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Sample records for adjuvant-induced arthritis model

  1. Ciclamilast Ameliorates Adjuvant-Induced Arthritis in a Rat Model

    PubMed Central

    Zhang, Zhi-cheng; Zhang, Shui-juan; Jin, Bo; Wu, Yujin; Yang, Xin-fu; Yu, Bing; Xie, Qiang-min

    2015-01-01

    We assessed the effect of a novel and selective phosphodiesterase 4 (PDE4) inhibitor, ciclamilast, on chronic inflammation in adjuvant-induced arthritis (AIA), a rat model of rheumatoid arthritis (RA), and acute inflammation in the rat and mouse model of carrageenan-induced paw edema and peritonitis. Our results showed that daily oral administration of ciclamilast at 1, 3, and 10 mg/kg dose-dependently inhibited the increase in hind paw volume of rats with AIA. The inhibition of paw edema was associated with inhibition of both the production of cytokines such as TNF-α, IL-1β, and IL-6 and cell infiltration assessed in subcutaneous paw tissue. Moreover, there was significantly less tissue destruction in the ciclamilast-treated rats compared to the vehicle-treated rats, as assessed by radiographic analysis and histopathological evaluation. In the two acute inflammation models, ciclamilast inhibited carrageenan-induced paw edema in rats and inflammatory cell migration into the peritoneal cavity in mice in a dose-dependent manner. These results not only suggest that ciclamilast, as a disease-modifying antirheumatic drug (DMARD), can attenuate RA but also provide proof of principle that a PDE4 inhibitor may be useful for the treatment of arthritis. PMID:26000303

  2. Lipid-Core Nanocapsules Improved Antiedematogenic Activity of Tacrolimus in Adjuvant-Induced Arthritis Model.

    PubMed

    Friedrich, Rossana B; Coradini, Karine; Fonseca, Francisco N; Guterres, Silvia S; Beck, Ruy C R; Pohlmann, Adriana R

    2016-02-01

    Despite significant technological advances, rheumatoid arthritis remains an incurable disease with great impact on the life quality of patients. We studied the encapsulation of tacrolimus in lipidcore nanocapsules (TAC-LNC) as a strategy to enhance its systemic anti-arthritic properties. TAC-LNC presented unimodal distribution of particles with z-average diameter of 212 +/- 11, drug content close to the theoretical value (0.80 mg mL(-1)), and 99.43% of encapsulation efficiency. An in vitro sustained release was determined for TAC-LNC with anomalous transport mechanism (n = 0.61). In vivo studies using an arthritis model induced by Complete Freund's Adjuvant demonstrated that the animals treated with TAC-LNC presented a significantly greater inhibition of paw oedema after intraperitoneal administration. Furthermore, the encapsulation of TAC in lipid-core nanocapsules was potentially able to prevent hyperglycemia in the animals. In conclusion, TAC-LNC was prepared with 100% yield of nanoscopic particles having satisfactory characteristics for systemic use. This formulation represents a promising strategy to the treatment of rheumatoid arthritis in the near future. PMID:27433576

  3. Evaluation of antiarthritic activity of isoeugenol in adjuvant induced arthritis in murine model.

    PubMed

    Kaur, Gurpreet; Sultana, Sarwat

    2012-08-01

    Isoeugenol, a component of clover oil, possesses potent anti-inflammatory and antioxidant activity. In the present study, we investigated the effect on experimentally induced adjuvant arthritis in rats. Induction of arthritis in adjuvant exposed rats was confirmed by appearance of several physical symptoms such as redness, swelling and stiffness of paws, radiographic analysis revealing joint damage, soft tissue swelling of the footpad, histopathologic changes and expression of proinflammatory enzymes and mediators in the joint tissue. Treatment of rats with isoeugenol, however, conferred a significant protection against almost all the investigated parameters. Isoeugenol significantly and dose dependently attenuated arthritic index, paw circumference, joint stiffness and the levels of proinflammatory mediators. Exposure to isoeugenol inhibited the release of nitric oxide and proinflammatory cytokines the including PGE(2) and TNFα from lipopolysaccharide primed macrophages. Isoeugenol also showed a significant analgesic activity in acetic acid-induced writhing model. Further, unlike most antiarthritic drugs, isoeugenol had no damaging effect on gastric mucosa, which makes it a favorable antiarthritic drug. Thus, the results obtained in the present study indicate isoeugenol to possess a promising antiarthritic activity and further advocate the efficacy of natural products as antiarthritic therapeutics.

  4. Methanolic extract of Ruta graveolens L. inhibits inflammation and oxidative stress in adjuvant induced model of arthritis in rats.

    PubMed

    Ratheesh, M; Shyni, G L; Helen, A

    2009-04-01

    Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India. The purpose of this study was to investigate anti-inflammatory and anti-oxidant effects of methanolic extract of Ruta graveolens L. in adjuvant induced arthritis in rats. Methanolic extract of Ruta graveolens (MER) exhibited maximum percentage of oedema inhibition at a dose of 20 mg/kg on 21st day of adjuvant arthritis. The effect was higher than that of standard drug indomethacin. The activities of cycloxygenase-2 and myeloperoxidase and concentration of thiobarbituric acid reactive substance (TBARS) were decreased and the activities of antioxidant enzymes, vitamins C & E and reduced glutathione level were increased on treatment with MER. The increment in ESR and total WBC, reduction in RBC count and haemoglobin and aberrant changes to the C-reactive protein (CRP) and ceruloplasmin levels observed in the arthritic animals were also found to be significantly restored in MER treated rats. Histopathology of paw tissue showed decreased oedema formation and cellular infiltration on supplementation with MER. Thus the results demonstrated the potential beneficiary effect of methanolic extract of Ruta graveolens on adjuvant induced arthritis in rats.

  5. Profiling of dihydroorotate dehydrogenase, p38 and JAK inhibitors in the rat adjuvant-induced arthritis model: a translational study

    PubMed Central

    Balagué, C; Pont, M; Prats, N; Godessart, N

    2012-01-01

    BACKGROUND AND PURPOSE Translational animal models are essential in the prediction of the efficacy and side effects of new chemical entities. We have carried out a thorough study of three distinct disease-modifying antirheumatic drugs (DMARDs) in an adjuvant-induced arthritis (AIA) model in the rat and critically appraised the results in the context of the reported clinical experience in rheumatoid arthritis (RA) patients. EXPERIMENTAL APPROACH Teriflunomide – a dihydroorotate dehydrogenase (DHODH) inhibitor; AL8697 – a selective p38 MAPK inhibitor; and tofacitinib – a Janus kinase (JAK) inhibitor; were selected as representatives of their class and dose-response studies carried out using a therapeutic 10-day administration scheme in arthritic rats. Paw swelling and body weight were periodically monitored, and joint radiology and histology, lymph organ weight and haematological and biochemical parameters evaluated at study completion. KEY RESULTS All three drugs demonstrated beneficial effects on paw swelling, bone lesions and splenomegalia, with p38 inhibition providing the best anti-inflammatory effect and JAK inhibition the best DMARD effect. Leukopenia, body weight loss and gastrointestinal toxicity were dose-dependently observed with teriflunomide treatment. p38 MAPK inhibition induced leukocytosis and increased total plasma cholesterol. JAK inhibition, normalized platelet, reticulocyte and neutrophil counts, and alanine aminotransferase (ALT) levels while inducing lymphopenia and cholesterolemia. CONCLUSIONS AND IMPLICATIONS This multiparametric approach can reveal specific drug properties and provide translational information. Whereas the complex profile for p38 inhibition in AIA is not observed in human RA, immunosuppressants such as DHODH and JAK inhibitors show DMARD properties and side effects seen in both AIA and RA. PMID:22229697

  6. 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.

  7. Effective treatment of rat adjuvant-induced arthritis by celastrol

    PubMed Central

    Cascão, R.; Vidal, B.; Raquel, H.; Neves-Costa, A.; Figueiredo, N.; Gupta, V.; Fonseca, J.E.; Moita, L.F.

    2012-01-01

    We have previously reported an increase in interleukin (IL)-1β and IL-17 levels, and a continuous activation of caspase-1 in early rheumatoid arthritis (RA) patients. These results suggest that drugs targeting IL-1β regulatory pathways, in addition to tumor necrosis factor (TNF), may constitute promising therapeutic agents in early RA. We have recently used a THP-1 macrophage-like cell line to screen 2320 compounds for those that down-regulate both IL-1β and TNF secretion. Celastrol was one of the most promising therapeutic candidates identified in that study. Our main goal in the present work was to investigate whether administration of celastrol is able to attenuate inflammation in a rat model of adjuvant-induced arthritis (AIA). Moreover, since IL-1β is known to play a role in the polarization of Th17 cells, we also investigate whether administration of digoxin, a specific inhibitor of Th17 cells polarization, is able to attenuate inflammation in the same rat model. We found that celastrol administration significantly suppressed joint inflammation. The histological and immunohistochemical evaluation revealed that celastrol-treated rats had a normal joint structure with complete abrogation of the inflammatory infiltrate and cellular proliferation. In contrast, we observed that digoxin administration significantly ameliorated inflammation but only if administrated in the early phase of disease course (after 4 days of disease induction), and it was not efficient at inhibiting the infiltration of immune cells within the joint and in preventing damage. Thus, our results suggest that celastrol has significant anti-inflammatory and anti-proliferative properties and can constitute a potential anti-inflammatory drug with therapeutic efficacy in the treatment of immune-mediated inflammatory diseases such as RA. Furthermore, we find that early inhibition of Th17 cells polarization ameliorates arthritis but it is not as effective as celastrol. PMID:22415021

  8. Oxidative state and oxidative metabolism of the heart from rats with adjuvant-induced arthritis.

    PubMed

    Schubert, Amanda Caroline; Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; Amado, Ciomar Aparecida Bersani; Peralta, Rosane Marina; Comar, Jurandir Fernando; Bracht, Adelar

    2016-06-01

    The aim of the present work was to investigate, in a more extensive way, the oxidative state and parameters related to energy metabolism of the heart tissue of rats using the model of adjuvant-induced arthritis. The latter is a model for the human arthritic disease. Measurements were done in the total tissue homogenate, isolated mitochondria and cytosolic fraction. The adjuvant-induced arthritis caused several modifications in the oxidative state of the heart which, in general, indicate an increased oxidative stress (+80% reactive oxygen species), protein damage (+53% protein carbonyls) and lipid damage (+63% peroxidation) in the whole tissue. The distribution of these changes over the various cell compartments was frequently unequal. For example, protein carbonyls were increased in the whole tissue and in the cytosol, but not in the mitochondria. No changes in GSH content of the whole tissue were found, but it was increased in the mitochondria (+33%) and decreased in the cytosol (-19%). The activity of succinate dehydrogenase was 77% stimulated by arthritis; the activities of glutamate dehydrogenase, isocitrate dehydrogenase and cytochrome c oxidase were diminished by 31, 25 and 35.3%, respectively. In spite of these alterations, no changes in the mitochondrial respiratory activity and in the efficiency of energy transduction were found. It can be concluded that the adjuvant-induced arthritis in rats causes oxidative damage to the heart with an unequal intracellular distribution. Compared to the liver and brain the modifications caused by arthritis in the heart are less pronounced on variables such as GSH levels and protein integrity. Possibly this occurs because the antioxidant system of the heart is less impaired by arthritis than that reported for the former tissues. Even so, the modifications caused by arthritis represent an imbalanced situation that probably contributes to the cardiac symptoms of the arthritis disease. PMID:27032477

  9. Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

    PubMed

    Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-02-01

    Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically.

  10. Topical Anti-Inflammatory and Analgesic Effects of Multiple Applications of S(+)-Flurbiprofen Plaster (SFPP) in a Rat Adjuvant-Induced Arthritis Model.

    PubMed

    Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-06-01

    Preclinical Research The aim of this study was to evaluate the efficacy of multiple applications of S(+)-flurbiprofen plaster (SFPP), a novel Nonsteroidal anti-inflammatory drug (NSAID) patch, for the alleviation of inflammatory pain and edema in rat adjuvant-induced arthritis (AIA) model as compared to other NSAID patches. The AIA model was induced by the injection of Mycobacterium butyricum and rats were treated with a patch (1.0 cm × 0.88 cm) containing each NSAID (SFP, ketoprofen, loxoprofen, diclofenac, felbinac, flurbiprofen, or indomethacin) applied to the paw for 6 h per day for 5 days. The pain threshold was evaluated using a flexion test of the ankle joint, and the inflamed paw edema was evaluated using a plethysmometer. cyclooxygenase (COX)-1 and COX-2 inhibition was evaluated using human recombinant proteins. Multiple applications of SFPP exerted a significant analgesic effect from the first day of application as compared to the other NSAID patches. In terms of paw edema, SFPP decreased edema from the second day after application, Multiple applications of SFPP were superior to those of other NSAID patches, in terms of the analgesic effect with multiple applications. These results suggest that SFPP may be a beneficial patch for providing analgesic and anti-inflammatory effects clinically. Drug Dev Res 77 : 206-211, 2016. © 2016 The Authors Drug Development Research Published by Wiley Periodicals, Inc.

  11. Analgesic Effect of the Newly Developed S(+)-Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant-Induced Arthritis Model.

    PubMed

    Sugimoto, Masanori; Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-02-01

    Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti-inflammatory drug) patch, SFPP (S(+)-flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)-flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant-induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX-1 (IC50  = 8.97 nM) and COX-2 (IC50  = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. PMID:26763139

  12. Margaritaria discoidea (Euphorbiaceae) stem bark extract attenuates allergy and Freund's adjuvant-induced arthritis in rodents

    PubMed Central

    Obiri, David D.; Osafo, Newman; Oppong-Sarfo, Joshua; Prah, Jude K.

    2014-01-01

    Background: Various parts of Margaritaria discoidea find use in traditional medicine in the treatment of pain and oedema. This study evaluated the anti-allergic, anti-inflammatory and anti-arthritic effects of a 70% (v/v) aqueous ethanol extract of the stem bark of Margaritaria discoidea, MDE in rodents. Materials and Methods: Systemic anaphylaxis was induced by the injection of compound 48/80 into mice and their survival rate was monitored to evaluate the anti-allergic action of the extract. The effect of MDE assessed on the maximal and total oedema responses in the mouse carrageenan-induced paw oedema was used to evaluate the anti-inflammatory action of the extract while the Freund's adjuvant-induced arthritis model was employed to study the anti-arthritic effects of MDE. Results: MDE dose-dependently increased the time for compound 48/80-induced mortality in mice. MDE suppressed the mean maximal swelling and the total paw swellings induced over 6 h in the carrageenan-induced paw oedema when administered either prophylactically or therapeutically. MDE caused a reduction in serum levels of TNFα and IL-6 and significantly suppressed Freund's adjuvant-induced arthritis. Conclusion: Margaritaria discoidea suppresses allergy and exhibits anti-inflammatory activity in mice. In addition it attenuates Freund's adjuvant-induced arthritis through a reduction in serum levels of TNFα and IL-6 in rats. PMID:24761122

  13. Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-induced rheumatoid arthritis in rats.

    PubMed

    Pal, Rishi; Chaudhary, Manju J; Tiwari, Prafulla C; Babu, Suresh; Pant, K K

    2015-12-01

    Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05).

  14. Inhibition of HIF-1{alpha} activity by BP-1 ameliorates adjuvant induced arthritis in rats

    SciTech Connect

    Shankar, J.; Thippegowda, P.B.; Kanum, S.A.

    2009-09-18

    Rheumatoid arthritis (RA) is a chronic inflammatory, angiogenic disease. Inflamed synovitis is a hallmark of RA which is hypoxic in nature. Vascular endothelial growth factor (VEGF), one of the key regulators of angiogenesis, is overexpressed in the pathogenesis of RA. VEGF expression is regulated by hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), a master regulator of homeostasis which plays a pivotal role in hypoxia-induced angiogenesis. In this study we show that synthetic benzophenone analogue, 2-benzoyl-phenoxy acetamide (BP-1) can act as a novel anti-arthritic agent in an experimental adjuvant induced arthritis (AIA) rat model by targeting VEGF and HIF-1{alpha}. BP-1 administered hypoxic endothelial cells and arthritic animals clearly showed down regulation of VEGF expression. Further, BP-1 inhibits nuclear translocation of HIF-1{alpha}, which in turn suppresses transcription of the VEGF gene. These results suggest a further possible clinical application of the BP-1 derivative as an anti-arthritic agent in association with conventional chemotherapeutic agents.

  15. Antioxidant and Angiostatic Effect of Spirulina platensis Suspension in Complete Freund’s Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Ali, Eman A. I.; Barakat, Bassant M.; Hassan, Ranya

    2015-01-01

    Background Currently, natural products have built a well-recognized role in the management of many degenerative diseases, mainly rheumatoid arthritis. Recent studies suggest that Spirulina, a unicellular blue-green alga, may have a variety of health benefits and curative properties and is also competent of acting as an anti-inflammatory, antioxidant and recently anti-angiogenic agent. In the present study, the antioxidant and the immunomodulatory effect of Spirulina platensis as well as its anti-angiogenic effect against complete Freund's adjuvant-induced arthritis (AIA) in rat model were tested. Results We found that the development of arthritis was concealed; moreover it successfully inhibited the development of macroscopic as well as microscopic and histopathological lesions in AIA rats when compared to control. Spirulina treated group showed a higher survival rate and moreover, it reduced the clinical score of RA in a dose dependent manner. Furthermore, Spirulina decreased serum levels of COX-2, TNF-α, IL-6, TBARS, VEGF and increased serum levels of GSH compared to the RA non-treated group. Conclusions The present study concluded that Spirulina is able to restrain the changes produced through adjuvant-induced arthritis. The suppressing effect of Spirulina could be attributed, at least in part, to anti-inflammatory, antioxidant and anti-angiogenic properties. PMID:25853428

  16. Effect of galantamine on adjuvant-induced arthritis in rats.

    PubMed

    Gowayed, Mennatallah A; Refaat, Rowaida; Ahmed, Walid M; El-Abhar, Hanan S

    2015-10-01

    Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis. PMID:26189022

  17. Angiotensin II type 2 receptor correlates with therapeutic effects of losartan in rats with adjuvant-induced arthritis.

    PubMed

    Wang, Di; Hu, Shanshan; Zhu, Jie; Yuan, Jun; Wu, Jingjing; Zhou, Aiwu; Wu, Yujing; Zhao, Wendi; Huang, Qiong; Chang, Yan; Wang, Qingtong; Sun, Wuyi; Wei, Wei

    2013-12-01

    The angiotensin II type 1 receptor (AT1R) blocker losartan ameliorates rheumatoid arthritis (RA) in an experimental model. In RA, AT2R mainly opposes AT1R, but the mechanism by which this occurs still remains obscure. In the present study, we investigated the role of AT2R in the treatment of rats with adjuvant-induced arthritis (AIA) by losartan. Adjuvant-induced arthritis rats were treated with losartan (5, 10 and 15 mg/kg) and methotrexate (MTX; 0.5 mg/kg) in vivo from day 14 to day 28. Arthritis was evaluated by the arthritis index and histological examination. Angiotensin II, tumour necrosis factor-α, and VEGF levels were examined by ELISA. The expression of AT1R and AT2R was detected by western blot and immunohistochemistry analysis. After stimulation with interleukin-1β in vitro, the effects of the AT2R agonist CGP42112 (10(-8) -10(-5)  M) on the chemotaxis of monocytes induced by 10% foetal calf serum (FCS) were analysed by using Transwell assay. Subsequently, the therapeutic effects of CGP42112 (5, 10 and 20 μg/kg) were evaluated in vivo by intra-articular injection in AIA rats. After treatment with losartan, the down-regulation of AT1R expression and up-regulation of AT2R expression in the spleen and synovium of AIA rats correlated positively with reduction in the polyarthritis index. Treatment with CGP42112 inhibited the chemotaxis of AIA monocytes in vitro, possibly because of the up-regulation of AT2R expression. Intra-articular injection with CGP42112 (10 and 20 μg/kg) ameliorated the arthritis index and histological signs of arthritis. In summary, the present study strongly suggests that the up-regulation of AT2R might be an additional mechanism by which losartan exerts its therapeutic effects in AIA rats.

