulları, Uğur C

    2017-04-01

    Background The aim of the present study was to investigate the role of inflammatory markers to predict amputation following embolectomy in acute arterial occlusion. Methods A total of 123 patients operated for arterial thromboembolectomy due to acute embolism were included in the study. The patients without an extremity amputation following thromboembolectomy were classified as Group 1 ( n = 91) and the rest were classified as Group 2 ( n = 32). These groups were compared in terms of clinical and demographic characteristics, C-reactive protein, complete blood count parameters, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and red cell distribution width. Results The average age was 68.0 ± 11.7 years. The most common thromboembolism localization was femoral artery. When preoperative mean C-reactive protein ( p = 0.0001), mean platelet volume ( p = 0.0001), platelet-lymphocyte ratio ( p = 0.0001), neutrophil-lymphocyte ratio ( p = 0.0001) and red cell distribution width ( p = 0.0001) were compared, a statistically significant difference was observed between groups. In univariate and multivariate regression analysis, higher levels of preoperative C-reactive protein ( p = 0.009) and mean platelet volume ( p = 0.04) were detected as independent risk factors of early extremity amputation. Conclusion We observed that preoperative mean platelet volume and C-reactive protein were predictors of amputation after thromboembolectomy in acute arterial occlusion.

  12. Early identification of ‘acute-onset’ chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B.; Kiernan, Matthew C.

    2014-01-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  13. Evaluation of anti-inflammatory potential of the multidrug herbomineral formulation in male Wistar rats against rheumatoid arthritis

    PubMed Central

    Patel, Snehal S.; Shah, Praboth V.

    2013-01-01

    Background: Immunological and inflammatory mechanisms, which may play a role in a number of disorders like rheumatoid arthritis (RA). Ancient ayurvedic physicians had developed certain dietary and therapeutic measures to arrest or prevent these disorders. Objective: Rheuma off gold (RG) is a herbomineral formulation recommended by ayurvedic medical practitioners for treatment of RA. This study was carried out to lend scientific evidence to the efficacy claim for RG in the management of RA in folklore medicine. Materials and Methods: Arthritis was induced by complete Freund's adjuvant. Treatment with formulation 100 mg/kg and dexamethasone 2 mg/kg was given to rats intragastrically once a day from day 1 to day 21 and after which estimation of physical, biochemical, and hematological parameters were carried out. Results: Treatment of formulation to adjuvant induced arthritic animal showed statistically significant (P < 0.05) improvement in physical parameters like arthritic index, paw edema, paw thickness as well as reduction of inflammatory markers like C-reactive protein, serum rheumatoid factor, erythrocyte sedimentation rate. The treatment also produced statistically significant (P < 0.05) increase in hemoglobin percent and improvement in splenomegaly and thymus index. In the histopathological examination, ameliorative effect of formulation was observed in hyperplasia of synovium, pannus formation, and destruction of the joint space. Conclusion: The results obtained in experiments indicated that the formulation significantly inhibited the adjuvant-induced arthritis which was comparable to dexamethasone and had preferable anti-inflammatory effect without significant side effect. Thus, the formulation may be a potential preventive or therapeutic candidate for the treatment of chronic inflammation and arthritis. PMID:23930040

  14. C17 prevents inflammatory arthritis and associated joint destruction in mice.

    PubMed

    Chao, Connie; Joyce-Shaikh, Barbara; Grein, Jeff; Moshrefi, Mehrdad; Raoufi, Fahimeh; Laface, Drake M; McClanahan, Terril K; Bourne, Patricia A; Pierce, Robert H; Gorman, Daniel M; Pflanz, Stefan

    2011-01-01

    C17 was first described about ten years ago as a gene expressed in CD34+ cells. A more recent study has suggested a role for C17 in chondrogenesis and development of cartilage. However, based on sequence analysis, we believe that C17 has homology to IL-2 and hence we present the hypothesis that C17 is a cytokine possessing immune-regulatory properties. We provide evidence that C17 is a secreted protein preferentially expressed in chondrocytes, hence in cartilage-rich tissues. Systemic expression of C17 in vivo reduces disease in a collagen antibody-induced arthritis model in mice (CAIA). Joint protection is evident by delayed disease onset, minimal edema, bone protection and absence of diverse histological features of disease. Expression of genes typically associated with acute joint inflammation and erosion of cartilage or bone is blunted in the presence of C17. Consistent with the observed reduction in bone erosion, we demonstrate reduced levels of RANKL in the paws and sera of mice over-expressing C17. Administration of C17 at the peak of disease, however, had no effect on disease progression, indicating that C17's immune-regulatory activity must be most prominent prior to or at the onset of severe joint inflammation. Based on this data we propose C17 as a cytokine that s contributes to immune homeostasis systemically or in a tissue-specific manner in the joint.

  15. Macrophage inflammatory protein-1 alpha. A novel chemotactic cytokine for macrophages in rheumatoid arthritis.

    PubMed Central

    Koch, A E; Kunkel, S L; Harlow, L A; Mazarakis, D D; Haines, G K; Burdick, M D; Pope, R M; Strieter, R M

    1994-01-01

    We have shown that human macrophages (m phi s) play an important role in the elaboration of chemotactic cytokines in rheumatoid arthritis (RA) (Koch, A. E., S. L. Kunkel, J. C. Burrows, H. L. Evanoff, G. K. Haines, R. M. Pope, and R. M. Strieter. 1991. J. Immunol. 147:2187; Koch, A. E., S. L. Kunkel, L. A. Harlow, B. Johnson, H. L. Evanoff, G. K. Haines, M. D. Burdick, R. M. Pope, and R. M. Strieter. 1992. J. Clin. Invest. 90:772; Koch, A. E., P. J. Polverini, S. L. Kunkel, L. A. Harlow, L. A. DiPietro, V. M. Elner, S. G. Elner, and R. M. Strieter. 1992. Science (Wash. DC). 258:1798). Recently, m phi inflammatory protein-1 (MIP-1 alpha), a cytokine with chemotactic activity for m phi s and neutrophils (PMNs), has been described. We have examined the production of MIP-1 alpha using sera, synovial fluid (SF), and synovial tissue (ST) from 63 arthritic patients. MIP-1 alpha was higher in RA SF (mean, 29 +/- 8 ng/ml [SE]) compared with other forms of arthritis (2.8 +/- 1.7), or osteoarthritis (0.7 +/- 0.4; P < 0.05). RA SF MIP-1 alpha was greater than that found in either RA or normal peripheral blood (PB) (P < 0.05). Anti-MIP-1 alpha neutralized 36 +/- 3% (mean +/- SE) of the chemotactic activity for m phi s, but not PMNs, found in RA SFs. RA SF and PB mononuclear cells produced antigenic MIP-1 alpha. Mononuclear cell MIP-1 alpha production was augmented with phytohemagglutinin or LPS. Isolated RA ST fibroblast production of antigenic MIP-1 alpha was augmented upon incubation of cells with LPS, and to a lesser extent with tumor necrosis factor-alpha. Isolated RA ST m phi s expressed constitutive MIP-1 alpha mRNA and antigenic MIP-1 alpha. Using ST immunohistochemistry, MIP-1 alpha+ cells from RA compared with normal were predominantly m phi s and lining cells (P < 0.05). These results suggest that MIP-1 alpha plays a role in the selective recruitment of m phi s in synovial inflammation associated with RA. Images PMID:8132778

  16. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*

    PubMed Central

    Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2014-01-01

    The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

  17. Grape polyphenols and propolis mixture inhibits inflammatory mediator release from human leukocytes and reduces clinical scores in experimental arthritis.

    PubMed

    Mossalayi, M D; Rambert, J; Renouf, E; Micouleau, M; Mérillon, J M

    2014-02-15

    Polyphenols from red fruits and bee-derived propolis (PR) are bioactive natural products in various in vitro and in vivo models. The present study shows that hematotoxicity-free doses of grape polyphenols (GPE) and PR differentially decreased the secretion of pro-inflammatory cytokines from activated human peripheral blood leucocytes. While GPE inhibited the monocytes/macrophage response, propolis decreased both monokines and interferon γ (IFNγ) production. When used together, their distinct effects lead to the attenuation of all inflammatory mediators, as supported by a significant modulation of the transcriptomic profile of pro-inflammatory genes in human leukocytes. To enforce in vitro data, GPE+PR were tested for their ability to improve clinical scores and cachexia in chronic rat adjuvant-induced arthritis (AA). Extracts significantly reduced arthritis scores and cachexia, and this effect was more significant in animals receiving continuous low doses compared to those receiving five different high doses. Animals treated daily had significantly better clinical scores than corticoid-treated rats. Together, these findings indicate that the GPE+PR combination induces potent anti-inflammatory activity due to their complementary immune cell modulation.

  18. IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation

    PubMed Central

    Park, Hye-Lim; Lee, Sang-Myeong; Min, Jun-Ki; Moon, Su-Jin; Kim, Inki; Kang, Kyung-Won; Park, Sooho; Choi, SeulGi; Jung, Ha-Na; Lee, Dong-Hee; Nam, Jae-Hwan

    2017-01-01

    Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA. PMID:28071693

  19. An Intense and Short-Lasting Burst of Neutrophil Activation Differentiates Early Acute Myocardial Infarction from Systemic Inflammatory Syndromes

    PubMed Central

    Maugeri, Norma; Rovere-Querini, Patrizia; Evangelista, Virgilio; Godino, Cosmo; Demetrio, Monica; Baldini, Mattia; Figini, Filippo; Coppi, Giovanni; Slavich, Massimo; Camera, Marina; Bartorelli, Antonio; Marenzi, Giancarlo; Campana, Lara; Baldissera, Elena; Sabbadini, Maria Grazia; Cianflone, Domenico; Tremoli, Elena; D’Angelo, Armando; Manfredi, Angelo A.; Maseri, Attilio

    2012-01-01

    Background Neutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases. Methods and Findings The myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils. Conclusions ACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin

  20. Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product.

    PubMed

    Abdalla, Abuelmagd; Byrne, Niamh; Conway, Richard; Walsh, Thomas; Mannion, Geraldine; Hanly, Michael; O'Sullivan, Miriam; Curran, Ann Maria; Carey, John J

    2017-01-01

    To evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center. In April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval. Around 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9), mean disease duration 14.79 years (9.7), median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3) months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively). There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7%) patients discontinued the biosimilar infliximab. Our patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost.

  1. Acute inflammatory demyelinating polyradiculoneuropathy in a newborn infant.

    PubMed

    Anastasopoulou, Stavroula; Lindefeldt, Marie; Bartocci, Marco; Wickström, Ronny

    2016-09-01

    Acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barré syndrome, is an immune-mediated polyneuropathy usually triggered by infections or vaccinations. In childhood AIDP is commonly described after the first year of life. Here, we present a case of a newborn infant with AIDP manifestation directly after delivery. A newborn girl with a healthy mother, without known exposure to immunomodulating factors, was admitted to the neuropediatric department due to ascending hypotonia, weakness, pain and areflexia in the lower extremities. The clinical presentation, laboratory and neurophysiological studies supported the diagnosis of AIDP. The infant showed first signs of clinical improvement following administration of intravenous immunoglobulin and her recovery was complete at one year. AIDP should be considered as a differential diagnosis in ascending hypotonia also in the neonatal period. Copyright © 2016 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

  2. Antibodies to mutated citrullinated vimentin and anti-cyclic citrullinated peptide antibodies in inflammatory bowel disease and related arthritis.

    PubMed

    Al-Jarallah, Khaled; Shehab, Diaa; Al-Attiyah, Rajaa; Al-Azmi, Waleed; Al-Fadli, Ahmad; Zafar Haider, Mohammed; Panaccione, Remo; Ghosh, Subrata

    2012-09-01

    Antibodies that react with citrullinated proteins (anti-mutated citrullinated vimentin [anti-MCV] and second-generation anti-cyclic citrullinated peptide antibodies [anti-CCP2]) are markers for rheumatoid arthritis. Recent studies have demonstrated that these antibodies are present in other arthropathies including the spondyloarthritis, psoriatic arthritis, and juvenile idiopathic arthritis. Arthritis associated with inflammatory bowel disease (IBD) takes various forms, with some shared similarities with classic spondylarthropathies. Our objective was to investigate the role of anti-MCV and anti-CCP2 as potential biomarkers in IBD and related arthritis. In all, 125 IBD patients (71 males, 54 females) were compared to 81 age- and sex-matched healthy controls. Anti-MCV and Anti-CCP2 IgG were measured using an enzyme linked immunosorbent assay. In the 125 IBD patients (mean age 32.6 ± 12.3 years), 44 (35.2%) had ulcerative colitis and 81 (64.8%) had Crohn's disease. Forty-four (35.2%) IBD patients developed arthritic manifestations. Antibody positivity was observed in 24/125 (19.2%) IBD patients and in 18/81 (22.2%) healthy subjects. The proportion of anti-MCV positivity among IBD patients and healthy individuals were similar: 16.8% vs. 16.0%, P = 0.887. Anti-CCP2 positivity among IBD patients and healthy individuals was also comparable: 6.4% vs. 6.2%, P = 0.948. Similarly, the presence of anti-MCV and anti-CCP2 antibodies was not different among IBD patients with and without arthritis. The mean titers of antibodies were low: anti-MCV (29.6 ± 7.5 U/mL) and anti-CCP2 (27.6 ± 4.0 U/mL) in IBD patients with arthritis. Autoantibodies to citrullinated proteins were low in IBD-related arthritis. These findings suggest that these antibodies are not useful biomarkers in IBD to predict who may develop IBD-related arthropathy. Copyright © 2011 Crohn's & Colitis Foundation of America, Inc.

  3. Acute postoperative inflammatory polyarthritis associated with a lone IgM cardiolipin antibody

    PubMed Central

    Chua, Ignatius; Jawad, Ali

    2015-01-01

    While the most recognised complication after joint surgery is septic arthritis, other forms of joint pathology may occur. We present a case of postoperative polyarthritis with high inflammatory markers, which responded to a course of prednisolone. The occurrence of high IgM cardiolipin antibodies that normalised with treatment suggests that this condition is a form of transient autoimmunity. PMID:25733090

  4. Therapeutic effect of the immunomodulatory drug lenalidomide, but not pomalidomide, in experimental models of rheumatoid arthritis and inflammatory bowel disease

    PubMed Central

    Lopez-Millan, Belen; Diaz de la Guardia, Rafael; Roca-Ho, Heleia; García-Herrero, Carmen M; Lavoie, Jessie R; Rosu-Myles, Michael; Gonzalez-Rey, Elena; O'Valle, Francisco; Criado, Gabriel; Delgado, Mario; Menendez, Pablo

    2017-01-01

    Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases. PMID:28154372

  5. Therapeutic effect of the immunomodulatory drug lenalidomide, but not pomalidomide, in experimental models of rheumatoid arthritis and inflammatory bowel disease.

    PubMed

    Lopez-Millan, Belen; Diaz de la Guardia, Rafael; Roca-Ho, Heleia; García-Herrero, Carmen M; Lavoie, Jessie R; Rosu-Myles, Michael; Gonzalez-Rey, Elena; O'Valle, Francisco; Criado, Gabriel; Delgado, Mario; Menendez, Pablo

    2017-02-03

    Thalidomide is an immunomodulatory drug (IMiD) with proven therapeutic action in several autoimmune/inflammatory diseases; however, its inherent high toxicity has led to the development of more powerful and safer thalidomide analogs, including lenalidomide and pomalidomide. These are new generation IMiDs that exhibit direct antitumor activity as well as anti-inflammatory/immunomodulatory properties, and are FDA-approved for the treatment of several hematological malignances. Here we investigated the potential therapeutic effects of lenalidomide and pomalidomide in several experimental murine models of autoimmune/inflammatory diseases: 2,4,6-trinitrobenzene sulfonic acid- and dextran sulfate sodium-induced inflammatory bowel disease and type II collagen-induced arthritis. Lenalidomide displayed a strong therapeutic effect in all these models of autoimmune/inflammatory diseases, while the effect of pomalidomide was less pronounced. In vitro experiments confirmed the immunosuppressive effect of both IMiDs on the proliferative response of stimulated human lymphocytes and on the balance of secreted cytokines toward an anti-inflammatory profile. We conclude that lenalidomide may offer a therapeutic opportunity against autoimmune/inflammatory diseases.

  6. Anti-inflammatory activities of light emitting diode irradiation on collagen-induced arthritis in mice (a secondary publication)

    PubMed Central

    Ohta, Mitsuhiro; Sato, Yusuke; Abiko, Yoshimitsu

    2014-01-01

    Background and aims: Rheumatoid arthritis (RA) is an auto-immune disease afflicting multiple joints of the body, where as a result of the increase in inflammatory cytokines and tissue destructive factors such as matrix metalloproteinase (MMP)-3, deterioration of the bones and cartilages of the joints occurs. The present investigation was carried out to study the anti-inflammatory activities of light emitting diode (LED) irradiation on hind paw inflammation in collagen-induced arthritis (CIA) mice models. Materials and method: RA in the CIA mouse model was induced by immunization of DBA/1J mice with intradermal injections of an emulsion of bovine type II collagen and complete Freund's adjuvant. A total of 20 CIA mice were subdivided into the following groups: control group, CIA group and 2 groups of LED irradiated CIA mice (LED groups) (n=5 per group). The mouse knee joint area in the LED groups (the 570 nm and 940 nm groups) was irradiated with LED energy, three times a week for 500 s per session over 8 weeks at a dose of 5 J/cm2. The hind paw swelling was assessed by the increase in hind paw thickness. The serum levels of the inflammatory cytokines and arthritic factor MMP-3 were determined with an enzyme-linked immunosorbent assay (ELISA). Results: In the LED-570 and LED-940 groups at 4 weeks after arthritis induction, the swelling inhibition index was 18.1±4.9 and 29.3±4.0 respectively. Interleukin (IL)-1β, IL-6 and MMP-3 serum levels were significantly lower in the LED-940 group. Conclusions: LED irradiation, particularly in the near-infrared was effective for inhibition of the inflammatory reactions caused by RA. PMID:25368445

  7. Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints.

    PubMed

    Krustev, Eugene; Reid, Allison; McDougall, Jason J

    2014-09-27

    During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful. Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common. Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation. One enzyme responsible for endocannabinoid breakdown is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis. Acute joint inflammation was induced in male C57BL/6 mice by intra-articular injection of 2% kaolin/2% carrageenan. After 24 hr, articular leukocyte kinetics and blood flow were used as measures of inflammation, while hindlimb weight bearing and von Frey hair algesiometry were used as measures of joint pain. The effects of local URB597 administration were then determined in the presence or absence of either the cannabinoid (CB)1 receptor antagonist AM251, or the CB2 receptor antagonist AM630. URB597 decreased leukocyte rolling and adhesion, as well as inflammation-induced hyperaemia. However, these effects were only apparent at low doses and the effects of URB597 were absent at higher doses. In addition to the anti-inflammatory effects of URB597, fatty acid amide hydrolase (FAAH) inhibition improved both hindlimb weight bearing and von Frey hair withdrawal thresholds. The anti-inflammatory effects of URB597 on leukocyte rolling and vascular perfusion were blocked by both CB1 and CB2 antagonism, while the effect on leukocyte adherence was independent of cannabinoid receptor activation. The analgesic effects of URB597 were CB1 mediated. These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these

  8. "Employment and arthritis: making it work" a randomized controlled trial evaluating an online program to help people with inflammatory arthritis maintain employment (study protocol).

    PubMed

    Carruthers, Erin C; Rogers, Pamela; Backman, Catherine L; Goldsmith, Charles H; Gignac, Monique A; Marra, Carlo; Village, Judy; Li, Linda C; Esdaile, John M; Lacaille, Diane

    2014-07-21

    Arthritis and musculoskeletal conditions are the leading cause of long-term work disability (WD), an outcome with a major impact on quality of life and a high cost to society. The importance of decreased at-work productivity has also recently been recognized. Despite the importance of these problems, few interventions have been developed to reduce the impact of arthritis on employment. We have developed a novel intervention called "Making It Work", a program to help people with inflammatory arthritis (IA) deal with employment issues, prevent WD and improve at-work productivity. After favorable results in a proof-of-concept study, we converted the program to a web-based format for broader dissemination and improved accessibility. The objectives of this study are: 1) to evaluate in a randomized controlled trial (RCT) the effectiveness of the program at preventing work cessation and improving at-work productivity; 2) to perform a cost-utility analysis of the intervention. 526 participants with IA will be recruited from British Columbia, Alberta, and Ontario in Canada. The intervention consists of a) 5 online group sessions; b) 5 web-based e-learning modules; c) consultations with an occupational therapist for an ergonomic work assessment and a vocational rehabilitation counselor. Questionnaires will be administered online at baseline and every 6 months to collect information about demographics, disease measures, costs, work-related risk factors for WD, quality of life, and work outcomes. Primary outcomes include at-work productivity and time to work cessation of > 6 months for any reason. Secondary outcomes include temporary work cessation, number of days missed from work per year, reduction in hours worked per week, quality adjusted life year for the cost utility analysis, and changes from baseline in employment risk factors. Analysis of Variance will evaluate the intervention's effect on at-work productivity, and multivariable Cox regression models will

  9. “Employment and arthritis: making it work” a randomized controlled trial evaluating an online program to help people with inflammatory arthritis maintain employment (study protocol)

    PubMed Central

    2014-01-01

    Background Arthritis and musculoskeletal conditions are the leading cause of long-term work disability (WD), an outcome with a major impact on quality of life and a high cost to society. The importance of decreased at-work productivity has also recently been recognized. Despite the importance of these problems, few interventions have been developed to reduce the impact of arthritis on employment. We have developed a novel intervention called “Making It Work”, a program to help people with inflammatory arthritis (IA) deal with employment issues, prevent WD and improve at-work productivity. After favorable results in a proof-of-concept study, we converted the program to a web-based format for broader dissemination and improved accessibility. The objectives of this study are: 1) to evaluate in a randomized controlled trial (RCT) the effectiveness of the program at preventing work cessation and improving at-work productivity; 2) to perform a cost-utility analysis of the intervention. Methods/Design 526 participants with IA will be recruited from British Columbia, Alberta, and Ontario in Canada. The intervention consists of a) 5 online group sessions; b) 5 web-based e-learning modules; c) consultations with an occupational therapist for an ergonomic work assessment and a vocational rehabilitation counselor. Questionnaires will be administered online at baseline and every 6 months to collect information about demographics, disease measures, costs, work-related risk factors for WD, quality of life, and work outcomes. Primary outcomes include at-work productivity and time to work cessation of > 6 months for any reason. Secondary outcomes include temporary work cessation, number of days missed from work per year, reduction in hours worked per week, quality adjusted life year for the cost utility analysis, and changes from baseline in employment risk factors. Analysis of Variance will evaluate the intervention’s effect on at-work productivity, and multivariable

  10. Investigation of Antiarthritic Potential of Plumeria alba L. Leaves in Acute and Chronic Models of Arthritis

    PubMed Central

    Kumar, Vipin; Gupta, Pankaj; Singh, Surender

    2014-01-01

    Aim. The present investigation was designed to evaluate antiarthritic potential of fractions of hydroalcoholic extract from leaves of P. alba. Materials and Methods. Plumeria alba L. leaves were extracted with hydroalcohol (30 : 70) to obtain hydroalcoholic extract of P. alba. This extract was further fractionated with solvents ethyl acetate and n-butanol to obtain EAPA and BPA, respectively. These fractions were tested against formaldehyde and Freund's complete adjuvant (FCA) induced arthritis. Arthritis assessment, paw volume, body weight, motor incoordination, and nociceptive threshold were measured. On day 21, the animals were sacrificed and histopathology was done. Results. The 100 and 200 mg/kg doses of EAPA and BPA caused a significant (P ≤ 0.05–0.01) reduction in paw swelling in both models. Erythrocyte sedimentation rate (ESR) and spleen weight decreased significantly (P < 0.01) in arthritic rats treated with extracts. There was significant (P < 0.05) improvement in thymus weight in EAPA treated rats whereas significant (P < 0.01) improvement was also seen in haemoglobin level (Hb) in diclofenac treated group. Motor incoordination and nociceptive threshold were also significantly (P ≤ 0.05–0.01) improved. Conclusion. The present study suggests that Plumeria alba L. has protective activity against arthritis and supports the traditional use of P. alba for rheumatism and other inflammatory diseases. PMID:25025056

  11. Diagnostic and prognostic value of history-taking and physical examination in undifferentiated peripheral inflammatory arthritis: a systematic review.

    PubMed

    Kuriya, Bindee; Villeneuve, Edith; Bombardier, Claire

    2011-03-01

    To review the diagnostic and prognostic value of history/physical examination among patients with undifferentiated peripheral inflammatory arthritis (UPIA). We conducted a systematic review evaluating the association between history/physical examination features and a diagnostic or prognostic outcome. Nineteen publications were included. Advanced age, female sex, and morning stiffness were predictive of a diagnosis of rheumatoid arthritis (RA) from UPIA. A higher number of tender and swollen joints, small/large joint involvement in the upper/lower extremities, and symmetrical involvement were associated with progression to RA. Similar features were associated with persistent disease and erosions, while disability at baseline and extraarticular features were predictive of future disability. History/physical examination features are heterogeneously reported. Several features predict progression from UPIA to RA or a poor prognosis. Continued measurements in the UPIA population are needed to determine if these features are valid and reliable predictors of outcomes, especially as new definitions for RA and disease states emerge.

  12. The 1st National Clinical audit for Rheumatoid and Early Inflammatory Arthritis: findings and implications for nursing practice

    PubMed Central

    Firth, J; Snowden, N; Ledingham, J; Rivett, A; Galloway, J; Dennison, EM; MacPhie, E; Ide, Z; Rowe, I; Kandala, N; Jameson, K

    2016-01-01

    The first national audit for rheumatoid and early inflammatory arthritis has benchmarked care for the first three months of follow up activity from first presentation to a rheumatology service. Access to care, management of early RA and support for self care were measured against NICE quality standards and impact of early arthritis and experience of care were measured using patient reported outcome and experience measures. The results demonstrate delays in referral and accessing specialist care and the need for service improvement in treating to target, suppression of high levels of disease activity and support for self-care. Improvements in patient -reported outcomes within three months and high levels of overall satisfaction were reported but these results were affected by low response rates. Here we present a summary of the national data from the audit and discuss the implications for nursing practice. PMID:27281595

  13. Sleep Disturbance and Older Adults' Inflammatory Responses to Acute Stress

    PubMed Central

    Heffner, Kathi L.; Ng, H. Mei; Suhr, Julie A.; France, Christopher R.; Marshall, Gailen D.; Pigeon, Wilfred R.; Moynihan, Jan A.