  18. Oxidative state and oxidative metabolism in the brain of rats with adjuvant-induced arthritis.

    PubMed

    Wendt, Mariana Marques Nogueira; de Sá-Nakanishi, Anacharis Babeto; de Castro Ghizoni, Cristiane Vizioli; Bersani Amado, Ciomar Aparecida; Peralta, Rosane Marina; Bracht, Adelar; Comar, Jurandir Fernando

    2015-06-01

    The purpose of the present study was to evaluate the oxidative status of the brain of arthritic rats, based mainly on the observation that arthritis induces a pronounced oxidative stress in the liver of arthritis rats and that morphological alterations have been reported to occur in patients with rheumatoid arthritis. Rats with adjuvant-induced arthritis were used. These animals presented higher levels of reactive oxygen species (ROS) in the total brain homogenate (25% higher) and in the mitochondria (+55%) when compared to healthy rats. The nitrite plus nitrate contents, nitric oxide (NO) markers, were also increased in both mitochondria (+27%) and cytosol (+14%). Arthritic rats also presented higher levels of protein carbonyl groups in the total homogenate (+43%), mitochondria (+69%) and cytosol (+145%). Arthritis caused a diminution of oxygen consumption in isolated brain mitochondria only when ascorbate was the electron donor. The disease diminished the mitochondrial cytochrome c oxidase activity by 55%, but increased the transmembrane potential by 16%. The pro-oxidant enzyme xanthine oxidase was 150%, 110% and 283% higher, respectively, in the brain homogenate, mitochondria and cytosol of arthritic animals. The same occurred with the calcium-independent NO-synthase activity that was higher in the brain homogenate (90%) and cytosol (122%) of arthritic rats. The catalase activity, on the other hand, was diminished by arthritis in all cellular fractions (between 30 and 40%). It is apparent that the brain of rats with adjuvant-induced arthritis presents a pronounced oxidative stress and a significant injury to lipids and proteins, a situation that possibly contributes to the brain symptoms of the arthritis disease.

  19. Free radical scavenging activity of Cleome gynandra L. leaves on adjuvant induced arthritis in rats.

    PubMed

    Narendhirakannan, R T; Subramanian, S; Kandaswamy, M

    2005-08-01

    The generation of free radicals has been implicated in the causation of several diseases of known and unknown etiologies such as, rheumatoid arthritis, diabetes, cancer, etc., and compounds that can scavenge free radicals have great potential in ameliorating these disease processes. The present study was aimed to investigate the possible anti-oxidant potential of Cleome gynandra leaf extract at a dose of 150 mg/kg body weight for 30 days on adjuvant induced arthritis in experimental rats. Oral administration of C. gynandra leaf extract significantly increased the levels of lipid peroxides and activities of catalase, glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological observations made on the limb tissue. The presence of biologically active ingredients and vital trace elements in the leaves readily account for free radical scavenging property of C. gynandra. PMID:16132687

  20. Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

    PubMed Central

    Petchi, R. Ramesh; Parasuraman, S.; Vijaya, C.; Gopala Krishna, S. V.; Kumar, M. Kiran

    2015-01-01

    Objectives: To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats. Materials and Methods: Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study. Results: Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis. Conclusion: The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats. PMID:26229343

  1. Mechanism of Xinfeng Capsule on Adjuvant-Induced Arthritis via Analysis of Urinary Metabolomic Profiles

    PubMed Central

    Jiang, Hui; Liu, Jian; Wang, Ting; Gao, Jia-rong; Sun, Yue; Huang, Chuan-bing; Meng, Mei; Qin, Xiu-juan

    2016-01-01

    We aimed to explore the potential effects of Xinfeng capsule (XFC) on urine metabolic profiling in adjuvant-induced arthritis (AA) rats by using gas chromatography time-of-flight mass spectrometry (GC-TOF/MS). GC-TOF/MS technology was combined with multivariate statistical approaches, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal projections to latent structures discriminant analysis (OPLS-DA). These methods were used to distinguish the healthy group, untreated group, and XFC treated group and elucidate potential biomarkers. Nine potential biomarkers such as hippuric acid, adenine, and L-dopa were identified as potential biomarkers, indicating that purine metabolism, fat metabolism, amino acid metabolism, and energy metabolism were disturbed in AA rats. This study demonstrated that XFC is efficacious for RA and explained its potential metabolomics mechanism. PMID:26989506

  2. CCR5 small interfering RNA ameliorated joint inflammation in rats with adjuvant-induced arthritis.

    PubMed

    Duan, Hongmei; Yang, Pingting; Fang, Fang; Ding, Shuang; Xiao, Weiguo

    2014-12-01

    Rheumatoid arthritis (RA) is a systemic inflammatory disease. C-C chemokine receptor type 5 (CCR5) is found in inflamed synovium of RA patients and is necessary for formation of RA. We aimed to check whether delivery of CCR5-specific small interfering RNA (siRNA) via electroporation suppresses local inflammation in arthritis rats. Vectors encoding siRNA that target CCR5 or negative control siRNA were constructed for gene silencing and the silencing effects of suppressing CCR5 expression in synovium examined by western blot. The vector with strongest effect was delivered into the knee joint of adjuvant-induced arthritis (AIA) rats by the in vivo electroporation method 7, 10, 13, and 16 days after immunization with Complete Freund's adjuvant. During an observation of 28 days, behavior, paw swelling, arthritis and histopathologic scoring were estimated. The expression level of CCR5 in synovium was evaluated by western blot and real-time PCR. Anti-CCR5 D1 siRNA was effectively inhibited CCR5 expression in vitro. Moreover, delivery of the siRNA into inflammatory joint also suppressed the expression of CCR5 in vivo and markedly suppressed paw swelling and inflammation. Local electroporation of anti-CCR5 siRNA into the left inflamed joints could achieve the silencing of CCR5 gene and alleviate local inflammation just in the knee joint injected with siRNA other than the opposite joint. Inhibition of CCR5 expression may provide a potential for treatment of RA.

  3. Lymphoid abnormalities in rats with adjuvant-induced arthritis. I. Mitogen responsiveness and lymphokine synthesis.

    PubMed Central

    Gilman, S C; Daniels, J F; Wilson, R E; Carlson, R P; Lewis, A J

    1984-01-01

    Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals. PMID:6335388

  4. Xanthones from Securidaca inappendiculata exert significant therapeutic efficacy on adjuvant-induced arthritis in mice.

    PubMed

    Zuo, Jian; Xia, Yan; Li, Xiang; Chen, Jian-Wei

    2014-06-01

    The study was designed to investigate effects of the xanthones from Securidaca inappendiculata on adjuvant-induced arthritis (AA) mice in vivo. Arthritis severity was evaluated by arthritic score, body weight loss, paw circumference, histological changes and hyperplasia of lymphatic tissues. Plasma samples were collected for estimation of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), monocyte chemotactic protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) using enzyme-linked immunosorbent assay method. The levels of glutathione (GSH), malondialdehyde (MDA), N-acetyl glucosaminidase (NAG) and sialic acid (SA) in liver were assessed by colorimetric method. Xanthones significantly ameliorated the severity of AA indicated by the physical parameters changes, and reverted the abnormal changes of MDA, GSH, NAG and SA in liver. Levels of IL-1, TNF-α, MCP-1 and VEGF reduced dramatically meanwhile. The effects of xanthones on AA were the outcome of the multitargets activities, and probably associated with NF-κB signaling pathway. PMID:24419745

  5. 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

  6. Serum IL-10 involved in morphine tolerance development during adjuvant-induced arthritis.

    PubMed

    Zaringhalam, Jalal; Hormozi, Asef; Tekieh, Elaheh; Razavi, Jafar; Khanmohammad, Ramin; Golabi, Sahar

    2014-06-01

    Opioid receptors play an important role in modulation of hyperalgesia in inflamed tissues, but chronic morphine application induces such side effects as tolerance. There is near communications between cytokines and mu opioid receptor expression. This study was aimed to assess the role of serum IL-10 in morphine tolerance development during adjuvant-induced arthritis. Adjuvant arthritis (AA) was induced on day 0 by single injection of Complete Freund's Adjuvant (CFA) into the rats' hindpaw. Hyperalgesia, edema, and spinal mu opioid receptor (mOR) variations were assessed on 0, 7, 14, and 21 days of the study. For assessment of the morphine tolerance development, morphine effective dose (4 mg/kg) was administered from the 14th day after CFA injection and continued until the morphine post-dose paw withdrawal latency (PWL); it did not significantly differ from the baseline. For assessment of the effects of IL-10 on tolerance induction, a neutralizing dose (ND50) of anti-IL-10 was administered daily during different stages of the study. AA induction in the right hindpaw of rats resulted in unilateral inflammation and hyperalgesia within 21 days of the study. Anti-IL-10 antibody administration in the AA rats induced marked elevation of hyperalgesia compared to the AA control group. Our data also indicated that morphine effective anti-hyperalgesic dose significantly decreased in the AA rats compared to the control group, which this symptom was aligned with spinal mu opioid receptor (mOR) expression increase during AA. Moreover, there was a significant difference in morphine tolerance induction between the AA and control rats, and our results also demonstrated that IL-10 played an important role in tolerance-induction process. It can be concluded that morphine tolerance slowly progressed when administered morphine effective dose was reduced during AA chronic inflammation. On the other hand, it seems that increased level of serum IL-10 may affect morphine tolerance

  7. The effects of a minimally invasive laser needle system on complete Freund's adjuvant-induced arthritis.

    PubMed

    Kang, Heesung; Son, Taeyoon; Lee, Aeju; Youn, Inchan; Seo, Dong Hyun; Kim, Han Sung; Jung, Byungjo

    2014-09-01

    The present study aimed to investigate the effects of a minimally invasive laser needle system (MILNS) on the acute progression of arthritis. Previous studies showed controversial clinical results regarding the effects of low-level laser therapy on arthritis, with the outcomes depending upon stimulation parameters such as laser wavelength and dosage. Based on the positive effects of MILNS on osteoporotic mice, we hypothesized that MILNS could potentially suppress the progression of arthritis owing to its biostimulation effects. Eight C57BL/6 mice with complete Freund's adjuvant (CFA)-induced arthritis were used as acute progression arthritis models and divided into the laser and control groups (n = 4 each). In the laser group, after minimally invasive laser stimulation, laser speckle contrast images (LSCIs) were obtained every 6 h for a total of 108 h. The LSCIs in the control group were obtained without laser stimulation. The effects of MILNS on the acute progression of arthritis were indirectly evaluated by calculating the paw area and the average laser speckle index (LSI) at the arthritis-induced area. Moreover, the macrophage population was estimated in the arthritis-induced area. Compared to the control group, the laser group showed (1) lower relative variations of the paw area, (2) lower average LSI in the arthritis-induced area, and (3) lower macrophage population in the arthritis-induced area. These results indicate that MILNS may suppress the acute progression of CFA-induced arthritis in mice and may thus be used as a potential treatment modality of arthritis in clinics.

  8. Bone-protective effects of nonviral gene therapy with folate-chitosan DNA nanoparticle containing interleukin-1 receptor antagonist gene in rats with adjuvant-induced arthritis.

    PubMed

    Fernandes, Julio C; Wang, Huijie; Jreyssaty, Christian; Benderdour, Mohamed; Lavigne, Patrick; Qiu, Xingpin; Winnik, Francoise M; Zhang, Xiaoling; Dai, Kerong; Shi, Qin

    2008-07-01

    Interleukin-1 receptor antagonist (IL-1Ra), is a natural blocker of the inflammatory cytokine interleukin-1. Using a rat adjuvant-induced arthritis (AIA) model of rheumatoid arthritis (RA), we examined the protective effects of IL-1Ra in bone metabolism in vivo after folate-mediated nonviral gene delivery. We detected secreted human IL-1Ra protein in serum and cultured primary osteoblasts of rats that were treated with chitosan-IL-1Ra and folate-IL-1Ra-chitosan nanoparticles, respectively. In vivo, IL-1Ra gene delivery significantly reverted alterations in bone turnover observed in arthritic animals by modulating the level of osteocalcin (OC) as well as the activities of alkaline phosphatase and tartrate-resistant acid phosphatase. The protective effects of these nanoparticles were evident from the decrease in the expression levels of interleukine-1beta and prostaglandin E(2) as well as osteoclast number and other histopathological findings. Compared to naked DNA and chitosan-DNA, folate-chitosan-DNA nanoparticles were less cytotoxic and enhanced IL-1Ra protein synthesis in vitro and offered a better protection against inflammation and abnormal bone metabolism in vivo. Nonviral gene therapy with folate-chitosan-DNA nanoparticles containing the IL-1 Ra gene seemed to protect against bone damage and inflammation in rat adjuvant-induced arthritis model.

  9. Therapeutic Effect of Saponin Rich Fraction of Achyranthes aspera Linn. on Adjuvant-Induced Arthritis in Sprague-Dawley Rats

    PubMed Central

    Kothavade, Pankaj S.; Bulani, Vipin D.; Nagmoti, Dnyaneshwar M.; Deshpande, Padmini S.; Gawali, Nitin B.; Juvekar, Archana R.

    2015-01-01

    Objective. Achyranthes aspera Linn. (AA) is used in folklore for the treatment of various inflammatory ailments and arthritis like conditions. Anti-inflammatory activity of saponin rich (SR) fraction of AA has been previously reported. The objective of this study was to assess the antiarthritic effect of SR fraction of Achyranthes aspera in adjuvant-induced arthritic rats. Methods. Arthritis was assessed by arthritis score, paw volume, changes in tibiotarsal joint thickness, hyperalgesic parameters, and spleen and thymus index. Haematological, serum, biochemical, and inflammatory cytokine and in vivo antioxidant parameters were measured on the last day of the study. Results. SR fraction significantly suppressed paw swelling and arthritic score and improved the pain threshold in motility and stair climbing tests. There was a reversal in the levels of altered parameters, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and antioxidant parameters like superoxide dismutase, catalase, glutathione, malondialdehyde, and nitric oxide. SR fraction significantly decreased plasma levels of tumor necrosis factor-alpha and interleukin-6. Moreover, histopathology revealed a significant reduction in synovial hyperplasia, inflammatory cell infiltration, and bone destruction in the joints. Conclusion. These observations explain the therapeutic benefit of SR fraction of AA in suppressing the progression of adjuvant-induced arthritis in rats. PMID:26273477

  10. The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats

    PubMed Central

    Zheng, Zhaoling; Sun, YanHua; Liu, Ziliang; Zhang, Mingqin; Li, Chunqing; Cai, Hui

    2015-01-01

    Background Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil–water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. Methods The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. Results CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax

  11. 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.

  12. Topical therapies for rheumatoid arthritis by gel ointments containing indomethacin nanoparticles in adjuvant-induced arthritis rat.

    PubMed

    Nagai, Noriaki; Yoshioka, Chiaki; Ito, Yoshimasa

    2015-01-01

    Indomethacin (IMC), a nonsteroidal anti-inflammatory drug, has been used in the treatment of rheumatoid arthritis (RA), although its clinical use has been limited by its systemic side effects that include gastrointestinal lesions. Therefore, the development of IMC formulations that do not cause gastrointestinal lesions is highly anticipated. In this study, we designed new topical formulations containing IMC solid nanoparticles (IMCnano gel ointment), and investigated their pharmacokinetics. In addition, we demonstrate the preventive effects of this topical application of IMC nanoparticles on inflammation in adjuvant-induced arthritis rat (AA rat). The IMCnano gel ointment was prepared using Bead Smash 12 (a bead mill) and additives including 2-hydroxypropyl-β-cyclodextrin, methylcellulose and Carbopol 934; the mean particle size of the IMC nanoparticles was 173 ± 91 nm (means ± S.D.). The application of the IMCnano gel ointment attenuated the increase in paw edema of the hind feet of AA rats in comparison with AA rats treated with gel ointment containing IMC microparticles (IMCmicro gel ointment, particle diameter 17.1 ± 11.6 mm, means ± S.D). In addition, the accumulation of IMC from the IMCnano gel ointment in skin tissue was significantly large than for the IMCmicro gel ointment; however, the plasma IMC concentrations were similar for the IMCmicro and IMCnano gel ointments. Our findings suggest that the dermal application of nanoparticles may enable a medication to be applied without high-systemic drug levels, which could provide efficient and effective therapy that spares patients from unwanted side effects. A formulation of a topical drug delivery system using IMC nanoparticles may provide a delivery option for the clinical treatment of RA.

  13. Effect of solid nanoparticle of indomethacin on therapy for rheumatoid arthritis in adjuvant-induced arthritis rat.

    PubMed

    Nagai, Noriaki; Ito, Yoshimasa

    2014-01-01

    We designed new oral formulations containing indomethacin (IMC) solid nanoparticles, and investigate their usefulness by evaluating bioavailability and gastrointestinal lesions. The IMC solid nanoparticles were prepared using methylcellulose (MC), 2-hydroxypropyl-β-cyclodextrin (HPβCD), and the bead mill method, and high quality dispersions containing 1.0% IMC nanoparticles were prepared (IMC(nano), particle size: 76 ± 58 nm, means ± S.D.). The fate of serum IMC and the induction of paw edema in adjuvant-induced arthritis (AA) rats receiving low-doses IMC(nano) (0.4 mg/kg) were similar to those following the administration of a therapeutic dose of conventional IMC prepared with MC and HPβCD (conventional IMC, 2 mg/kg), and the bioavailability in 0.4 mg/kg IMC(nano) was 5.3-fold higher in comparison with that in 2 mg/kg conventional IMC. IMC-induced gastrointestinal lesions in AA rats administered IMC(nano) (8 mg/kg), in consideration of bioavailability, were significantly less than for conventional IMC (40 mg/kg). On the other hand, the toxicity caused by conventional IMC and IMC(nano) was similar in Caco-2 cells. It is possible that the oral administration of IMC solid nanoparticles will show increased effectiveness in treating RA without causing IMC-induced gastrointestinal lesions, since the bioavailability is higher than that of conventional IMC. An oral drug delivery system using drug nanoparticles may expand the usage of NSAIDs for therapy in the inflammatory field.

  14. 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.

  15. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed Central

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-01-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity. PMID:892904

  16. Effect of oil composition on both adjuvant-induced arthritis and delayed hypersensitivity to purified protein derivative and peptidoglycans in various rat strains.