    2013-01-01

    Objectives Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Design Observational study of community-dwelling, healthy older adults. Setting Participants completed the study in a clinical research laboratory of a mid-sized university. Participants Generally healthy, community-dwelling men and women 50 years of age and older. Measurements IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Results Participants categorized as poor sleepers based on Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors compared to good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Conclusions Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation. PMID:22327621

  14. Anti-inflammatory activity and acute toxicity of Anredera leptostachys.

    PubMed

    Saénz, M T; García, M D; Fernández, M A

    1998-05-01

    Anredera leptostachys (Basellaceae) is a tropical plant, frequently found in the Dominica Republic. The decoction of the tubercles from this species are used in popular medicine, but there is no information on the biological activities of this species nor its toxicity. In the present work, the anti-inflammatory activity and the toxicity of an extract of tubercles from Anredera leptostachys have been studied. The antiinflammatory activity was investigated using two acute inflammation models: carrageenan induced-edema of the rat paw and tetradecanoylphorbol acetate (TPA) induced edema on the mouse ear. Indomethacin was used as standard drug. Myeloperoxidase activity (MPO) was also assessed as an indicator of leukocyte migration in the inflamed mouse ear. The extract given orally at doses of 250 and 500 mg/kg reduced the carrageenan induced edema in a dose-dependent manner: 27, 24, 25 and 10%; 44, 51, 61 and 57% at 2, 3, 4 and 5 h respectively. The extract applied topically, at doses of 3 and 5 mg/ear in the TPA test, produced an edema reduction of 14 and 20% respectively. The levels of myeloperoxidase enzyme were reduced in the inflammed tissue by 31 and 40% respectively. Acute toxicity also was investigated and the results indicated a low toxicity (LD(50):1043.38 ± 137.14 mg/kg; 61.07 ± 7.93 g plant/kg). Copyright © 1998 Gustav Fischer Verlag. Published by Elsevier GmbH.. All rights reserved.

  15. Sleep disturbance and older adults' inflammatory responses to acute stress.

    PubMed

    Heffner, Kathi L; Ng, H Mei; Suhr, Julie A; France, Christopher R; Marshall, Gailen D; Pigeon, Wilfred R; Moynihan, Jan A

    2012-09-01

    Poor sleep diminishes mental and physical health. The objective of this study was to examine associations between sleep disturbance and interleukin-6 (IL-6) responses to acute mental stress in older adults. Observational study of community-dwelling, healthy older adults. Participants completed the study in a clinical research laboratory of a mid-sized university. Generally healthy, community-dwelling men and women age 50 and older. IL-6 and negative affect at rest and following a series of challenging cognitive tests; sleep quality; depressive symptoms; perceived stress; loneliness. Participants categorized as poor sleepers on the basis of Pittsburgh Sleep Quality Index scores had significantly larger IL-6 responses to the cognitive stressors than good sleepers. The association between poor sleep and heightened IL-6 response to acute stress was not explained by other psychosocial factors previously linked to immune dysregulation, including depressive symptoms, perceived stress, and loneliness. Findings add to the growing evidence for poor sleep as an independent risk factor for poor mental and physical health. Older adults may be particularly vulnerable to effects of sleep disturbance due to significant age-related changes in both sleep and inflammatory regulation.

  16. Complementary and alternative medicine use in adolescents with inflammatory bowel disease and juvenile idiopathic arthritis

    PubMed Central

    2014-01-01

    Background The use of complementary alternative medicine (CAM) is potentially prevalent among paediatric patients with chronic diseases but with variable rates among different age groups, diseases and countries. There are no recent reports on CAM use among paediatric patients with inflammatory bowel disease (IBD) and juvenile idiopathic arthritis (JIA) in Europe. We hypothesized that CAM use associates with a more severe disease in paediatric IBD and JIA. Methods A cross-sectional questionnaire study among adolescent outpatients with IBD and JIA addressing the frequency and type of CAM use during the past year. The patients were recruited at the Children’s Hospital, University of Helsinki, Finland. Results Of the 147 respondents, 97 had IBD (Crohn’s disease: n = 46; median age 15.5, disease duration 3.4 years) and 50 had JIA (median age 13.8, disease duration 6.9 years). During the past 12 months, 48% regularly used CAM while 81% reported occasional CAM use. Compared to patients with JIA, the use of CAM in IBD patients tended to be more frequent. The most commonly used CAM included probiotics, multivitamins, and mineral and trace element supplements. Self-imposed dietary restrictions were common, involving 27.6% of the non-CAM users but 64.8% of all CAM users. Disease activity was associated with CAM use in JIA but not in IBD. Conclusions CAM use is frequent among adolescents with IBD and JIA and associates with self-imposed dietary restrictions. Reassuringly, adherence to disease modifying drugs is good in young CAM users. In JIA, patients with active disease used more frequently CAM than patients with inactive disease. As CAM use is frequent, physicians should familiarise themselves with the basic concepts of CAM. The potential pharmacological interaction or the toxicity of certain CAM products warrants awareness and hence physicians should actively ask their patients about CAM use. PMID:24708564

  17. Juvenile idiopathic arthritis patients with low inflammatory activity have increased adiposity.

    PubMed

    Grönlund, M-M; Kaartoaho, M; Putto-Laurila, A; Laitinen, K

    2014-01-01

    The aim of this study was to assess the effect of juvenile idiopathic arthritis (JIA), its subtypes and disease activity on anthropometric measurements, body composition, and nutritional parameters. A cross-sectional cohort of 40 JIA patients, aged 3-10 years, was compared with 40 healthy children matched for age and gender. Concentrations of nutritional and inflammatory biomarkers in the blood, anthropometric measures, and clinical status were recorded and the parents filled in a 7-day food diary and completed the Childhood Health Assessment Questionnaire (CHAQ). The JIA patients had low disease activity: 60% had inactive disease, the median CHAQ score was 0.125, and the median erythrocyte sedimentation rate (ESR) was 6 mm/h. Significantly higher values for central and peripheral adiposity were found in JIA patients compared with in healthy controls [waist circumference mean (SD) 55.9 (4.9) vs. 53.4 (3.7) cm, p < 0.0001, and biceps skinfold thickness 6.2 (2.3) vs. 5.3 (1.7) cm, p = 0.035, respectively], and obesity/overweight was more common (30% vs. 12.5%, p = 0.056, respectively) despite no differences in weight-for-height. The intake of energy (kcal/day) was significantly higher in the JIA patients (p = 0.036). The nutritional biomarkers were comparable in both groups. The JIA subtype and disease activity did not affect body composition, energy intake, or the nutritional biomarkers. Even JIA patients with low disease activity have a higher central and peripheral adiposity and a higher energy intake than their healthy peers. Neither disease subtype nor disease activity had any association with changes in body composition.

  18. Performance of the Existing Classification Criteria for Gout in Thai Patients Presenting With Acute Arthritis

    PubMed Central

    Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya; Kasitanon, Nuntana; Wangkaew, Suparaporn; Louthrenoo, Worawit

    2016-01-01

    Abstract Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis. All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (≤2 years), established disease (>2 years), and those without tophus. There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout. The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available. PMID:26844519

  19. Performance of the Existing Classification Criteria for Gout in Thai Patients Presenting With Acute Arthritis.

    PubMed

    Jatuworapruk, Kanon; Lhakum, Panomkorn; Pattamapaspong, Nuttaya; Kasitanon, Nuntana; Wangkaew, Suparaporn; Louthrenoo, Worawit

    2016-02-01

    Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis.All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (≤2 years), established disease (>2 years), and those without tophus.There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout.The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available.

  20. Local Joint inflammation and histone citrullination in a murine model of the transition from preclinical autoimmunity to inflammatory arthritis.

    PubMed

    Sohn, Dong Hyun; Rhodes, Christopher; Onuma, Kazuhiro; Zhao, Xiaoyan; Sharpe, Orr; Gazitt, Tal; Shiao, Rani; Fert-Bober, Justyna; Cheng, Danye; Lahey, Lauren J; Wong, Heidi H; Van Eyk, Jennifer; Robinson, William H; Sokolove, Jeremy

    2015-11-01

    Anti-citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition. We performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme-linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti-citrullinated H2B antibodies to mediate arthritis in vivo. We identified robust targeting of neutrophil-derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti-citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation. Our findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low-grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis

  1. Anti-inflammatory effect of Curcuma longa (turmeric) on collagen-induced arthritis: an anatomico-radiological study.

    PubMed

    Taty Anna, K; Elvy Suhana, M R; Das, S; Faizah, O; Hamzaini, A H

    2011-01-01

    Curcuma longa (CL) or turmeric is an Ayurvedic herb that has been traditionally used to treat inflammatory conditions like rheumatoid arthritis (RA). Collagen-induced arthritis (CIA) is a well established experimental auto-immune mediated polyarthritis in susceptible strains of rodents. The main aim of the study was to observe the inflammatory, macroscopic and radiological changes in the arthritic ankle joints of experimentally collagen-induced arthritis animals treated with or without CL extract. Thirty six male Sprague-Dawley (6-8 weeks-old, 150 ± 50) rats were equally divided into six groups. The first group served as a control while the rest five groups were immunized subdermally with 150 µg collagen type-II on day-0. All rats with established CIA with arthritis score (AS) exceeding 1 were treated orally with betamethasone (0.5 mg/ml/kg body weight) and varying doses of CL extract (30, 60 and 110 mg/ml/kg body weight) using olive oil as vehicle, daily for four weeks. Arthritic scoring (AS) of the paws, measurement of erythrocyte sedimentation rate (ESR) and paw thickness and radiological scoring were performed. Treatment with 110 mg/ml/kg CL showed significant mean difference in the ESR (p<0.01), AS (p<0.05) and radiological scores (p<0.01) on day-28 compared to the vehicle treated group. The mean difference for the ESR, AS and radiological scores of this highest CL dose group were found to be insignificant compared to the betamethasone treated group. The administration of CL extract arrested the degenerative changes in the bone and joints of collagen-induced arthritic rats.

  2. Hypothermia induced by adenosine 5'-monophosphate attenuates early stage injury in an acute gouty arthritis rat model.

    PubMed

    Miao, Zhimin; Guo, Weiting; Lu, Shulai; Lv, Wenshan; Li, Changgui; Wang, Yangang; Zhao, Shihua; Yan, Shengli; Tao, Zhenyin; Wang, Yunlong

    2013-08-01

    To investigate whether the hypothermia induced by Adenosine 5'-Monophosphate (5'-AMP) could attenuate early stage injury in a rat acute gouty arthritis model. Ankle joint injection with monosodium urate monohydrate crystals (MSU crystals) in hypothermia rat model which was induced by 5'-AMP and then observe whether hypothermia induced by 5'-AMP could be effectively inhibit the inflammation on acute gouty arthritis in rats. AMP-induced hypothermia has protective effects on our acute gouty arthritis, which was demonstrated by the following criteria: (1) a significant reduction in the ankle swelling (p < 0.001); (2) a significant decrease in the occurrence of leukocyte infiltration and mild hemorrhage; (3) a significant reduction in the presence of serum Interleukin-1β (IL-1β, p < 0.001) and metalloproteinase-9 (MMP-9, p < 0.001); and (4) a significant inhibition in the Nuclear Factor -κappaB (NF-κB) activity (p < 0.001). AMP-induced hypothermia could inhibit acute inflammation reaction and protect the synovial tissue against acute injury in a rat acute gouty arthritis model.

  3. Human neutrophil FcγRIIA regulation by C5aR promotes inflammatory arthritis in mice

    PubMed Central

    Tsuboi, Naotake; Ernandez, Thomas; Li, Xun; Nishi, Hiroshi; Cullere, Xavier; Mekala, Divya; Hazen, Melissa; Köhl, Jörg; Lee, David M.; Mayadas, Tanya N.

    2010-01-01

    Objective Rheumatoid arthritis culminates in joint destruction that in mouse models of disease, is supported by innate immune molecules including FcγRs and complement. However, the results may not predict outcomes in humans given the structural differences between murine and human activating FcγRs on neutrophils, a prominent component of joint exudates. In this study, we examined the role of the human neutrophil FcγRIIA in the development of arthritis and probed the underlying mechanism by which FcγRIIA initiated disease. Methods K/BxN serum transfer-induced arthritis was examined in mice that express FcγRIIA on neutrophils but lack their own activating FcγRs (γ-chain-deficient). The role of mast cells, complement (C3 and C5a) and CD18 integrins in FcγRIIA-initiated disease was examined using cell reconstitution approaches, inhibitors, and functional blocking antibodies respectively. Cross-talk between C5aR and FcγRIIA on neutrophils was evaluated in vitro. Results Neutrophil FcγRIIA expression was sufficient to restore susceptibility to K/BxN serum induced neutrophil recruitment, synovitis and bone destruction in γ-chain-deficient mice. Joint inflammation was robust and proceeded even in the absence of mast cells and vascular permeability, shown to contribute to disease in wild-type mice. Neutrophil recruitment was dependent on CD18 integrin LFA-1 and C5aR. C5aR in addition significantly enhanced FcγRIIA mediated phagocytosis and oxidative burst in vitro. Conclusion Human and murine activating FcγRs on neutrophils are not functionally equivalent, and in humans may play a primary role in arthritis. Cross-talk between neutrophil C5aR and FcγRIIA is essential for disease thus highlighting a new aspect of complement during the effector phase of inflammatory arthritis. PMID:21280001

  4. Associations of Smoking and Age With Inflammatory Joint Signs Among Unaffected First-Degree Relatives of Rheumatoid Arthritis Patients: Results From Studies of the Etiology of Rheumatoid Arthritis.

    PubMed

    Sparks, Jeffrey A; Chang, Shun-Chiao; Deane, Kevin D; Gan, Ryan W; Kristen Demoruelle, M; Feser, Marie L; Moss, LauraKay; Buckner, Jane H; Keating, Richard M; Costenbader, Karen H; Gregersen, Peter K; Weisman, Michael H; Mikuls, Ted R; O'Dell, James R; Michael Holers, V; Norris, Jill M; Karlson, Elizabeth W

    2016-08-01

    To examine whether genetic, environmental, and serologic rheumatoid arthritis (RA) risk factors are associated with inflammatory joint signs in a cohort of first-degree relatives (FDRs) of RA patients. We evaluated RA risk factors and inflammatory joint signs in a prospective cohort of FDRs without RA in the Studies of the Etiology of RA. Genetic factors included 5 HLA-DRB1 shared epitope alleles and 45 RA-associated single-nucleotide polymorphisms; loci were combined using genetic risk scores weighted by RA risk. Environmental factors (smoking, body mass index, education, and parity) and RA-related autoantibodies were assessed at baseline. Physical examination was performed at baseline and 2-year follow-up, by observers who were blinded with regard to autoantibody status, to assess inflammatory joint signs as tender or swollen joints at sites typical for RA. Logistic regression was performed to evaluate associations of genetic, environmental, and serologic factors with inflammatory joint signs. We analyzed 966 non-Hispanic white FDRs at baseline and 262 at 2-year follow-up after excluding those with inflammatory joint signs at baseline. The mean ± SD age was 47.2 ± 15.5 years, 71% were female, and 55% were shared epitope positive. Smoking >10 pack-years was associated with inflammatory joint signs at baseline (odds ratio [OR] 1.89 [95% confidence interval (95% CI) 1.26-2.82]) and at 2 years (OR 2.66 [95% CI 1.01-7.03]), compared to never smokers. There was a significant interaction between smoking and age with regard to risk of inflammatory joint signs (P = 0.02). FDRs younger than 50 years with >10 pack-years had the highest risk of inflammatory joint signs (OR 4.39 [95% CI 2.22-8.66], compared to never smokers younger than 50 years). In a high-risk cohort of FDRs, smoking and age were associated with both prevalent and incident inflammatory joint signs at sites typical for RA. Further prospective investigations of the factors affecting the

  5. Anti-inflammatory drugs and analgesics for managing symptoms in people with cystic fibrosis-related arthritis.

    PubMed

    Thornton, Judith; Rangaraj, Satyapal

    2016-01-21

    Arthritis remains a relatively infrequent complication of cystic fibrosis, but is a cause of significant morbidity when it does occur. Two distinct types of arthritis are described in cystic fibrosis: cystic fibrosis-related arthropathy (CFA) and hypertrophic pulmonary osteoarthropathy (HPO). Management of arthritis in people with cystic fibrosis is uncertain and complex because of the underlying disease and its intense treatment. This is an update of a previously published review. To review the effectiveness and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis in adults and children with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 19 January 2016. Randomised controlled studies which compared the efficacy and safety of anti-inflammatory and analgesic agents (e.g. non-steroidal anti-inflammatory agents, systemic corticosteroids, intra-articular corticosteroids) with each other, with no treatment or with placebo for CFA and HPO. No relevant studies were identified. No studies were included in this review. Although it is generally recognised that CFA may be episodic and resolve spontaneously, treatment with analgesics and anti-inflammatory agents may be needed. While this approach may be sufficient to manage symptoms, it is disappointing that no randomised controlled trials to rigorously evaluate these agents were found, nor could the authors identify any quasi-randomised. This systematic review has identified the need for a well-designed adequately-powered randomised controlled trial to assess the efficacy and safety of pharmacological agents for the symptomatic management of cystic fibrosis-related arthritis (CFA and HPO) in adults and children with cystic fibrosis

  6. Anti-inflammatory functions of Houttuynia cordata Thunb. and its compounds: A perspective on its potential role in rheumatoid arthritis

    PubMed Central

    LI, JUN; ZHAO, FUTAO

    2015-01-01

    The aim of this review was to take a look at the anti-inflammatory functions of Houttuynia cordata Thunb. (HCT) that have been illustrated in the literature and to explore new fields in which HCT could be used in the future. The use of HCT has been described in broad inflammatory domains, where it has exhibited a variety of activities, including antiviral, antibacterial, antiparasitic and immunostimulant activity, with high efficiency, mild features and definite therapeutic effects. The numerous anti-inflammatory functions of HCT have demonstrated that HCT has wide application prospects. New uses of HCT and the full extent of its utilization await further investigation. The basic pathological change of rheumatoid arthritis (RA) is synovial proliferation which leads to joint destruction in the long-term. There are types of drugs that have been used clinically for patients with RA, however, due to their side-effects or high prices their broad usage is limited. A safe and low-cost drug is urgently required to be developed for the clinical usage of patients with RA. Thus, HCT has the potential to be a good candidate in the treatment of rheumatoid arthritis. PMID:26170903

  7. Comparison of the suppressive effects of soluble CR1 and C5a receptor antagonist in acute arthritis induced in rats by blocking of CD59

    PubMed Central

    Mizuno, M; Nishikawa, K; Morgan, B P; Matsuo, S

    2000-01-01

    We investigated the effects of suppression of complement activation at C3 level and inhibition of C5a on acute synovitis in rats. Acute synovitis was induced in Wistar rats by intra-articular (i.a.) injection into one knee of 0.3 mg of MoAb 6D1 (anti-rat CD59 antibody). In the treatment groups, soluble CR1 (sCR1) or C5a receptor (C5aR) antagonist was administered intra-articularly or intravenously and effects on the course of the acute synovitis were monitored. Synovitis induced by 6D1 was characterized by joint swelling, thickening of synovial tissue, cellular infiltration and deposition of membrane attack complex (MAC) on the synovial surface. Neither inflammatory change nor MAC deposition was found in rats which received an i.a. injection of sCR1 to suppress complement activity in the joint. Intra-articular injection of sCR1 did not reduce plasma complement activity. Intravenous administration of sCR1 suppressed plasma complement activity but had no effect on the course of the arthritis and synovitis with MAC deposition was observed. Neither i.a. nor i.v. injection of C5aR antagonist had any suppressive effects on inflammatory change or MAC deposition in synovium. The data show that inflammatory change induced by 6D1 was mediated by local complement activation and was not accompanied by systemic complement activation. C5a generation was not responsible for the observed inflammation, suggesting that other complement activation products, possibly MAC, mediate the inflammatory change observed in this model of acute synovitis in rats. PMID:10632677

  8. Topical delivery of leflunomide for rheumatoid arthritis treatment: evaluation of local tissue deposition of teriflunomide and its anti-inflammatory effects in an arthritis rat model.

    PubMed

    Bae, Joonho; Park, Jin Woo

    2016-01-01

    We investigated whether leflunomide can be delivered topically and metabolized into teriflunomide through the skin, and evaluated the therapeutic effect of topical leflunomide. Permeation of leflunomide across and formation of its active metabolite within the skin was examined ex vivo. Deposition of teriflunomide in micropig knee joints after applying topical and transdermal patches containing leflunomide was investigated by determining the plasma and joint tissue concentrations. Finally, the anti-inflammatory effects and inhibition of skin sensitization by topical leflunomide were evaluated in a rat adjuvant arthritis model and mice with delayed-type induced hypersensitivity. We found that after topical application of leflunomide on freshly excised mouse, rat and guinea pig skin, ∼24% of the permeated drug existed as teriflunomide. In micropigs treated topically with leflunomide on the knee joint, significantly lower teriflunomide concentrations were found in plasma, but its concentrations in the knee joint were 3.4-fold to 54.6-fold higher than those after oral administration. In a rat arthritis model, the plasma concentration of teriflunomide after treatment with 10% leflunomide topical solution was 7.54-fold lower than that after 10 mg/kg oral leflunomide. However, topical leflunomide was nearly as effective as oral in inhibiting paw edema (37% versus 56%, respectively). The values for hypersensitized mouse ear weight after treatment with topical leflunomide decreased significantly by 26% compared to vehicle. These results demonstrate that topically applied leflunomide can be delivered effectively and deposited as teriflunomide in an arthritic joint, possibly allowing better compliance in rheumatoid arthritis patients by avoiding leflunomide's side effects.

  9. Inflammatory arthritis mimicking Complex Regional Pain Syndrome (CRPS) in a child: A case report

    PubMed Central

    Egilmez, Zeliha; Turgut, Selin Turan; Icagasioglu, Afitap; Bicakci, Irem

    2016-01-01

    Joint complaints in childhood are seen frequently and differential diagnosis can be difficult. Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. It involves peripheral joint arthritis, chronic synovitis, and extra-articular manifestations. Accurate diagnosis can take a long time and sometimes multiple diagnoses are used while following the patient until a final diagnosis can be reached. Arthritis may be triggered by trauma and confused with other diseases like complex regional pain syndrome (CRPS), in which trauma plays a role in the etiology. In the present case, ankle pain in an 8-year-old girl was misdiagnosed as CRPS. PMID:28058400

  10. Inflammatory arthritis mimicking Complex Regional Pain Syndrome (CRPS) in a child: A case report.

    PubMed

    Egilmez, Zeliha; Turgut, Selin Turan; Icagasioglu, Afitap; Bicakci, Irem

    2016-01-01

    Joint complaints in childhood are seen frequently and differential diagnosis can be difficult. Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood. It involves peripheral joint arthritis, chronic synovitis, and extra-articular manifestations. Accurate diagnosis can take a long time and sometimes multiple diagnoses are used while following the patient until a final diagnosis can be reached. Arthritis may be triggered by trauma and confused with other diseases like complex regional pain syndrome (CRPS), in which trauma plays a role in the etiology. In the present case, ankle pain in an 8-year-old girl was misdiagnosed as CRPS.

  11. Subsidence of total ankle component associated with deterioration of an ankle scale in non-inflammatory arthritis but not in rheumatoid arthritis.

    PubMed

    Iwata, Takahiro; Ito, Hiromu; Furu, Moritoshi; Ishikawa, Masahiro; Azukizawa, Masayuki; Yoshitomi, Hiroyuki; Fujii, Takayuki; Akiyama, Haruhiko; Matsuda, Shuichi

    2017-05-01

    Modern three-component total ankle arthroplasty (TAA) has favorable clinical results and survival rates. However, radiographic deterioration and worsening of clinical symptoms may occur in patients with rheumatoid arthritis (RA) or non-inflammatory arthritis (NA). The associations between outcomes and clinical and radiological factors are not clear. We compared midterm clinical and radiographic outcomes after TAA between patients with RA and those with NA. Twenty-six TAAs were performed using a three-component prosthesis, the FINE Total Ankle System during the study period. Fourteen TAAs with 11 RA patients undergoing primary TAA were compared with twelve TAAs with 12 NA patients. Clinical and radiographic outcomes were evaluated before and after operation, and at the final follow-up. The Japanese Society for Surgery of the Foot (JSSF) scale improved significantly following TAA in both groups (p = 0.0039 and 0.0156, respectively). Tibial subsidence, talar subsidence and age were significantly associated with postoperative JSSF score only in the NA group (p = 0.0027, 0.0017 and p < 0.0001, respectively). Stepwise regression analysis showed that talar subsidence was an independent predictor of a worse JSSF score in the NA group (F = 10.3). The final clinical outcome was negatively influenced by talar subsidence in patients with NA, but not in those with RA.

  12. Dietary Intake of Polyunsaturated Fatty Acids and Pain in spite of Inflammatory Control among Methotrexate Treated Early Rheumatoid Arthritis Patients.

    PubMed

    Lourdudoss, Cecilia; Di Giuseppe, Daniela; Wolk, Alicja; Westerlind, Helga; Klareskog, Lars; Alfredsson, Lars; van Vollenhoven, Ronald F; Lampa, Jon

    2017-03-28

    Objective To investigate potential associations between dietary intake of polyunsaturated fatty acids (PUFA) and pain patterns in early rheumatoid arthritis (RA) patients after three months of methotrexate (MTX) treatment. Methods We included 591 early RA patients with MTX monotherapy from a population based prospective case-control study, the Epidemiological Investigation of Rheumatoid Arthritis (EIRA). Dietary data on PUFA (food frequency questionnaires) were linked with data on unacceptable pain (visual analogue scale (VAS) >40mm), non-inflammatory/refractory pain (VAS >40mm and C-reactive protein (CRP) <10mg/L) and inflammatory pain (VAS >40mm and CRP >10mg/L) after three months. Statistical analysis included logistic regression. Results After three months of MTX treatment, 125 patients (21.2%) had unacceptable pain, of which 92 patients had refractory pain and 33 patients had inflammatory pain. Omega-3 fatty acid (FA) intake was inversely associated with unacceptable pain and refractory pain (OR=0.57 [95% CI 0.35-0.95] and OR=0.47 [95% CI 0.26-0.84], respectively). Omega-6 to -3 FA ratio, but not omega-6 FA alone, was directly associated with unacceptable pain and refractory pain (OR=1.70 [95% CI 1.03-2.82] and OR=2.33 [95% CI 1.28-4.24], respectively). Furthermore, PUFA was not associated with neither inflammatory pain nor CRP and erythrocyte sedimentation rate at follow-up. Omega-3 FA supplementation was not associated with any pain patterns. Conclusion Omega-3 FA was inversely associated with, and omega-6 to -3 FA ratio was directly associated with unacceptable and refractory pain, but not with inflammatory pain or systemic inflammation. The inverse association between omega-3 FA and refractory pain may have a role in pain suppression in RA. This article is protected by copyright. All rights reserved.