    PubMed

    Kohashi, O; Pearson, M; Beck, F J; Alexander, M

    1977-08-01

    We confirmed that, when immunized with a conventional complete Freund adjuvant (water in oil), Lewis rats were highly susceptible to adjuvant arthritis, Fisher rats were less susceptible, and Buffalo rats were much less susceptible. However, mycobacterial delipidated cells in squalane (squalane-type adjuvant) produced severe arthritis with almost 100% incidence even in the less susceptible rat strains except for Buffalo rats. With regard to an immune response, Freund complete adjuvant induced strong delayed hypersensitivity to purified protein derivative (PPD) and peptidoglycan (PG) in all rat strains used, Whereas the squalane-type adjuvant induced these hypersensitivities only in Lewis and Buffalo rats, but not in Fisher and Brown Norway rats. No correlation was found between development of arthritis and delayed hypersensitivity to either PPD or PG, or both. It seems that PPD hypersensitivity may be inherited differently from PG hypersensitivity.

  17. Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats.

    PubMed

    Jiang, Hui; Liu, Jian; Wang, Ting; Gao, Jia-Rong; Sun, Yue; Huang, Chuan-Bing; Meng, Mei; Qin, Xiu-Juan

    2016-09-01

    To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26856389

  18. Fish Oil and Adjuvant-Induced Arthritis: Inhibitory Effect on Leukocyte Recruitment.

    PubMed

    Estevão-Silva, Camila Fernanda; Ames, Franciele Queiroz; Silva-Comar, Francielli Maria de Souza; Kummer, Raquel; Tronco, Rafael Prizon; Cuman, Roberto Kenji Nakamura; Bersani-Amado, Ciomar Aparecida

    2016-02-01

    Fish oil, a rich source of n-3 fatty acids, has been studied for its beneficial effects in many diseases. Recent studies have shown the robust anti-inflammatory activity of fish oil (FO), when administered orally to rats, in models of acute inflammation. Herein, we investigated if treatment with fish oil preparation (FOP) could interfere with the recruitment of leukocytes into the joint cavity of arthritic rats. We also evaluated the effect of treatment on rolling behavior and leukocyte adhesion in vivo and on leukocyte chemotaxis in vitro. Treatment with FOP (75, 150, and 300 mg/kg) initiated on the day of induction of arthritis (day 0) and maintained for 21 days reduced the total number of leukocytes recruited into the joint cavity, the number of rolling and adhered leukocytes in arthritic rats, and leukocyte migration in response to stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) and leukotriene B4 (LTB4). Together, our data provide evidence that FOP plays an important inhibitory role in the recruitment of leukocytes into the joint cavity of arthritic rats. PMID:26378008

  19. Regression of Adjuvant-Induced Arthritis in Rats Following Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    van Bekkum, Dirk W.; Bohre, Els P. M.; Houben, Paul F. J.; Knaan-Shanzer, Shoshan

    1989-12-01

    Total body irradiation followed by bone marrow transplantation was found to be an effective treatment for adjuvant arthritis induced in rats. This treatment is most effective when applied shortly after the clinical manifestation of arthritis--i.e., 4-7 weeks after administration of Mycobacterium tuberculosis. Transplantation of bone marrow at a later stage results in a limited recovery, in that the inflammatory reaction regresses but the newly formed excessive bone is not eliminated. Local irradiation of the affected joints had no effect on the disease. It could also be excluded that the recovery of arthritis following marrow transplantation is due to lack of available antigen. Transplantation of syngeneic bone marrow is as effective as that of allogeneic bone marrow from a rat strain that is not susceptible to induction of adjuvant arthritis. The beneficial effect of this treatment cannot be ascribed to the immunosuppressive effect of total body irradiation, since treatment with the highly immunosuppressive drug Cyclosporin A resulted in a regression of the joint swelling but relapse occurred shortly after discontinuation of the treatment.

  20. Anti-arthritic activity of root bark of Oroxylum indicum (L.) vent against adjuvant-induced arthritis

    PubMed Central

    Karnati, Mamatha; Chandra, Rodda H; Veeresham, Ciddi; Kishan, Bookya

    2013-01-01

    Background: Oroxylum indicum (Bignoniaceae) also known as Sonapatha is an indigenous medicinal plant widely used in Ayurvedic medicine for over thousands of years. It is an active ingredient of well-known Ayurvedic formulations such as Chyawanprash and Dasamula. Root bark of this plant has tonic and astringent properties and it is also used in rheumatism. Objective: The present investigation was carried out to evaluate the anti-arthritic activity of different extracts of root bark of Oroxylum indicum against adjuvant - induced arthritis in rats. Materials and Methods: Male Wistar rats were used in this study. Arthritis was induced by injecting 0.1 ml Freund's complete adjuvant intra-dermally into the left hind paw of the rats. The paw volume, hematological, biochemical, radiographic and histopathological aspects were evaluated. Results: The relative percentage inhibition potential of paw volume in rats treated with various extracts of Oroxylum indicum was found to be ethyl acetate extract (67.69%) >chloroform extract (64.61%) >n-butanol extract (58.46%) respectively. The hematological parameters like RBC count, hemoglobin content showed significant increase while there was a significant decrease in total WBC count and ESR in all the groups of animals pretreated with root bark extracts. The biochemical parameters such as catalase, glutathione contents showed a significant increase while the lipid peroxide and Cathepsin-D content decreased significantly only in case of ethyl acetate pretreated rats when compared to others. Conclusion: The present study suggests that the chloroform, ethyl acetate and n-butanol extracts of root bark of Oroxylum indicum exhibit anti-arthritic activity. The order of activity of extracts was found to be ethyl acetate >chloroform >n-butanol respectively. PMID:23798888

  1. Trichilia monadelpha bark extracts inhibit carrageenan-induced foot-oedema in the 7-day old chick and the oedema associated with adjuvant-induced arthritis in rats.

    PubMed

    Ainooson, G K; Owusu, G; Woode, E; Ansah, C; Annan, K

    2012-01-01

    Trichilia monadelpha (Thonn) JJ De Wilde (Meliaceae) bark extract is used in African traditional medicine for the management of various disease conditions including inflammatory disorders such as arthritis. The present study was undertaken to evaluate the anti-inflammatory properties of aqueous (TWE), alcoholic (TAE) and petroleum ether extract (TPEE) of T. monadelpha using the 7-day old chick-carrageenan footpad oedema (acute inflammation) and the adjuvant-induced arthritis model in rats (chronic inflammation). TWE and TPEE significantly inhibited the chick-carrageenan footpad oedema with maximal inhibitions of 57.79±3.92 and 63.83±12 respectively, but TAE did not. The reference anti-inflammatory drugs (diclofenac and dexamethasone) inhibited the chick-carrageenan-induced footpad oedema, with maximal inhibitions of 64.92±2.03 and 71.85±15.34 respectively. Furthermore, all the extracts and the reference anti-inflammatory agents (diclofenac, dexamethasone, methotrexate) inhibited the inflammatory oedema associated with adjuvant arthritis with maximal inhibitions of 64.41±5.56, 57.04±8.57, 62.18±2.56%, for TWE, TAE and TPEE respectively and 80.28±5.79, 85.75±2.96, 74.68±3.03% for diclofenac, dexamethasone and methotrexate respectively. Phytochemical screening of the plant bark confirmed the presence of a large array of plant constituents such as alkaloids, glycosides, flavonoids, saponins, steroids, tannins and terpenoids, all of which may be potential sources of phyto-antiinflammatory agents. In conclusion, our work suggests that T. monadelpha is a potential source of antiinflammatory agents.

  2. Suppression of NF-κB p65 nuclear translocation and tumor necrosis factor-α by Pongamia pinnata seed extract in adjuvant-induced arthritis.

    PubMed

    Bose, Madhura; Chakraborty, Mousumi; Bhattacharya, Sourav; Bhattacharjee, Pushpak; Mandal, Suvra; Kar, Manoj; Mishra, Roshnara

    2014-01-01

    Pongamia pinnata is a plant known for its therapeutic usage in Indian traditional medicine. Despite the controversy regarding toxic flavonoid and erucic acid content, the seed of this plant is consumed in tribal medicine and its oil is used in Ayurveda to treat psoriasis and arthritis. This study explored the potential anti-arthritic effects of a P. pinnata seed (hexane) extract (PSE) at non-lethal doses in an adjuvant-induced arthritic rat model; possible mechanisms of any observed effects were also explored. After establishing the lethal doses arising from oral exposure to the extract, the material was administered per os daily at two doses (0.3 g/kg/day; 0.5 g/kg/day) to arthritic rats. Other rats received indomethacin or vehicle (control). Treatments were performed for a total of 14 days. One day after the final exposure, the rats were euthanized to permit harvest of various cells, blood, and tissues for analyses. Paw diameter and tissue myeloperoxidase activity in the paws were evaluated as indices for edema and neutrophil infiltration into the tissue. The severity of arthritis in the experimental rats was assessed via measures of urinary hydroxyproline (HP) and glucosamine, and of serum pro-inflammatory TNFα and anti-inflammatory IL-10. The extent of NF-κB p65 nuclear translocation in peritoneal macrophages harvested from naïve rats and then treated in vitro was also assessed. The results indicated that exposure to PSE significantly decreased paw diameter, tissue myeloperoxidase level, and levels of urinary HP and glucosamine, as well as of serum TNFα and IL-10 in adjuvant-injected (arthritic) rats. In vitro PSE treatment also resulted in a marked inhibition of NF-κB p65 nuclear translocation in primary cultures of peritoneal macrophages. Thus, PSE appears to be able to prevent experimental arthritis, in part, by helping to maintain the balance between pro- and anti-inflammatory cytokines and by inhibiting NF-κB activation. PMID:23971718

  3. Berberis aristata Ameliorates Adjuvant-Induced Arthritis by Inhibition of NF-κB and Activating Nuclear Factor-E2-related Factor 2/hem Oxygenase (HO)-1 Signaling Pathway.

    PubMed

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

    2016-08-01

    The present study was carried out to investigate the anti-arthritic activity of Berberis aristata hydroalcoholic extract (BAHE) in formaldehyde-induced arthritis and adjuvant-induced arthritis (AIA) model. Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. In formaldehyde-induced arthritis and AIA, treatment of BAHE at doses 50, 100 and 200 mg/kg orally significantly decreased joint inflammation as evidenced by decrease in joint diameter and reduced inflammatory cell infiltration in histopathological examination. BAHE treatment demonstrated dose-dependent improvement in the redox status of synovium (decrease in GSH, MDA, and NO levels and increase in SOD and CAT activities). The beneficial effect of BAHE was substantiated with decreased expression of inflammatory markers such as IL-1β, IL-6, TNF-R1, and VEGF by immunohistochemistry analysis in AIA model. BAHE increased HO-1/Nrf-2 and suppressed NF-κB mRNA and protein expression in adjuvant immunized joint. Additionally, BAHE abrogated degrading enzymes, as there was decreased protein expression of MMP-3 and -9 in AIA. In conclusion, we demonstrated the anti-arthritic activity of Berberis aristata hydroalcoholic extract via the mechanism of inhibition of NF-κB and activation of Nrf-2/HO-1.

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

    PubMed

    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 (10mg/kg/day p.o. for 21days) effectively suppressed inflammation in both models with comparable efficacy to the standard anti-inflammatory diclofenac (5mg/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 & IL-6), and eicosanoids (PGE2 & LTB4) 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.

  5. 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

  6. Therapeutic effects of total steroid saponin extracts from the rhizome of Dioscorea zingiberensis C.H.Wright in Freund's complete adjuvant induced arthritis in rats.

    PubMed

    Zhang, Xin-xin; Ito, Yoichiro; Liang, Jin-ru; Liu, Jian-li; He, Jiao; Sun, Wen-ji

    2014-12-01

    The aim of our present study is to explore the anti-arthritic potential effect of total steroid saponins (TSSNs) extracted from the rhizome of Dioscorea zingiberensis C.H.Wright (DZW) and to investigate the underlying mechanisms. This work was performed using adjuvant-induced arthritis (AIA) rats in vivo and lipopolysaccharide (LPS) simulated 264.7 macrophage cells in vitro. In AIA-induced arthritic rats, TSSN significantly alleviated the arthritic progression through evaluating arthritic score, immune organ indexes, paw swelling, and body weight. This phenomenon was well correlated with significant suppression of the overproduction of inflammation cytokines (IL-1, IL-1β, IL-6, and TNF-α), oxidant stress makers (MDA and NO), eicosanoids (LTB4 and PGE2), and inflammatory enzymes (5-LOX and COX-2) versus the AIA rats without treatment. On the contrary, the release of SOD and IL-10 was profoundly increased. What's more, TSSN could obviously ameliorate the translocation of NF-κB to the nucleus through phosphorylation of the p65 and IκBα in vivo and in vitro. The current findings demonstrated that TSSN could protect the injured ankle joint from further deterioration and exert its satisfactory anti-arthritis properties through anti-inflammatory and anti-oxidant effects via inactivating the NF-κB signal pathway. This research implies that DZW may be a useful therapeutic agent for the treatment of human arthritis.

  7. Therapeutic effects of total steroid saponin extracts from the rhizome of Dioscorea zingiberensis C.H.Wright in Freund’s complete adjuvant induced arthritis in rats

    PubMed Central

    Zhang, Xin-xin; Ito, Yoichiro; Liang, Jin-ru; Liu, Jian-li; He, Jiao; Sun, Wen-ji

    2014-01-01

    The aim of our present study is to explore the anti-arthritic potential effect of total steroid saponins (TSSN) extracted from the rhizome of Dioscorea zingiberensis C.H.Wright (DZW) and to investigate the underlying mechanisms. This work was performed using adjuvant-induced arthritis (AIA) rats in vivo and lipopolysaccharide (LPS) simulated 264.7 macrophage cells in vitro. In AIA-induced arthritic rats, TSSN significantly alleviated the arthritic progression through evaluating arthritic score, immune organ indexes, paw swelling, and body weight. This phenomenon was well correlated with significant suppression of the overproduction of inflammation cytokines (IL-1, IL-1β, IL-6, and TNF-α), oxidant stress makers (MDA and NO), eicosanoids (LTB4 and PGE2), and inflammatory enzymes (5-LOX and COX-2) versus the AIA rats without treatment. On the contrary, the release of SOD and IL-10 was profoundly increased. What’s more, TSSN could obviously ameliorate the translocation of NF-κB to the nucleus through phosphorylation of the p65 and IκBα in vivo and vitro. The current findings demonstrated that TSSN could protect the injured ankle joint from further deterioration and exert its satisfactory anti-arthritis properties through anti-inflammatory and anti-oxidant effects via inactivating NF-κB signal pathway. This research implies that DZW may be a useful therapeutic agent for the treatment of human arthritis. PMID:25066758

  8. Evening primrose oil and celecoxib inhibited pathological angiogenesis, inflammation, and oxidative stress in adjuvant-induced arthritis: novel role of angiopoietin-1.

    PubMed

    El-Sayed, R M; Moustafa, Y M; El-Azab, M F

    2014-10-01

    Rheumatoid arthritis is a chronic inflammatory disease characterized by overproduction of inflammatory mediators along with undermined oxidative defensive mechanisms. Pathological angiogenesis was found to play a critical role in the progression of this disease. The current study was carried out to evaluate the anti-angiogenic, anti-inflammatory, and anti-oxidant effects of evening primrose oil (EPO), rich in gamma linolenic acid (GLA), either alone or in combination with aspirin or celecoxib, on adjuvant-induced arthritis. Arthritis was induced by subcutaneous injection of complete Freund's adjuvant (CFA) in the right hind paw of male albino rats. All treatments were administered orally from day 0 (EPO, 5 g/kg b.w.) or day 4 (celecoxib, 5 mg/kg; aspirin, 150 mg/kg) till day 27 after CFA injection. In the arthritic group, the results revealed significant decrease in the body weight and increase in ankle circumference, plasma angiopoietin-1 (ANG-1) and tumor necrosis factor-alpha (TNF-α) levels. Anti-oxidant status was suppressed as manifested by significant decline in reduced glutathione content along with decreased enzymatic activity of superoxide dismutase and increased lipid peroxidation. Oral administration of EPO exerted normalization of body weight, ANG-1, and TNF-α levels with restoration of activity as shown by reduced malondialdehyde levels. Moreover, histopathological examination demonstrated that EPO significantly reduced the synovial hyperplasia and inflammatory cells invasion in joint tissues, an effect that was enhanced by combination with aspirin or celecoxib. The joint use of GLA-rich natural oils, which possess anti-angiogenic, anti-inflammatory, and anti-oxidant activities, with traditional analgesics represents a promising strategy to restrain the progression of rheumatoid arthritis.

  9. A Soft Coral-Derived Compound, 11-epi-Sinulariolide Acetate Suppresses Inflammatory Response and Bone Destruction in Adjuvant-Induced Arthritis

    PubMed Central

    Lee, Hsin-Pai; Chen, Wu-Fu; Sun, Yu-Min; Su, Jui-Hsin; Lu, Yi; Huang, Shi-Ying; Hung, Han-Chun; Sung, Ping-Jyun; Sheu, Jyh-Horng; Wen, Zhi-Hong

    2013-01-01

    In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA. PMID:23675440

  10. A soft coral-derived compound, 11-epi-sinulariolide acetate suppresses inflammatory response and bone destruction in adjuvant-induced arthritis.

    PubMed

    Lin, Yen-You; Jean, Yen-Hsuan; Lee, Hsin-Pai; Chen, Wu-Fu; Sun, Yu-Min; Su, Jui-Hsin; Lu, Yi; Huang, Shi-Ying; Hung, Han-Chun; Sung, Ping-Jyun; Sheu, Jyh-Horng; Wen, Zhi-Hong

    2013-01-01

    In recent years, a significant number of metabolites with potent anti-inflammatory properties have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we isolated 11-epi-sinulariolide acetate (Ya-s11), a cembrane-type compound with anti-inflammatory effects, from the Formosa soft coral Sinularia querciformis. Preliminary screening revealed that Ya-s11 significantly inhibited the expression of the proinflammatory proteins induced nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated murine macrophages. We also examined the therapeutic effects of Ya-s11 on adjuvant-induced arthritis (AIA) in female Lewis rats, which demonstrate features similar to human rheumatoid arthritis (RA). Animal experiments revealed that Ya-s11 (subcutaneously 9 mg/kg once every 2 days from day 7 to day 28 postimmunization) significantly inhibited AIA characteristics. Moreover, Ya-s11 also attenuated protein expression of cathepsin K, matrix metalloproteinases-9 (MMP-9), tartrate-resistant acid phosphatase (TRAP), and tumor necrosis factor-α (TNF-α) in ankle tissues of AIA-rats. Based on its attenuation of the expression of proinflammatory proteins and disease progression in AIA rats, the marine-derived compound Ya-s11 may serve as a useful therapeutic agent for the treatment of RA.

  11. 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

  12. Effects of the selective EP4 antagonist, CJ-023,423 on chronic inflammation and bone destruction in rat adjuvant-induced arthritis.

    PubMed

    Okumura, Takako; Murata, Yoko; Taniguchi, Kana; Murase, Akio; Nii, Aisuke

    2008-06-01

    Prostaglandin E2 (PGE2) produced by cyclooxygenase (COX) is a potent pro-inflammatory mediator. We have recently discovered CJ-023,423, a highly selective antagonist of EP4 receptors, one of the PGE2 receptors. This agent is suitable for exploring the effects of blocking EP4 receptors following oral administration in rats. In this study, CJ-023,423 was used in rats with adjuvant-induced arthritis (AIA) to investigate the role of the EP4 receptor in chronic inflammation and bone destruction. These effects were compared with those of rofecoxib, a selective COX-2 inhibitor. CJ-023,423 had significant inhibitory effects on paw swelling, inflammatory biomarkers, synovial inflammation and bone destruction in AIA rats. In particular, the inhibitory effect on paw swelling in AIA rats was comparable to that of rofecoxib. These results suggest that PGE2 acting via the EP4 receptor is involved in the development of chronic inflammation and bone destruction, particularly with respect to oedema in AIA rats. This is the first study to confirm the in-vivo effects of EP4 receptor blockade on inflammation and bone destruction in AIA rats with a small-molecule compound.