  13. Monoarticular Arthritis.

    PubMed

    Singh, Namrata; Vogelgesang, Scott A

    2017-05-01

    Monoarticular arthritis is inflammation characterized by joint pain, swelling, and sometimes periarticular erythema. Although chronic causes are seen, the onset is often acute. An infected joint can quickly lead to permanent damage, making it a medical emergency. However, acute gout presenting as monoarticular arthritis is often so uncomfortable it requires urgent attention. Monoarticular crystalline arthritis is common and a septic joint is a medical emergency so it is no surprise that these diagnoses come to mind with complaint of inflammation in 1 joint. However, there are many causes of monoarticular arthritis that clinicians must consider. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Overuse of prescription and OTC non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis.

    PubMed

    Cavagna, L; Caporali, R; Trifiro, G; Arcoraci, V; Rossi, S; Montecucco, C

    2013-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) have been demonstrated to have significant cardiovascular and gastrointestinal toxicity; high dose of intake and concomitant use of multiple compounds or corticosteroids are factors that increase the risk of NSAID toxicity. In this paper we described our experience on NSAIDs misuse (both prescribing and OTC formulations), particularly relevant in the setting of rheumatoid arthritis (39.5 percent of patients) and osteoarthritis (47 percent of patients). We also evaluated causes underlying NSAIDs misuse (e.g. not satisfactory pain control, other painful conditions, etc).

  15. Joint blood flow is more sensitive to inflammatory arthritis than oxyhemoglobin, deoxyhemoglobin, and oxygen saturation.

    PubMed

    Rajaram, Ajay; Ioussoufovitch, Seva; Morrison, Laura B; St Lawrence, Keith; Lee, Ting-Yim; Bureau, Yves; Diop, Mamadou

    2016-10-01

    Joint hypoxia plays a central role in the progression and perpetuation of rheumatoid arthritis (RA). Thus, optical techniques that can measure surrogate markers of hypoxia such as blood flow, oxyhemoglobin, deoxyhemoglobin, and oxygen saturation are being developed to monitor RA. The purpose of the current study was to compare the sensitivity of these physiological parameters to arthritis. Experiments were conducted in a rabbit model of RA and the results revealed that joint blood flow was the most sensitive to arthritis and could detect a statistically significant difference (p<0.05, power = 0.8) between inflamed and healthy joints with a sample size of only four subjects. Considering that this a quantitative technique, the high sensitivity to arthritis suggests that joint perfusion has the potential to become a potent tool for monitoring disease progression and treatment response in RA.

  16. [SEIP-SERPE-SEOP Consensus document on the treatment of uncomplicated acute osteomyelitis and septic arthritis].

    PubMed

    Saavedra-Lozano, J; Calvo, C; Huguet Carol, R; Rodrigo, C; Núñez, E; Obando, I; Rojo, P; Merino, R; Pérez, C; Downey, F J; Colino, E; García, J J; Cilleruelo, M J; Torner, F; García, L

    2015-04-01

    This is a Consensus Document of the Spanish Society of Paediatric Infectious Diseases (Sociedad Española de Infectología Pediatrica), Spanish Society of Paediatric Rheumatology (Sociedad Española de Reumatología Pediátrica) and the Spanish Society of Paediatric Orthopaedics (Sociedad Española de Ortopedia Pediátrica), on the treatment of uncomplicated acute osteomyelitis and septic arthritis. A review is presented on the medical and surgical treatment of acute osteoarticular infection, defined as a process with less than 14 days of symptomatology, uncomplicated and community-acquired. The different possible options are evaluated based on the best available scientific knowledge, and a number of evidence-based recommendations for clinical practice are provided. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  17. Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

    PubMed

    Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

    2017-02-01

    Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and

  18. Early prediction of rheumatoid arthritis by magnetic resonance imaging in the absence of anti-cyclic citrullinated peptide antibodies and radiographic erosions in undifferentiated inflammatory arthritis patients: a prospective study.

    PubMed

    Ji, Lanlan; Li, Guangtao; Xu, Yufeng; Zhou, Wei; Zhang, Zhuoli

    2015-11-01

    To assess the practicability of magnetic resonance imaging (MRI) in confirming the diagnosis of clinically suspected rheumatoid arthritis (RA), when anti-cyclic citrullinated peptide antibody and radiographic erosions are absent. We prospectively involved 31 treatment-naive patients with early inflammatory arthritis. At the initial visit, X-rays and gadolinium-enhanced MRI of both hands, as well as serological examinations and acute phase reactants were performed. The scores of synovitis, bone edema, bone erosion and tenosynovitis of metacarpophalangeal and wrist joints were evaluated using the RA-MRI scoring system. For all the patients, radiographs at baseline were normal and anti-cyclic citrullinated peptide antibodies were negative. At the end of follow-up(median 15 months, range 12-20 months), 22 patients were diagnosed as having RA according to 1987 American College of Rheumatology criteria. Bone edema, erosions, synovitis and tenosynovitis were observed in all the patients. However, the frequency of symmetric synovitis in wrists was significantly higher in the RA group. Moreover this group turned out to have significantly higher MRI bone erosion score in wrists. Further, receiver operating characteristic curve analysis revealed a positive wrist bone erosion score at 5, with a specificity of 78% and a sensitivity of 68%. There was no significant difference between the two groups with respect to metacarpophalangeal synovitis, metacarpophalangeal bone erosion, bone edema or tenosynovitis. MRI evidence of symmetric synovitis at wrist and a high bone erosion score at that site may assist in making an early diagnosis of RA in those patients who are negative for anti-cyclic citrullinated peptide antibody. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  19. Diagnosis and treatment of enthesitis-related arthritis

    PubMed Central

    Weiss, Pamela F

    2012-01-01

    Juvenile idiopathic arthritis (JIA) is a chronic, inflammatory disease of unknown etiology. The enthesitis-related arthritis (ERA) JIA category describes a clinically heterogeneous group of children including some who have predominately enthesitis, enthesitis and arthritis, juvenile ankylosing spondylitis, or inflammatory bowel disease-associated arthropathy. ERA accounts for 10%–20% of JIA. Common clinical manifestations of ERA include arthritis, enthesitis, and acute anterior uveitis. Axial disease is also common in children with established ERA. Treatment regimens for ERA, many of them based on adults with rheumatoid arthritis and ankylosing spondylitis, include the use of nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs, and biologic agents either individually or in combination. PMID:23236258

  20. Drug-disease interactions: reduced β-adrenergic and potassium channel antagonist activities of sotalol in the presence of acute and chronic inflammatory conditions in the rat

    PubMed Central

    Kulmatycki, Kenneth M; Abouchehade, Kassem; Sattari, Saeed; Jamali, Fakhreddin

    2001-01-01

    Inflammation may influence response to pharmacotherapy. We investigated the effect of inflammation on response to sotalol, a β-adrenergic receptor and potassium channel antagonist. Racemic sotalol (40 mg kg−1) was administered to healthy, acutely (interferonα 2a-induced) and chronically (Mycobacterium butyricum-induced adjuvant arthritis) inflamed male Sprague-Dawley rats (n=4 – 6/group). Another group of interferon-treated rats received 3 mg kg−1 of anti-TNF antibody infliximab. Electrocardiogram (ECG) recorded and plasma sotalol concentration monitored for 6 h. The study was repeated in acutely inflamed rats following administration of stereochemically pure individual sotalol enantiomers [40 mg kg−1 S (potassium channel blocker) or 20 mg kg−1 R (β-adrenergic/potassium channel blocker)]. Chronic arthritis was readily evident. Acute arthritis was associated with elevated segmented neutrophils and increased plasma nitrite and tumour necrosis factor (TNF) concentrations. Sotalol affected ECG in all rats. In both inflamed groups, however, response to sotalol in prolongation of QT interval (potassium channel sensitivity) was reduced. The effect of PR interval (β-adrenergic activity) was also reduced following administration of the racemate and R-enantiomer. No significant differences in pharmacokinetics were observed between control and inflamed rats. Infliximab reduced nitrite and TNF concentrations and reversed the effect of acute inflammation on both PR and QT intervals. The reduced electrocardiographic responses to sotalol is likely due to the influence of inflammation on the action of the drug on both β-adrenergic and potassium channel receptors secondary to over-expression of pro-inflammatory cytokines and/or nitric oxide. Our observation may have therapeutic consequences in all conditions where inflammatory mediators are increased. PMID:11350865

  1. Fasitibant chloride, a kinin B2 receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats

    PubMed Central

    Valenti, Claudio; Giuliani, Sandro; Cialdai, Cecilia; Tramontana, Manuela; Maggi, Carlo Alberto

    2012-01-01

    BACKGROUND AND PURPOSE Bradykinin, through the kinin B2 receptor, is involved in inflammatory processes related to arthropathies. B2 receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. EXPERIMENTAL APPROACH Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. KEY RESULTS The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg9-[Leu8]-bradykinin (B2 receptor, leukotriene, catecholamine and B1 receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. CONCLUSIONS AND IMPLICATIONS Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by release of eicosanoids

  2. β-Glucuronidase, a Regulator of Lyme Arthritis Severity, Modulates Lysosomal Trafficking and MMP-9 Secretion in Response to Inflammatory Stimuli.

    PubMed

    Bramwell, Kenneth K C; Mock, Kelton; Ma, Ying; Weis, John H; Teuscher, Cory; Weis, Janis J

    2015-08-15

    The lysosomal enzyme β-glucuronidase (Gusb) is a key regulator of Lyme-associated and K/B×N-induced arthritis severity. The luminal enzymes present in lysosomes provide essential catabolic functions for the homeostatic degradation of a variety of macromolecules. In addition to this essential catabolic function, lysosomes play important roles in the inflammatory response following infection. Secretory lysosomes and related vesicles can participate in the inflammatory response through fusion with the plasma membrane and release of bioactive contents into the extracellular milieu. In this study, we show that GUSB hypomorphism potentiates lysosomal exocytosis following inflammatory stimulation. This leads to elevated secretion of lysosomal contents, including glycosaminoglycans, lysosomal hydrolases, and matrix metalloproteinase 9, a known modulator of Lyme arthritis severity. This mechanistic insight led us to test the efficacy of rapamycin, a drug known to suppress lysosomal exocytosis. Both Lyme and K/B×N-associated arthritis were suppressed by this treatment concurrent with reduced lysosomal release.

  3. beta-glucuronidase, a regulator of Lyme arthritis severity, modulates lysosomal trafficking and MMP-9 secretion in response to inflammatory stimuli

    PubMed Central

    Bramwell, Kenneth K.C.; Mock, Kelton; Ma, Ying; Weis, John H.; Teuscher, Cory; Weis, Janis J.

    2015-01-01

    The lysosomal enzyme beta-glucuronidase (Gusb) is a key regulator of Lyme-associated and K/B×N-induced arthritis severity. The luminal enzymes present in lysosomes provide essential catabolic functions for the homeostatic degradation of a variety of macromolecules. In addition to this essential catabolic function, lysosomes play important roles in the inflammatory response following infection. Secretory lysosomes and related vesicles can participate in the inflammatory response through fusion with the plasma membrane and release of bioactive contents into the extracellular milieu. Here we show that GUSB hypomorphism potentiates lysosomal exocytosis following inflammatory stimulation. This leads to elevated secretion of lysosomal contents, including glycosaminoglycans, lysosomal hydrolases, and Matrix Metalloproteinase 9, a known modulator of Lyme arthritis severity. This mechanistic insight led us to test the efficacy of Rapamycin, a drug known to suppress lysosomal exocytosis. Both Lyme and K/B×N-associated arthritis were suppressed by this treatment concurrent with reduced lysosomal release. PMID:26170381

  4. Lipid management among individuals with inflammatory arthritis in the national REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort.

    PubMed

    Navarro-Millán, Iris; Gamboa, Christopher M; Curtis, Jeffrey R; Safford, Monika M

    2017-01-01

    Objective Hyperlipidemia guidelines do not currently identify inflammatory arthritis (IA) as a cardiovascular disease (CVD) risk factor. We compared hyperlipidemia treatment of individuals with and without IA (rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis) in a large national cohort. Methods Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were classified as having IA (without diabetes or hypertension); diabetes (but no IA); hypertension (but no diabetes or IA); or no IA, diabetes, or hypertension. Multivariable logistic regression models examined the odds of medical treatment among those with hyperlipidemia. Results Thirty-nine participants had IA, 5423 had diabetes, 7534 had hypertension, and 5288 had no diabetes, hypertension, or IA. The fully adjusted odds of treatment were similar between participants with IA and those without IA, hypertension, or diabetes. Participants with diabetes and no IA and participants with hypertension and no IA were twice as likely to be treated for hyperlipidemia as those without IA, diabetes, or hypertension. Conclusion Despite their higher CVD risk, patients with IA were as likely to be treated for hyperlipidemia as those without diabetes, hypertension, or IA. Lipid guidelines should identify IA as a CVD risk factor to improve CVD risk optimization in IA.

  5. Inflammatory cytokine response is greater in acute tibial plafond fractures than acute tibial plateau fractures.

    PubMed

    Haller, Justin M; Marchand, Lucas; Rothberg, David L; Kubiak, Erik N; Higgins, Thomas F

    2017-04-01

    The purpose of the study was to compare the inflammatory cytokine and matrix metalloproteinase (MMP) concentrations in synovial fluid after acute plafond fracture with acute tibial plateau fracture. Between December 2011 and August 2014, we prospectively enrolled patients with acute tibial plateau and plafond fractures. Synovial fluid aspirations were obtained from injured and uninjured joints. The concentrations of IL-1β, IL-1RA, IL-6, IL-8, IL-10, MCP-1, TNF-α, MMP-1, -3, -9, -10, -12, and -13 were quantified using multiplex assays. A Bonferroni correction was used so that the adjusted alpha level for significance was p < 0.004. We enrolled 45 tibial plateau fractures and 19 plafond fractures. Mean patient age was 42 years (range, 20-60) and 64% were male patients. There were 24 low-energy (OTA 41B) plateau fractures and eight low-energy (OTA 43B) plafond fractures. There were 21 high-energy (6 OTA 41B3 and 15 OTA 41C) plateau fractures and 11 high-energy (OTA43C) plafond fractures. All cytokines and MMPs except MMP-13 were significantly elevated in plafond fractures compared to uninjured ankles. When comparing acutely injured joints, IL-8 (p < 0.001), IL-1β (p = 0.002), and MMP-12 (p = 0.001) were significantly higher in plafond fractures compared to plateau fractures. Concentrations of IL-1RA (p = 0.008) and MCP-1 (p = 0.005) were higher in plafond fractures, and MMP-10 (p = 0.01) was higher in plateau fractures, but these differences did not reach significance. In conclusion, several cytokines and MMPs were significantly elevated in acute plafond fractures as compared to acute tibial plateau fractures. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  6. Mast cell depletion in the preclinical phase of collagen-induced arthritis reduces clinical outcome by lowering the inflammatory cytokine profile.

    PubMed

    van der Velden, Daniël; Lagraauw, H Maxime; Wezel, Anouk; Launay, Pierre; Kuiper, Johan; Huizinga, Tom W J; Toes, René E M; Bot, Ilze; Stoop, Jeroen N

    2016-06-13

    Rheumatoid arthritis (RA) is a multifactorial autoimmune disease, which is characterized by inflammation of synovial joints leading to the destruction of cartilage and bone. Infiltrating mast cells can be found within the inflamed synovial tissue, however their role in disease pathogenesis is unclear. Therefore we have studied the role of mast cells during different phases of experimental arthritis. We induced collagen-induced arthritis (CIA), the most frequently used animal model of arthritis, in an inducible mast cell knock-out mouse and determined the effect of mast cell depletion on the development and severity of arthritis. Depletion of mast cells in established arthritis did not affect clinical outcome. However, depletion of mast cells during the preclinical phase resulted in a significant reduction in arthritis. This reduction coincided with a decrease in circulating CD4(+) T cells and inflammatory monocytes but not in the collagen-specific antibody levels. Mast cell depletion resulted in reduced levels of IL-6 and IL-17 in serum. Furthermore, stimulation of splenocytes from mast cell-depleted mice with collagen type II resulted in reduced levels of IL-17 and enhanced production of IL-10. Here we show that mast cells contribute to the preclinical phase of CIA. Depletion of mast cells before disease onset resulted in an altered collagen-specific T cell and cytokine response. These data may suggest that mast cells play a role in the regulation of the adaptive immune response during the development of arthritis.

  7. Biology of recently discovered cytokines: Interleukin-17 – a unique inflammatory cytokine with roles in bone biology and arthritis

    PubMed Central

    Gaffen, Sarah L

    2004-01-01

    IL-17 and its receptor are founding members of an emerging family of cytokines and receptors with many unique characteristics. IL-17 is produced primarily by T cells, particularly those of the memory compartment. In contrast, IL-17 receptor is ubiquitously expressed, making nearly all cells potential targets of IL-17. Although it has only limited homology to other cytokines, IL-17 exhibits proinflammatory properties similar to those of tumor necrosis factor-α, particularly with respect to induction of other inflammatory effectors. In addition, IL-17 synergizes potently with other cytokines, placing it in the center of the inflammatory network. Strikingly, IL-17 has been associated with several bone pathologies, most notably rheumatoid arthritis. PMID:15535837

  8. Phagocyte-derived catecholamines enhance acute inflammatory injury.

    PubMed

    Flierl, Michael A; Rittirsch, Daniel; Nadeau, Brian A; Chen, Anthony J; Sarma, J Vidya; Zetoune, Firas S; McGuire, Stephanie R; List, Rachel P; Day, Danielle E; Hoesel, L Marco; Gao, Hongwei; Van Rooijen, Nico; Huber-Lang, Markus S; Neubig, Richard R; Ward, Peter A

    2007-10-11

    It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines. To assess the importance of these findings in vivo, we chose two models of acute lung injury. Blockade of alpha2-adrenoreceptors or catecholamine-generating enzymes greatly suppressed lung inflammation, whereas the opposite was the case either for an alpha2-adrenoreceptor agonist or for inhibition of catecholamine-degrading enzymes. We were able to exclude T cells or sympathetic nerve endings as sources of the injury-modulating catecholamines. Our studies identify phagocytes as a new source of catecholamines, which enhance the inflammatory response.

  9. Majoon ushba, a polyherbal compound ameliorates rheumatoid arthritis via regulating inflammatory and bone remodeling markers in rats.

    PubMed

    Ganesan, Ramamoorthi; Doss, Hari Madhuri; Rasool, Mahaboobkhan

    2016-01-01

    The present study was aimed to investigate the anti-arthritic effect of majoon ushba (MU) and its underlying mechanism in adjuvant induced arthritis (AIA) rats. Arthritis was induced by intradermal injection of complete freund's adjuvant (0.1ml) into the right hind paw of the Wistar albino rats. MU (1000mg/kg/b.wt) and methotrexate (3mg/kg/b.wt) were administered from day 11 to day 18th for 8days after adjuvant induction. We have found that MU treatment significantly increased the level of anti-inflammatory cytokine (IL-10) and inhibited the over production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) and monocyte chemoattractant protein-1 (MCP-1) (ELISA) in the serum of adjuvant-induced arthritic rats. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), inflammatory enzymes (inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2)), MCP-1, receptor activator of nuclear factor-kB ligand (RANKL) and transcription factors (NF-кB and AP-1) (Real-Time PCR) was found significantly downregulated in the synovial tissues of MU treated arthritic rats. In addition, the protein expression of NF-кB, IL-17, COX-2, and RANKL (western blotting and immunohistochemistry analysis) was found reduced. On the other hand, osteoprotegerin (OPG), a bone remodeling marker was found to be elevated in synovial tissues of MU treated arthritic rats. Furthermore, MU treatment prevented body weight loss and reduced the joint paw edema, cell infiltration, cartilage and bone degradation as evidenced by the histopathological and radiological analysis. In conclusion, our current findings provide scientific evidence for the traditional claim of MU as an anti-arthritic drug.

  10. Evaluation of anti-inflammatory effect of Withania somnifera root on collagen-induced arthritis in rats.

    PubMed

    Gupta, Apurva; Singh, Surendra

    2014-03-01

    Withania somnifera (Linn.) Dunal (Solanaceae) has long been used as an herb in Ayurvedic and indigenous medicine and has received intense attention in recent years for its chemopreventive properties. The present study focuses on the effect of W. somnifera root powder on the behavioral and radiological changes in collagen-induced arthritic rats. The rats were randomly divided into five groups: normal control, arthritic control, arthritic rats treated with W. somnifera root powder (at dose levels 600 and 800 mg kg⁻¹) and arthritic rats treated with methotrexate (at dose level 0.3 mg kg⁻¹). The treatment with W. somnifera (daily) and methotrexate (weekly) was initiated from the 20th day post collagen immunization and continued up until the 45th day. Arthritis was assessed macroscopically by measuring paw thickness, ankle size and body weight. Arthritic pain was assessed by toe-spread and total print length of the affected paw. Functional recovery due to the oral treatment of W. somnifera and methotrexate was assessed by sciatic functional index and rota rod activity. Administration of W. somnifera root powder (600 mg kg⁻¹) to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery of motor activity and radiological score. W. somnifera root has a protective effect against collagen-induced arthritis (CIA) in rats. The results suggest that W. somnifera root powder acts as an anti-inflammatory and antioxidant agent in decreasing the arthritic effects in collagen-induced arthritic rats.

  11. Gratitude uniquely predicts lower depression in chronic illness populations: A longitudinal study of inflammatory bowel disease and arthritis.

    PubMed

    Sirois, Fuschia M; Wood, Alex M

    2017-02-01

    Although gratitude has been identified as a key clinically relevant trait for improving well-being, it is understudied within medical populations. The current study addressed this gap and extended previous and limited cross-sectional research by examining the longitudinal associations of gratitude to depression in 2 chronic illness samples, arthritis and inflammatory bowel disease (IBD). Two chronic illness samples, arthritis (N = 423) and IBD (N = 427), completed online surveys at Time 1 (T1). One hundred sixty-three people with arthritis and 144 people with IBD completed the 6-month follow-up survey (T2). Depression, gratitude, illness cognitions, perceived stress, social support, and disease-related variables were assessed at T1 and T2. At T2, 57.2% of the arthritis sample and 53.4% of the IBD sample met the cut off scores for significant depression. T1 gratitude was negatively associated with depressive symptoms at T1 and T2 in both samples (rs from -.43 to -.50). Regression analyses revealed that T1 gratitude remained a significant and unique predictor of lower T2 depression after controlling for T1 depression, relevant demographic variables, illness cognitions, changes in illness-relevant variables, and another positive psychological construct, thriving, in both samples. As the first investigation of the longitudinal associations of gratitude to psychological well-being in the context of chronic illness, the current study provides important evidence for the relevance of gratitude for health-related clinical populations. Further intervention-based research is warranted to more fully understand the potential benefits of gratitude for adjustment to chronic illness. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  12. Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis.

    PubMed

    Fujii, Wataru; Kawahito, Yutaka; Nagahara, Hidetake; Kukida, Yuji; Seno, Takahiro; Yamamoto, Aihiro; Kohno, Masataka; Oda, Ryo; Taniguchi, Daigo; Fujiwara, Hiroyoshi; Ejima, Akika; Kishida, Tsunao; Mazda, Osam; Ashihara, Eishi

    2015-11-01

    Synovial fluid pH is decreased in patients with rheumatoid arthritis (RA); however, the underlying mechanisms are unclear. We undertook this study to examine the mechanism by which synovial fluid pH is regulated and to explore the possibility of a therapeutic strategy by manipulating this mechanism. We determined the pH and lactate concentration in synovial fluid from 16 RA patients. Cultured synovial fibroblasts (SFs) from the inflamed joints of 9 RA patients (RASFs) were examined for the expression of ion transporters that regulate intracellular and extracellular pH. The ion transporter up-regulated in RASF lines was then suppressed in RASFs by small interfering RNA (siRNA), and the effect of transfection on viability and proliferation was investigated. Finally, we examined the therapeutic effect of electrotransfer of monocarboxylate transporter 4 (MCT4)-specific siRNA into the articular synovium of mice with collagen-induced arthritis (CIA). Synovial fluid pH correlated inversely with both the Disease Activity Score in 28 joints using the C-reactive protein level and the synovial fluid lactate levels. RASFs exhibited up-regulated transcription of MCT4 messenger RNA. MCT4 exported intracellular lactate into the extracellular space. RASFs had significantly higher MCT4 protein levels than did SFs from patients with osteoarthritis. Knockdown of MCT4 induced intrinsic apoptosis of RASFs, thereby inhibiting their proliferation. Moreover, electrotransfer of MCT4-specific siRNA into the articular synovium of mice with CIA significantly reduced the severity of arthritis. RA activity correlated with decreased synovial fluid pH. This may be due to increased MCT4 expression in RASFs. Silencing MCT4 induced apoptosis in RASFs and reduced the severity of CIA, suggesting that MCT4 is a potential therapeutic target for inflammatory arthritis. © 2015, American College of Rheumatology.