  13. Targeting TNF-α and NF-κB Activation by Bee Venom: Role in Suppressing Adjuvant Induced Arthritis and Methotrexate Hepatotoxicity in Rats

    PubMed Central

    Darwish, Samar F.; El-Bakly, Wesam M.; Arafa, Hossam M.; El-Demerdash, Ebtehal

    2013-01-01

    Low dose methotrexate is the cornerstone for the treatment of rheumatoid arthritis. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Dissatisfied arthritis patients are likely to seek the option of complementary and alternative medicine such as bee venom. The combination of natural products with modern medicine poses the possibility of potential interaction between the two groups and needs investigation. The present study was aimed to investigate the modulatory effect of bee venom acupuncture on efficacy, toxicity, and pharmacokinetics and tissue disposition of methotrexate. Complete Freund's adjuvant induced arthritic rats were treated for 3 weeks with methotrexate and/or bee venom. Arthritic score, ankle diameter, paw volume and tissue expression of NF-κB and TNF-α were determined to assess anti-arthritic effects, while anti-nociceptive effects were assessed by gait score and thermal hyperalgesia. Methotrexate toxicity was assessed by measuring serum TNF-α, liver enzymes and expression of NF-κB in liver. Combination therapy of bee venom with methotrexate significantly improved arthritic parameters and analgesic effect as compared to methotrexate alone. Bee venom ameliorated serum TNF-α and liver enzymes elevations as well as over expression of NF-κB in liver induced by methotrexate. Histological examination supported the results. And for the first time bee venom acupuncture was approved to increase methotrexate bioavailability with a significant decrease in its elimination. Conclusion: bee venom potentiates the anti-arthritic effects of methotrexate, possibly by increasing its bioavailability. Also, it provides a potent anti-nociceptive effect. Furthermore, bee venom protects against methotrexate induced hepatotoxicity mostly due to its inhibitory effect on TNF-α and NF-κB. PMID:24278124

  14. Role of Tachykinin 1 and 4 Gene-Derived Neuropeptides and the Neurokinin 1 Receptor in Adjuvant-Induced Chronic Arthritis of the Mouse

    PubMed Central

    Borbély, Éva; Hajna, Zsófia; Sándor, Katalin; Kereskai, László; Tóth, István; Pintér, Erika; Nagy, Péter; Szolcsányi, János; Quinn, John; Zimmer, Andreas; Stewart, James; Paige, Christopher; Berger, Alexandra; Helyes, Zsuzsanna

    2013-01-01

    Objective Substance P, encoded by the Tac1 gene, is involved in neurogenic inflammation and hyperalgesia via neurokinin 1 (NK1) receptor activation. Its non-neuronal counterpart, hemokinin-1, which is derived from the Tac4 gene, is also a potent NK1 agonist. Although hemokinin-1 has been described as a tachykinin of distinct origin and function compared to SP, its role in inflammatory and pain processes has not yet been elucidated in such detail. In this study, we analysed the involvement of tachykinins derived from the Tac1 and Tac4 genes, as well as the NK1 receptor in chronic arthritis of the mouse. Methods Complete Freund’s Adjuvant was injected intraplantarly and into the tail of Tac1−/−, Tac4−/−, Tacr1−/− (NK1 receptor deficient) and Tac1−/−/Tac4−/− mice. Paw volume was measured by plethysmometry and mechanosensitivity using dynamic plantar aesthesiometry over a time period of 21 days. Semiquantitative histopathological scoring and ELISA measurement of IL-1β concentrations of the tibiotarsal joints were performed. Results Mechanical hyperalgesia was significantly reduced from day 11 in Tac4−/− and Tacr1−/− animals, while paw swelling was not altered in any strain. Inflammatory histopathological alterations (synovial swelling, leukocyte infiltration, cartilage destruction, bone damage) and IL-1β concentration in the joint homogenates were significantly smaller in Tac4−/− and Tac1−/−/Tac4−/− mice. Conclusions Hemokinin-1, but not substance P increases inflammation and hyperalgesia in the late phase of adjuvant-induced arthritis. While NK1 receptors mediate its antihyperalgesic actions, the involvement of another receptor in histopathological changes and IL-1β production is suggested. PMID:23626716

  15. Anti-arthritic Effects of Total Flavonoids from Juniperus sabina on Complete Freund's Adjuvant Induced Arthritis in Rats

    PubMed Central

    Zhao, Jun; Liu, Tao; Xu, Fang; You, Shuping; Xu, Fang; Li, Chenyang; Gu, Zhengyi

    2016-01-01

    Context: Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of many ailments including rheumatoid arthritis (RA). Aims: To confirm the therapeutic effect of total flavonoids from J. sabina (JSTF) on RA-induced by Complete Freund's Adjuvant (CFA) in rats. Settings and Design: Wistar rats (200 ± 20 g) were immunized by intradermal injection of 0.1 mL of CFA into the right hind metatarsal footpad. JSTF was administered orally at the dose of 125,250 and 500 mg/kg on 14 days after the induction of adjuvant arthritis. Tripterygium glycoside (20 mg/kg) was used as a positive control. Paw swelling, arthritic score, body weight loss, serum cytokines, inflammatory mediators, and histological change were measured. Results: We found that JSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic score (P < 0.05). The overproduction of tumor necrosis factor alpha and interleukin 1beta were remarkably suppressed in the serum of JSTF (125,500 mg/kg) treated rats (P < 0.05). Histopathological studies also showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animals. Six flavonoids were isolated and from JSTF by various chromatographic methods and identified as follows: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L-rhamnoside, and rutin. Conclusions: These results suggest the potential therapeutically effect of JSTF as an anti-arthritis agent toward CFA-induced arthritis in rats, and verified therapeutic applications of J. sabina on RA in folk medicine. SUMMARY Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of rheumatoid arthritisJSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic scoreHistopathological studies showed a marked decrease

  16. Anti-arthritic Effects of Total Flavonoids from Juniperus sabina on Complete Freund's Adjuvant Induced Arthritis in Rats

    PubMed Central

    Zhao, Jun; Liu, Tao; Xu, Fang; You, Shuping; Xu, Fang; Li, Chenyang; Gu, Zhengyi

    2016-01-01

    Context: Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of many ailments including rheumatoid arthritis (RA). Aims: To confirm the therapeutic effect of total flavonoids from J. sabina (JSTF) on RA-induced by Complete Freund's Adjuvant (CFA) in rats. Settings and Design: Wistar rats (200 ± 20 g) were immunized by intradermal injection of 0.1 mL of CFA into the right hind metatarsal footpad. JSTF was administered orally at the dose of 125,250 and 500 mg/kg on 14 days after the induction of adjuvant arthritis. Tripterygium glycoside (20 mg/kg) was used as a positive control. Paw swelling, arthritic score, body weight loss, serum cytokines, inflammatory mediators, and histological change were measured. Results: We found that JSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic score (P < 0.05). The overproduction of tumor necrosis factor alpha and interleukin 1beta were remarkably suppressed in the serum of JSTF (125,500 mg/kg) treated rats (P < 0.05). Histopathological studies also showed a marked decrease of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animals. Six flavonoids were isolated and from JSTF by various chromatographic methods and identified as follows: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L-rhamnoside, and rutin. Conclusions: These results suggest the potential therapeutically effect of JSTF as an anti-arthritis agent toward CFA-induced arthritis in rats, and verified therapeutic applications of J. sabina on RA in folk medicine. SUMMARY Twigs and leaves of Juniperus sabina L. have been traditionally used as the medicinal herb in China for the treatment of rheumatoid arthritisJSTF could ameliorate paw swelling of CFA rats, and significantly inhibit arthritic scoreHistopathological studies showed a marked decrease

  17. Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant-induced arthritis rat.

    PubMed

    Uno, Satoshi; Uraki, Misato; Ito, Ayami; Shinozaki, Yuki; Yamada, Ayano; Kawase, Atsushi; Iwaki, Masahiro

    2009-01-01

    In this study, a real-time reverse transcription-polymerase chain reaction was used to determine the effects of adjuvant-induced arthritis (AA) on the amounts of mRNA of 12 types of rat ATP-binding cassette (ABC) and solute carrier (SLC) transporters in the liver and small intestine, 7 (D7) and 21 days (D21) after the injection of adjuvant. There were no significant differences in mRNA levels of ABC and SLC transporters between the livers of AA and control rats on D7, except in the case of Mdr1a. However, levels of Mdr1a, Mrp2 and Oatp SLC transporters were significantly lower in AA than in the control livers on D21. In contrast, the mRNA levels of several ABC and SLC transporters, especially Mrp2, Bcrp, LAT2 and Oatp1a5, were significantly lower in the small intestines of AA rats compared with the controls on D7, though there were no significant differences by D21. The time-dependent alterations in mRNA levels of the pregnane X receptor, but not the constitutive androstane receptor, in the liver and intestine were similar to the changes in mRNA levels of most transporters examined. The present study showed that AA was associated with reduced mRNA expression of several ABC and SLC transporters in the liver and small intestine, but that the time courses of the effects of AA on mRNA expression differed between the liver and small intestine. These results raise the possibility of a functional change of the transporters of liver and intestine in AA rats.

  18. Diurnal rhythms in ornithine decarboxylase activity and norepinephrine and acetylcholine synthesis in submaxillary lymph nodes and spleen of young and aged rats during Freund's adjuvant-induced arthritis.

    PubMed

    Cardinali, D P; Brusco, L I; Selgas, L; Esquifino, A I

    1998-04-13

    Aging has been associated with attenuation of amplitude and changes in period of many circadian rhythms. The present study was carried out to examine, in young (50 days old) and old (18 months old) rats, whether 24-h rhythms of cell proliferation (as assessed by measuring ornithine decarboxylase activity) and of presynaptic adrenergic and cholinergic markers change in lymph nodes and spleen during Freund's adjuvant-induced arthritis. Groups of young and old Sprague-Dawley rats were studied the day before, and on days 6, 12 and 18 after Freund's adjuvant injection. On day 16 after adjuvant injection, inflammation of hind paws, mainly in the ankle joints, was less marked in old than in young rats. Lymph node and splenic ornithine decarboxylase activity exhibited significant 24-h variations with maximal activity during daily hours. Before treatment, enzyme activity values were significantly lower in old rats in both tissues examined. During the immune reaction, lymph node and splenic ornithine decarboxylase augmented 8-10-fold, with progressively smaller amplitude of daily variations as arthritis developed. In every case, mesor and amplitude of ornithine decarboxylase activity were lowest in old rats. Submaxillary lymph node and splenic tyrosine hydroxylase activity attained maximal values at night. At every time interval after mycobacterium adjuvant injection, amplitude and mesor of tyrosine hydroxylase activity rhythm were lowest in old rats. A maximum in submaxillary lymph node 3H-acetylcholine synthesis occurred at the afternoon. On day 6 and 12 after Freund's adjuvant injection, lymph node 3H-acetylcholine synthesis was significantly smaller in old rats. Day-night differences in submaxillary lymph node or splenic ornithine decarboxylase and tyrosine hydroxylase activities, or in submaxillary lymph node 3H-acetylcholine synthesis, of rats treated with the adjuvant's vehicle, did not differ significantly from those seen in untreated controls. The results are

  19. Efficacy of Combined Ultrasound-and-Microbubbles-Mediated Diclofenac Gel Delivery to Enhance Transdermal Permeation in Adjuvant-Induced Rheumatoid Arthritis in the Rat.

    PubMed

    Liao, Ai-Ho; Chung, Huan-Yu; Chen, Wen-Shiang; Yeh, Ming-Kung

    2016-08-01

    A previous study that investigated the effect of ultrasound (US) on the transdermal permeation of the non-steroidal anti-inflammatory drug diclofenac found that therapeutic US can increase circulation in an inflamed joint and decrease arthritic pain. Transdermal drug delivery has recently been demonstrated by US combined with microbubbles (MB) contrast agent (henceforth referred to as "US-MB"). The present study evaluated the efficacy of US-MB-mediated diclofenac delivery for treating adjuvant-induced rheumatoid arthritis (RA) in rats. RA was induced by injecting 100 μL of complete Freund's adjuvant into the ankle joint of male Sprague-Dawley rats (250-300 g) that were randomly divided into five treatment groups: (i) carbopol gel alone (the control [group C]), (ii) diclofenac-carbopol gel (group D), (iii) US plus carbopol gel (group U), (iv) US plus diclofenac-carbopol gel (group DU) and (v) US-MB plus diclofenac-carbopol gel (group DUB). The ankle width was measured over 10 d using high-frequency (40-MHz) US B-mode and color Doppler-mode imaging, covering the period before and after treatment. Longitudinal US images of the induced RA showed synovitis and neovascularity. Only a small amount of neovascularity was observed after treatment. The recovery rate on day 10 was significantly higher in group DUB (97.7% ± 2.7%, mean ± standard deviation [SD]) than in groups C (1.0% ± 2.7%), D (37.5% ± 4.6%), U (75.5% ± 4.2%) and DU (87.3% ± 5.2%) (p < 0.05). The results obtained indicate that combining US and MB can increase the skin permeability and thereby enhance the delivery of diclofenac sodium gel and thereby inhibit inflammation of the tissues surrounding the arthritic ankle. Color Doppler-mode imaging revealed that US-MB treatment induced a rapid reduction in synovial neoangiogenesis in the arthritic area. PMID:27181685

  20. Anti-inflammation effect of methyl salicylate 2-O-β-D-lactoside on adjuvant induced-arthritis rats and lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells.

    PubMed

    Zhang, Xue; Sun, Jialin; Xin, Wenyu; Li, Yongjie; Ni, Lin; Ma, Xiaowei; Zhang, Dan; Zhang, Dongming; Zhang, Tiantai; Du, Guanhua

    2015-03-01

    Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway. PMID:25637446

  1. Tamarind Seed (Tamarindus indica) Extract Ameliorates Adjuvant-Induced Arthritis via Regulating the Mediators of Cartilage/Bone Degeneration, Inflammation and Oxidative Stress.

    PubMed

    Sundaram, Mahalingam S; Hemshekhar, Mahadevappa; Santhosh, Martin S; Paul, Manoj; Sunitha, Kabburahalli; Thushara, Ram M; NaveenKumar, Somanathapura K; Naveen, Shivanna; Devaraja, Sannaningaiah; Rangappa, Kanchugarakoppal S; Kemparaju, Kempaiah; Girish, Kesturu S

    2015-06-10

    Medicinal plants are employed in the treatment of human ailments from time immemorial. Several studies have validated the use of medicinal plant products in arthritis treatment. Arthritis is a joint disorder affecting subchondral bone and cartilage. Degradation of cartilage is principally mediated by enzymes like matrix metalloproteinases (MMPs), hyaluronidases (HAase), aggrecanases and exoglycosidases. These enzymes act upon collagen, hyaluronan and aggrecan of cartilage respectively, which would in turn activate bone deteriorating enzymes like cathepsins and tartrate resistant acid phosphatases (TRAP). Besides, the incessant action of reactive oxygen species and the inflammatory mediators is reported to cause further damage by immunological activation. The present study demonstrated the anti-arthritic efficacy of tamarind seed extract (TSE). TSE exhibited cartilage and bone protecting nature by inhibiting the elevated activities of MMPs, HAase, exoglycosidases, cathepsins and TRAP. It also mitigated the augmented levels of inflammatory mediators like interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-23 and cyclooxygenase-2. Further, TSE administration alleviated increased levels of ROS and hydroperoxides and sustained the endogenous antioxidant homeostasis by balancing altered levels of endogenous antioxidant markers. Overall, TSE was observed as a potent agent abrogating arthritis-mediated cartilage/bone degradation, inflammation and associated stress in vivo demanding further attention.

  2. Tamarind Seed (Tamarindus indica) Extract Ameliorates Adjuvant-Induced Arthritis via Regulating the Mediators of Cartilage/Bone Degeneration, Inflammation and Oxidative Stress

    PubMed Central

    Sundaram, Mahalingam S.; Hemshekhar, Mahadevappa; Santhosh, Martin S.; Paul, Manoj; Sunitha, Kabburahalli; Thushara, Ram M.; NaveenKumar, Somanathapura K.; Naveen, Shivanna; Devaraja, Sannaningaiah; Rangappa, Kanchugarakoppal S.; Kemparaju, Kempaiah; Girish, Kesturu S.

    2015-01-01

    Medicinal plants are employed in the treatment of human ailments from time immemorial. Several studies have validated the use of medicinal plant products in arthritis treatment. Arthritis is a joint disorder affecting subchondral bone and cartilage. Degradation of cartilage is principally mediated by enzymes like matrix metalloproteinases (MMPs), hyaluronidases (HAase), aggrecanases and exoglycosidases. These enzymes act upon collagen, hyaluronan and aggrecan of cartilage respectively, which would in turn activate bone deteriorating enzymes like cathepsins and tartrate resistant acid phosphatases (TRAP). Besides, the incessant action of reactive oxygen species and the inflammatory mediators is reported to cause further damage by immunological activation. The present study demonstrated the anti-arthritic efficacy of tamarind seed extract (TSE). TSE exhibited cartilage and bone protecting nature by inhibiting the elevated activities of MMPs, HAase, exoglycosidases, cathepsins and TRAP. It also mitigated the augmented levels of inflammatory mediators like interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-23 and cyclooxygenase-2. Further, TSE administration alleviated increased levels of ROS and hydroperoxides and sustained the endogenous antioxidant homeostasis by balancing altered levels of endogenous antioxidant markers. Overall, TSE was observed as a potent agent abrogating arthritis-mediated cartilage/bone degradation, inflammation and associated stress in vivo demanding further attention. PMID:26059174

  3. Tamarind Seed (Tamarindus indica) Extract Ameliorates Adjuvant-Induced Arthritis via Regulating the Mediators of Cartilage/Bone Degeneration, Inflammation and Oxidative Stress.

    PubMed

    Sundaram, Mahalingam S; Hemshekhar, Mahadevappa; Santhosh, Martin S; Paul, Manoj; Sunitha, Kabburahalli; Thushara, Ram M; NaveenKumar, Somanathapura K; Naveen, Shivanna; Devaraja, Sannaningaiah; Rangappa, Kanchugarakoppal S; Kemparaju, Kempaiah; Girish, Kesturu S

    2015-01-01

    Medicinal plants are employed in the treatment of human ailments from time immemorial. Several studies have validated the use of medicinal plant products in arthritis treatment. Arthritis is a joint disorder affecting subchondral bone and cartilage. Degradation of cartilage is principally mediated by enzymes like matrix metalloproteinases (MMPs), hyaluronidases (HAase), aggrecanases and exoglycosidases. These enzymes act upon collagen, hyaluronan and aggrecan of cartilage respectively, which would in turn activate bone deteriorating enzymes like cathepsins and tartrate resistant acid phosphatases (TRAP). Besides, the incessant action of reactive oxygen species and the inflammatory mediators is reported to cause further damage by immunological activation. The present study demonstrated the anti-arthritic efficacy of tamarind seed extract (TSE). TSE exhibited cartilage and bone protecting nature by inhibiting the elevated activities of MMPs, HAase, exoglycosidases, cathepsins and TRAP. It also mitigated the augmented levels of inflammatory mediators like interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-23 and cyclooxygenase-2. Further, TSE administration alleviated increased levels of ROS and hydroperoxides and sustained the endogenous antioxidant homeostasis by balancing altered levels of endogenous antioxidant markers. Overall, TSE was observed as a potent agent abrogating arthritis-mediated cartilage/bone degradation, inflammation and associated stress in vivo demanding further attention. PMID:26059174

  4. Reexamination of the difference in susceptibility to adjuvant-induced arthritis among LEW/Crj, Slc/Wistar/ST and Slc/SD rats.

    PubMed

    Banik, Ratan Kumar; Kasai, Masanori; Mizumura, Kazue

    2002-04-01

    The present investigations were performed to assess the differences among rat colonies commonly used for neurophysiological research regarding the development of complete Freund's adjuvant (CFA)-induced arthritis. Inflammatory signs including edema in the paw fluctuated remarkably among individual Wistar (Slc/Wistar/ST) and Sprague-Dawley (Slc/SD) rats, while the inflammatory signs of Lewis (LEW/Crj) rats appeared earlier and was severer and more consistent than Slc/Wistar/ST and Slc/SD rats. Edema in the hind paw developed in 100% of LEW/Crj rats with the lowest dose of CFA (0.6 mg/rat) used as compared with 64% of Slc/Wistar/ST (CFA 1 mg/rat) and 38% of Slc/SD rats (CFA 1.2 mg/rat). Retardation of weight gain was observed in Slc/Wistar/ST and Slc/SD rats in contrast to a severe weight decrease in inflamed LEW/Crj rats after the development of arthritis.

  5. Antiarthritic effect of aqueous and ethanolic leaf extracts of Pistia stratiotes in adjuvant-induced arthritis in Sprague-Dawley rats

    PubMed Central

    Kyei, Samuel; Koffuor, George A; Boampong, Johnson N

    2012-01-01

    Background Pistia stratiotes has been used effectively to treat a number of inflammatory conditions. This study aims to determine the antiarthritic effect of aqueous and ethanolic leaf extracts of P. stratiotes. Methods Arthritis was induced in Sprague-Dawley rats, paw swelling was measured, and arthritis indices were estimated in rats treated with aqueous and ethanolic leaf extracts of P. stratiotes (AQ PSE and ET PSE, respectively), methotrexate, diclofenac, dexamethasone, and normal saline-treated rats. Radiologic imaging, hematological assessment of red and white blood cells, C-reactive protein and erythrocyte sedimentation rate, as well as histopathological studies were also done. The data were analyzed using GraphPad Prism 5. Results The 30, 100, and 300 mg/kg doses of AQ PSE and the 30 and 100 mg/kg doses of ET PSE caused a significant (P ≤ 0.05–0.001) reduction in ipsilateral paw swelling, similar to the effects of methotrexate, dexamethasone, and diclofenac. Only the 30 mg/kg dose of AQ PSE caused a significant (P ≤ 0.01) reduction in contralateral paw swelling. Arthritic indices reduced significantly (P ≤ 0.05–0.001) at all drug doses, except for the 100 and 300 mg/kg doses of ET PSE. White blood cell levels decreased significantly (P ≤ 0.05–0.01) in arthritic rats treated with the 30 mg/kg dose of AQ PSE and those treated with methotrexate. Erythrocyte sedimentation rate and C-reactive protein levels were significantly (P ≤ 0.01–0.001) lower in all the treatment groups except for the rats treated with AQ PSE 300 mg/kg and ET PSE 100 and 300 mg/kg doses. The arthritic animals treated with 30 mg/kg of the aqueous extract showed no inflammatory changes in the ipsilateral paw, while the contralateral paw showed only foci of mild chronic inflammatory changes, as seen with the reference drug treatment in histopathological studies. Conclusion This study establishes that aqueous and ethanolic extracts of P. stratiotes have antiarthritic

  6. The histamine H2-receptor antagonist, cimetidine, inhibits the articular osteopenia in rats with adjuvant-induced arthritis by suppressing the osteoclast differentiation induced by histamine.

    PubMed

    Yamaura, Katsunori; Yonekawa, Taeko; Nakamura, Tomonori; Yano, Shingo; Ueno, Koichi

    2003-05-01

    The effects of cimetidine on rat adjuvant arthritis (AA) and rat osteoclast differentiation were studied. For the in vivo experiments, AA was induced by injections of Mycobacterium tuberculosis H37RA either subcutaneously into the base of the tail or into the right hind paw. The osteoclast differentiation was assessed by estimating the number of tartrate-resistant acid phosphatase-positive multinuclear cells in the bone marrow culture. Cimetidine, at the dose of 25 mg/kg body weight, reduced the paw swelling by 70% (P<0.01). Cimetidine, at 10 microM concentration, inhibited 1,25-dihydroxyvitamin D(3) (1,25[OH](2)D(3)) and histamine mediated osteoclast differentiations by 40% (P<0.01) and 60% (P<0.001), respectively. Dimaprit, at 0.3 microM, stimulated the cell differentiation by 100% (P<0.01). Mepyramine reduced osteoclast differentiation, but the reduction was not statistically significant. Measurements of bone mineral density of the femur indicated that 5 mg/kg of cimetidine treated animals had 30% (P<0.01) higher mineral density in comparison with that of the AA control group that received no cimetidine. These results suggest that histamine is a potent inducer of osteoclast differentiation, at least in part, through the histamine H(2)-receptor, and cimetidine has a preventive effect on articular destruction and accompanying inflammation in arthritic rats. These observations may provide critical insights into the pathogenesis of the bone pathology seen in patients with RA.

  7. Triphala exhibits anti-arthritic effect by ameliorating bone and cartilage degradation in adjuvant-induced arthritic rats.

    PubMed

    Kalaiselvan, Sowmiya; Rasool, MahaboobKhan

    2015-01-01

    The present study was aimed to investigate the anti-arthritic effect of triphala and its underlying mechanism on adjuvant-induced rat model. For comparison purpose, non-steroidal anti-inflammatory drug indomethacin was used. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 ml) into the right hind paw of the Wistar albino rats. Triphala (100 mg/kg body weight [bwt]) was administered intraperitoneally (from 11th to 20th day) after the arthritis induction. Arthritis induction increased the levels of reactive oxygen species (LPO and NO), elastase, and mRNA expression of pro-inflammatory cytokines (TNF-α, IL-β, IL-17, IL-6 and MCP-1), inflammatory marker enzymes (iNOS and COX-2), receptor activator of nuclear factor kappa-B ligand (RANKL), and transcription factors (NF-kB p65 and AP-1) in the paw tissues of rats. The levels of bone collagen were found to decrease with increased urinary constituents (hydroxyproline and total glycosaminoglycans) in arthritic rats. In addition, the immunohistochemistry analysis revealed increased expression of NF-kBp65 and COX-2 in the paw tissues of arthritic rats. However, administration of triphala significantly inhibited the biochemical and molecular alterations in adjuvant-induced arthritic rats compared to indomethacin (3 mg/kg bwt) as evidenced by the radiological and histopathological analysis. In conclusion, our results suggest that triphala administration ameliorate bone and cartilage degradation during rheumatoid arthritis. PMID:25942351

  8. Triphala exhibits anti-arthritic effect by ameliorating bone and cartilage degradation in adjuvant-induced arthritic rats.

    PubMed

    Kalaiselvan, Sowmiya; Rasool, MahaboobKhan

    2015-01-01

    The present study was aimed to investigate the anti-arthritic effect of triphala and its underlying mechanism on adjuvant-induced rat model. For comparison purpose, non-steroidal anti-inflammatory drug indomethacin was used. Arthritis was induced by intradermal injection of complete Freund's adjuvant (0.1 ml) into the right hind paw of the Wistar albino rats. Triphala (100 mg/kg body weight [bwt]) was administered intraperitoneally (from 11th to 20th day) after the arthritis induction. Arthritis induction increased the levels of reactive oxygen species (LPO and NO), elastase, and mRNA expression of pro-inflammatory cytokines (TNF-α, IL-β, IL-17, IL-6 and MCP-1), inflammatory marker enzymes (iNOS and COX-2), receptor activator of nuclear factor kappa-B ligand (RANKL), and transcription factors (NF-kB p65 and AP-1) in the paw tissues of rats. The levels of bone collagen were found to decrease with increased urinary constituents (hydroxyproline and total glycosaminoglycans) in arthritic rats. In addition, the immunohistochemistry analysis revealed increased expression of NF-kBp65 and COX-2 in the paw tissues of arthritic rats. However, administration of triphala significantly inhibited the biochemical and molecular alterations in adjuvant-induced arthritic rats compared to indomethacin (3 mg/kg bwt) as evidenced by the radiological and histopathological analysis. In conclusion, our results suggest that triphala administration ameliorate bone and cartilage degradation during rheumatoid arthritis.

  9. Mouse Models of Rheumatoid Arthritis.

    PubMed

    Caplazi, P; Baca, M; Barck, K; Carano, R A D; DeVoss, J; Lee, W P; Bolon, B; Diehl, L

    2015-09-01

    Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disorder characterized by synovitis that leads to cartilage and bone erosion by invading fibrovascular tissue. Mouse models of RA recapitulate many features of the human disease. Despite the availability of medicines that are highly effective in many patient populations, autoimmune diseases (including RA) remain an area of active biomedical research, and consequently mouse models of RA are still extensively used for mechanistic studies and validation of therapeutic targets. This review aims to integrate morphologic features with model biology and cover the key characteristics of the most commonly used induced and spontaneous mouse models of RA. Induced models emphasized in this review include collagen-induced arthritis and antibody-induced arthritis. Collagen-induced arthritis is an example of an active immunization strategy, whereas antibody- induced arthritis models, such as collagen antibody-induced arthritis and K/BxN antibody transfer arthritis, represent examples of passive immunization strategies. The coverage of spontaneous models in this review is focused on the TNFΔ (ARE) mouse, in which arthritis results from overexpression of TNF-α, a master proinflammatory cytokine that drives disease in many patients.

  10. UP1304, a Botanical Composition Containing Two Standardized Extracts of Curcuma longa and Morus alba, Mitigates Pain and Inflammation in Adjuvant-induced Arthritic Rats

    PubMed Central

    Yimam, Mesfin; Lee, Young-Chul; Moore, Breanna; Jiao, Ping; Hong, Mei; Nam, Jeong-Bum; Kim, Mi-Ran; Kim, Tae-Woo; Kim, Hyun-Jin; Hyun, Eu-Jin; Chu, Min; Brownell, Lidia; Jia, Qi

    2016-01-01

    Background: Though, the initial etiologies of arthritis are multifactorial, clinically, patients share pain as the prime complaints. Present day pain relief therapeutics heavily relies on the use of prescription and over the counter nonsteroidal anti-inflammatory drugs as the first line of defense where their long-term usage causes gastrointestinal and cardiovascular-related side effects. Hence, the need for evidence-based safer and efficacious alternatives from natural sources to overcome the most prominent and disabling symptoms of arthritis is an overdue. Here, we evaluated the anti-inflammatory and analgesic effect of UP1304, a composition that contains a standardized blend of two extracts from the rhizome of Curcuma longa and the root bark of Morus alba in adjuvant-induced arthritis models in rats. Materials and Methods: The anti-inflammatory and analgesic effects of the botanical composition were demonstrated in adjuvant-induced arthritis models in rats with oral dose ranges of 50–200 mg/kg. Ibuprofen at a dose of 100 mg/kg was used as a reference compound. Ex vivo sulfated glycosaminoglycan inhibition assays were performed. Results: Statistically significant improvements in pain resistance, suppression of paw edema and ankle thickness were observed in animals treated with UP1304 compared to vehicle-treated diseased rats. These results were similar to those achieved by ibuprofen treatment. Inhibitions of proteoglycan degradation were observed in a range of 37.5–61.7% for concentration of UP1304 at 50–200 μg/mL when compared to interleukin-1α-exposed untreated explants. Conclusions: These data suggest that UP1304, for its analgesic and anti-inflammatory effects, could potentially be considered agent of botanical origin for the improvement of arthritis associated symptoms. SUMMARY Pain is one of the cardinal signs of arthritis.Long term applications of commonly used non-steroidal anti-inflammatory drugs for pain relief are associated with cardiovascular

  11. Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats.

    PubMed

    Sukketsiri, Wanida; Chonpathompikunlert, Pennapa; Tanasawet, Supita; Choosri, Nutjanat; Wongtawatchai, Tulaporn

    2016-06-01

    Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund's adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity. PMID:27390722

  12. Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats.

    PubMed

    Sukketsiri, Wanida; Chonpathompikunlert, Pennapa; Tanasawet, Supita; Choosri, Nutjanat; Wongtawatchai, Tulaporn

    2016-06-01

    Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund's adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity.

  13. Effects of Apium graveolens Extract on the Oxidative Stress in the Liver of Adjuvant-Induced Arthritic Rats

    PubMed Central

    Sukketsiri, Wanida; Chonpathompikunlert, Pennapa; Tanasawet, Supita; Choosri, Nutjanat; Wongtawatchai, Tulaporn

    2016-01-01

    Apium graveolens Linn. (Apiaceae) is an indigenous plant of the North and South Americas, Southern Europe, and Asia and has been widely used as a food or a traditional medicine for treatment of inflammation and arthritis. The purpose of this study was to investigate the antioxidant effects of a methanolic extract of A. graveolens (AGE) against liver oxidative stress in an adjuvant-induced arthritic rat model. The AGE (250, 500, and 1,000 mg/kg) was given orally for 24 consecutive days after induction by injecting complete Freund’s adjuvant. Liver and spleen weights were recorded. The superoxide anion level, total peroxide (TP), glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, total antioxidant status, and oxidative stress index (OSI) were also measured. AGE treatment significantly decreased the levels of the superoxide anion, TP, and OSI whereas the GPx and SOD activities significantly increased in the liver of the arthritic rats. These results indicated that AGE showed an ameliorative effect against liver oxidative stress in adjuvant-induced arthritic rats by reducing the generation of liver free radicals and increasing the liver antioxidant enzyme activity. PMID:27390722

  14. Formoterol decreases muscle wasting as well as inflammation in the rat model of rheumatoid arthritis.

    PubMed

    Gómez-SanMiguel, Ana Belén; Gomez-Moreira, Carolina; Nieto-Bona, María Paz; Fernández-Galaz, Carmen; Villanúa, Maria Ángeles; Martín, Ana Isabel; López-Calderón, Asunción

    2016-06-01

    Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that is associated with body weight loss and muscle wasting. β2-adrenergic receptor agonists are powerful anabolic agents that trigger skeletal muscle hypertrophy and have been proposed as a promising treatment for muscle wasting in human patients. The aim of this work was to determine whether formoterol, a selective β2-adrenoreceptor agonist, is able to ameliorate muscle wasting in arthritic rats. Arthritis was induced in male Wistar rats by intradermal injection of Freund's adjuvant. Control and arthritic rats were injected daily with 50 μg/kg sc formoterol or saline for 12 days. Body weight change, food intake, and arthritis index were analyzed. After euthanasia, in the gastrocnemius mRNA was analyzed by PCR, and proteins were analyzed by Western blotting. Arthritis decreased gastrocnemius weight, cross-sectional area, and myofiber size, whereas formoterol increased those variables in both arthritic and control rats. Formoterol decreased the external signs of arthritis as well as NF-κB(p65) activation, TNFα, and COX-2 levels in the gastrocnemius of arthritic and control rats. Those effects of formoterol were associated with a decreased expression of myostatin, atrogin-1, and MuRF1 and in LC3b lipidation. Arthritis increased the expression of MyoD, myogenin, IGF-I, and IGFBP-3 and -5 in the gastrocnemius. In control and in arthritic rats, treatment with formoterol increased Akt phosphorylation and myogenin levels, whereas it decreased IGFBP-3 expression in the gastrocnemius. These data suggest that formoterol has an anti-inflammatory effect and decreases muscle wasting in arthritic rats through increasing Akt activity and myogenin and decreasing myostatin, the p-NF-κB(p65)/TNF pathway, and IGFBP-3. PMID:27245339

  15. Anti-inflammatory effects of polyphenolic-enriched red raspberry extract in an antigen-induced arthritis rat model.

    PubMed

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

    2012-06-13

    The red raspberry ( Rubus idaeus ) fruit contains bioactive polyphenols including anthocyanins and ellagitannins with reported anti-inflammatory properties. This study 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.

  16. 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 ...

  17. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis

    PubMed Central

    Hammell, D.C.; Zhang, L.P.; Ma, F.; Abshire, S.M.; McIlwrath, S.L.; Stinchcomb, A.L.; Westlund, K.N.

    2015-01-01

    Background Current arthritis treatments often have side-effects attributable to active compounds as well as route of administration. Cannabidiol (CBD) attenuates inflammation and pain without side-effects, but CBD is hydrophobic and has poor oral bioavailability. Topical drug application avoids gastrointestinal administration, first pass metabolism, providing more constant plasma levels. Methods This study examined efficacy of transdermal CBD for reduction in inflammation and pain, assessing any adverse effects in a rat complete Freund’s adjuvant-induced monoarthritic knee joint model. CBD gels (0.6, 3.1, 6.2 or 62.3 mg/day) were applied for 4 consecutive days after arthritis induction. Joint circumference and immune cell invasion in histological sections were measured to indicate level of inflammation. Paw withdrawal latency (PWL) in response to noxious heat stimulation determined nociceptive sensitization, and exploratory behaviour ascertained animal’s activity level. Results Measurement of plasma CBD concentration provided by transdermal absorption revealed linearity with 0.6–6.2 mg/day doses. Transdermal CBD gel significantly reduced joint swelling, limb posture scores as a rating of spontaneous pain, immune cell infiltration and thickening of the synovial membrane in a dose-dependent manner. PWL recovered to near baseline level. Immunohistochemical analysis of spinal cord (CGRP, OX42) and dorsal root ganglia (TNFα) revealed dose-dependent reductions of pro-inflammatory biomarkers. Results showed 6.2 and 62 mg/day were effective doses. Exploratory behaviour was not altered by CBD indicating limited effect on higher brain function. Conclusions These data indicate that topical CBD application has therapeutic potential for relief of arthritis pain-related behaviours and inflammation without evident side-effects. PMID:26517407

  18. Topical mannitol reduces inflammatory edema in a rat model of arthritis.

    PubMed

    Cavone, L; Calosi, L; Cinci, L; Moroni, F; Chiarugi, A

    2012-01-01

    The hexahydric alcohol mannitol is widely used to shift fluids from the intracellular to the extracellular compartments, to increase diuresis and improve mucus clearance in the airways. In principle, because of its physicochemical properties, topical mannitol might also draw fluids out of epidermis or mucosa. Here, we report that topical mannitol applications on the hind paws of rats with adjuvant-induced arthritis reduced paw thickness and tissue edema without affecting the inflammatory infiltrates. Of note, the anti-edema effects of acute (4 h) mannitol application occurred earlier than those prompted by a similar treatment with classic anti-inflammatory drugs such as diclofenac or ketoprofen. Yet, the extent of edema reduction was higher with diclofenac or ketoprofen than with mannitol when the drugs were applied in a chronic (16 h) paradigm. Together, data demonstrate that topical application of mannitol exerts potent and fast anti-edema effects in a rat model of joint inflammation, suggesting a possible utilization in patients affected by osseo-arthritic disorders.