  13. Pharmacological Basis for Use of Selaginella moellendorffii in Gouty Arthritis: Antihyperuricemic, Anti-Inflammatory, and Xanthine Oxidase Inhibition

    PubMed Central

    Zhao, Ping; Chen, Ke-li; Zhang, Guo-li

    2017-01-01

    This study was aimed at evaluating the effects of Selaginella moellendorffii Hieron. (SM) on gouty arthritis and getting an insight of the possible mechanisms. HPLC method was developed for chemical analysis. The paw oedema, the neutrophil accumulation, inflammatory mediators, lipid peroxidation, and histopathological changes of the joints were analyzed in gouty arthritis rat model, and the kidney injury and serum urate were detected in hyperuricemic mice. Pharmacokinetic result demonstrated that the main apigenin glycosides might be quantitatively transformed into apigenin in the mammalian body. Among these compounds, the apigenin exhibited the strongest effect on xanthine oxidase (XOD). SM aqueous extract has proved to be active in reducing hyperuricemia in dose-dependent manner, and the levels of blood urea nitrogen (BUN) and creatinine (Cr) in high dose group were decreased significantly as compared with hyperuricemic control group (P < 0.01). The high dose of SM extract could significantly prevent the paw swelling, reduce gouty joint inflammatory features, reduce the release of IL-1β and TNF-α, lower malondialdehyde (MDA) and myeloperoxidase (MPO) levels, and increase superoxide dismutase (SOD) level (P < 0.01). For the first time, this study provides a rational basis for the traditional use of SM aqueous extract against gout in folk medicine. PMID:28250791

  14. Stepwise inhibition of T cell recruitment at post-capillary venules by orally active desulfated heparins in inflammatory arthritis

    PubMed Central

    Al Faruque, Hasan; Kang, Jin Hee; Hwang, Seung Rim; Sung, Shijin; Alam, Md. Mahmudul; Sa, Keum Hee; Nam, Eon Jeong; Byun, Young Ro; Kang, Young Mo

    2017-01-01

    Identification of the structure-function relationship of heparin, particularly between 2-O-, 6-O-, and N-sulfation and its anticoagulant or anti-inflammatory activities, is critical in order to evaluate the biological effects of heparin, especially in conjunction with modifications for oral formulation. In this study, we demonstrated that removal of 2-O, 6-O, or N-desulfation and their hydrophobic modifications have differential effects on the blocking of interactions between sLeX and P-and L-selectins, with highest inhibition by 6-O desulfation, which was consistent with their in vivo therapeutic efficacies on CIA mice. The 6-O desulfation of lower molecular weight heparin (LMWH) retained the ability of LMWH to interfere with T cell adhesion via selectin-sLeX interactions. Furthermore, 6DSHbD coated on the apical surface of inflamed endothelium directly blocked the adhesive interactions of circulating T cells, which was confirmed in vivo by suppressing T cell adhesion at post-capillary venular endothelium. Thus, in series with our previous study demonstrating inhibition of transendothelial migration, oral delivery of low anticoagulant LMWH to venular endothelium of inflamed joint tissues ameliorated arthritis by the stepwise inhibition of T cell recruitment and provides a rationale for the development of modified oral heparins as innovative agents for the treatment of chronic inflammatory arthritis. PMID:28419144

  15. Syndecan-3 is selectively pro-inflammatory in the joint and contributes to antigen-induced arthritis in mice

    PubMed Central

    2014-01-01

    Introduction Syndecans are heparan sulphate proteoglycans expressed by endothelial cells. Syndecan-3 is expressed by synovial endothelial cells of rheumatoid arthritis (RA) patients where it binds chemokines, suggesting a role in leukocyte trafficking. The objective of the current study was to examine the function of syndecan-3 in joint inflammation by genetic deletion in mice and compare with other tissues. Methods Chemokine C-X-C ligand 1 (CXCL1) was injected in the joints of syndecan-3−/−and wild-type mice and antigen-induced arthritis performed. For comparison chemokine was administered in the skin and cremaster muscle. Intravital microscopy was performed in the cremaster muscle. Results Administration of CXCL1 in knee joints of syndecan-3−/−mice resulted in reduced neutrophil accumulation compared to wild type. This was associated with diminished presence of CXCL1 at the luminal surface of synovial endothelial cells where this chemokine clustered and bound to heparan sulphate. Furthermore, in the arthritis model syndecan-3 deletion led to reduced joint swelling, leukocyte accumulation, cartilage degradation and overall disease severity. Conversely, CXCL1 administration in the skin of syndecan-3 null mice provoked increased neutrophil recruitment and was associated with elevated luminal expression of E-selectin by dermal endothelial cells. Similarly in the cremaster, intravital microscopy showed increased numbers of leukocytes adhering and rolling in venules in syndecan-3−/−mice in response to CXCL1 or tumour necrosis factor alpha. Conclusions This study shows a novel role for syndecan-3 in inflammation. In the joint it is selectively pro-inflammatory, functioning in endothelial chemokine presentation and leukocyte recruitment and cartilage damage in an RA model. Conversely, in skin and cremaster it is anti-inflammatory. PMID:25015005

  16. Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product

    PubMed Central

    Abdalla, Abuelmagd; Byrne, Niamh; Conway, Richard; Walsh, Thomas; Mannion, Geraldine; Hanly, Michael; O’Sullivan, Miriam; Curran, Ann Maria; Carey, John J

    2017-01-01

    Purpose To evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center. Patients and methods In April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval. Results Around 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9), mean disease duration 14.79 years (9.7), median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3) months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively). There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7%) patients discontinued the biosimilar infliximab. Conclusion Our patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost. PMID:28331376

  17. Level of inflammatory cytokines in rheumatoid arthritis patients: Correlation with 25-hydroxy vitamin D and reactive oxygen species.

    PubMed

    Mateen, Somaiya; Moin, Shagufta; Shahzad, Sumayya; Khan, Abdul Qayyum

    2017-01-01

    Rheumatoid arthritis (RA) is an autoimmune inflammatory disorder. Reactive oxygen species (ROS) and pro-inflammatory cytokines have been believed to be involved in the etiopathogenesis of the disease. The aim of the study was to determine the correlation of inflammatory cytokines with 25-hydroxy vitamin D and ROS. 100 RA patients and 50 healthy age and sex matched individuals were included in the study. Patients were further divided on the basis of presence or absence of rheumatoid factor and disease severity. Serum 25-hydroxy vitamin D levels were monitored by chemiluminescent immunoassay. 10% hematocrit was used to detect the level of ROS by spectro fluorometer. The levels of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10 and IL-17) were determined in plasma by ELISA. The level of 25-hydroxy vitamin D was found to be decreased in RA patients in comparison to the control group. However the level of ROS and inflammatory cytokines were found to be elevated in RA patients in comparison with the healthy controls, with the increase being more pronounced in seropositive and RA patients having high disease severity. Inflammatory cytokines showed negative correlation with 25-hydroxy vitamin D and positive correlation with ROS. This study for the first time shows the association of inflammatory cytokines with 25-hydroxy vitamin D and ROS in RA patients. The results suggest that 25-hydroxy vitamin D being an immune modulator is decreased in the serum of RA patients. Further ROS and cytokines play an important role in the pathogenesis of RA and are responsible for increasing the severity of disease.

  18. Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome.

    PubMed

    Martínez, Gonzalo J; Robertson, Stacy; Barraclough, Jennifer; Xia, Qiong; Mallat, Ziad; Bursill, Christina; Celermajer, David S; Patel, Sanjay

    2015-08-24

    Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production. Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively). ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  19. Anti-inflammatory and anti-oxidant properties of Curcuma longa (turmeric) versus Zingiber officinale (ginger) rhizomes in rat adjuvant-induced arthritis.

    PubMed

    Ramadan, Gamal; Al-Kahtani, Mohammed Ali; El-Sayed, Wael Mohamed

    2011-08-01

    Turmeric (rich in curcuminoids) and ginger (rich in gingerols and shogaols) rhizomes have been widely used as dietary spices and to treat different diseases in Ayurveda/Chinese medicine since antiquity. Here, we compared the anti-inflammatory/anti-oxidant activity of these two plants in rat adjuvant-induced arthritis (AIA). Both plants (at dose 200 mg/kg body weight) significantly suppressed (but with different degrees) the incidence and severity of arthritis by increasing/decreasing the production of anti-inflammatory/pro-inflammatory cytokines, respectively, and activating the anti-oxidant defence system. The anti-arthritic activity of turmeric exceeded that of ginger and indomethacin (a non-steroidal anti-inflammatory drug), especially when the treatment started from the day of arthritis induction. The percentage of disease recovery was 4.6-8.3% and 10.2% more in turmeric compared with ginger and indomethacin (P < 0.05), respectively. The present study proves the anti-inflammatory/anti-oxidant activity of turmeric over ginger and indomethacin, which may have beneficial effects against rheumatoid arthritis onset/progression as shown in AIA rat model.

  20. Endogenous Acute Phase Serum Amyloid A Lacks Pro-Inflammatory Activity, Contrasting the Two Recombinant Variants That Activate Human Neutrophils through Different Receptors

    PubMed Central

    Christenson, Karin; Björkman, Lena; Ahlin, Sofie; Olsson, Maja; Sjöholm, Kajsa; Karlsson, Anna; Bylund, Johan

    2013-01-01

    Most notable among the acute phase proteins is serum amyloid A (SAA), levels of which can increase 1000-fold during infections, aseptic inflammation, and/or trauma. Chronically elevated SAA levels are associated with a wide variety of pathological conditions, including obesity and rheumatic diseases. Using a recombinant hybrid of the two human SAA isoforms (SAA1 and 2) that does not exist in vivo, numerous in vitro studies have given rise to the notion that acute phase SAA is a pro-inflammatory molecule with cytokine-like properties. It is however unclear whether endogenous acute phase SAA per se mediates pro-inflammatory effects. We tested this in samples from patients with inflammatory arthritis and in a transgenic mouse model that expresses human SAA1. Endogenous human SAA did not drive production of pro-inflammatory IL-8/KC in either of these settings. Human neutrophils derived from arthritis patients displayed no signs of activation, despite being exposed to severely elevated SAA levels in circulation, and SAA-rich sera also failed to activate cells in vitro. In contrast, two recombinant SAA variants (the hybrid SAA and SAA1) both activated human neutrophils, inducing L-selectin shedding, production of reactive oxygen species, and production of IL-8. The hybrid SAA was approximately 100-fold more potent than recombinant SAA1. Recombinant hybrid SAA and SAA1 activated neutrophils through different receptors, with recombinant SAA1 being a ligand for formyl peptide receptor 2 (FPR2). We conclude that even though recombinant SAAs can be valuable tools for studying neutrophil activation, they do not reflect the nature of the endogenous protein. PMID:23626589

  1. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes.

    PubMed

    Shin, Kichul; Nigrovic, Peter A; Crish, James; Boilard, Eric; McNeil, H Patrick; Larabee, Katherine S; Adachi, Roberto; Gurish, Michael F; Gobezie, Reuben; Stevens, Richard L; Lee, David M

    2009-01-01

    Although mast cells (MCs) often are abundant in the synovial tissues of patients with rheumatoid arthritis, the contribution of MCs to joint inflammation and cartilage loss remains poorly understood. MC-restricted tryptase/heparin complexes have proinflammatory activity, and significant amounts of human tryptase beta (hTryptase-beta) are present in rheumatoid arthritis synovial fluid. Mouse MC protease-6 (mMCP-6) is the ortholog of hTryptase-beta, and this serine protease is abundant in the synovium of arthritic mice. We now report that C57BL/6 (B6) mice lacking their tryptase/heparin complexes have attenuated arthritic responses, with mMCP-6 as the dominant tryptase responsible for augmenting neutrophil infiltration in the K/BxN mouse serum-transfer arthritis model. While inflammation in this experimental arthritis model was not dependent on protease-activated receptor-2, it was dependent on the chemokine receptor CXCR2. In support of the latter data, exposure of synovial fibroblasts to hTryptase-beta/heparin or mMCP-6/heparin complexes resulted in expression of the neutrophil chemotactic factors CXCL1/KC, CXCL5/LIX, and CXCL8/IL-8. Our proteomics, histochemistry, and immunohistochemistry data also revealed substantial loss of cartilage-derived aggrecan proteoglycans in the arthritic joints of wild-type B6 mice but not mMCP-6-null B6 mice. These observations demonstrate the functional contribution of MC-restricted tryptase/heparin complexes in the K/BxN mouse arthritis model and connect our mouse findings with rheumatoid arthritis pathophysiology.

  2. Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.

    PubMed

    Li, Yu; Wang, Li-Min; Xu, Jian-Zhong; Tian, Ke; Gu, Chen-Xi; Li, Zhi-Fu

    2017-01-01

    Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.

  3. A novel therapeutic approach targeting rheumatoid arthritis by combined administration of morin, a dietary flavanol and non-steroidal anti-inflammatory drug indomethacin with reference to pro-inflammatory cytokines, inflammatory enzymes, RANKL and transcription factors.

    PubMed

    Sultana, Farhath; Rasool, MahaboobKhan

    2015-03-25

    The present study was designed to assess the combined efficacy of morin, a dietary flavanol and non-steroidal anti-inflammatory drug indomethacin against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis. Arthritis was induced by intradermal injection of complete freund's adjuvant (0.1 ml) into the right hind paw of the Wistar albino rats. Morin (30 mg/kg b.wt), indomethacin (3 mg/kg b.wt) and combination of morin and indomethacin were administered intraperitoneally (from 11th to 20th day) after adjuvant injection. We have found that the activities/levels of lysosomal acid hydrolases (acid phosphatase, β-galactosidase, N-acetyl glucosaminidase and cathepsin-D), glycoproteins (hexose and hexosamine), urinary constituents (hydroxyproline and glycosaminoglycans), reactive oxygen species (LPO and NO), elastase, inflammatory mediators (TNF-α, IL-1β, MCP-1, VEGF and PGE2) and paw edema were significantly increased in arthritic rats compared to controls. Whereas, the anti-oxidant status (SOD, CAT, GPx, glutathione, and ceruloplasmin), body weight and bone collagen was found to be decreased. The mRNA expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-17, IL-6 and MCP-1), inflammatory enzymes (iNOS and COX-2), RANKL, and transcription factors (NF-kB p65 and AP-1) was found upregulated in the ankle joints of arthritic rats in qRT-PCR analysis. In addition, the increased protein expression of NF-kB p65 and COX-2 was also detected by immunohistochemical analysis. On the other hand, the above said imbalances were regulated back effectively to near normal as evidenced by the histopathological and radiological analysis on combined treatment with morin and indomethacin. Our study indicates that the combination therapy was more effective than either single drug alone in suppressing the pathogenesis of RA. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. Macrophages from the synovium of active rheumatoid arthritis exhibit an activin A-dependent pro-inflammatory profile.

    PubMed

    Soler Palacios, Blanca; Estrada-Capetillo, Lizbeth; Izquierdo, Elena; Criado, Gabriel; Nieto, Concha; Municio, Cristina; González-Alvaro, Isidoro; Sánchez-Mateos, Paloma; Pablos, Jose Luis; Corbí, Angel L; Puig-Kröger, Amaya

    2015-02-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease whose pathogenesis and severity correlates with the presence of macrophage-derived pro-inflammatory cytokines within the inflamed synovium. Macrophage-derived cytokines fuel the pathological processes in RA and are targets of clinically successful therapies. However, although macrophage polarization determines cytokine production, the polarization state of macrophages in RA joints remains poorly defined. To dissect the molecular basis for the tissue-damaging effects of macrophages in RA joints, we undertook the phenotypic and transcriptomic characterization of ex vivo isolated CD14(+) RA synovial fluid (RA-SF) macrophages. Flow cytometry and gene profiling indicated that RA-SF macrophages express pro-inflammatory polarization markers (MMP12, EGLN3, CCR2), lack expression of markers associated with homeostatic and anti-inflammatory polarization (IGF1, HTR2B) and exhibit a transcriptomic profile that resembles the activin A-dependent gene signature of pro-inflammatory in vitro-generated macrophages. In fact, high levels of Smad-activating activin A were found in RA-SF and, accordingly, the Smad signalling pathway was activated in ex vivo-isolated RA-SF macrophages. In vitro experiments on monocytes and macrophages indicated that RA-SF promoted the acquisition of pro-inflammatory markers (INHBA, MMP12, EGLN3, CCR2) but led to a significant reduction in the expression of genes associated with homeostasis and inflammation resolution (FOLR2, SERPINB2, IGF1, CD36), thus confirming the pro-inflammatory polarization ability of RA-SF. Importantly, the macrophage-polarizing ability of RA-SF was inhibited by an anti-activin A-neutralizing antibody, thus demonstrating that activin A mediates the pro-inflammatory macrophage-polarizing ability of RA-SF. Moreover, and in line with these findings, multicolour immunofluorescence evidenced that macrophages within RA synovial membranes (RA-SM) also express pro-inflammatory

  5. Novel hematologic inflammatory parameters to predict acute mesenteric ischemia.

    PubMed

    Toptas, Mehmet; Akkoc, İbrahim; Savas, Yildiray; Uzman, Sinan; Toptas, Yasar; Can, Mehmet Mustafa

    2016-03-01

    Acute mesenteric ischaemia (AMI) is an emergency condition that requires urgent diagnosis. Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been studied as inflammatory biomarkers in atherosclerosis, but data regarding AMI are lacking. The study population included patients with AMI (n = 46) versus age and sex-matched healthy controls (n = 46). Computed multidetector tomographic angiography was performed to diagnose AMI. NLR and PLR were calculated using complete blood count. C-reactive protein (CRP) levels were also analyzed. Neutrophil levels and lymphocytes were significantly higher in patients with AMI than in the control individuals (P < 0.001 and P = 0.43, respectively). NLR levels were significantly higher in patients with AMI compared with that in the control individuals (P < 0.001). Platelet levels did not reach statistical significance between the groups (P = 0.709). However, patients with AMI had significantly higher PLR levels than the control group (P = 0.039). CRP levels on admission were higher in patients with AMI in comparison with control individuals. There was also a positive correlation between NLR and CRP (r = 0.548, P < 0.001), and between PLR and CRP (r = 0.528, P < 0.001). NLR level greater than 4.5, measured on admission, yielded an area under the curve value of 0.790 (95% confidence interval 0.681-0.799, sensitivity 77%, specificity 72%), and PLR level of greater than 157 yielded an area under the curve value of 0.604 (95% confidence interval 0.486-0.722, sensitivity 59%, specificity 65%). Patients with AMI had increased NLR, PLR, and CRP levels compared with controls. Increased NLR and PLR was an independent predictor of AMI.

  6. Spontaneous ultra-weak photon emission in correlation to inflammatory metabolism and oxidative stress in a mouse model of collagen-induced arthritis.

    PubMed

    He, Min; van Wijk, Eduard; van Wietmarschen, Herman; Wang, Mei; Sun, Mengmeng; Koval, Slavik; van Wijk, Roeland; Hankemeier, Thomas; van der Greef, Jan

    2017-03-01

    The increasing prevalence of rheumatoid arthritis has driven the development of new approaches and technologies for investigating the pathophysiology of this devastating, chronic disease. From the perspective of systems biology, combining comprehensive personal data such as metabolomics profiling with ultra-weak photon emission (UPE) data may provide key information regarding the complex pathophysiology underlying rheumatoid arthritis. In this article, we integrated UPE with metabolomics-based technologies in order to investigate collagen-induced arthritis, a mouse model of rheumatoid arthritis, at the systems level, and we investigated the biological underpinnings of the complex dataset. Using correlation networks, we found that elevated inflammatory and ROS-mediated plasma metabolites are strongly correlated with a systematic reduction in amine metabolites, which is linked to muscle wasting in rheumatoid arthritis. We also found that increased UPE intensity is strongly linked to metabolic processes (with correlation co-efficiency |r| value >0.7), which may be associated with lipid oxidation that related to inflammatory and/or ROS-mediated processes. Together, these results indicate that UPE is correlated with metabolomics and may serve as a valuable tool for diagnosing chronic disease by integrating inflammatory signals at the systems level. Our correlation network analysis provides important and valuable information regarding the disease process from a system-wide perspective.

  7. Cost-Effectiveness Model for Evaluating New Diagnostic Tests in the Evaluation of Patients With Inflammatory Arthritis at Risk of Having Rheumatoid Arthritis.

    PubMed

    Luime, Jolanda J; Buisman, Leander R; Oppe, Mark; Hazes, Johanna M W; Rutten-van Mölken, Maureen P M H

    2016-07-01

    New opportunities have emerged for early diagnosis with the arrival of new technologies that assess the impact of genomics, proteomics, metabolomics, and cytomics on rheumatoid arthritis (RA) risk. This early health technology assessment study assesses the short-term cost effectiveness of 4 add-on diagnostic tests in early inflammatory arthritis patients at risk of RA. We modeled 4 diagnostic add-on tests to the American College of Rheumatology/European League Against Rheumatism 2010 RA classification criteria, covering the first year after diagnosis, using Rotterdam Early Arthritis Cohort data. Sensitivity, specificity, and costs were assigned to the magnetic resonance imaging of hands and feet (sensitivity 0.90, specificity 0.60, cost €756), interleukin-6 (IL-6) serum level test (sensitivity 0.70, specificity 0.53, cost €50), B cell-related gene expression (sensitivity 0.60, specificity 0.90, cost €150), and gene assay for RA (sensitivity 0.40, specificity 0.85, cost €750), based on literature and expert opinion. Outcomes were evaluated using the unweighted diagnostic net benefit (UDNB) and the incremental cost-effectiveness ratio (ICER) in all patients (n = 552), intermediate-risk patients (n = 263), and seronegative patients (n = 329). The highest UDNB was found when using the B cell assay in intermediate-risk patients (43%, ICER €5,314), while the IL-6 test in seronegative patients resulted in the lowest UDNB (-11.4%, ICER €7,650). If a threshold of €20,000 is applied, the B cell assay would be preferred over the other alternatives, with a 78% probability of being cost effective for intermediate-risk patients, 57% for all patients, and 73% for seronegative patients. Diagnostic add-on tests favoring specificity over sensitivity with a headroom less than €370 per test are cost effective, with the largest diagnostic benefit occurring in intermediate-risk patients. © 2016, American College of Rheumatology.

  8. Histopathology of Lyme arthritis in LSH hamsters

    SciTech Connect

    Hejka, A.; Schmitz, J.L.; England, D.M.; Callister, S.M.; Schell, R.F.

    1989-05-01

    The authors studied the histopathologic evolution of arthritis in nonirradiated and irradiated hamsters infected with Borrelia burgdorferi. Nonirradiated hamsters injected in the hind paws with B. burgdorferi developed an acute inflammatory reaction involving the synovium, periarticular soft tissues, and dermis. This acute inflammatory reaction was short-lived and was replaced by a mild chronic synovitis as the number of detectable spirochetes in the synovium, periarticular soft tissues, and perineurovascular areas diminished. Exposing hamsters to radiation before inoculation with B. burgdorferi exacerbated and prolonged the acute inflammatory phase. Spirochetes also persisted longer in the periarticular soft tissues. A major histopathologic finding was destructive and erosive bone changes of the hind paws, which resulted in deformation of the joints. These studies should be helpful in defining the immune mechanism participating in the onset, progression, and resolution of Lyme arthritis.

  9. The Acute Exercise-Induced Inflammatory Response: A Comparison of Young-Adult Smokers and Nonsmokers

    ERIC Educational Resources Information Center

    Kastelein, Tegan E.; Donges, Cheyne E.; Mendham, Amy E.; Duffield, Rob

    2017-01-01

    Purpose: This study examined postexercise inflammatory and leukocyte responses in smokers and nonsmokers, as well as the effects of cigarette smoking on the acute postexercise inflammatory and leukocyte response in habitual smokers. Method: Eleven recreationally active male smokers and 11 nonsmokers matched for age and aerobic fitness were…

  10. Differential expression of CD148 on leukocyte subsets in inflammatory arthritis

    PubMed Central

    2013-01-01

    Introduction Monocytic cells play a central role in the aetiology of rheumatoid arthritis, and manipulation of the activation of these cells is an approach currently under investigation to discover new therapies for this and associated diseases. CD148 is a transmembrane tyrosine phosphatase that is highly expressed in monocytes and macrophages and, since this family of molecules plays an important role in the regulation of cell activity, CD148 is a potential target for the manipulation of macrophage activation. For any molecule to be considered a therapeutic target, it is important for it to be increased in activity or expression during disease. Methods We have investigated the expression of CD148 in two murine models of arthritis and in joints from rheumatoid arthritis (RA) patients using real-time PCR, immunohistochemistry, and studied the effects of proinflammatory stimuli on CD148 activity using biochemical assays. Results We report that CD148 mRNA is upregulated in diseased joints of mice with collagen-induced arthritis. Furthermore, we report that in mice CD148 protein is highly expressed in infiltrating monocytes of diseased joints, with a small fraction of T cells also expressing CD148. In human arthritic joints both T cells and monocytes expressed high levels of CD148, however, we show differential expression of CD148 in T cells and monocytes from normal human peripheral blood compared to peripheral blood from RA and both normal and RA synovial fluid. Finally, we show that synovial fluid from rheumatoid arthritis patients suppresses CD148 phosphatase activity. Conclusions CD148 is upregulated in macrophages and T cells in human RA samples, and its activity is enhanced by treatment with tumour necrosis factor alpha (TNFα), and reduced by synovial fluid or oxidising conditions. A greater understanding of the role of CD148 in chronic inflammation may lead to alternative therapeutic approaches to these diseases. PMID:24016860

  11. Kaempferol, a dietary flavonoid, ameliorates acute inflammatory and nociceptive symptoms in gastritis, pancreatitis, and abdominal pain.

    PubMed

    Kim, Shi Hyoung; Park, Jae Gwang; Sung, Gi-Ho; Yang, Sungjae; Yang, Woo Seok; Kim, Eunji; Kim, Jun Ho; Ha, Van Thai; Kim, Han Gyung; Yi, Young-Su; Kim, Ji Hye; Baek, Kwang-Soo; Sung, Nak Yoon; Lee, Mi-nam; Kim, Jong-Hoon; Cho, Jae Youl

    2015-07-01

    Kaempferol (KF) is the most abundant polyphenol in tea, fruits, vegetables, and beans. However, little is known about its in vivo anti-inflammatory efficacy and mechanisms of action. To study these, several acute mouse inflammatory and nociceptive models, including gastritis, pancreatitis, and abdominal pain were employed. Kaempferol was shown to attenuate the expansion of inflammatory lesions seen in ethanol (EtOH)/HCl- and aspirin-induced gastritis, LPS/caerulein (CA) triggered pancreatitis, and acetic acid-induced writhing.

  12. Ginsenoside Rc from Korean Red Ginseng (Panax ginseng C.A. Meyer) Attenuates Inflammatory Symptoms of Gastritis, Hepatitis and Arthritis.

    PubMed

    Yu, Tao; Rhee, Man Hee; Lee, Jongsung; Kim, Seung Hyung; Yang, Yanyan; Kim, Han Gyung; Kim, Yong; Kim, Chaekyun; Kwak, Yi-Seong; Kim, Jong-Hoon; Cho, Jae Youl

    2016-01-01

    Korean Red Ginseng (KRG) is an herbal medicine prescribed worldwide that is prepared from Panax ginseng C.A. Meyer (Araliaceae). Out of ginseng's various components, ginsenosides are regarded as the major ingredients, exhibiting anticancer and anti-inflammatory activities. Although recent studies have focused on understanding the anti-inflammatory activities of KRG, compounds that are major anti-inflammatory components, precisely how these can suppress various inflammatory processes has not been fully elucidated yet. In this study, we aimed to identify inhibitory saponins, to evaluate the in vivo efficacy of the saponins, and to understand the inhibitory mechanisms. To do this, we employed in vitro lipopolysaccharide-treated macrophages and in vivo inflammatory mouse conditions, such as collagen (type II)-induced arthritis (CIA), EtOH/HCl-induced gastritis, and lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-triggered hepatitis. Molecular mechanisms were also verified by real-time PCR, immunoblotting analysis, and reporter gene assays. Out of all the ginsenosides, ginsenoside Rc (G-Rc) showed the highest inhibitory activity against the expression of tumor necrosis factor (TNF)-[Formula: see text], interleukin (IL)-1[Formula: see text], and interferons (IFNs). Similarly, this compound attenuated inflammatory symptoms in CIA, EtOH/HCl-mediated gastritis, and LPS/D-galactosamine (D-GalN)-triggered hepatitis without altering toxicological parameters, and without inducing gastric irritation. These anti-inflammatory effects were accompanied by the suppression of TNF-[Formula: see text] and IL-6 production and the induction of anti-inflammatory cytokine IL-10 in mice with CIA. G-Rc also attenuated the increased levels of luciferase activity by IRF-3 and AP-1 but not NF-[Formula: see text]B. In support of this phenomenon, G-Rc reduced TBK1, IRF-3, and ATF2 phosphorylation in the joint and liver tissues of mice with hepatitis. Therefore, our results strongly suggest that

  13. Biologic therapy for inflammatory arthritis and latent tuberculosis: real world experience from a high prevalence area in the United Kingdom.

    PubMed

    Nisar, Muhammad K; Rafiq, Aneesa; Östör, Andrew J K

    2015-12-01

    Biologic therapies have resulted in a sea change in the management of inflammatory arthritis; however, a higher risk of opportunistic infection, particularly tuberculosis (TB), is well recognised. This has led to the development of TB screening guidelines. The aim of this study was to investigate the prevalence of latent TB in patients prescribed biologic therapy in an endemic area (prevalence of TB 50/100,000) and to assess the risk of subsequent reactivation. Retrospective case note review of all patients with inflammatory arthritis ever prescribed biologic therapy between 1998 and 2014 at our centre. Two hundred ninety-nine patients (109 men, 190 women) who had ever been prescribed biologic therapy over a 16-year period were included. Mean age upon commencing the biologic therapy was 51 years. Two hundred eighteen (73 %) patients were Caucasian with remaining from ethnic minorities. Two hundred thirty-nine (80 %) prescriptions were for TNF inhibitors. Median duration of biologic therapy was 4.2 years for those who remained on treatment prior to stopping or switching therapies. During 1998-2007, 112 patients underwent clinical assessment, chest X-ray and check for BCG scar. One patient of Asian origin developed extrapulmonary TB within 6 weeks of adalimumab initiation. Following a year of anti-TB treatment, he restarted the biologic therapy with no ill effects. One hundred eighty-seven participants (who started on biologic therapy between 2008 and 2014) underwent additional interferon gamma release assays (IGRA) testing as part of a new TB screening protocol (T-spot test). Eighteen (10 %) had positive test with normal chest X-rays. Six patients were white, nine of Asian origin and three others. Three Caucasian patients had a borderline result. All had 3 months of isoniazid and rifampicin with simultaneous prescription of biologic agent (13 had TNF antagonist, 5 rituximab and 3 tocilizumab). No cases of active TB infection were observed. Overall prevalence of

  14. The Cyclin Dependent Kinase Inhibitor p21 Is Essential for Resolution of Murine Inflammatory Arthritis via its C-Terminal Domain

    PubMed Central

    Mavers, Melissa; Cuda, Carla M.; Misharin, Alexander V.; Gierut, Angelica K.; Agrawal, Hemant; Weber, Evan; Novack, Deborah Veis; Haines, G. Kenneth; Balomenos, Dimitrios; Perlman, Harris

    2011-01-01

    Objective The mechanism responsible for persistent inflammation of the synovium that occurs in patients with rheumatoid arthritis (RA) is unknown. Previously, we were the first to demonstrate that expression of the cyclin dependent kinase (CDK) inhibitor p21(WAF1/CIP1) is reduced in synovial tissue from RA patients compared to osteoarthritis patients and that p21 is a novel suppressor of the inflammatory response in macrophages. Here, we sought to determine the role and mechanism of p21-mediated suppression of experimental inflammatory arthritis. Methods Experimental arthritis was induced in WT or p21−/− (C57BL/6) mice using the K/BxN serum transfer induced model. p21-peptide mimetics were administered to mice as a prophylactic for arthritis development. LPS-induced cytokine and signal transduction pathways were examined in macrophages that were treated with p21-peptide mimetics using Luminex-based assays, flow cytometry, or ELISAs. Results p21−/− mice exhibit enhanced and sustained development of experimental inflammatory arthritis, which is associated with markedly increased numbers of macrophages and severe articular destruction. Administration of a p21-peptide mimetic suppresses activation of macrophages and reduces the severity of experimental arthritis only in p21-intact mice. Mechanistically, treatment with the p21-peptide mimetic leads to activation of the serine/threonine kinase Akt and subsequent reduction in the activated isoform of mitogen-activated protein kinase p38 in macrophages. Conclusion These data are the first to reveal that p21 plays an important role in limiting the activation response of macrophages in an inflammatory disease such as RA. Thus, targeting p21 in macrophages may be crucial for suppressing the development and persistence of RA. PMID:21898359

  15. Identification and quantification of selected inflammatory genes modulated by leflunomide and prednisone treatment in early rheumatoid arthritis patients.

    PubMed

    Cutolo, Maurizio; Villaggio, Barbara; Brizzolara, Renata; Montagna, Paola; Gallo, Fabio; Moretti, Stefano; Bonassi, Stefano; Sulli, Alberto; Soldano, Stefano

    2011-01-01

    The present study evaluates the effects of combined leflunomide (LEF) and low dose of prednisone therapy, on selected inflammatory gene expression in peripheral blood mononuclear cells (PBMCs) of early rheumatoid arthritis (ERA) patients by gene microarray analysis and quantitative real time-polymerase chain reaction (qRT-PCR). Ten ERA patients (mean age 53 ± 10 years) were assigned as untreated (group 1) or pre-treated (group 2) with prednisone (5 mg/day for 3 months) after informed consent and ethics committee approval. Five sex- and age-matched healthy subjects were used as controls (CNT). RNA was extracted by PBMCs, amplified, labelled and hybridised on inflammation DualChip microarray. The expression ratio of 282 inflammatory genes between CNT and ERA patients, before (T0) and after 12 weeks (T1) of combined therapy was detected. qRT-PCR was performed on 7 selected inflammatory RA-related genes (STAT4, MAPK9, HIF1A, MIF, STAT6, NFKB1, TNFRSF1B). At T0, microarray analysis showed 34 altered genes in both ERA groups when compared to CNT (vs. CNT). Seven RA-related genes, investigated in further details, were found up-regulated in group 1 and down-regulated or unchanged in group 2 vs. CNT. At T1, combined therapy induced the down-regulation of these genes in both groups vs. CNT as also confirmed by qRT-PCR performed on selected genes. Untreated ERA patients seem characterised by up-regulation of specific genes involved both in the resistance/inhibition to apoptosis and in the stimulation of pro-inflammatory cytokine production by immune inflammatory cells. Combined LEF and low dose of prednisone therapy seems to play synergistic effects on down-regulation of these genes.

  16. Trikatu, a herbal compound that suppresses monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis.

    PubMed

    Murunikkara, Vachana; Rasool, Mahaboobkhan

    2014-01-01

    Gout is an inflammatory joint disorder characterized by hyperuricaemia and precipitation of monosodium urate crystals in the joints. In the present study, we aimed to investigate the anti-inflammatory effect of trikatu, a herbal compound in monosodium urate crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and histopathological examination of ankle joints were determined in control and monosodium urate crystal-induced rats. In addition, analgesic (acetic acid-induced writhing response), anti-pyretic (yeast-induced pyrexia) and gastric ulceration effects were tested. The levels of lysosomal enzymes, lipid peroxidation and paw volume were significantly increased, and anti-oxidant status was found to be reduced in monosodium urate crystal-induced rats, whereas the biochemical changes were reverted to near normal levels upon trikatu (1000 mg/kg b.wt) administration. The trikatu has also been found to exhibit significant analgesic and anti-pyretic effects with the absence of gastric damage. In conclusion, the present results clearly indicated that trikatu exert a potent anti-inflammatory effect against monosodium urate crystal-induced inflammation in rats in association with analgesic and anti-pyretic effects in the absence of gastrointestinal damage.

  17. [Clinical and microbiological study of acute pelvic inflammatory disease].

    PubMed

    Ovalle, A; Martínez, M A; Casals, A; Yuhaniak, R; Giglio, M S

    1993-01-01

    Upper genital tract infection was investigated in 46 women admitted to hospital with clinic diagnosis of acute pelvic inflammatory disease (PID) and 62 control women accepted to hospital for laparoscopy Fallopian tubes sterilization. Diagnosis was ratified by laparoscopy in mild and moderate salpingitis; culdocentesis and ultrasonography were performed in severe salpingitis and endometrial sample was made in endometritis. Microbiological specimens were taken from the cervix and abdomen. Antecedents and complete clinical studies were obtained. Patients were treated with antibiotic association sodic G penicillin, chloramphenicol and gentamicin. Risk factors to development PID were: single female (p < 0.05), multiple sexual partner (p < 0.01), previous PID (p < 0.05), infertility (p < 0.05), mean year of IUD use in severe salpingitis (p = 0.05) and mean years of age from women with sexually transmitted bacterias (STB) vs endogenous bacterias (EB) (p < 0.05). In the control group no abdomen bacterias were isolated. In patients with PID, C. trachomatis was detected by serology in 28.3%. N. gonorrhoeae was isolated from the cervix in 23.9% and from the abdomen 17.4%. Besides it was isolated from the abdomen: M. hominis 17.3% and E. coli 15.2%. STB were isolated in 54.3% and EB in 47.8% of the patients. Bacterial association was present on the 37%. Cervix isolation of G. vaginalis and Mycoplasma were not correlated with development of PID. Cervix microbiological samples were useful to know abdomen microbic etiology. They coincide with those in the 90.9%. EB were more frequently isolated from severe salpingitis (p = 0.05) and STB from mild and moderate salpingitis (p = 0.05). Antibiotic association cured all the mild and moderate salpingitis with independence of bacterial etiology. Failure occurred in 2 diffuse peritonitis and 13/14 tubo-ovarian abscesses. Surgery used in severe salpingitis and diffuse peritonitis, principally consisted in anexectomy, peritoneal toilet and

  18. Anti-inflammatory and joint protective effects of extra-virgin olive-oil polyphenol extract in experimental arthritis.

    PubMed

    Rosillo, María Ángeles; Alcaraz, María José; Sánchez-Hidalgo, Marina; Fernández-Bolaños, José G; Alarcón-de-la-Lastra, Catalina; Ferrándiz, María Luisa

    2014-12-01

    The consumption of extra virgin olive oil (EVOO) in Mediterranean countries has shown beneficial effects. A wide range of evidence indicates that phenolic compounds present in EVOO are endowed with anti-inflammatory properties. In this work, we evaluated the effects of EVOO-polyphenol extract (PE) in a model of rheumatoid arthritis, the collagen-induced arthritis model in mice. On day 0, DBA-1/J mice were immunized with bovine type II collagen. On day 21, mice received a booster injection. PE (100 and 200 mg/kg) was orally administered once a day from days 29 to 41 to arthritic mice. We have demonstrated that PE decreases joint edema, cell migration, cartilage degradation and bone erosion. PE significantly reduced the levels of proinflammatory cytokines and prostaglandin E2 in the joint as well as the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1. Our data indicate that PE inhibits c-Jun N-terminal kinase, p38 and signal transducer and activator of transcription-3. In addition, PE decreases nuclear factor κB translocation leading to the down-regulation of the arthritic process. These results support the interest of natural diet components in the development of therapeutic products for arthritic conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Deficiencies in provision of integrated multidisciplinary podiatry care for patients with inflammatory arthritis: a UK district general hospital experience.

    PubMed

    Juarez, M; Price, E; Collins, D; Williamson, L

    2010-01-01

    Foot problems are highly prevalent in inflammatory arthritis (IA), especially rheumatoid arthritis (RA). Chronic inflammation can lead to permanent structural changes, deformity and disability. Early podiatry intervention in RA improves long term outcomes. National guidelines recommend that patients should be treated by a multidisciplinary team with dedicated podiatry services. In clinical practice funding constraints limit availability of these services. To assess prevalence of foot problems and quality and availability of foot care services at a UK district general hospital. 1200 IA patients in Swindon (Wiltshire, UK) were invited to complete an anonymised questionnaire regarding access to foot care services and education/information on foot problems. 448 patients. Prevalence of foot problems: 68%. Only 31% of patients had access to appropriate foot specialist. 24% had received foot assessment within 3 months of diagnosis of IA and 17% yearly review thereafter. Despite high prevalence of foot problems in our population we identified significant deficiencies in provision of integrated multidisciplinary podiatry care. The data we present could be used by others to support business cases to obtain funding to improve the links between rheumatology and podiatry services. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Synovial fluid antigen-presenting cells unmask peripheral blood T cell responses to bacterial antigens in inflammatory arthritis.

    PubMed Central

    Life, P F; Viner, N J; Bacon, P A; Gaston, J S

    1990-01-01

    We and others have previously shown that synovial fluid (SF) mononuclear cells (MC) from patients with both reactive arthritis and other inflammatory arthritides proliferate in vitro in response to bacteria clinically associated with the triggering of reactive arthritis. In all cases, such SFMC responses are greater than the corresponding peripheral blood (PB) MC responses, often markedly so, and the mechanism for this is unclear. We have investigated this phenomenon by comparing the relative abilities of irradiated non-T cells derived from PB and SF to support autologous T cell responses to ReA-associated bacteria. Seven patients whose SFMC had been shown previously to respond to bacteria were studied. We demonstrate antigen-specific responses of PB T cells to bacteria in the presence of SF non-T cells which are in marked contrast to the minimal responses of either unfractionated PBMC or PB T cells reconstituted with PB non-T cells. We also show that PB, but not SF T cells respond strongly to autologous SF non-T cells in the absence of antigen or mitogen. These findings demonstrate that SF antigen-presenting cells (APC) are potent activators of PB T cells. We conclude that the contrasting responses of SFMC and PBMC to bacterial antigens may be accounted for at least in part by an enhanced ability of SF APC to support T cell proliferative responses. PMID:2311298

  1. Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a rat model of collagen-induced arthritis

    PubMed Central

    XU, WEI; HUANG, MINGQING; ZHANG, YUQIN; LI, HUANG; ZHENG, HAIYIN; YU, LISHUANG; CHU, KEDAN; LIN, YU; CHEN, LIDIAN

    2016-01-01

    Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)-6, IL-8, tumor necrosis factor-α and nuclear factor-κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription-polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE-treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action. PMID:27035125

  2. Safety of nonsteroidal antiinflammatory drugs and/or paracetamol in people receiving methotrexate for inflammatory arthritis: a Cochrane systematic review.

    PubMed

    Colebatch, Alexandra N; Marks, Jonathan L; van der Heijde, Désirée M; Edwards, Christopher J

    2012-09-01

    To systematically review the literature on the safety of using nonsteroidal antiinflammatory drugs (NSAID) and/or paracetamol in people receiving methotrexate (MTX) for inflammatory arthritis (IA), as an evidence base for generating clinical practice recommendations. A systematic literature review was performed using the Cochrane Library, Medline, Embase, and conference proceedings for the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) for 2008-2009. The search aimed to identify studies describing adverse events (AE) with the concurrent use of paracetamol and/or NSAID in people taking MTX for IA. Articles fulfilling our predefined inclusion criteria were systematically reviewed and quality appraised. Seventeen publications out of 8681 identified studies were included in the review, all of which included people with rheumatoid arthritis (RA) using various NSAID; there were no identified studies for other forms of IA or with paracetamol. Of the studies examining concurrent use of MTX and NSAID, there were no reported adverse effects on lung, liver, or renal function, and no increase in MTX withdrawal or in major toxic reactions. However, transient thrombocytopenia was demonstrated in 1 study. Looking at specific NSAID, there were no clinically significant AE with concomitant piroxicam or etodolac, and only mild AE with celecoxib or etoricoxib. Antiinflammatory dose aspirin was demonstrated to have an adverse effect on liver and renal function. In the management of RA, concurrent use of NSAID with MTX appears to be safe, provided appropriate monitoring is performed. The use of antiinflammatory doses of aspirin should be avoided.

  3. Anti-citrullinated protein antibodies suppress let-7a expression in monocytes from patients with rheumatoid arthritis and facilitate the inflammatory responses in rheumatoid arthritis.

    PubMed

    Lai, Ning-Sheng; Yu, Hui-Chun; Yu, Chia-Li; Koo, Malcolm; Huang, Hsien-Bin; Lu, Ming-Chi

    2015-12-01

    We hypothesized that anti-citrullinated protein antibodies (ACPAs) could affect the expression of miRNAs in monocytes and contribute to the inflammatory responses in rheumatoid arthritis (RA). The expression profiles of 270 human miRNAs, co-cultured with ACPAs or human immunoglobulin G (IgG), were analyzed using real-time polymerase chain reaction. Ten miRNAs exhibited differential expression in U937 cells after co-cultured with ACPAs compared with human IgG. The expression levels of these miRNAs were investigated in monocytes from 21 ACPA-positive RA patients and 13 controls. Among these miRNAs, the expression levels of let-7a was decreased in monocytes from ACPA-positive RA patients. The expression levels of let-7a showed a negative correlation with positivity of rheumatoid factor in patients sampled. We found that transfection of U937 cells with let-7a mimic suppressed K-Ras protein expression. In the ACPA-mediated signaling pathway, transfection of U937 cells with let-7a mimic suppressed the ACPA-enhanced phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression and secretion of interleukin (IL)-1β. In conclusion, ACPA-mediated decreased let-7a expression in monocytes from ACPA-positive RA patients. Decreased let-7a expression was associated with the positivity of RF in ACPA-positive RA patients. The decreased expression of let-7a could facilitate the inflammatory pathway via enhanced ACPA-mediated phosphorylation of ERK1/2 and JNK and increased expression of IL-1β through an increase in the expression of Ras proteins. Copyright © 2015 Elsevier GmbH. All rights reserved.

  4. Comparing guideline-based care quality for inflammatory bowel disease and rheumatoid arthritis patients within a medical home.

    PubMed

    Caldera, Freddy; Saha, Sumona; Wald, Arnold; Cooley, David M; Zhao, Ying-Qi; Li, Zhanhai; Bartels, Christie M

    2016-06-01

    Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patient populations face similar risks of chronic immunosuppression including corticosteroid use. We compared the receipt of preventive services between IBD and RA populations according to published quality metrics. We defined a single-center cohort of patients with IBD or RA receiving specialty and primary care. Electronic health record abstraction assessed quality metrics, sociodemographics, comorbidity, and utilization. Comparisons used multivariate odds ratios and Student's t-tests. 218 RA and 190 IBD patients were included. In multivariate analysis, IBD patients were less likely to receive pneumococcal vaccination (OR=0.29, 95% CI: 0.11-0.85), while RA patients underwent glucocorticoid-induced osteoporosis screening more often (100% vs. 82.5%, p = 0.023). Gastroenterologists can improve care quality for IBD patients by assuming greater responsibility for preventive care in IBD patients and/or collaborating with primary care and health systems to improve preventive care delivery.

  5. Non-steroidal anti-inflammatory drugs and slow-acting anti-rheumatic drugs in juvenile rheumatoid arthritis.

    PubMed

    Fujikawa, S

    1993-10-01

    The preferred drugs for the initial treatment of juvenile rheumatoid arthritis (JRA) are salicylates or other non-steroidal anti-inflammatory drugs (NSAID) such as tolmetin or naproxen. If the disease activity does not respond adequately to the treatment, slow-acting anti-rheumatic drugs (SAARD) such as oral gold agents, low-dose D-penicillamine, or sulfasalazine should be given in addition to NSAID. If the systemic manifestations are severe, corticosteroid therapy may be commenced. Furthermore, if the joint destruction is progressive, immunosuppressants such as methotrexate would be selected as the third-line drugs of choice. The safety and efficacy of SAARD and immunosuppressants for the treatment of children with JRA, however, have not yet been confirmed, as the adverse effects such as bone marrow suppression, oncogenicity and mutagenicity are sometimes intense. Consequently, the strict indications for use and new therapeutic concepts for the management of JRA based on its pathogenesis are required.

  6. Semaphorin 4D Contributes to Rheumatoid Arthritis by Inducing Inflammatory Cytokine Production: Pathogenic and Therapeutic Implications

    PubMed Central

    Yoshida, Yuji; Kang, Sujin; Ebina, Kousuke; Shi, Kenrin; Nojima, Satoshi; Kimura, Tetsuya; Ito, Daisuke; Morimoto, Keiko; Nishide, Masayuki; Hosokawa, Takashi; Hirano, Toru; Shima, Yoshihito; Narazaki, Masashi; Tsuboi, Hideki; Saeki, Yukihiko; Tomita, Tetsuya; Tanaka, Toshio; Kumanogoh, Atsushi

    2015-01-01

    Objective Semaphorin 4D (Sema4D)/CD100 has pleiotropic roles in immune activation, angiogenesis, bone metabolism, and neural development. We undertook this study to investigate the role of Sema4D in rheumatoid arthritis (RA). Methods Soluble Sema4D (sSema4D) levels in serum and synovial fluid were analyzed by enzyme‐linked immunosorbent assay. Cell surface expression and transcripts of Sema4D were analyzed in peripheral blood cells from RA patients, and immunohistochemical staining of Sema4D was performed in RA synovium. Generation of sSema4D was evaluated in an ADAMTS‐4–treated monocytic cell line (THP‐1 cells). The efficacy of anti‐Sema4D antibody was evaluated in mice with collagen‐induced arthritis (CIA). Results Levels of sSema4D were elevated in both serum and synovial fluid from RA patients, and disease activity markers were correlated with serum sSema4D levels. Sema4D‐expressing cells also accumulated in RA synovium. Cell surface levels of Sema4D on CD3+ and CD14+ cells from RA patients were reduced, although levels of Sema4D transcripts were unchanged. In addition, ADAMTS‐4 cleaved cell surface Sema4D to generate sSema4D in THP‐1 cells. Soluble Sema4D induced tumor necrosis factor α (TNFα) and interleukin‐6 (IL‐6) production from CD14+ monocytes. IL‐6 and TNFα induced ADAMTS‐4 expression in synovial cells. Treatment with an anti‐Sema4D antibody suppressed arthritis and reduced proinflammatory cytokine production in CIA. Conclusion A positive feedback loop involving sSema4D/IL‐6 and TNFα/ADAMTS‐4 may contribute to the pathogenesis of RA. The inhibition of arthritis by anti‐Sema4D antibody suggests that Sema4D represents a potential therapeutic target for RA. PMID:25707877

  7. The patient experience of musculoskeletal imaging tests for investigation of inflammatory arthritis: a mixed-methods study.

    PubMed

    Bourke, Sandra; Taylor, William J; Doyle, Anthony J; Gott, Merryn; Dalbeth, Nicola

    2017-07-20

    The objective of this study was to understand the patient experience of musculoskeletal imaging tests for investigation of inflammatory arthritis and factors that contribute to this experience. We conducted a thematic analysis of semi-structured interviews with 33 patients who had a recent peripheral joint musculoskeletal imaging test for investigation of inflammatory arthritis. Data from these interviews were used to generate an 18-item questionnaire which was posted to rheumatology clinic patients within 6 weeks of peripheral joint imaging. Variables associated with the overall experience of the test were analysed using stepwise linear regression. Analysis of the interviews identified six themes: knowledge about the test, awareness of potential harm, the role of imaging in clinical care, discomfort, experience of waiting and 'seeing is believing'. Completed questionnaires were available from 132 patients. In regression analysis, a strong negative association was observed between the 'discomfort during the test' item and the overall experience of the test (standardised beta -0.35, p < 0.001). 'Staff made the experience better' (0.26, p < 0.001) and 'information provided' (0.28, p < 0.001) were positively associated with the overall experience of the test. For those who viewed their images, 'looking at the images with my doctor made me feel more involved in my care' (0.24, p = 0.022) was also associated positively with overall experience. Factors before, during and after a musculoskeletal imaging test contribute to the patient experience. The overall experience is most influenced by patient discomfort and interactions with staff during the test, information provided and viewing images to improve patient involvement in clinical care.

  8. The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links between innate immune recognition and bone homeostasis.

    PubMed

    Kragstrup, T W

    2016-08-01

    The treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA) was transformed a little over a decade ago by the introduction of agents neutralizing the pro-inflammatory cytokine tumour necrosis factor (TNF)-α. Nevertheless, some patients do not achieve remission and the inhibition of the normal immune system with current drugs increases the risk of infection. The interleukin (IL)-20 receptor (IL-20R) axis is pivotal for tissue homeostasis. By contrast, this axis does not seem to directly activate cells of the immune system. Thus, modulation of the IL-20R axis might not result in increased risk of infection. The IL-20R axis consists of the three cytokines IL-19, IL-20, and IL-24 (termed the IL-20R cytokines) and their shared receptors. All three cytokines bind the receptor complex of IL-20R2/IL-20R1 whereas only IL-20 and IL-24 also bind the receptor complex of IL-20R2/IL-22R1. This short review describes how the IL-20R axis could be a novel link between innate immune recognition and bone homeostasis. The IL-20R cytokines are produced in response to both danger-associated molecular patterns and immune complexes formed by RA-associated autoantibodies. This could be of importance because these mediators can thus be present even in situations without inflammation. IL-19 shows anti-inflammatory properties in arthritis through IL-20R1. IL-20 and IL-24 through IL-22R seem to participate in the recruitment of mononuclear cells to the synovial joint and to sites of bone erosion in particular. Our results indicate that dual inhibition of IL-20 and IL-24 or attenuation of the shared IL-22R subunit could have a beneficial effect on radiographic progression, especially in seropositive RA.