  19. Hormones and autoimmunity: animal models of arthritis.

    PubMed

    Wilder, R L

    1996-05-01

    Hormones, particularly those involved in the hypothalamic-pituitary-gonadal and -adrenal axes (HPG and HPA), play important roles in various animal models of autoimmunity such as systemic lupus erythematosus in mice and collagen-induced arthritis (CIA) in mice and rats, and the streptococcal cell wall, adjuvant and avridine arthritis models in rats. Intimately linked to the subject of hormones and autoimmunity are gender, sex chromosomes and age. The importance of these factors in the various animal models is emphasized in this chapter. Several major themes are apparent. First, oestrogens promote B-cell dependent immune-complex mediated disease (e.g. lupus nephritis) but suppress T-cell dependent pathology (CIA in mice and rats), and vice versa. Second, testosterone's effects are complicated and depend on species and disease model. In rats, testosterone suppresses both T-cell and B-cell immunity. In mice, the effects are complex and difficult to interpret, e.g. they tend to enhance CIA arthritis and suppress lupus. Sex chromosome/sex hormone interactions are clearly involved in generating these complicated effects. Third, studies in Lewis and Fischer F344 rats exemplify the importance of corticosteroids, corticotrophin releasing hormone and the HPA axis in the regulation of inflammation and the predisposition to autoimmune diseases. Fourth, the HPA axis is intimately linked to the HPG axis and is sexually dimorphic. Oestrogens stimulate higher corticosteroid responses in females. The animal model data have major implications for understanding autoimmunity in humans. In particular, adrenal and gonadal hormone deficiency is likely to facilitate T-cell dependent diseases like rheumatoid arthritis, while high oestrogen levels or effects, relative to testosterone, are likely to promote B-cell dependent immune-complex-mediated diseases such as lupus nephritis.

  20. Anti-inflammatory and immunomodulating properties of grape melanin. Inhibitory effects on paw edema and adjuvant induced disease.

    PubMed

    Avramidis, N; Kourounakis, A; Hadjipetrou, L; Senchuk, V

    1998-07-01

    Natural or synthetic melanin (CAS 8049-97-6) is a high molecular weight heteropolymer, product of the enzyme tyrosinase, found to possess radical scavenging and antioxidant functions. It was of interest, therefore, to study in detail the possible anti-inflammatory and/or immunosuppressive properties of a melanin isolated from grapes. The inhibitory effect of melanin on carrageenin-induced edema, as well as on edemas produced by other phlogistics, was remarkable suggesting that melanin interferes with the prostaglandin as well as the leukotriene and/or complement system mediated inflammation. Grape melanin showed potent inhibitory effect on adjuvant induced disease (AID) in rat, suppressing significantly the primary inflammation and almost totally the secondary lesions of arthritis. Melanin under the present experimental conditions not only strongly inhibited the in vitro lipid peroxidation of rat liver microsomal membranes, but furthermore protected the in vivo hepatic peroxidation occurring in AID rats, demonstrating its antioxidant and cytoprotective properties. The serum proinflammatory cytokines IL-1, IL-6 and TNF-a and the serum globulin fraction were elevated in AID rats, parameters which were more or less normalised by melanin treatment in contrast to the reduced serum levels of IL-2 which were not affected. Similarly to other lipoxygenase inhibitors and hydroxyl radical scavenger NSAIDs, melanin treatment did not affect IL-1 neither increased the splenic mitogenic responses, unlike the classical cyclooxygenase inhibitory NSAIDs. The subpopulation Th1 (T4+ or T8+) of lymphocytes is mainly responsible for cellular immune responses and thus their possible inhibition by melanin could lead to suppression of the development of AID, a model for cell-mediated immunity. The effect of melanin on T-cells is exhibited by the reduced spleen mitogenic responses to a T-cell mitogen and the reduced serum levels of IL-2 of treated rats. In conclusion, grape melanin is an

  1. Triphala herbal extract suppresses inflammatory responses in LPS-stimulated RAW 264.7 macrophages and adjuvant-induced arthritic rats via inhibition of NF-κB pathway.

    PubMed

    Kalaiselvan, Sowmiya; Rasool, Mahaboob Khan

    2016-07-01

    This study sought to explore the mechanism of anti-inflammatory effect of triphala in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and in adjuvant-induced arthritic rats. In stimulated RAW 264.7 cells, triphala (100-300 μg/ml) significantly suppressed production of inflammatory mediators (e.g. TNFα, IL-1β, IL-6, MCP-1, VEGF, NO, PGE2), intracellular free radicals and release of lysosomal enzymes (e.g. acid phosphatase, β-galactosidase, N-acetyl glucosamindase and cathepsin D) in a dose-related manner. With triphala, mRNA levels of genes for pro-inflammatory TNFα, IL-1β, IL-6 and MCP-1, inflammatory iNOS and COX-2 enzymes and NF-κBp65 were down-regulated in the stimulated cells; in contrast, there was up-regulation of heme oxygenase-1 (HO-1) expression. Western blot analyses revealed that triphala suppressed the protein expression of NF-κB p65 and p-NF-κB p65 in the stimulated cells, which subsequently reduced over-expression of TNFα, IL-17, iNOS and COX-2 in a manner similar to that observed with BAY 11-7082, an IκB kinase inhibitor. Immunofluorescence analysis revealed inhibition of p-NF-κB p65 nuclear translocation and COX-2 protein expression caused by triphala. Consistent with these findings, the animal studies presented confirmed that triphala exhibited anti-inflammatory effects in a rat adjuvant-induced arthritis model by reducing of inflammatory mediator (e.g. IL-17, COX-2 and RANKL) expression via inhibition of NF-κB activation. Taken together, the results here demonstrated that triphala has potential anti-inflammatory applications that could be used for the treatment of inflammatory disorders, including rheumatoid arthritis. PMID:27438966

  2. Topically Applied Phospho-Sulindac Hydrogel is Efficacious and Safe in the Treatment of Experimental Arthritis in Rats

    PubMed Central

    Mattheolabakis, George; Mackenzie, Gerardo G.; Huang, Liqun; Ouyang, Nengtai; Cheng, Ka Wing

    2015-01-01

    Purpose Formulate phospho-sulindac (P-S, OXT-328) in a Pluronic hydrogel to be used as a topical anti-inflammatory agent and study its efficacy, safety and pharmacokinetics in an arthritis model. Methods LEW/crlBR rats with Freund's adjuvant-induced arthritis were treated with P-S formulated in Pluronic hydrogel (PSH). We determined the clinical manifestations of arthritis including the locomotor activity of the rats; evaluated joints for inflammation, bone resorption, cartilage damage, COX-2 expression and NF-κB activation; assayed plasma IL-6 and IL-10 levels; and studied the pharmacokinetics of P-S in rats after topical or oral administration. Results PSH applied at the onset of arthritis or when arthritis was fully developed, suppressed it by 56–82%, improved the locomotor activity of the rats 2.1–4.4 fold, suppressed synovial inflammation, bone resorption, cartilage damage, NF-κB activation and COX-2 expression but not plasma IL-6 and IL-10 levels. There were no side effects. PSH produced rapidly high local levels of P-S with < 14% of P-S reaching the circulation, while orally administered PS was rapidly metabolized generating much lower joint levels of P-S. Conclusions Topical application of PSH is efficacious and safe in the treatment of Freund's adjuvant-induced arthritis; has a favorable pharmacokinetic profile; and likely acts by suppressing key pro-inflammatory signaling pathways. PMID:23483440

  3. Animal Models of Rheumatoid Arthritis (I): Pristane-Induced Arthritis in the Rat

    PubMed Central

    Tuncel, Jonatan; Haag, Sabrina; Hoffmann, Markus H.; Yau, Anthony C. Y.; Hultqvist, Malin; Olofsson, Peter; Bäcklund, Johan; Nandakumar, Kutty Selva; Weidner, Daniela; Fischer, Anita; Leichsenring, Anna; Lange, Franziska; Haase, Claus; Lu, Shemin; Gulko, Percio S.; Steiner, Günter; Holmdahl, Rikard

    2016-01-01

    Background To facilitate the development of therapies for rheumatoid arthritis (RA), the Innovative Medicines Initiative BTCure has combined the experience from several laboratories worldwide to establish a series of protocols for different animal models of arthritis that reflect the pathogenesis of RA. Here, we describe chronic pristane-induced arthritis (PIA) model in DA rats, and provide detailed instructions to set up and evaluate the model and for reporting data. Methods We optimized dose of pristane and immunization procedures and determined the effect of age, gender, and housing conditions. We further assessed cage-effects, reproducibility, and frequency of chronic arthritis, disease markers, and efficacy of standard and novel therapies. Results Out of 271 rats, 99.6% developed arthritis after pristane-administration. Mean values for day of onset, day of maximum arthritis severity and maximum clinical scores were 11.8±2.0 days, 20.3±5.1 days and 34.2±11 points on a 60-point scale, respectively. The mean frequency of chronic arthritis was 86% but approached 100% in long-term experiments over 110 days. Pristane was arthritogenic even at 5 microliters dose but needed to be administrated intradermally to induce robust disease with minimal variation. The development of arthritis was age-dependent but independent of gender and whether the rats were housed in conventional or barrier facilities. PIA correlated well with weight loss and acute phase reactants, and was ameliorated by etanercept, dexamethasone, cyclosporine A and fingolimod treatment. Conclusions PIA has high incidence and excellent reproducibility. The chronic relapsing-remitting disease and limited systemic manifestations make it more suitable than adjuvant arthritis for long-term studies of joint-inflammation and screening and validation of new therapeutics. PMID:27227821

  4. Ameliorative Effects of a Polyphenolic Fraction of Cinnamomum zeylanicum L. Bark in Animal Models of Inflammation and Arthritis.

    PubMed

    Rathi, Badal; Bodhankar, Subhash; Mohan, V; Thakurdesai, Prasad

    2013-01-01

    Cinnamon bark (Cinnamomum zeylanicum Syn C. verum, family: Lauraceae) is one of the oldest traditional medicines for inflammatory- and pain-related disorders. The objective of the present study was to evaluate the efficacy of the polyphenol fraction from Cinnamomum zeylanicum bark (CPP) in animal models of inflammation and rheumatoid arthritis. Dose-response studies of CPP (50, 100, and 200 mg/kg) used in a separate set of in vivo experiments were conducted in acute (carrageenan-induced rat paw edema), subacute (cotton pellet-induced granuloma), and sub-chronic (AIA, adjuvant-induced established polyarthrtis) models of inflammation in rats and the acetic acid-induced writhing model of pain in mice. Effects of CPP on cytokine (IL-2, IL-4, and IFNγ) release from Concanavalin (ConA)-stimulated lymphocytes were also evaluated in vitro. CPP showed a strong and dose-dependent reduction in paw volume, weight loss reversal effects against carrageenan-induced paw edema, and cotton pellet-induced granuloma models in rats. CPP (200 mg/kg p.o. for 10 days) showed a significant reduction in elevated serum TNF-α concentration without causing gastric ulcerogenicity in the AIA model in rats. CPP also demonstrated mild analgesic effects during acute treatment as evidenced by the reduction in the writhing and paw withdrawal threshold of the inflamed rat paw during the acetic acid-induced writhing model and Randall-Selitto test. CPP was found to inhibit cytokine (IL-2, IL-4, and IFNγ) release from ConA-stimulated lymphocytes in vitro. In conclusion, CPP demonstrated prominent action in animal models of inflammation and arthritis and therefore can be considered as a potential anti-rheumatic agent with disease-modifying action.

  5. Arthritis

    MedlinePlus

    ... training for muscle tone. Your provider may suggest physical therapy. This might include: Heat or ice Splints or ... American College of Rheumatology guidelines for management of gout. Part 2: therapy and anti-inflammatory prophylaxis of acute gouty arthritis. ...

  6. Distinct alterations in ATP-binding cassette transporter expression in liver, kidney, small intestine, and brain in adjuvant-induced arthritic rats.

    PubMed

    Kawase, Atsushi; Norikane, Sari; Okada, Ayaka; Adachi, Mamiko; Kato, Yukio; Iwaki, Masahiro

    2014-08-01

    Pathophysiological changes of infection or inflammation are associated with alterations in the production of numerous absorption, distribution, metabolism and excretion-related proteins. However, little information is available on the effects of inflammation on the expression levels and activities of ATP-binding cassette (ABC) transporters. We examined the effect of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rat. Adjuvant-induced arthritis (AA) in rats was used as an animal model for inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in livers of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in membranes but not homogenates of AA rats after 7 days and after 21 days of treatment with adjuvant. Contrary to liver, protein levels of P-gp and Mrp2, but not Bcrp in kidney, increased significantly in membranes. The biliary excretion of rhodamine 123 was decreased in rats with chronic inflammation owing to decreases in efflux activities of P-gp. Our results showed that the expression of transporters in response to inflammation was organ dependent. In particular, hepatic and renal P-gp and Mrp2 exhibited opposite changes in membrane protein levels.

  7. Glutaminase Increases in Rat Dorsal Root Ganglion Neurons after Unilateral Adjuvant-Induced Hind Paw Inflammation

    PubMed Central

    Hoffman, E. Matthew; Zhang, Zijia; Schechter, Ruben; Miller, Kenneth E.

    2016-01-01

    Glutamate is a neurotransmitter used at both the peripheral and central terminals of nociceptive primary sensory neurons, yet little is known concerning regulation of glutamate metabolism during peripheral inflammation. Glutaminase (GLS) is an enzyme of the glutamate-glutamine cycle that converts glutamine into glutamate for neurotransmission and is implicated in producing elevated levels of glutamate in central and peripheral terminals. A potential mechanism for increased levels of glutamate is an elevation in GLS expression. We assessed GLS expression after unilateral hind paw inflammation by measuring GLS immunoreactivity (ir) with quantitative image analysis of L4 dorsal root ganglion (DRG) neurons after one, two, four, and eight days of adjuvant-induced arthritis (AIA) compared to saline injected controls. No significant elevation in GLS-ir occurred in the DRG ipsilateral to the inflamed hind paw after one or two days of AIA. After four days AIA, GLS-ir was elevated significantly in all sizes of DRG neurons. After eight days AIA, GLS-ir remained elevated in small (<400 µm2), presumably nociceptive neurons. Western blot analysis of the L4 DRG at day four AIA confirmed the elevated GLS-ir. The present study indicates that GLS expression is increased in the chronic stage of inflammation and may be a target for chronic pain therapy. PMID:26771651

  8. 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

  9. Quantitative gait analysis as a method to assess mechanical hyperalgesia modulated by disease-modifying antirheumatoid drugs in the adjuvant-induced arthritic rat

    PubMed Central

    Simjee, Shabana Usman; Jawed, Huma; Quadri, Javeria; Saeed, Sheikh Arshad

    2007-01-01

    In the present study, azothioprine, chloroquine, D-penicillamine, methotrexate and sodium aurothiomalate (gold salt) were evaluated for possible disease-modifying effects in the adjuvant-induced arthritis model of human rheumatoid arthritis in rats. Gait analysis was used to examine the role of disease-modifying antirheumatic drugs in the development of pain. Body weights were also measured to monitor the progression of disease and the systemic antiarthritic effects of the test compounds used in this study, as well as their systemic toxicity. Our results showed that azothioprine (5 mg/kg/day), chloroquine (12.5 mg/kg/day), sodium aurothiomalate (2.5 mg/kg/day) and methotrexate (1 mg/kg/week) not only inhibited the macroscopic changes such as erythema and swelling of limbs, but also exhibited significant reversal of gait deficits seen in the untreated or saline-treated arthritic rats. No reduction in the body weights were observed in the arthritic rats treated with azothioprine, chloroquine, sodium aurothiomalate and methotrexate. D-Penicillamine (12.5 mg/kg/day), however, showed a significant reduction (P < 0.03) in the body weights of the arthritic rats over a period of 22 days; furthermore, it was unable to show any reduction in arthritic score (P < 0.1). In earlier experiments, chloroquine and methotrexate failed to suppress carageenan-induced edema, suggesting that the mode of antiarthritic action may be different from those of nonsteroidal anti-inflammatory agents. Since these disease-modifying antirheumatic drugs are reported to have an immunomodulatory role, especially the gold salt, which influences the monocyte–macrophage system, it is suggested that the observed antiarthritic effects of disease-modifying antirheumatic drugs may be partly attributed to their immunomodulatory activity. PMID:17848187

  10. SKG arthritis as a model for evaluating therapies in rheumatoid arthritis with special focus on bone changes.

    PubMed

    Keller, Kresten Krarup; Lindgaard, Lisa Mejlvang; Wogensen, Lise; Dagnæs-Hansen, Frederik; Thomsen, Jesper Skovhus; Sakaguchi, Shimon; Stengaard-Pedersen, Kristian; Hauge, Ellen-Margrethe

    2013-05-01

    The aim was to further characterize the SKG model of rheumatoid arthritis (RA) and its potential for studying intervention treatments, with special focus on bone targeting therapies. Three individual studies were conducted, using a total of 71 SKG mice, comparing arthritis induction with mannan versus zymosan A, female versus male mice, and the effect of dexamethasone intervention treatment initiated at different time points after arthritis induction. Hind paws were embedded undecalcified in methyl methacrylate, and sections were stained with Masson-Goldner trichrome. Areal Bone Mineral Density (aBMD) of the femora was determined with pDXA. RNA was extracted from the hind paws followed by the quantification by reverse transcriptase PCR. SKG mice stimulated with mannan presented a higher arthritis score than mice stimulated with zymosan A. Female SKG mice developed a more severe arthritis than male SKG mice. Dexamethasone inhibited arthritis clinically as well as histologically when the treatment was initiated prophylactically or within the first week of arthritis. Femoral aBMD was lower in animals with arthritis than in control animals. The RANKL RNA expression was elevated in arthritic mice, whereas OPG RNA expression was unchanged. The results suggest mannan as arthritis inductor and female instead of male mice in experiments as well as an optimal time window for the initiation of treatment. Systemic bone loss as well as local up regulation of RANKL was present early in SKG arthritis. These results demonstrate that SKG arthritis is a suitable new model for evaluating therapies in RA.

  11. Hamster and murine models of severe destructive Lyme arthritis.

    PubMed

    Munson, Erik; Nardelli, Dean T; Du Chateau, Brian K; Callister, Steven M; Schell, Ronald F

    2012-01-01

    Arthritis is a frequent complication of infection in humans with Borrelia burgdorferi. Weeks to months following the onset of Lyme borreliosis, a histopathological reaction characteristic of synovitis including bone, joint, muscle, or tendon pain may occur. A subpopulation of patients may progress to a chronic, debilitating arthritis months to years after infection which has been classified as severe destructive Lyme arthritis. This arthritis involves focal bone erosion and destruction of articular cartilage. Hamsters and mice are animal models that have been utilized to study articular manifestations of Lyme borreliosis. Infection of immunocompetent LSH hamsters or C3H mice results in a transient synovitis. However, severe destructive Lyme arthritis can be induced by infecting irradiated hamsters or mice and immunocompetent Borrelia-vaccinated hamsters, mice, and interferon-gamma- (IFN-γ-) deficient mice with viable B. burgdorferi. The hamster model of severe destructive Lyme arthritis facilitates easy assessment of Lyme borreliosis vaccine preparations for deleterious effects while murine models of severe destructive Lyme arthritis allow for investigation of mechanisms of immunopathology.