  9. Septic arthritis of the temporomandibular joint as a complication of acute otitis media in a child: A rare case and the importance of real-time PCR for diagnosis.

    PubMed

    Bast, F; Collier, S; Chadha, P; Collier, J

    2015-11-01

    We document the case of a 7-year-old boy who presented with pain in his left ear and trismus after a diagnosis of acute otitis media one week previously. His blood inflammatory markers were raised and magnetic resonance imaging (MRI) showed significant left temporomandibular joint effusion and partial attenuation of the left mastoid. A clinical diagnosis of septic arthritis of the TMJ was made and the patient was commenced on broad-spectrum antibiotics. Analysis using real time PCR enabled identification of the offending organism, confirmation of the diagnosis and antibiotic treatment to be specifically tailored for treatment.

  10. Hydrogen sulfide releasing naproxen offers better anti-inflammatory and chondroprotective effect relative to naproxen in a rat model of zymosan induced arthritis.

    PubMed

    Dief, A E; Mostafa, D K; Sharara, G M; Zeitoun, T H

    2015-04-01

    Hydrogen sulfide (H2S) is rapidly gaining ground as a physiological mediator of inflammation, but there is no clear consensus as to its precise role in inflammation. Therefore, this study was undertaken to evaluate the effects of ATB-346 as a novel H2S-releasing naproxen compared to naproxen, as a traditional non-steroidal anti-inflammatory drug on zymosan induced mono-arthritis in rats. Male Wistar rats (n=48) were randomly assigned to four main groups: normal control, untreated arthritis, Naproxen and ATB-346 treated groups. Mono-arthritis was induced by intra-articular injection of zymosan into the knee joints. Mechanical hypernociception and joint swelling were evaluated at 6 hours and 5 days. Inflammatory cellular recruitment and adherence, tumor necrosis factor alpha, nuclear factor kappa β, total sulfide levels, and histological changes were evaluated in knee lavages, blood or joint tissues at selected time points. Zymosan injection evoked knee inflammation and pain as characterized by mechanical hypernociception, impaired gait, joint swelling with inflammatory exudation and histological changes. Treatment with ATB-346 attenuated nociceptive responses, inflammatory cellular and biochemical changes in comparison to naproxen. Only ATB-346 was able to suppress neutrophil adherence and to preserve normal articular structure. H2S releasing naproxen represents an advancement over the parent drug, naproxen. Apart from the superior anti-inflammatory and anti-noceiceptive activity, ATB-346 offered a distinguished chondroprotective effect and is almost devoid from naproxen deleterious effects on articular cartilage.

  11. Anti-inflammatory effect of resveratrol on adjuvant arthritis rats with abnormal immunological function via the reduction of cyclooxygenase-2 and prostaglandin E2.

    PubMed

    Chen, Xiaoyu; Lu, Jinseng; An, Mei; Ma, Zhongfei; Zong, Hexiang; Yang, Jun

    2014-06-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease with unknown etiology. The present study investigated the anti-inflammatory effect of resveratrol on rats with adjuvant arthritis (AA) with abnormal immunological function via the reduction of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2). AA model rats were established by injection of complete Freund's adjuvant and alterations in the rats secondary paw swelling and the polyarthritic scores were observed. Pathological examination of joint tissues was observed by hematoxylin and eosin staining. The proliferation of spleen cells was examined using a 3-(4,5-dimethylthiazol-2‑yl)-2,5-diphenyltetrazolium bromide assay in vitro. The protein expression of COX-2 in the synovial tissues was detected by western blotting. The level of PGE2 in the serum was assayed using an ELISA kit. The results demonstrated that resveratrol (10 or 50 mg/kg) was able to significantly reduce paw swelling and decrease the arthritis scores. Compared with the AA model rats, a significant reduction in the proliferation of concanavalin A-stimulated spleen cells was observed, articular cartilage degeneration with synovial hyperplasia and inflammatory cell infiltration was suppressed and the production of COX-2 and PGE2 in AA rats was reduced by treatment with resveratrol. These results suggest that resveratrol has significant anti-inflammatory effects on AA rats, which may be associated with the reduction of COX-2 and PGE2 inflammatory mediators.

  12. Effect of acupuncture on rats with acute gouty arthritis inflammation: a metabonomic method for profiling of both urine and plasma metabolic perturbation.

    PubMed

    Wen, Si-Lan; Liu, Yu-Jie; Yin, Hai-Lin; Zhang, Liu; Xiao, Jin; Zhu, Hong-Yuan; Xue, Jin-Tao; Ye, Li-Ming

    2011-01-01

    Acute gouty arthritis is a common inflammation model with multiple pathogenic mechanisms seen in clinical practice, for which acupuncture may potentially be an alternative therapy. To investigate the effect of acupuncture on acute gouty arthritis and search for its mechanism, a metabonomic method was developed in this investigation. Acute gouty arthritis model rats were induced by monosodium urate (MSU) crystals. The urine and plasma samples were collected at several time points and the endogenous metabolites were analyzed by an ultra-performance liquid chromatography coupled with a mass spectrometry (UPLC-MS). Data were analyzed using principal components analysis (PCA) and partial least squares (PLS) analysis to compare metabolic profiles of MSU crystal-induced acute gouty arthritis rats with MSU crystal-induced acute gouty arthritis, treated with acupuncture rats. The results showed that acupuncture could restore the metabolite network that disturbed by MSU administration. Our study indicates that UPLC-MS-based metabonomics can be used as a potential tool for the investigation of biological effect of acupuncture on acute gouty arthritis.

  13. Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects.

    PubMed

    Han, Jieru; Xie, Ying; Sui, Fangyu; Liu, Chunhong; Du, Xiaowei; Liu, Chenggang; Feng, Xiaoling; Jiang, Deyou

    2016-09-01

    Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal‑induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine‑rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor‑α and interleukin‑1β, and inhibited activation of nuclear factor‑κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal‑induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti‑oxidative and anti‑inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis.

  14. Zisheng Shenqi decoction ameliorates monosodium urate crystal-induced gouty arthritis in rats through anti-inflammatory and anti-oxidative effects

    PubMed Central

    Han, Jieru; Xie, Ying; Sui, Fangyu; Liu, Chunhong; Du, Xiaowei; Liu, Chenggang; Feng, Xiaoling; Jiang, Deyou

    2016-01-01

    Based on traditional Chinese medicinal theories on gouty arthritis, Zisheng Shenqi decoction (ZSD), a novel Chinese medicinal formula, was developed due to its multiple functions, including reinforcing renal function, promoting blood circulation and relieving pain. In the present study, the effect of ZSD on monosodium urate (MSU) crystal-induced gouty arthritis in rats was investigated and the underlying mechanisms were examined. The data from these investigations showed that the injection of MSU crystals into the ankle joint cavity caused significant elevations in ankle swelling and inflammatory cell infiltration into the synovium, whereas these abnormal changes were markedly suppressed by oral administration of ZSD (40 mg/kg) for 7 days. Mechanically, ZSD treatment prevented MSU crystal-induced inflammatory responses, as evidenced by downregulation in the expression levels of NACHT domain, leucine-rich repeat and pyrin domain containing protein (NALP) 1 and NALP6 inflammasomes, decreased serum levels of tumor necrosis factor-α and interleukin-1β, and inhibited activation of nuclear factor-κB. In addition, ZSD administration markedly enhanced the anti-oxidant status in MSU crystal-induced rats by the increase in the activities of superoxide dismutase and glutathione peroxidase, and the levels of reduced glutathione. These results indicated that ZSD effectively prevented MSU crystal-induced gouty arthritis via modulating multiple anti-oxidative and anti-inflammatory pathways, suggesting a promising herbal formula for the prevention and treatment of gouty arthritis. PMID:27432278

  15. Fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, attenuates experimental arthritis by activating anti-inflammatory adenosinergic pathway.

    PubMed

    Veras, Flávio P; Peres, Raphael S; Saraiva, André L L; Pinto, Larissa G; Louzada-Junior, Paulo; Cunha, Thiago M; Paschoal, Jonas A R; Cunha, Fernando Q; Alves-Filho, José C

    2015-10-19

    Fructose 1,6-bisphosphate (FBP) is an endogenous intermediate of the glycolytic pathway. Exogenous administration of FBP has been shown to exert protective effects in a variety of ischemic injury models, which are attributed to its ability to sustain glycolysis and increase ATP production. Here, we demonstrated that a single treatment with FBP markedly attenuated arthritis, assessed by reduction of articular hyperalgesia, joint swelling, neutrophil infiltration and production of inflammatory cytokines, TNF and IL-6, while enhancing IL-10 production in two mouse models of arthritis. Our mechanistic studies showed that FBP reduces joint inflammation through the systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a (A2aR). Moreover, we showed that FBP-induced adenosine generation requires hydrolysis of extracellular ATP through the activity of the ectonucleosides triphosphate diphosphohydrolase-1 (ENTPD1, also known as CD39) and ecto-5'-nucleotidase (E5NT, also known as CD73). In accordance, inhibition of CD39 and CD73 abolished anti-arthritic effects of FBP. Taken together, our findings provide a new insight into the molecular mechanism underlying the anti-inflammatory effect of FBP, showing that it effectively attenuates experimental arthritis by activating the anti-inflammatory adenosinergic pathway. Therefore, FBP may represent a new therapeutic strategy for treatment of rheumatoid arthritis (RA).

  16. Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis

    PubMed Central

    Yeo, L; Lom, H; Juarez, M; Snow, M; Buckley, C D; Filer, A; Raza, K; Scheel-Toellner, D

    2015-01-01

    Objectives The success of B cell targeting therapies has highlighted the importance of B cells in rheumatoid arthritis pathogenesis. We have previously shown that B cells in the RA synovium are capable of producing pro-inflammatory and bone-destructive cytokines including RANKL. Here we sought to characterise the nature and functional relevance of the RANKL-producing B cell subset in the RA synovium. Methods Synovial fluid and peripheral blood B cells from patients with RA were analysed by flow cytometry for markers of B cell differentiation and activation and for chemokine receptors. FcRL4+ and FcRL4− B cells sorted from synovial fluid were analysed for cytokine expression using Taqman low-density arrays. Synovial tissue biopsies obtained from patients with RA were analysed by immunofluorescence for CD20, RANKL and FcRL4. FCRL4 mRNA expression was determined in synovial tissue of RA patients and non-inflammatory control subjects by real-time PCR. Results RANKL-producing B cells in RA synovial tissue and fluid were identified as belonging to a distinct subset of B cells defined by expression of the transmembrane protein FcRL4. FcRL4+ B cells express a distinct combination of cytokines and surface proteins indicating a function distinct from that of FcRL4− B cells. Notably, FcRL4+ B cells expressed high levels of TNF-α and RANKL mRNA. Conclusions We have identified a novel pro-inflammatory B cell population in the RA synovium which is defined by expression of FcRL4 and responsible for RANKL production. This B cell population expresses high levels of CD20, and its removal by rituximab may contribute to the anti-inflammatory effect of this drug. PMID:24431391

  17. A rare case of pulmonary toxoplasmosis in a patient with undifferentiated inflammatory arthritis on chronic methotrexate and corticosteroid therapy.

    PubMed

    Abdulkareem, Abdullateef; D'Souza, Ryan Steven; Patel, Nitin; Donato, Anthony A

    2017-08-23

    Pulmonary toxoplasmosis is a serious pulmonary condition caused by the protozoan Toxoplasma gondii It typically affects immunocompromised patients presenting acutely with cough, fever, myalgias, arthralgias and lymphadenopathy, and chronically with persistent cough and dyspnoea. Because of its protean features, it can mimic many more common lung conditions in the immunocompromised patient, including atypical pneumonia, Pneumocystis pneumonia and interstitial lung disease. In this article, we present the case of a 55-year-old woman who presented to our hospital with persistent dyspnoea and cough, initially suspected to have an arthritis-related interstitial lung disease. She received a final diagnosis of pulmonary toxoplasmosis after lung biopsy demonstrated Toxoplasma cysts, later confirmed by serology. Treatment with trimethoprim-sulfamethoxazole resulted in significant improvement of her respiratory symptoms after 3 months. © 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.

  18. Viral arthritis

    PubMed Central

    Marks, Michael; Marks, Jonathan L

    2016-01-01

    Acute-onset arthritis is a common clinical problem facing both the general clinician and the rheumatologist. A viral aetiology is though to be responsible for approximately 1% of all cases of acute arthritis with a wide range of causal agents recognised. The epidemiology of acute viral arthritis continues to evolve, with some aetiologies, such as rubella, becoming less common due to vaccination, while some vector-borne viruses have become more widespread. A travel history therefore forms an important part of the assessment of patients presenting with an acute arthritis. Worldwide, parvovirus B19, hepatitis B and C, HIV and the alphaviruses are among the most important causes of virally mediated arthritis. Targeted serological testing may be of value in establishing a diagnosis, and clinicians must also be aware that low-titre autoantibodies, such as rheumatoid factor and antinuclear antibody, can occur in the context of acute viral arthritis. A careful consideration of epidemiological, clinical and serological features is therefore required to guide clinicians in making diagnostic and treatment decisions. While most virally mediated arthritides are self-limiting some warrant the initiation of specific antiviral therapy. PMID:27037381

  19. Inflammatory cytokines compromise programmed cell death-1 (PD-1)-mediated T cell suppression in inflammatory arthritis through up-regulation of soluble PD-1.

    PubMed

    Bommarito, D; Hall, C; Taams, L S; Corrigall, V M

    2017-02-28

    The programmed cell death 1 (PD-1) receptor plays a major role in regulating T cell activation. Our aim was to determine how inflammation influences PD-1-mediated T cell suppression. Flow cytometry analysis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) synovial fluid (SF) mononuclear cells showed an increase in the percentage of PD-1(+) cells within the CD4(+) and CD8(+) T cell compartment compared to paired peripheral blood (PB). Upon in-vitro T cell receptor (TCR) stimulation of healthy control (HC) CD4(+) T cells in the presence of plate-bound PD-L1fc chimera, significantly decreased proliferation and interferon (IFN)-γ secretion was observed. In contrast, CD4(+) T cells from RA and PsA PB and SF appeared resistant to such PD-1-mediated inhibition. Addition of the proinflammatory cytokines tumour necrosis factor (TNF)α, interleukin (IL)-6 and IL-1β, which were increased in RA and PsA SF compared to osteoarthritis (OA) SF, consistently abrogated PD-1-mediated suppression in HC CD4(+) T cell cultures. This effect was reversed by inhibitors of these cytokines. Soluble PD-1 (sPD-1) levels were increased in cell culture supernatants from TNFα and IL-6-stimulated cultures compared to untreated controls, and also in RA and PsA, but not in OA, serum and SF. Functionally, addition of sPD-1fc counteracted PD-1-mediated suppression of HC CD4(+) T cells, and increased T cell proliferation in HC CD4(+) T cell/monocyte co-cultures. These in-vitro findings indicate that CD4(+) T cells from patients with RA and PsA show increased resistance to PD-1-mediated suppression, which may be explained in part by the presence of soluble PD-1 in the inflammatory environment.

  20. Telemedicine delivery of patient education in remote Ontario communities: feasibility of an Advanced Clinician Practitioner in Arthritis Care (ACPAC)-led inflammatory arthritis education program

    PubMed Central

    Warmington, Kelly; Flewelling, Carol; Kennedy, Carol A; Shupak, Rachel; Papachristos, Angelo; Jones, Caroline; Linton, Denise; Beaton, Dorcas E; Lineker, Sydney

    2017-01-01

    Objective Telemedicine-based approaches to health care service delivery improve access to care. It was recognized that adults with inflammatory arthritis (IA) living in remote areas had limited access to patient education and could benefit from the 1-day Prescription for Education (RxEd) program. The program was delivered by extended role practitioners with advanced training in arthritis care. Normally offered at one urban center, RxEd was adapted for videoconference delivery through two educator development workshops that addressed telemedicine and adult education best practices. This study explores the feasibility of and participant satisfaction with telemedicine delivery of the RxEd program in remote communities. Materials and methods Participants included adults with IA attending the RxEd program at one of six rural sites. They completed post-course program evaluations and follow-up interviews. Educators provided post-course feedback to identify program improvements that were later implemented. Results In total, 123 people (36 in-person and 87 remote, across 6 sites) participated, attending one of three RxEd sessions. Remote participants were satisfied with the quality of the video-conference (% agree/strongly agree): could hear the presenter (92.9%) and discussion between sites (82.4%); could see who was speaking at other remote sites (85.7%); could see the slides (95.3%); and interaction between sites adequately facilitated (94.0%). Educator and participant feedback were consistent. Suggested improvements included: use of two screens (speaker and slides); frontal camera angles; equal interaction with remote sites; and slide modifications to improve the readability on screen. Interview data included similar constructive feedback but highlighted the educational and social benefits of the program, which participants noted would have been inaccessible if not offered via telemedicine. Conclusion Study findings confirm the feasibility of delivering the RxEd program

  1. Sleep and physical activity: a survey of people with inflammatory arthritis and their engagement by health professionals in rheumatology in Ireland.

    PubMed

    McKenna, Sean; Donnelly, Alan; Fraser, Alexander; Kennedy, Norelee

    2017-06-02

    Sleep is important in maintaining the body's circadian rhythm and in maintaining health. Aim was to investigate sleep and physical activity among people who have inflammatory arthritis and their engagement with Health Professionals. Members from a national charitable organisation for patients with arthritis and a national rheumatology health professionals society were invited to participate in separate cross-sectional surveys hosted on SurveyMonkey((R)TM). Ninety people responded and report an average of 5.7 (SD 1.46) hours sleep per night. A majority (61%) report their sleep quality as bad, with 31% taking medications at least once a week to help sleep. There was a statistically significant association between longer years with symptoms, taking medication at least once a week and limited in their activities, when rating their sleep quality as bad. Twenty eight (65%) health professional's responded with 53% discussing sleep with their patients. People with inflammatory arthritis report low sleep with those having symptoms longer, taking medications regularly and having limitations with their activities, reporting poorer sleep quality. Only half of health professionals discuss sleep. More research is needed in investigating poor sleep quality, disturbances, and physical activity in order to promote health and well-being in this population. Implications for Rehabilitation People with inflammatory arthritis fall far below the National Sleep Foundations' "sleep needs spectrum", which is concerning as those who have reduced levels of sleep have been associated with decreased quality of life and physical function. Due to the importance of receiving sufficient sleep, there is a need to develop education and training for health professionals in the importance of engaging their patients in their sleep quality and disturbances. The effects of physical activity interventions on poor sleep need to be examined to show if it is a positive non-pharmacological treatment approach

  2. Enhanced natural killer activity and production of pro-inflammatory cytokines in mice selected for high acute inflammatory response (AIRmax).

    PubMed

    Castoldi, Lindsey; Golim, Marjorie Assis; Filho, Orlando Garcia Ribeiro; Romagnoli, Graziela Gorete; Ibañez, Olga Célia Martinez; Kaneno, Ramon

    2007-03-01

    Strains of mice with maximal and minimal acute inflammatory responsiveness (AIRmax and AIRmin, respectively) were developed through selective breeding based on their high- or low-acute inflammatory responsiveness. Previous reports have shown that AIRmax mice are more resistant to the development of a variety of tumours than AIRmin mice, including spontaneous metastasis of murine melanoma. Natural killer activity is involved in immunosurveillance against tumour development, so we analysed the number and activity of natural killer cells (CD49b(+)), T-lymphocyte subsets and in vitro cytokine production by spleen cells of normal AIRmax and AIRmin mice. Analysis of lymphocyte subsets by flow cytometry showed that AIRmax mice had a higher relative number of CD49b(+) cells than AIRmin mice, as well as cytolytic activity against Yac.1 target cells. The number of CD3(+) CD8(+) cells was also higher in AIRmax mice. These findings were associated with the ability of spleen cells from AIRmax mice in vitro to produce higher levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin-12p40 and interferon-gamma but not the anti-inflammatory interleukin-10. Taken together, our data suggest that the selective breeding to achieve the AIRmax and AIRmin strains was able to polarize the genes associated with cytotoxic activity, which can be responsible for the antitumour resistance observed in AIRmax mice.

  3. Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced arthritis in rats.

    PubMed

    da S Rocha, José C; Peixoto, Magno E B; Jancar, Sônia; de Q Cunha, Fernando; de A Ribeiro, Ronaldo; da Rocha, Francisco A C

    2002-06-01

    The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI). Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10 - 100 mg kg(-1) i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10 - 100 mg kg(-1) i.p.) or 1400W (0.5 - 1 mg kg(-1) s.c.) inhibited the AI induced by injection of zymosan 30 min later. Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1 - 1 micromol; 1400W, 0.01 (micromol) 30 min before zymosan also inhibited the AI. Systemic or local treatment with the NOS inhibitors (L-NAME; AG, 100 mg kg(-1) i.p. or 0.1 micromol joint(-1); 1400W, 1 mg kg(-1) s.c. or 0.01 micromol joint(-1)), 2 h after zymosan did not affect the subsequent AI. Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI. L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E(2) (PGE(2)) levels in the joints. L-NAME (100 mg kg(-1)) but not AG (100 mg kg(-1)) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan. In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE(2) release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema.

  4. Recommendations of the ESSR Arthritis Subcommittee on Ultrasonography in Inflammatory Joint Disease.

    PubMed

    Plagou, Athena; Teh, James; Grainger, Andrew J; Schueller-Weidekamm, Claudia; Sudoł-Szopińska, Iwona; Rennie, Winston; Åström, Gunnar; Feydy, Antoine; Giraudo, Chiara; Guerini, Henri; Guglielmi, Giuseppe; Isaac, Amanda; Jans, Lennart; Jurik, Anne Grethe; Kainberger, Franz; Maas, Mario; Martinoli, Carlo; Mascarenhas, Vasco V; Miese, Falk; O'Connor, Philip; Oei, Edwin H; Østergaard, Mikkel; Peetrons, Philippe; Platzgummer, Hannes; Reijnierse, Monique; Robinson, Philip; Rupreht, Mitja; Simoni, Paolo; Wick, Marius C; Zejden, Anna; Klauser, Andrea S

    2016-11-01

    This article presents the recommendations of the European Society of Musculoskeletal Radiology Arthritis Subcommittee on the use of ultrasonography (US) in rheumatic disease, focused on the examination of joints in the adult population. The recommended examination technique and protocols used in a radiologic work-up are discussed. The main US features that can lead to a final diagnosis in the most common rheumatic diseases are addressed. The differential diagnosis that should be considered at image interpretation is presented. The role of US in interventional procedures and clinically important recent developments is also discussed.

  5. Inhibitory effect of TRK-530 on inflammatory cytokines in bone marrow of rats with adjuvant arthritis.

    PubMed

    Tanahashi, M; Koike, J; Kawabe, N; Nakadate-Matsushita, T

    1998-05-01

    TRK-530 is a novel synthetic bisphosphonate compound which exhibits inhibitory activity in the rat adjuvant arthritis (AA) model. We found that, during AA development, the concentrations of cytokine-induced neutrophil chemoattractant-1 (CINC-1) and tumor necrosis factor alpha (TNF-alpha) in the bone marrow increased, and that administration of TRK-530 decreased the concentrations of these cytokines. The suppression of these concentration increases paralleled the inhibition of paw edema. Paw edema inhibition by TRK-530 in rat AA may be the result of decreasing CINC-1 and TNF-alpha concentrations.

  6. Anti-inflammatory activity of Ocimum americanum L. essential oil in experimental model of zymosan-induced arthritis.

    PubMed

    Yamada, Alciléia Nunes; Grespan, Renata; Yamada, Áureo Tatsumi; Silva, Expedito Leite; Silva-Filho, Saulo Euclides; Damião, Marcio José; de Oliveira Dalalio, Márcia Machado; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

    2013-01-01

    Essential oils are potential sources of novel components for medicinal use. The present study was performed to investigate the composition and anti-inflammatory activity of Ocimum americanum L. essential oil (OEO) and its components in an experimental model of zymosan-induced arthritis and paw edema. The essential oil was obtained by hydro-distillation and analyzed by gas chromatography-mass spectrometry. Twenty-six components, representing 98.9% of the total oil, were characterized, with linalool (19.63%) and 1,8-cineole (17.27%) as the main components. The OEO and its two constituents inhibited leukocyte influx into the synovial space and reduced paw edema induced by zymosan. The OEO also inhibited interferon-γ levels but did not reduce transforming growth factor-β levels. Additionally, the OEO protected against leukocyte influx into the synovial membrane and cartilage destruction in knee joints in arthritic mice. These findings indicate that the essential oil of Ocimum americanum L. exerted significant anti-inflammatory effects, likely related to its main compounds.

  7. Magnetic resonance imaging of the wrist in rheumatoid arthritis: comparison with other inflammatory joint diseases and control subjects.

    PubMed

    Tonolli-Serabian, I; Poet, J L; Dufour, M; Carasset, S; Mattei, J P; Roux, H

    1996-03-01

    The aim of this study was to evaluate magnetic resonance images (MRI) of the wrist of rheumatoid arthritis (RA) patients. MRI and plain X-ray of the wrists were performed in 15 patients with RA, 7 patients with another chronic inflammatory joint disease (CIJD), and 10 control subjects. Patients had only minor changes on plain X-ray. Coronal T1 weighted spin echo sequences were performed before and after an intravenous pulse of gadolinium (GD). Contiguous 3 mm thick slices were obtained. Synovitis was frequently objectivized in the two groups of patients. MRI detected far more erosions and central bone geodes than plain X-ray. Geodes were frequent among controls while cortical bone erosions were frequent in patients. Most of the erosions were enhanced after GD injection in the RA patients but not in the 2 other groups. Thus MRI is not only useful in diagnosing inflammatory changes of the wrist but also in distinguishing early stage RA from other CIJD.

  8. Synergistic effects of anethole and ibuprofen in acute inflammatory response.

    PubMed

    Wisniewski-Rebecca, Edirlene S; Rocha, Bruno A; Wiirzler, Luiz A M; Cuman, Roberto K N; Velazquez-Martinez, Carlos A; Bersani-Amado, Ciomar A

    2015-12-05

    This study assessed the effect of the combination of anethole and ibuprofen in comparison with monotherapy by either drug alone, using two in vivo inflammatory models, namely the pleurisy and paw edema in rats. We also measured the levels of the TNF protein in plasma, and the ability of anethole to inhibit, in vitro, the activity of the cyclooxygenase 1 and cyclooxygenase 2 enzymes. The test drugs (anethole; ibuprofen; anethole + ibuprofen), at different doses, were administered once (p.o.) 60 min before the induction of the inflammatory response. The association of anethole + ibuprofen inhibited the development of the inflammatory response in both models used. This effect can be partially explained by the inhibitory action on the production of TNF and of COX isoforms. The isobologram analysis evidenced a synergistic effect between ibuprofen and anethole, because the combination of drugs showed a higher inhibitory potential than either drug alone.