  12. Anti-inflammatory and anti-oxidant properties of Sida rhombifolia stems and roots in adjuvant induced arthritic rats.

    PubMed

    Narendhirakannan, R T; Limmy, T P

    2012-04-01

    Free radical stress leads to tissue injury and progression of disease conditions such as arthritis, hemorrhagic shock, atherosclerosis, diabetes, hepatic injury, aging and ischemia, reperfusion injury of many tissues, gastritis, tumor promotion, neurodegenerative diseases and carcinogenesis. Safer anti-oxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders. Herbal medicine provides a foundation for various traditional medicine systems worldwide. The Sida species is one of the most important families of medicinal plants in India. Hence, the present study was aimed to investigate the possible anti-oxidant potential of Sida rhombifolia extracts for 30 days on adjuvant induced arthritis in experimental rats. The altered levels of hematological parameters were reverted to near normal levels, especially the elevated rate of erythrocyte sedimentation was significantly reduced by S. rhombifolia extracts in experimental rats. Oral administration of root and stem of S. rhombifolia extracts significantly increased the levels of thiobarbituric acid reactive substances and activities of catalase and glutathione peroxidase and decreased the levels of reduced glutathione and superoxide dismutase activity in arthritis induced rats. The free radical scavenging activity of the plant was further evidenced by histological and transmission electron microscopy observations made on the hind limb tissue.

  13. Animal models of rheumatoid arthritis: How informative are they?

    PubMed

    McNamee, Kay; Williams, Richard; Seed, Michael

    2015-07-15

    Animal models of arthritis are widely used to de-convolute disease pathways and to identify novel drug targets and therapeutic approaches. However, the high attrition rates of drugs in Phase II/III rates means that a relatively small number of drugs reach the market, despite showing efficacy in pre-clinical models. There is also increasing awareness of the ethical issues surrounding the use of animal models of disease and it is timely, therefore, to review the relevance and translatability of animal models of arthritis. In this paper we review the most commonly used animal models in terms of their pathological similarities to human rheumatoid arthritis as well as their response to drug therapy. In general, the ability of animal models to predict efficacy of biologics in man has been good. However, the predictive power of animal models for small molecules has been variable, probably because of differences in the levels of target knockdown achievable in vivo.

  14. Vascular endothelial dysfunction associated with elevated serum homocysteine levels in rat adjuvant arthritis: effect of vitamin E administration.

    PubMed

    Can, Cenk; Cinar, Mehtap G; Koşay, Sezen; Evinç, Akgün

    2002-06-14

    We aimed to study the alterations in serum homocysteine levels and endothelium-dependent and -independent vascular relaxant responses in adjuvant-induced arthritis of the rat and to determine the effects of vitamin E administration on these changes. Arthritis was induced by a single intradermal injection of Freund's complete adjuvant into the paw. 26 days after the induction of arthritis, serum homocysteine levels and relaxant responses to acetylcholine and sodiumnitroprusside in thoracic aortas were evaluated. The relaxant responses to acetylcholine were decreased in aortas from arthritic rats, whereas the responses to sodiumnitroprusside were not significantly different when compared to the aortas from control rats. A significant increase was observed in serum homocysteine levels of the arthritic rats in comparison to those of controls. Vitamin E administration (100 mg/kg/day, i.m. for 26 days) to arthritic rats resulted in a significant increase in endothelium-dependent aortic responses to acetylcholine and a significant decrease in serum homocysteine levels with respect to the non-treated arthritic rats. However, in healthy rats, vitamin E treatment significantly decreased the acetylcholine-induced relaxant responses. We conclude that adjuvant-induced arthritis in the rat is associated with increased serum homocysteine levels and this is accompanied by a reduction in endothelium-dependent vascular responses in the thoracic aortas. Vitamin E treatment leads to normalization of the increased serum homocysteine levels and improves the endothelium-dependent relaxant responses in this experimental model. PMID:12044840

  15. 1-Methyl-Tryptophan Synergizes with Methotrexate to Alleviate Arthritis in a Mouse Model of Arthritis

    PubMed Central

    Pigott, Elizabeth; DuHadaway, James B.; Muller, Alexander J.; Gilmour, Susan; Prendergast, George C.; Mandik-Nayak, Laura

    2014-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disease with no known cure. Current strategies to treat RA, including methotrexate (MTX), target the later inflammatory stage of disease. Recently, we showed that inhibiting indoleamine-2,3-dioxygenase (IDO) with 1-methyl-tryptophan (1MT) targets autoantibodies and cytokines that drive the initiation of the autoimmune response. Therefore, we hypothesized that combining 1MT with MTX would target both the initiation and chronic inflammatory phases of the autoimmune response and be an effective co-therapeutic strategy for arthritis. To test this, we used K/BxN mice, a pre-clinical model of arthritis that develops joint-specific inflammation with many characteristics of human RA. Mice were treated with 1MT, MTX, alone or in combination, and followed for arthritis, autoantibodies, and inflammatory cytokines. Both 1MT and MTX were able to partially inhibit arthritis when used individually; however, combining MTX + 1MT was significantly more effective than either treatment alone at delaying the onset and alleviating the severity of joint inflammation. We went on to show that combination of MTX + 1MT did not lower inflammatory cytokine or autoantibody levels, nor could the synergistic co-therapeutic effect be reversed by the adenosine receptor antagonist theophylline or be mimicked by inhibition of polyamine synthesis. However, supplementation with folinic acid did reverse the synergistic co-therapeutic effect, demonstrating that, in the K/BxN model, MTX synergizes with 1MT by blocking folate metabolism. These data suggest that pharmacological inhibition of IDO with 1MT is a potential candidate for use in combination with MTX to increase its efficacy in the treatment of RA. PMID:24798341

  16. Mucosal SIV Vaccines Comprising Inactivated Virus Particles and Bacterial Adjuvants Induce CD8+ T-Regulatory Cells that Suppress SIV-Positive CD4+ T-Cell Activation and Prevent SIV Infection in the Macaque Model

    PubMed Central

    Andrieu, Jean-Marie; Chen, Song; Lai, Chunhui; Guo, Weizhong; Lu, Wei

    2014-01-01

    A new paradigm of mucosal vaccination against human immunodeficiency virus (HIV) infection has been investigated in the macaque model. A vaccine consisting of inactivated simian immunodeficiency virus (SIV)mac239 particles together with a living bacterial adjuvant (either the Calmette and Guerin bacillus, Lactobacillus plantarum or Lactobacillus rhamnosus) was administered to macaques via the vaginal or oral/intragastric route. In contrast to all established human and veterinary vaccines, these three vaccine regimens did not elicit SIV-specific antibodies nor cytotoxic T-lymphocytes but induced a previously unrecognized population of non-cytolytic MHCIb/E-restricted CD8+ T-regulatory cells that suppressed the activation of SIV-positive CD4+ T-lymphocytes. SIV reverse transcription was thereby blocked in inactivated CD4+ T-cells; the initial burst of virus replication was prevented and the vaccinated macaques were protected from a challenge infection. For 3–14 months after intragastric immunization, 24 macaques were challenged intrarectally with a high dose of SIVmac239 or with the heterologous strain SIV B670 (both strains grown on macaques PBMC). Twenty-three of these animals were found to be protected for up to 48 months while all 24 control macaques became infected. This protective effect against SIV challenge together with the concomitant identification of a robust ex vivo correlate of protection suggests a new approach for developing an HIV vaccine in humans. The induction of this new class of CD8+ T-regulatory cells could also possibly be used therapeutically for suppressing HIV replication in infected patients and this novel tolerogenic vaccine paradigm may have potential applications for treating a wide range of immune disorders and is likely to may have profound implications across immunology generally. PMID:25071760

  17. Rheumatoid arthritis: identifying and characterising polymorphisms using rat models

    PubMed Central

    2016-01-01

    ABSTRACT Rheumatoid arthritis is a chronic inflammatory joint disorder characterised by erosive inflammation of the articular cartilage and by destruction of the synovial joints. It is regulated by both genetic and environmental factors, and, currently, there is no preventative treatment or cure for this disease. Genome-wide association studies have identified ∼100 new loci associated with rheumatoid arthritis, in addition to the already known locus within the major histocompatibility complex II region. However, together, these loci account for only a modest fraction of the genetic variance associated with this disease and very little is known about the pathogenic roles of most of the risk loci identified. Here, we discuss how rat models of rheumatoid arthritis are being used to detect quantitative trait loci that regulate different arthritic traits by genetic linkage analysis and to positionally clone the underlying causative genes using congenic strains. By isolating specific loci on a fixed genetic background, congenic strains overcome the challenges of genetic heterogeneity and environmental interactions associated with human studies. Most importantly, congenic strains allow functional experimental studies be performed to investigate the pathological consequences of natural genetic polymorphisms, as illustrated by the discovery of several major disease genes that contribute to arthritis in rats. We discuss how these advances have provided new biological insights into arthritis in humans. PMID:27736747

  18. Anti-bone resorption activity of deer antler aqua-acupunture, the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe (Nokyong) in adjuvant-induced arthritic rats.

    PubMed

    Kim, Kyung-Ho; Kim, Kap-Sung; Choi, Byeong-Joon; Chung, Kang-Hyun; Chang, Young-Chae; Lee, Seung-Duk; Park, Kwan-Kyu; Kim, Hyung-Min; Kim, Cheorl-Ho

    2005-01-15

    Effect of deer antler aqua-acupunture (DAA), prepared from the pilose antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe, a traditional immunosuppressive acupuncture, was evaluated to assess the reductions in bone mass, strength, and turnover in adjuvant-induced arthritic rats. For measuring the above parameters, a 20-day dosing experiment was performed using 6-week-old female Lewis rats. Arthritis was induced by injecting the adjuvant into the hind paw of the Lewis rats. The age-dependent increases in the body weight, lumbar bone mineral content and density (BMC and BMD) and compressive strength were disturbed in the arthritic rats. At 10 days, the histomorphometric parameters of bone formation (BFR/BS and BFR/BV) and the serum osteocalcin levels were significantly reduced compared with the baseline controls of Lewis rats. However, the BMC values corrected for body weight did not differ significantly between the arthritic and normal rats, and the bone minerals were not reduced when they were compared with the baseline controls. At 20 days, the parameters of bone minerals and strength of the lumbar body in the arthritic rats, both with and without correction for body weight, were significantly reduced compared with the baseline controls. The trabecular mineralizing surface remained significantly reduced and the osteoclast numbers were increased. DAA at the doses of 10, 20, 50 and 100 microg/kg, administered by Shinsu (B23) acupuncture daily from the start of the experiment, significantly prevented the development of the chronic paw edema at 20 days. The reductions in the parameters such as bone minerals, strength, and trabecular bone formation, and the increase in osteoclast number were alleviated by this DAA. Age-dependent increases in the lumbar height, disturbed by the adjuvant injection, were also maintained. These results indicated that a 20-day-period is necessary to obtain sufficient reductions in the bone mass and strength of the lumbar body

  19. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

    PubMed

    Oh, Djin-Ye; Dowling, David J; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T; Sauld, John F; Pettengill, Matthew; Kho, Alvin T; Pollack, Henry J; Steen, Hanno; Levy, Ofer

    2016-06-01

    Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles

  20. Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures*

    PubMed Central

    Oh, Djin-Ye; Dowling, David J.; Ahmed, Saima; Choi, Hyungwon; Brightman, Spencer; Bergelson, Ilana; Berger, Sebastian T.; Sauld, John F.; Pettengill, Matthew; Kho, Alvin T.; Pollack, Henry J.; Steen, Hanno; Levy, Ofer

    2016-01-01

    Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations. In this study, we employed proteomics to characterize the adjuvant-induced changes of secretomes from human newborn and adult monocytes in response to Alum, the most commonly used adjuvant in licensed vaccines; Monophosphoryl Lipid A (MPLA), a TLR4-activating adjuvant component of a licensed Human Papilloma Virus vaccine; and R848 an imidazoquinoline TLR7/8 agonist that is a candidate adjuvant for early life vaccines. Monocytes were incubated in vitro for 24 h with vehicle, Alum, MPLA, or R848 and supernatants collected for proteomic analysis employing liquid chromatography-mass spectrometry (LC-MS) (data available via ProteomeXchange, ID PXD003534). 1894 non-redundant proteins were identified, of which ∼30 - 40% were common to all treatment conditions and ∼5% were treatment-specific. Adjuvant-stimulated secretome profiles, as identified by cluster analyses of over-represented proteins, varied with age and adjuvant type. Adjuvants, especially Alum, activated multiple innate immune pathways as assessed by functional enrichment analyses. Release of lactoferrin, pentraxin 3, and matrix metalloproteinase-9 was confirmed in newborn and adult whole blood and blood monocytes stimulated with adjuvants alone or adjuvanted licensed vaccines with distinct clinical reactogenicity profiles. MPLA-induced adult monocyte secretome profiles correlated in silico with transcriptome profiles induced in adults immunized with the MPLA-adjuvanted RTS,S malaria vaccine (Mosquirix™). Overall, adjuvants such as Alum, MPLA and R848 give rise to distinct and age-specific monocyte secretome profiles

  1. Adjuvant-induced antired blood cell activity in CBA mice

    PubMed Central

    McCracken, Ann; McBride, W. H.; Weir, D. M.

    1971-01-01

    Various micro-organisms are known to act as immunological adjuvants and included amongst these are Corynebacteriaceae. Numerous studies on Corynebacterium parvum have shown, in particular, its ability to cause proliferation and enhanced activity of the reticulo-endothelial system. This organism also leads in mice to anaemia and this report describes the simultaneous appearance of a red cell autoantibody in mice injected with C. parvum or another diphtheroid (SF 16) isolated from rheumatoid joint fluid. The significance of this latter observation is considered in relation to the unexplained anaemia of rheumatoid arthritis. PMID:4933319

  2. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra.

    PubMed

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  3. Suppression of Inflammation and Arthritis by Orally Administrated Cardiotoxin from Naja naja atra

    PubMed Central

    Chen, Cao-Xin; Chen, Jie-Yu; Kou, Jian-Qun; Xu, Yin-Li; Wang, Shu-Zhi; Zhu, Qi; Yang, Lu; Qin, Zheng-Hong

    2015-01-01

    Cardiotoxin (CTX) from Naja naja atra venom (NNAV) reportedly had analgesic effect in animal models but its role in inflammation and arthritis was unknown. In this study, we investigated the analgesic, anti-inflammatory, and antiarthritic actions of orally administered CTX-IV isolated from NNAV on rodent models of inflammation and adjuvant arthritis. CTX had significant anti-inflammatory effects in models of egg white induced nonspecific inflammation, filter paper induced rat granuloma formation, and capillary osmosis tests. CTX significantly reduced the swelling of paw induced by egg white, the inflammatory exudation, and the formation of granulomas. CTX reduced the swelling of paw, the AA clinical scores, and pathological alterations of joint. CTX significantly decreased the number of the CD4 T cells and inhibited the expression of relevant proinflammatory cytokines IL-17 and IL-6. CTX significantly inhibited the secretion of proinflammatory cytokine IL-6 and reduced the level of p-STAT3 in FLS. These results suggest that CTX inhibits inflammation and inflammatory pain and adjuvant-induced arthritis. CTX may be a novel therapeutic drug for treatment of arthritis. PMID:25767552

  4. Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract.

    PubMed

    Bose, Madhura; Chakraborty, Mousumi; Bhattacharya, Sourav; Mukherjee, Debarati; Mandal, Suvra; Mishra, Roshnara

    2014-08-01

    Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action. PMID:24399783

  5. Combination of coenzyme Q10 with methotrexate suppresses Freund's complete adjuvant-induced synovial inflammation with reduced hepatotoxicity in rats: Effect on oxidative stress and inflammation.

    PubMed

    Tawfik, Mona K

    2015-01-01

    Methotrexate (MTX) is a cornerstone disease modifying anti-rheumatic drug. One of its major drawbacks is hepatotoxicity, resulting in poor compliance of therapy. Coenzyme Q10 (CoQ10) is an antioxidant and anti-inflammatory compound, possessing both anti-arthritic and hepatoprotective potential. The present study was carried out to evaluate the effect of CoQ10 (10mg/kg) alone and in combination with MTX (2mg/kg) on the progression of adjuvant-induced arthritis in rats, and to elucidate the potential properties of CoQ10 in ameliorating MTX-induced liver damage in rats. Rats were assigned to; normal, arthritic, MTX treated, CoQ10 treated or a combination of MTX and CoQ10. CoQ10 administration potentiated the antiarthritic effect of MTX. Moreover, the combination therapy was effective in attenuating the severity of MTX-induced liver damage displayed by the improvement in hepatospecific serum markers and confirmed by the histo-pathological evaluation. Additionally, it attenuated the hepatic oxidative stress and the intensity of inflammatory mediators associated with MTX administration as evident by the regulation of oxidant/anti-oxidant balance and the inhibitory effects on TNF-α and IL-6 levels. These results revealed that CoQ10 can serve as a useful adjuvant and promote the safe use of MTX in the management of arthritis, not only by potentiating the antiarthritic effect of MTX, but also by alleviating MTX-induced hepatocellular injury.

  6. Spatial modelling of rheumatoid arthritis in Turkey by geographic information systems (GIS).

    PubMed

    İnanır, Ahmet; Dogan, Hakan Mete; Çeçen, Osman; Dogan, Cisem Nildem

    2013-11-01

    We described the recent spatial distribution of rheumatoid arthritis in Turkey and assessed the role of environmental variables in this distribution. We developed an observed rheumatoid arthritis (RA) incidence grid map by using georeferenced rheumatoid arthritis case data (2011) from the centres of 81 provinces and the kriging method with a spherical variogram model in geographic information systems (GIS). We also modelled rheumatoid arthritis incidence in GIS by using complementary spatial database including the grid map layers of 14 environmental variables of Turkey. We conducted principle component analysis and multiple regression to investigate the relationships among variables and develop a model, respectively. The produced model was run in GIS to obtain a predicted (model) RA map. We tested the reliability of the model map by residual statistics and found the model map dependable. Observed and model incidence maps revealed the geographic distribution of rheumatoid arthritis cases in Turkey. The mean temperature, minimum temperature, maximum temperature, water vapour pressure, elevation, potential evapotranspiration, latitude, distance to seas, sunshine fraction, precipitation, longitude and aspect variables were found to have significant impacts on rheumatoid arthritis. Consequently, the model incidence map established a good background to predict rheumatoid arthritis cases following environmental changes.

  7. Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis.

    PubMed

    Rosenthal, Kenneth S; Mikecz, Katalin; Steiner, Harold L; Glant, Tibor T; Finnegan, Alison; Carambula, Roy E; Zimmerman, Daniel H

    2015-06-01

    The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune conditions.

  8. Rheumatoid arthritis vaccine therapies: perspectives and lessons from therapeutic ligand epitope antigen presentation system vaccines for models of rheumatoid arthritis

    PubMed Central

    Rosenthal, Kenneth S.; Mikecz, Katalin; Steiner, Harold L.; Glant, Tibor T.; Finnegan, Alison; Carambula, Roy E.; Zimmerman, Daniel H.

    2016-01-01

    The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune conditions. PMID:25787143

  9. 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.

  10. Disability intervention model for older adults with arthritis: an integration of theory of symptom management and disablement process model.