  9. A case of chikungunya virus disease presenting with remarkable acute arthritis of a previously damaged finger joint.

    PubMed

    Eyer-Silva, Walter de Araujo; Pinto, Henrique de Barros; Silva, Guilherme Almeida Rosa da; Ferry, Fernando Raphael de Almeida

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne arthritogenic alphavirus that has recently been introduced to Brazil. We report the case of a 36-year-old male patient from the City of Rio de Janeiro who developed molecularly-confirmed CHIKV disease and whose clinical picture was remarkable because of acute arthritis of an interphalangeal joint that had been damaged by trauma 8 years previously. This case illustrates that acute CHIKV disease may preferentially target previously damaged joints. Careful study of individual cases may provide valuable information on the presentation and management of this emerging zoonosis in Brazil.

  10. Clopidogrel, a P2Y12 Receptor Antagonist, Potentiates the Inflammatory Response in a Rat Model of Peptidoglycan Polysaccharide-Induced Arthritis

    PubMed Central

    Rico, Mario C.; Dela Cadena, Raul A.; Kunapuli, Satya P.

    2011-01-01

    The P2Y12 receptor plays a crucial role in the regulation of platelet activation by several agonists, which is irreversibly antagonized by the active metabolite of clopidogrel, a widely used anti-thrombotic drug. In this study, we investigated whether reduction of platelet reactivity leads to reduced inflammatory responses using a rat model of erosive arthritis. We evaluated the effect of clopidogrel on inflammation in Lewis rats in a peptidoglycan polysaccharide (PG-PS)-induced arthritis model with four groups of rats: 1) untreated, 2) clopidogrel-treated, 3) PG-PS-induced, and 4) PG-PS-induced and clopidogrel-treated. There were significant differences between the PG-PS+clopidogrel group when compared to the PG-PS group including: increased joint diameter and clinical manifestations of inflammation, elevated plasma levels of pro-inflammatory cytokines (IL-1 beta, interferon (IFN) gamma, and IL-6), an elevated neutrophil blood count and an increased circulating platelet count. Plasma levels of IL-10 were significantly lower in the PG-PS+clopidogrel group compared to the PG-PS group. Plasma levels of platelet factor 4 (PF4) were elevated in both the PG-PS and the PG-PS+clopidogrel groups, however PF4 levels showed no difference upon clopidogrel treatment, suggesting that the pro- inflammatory effect of clopidogrel may be due to its action on cells other than platelets. Histology indicated an increase in leukocyte infiltration at the inflammatory area of the joint, increased pannus formation, blood vessel proliferation, subsynovial fibrosis and cartilage erosion upon treatment with clopidogrel in PG-PS-induced arthritis animals. In summary, animals treated with clopidogrel showed a pro-inflammatory effect in the PG-PS-induced arthritis animal model, which might not be mediated by platelets. Elucidation of the mechanism of clopidogrel-induced cell responses is important to understand the role of the P2Y12 receptor in inflammation. PMID:22028806

  11. The role of rheumatoid arthritis genetic susceptibility markers in the prediction of erosive disease in patients with early inflammatory polyarthritis: results from the Norfolk Arthritis Register

    PubMed Central

    Plant, Darren; Thomson, Wendy; Lunt, Mark; Flynn, Edward; Martin, Paul; Eyre, Steven; Farragher, Tracey; Bunn, Diane; Worthington, Jane; Symmons, Deborah

    2011-01-01

    Objectives. Recent whole-genome and candidate gene association studies in RA have identified a number of single nucleotide polymorphisms (SNPs) that predispose to disease with moderate risk. It remains poorly understood how recently identified genetic factors may contribute to RA severity. We therefore sought to investigate the role of recently identified RA susceptibility SNP markers in predicting erosive outcome in patients with recent-onset inflammatory polyarthritis (IP). Methods. DNA and X-ray data were available for 1049 patients who were registered between 1990 and 2003 with the Norfolk Arthritis Register (NOAR); a primary care-based inception cohort of patients with recent-onset IP. Demographic and clinical data were recorded at inclusion, and at yearly assessments thereafter. Patients were genotyped for 18 SNP markers. The presence of serum anti citrullinated peptide antibodies (ACPAs) was assessed in samples collected at inclusion to the NOAR. The association of serological and genetic markers with poor radiological (Larsen) score at Years 1 and 5, and erosions at Years 1 and 5 was investigated. Results. Baseline ACPA positivity was associated with erosive disease and higher radiological damage. SNP markers within the TRAF1/C5 locus were associated with erosive disease at Year 1 [rs2900180: odds ratio (OR) 1.53 (95% CI 1.14, 2.05)] and Year 5 [rs2900180: OR 1.47 (95% CI 1.07, 2.02)]. None of the SNP markers tested was associated with Larsen score. Conclusion. Our results are in keeping with a previous report and suggest that the TRAF1/C5 region is associated with risk of development of radiological erosions in IP/RA patients. The finding requires replication in other large data sets. PMID:20219786

  12. Peripheral NLCR4 inflammasome participates in the genesis of acute inflammatory pain.

    PubMed

    Lopes, Alexandre H; Talbot, Jhimmy; Silva, Rangel L; Lima, Jonilson B; França, Rafael O; Verri, Waldiceu A; Mascarenhas, Danielle P; Ryffel, Bernhard; Cunha, Fernando Q; Zamboni, Dario S; Cunha, Thiago M

    2015-03-01

    Inflammatory hyperalgesia is a complex process that depends on the sensitization of primary nociceptive neurons triggered by proinflammatory mediators, such as interleukin 1β (IL-1β). Recently, the peripheral activation of caspase-1 (previously known as IL-1β-converting enzyme) was implicated in the induction of acute inflammatory pain by promoting the processing of IL-1β from its precursor form, pro-IL-1β. Caspase-1 activation in several systems requires the assembly of an intracellular molecular platform called an inflammasome. Inflammasomes consist of 1 nucleotide-binding oligomerization domain-like receptor (NLR), the adapter molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), and caspase-1. NLRP3 and NLRC4 inflammasomes are well described. However, the identity of the inflammasome that is involved in the peripheral activation of caspase-1 that accounts for acute inflammatory hyperalgesia has not been described. The present findings demonstrated that mice deficient in NLRC4 or ASC, but not in NLRP3, present reduced mechanical and thermal acute inflammatory hyperalgesia induced by carrageenan. The reduced hyperalgesia was accompanied by significant impairments in the levels of mature forms of IL-1β (p17) and caspase-1 (p20) compared to wild-type mice at the inflammatory site. Therefore, these results identified the inflammasome components NLRC4 and ASC as the molecular platform involved in the peripheral activation of caspase-1 and IL-1β maturation, which are responsible for the induction of acute inflammatory pain. In conclusion, our study provides new therapeutic targets for the control of acute inflammatory pain.

  13. TNFR1 and TNFR2 differentially mediate TNF-α-induced inflammatory responses in rheumatoid arthritis fibroblast-like synoviocytes.

    PubMed

    Zhang, Hongfeng; Xiao, Weiguo

    2017-04-01

    TNF-α has long been implicated in the progression of rheumatoid arthritis (RA). However, how the receptors of TNF-α, namely TNFR1 and TNFR2, mediate TNF-α-induced inflammatory responses in fibroblast-like synoviocytes (FLS) in RA has not been elucidated. In the present study, primary FLS cells were isolated from RA patients and treated with TNF-α in vitro. The exogenous TNF-α induced the expression and release of endogenous TNF-α in FLS. In addition, TNF-α led to gradual downregulation of TNFR1 following 1 h treatment. By contrast, the expression of TNFR2 was markedly upregulated after 12 h treatment with TNF-α. Moreover, following TNF-α treatment, the expression of interleukin (IL)-2, IL-6, and IL-8 was gradually increased with time, but their mRNA levels dropped significantly at 48 h. We further investigated the differential functions of TNFR1 and TNFR2 in FLS by conducting siRNA-mediated knockdown. The TNF-α autocrine was inhibited to a greater extent in TNFR1-silenced FLS compared with TNFR2-silenced FLS. Silencing of TNFR1, not TNFR2, activated intrinsic apoptosis and inhibited TNF-α-induced cytokine production in FLS. These results suggest that TNFR1 is the major pro-inflammatory mediator of TNF-α in FLS, whereas TNFR2, which is upregulated in response to prolonged TNF-α stimulation, may act as an immunosuppressor in FLS for the prevention of overwhelming inflammatory reactions.

  14. Dual effect of nitric oxide in articular inflammatory pain in zymosan-induced arthritis in rats

    PubMed Central

    Rocha, José C da S; Peixoto, Magno E B; Jancar, Sônia; Cunha, Fernando de Q; Ribeiro, Ronaldo de A; Rocha, Francisco A C da

    2002-01-01

    The contribution of nitric oxide (NO) to articular pain in arthritis induced by zymosan (1 mg, intra articular) in rats was assessed by measuring articular incapacitation (AI).Systemic treatment with the non-selective NO synthase (NOS) inhibitor L-NAME (10–100 mg kg−1 i.p.) or with the selective iNOS inhibitors aminoguanidine (AG; 10–100 mg kg−1 i.p.) or 1400W (0.5–1 mg kg−1 s.c.) inhibited the AI induced by injection of zymosan 30 min later.Local (intra articular) treatment with the NOS inhibitors (L-NAME or AG, 0.1–1 μmol; 1400W, 0.01 (μmol) 30 min before zymosan also inhibited the AI.Systemic or local treatment with the NOS inhibibitors (L-NAME; AG, 100 mg kg−1 i.p. or 0.1 μmol joint−1; 1400W, 1 mg kg−1 s.c. or 0.01 μmol joint−1), 2 h after zymosan did not affect the subsequent AI.Local treatment with the NO donors SNP or SIN-1, 2 h after zymosan did inhibit AI.L-NAME and AG, given i.p. inhibited nitrite but not prostaglandin E2 (PGE2) levels in the joints. L-NAME (100 mg kg−1) but not AG (100 mg kg−1) increased mean arterial blood pressure. Neither L-NAME, AG nor the NO donor SIN-1 altered articular oedema induced by zymosan.In conclusion, inhibitors of iNOS decrease pain in zymosan arthritis only when given before the zymosan. This was not due to inhibition of articular PGE2 release or oedema. NO donors also promoted antinociception in zymosan arthritis without affecting oedema. PMID:12055137

  15. Safety of celecoxib and nonselective nonsteroidal anti-inflammatory drugs in juvenile idiopathic arthritis: results of the phase 4 registry

    PubMed Central

    2014-01-01

    Background This study aimed to assess long-term safety and developmental data on juvenile idiopathic arthritis (JIA) patients treated in routine clinical practice with celecoxib or nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs). Methods Children aged ≥2 to <18 years with rheumatoid-factor–positive or –negative polyarthritis, persistent or extended oligoarthritis, or systemic arthritis were enrolled into this prospective, observational, multicenter standard-of-care registry. Eligible patients were newly or recently prescribed (≤6 months) an nsNSAID or celecoxib. Enrolled patients were followed to the end of the study, whether they remained on the original NSAID, switched, or discontinued therapy altogether. All adverse events (AEs) regardless of severity were captured in the database. Results A total of 274 patients (nsNSAID, n = 219; celecoxib, n = 55) were observed for 410 patient-years of observation. Naproxen, meloxicam, and nabumetone were the most frequently used nsNSAIDs. At baseline, the celecoxib group was older, had a numerically longer median time since diagnosis, and a numerically higher proportion of patients with a history of gastrointestinal-related NSAID intolerance. AEs reported were those frequently observed with NSAID treatment and were similar across groups (nsNSAIDs: 52.0%; celecoxib: 52.9%). Twelve unique patients experienced a total of 18 serious AEs; the most frequent were infections, and none was attributed to NSAID use. Conclusions The safety profile of celecoxib and nsNSAIDs appears similar overall. The results from this registry, ongoing pharmacovigilance, and the phase 3 trial that led to the approval of celecoxib for children with JIA provide evidence that the benefit-risk for celecoxib treatment in JIA remains positive. Trial registration ClinicalTrials.gov identifier NCT00688545. PMID:25057265

  16. Peroxiredoxin 6 differentially regulates acute and chronic cigarette smoke–mediated lung inflammatory response and injury

    PubMed Central

    Sundar, Isaac K.; Chung, Sangwoon; Hwang, Jae-Woong; Arunachalam, Gnanapragasam; Cook, Suzanne; Yao, Hongwei; Mazur, Witold; Kinnula, Vuokko L.; Fisher, Aron B.; Rahman, Irfan

    2011-01-01

    Peroxiredoxin 6 (Prdx6) exerts its protective role through peroxidase activity against H2O2 and phospholipid hydroperoxides. We hypothesized that targeted disruption of Prdx6 would lead to enhanced susceptibility to cigarette smoke (CS)-mediated lung inflammation and/or emphysema in mouse lung. Prdx6 null (Prdx6−/−) mice exposed to acute CS showed no significant increase of inflammatory cell influx or any alterations in lung levels of pro inflammatory cytokines compared to wild-type (WT) mice. Lung levels of antioxidant enzymes were significantly increased in acute CS-exposed Prdx6−/− compared to WT mice. Overexpressing (Prdx6+/+) mice exposed to acute CS showed significant decrease in lung antioxidant enzymes associated with increased inflammatory response compared to CS-exposed WT mice or air-exposed Prdx6−/− mice. However, chronic 6 months of CS exposure resulted in increased lung inflammatory response, mean linear intercept (Lm), and alteration in lung mechanical properties in Prdx6−/− when compared to WT mice exposed to CS. These data show that targeted disruption of Prdx6 does not lead to increased lung inflammatory response but is associated with increased antioxidants, suggesting a critical role of lung Prdx6 and several compensatory mechanisms during acute CS-induced adaptive response, whereas this protection is lost in chronic CS exposure leading to emphysema. PMID:20939758

  17. Cyclophilin A may contribute to the inflammatory processes in rheumatoid arthritis through induction of matrix degrading enzymes and inflammatory cytokines from macrophages.

    PubMed

    Kim, Ho; Kim, Won-Jung; Jeon, Sung-Tak; Koh, Eun-Mi; Cha, Hoon-Suk; Ahn, Kwang-Sung; Lee, Won-Ha

    2005-09-01

    Cyclophilin A (CypA) levels increase in the sera and synovial fluids of rheumatoid arthritis (RA) patients, but the cell types expressing CypA and the function of CypA in the pathogenesis of RA are not known yet. Immunohistochemistry analyses revealed high level CypA staining in the macrophages in the lining layers of human RA and osteoarthritis synovium. Low level CypA staining was also detected in endothelial cells, lymphocytes, and smooth muscle cells in RA synovium. Further investigation of the CypA function using monocyte/macrophage cell lines revealed that CypA induced expression of cytokine/chemokines such as TNF-alpha, IL-8, MCP-1, and IL-1beta and matrix metalloproteinase (MMP)-9 through a pathway that is dependent on NFkappaB activation. Furthermore, MMP-9 staining pattern overlapped with that of CypA in both RA and OA synovium. Our data suggest that CypA may stimulate macrophages to degrade joint cartilage via MMP-9 expression and promote inflammation via pro-inflammatory cytokine secretion.

  18. Are acute exacerbations of chronic inflammatory appendicitis triggered by coprostasis and/or coproliths?

    PubMed

    Sgourakis, George; Sotiropoulos, Georgios C; Molmenti, Ernesto P; Eibl, Charis; Bonticous, Stylianous; Moege, Jurgen; Berchtold, Christoph

    2008-05-28

    To examine the role of coprostasis and coproliths in recurrent appendicitis. We evaluated four hundred and twenty seven consecutive pathology reports of all appendectomy specimens from January 2003 to December 2004. Findings were categorised as showing acute appendicitis, acute recurrent appendicitis, subacute recurrent appendicitis, chronic appendicitis, or appendices without inflammation. All patients had presented with acute right lower quadrant pain. In 94 instances, there was a history of recurrent similar episodes in the past. Of the 427 histology reports, 294 were inter-preted as showing acute appendicitis, 56 acute recurrent appendicitis, 34 subacute recurrent appen-dicitis, 28 chronic appendicitis, and 15 non-inflamed appendices. Coprostasis was observed in 58 patients (13.58%) and the presence of coprolith in 6 (1.4%). Coprostasis, and age, were among the predictors in the final model. Coprostasis but not coproliths seems to be a contributing factor to acute exacerbations of chronic inflammatory appendicitis.

  19. Novel phosphoinositide 3-kinase δ,γ inhibitor: potent anti-inflammatory effects and joint protection in models of rheumatoid arthritis.

    PubMed

    Boyle, David L; Kim, Hae-Rim; Topolewski, Katharyn; Bartok, Beatrix; Firestein, Gary S

    2014-02-01

    Phosphoinositide 3-kinases γ and δ (PI3Kγ and PI3Kδ) are expressed in rheumatoid arthritis (RA) synovium and regulate innate and adaptive immune responses. We determined the effect of a potent PI3Kδ,γ inhibitor, IPI-145, in two preclinical models of RA. IPI-145 was administered orally in rat adjuvant-induced arthritis (AA) and intraperitoneally in mouse collagen-induced arthritis (CIA). Efficacy was assessed by paw swelling, clinical scores, histopathology and radiography, and microcomputed tomography scanning. Gene expression and Akt phosphorylation in joint tissues were determined by quantitative real-time polymerase chain reaction and Western blot analysis. Serum concentrations of anti-type II collagen (CII) IgG and IgE were measured by immunoassay. T-cell responses to CII were assayed using thymidine incorporation and immunoassay. IPI-145 significantly reduced arthritis severity in both RA models using dosing regimens initiated before onset of clinical disease. Treatment of established arthritis with IPI-145 in AA, but not CIA, significantly decreased arthritis progression. In AA, histology scores, radiographic joint damage, and matrix metalloproteinase (MMP)-13 expression were reduced in IPI-145-treated rats. In CIA, joint histology scores and expression of MMP-3 and MMP-13 mRNA were lower in the IPI-145 early treatment group than in the vehicle group. The ratio of anti-CII IgG2a to total IgG in CIA was modestly reduced. Interleukin-17 production in response to CII was decreased in the IPI-145-treated group, suggesting an inhibitory effect on T-helper cell 17 differentiation. These data show that PI3Kδ,γ inhibition suppresses inflammatory arthritis, as well as bone and cartilage damage, through effects on innate and adaptive immunity and that IPI-145 is a potential therapy for RA.

  20. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  1. Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

    PubMed

    Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

    2014-06-15

    Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.

  2. Immune reconstitution inflammatory syndrome presenting as secondary syphilis with polymorphous erythema and knee arthritis.

    PubMed

    Brochard, J; Khatchatourian, L; Woaye-Hune, P; Biron, C; Lefebvre, M; Denis-Musquer, M; Grange, P; Dupin, N; Raffi, F

    2017-03-08

    Syphilis and HIV are strongly linked to one another and immune reconstitution inflammatory syndrome (IRIS) after antiretroviral therapy (ART) initiation can complicate matters. A 24-years-old homosexual man was hospitalized for fever, cough and headache. HIV infection had been diagnosed 5 years earlier but he discontinued ART for the last 2 years. This article is protected by copyright. All rights reserved.

  3. Collagen-induced arthritis and related animal models: how much of their pathogenesis is auto-immune, how much is auto-inflammatory?

    PubMed

    Billiau, Alfons; Matthys, Patrick

    2011-01-01

    In this review, we discuss our studies on the pathogenesis of collagen-induced arthritis (CIA) and related mouse models for rheumatoid arthritis. Of note, these models invariably rely on the use of complete Freund's adjuvant (CFA). Our analysis has focused on explaining the dichotomous - either protective or disease-promoting - role of endogenous IFN-γ. Induction of a myelopoietic burst by CFA was identified as an important and underestimated factor in mediating the role of IFN-γ and other cytokines (IL-6, IL-17, GCP-2, RANK-L). Myelopoiesis provides an excess in precursors for joint-infiltrating neutrophils and osteoclasts. We postulate that classical CIA is primarily an auto-inflammatory disease, in part because of a strong innate immune response to the adjuvant. Superimposed on this, collagen-specific auto-immunity reinforces inflammatory reactivity in joints.

  4. Speckle tracking imaging in acute inflammatory pericardial diseases.

    PubMed

    Leitman, Marina; Bachner-Hinenzon, Noa; Adam, Dan; Fuchs, Therese; Theodorovich, Nickolas; Peleg, Eli; Krakover, Ricardo; Moravsky, Gil; Uriel, Nir; Vered, Zvi

    2011-05-01

    Left ventricular (LV) function in acute perimyocarditis is variable. We evaluated LV function in patients with acute perimyocarditis with speckle tracking. Thirty-eight patients with acute perimyocarditis and 20 normal subjects underwent echocardiographic examination. Three-layers strain and twist angle were assessed with a speckle tracking. Follow-up echo was available in 21 patients. Strain was higher in normal subjects than in patients with perimyocarditis. Twist angle was reduced in perimyocarditis--10.9° ± 5.4 versus 17.6° ± 5.8, P < 0.001. Longitudinal strain and twist angle were higher in normal subjects than in patients with perimyocarditis and apparently normal LV function. Follow-up echo in 21 patients revealed improvement in longitudinal strain. Patients with acute perimyocarditis have lower twist angle, longitudinal and circumferential strain. Patients with perimyocarditis and normal function have lower longitudinal strain and twist angle. Short-term follow-up demonstrated improvement in clinical parameters and longitudinal strain despite of residual regional LV dysfunction. © 2011, Wiley Periodicals, Inc.

  5. Rheumatoid Arthritis: Can It Affect the Eyes?

    MedlinePlus

    Rheumatoid arthritis: Can it affect the eyes? Can rheumatoid arthritis affect the eyes? Answers from April Chang-Miller, M.D. Rheumatoid arthritis is a chronic inflammatory disease that primarily affects ...

  6. Rheumatoid Arthritis and Complementary Health Approaches

    MedlinePlus

    ... R S T U V W X Y Z Rheumatoid Arthritis: In Depth Share: On This Page Key Points ... will help ensure coordinated and safe care. About Rheumatoid Arthritis Rheumatoid arthritis is an inflammatory autoimmune disease—a ...

  7. Bioassay-guided evaluation of Dioscorea villosa – an acute and subchronic toxicity, antinociceptive and anti-inflammatory approach

    PubMed Central

    2013-01-01

    Background Dioscorea villosa (DV) has been used in Brazil as an alternative medicine to attenuate menopause symptoms, as well as for the treatment of joint pain and rheumatoid arthritis. In spite of the popular use of DV for the treatment of various disorders, there are limited scientific data regarding safety aspects of this herb. In this regard, we carried out to evaluated both antinociceptive and anti-inflammatory activities in experimental models and assess the toxic effects of the acute (single dose) and subchronic (30 days) oral administration of dry extract of Dioscorea villosa in rodents. Methods The LC analyses were performed to assess the presence of the diosgenin in samples of DV. The antinociceptive study of DV was performed using models of acetic acid-induced writhing and formalin-induced pain in mice. The anti-inflammatory study was accomplished by leukocyte migration to the peritoneal cavity. A dry extract of DV was tested at doses of 100, 200 and 400 mg/kg (per os or p.o.). The toxicological properties of the dry extract were evaluated by toxicity assays of acute (5 g/kg, single dose) and subchronic (1 g/kg/day, 30 days) treatment. Haematological, biochemical, and histopathological parameters were studied. The results are expressed as mean ± S.D., and statistical analysis of the data were performed with the Student’s t-test or one-way analysis of variance (ANOVA) followed by Tukey’s test. In all cases differences were considered significant if p < 0.05. Results HPLC-DAD analysis of the extract from DV revealed the presence of diosgenin as the major compound. Doses of 200 and 400 mg⁄kg significantly reduced the amount of acetic acid-induced writhing in relation to the vehicle (p < 0.0001). In the first phase, using the formalin-induced neurogenic pain test, only the 400 mg/kg dose of DV showed significant inhibition of neurogenic pain (p < 0.001). In the second phase, 200 and 400 mg/kg of DV showed significant

  8. Animal Models of Bone Loss in Inflammatory Arthritis: from Cytokines in the Bench to Novel Treatments for Bone Loss in the Bedside-a Comprehensive Review.

    PubMed

    Alves, C Henrique; Farrell, Eric; Vis, Marijn; Colin, Edgar M; Lubberts, Erik

    2016-08-01

    Throughout life, bone is continuously remodelled. Bone is formed by osteoblasts, from mesenchymal origin, while osteoclasts induce bone resorption. This process is tightly regulated. During inflammation, several growth factors and cytokines are increased inducing osteoclast differentiation and activation, and chronic inflammation is a condition that initiates systemic bone loss. Rheumatoid arthritis (RA) is a chronic inflammatory auto-immune disease that is characterised by active synovitis and is associated with early peri-articular bone loss. Peri-articular bone loss precedes focal bone erosions, which may progress to bone destruction and disability. The incidence of generalised osteoporosis is associated with the severity of arthritis in RA and increased osteoporotic vertebral and hip fracture risk. In this review, we will give an overview of different animal models of inflammatory arthritis related to RA with focus on bone erosion and involvement of pro-inflammatory cytokines. In addition, a humanised endochondral ossification model will be discussed, which can be used in a translational approach to answer osteoimmunological questions.

  9. An animal model of chronic inflammatory pain: pharmacological and temporal differentiation from acute models.

    PubMed

    Wilson, Alex W; Medhurst, Stephen J; Dixon, Claire I; Bontoft, Nick C; Winyard, Lisa A; Brackenborough, Kim T; De Alba, Jorge; Clarke, Christopher J; Gunthorpe, Martin J; Hicks, Gareth A; Bountra, Chas; McQueen, Daniel S; Chessell, Iain P

    2006-08-01

    Clinically, inflammatory pain is far more persistent than that typically modelled pre-clinically, with the majority of animal models focussing on short-term effects of the inflammatory pain response. The large attrition rate of compounds in the clinic which show pre-clinical efficacy suggests the need for novel models of, or approaches to, chronic inflammatory pain if novel mechanisms are to make it to the market. A model in which a more chronic inflammatory hypersensitivity phenotype is profiled may allow for a more clinically predictive tool. The aims of these studies were to characterise and validate a chronic model of inflammatory pain. We have shown that injection of a large volume of adjuvant to the intra-articular space of the rat knee results in a prolonged inflammatory pain response, compared to the response in an acute adjuvant model. Additionally, this model also results in a hypersensitive state in the presence and absence of inflammation. A range of clinically effective analgesics demonstrate activity in this chronic model, including morphine (3mg/kg, t.i.d.), dexamethasone (1mg/kg, b.i.d.), ibuprofen (30mg/kg, t.i.d.), etoricoxib (5mg/kg, b.i.d.) and rofecoxib (0.3-10mg/kg, b.i.d.). A further aim was to exemplify the utility of this chronic model over the more acute intra-plantar adjuvant model using two novel therapeutic approaches; NR2B selective NMDA receptor antagonism and iNOS inhibition. Our data shows that different effects were observed with these therapies when comparing the acute model with the model of chronic inflammatory joint pain. These data suggest that the chronic model may be more relevant to identifying mechanisms for the treatment of chronic inflammatory pain states in the clinic.

  10. Glucocorticoid Receptor-Mediated Repression of Pro-Inflammatory Genes in Rheumatoid Arthritis

    DTIC Science & Technology

    2015-10-01

    pathologies (1, 5, 6). Since the discovery of GC in the late 1940s, their potent immunomodulatory and anti- inflammatory activities have been actively...atrophy or wasting of the skin and musculoskeletal system. Eventually, mechanistic information on GC signaling led to the structural characterization of GC...ultimately lead to skeletal muscle atrophy and weakness (121, 122). Indeed, pathological conditions associated with high circulating levels of GC promote

  11. How to differentiate acute pelvic inflammatory disease from acute appendicitis ? A decision tree based on CT findings.

    PubMed

    El Hentour, Kim; Millet, Ingrid; Pages-Bouic, Emmanuelle; Curros-Doyon, Fernanda; Molinari, Nicolas; Taourel, Patrice

    2017-09-11

    To construct a decision tree based on CT findings to differentiate acute pelvic inflammatory disease (PID) from acute appendicitis (AA) in women with lower abdominal pain and inflammatory syndrome. This retrospective study was approved by our institutional review board and informed consent was waived. Contrast-enhanced CT studies of 109 women with acute PID and 218 age-matched women with AA were retrospectively and independently reviewed by two radiologists to identify CT findings predictive of PID or AA. Surgical and laboratory data were used for the PID and AA reference standard. Appropriate tests were performed to compare PID and AA and a CT decision tree using the classification and regression tree (CART) algorithm was generated. The median patient age was 28 years (interquartile range, 22-39 years). According to the decision tree, an appendiceal diameter ≥ 7 mm was the most discriminating criterion for differentiating acute PID and AA, followed by a left tubal diameter ≥ 10 mm, with a global accuracy of 98.2 % (95 % CI: 96-99.4). Appendiceal diameter and left tubal thickening are the most discriminating CT criteria for differentiating acute PID from AA. • Appendiceal diameter and marked left tubal thickening allow differentiating PID from AA. • PID should be considered if appendiceal diameter is < 7 mm. • Marked left tubal diameter indicates PID rather than AA when enlarged appendix. • No pathological CT findings were identified in 5 % of PID patients.

  12. Inflammatory triggers of acute rejection of organ allografts.

    PubMed

    Mori, Daniel N; Kreisel, Daniel; Fullerton, James N; Gilroy, Derek W; Goldstein, Daniel R

    2014-03-01

    Solid organ transplantation is a vital therapy for end stage diseases. Decades of research have established that components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the innate immune system is activated at the time of organ implantation by the release of endogenous inflammatory triggers. This review discusses the nature of these triggers in organ transplantation and also potential mediators that may enhance inflammation resolution after organ implantation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Inflammatory triggers of acute rejection of organ allografts

    PubMed Central

    Mori, Daniel N.; Kreisel, Daniel; Fullerton, James N.; Gilroy, Derek W.; Goldstein, Daniel R.

    2014-01-01

    Summary Solid organ transplantation is a vital therapy for end stage diseases. Decades of research has established that the components of the adaptive immune system are critical for transplant rejection, but the role of the innate immune system in organ transplantation is just emerging. Accumulating evidence indicates that the innate immune system is activated at the time of organ implantation by the release of endogenous inflammatory triggers. This review discusses the nature of these triggers in organ transplantation and also potential mediators that may enhance inflammation resolution after organ implantation. PMID:24517430

  14. Pathophysiological mechanisms of acute pancreatitis define inflammatory markers of clinical prognosis.

    PubMed

    Minkov, Georgi A; Halacheva, Krasimira S; Yovtchev, Yovcho P; Gulubova, Maya V

    2015-07-01

    Development of acute pancreatitis illustrates the need to understand the basic mechanisms of disease progression to drive the exploration of therapeutic options. Cytokines play a major role in the pathogenesis of acute pancreatitis as underlying systemic inflammatory response, tissue damage, and organ dysfunction. However, little is known about circulating concentrations of these inflammatory markers and their real impact on clinical practice. Experimental studies have suggested that the prognosis for acute pancreatitis depends on the degree of pancreatic necrosis and the intensity of multisystem organ failure generated by the systemic inflammatory response. This suggests an intricate balance between localized tissue damage with proinflammatory cytokine production and a systemic anti-inflammatory response that restricts the inappropriate movement of proinflammatory agents into the circulation. Implication of such mediators suggests that interruption or blunting of an inappropriate immune response has the potential to improve outcome. A detailed understanding of pathophysiological processes and immunological aspects in patients with acute pancreatitis is the basis for the development of therapeutic strategies that will provide significant reductions in morbidity and mortality.

  15. Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome.

    PubMed

    Bhatia, Madhav; Moochhala, Shabbir

    2004-02-01

    Inflammatory response leading to organ dysfunction and failure continues to be the major problem after injury in many clinical conditions such as sepsis, severe burns, acute pancreatitis, haemorrhagic shock, and trauma. In general terms, systemic inflammatory response syndrome (SIRS) is an entirely normal response to injury. Systemic leukocyte activation, however, is a direct consequence of a SIRS and if excessive, can lead to distant organ damage and multiple organ dysfunction syndrome (MODS). When SIRS leads to MODS and organ failure, the mortality becomes high and can be more than 50%. Acute lung injury that clinically manifests as acute respiratory distress syndrome (ARDS) is a major component of MODS of various aetiologies. Inflammatory mediators play a key role in the pathogenesis of ARDS, which is the primary cause of death in these conditions. This review summarizes recent studies that demonstrate the critical role played by inflammatory mediators such as tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, platelet activating factor (PAF), IL-10, granulocyte macrophage-colony stimulating factor (GM-CSF), C5a, intercellular adhesion molecule (ICAM)-1, substance P, chemokines, VEGF, IGF-I, KGF, reactive oxygen species (ROS), and reactive nitrogen species (RNS) in the pathogenesis of ARDS. It is reasonable to speculate that elucidation of the key mediators in ARDS coupled with the discovery of specific inhibitors would make it possible to develop clinically effective anti-inflammatory therapy.

  16. Serum inflammatory biomarkers fail to identify early axial spondyloarthritis: results from the SpondyloArthritis Caught Early (SPACE) cohort

    PubMed Central

    Turina, Maureen C; Yeremenko, Nataliya; van Gaalen, Floris; van Oosterhout, Maikel; Berg, Inger J; Ramonda, Ramona; Lebre, Cristina (M C); Landewé, Robert; Baeten, Dominique

    2017-01-01

    Introduction Decreasing the diagnostic delay in axial spondyloarthritis (axSpA) remains a major challenge. Here, we assessed the value of serum inflammatory biomarkers to distinguish early axSpA from other pathologies in a large cohort of patients referred with early back pain. Methods Serum c reactive protein (CRP), erythrocyte sedimentation rate (ESR) and calprotectin were determined in the SPondyloArthritis Caught Early (SPACE) cohort (n=310), an early back pain inception cohort. Additionally, explorative serum biomarkers derived from the literature (interleukin-27 (IL-27), human β-defensin-2 (hBD-2) and lipcolin-2 (LCN-2)) were determined by ELISA in full-blown patients with ankylosing spondylitis (AS) (n=21) and healthy controls (n=20). Results Serum CRP and ESR levels were not elevated in early axSpA versus ‘control’ back pain patients. Serum calprotectin was elevated in early axSpA versus controls (p=0.01) but failed to identify early axSpA at the individual level (positive predictive value of 38.7%). As to explorative biomarkers, serum levels of IL-27 were not detectable, and hBD-2 and LCN-2 serum levels were not elevated in full-blown AS versus healthy controls (p=0.572, p=0.562, respectively). Therefore, these markers were not further determined in the SPACE cohort. Conclusions None of the candidate serum inflammatory markers were useful as diagnostic markers in the early phase of axSpA. PMID:28123777

  17. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease.

    PubMed

    Scher, Jose U; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G; Littman, Dan R; Abramson, Steven B

    2015-01-01

    To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). High-throughput 16S ribosomal RNA pyrosequencing was utilized to compare the community composition of gut microbiota in patients with PsA (n = 16), patients with psoriasis of the skin (n = 15), and healthy, matched control subjects (n = 17). Samples were further assessed for the presence and levels of fecal and serum secretory IgA (sIgA), proinflammatory proteins, and fatty acids. The gut microbiota observed in patients with PsA and patients with skin psoriasis was less diverse when compared to that in healthy controls. This could be attributed to the reduced presence of several taxa. Samples from both patient groups showed a relative decrease in abundance of Coprococcus species, while samples from PsA patients were also characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA levels and decrease in RANKL levels. Analysis of fatty acids revealed low fecal quantities of hexanoate and heptanoate in both patients with PsA and patients with psoriasis. Patients with PsA and patients with skin psoriasis had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had a lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that previously described in patients with inflammatory bowel disease and was associated with changes in specific inflammatory proteins unique to this group, and distinct from that in patients with skin psoriasis and healthy controls. Thus, the role of the gut microbiome in the continuum of psoriasis-PsA pathogenesis and the associated immune response merits further study. Copyright © 2015 by the American College of Rheumatology.

  18. Decreased Bacterial Diversity Characterizes an Altered Gut Microbiota in Psoriatic Arthritis and Resembles Dysbiosis of Inflammatory Bowel Disease

    PubMed Central

    Scher, Jose U.; Ubeda, Carles; Artacho, Alejandro; Attur, Mukundan; Isaac, Sandrine; Reddy, Soumya M.; Marmon, Shoshana; Neimann, Andrea; Brusca, Samuel; Patel, Tejas; Manasson, Julia; Pamer, Eric G.; Littman, Dan R.; Abramson, Steven B.

    2014-01-01

    Objective To characterize the diversity and taxonomic relative abundance of the gut microbiota in patients with never-treated, recent-onset psoriatic arthritis (PsA). Methods High-throughput 16S rRNA pyrosequencing was utilized to compare community composition of gut microbiota in PsA patients (n=16), subjects with psoriasis of the skin (Ps) (n=15) and healthy, matched-controls (n=17). Samples were further assessed for the presence and levels of fecal and serum secretory immunoglobulin A (sIgA), pro-inflammatory proteins and fatty-acids. Results The gut microbiota observed in PsA and Ps patients was less diverse when compared to healthy controls. These could be attributed to the reduced presence of several taxa. While both groups showed a relative decrease in Coprococcus spp., PsA samples were characterized by a significant reduction in Akkermansia, Ruminococcus, and Pseudobutyrivibrio. Supernatants of fecal samples from PsA patients revealed an increase in sIgA and a decrease in receptor activator of nuclear factor kappa-B ligand (RANKL) levels. Fatty acid analysis revealed low levels of hexanoate and heptanoate in PsA and Ps patients. Conclusion PsA and Ps patients had a lower relative abundance of multiple intestinal bacteria. Although some genera were concomitantly decreased in both conditions, PsA samples had lower abundance of reportedly beneficial taxa. This gut microbiota profile in PsA was similar to that published for patients with IBD and was associated with changes in specific inflammatory proteins unique to this group, and distinct from Ps and controls. Thus, the role of gut microbiota in the continuum of Ps-PsA pathogenesis and the associated immune response merits further study. PMID:25319745

  19. Gingival crevicular fluid MMP-8 and -13 and TIMP-1 levels in patients with rheumatoid arthritis and inflammatory periodontal disease.

    PubMed

    Biyikoğlu, Başak; Buduneli, Nurcan; Kardeşler, Levent; Aksu, Kenan; Pitkala, Marjut; Sorsa, Timo

    2009-08-01

    The purpose of this study was to compare gingival crevicular fluid (GCF) levels of matrix metalloproteinase (MMP)-8 and -13 and tissue inhibitor of MMP (TIMP)-1 in patients with rheumatoid arthritis (RA) and systemically healthy counterparts with inflammatory periodontal disease. Subjects (N = 74) were divided into five groups: 12 patients with RA and gingivitis; 13 patients with RA and periodontitis; 12 systemically healthy patients with gingivitis; 13 systemically healthy patients with periodontitis; and 24 periodontally and systemically healthy volunteers. Full-mouth clinical periodontal measurements were performed at six sites/tooth. GCF samples obtained from two sites in single-rooted teeth were analyzed by immunofluorometric assay and enzyme-linked immunosorbent assay. Data were assessed statistically by parametric tests. The total amounts of MMP-8 were lower in the healthy control group than in RA-gingivitis, RA-periodontitis, and healthy-periodontitis groups (P <0.05). MMP-13 levels were similar in all five study groups (P >0.05). Patients with RA and gingivitis or periodontitis exhibited levels of MMP-8 and -13 and TIMP-1 that were similar to systemically healthy counterparts (P >0.05). The coexistence of RA and periodontitis did not significantly affect the investigated parameters. GCF MMP-8 levels increased with periodontal inflammation. Despite the long-term usage of corticosteroids and non-steroidal anti-inflammatory drugs, similar GCF MMP-8 and -13 levels in patients with RA and systemically healthy counterparts suggest that RA may create a tendency to overproduce these enzymes.

  20. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy

    PubMed Central

    Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E.; Maverakis, Emanual; Wilkins, Danice E.C.; Alderson, Kory L.; Hsiao, Hui-Hua; Weiss, Jonathan M.; Monjazeb, Arta M.; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Redelman, Doug; Taub, Dennis D.

    2013-01-01

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice. PMID:24081947

  1. Aging predisposes to acute inflammatory induced pathology after tumor immunotherapy.

    PubMed

    Bouchlaka, Myriam N; Sckisel, Gail D; Chen, Mingyi; Mirsoian, Annie; Zamora, Anthony E; Maverakis, Emanual; Wilkins, Danice E C; Alderson, Kory L; Hsiao, Hui-Hua; Weiss, Jonathan M; Monjazeb, Arta M; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L; Blazar, Bruce R; Wiltrout, Robert H; Redelman, Doug; Taub, Dennis D; Murphy, William J

    2013-10-21

    Cancer commonly occurs in the elderly and immunotherapy (IT) is being increasingly applied to this population. However, the majority of preclinical mouse tumor models assessing potential efficacy and toxicities of therapeutics use young mice. We assessed the impact of age on responses to systemic immune stimulation. In contrast to young mice, systemic cancer IT regimens or LPS given to aged mice resulted in rapid and lethal toxicities affecting multiple organs correlating with heightened proinflammatory cytokines systemically and within the parenchymal tissues. This inflammatory response and increased morbidity with age was independent of T cells or NK cells. However, prior in vivo depletion of macrophages in aged mice resulted in lesser cytokine levels, increased survival, and decreased liver histopathology. Furthermore, macrophages from aged mice and normal human elderly volunteers displayed heightened TNF and IL-6 production upon in vitro stimulation. Treatment of both TNF knockout mice and in vivo TNF blockade in aged mice resulted in significant increases in survival and lessened pathology. Importantly, TNF blockade in tumor-bearing, aged mice receiving IT displayed significant anti-tumor effects. These data demonstrate the critical role of macrophages in the age-associated hyper-inflammatory cytokine responses to systemic immunostimulation and underscore the importance of performing preclinical assessments in aged mice.

  2. Comparing guideline-based care quality for inflammatory bowel disease and rheumatoid arthritis patients within a medical home

    PubMed Central

    Caldera, Freddy; Saha, Sumona; Wald, Arnold; Cooley, David M.; Zhao, Ying-Qi; Li, Zhanhai; Bartels, Christie M.

    2016-01-01

    Background Rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) patient populations face similar risks of chronic immunosuppression including corticosteroid use. We compared the receipt of preventive services between IBD and RA populations according to published quality metrics. Methods We defined a single-center cohort of patients with IBD or RA receiving specialty and primary care. Electronic health record abstraction assessed quality metrics, sociodemographics, comorbidity, and utilization. Comparisons used multivariate odds ratios and Student’s t-tests. Results 218 RA and 190 IBD patients were included. In multivariate analysis, IBD patients were less likely to receive pneumococcal vaccination (OR=0.29, 95% CI: 0.11–0.85), while RA patients underwent glucocorticoid-induced osteoporosis screening more often (100% vs. 82.5%, p = 0.023). Conclusions Gastroenterologists can improve care quality for IBD patients by assuming greater responsibility for preventive care in IBD patients and/or collaborating with primary care and health systems to improve preventive care delivery. PMID:27029237

  3. Evaluation of selected ergonomic assessment tools for use in providing job accommodation for people with inflammatory arthritis.

    PubMed

    Village, Judy; Backman, Catherine L; Lacaille, Diane

    2008-01-01

    Inflammatory arthritis (IA) is a leading cause of work disability, especially for those with jobs involving repetitive, hand-intensive or manual work. Ergonomic interventions may mediate against job loss. Our objective was to identify desirable features of an ergonomic tool for use in providing job accommodation for people with IA, and to evaluate a selection of ergonomic and rehabilitation tools against these features. Eight desirable features were compared across 16 assessment tools. None of the tools met all the pre-determined features. Ergonomic assessment tools should incorporate objective assessment of risk factors together with subjective perceptions of symptom aggravation, and identify risk factors that may not currently be causing problems, but may increase risk of aggravation or injury in the future. To accommodate the needs of people with IA, the tool should allow for evaluation of risks and generation of solutions without a worksite visit in situations where the client does not want to disclose their illness. Finally, an assessment tool needs to be applicable to a wide range of worksites, easy to use, valid, and reliable. Against these criteria, it appears that there is a lack of appropriate ergonomic assessment tools for use in people with IA.

  4. Depression and inflammatory arthritis are associated in both Western and Non-Western countries: Findings from the World Health Survey 2002.

    PubMed

    Apfelbacher, Christian; Brandstetter, Susanne; Herr, Raphael; Ehrenstein, Boris; Loerbroks, Adrian

    2017-01-01

    Epidemiological studies have linked arthritis to depression. However, it remains unclear to what degree the association between arthritis and depression extends to low income countries and whether it can be replicated for inflammatory arthritis (IA). We aimed to address these knowledge gaps based on a large multi-national sample. Cross-sectional data was drawn from the 2002 World Health Survey. IA was defined as reports of either a diagnosis or treatment of arthritis and morning stiffness for >30min. Self-reported depression was defined as positive if participants reported its prior diagnosis or treatment or if they were classified as suffering from a major depressive episode by a seven-item screening instrument. Multivariable logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the entire sample and stratified by sex and continent. The odds of IA was 2.6-fold increased in those with depression compared to those without (OR=2.64, 95% CI 2.18-3.21) in the entire sample. This association was observed in both men (OR=3.06, 95% CI 2.19-4.27) and women (OR=2.50, 95% CI 1.95-3.21). Similar associations were found on the continent level, but were generally stronger for the Americas and Asia compared to Africa and Europe. Although our definition of IA was limited by the use of self-reported morning stiffness, this study suggests that there is a positive association between inflammatory arthritis and depression in Western and Non-Western countries, suggesting that this relationship represents a universal phenomenon. Copyright © 2016. Published by Elsevier Inc.

  5. SIRT1/Adenosine Monophosphate-Activated Protein Kinase α Signaling Enhances Macrophage Polarization to an Anti-inflammatory Phenotype in Rheumatoid Arthritis.

    PubMed

    Park, So Youn; Lee, Sung Won; Lee, Sang Yeob; Hong, Ki Whan; Bae, Sun Sik; Kim, Koanhoi; Kim, Chi Dae

    2017-01-01

    Macrophages are crucially involved in the pathogenesis of rheumatoid arthritis (RA). Macrophages of the M1 phenotype act as pro-inflammatory mediators in synovium, whereas those of the M2 phenotype suppress inflammation and promote tissue repair. SIRT1 is a class 3 histone deacetylase with anti-inflammatory characteristics. However, the role played by SIRT1 in macrophage polarization has not been defined in RA. We investigated whether SIRT1 exerts anti-inflammatory effects by modulating M1/M2 polarization in macrophages from RA patients. In this study, SIRT1 activation promoted the phosphorylation of an adenosine monophosphate-activated protein kinase (AMPK) α/acetyl-CoA carboxylase in macrophages exposed to interleukin (IL)-4, and that this resulted in the expressions of M2 genes, including MDC, FcεRII, MrC1, and IL-10, at high levels. Furthermore, these expressions were inhibited by sirtinol (an inhibitor of SIRT1) and compound C (an inhibitor of AMPK). Moreover, SIRT1 activation downregulated LPS/interferon γ-mediated NF-κB activity by inhibiting p65 acetylation and the expression of M1 genes, such as CCL2, iNOS, IL-12 p35, and IL-12 p40. Macrophages from SIRT1 transgenic (Tg)-mice exhibited enhanced polarization of M2 phenotype macrophages and reduced polarization of M1 phenotype macrophages. In line with these observations, SIRT1-Tg mice showed less histological signs of arthritis, that is, lower TNFα and IL-1β expressions and less severe arthritis in the knee joints, compared to wild-type mice. Taken together, the study shows activation of SIRT1/AMPKα signaling exerts anti-inflammatory activities by regulating M1/M2 polarization, and thereby reduces inflammatory responses in RA. Furthermore, it suggests that SIRT1 signaling be viewed as a therapeutic target in RA.

  6. Comparative Expression Analyses of Pro- versus Anti-Inflammatory Mediators within Synovium of Patients with Joint Trauma, Osteoarthritis, and Rheumatoid Arthritis

    PubMed Central

    Shaqura, Mohammed; John, Thilo; Likar, Rudolf; Ebied, Reham Said; Schäfer, Michael

    2017-01-01

    Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium. PMID:28316377

  7. Cellular and molecular mechanisms of bone damage and repair in inflammatory arthritis.

    PubMed

    Swales, Catherine; Sabokbar, Afsie

    2014-08-01

    Bone remodelling relies on tightly controlled cycles of bone resorption and formation, mediated by osteoclasts and osteoblasts, respectively. The past two decades have seen a huge increase in our understanding of immune modulation and disruption of bone homeostasis in rheumatic diseases; identification of the molecular pathways responsible for accelerated bone loss in such conditions has given rise to potential novel therapeutic targets. Most recently, the role of microRNAs in inflammatory and noninflammatory bone loss raises the intriguing possibility that modification of cellular protein translation could also be a treatment strategy for bone damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. WITHDRAWN: Antibiotics / anti-inflammatories for reducing acute inflammatory episodes in lymphoedema of the limbs.

    PubMed

    Badger, Caroline M A; Preston, Nancy J; Seers, Kate; Mortimer, Peter S

    2009-01-21

    Lymphoedema is a chronic, progressive condition and one area of debate is the optimum management for infective/inflammatory episodes (AIE's). To determine whether antibiotic/anti-inflammatory drugs given prophylactically reduce the number and severity of AIE's in patients with lymphoedema. We searched the Cochrane Breast Cancer Group register in September 2003, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2003), CINAHL, MEDLINE, PASCAL, SIGLE, UnCover, reference lists produced by The British Lymphology Society, the National Research Register (NRR) and the International Society of Lymphology congress proceedings. Randomised controlled trials testing an antibiotic or anti-inflammatory drug against placebo (with or without physical therapies) were included. Eligibility for inclusion was confirmed by two blinded reviewers. The papers were screened independently using a checklist of criteria relating to quality. Both reviewers extracted data from the eligible studies using a data extraction form. Four studies (364 randomised patients) were included. Two studied the effects of intensive physical treatment plus selenium or placebo in preventing AIE's, and two studied the effects of Ivermectin, Diethylcarbamazine (DEC) (anti-filarial agents) and penicillin as prophylactic treatment for adeno lymphangitis(ADL) versus placebo.Both selenium trials reported no inflammatory episodes during the trial period in the treated group but one case of infection in the two placebo groups respectively. Seven additional cases of infection in trial one and 14 cases in trial two required treatment in the three month follow up period.One anti-filarial trial reported 127 ADL episodes for all groups during the treatment year (compared with 684 episodes during the pre-treatment year). There were 228 ADL episodes during the trial follow-up year but no findings were significant. No link was found between the grade of oedema and the frequency of ADL episodes

  9. Inflammatory bone spur formation in psoriatic arthritis is different from bone spur formation in hand osteoarthritis.

    PubMed

    Finzel, Stephanie; Sahinbegovic, Enijad; Kocijan, Roland; Engelke, Klaus; Englbrecht, Matthias; Schett, Georg

    2014-11-01

    To investigate the different patterns of bone spur formation in psoriatic arthritis (PsA) and hand osteoarthritis (OA), using high-resolution peripheral quantitative computed tomography (QCT). The study group comprised 70 subjects (25 patients with PsA, 25 patients with hand OA, and 20 healthy controls). The 2 patient groups were similar with regard to age and sex distribution and clinical involvement of the metacarpophalangeal (MCP) joints. All patients underwent high-resolution peripheral QCT scanning of the second, third, and fourth MCP joints of the dominantly affected hand. Demographic and disease-specific data were recorded, and the number, size, and distribution of bone spurs were assessed and compared between patients with PsA and patients with hand OA. The overall number and size of bone spurs were similar in patients with PsA and patients with hand OA. However, localization of lesions within individual joints was substantially different between patients with PsA and those with hand OA. In PsA, bone spurs dominated the radial sides of the joints (for the metacarpal head of the second joint, P < 0.001 versus hand OA; for the base of the second phalangeal joint, P < 0.001 versus hand OA), whereas the palmar and dorsal quadrants were the predilection sites in hand OA. Detailed anatomic analysis showed that bone spurs in the entheseal regions were prominent in patients with PsA but rare in patients with hand OA, and that bone spurs in patients with hand OA typically emerged at the cartilage-bone interphase and the joint margins. Our findings show that the overall number and size of bone spurs are similar in patients with PsA and patients with hand OA. Nonetheless, the anatomic sites of bone proliferation are different betwee