    PubMed

    Shin, So Young

    2014-12-01

    To evolve a management plan for rheumatoid arthritis, it is necessary to understand the patient's symptom experience and disablement process. This paper aims to introduce and critique two models as a conceptual foundation from which to construct a new model for arthritis care. A Disability Intervention Model for Older Adults with Arthritis includes three interrelated concepts of symptom experience, symptom management strategies, and symptom outcomes that correspond to the Theory of Symptom Management. These main concepts influence or are influenced by contextual factors that are situated within the domains of person, environment, and health/illness. It accepts the bidirectional, complex, dynamic interactions among all components within the model representing the comprehensive aspects of the disablement process and its interventions in older adults with rheumatoid arthritis. In spite of some limitations such as confusion or complexity within the model, the Disability Intervention Model for Older Adults with Arthritis has strengths in that it encompasses the majority of the concepts of the two models, attempts to compensate for the limitations of the two models, and aims to understand the impact of rheumatoid arthritis on a patient's physical, cognitive, and emotional health status, socioeconomic status, and well-being. Therefore, it can be utilized as a guiding theoretical framework for arthritis care and research to improve the functional status of older adults with rheumatoid arthritis.

  11. Anti-arthritic effect of eugenol on collagen-induced arthritis experimental model.

    PubMed

    Grespan, Renata; Paludo, Marcia; Lemos, Henrique de Paula; Barbosa, Carmem Patrícia; Bersani-Amado, Ciomar Aparecida; Dalalio, Marcia Machado de Oliveira; Cuman, Roberto Kenji Nakamura

    2012-01-01

    This study was designed to test the efficacy of eugenol, a compound obtained from the essential oil of cloves (Syzygium aromaticum) in collagen-induced arthritis (CIA), a well characterized murine model of rheumatoid arthritis. Macroscopic clinical evidence of CIA manifests first as periarticular erythema and edema in the hind paws. Treatment with eugenol starting at the onset of arthritis (day 25) ameliorated these clinical signs of CIA. Furthermore, eugenol inhibited mononuclear cell infiltration into the knee joints of arthritic mice and also lowered the levels of cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ and tumor growth factor (TGF)-β) within the ankle joints. Eugenol treatment did not affect the in vitro cell viability as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, eugenol ameliorates experimental arthritis and could be useful as a beneficial supplement in treating human arthritis. PMID:23037170

  12. Effect of intraarticular propolis in an experimental septic arthritis model.

    PubMed

    Oner, Mithat; Kafadar, Ibrahim; Guney, Ahmet; Halici, Mehmet; Deniz, Kemal; Turk, Yildirim; Argun, Mahmut

    2011-01-01

    To evaluate the efficacy and safety of intraarticular propolis compared with systemic antibiotic treatment in an experimental septic arthritis model. Thirty-two rabbits were infected intraarticularly by Staphylococcus aureus. The rabbits were randomly divided into four groups, including a control group and three experimental groups. Drainage was the only procedure performed in group I (control group). The animals were treated with daily intramuscular cefazolin sodium (75 mg/kg) for 7 days in group II. In group III, intraarticular ethanolic extract of propolis (0.5 mg/ml) was injected to the infected knees under sterile conditions on days 7, 14, and 21 after drainage. In group IV, the rabbits received both intramuscular cefazolin sodium as in group II and intraarticular ethanolic extract of propolis as in group III. After 8 weeks, the animals were killed and joint histopathological and scanning electron microscopic parameters were assessed. The best clinical score was obtained in group IV. There were statistically significant differences among all the groups (P<0.05). The highest total score of the histological examination was found in group I and the best total score was obtained in group IV. There were statistically significant differences among the groups when we evaluated the scores of the parameters as loss of chondrocytes, loss of matrix, and pannus in-growth (P<0.05). But there was no significant difference among the groups for the scores of cloning of the chondrocytes (P>0.05). The highest scanning electron microscopy score was found in group I and the best score was obtained in group IV. Our results confirm the safety and efficacy of intraarticular propolis and synergistic effect of propolis when used with cefazolin in an experimental septic arthritis model.

  13. Animal models for arthritis: innovative tools for prevention and treatment.

    PubMed

    Kollias, George; Papadaki, Piyi; Apparailly, Florence; Vervoordeldonk, Margriet J; Holmdahl, Rikard; Baumans, Vera; Desaintes, Christian; Di Santo, James; Distler, Jörg; Garside, Paul; Hegen, Martin; Huizinga, Tom W J; Jüngel, Astrid; Klareskog, Lars; McInnes, Iain; Ragoussis, Ioannis; Schett, Georg; Hart, Bert 't; Tak, Paul P; Toes, Rene; van den Berg, Wim; Wurst, Wolfgang; Gay, Steffen

    2011-08-01

    The development of novel treatments for rheumatoid arthritis (RA) requires the interplay between clinical observations and studies in animal models. Given the complex molecular pathogenesis and highly heterogeneous clinical picture of RA, there is an urgent need to dissect its multifactorial nature and to propose new strategies for preventive, early and curative treatments. Research on animal models has generated new knowledge on RA pathophysiology and aetiology and has provided highly successful paradigms for innovative drug development. Recent focus has shifted towards the discovery of novel biomarkers, with emphasis on presymptomatic and emerging stages of human RA, and towards addressing the pathophysiological mechanisms and subsequent efficacy of interventions that underlie different disease variants. Shifts in the current paradigms underlying RA pathogenesis have also led to increased demand for new (including humanised) animal models. There is therefore an urgent need to integrate the knowledge on human and animal models with the ultimate goal of creating a comprehensive 'pathogenesis map' that will guide alignment of existing and new animal models to the subset of disease they mimic. This requires full and standardised characterisation of all models at the genotypic, phenotypic and biomarker level, exploiting recent technological developments in 'omics' profiling and computational biology as well as state of the art bioimaging. Efficient integration and dissemination of information and resources as well as outreach to the public will be necessary to manage the plethora of data accumulated and to increase community awareness and support for innovative animal model research in rheumatology.

  14. The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview.

    PubMed

    Clapp, Carmen; Adán, Norma; Ledesma-Colunga, María G; Solís-Gutiérrez, Mariana; Triebel, Jakob; Martínez de la Escalera, Gonzalo

    2016-08-01

    Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.

  15. Psoriatic arthritis

    MedlinePlus

    Arthritis - psoriatic; Psoriasis - psoriatic arthritis; Spondylitis - psoriatic arthritis ... inflammatory condition. About 1 in 20 people with psoriasis may develop arthritis with the skin condition. Nail psoriasis is linked ...

  16. A novel model of rheumatoid arthritis-associated interstitial lung disease in SKG mice.

    PubMed

    Keith, Rebecca C; Powers, Jennifer L; Redente, Elizabeth F; Sergew, Amen; Martin, Richard J; Gizinski, Alison; Holers, V Michael; Sakaguchi, Shimon; Riches, David W H

    2012-03-01

    Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is associated with increased mortality in up to 10% of patients with rheumatoid arthritis. Lung exposure to cigarette smoke has been implicated in disease development. Little is known about the mechanisms underlying the development of RA-ILD, in part due to the lack of an appropriate mouse model. The objectives of this study were (i) to test the suitability of SKG mice as a model of cellular and fibrotic interstitial pneumonia in the setting of autoimmune arthritis, and (ii) to determine the role of lung injury in the development of arthritis in SKG mice. Lung tissues were evaluated in arthritic SKG mice by quantifying cell accumulation in bronchoalveolar lavage, static compliance, collagen levels, and infiltrating cell phenotypes by flow cytometry and histology. Lung injury was induced by exposure to cigarette smoke or bleomycin. Arthritic SKG mice developed a patchy cellular and fibrotic interstitial pneumonia associated with reduced static compliance, increased collagen levels, and accumulation of inflammatory cells. Infiltrating cells comprised CD4+ T cells, B cells, macrophages, and neutrophils. Chronic exposure to cigarette smoke or initiation of lung injury with bleomycin did not cause arthritis. The pattern of lung disease suggests that arthritic SKG mice represent an authentic model of nonspecific interstitial pneumonia in RA-ILD patients. The lack of arthritis development after cigarette smoke or lung injury suggests that a model where breaches in immunologic tolerance are induced by lung inflammation and injury alone may be overly simplistic.

  17. Arthritis - resources

    MedlinePlus

    Resources - arthritis ... The following organizations provide more information on arthritis : American Academy of Orthopaedic Surgeons -- orthoinfo.aaos.org/menus/arthritis.cfm Arthritis Foundation -- www.arthritis.org Centers for Disease Control and Prevention -- www. ...

  18. The influence of simvastatin in rats mandible and femur bone mass under Freund's adjuvant arthritis.

    PubMed

    Seferos, Nikos; Pantopoulou, Alkistis; Kotsiou, Antonia; Rallis, Georgios; Tesseromatis, Christine

    2012-01-01

    OBJECTIVES. Complete Freund's Adjuvant (CFA)-induced arthritis in rats has been used widely as a model of rodent arthropathy and polyarthritis followed by osteoporosis, decreased bone formation and increased bone formation. Osteoporosis is characterized by rapid reduce of bone mass affecting more than 100 million people worldwide. Periodontitis a chronic inflammatory, of multifactorian origin disease has been associated with general osteoporosis. Protective bone-specific anabolic and antiresorptive effects of HMG-CoA reductase inhibitors have also been evaluated in normal and osteoporotic bone. AIM. The aim of the study was to investigate mandible and femur bone density in Freund's adjuvant induced arthritis rats under the influence of simvastatin. METHODS. Three groups (A, B, C) of 7 Wistar male rats each aged 3 months, (292±48.38 g) were used. A control. Group B and C subjected experimental arthritis via complete Freund's adjuvant injected in right paw. Group C was treated with simvastatin 0.5 mg/kg/daily po 14 days. Femur, mandible were isolated and sizes parameters, biochemical serum findings and BMD were estimated. RESULTS. CFA established by paw diameter, adrenals and spleen weight increase and thymus weight decrease, while biochemical serum findings were also affected. Reduced femur, mandible weight and general bone mass parameters BMD evaluated via DEXA occurred and restored under simvastatin treatment. CONCLUSIONS. CFA induced mandible and femur injuries are repaired by ssimvatatin treatment that could be therapeutically useful.

  19. Regulation of autoimmune arthritis by the pro-inflammatory cytokine interferon-γ

    PubMed Central

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

    2008-01-01

    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.1l) rats at the recovery phase of AA showed the highest level of IFN-γ in recall response to mycobacterial heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1l) rats secreted high levels of IFN-γ much earlier following disease induction. However, no significant secretion of IL-10 or TGF-β 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-γ, 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. PMID:18276192

  20. A model of impairment and functional limitation in rheumatoid arthritis

    PubMed Central

    Escalante, Agustín; Haas, Roy W; del Rincón, Inmaculada

    2005-01-01

    Background We have previously proposed a theoretical model for studying physical disability and other outcomes in rheumatoid arthritis (RA). The purpose of this paper is to test a model of impairment and functional limitation in (RA), using empirical data from a sample of RA patients. We based the model on the disablement process framework. Methods We posited two distinct types of impairment in RA: 1) Joint inflammation, measured by the tender, painful and swollen joint counts; and 2) Joint deformity, measured by the deformed joint count. We hypothesized direct paths from the two impairments to functional limitation, measured by the shirt-button speed, grip strength and walking velocity. We used structural equation modeling to test the hypothetical relationships, using empirical data from a sample of RA patients recruited from six rheumatology clinics. Results The RA sample was comprised of 779 RA patients. In the structural equation model, the joint inflammation impairment displayed a strong significant path toward the measured variables of joint pain, tenderness and swelling (standardized regression coefficients 0.758, 0.872 and 0.512, P ≤ 0.001 for each). The joint deformity impairment likewise displayed significant paths toward the measured upper limb, lower limb, and other deformed joint counts (standardized regression coefficients 0.849, 0.785, 0.308, P ≤ 0.001 for each). Both the joint inflammation and joint deformity impairments displayed strong direct paths toward functional limitation (standardized regression coefficients of -0.576 and -0.564, respectively, P ≤ 0.001 for each), and explained 65% of its variance. Model fit to data was fair to good, as evidenced by a comparative fit index of 0.975, and the root mean square error of approximation = 0.058. Conclusion This evidence supports the occurrence of two distinct impairments in RA, joint inflammation and joint deformity, that together, contribute strongly to functional limitations in this disease

  1. Ferulic acid ethyl ester diminished Complete Freund's Adjuvant-induced incapacitation through antioxidant and anti-inflammatory activity.

    PubMed

    Cunha, Francisco Valmor Macedo; Gomes, Bruno de Sousa; Neto, Benedito de Sousa; Ferreira, Alana Rodrigues; de Sousa, Damião Pergentino; de Carvalho e Martins, Maria do Carmo; Oliveira, Francisco de Assis

    2016-01-01

    Ferulic acid ethyl ester (FAEE) is a derivate from ferulic acid which reportedly has antioxidant effect; however, its role on inflammation was unknown. In this study, we investigated the orally administered FAEE anti-inflammatory activity on experimental inflammation models and Complete Freund's Adjuvant (CFA)-induced arthritis in rats. CFA-induced arthritis has been evaluated by incapacitation model and radiographic knee joint records at different observation time. FAEE (po) reduced carrageenan-induced paw edema (p < 0.001) within the 1st to 5th hours at 50 and 100 mg/kg doses. FAEE 50 and 100 mg/kg, po inhibited leukocyte migration into air pouch model (p < 0.001), and myeloperoxidase, superoxide dismutase, and catalase activities (p < 0.001) increased total thiol concentration and decreased the TNF-α and IL-1β concentrations, NO, and thiobarbituric acid reactive species. In the CFA-induced arthritis, FAEE 50 and 100 mg/kg significantly reduced the edema and the elevation paw time, a joint disability parameter, since second hour after arthritis induction (p < 0.001). FAEE presented rat joint protective activity in radiographic records (p < 0.001). The data suggest that the FAEE exerts anti-inflammatory activity by inhibiting leukocyte migration, oxidative stress reduction, and pro-inflammatory cytokines.

  2. Glorisa superba Hydroalcoholic Extract from Tubers Attenuates Experimental Arthritis by Downregulating Inflammatory Mediators, and Phosphorylation of ERK/JNK/p-38.

    PubMed

    Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender; Patil, Amol

    2016-10-01

    Glorisa superba (GS) is a medicinal plant that has been traditionally used in the treatment of joint pain and rheumatoid arthritis (RA). The present study was carried out to investigate the antiarthritic activity of Glorisa superba hydroalcoholic extract (GSHE) in an adjuvant-induced arthritis (AIA) rat model. Arthritis was induced by sub-plantar administration of complete Freund's adjuvant (CFA) and GSHE (25, 50, or 100 mg/kg/day) was administered orally for 21 consecutive days. Joint diameter was measured on Days 0, 3, 7, 14, and 21. GSHE dose dependently attenuates the increased joint diameter and serum tumor necrosis factor (TNF)-α level following induction of arthritis by adjuvant. This attenuation was well substantiated with reduced mRNA expression of interleukin (IL)-1β, IL-6, TNF-α, and NF-κB. Additionally, GSHE inhibited phosphorylation of the mitogen-activated protein kinases (MAPK) signaling pathway as there was decreased protein expression of MAPK (p-p38/p38 and p-ERK/ERK p-JNK/JNK ratio). Moreover, GSHE in a dose-dependent fashion normalized the redox status of ankle joint (GSH, malonaldialdehyde [MDA], and NO levels and superoxide dismutase [SOD] and catalase [CAT] activities) and displayed decreased inflammatory cell infiltration in histopathological findings. Taken together, these findings indicate that GSHE protects against AIA by modulating MAPK. PMID:27603689

  3. Suppression of Ongoing Experimental Arthritis by a Chinese Herbal Formula (Huo-Luo-Xiao-Ling Dan) Involves Changes in Antigen-Induced Immunological and Biochemical Mediators of Inflammation

    PubMed Central

    Yang, Ying-Hua; Rajaiah, Rajesh; Lee, David Y.-W; Ma, Zhongze; Yu, Hua; Fong, Harry H. S.; Lao, Lixing; Berman, Brian M.; Moudgil, Kamal D.

    2011-01-01

    Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.11) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1β but enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients. PMID:20981317

  4. Antiallergic and Antiarthritic Effects of Stem Bark Extract of Glyphaea brevis (Spreng) Monachino (Tiliaceae) in Murine Models

    PubMed Central

    Obiri, David D.; Osafo, Newman; Abotsi, Regina E.

    2013-01-01

    Background. Various parts of Glyphaea brevis (Spreng) Monachino (Tiliaceae) find a use in traditional medicine in the treatment of pain and oedema among others. This study evaluates the anti-inflammatory, antiallergic, and antiarthritic effects of a 70% (v/v) aqueous ethanol extract of the stem bark of Glyphaea brevis in murine models. Materials and Methods. The effect of the aqueous ethanol extract of Glyphaea brevis extract (GBE) was assessed on the maximal and total oedema responses in the carrageenan-induced paw oedema in mice to evaluate the acute anti-inflammatory actions of the extract. Systemic anaphylaxis was induced with compound 48/80 and survival rates monitored for 1 h in mice with prior treatment with GBE to assess the anti-allergic action of the extract. The indirect antihistamine effect of GBE was evaluated on clonidine-induced catalepsy. Rat adjuvant-induced arthritis model was used to study GBE's antiarthritic action. Results. GBE significantly suppressed the mean maximal swelling and the total paw swellings over 6 h in the carrageenan-induced paw oedema when administered either prophylactically or therapeutically. GBE dose dependently increased the time for compound 48/80-induced mortality. Administered either prophylactically or therapeutically, GBE inhibited clonidine-induced catalepsy while it had no effect on haloperidol-induced catalepsy. GBE caused a significant dose-dependent suppression of Freund's adjuvant-induced arthritis. Conclusion. Glyphaea brevis inhibits the in vivo degranulation of mast cells and thereby suppress allergy. In addition it exhibits anti-inflammatory action and attenuates Freund's adjuvant-induced arthritis. The results of this work contribute to validate the traditional use of Glyphaea brevis in the management of inflammatory disorders. PMID:24167739

  5. Protective potential of MMR vaccine against complete Freund's adjuvant-induced inflammation in rats.

    PubMed

    Abd El-Rahman, Rehab S; Suddek, Ghada M; Gameil, Nariman M; El-Kashef, Hassan A

    2011-12-01

    The aim of the present study was to investigate the effect of MMR vaccine on inflammation which was induced by complete Freund's adjuvant (CFA) in male Sprague-Dawley rats. Rats were randomly divided into the control, CFA, MMR and CFA + MMR groups. Inflammatory symptoms such as paw oedema was measured in CFA-injected rats' paw. Body weight changes and alterations in some haematological parameters and oxidative stress markers following CFA injection were checked. In CFA-inflammed rats, there was a significant increase in rat paw thickness and decrease in body weight increment. MMR exhibited a significant anti-inflammatory effect as manifested by reduction in paw thickness and normal gain in body weight when administered 1 week prior to induction of inflammation. The altered haematological parameters (TLC) and oxidative stress markers (MDA, GSH, SOD) in the inflammed rats were significantly brought back to near normal by MMR treatment. In conclusion, MMR vaccine showed a reduction in rat paw thickness and it could significantly normalize the haematological and biochemical abnormalities in CFA-induced inflammatory pain model in rats. Our data suggested that MMR could be a potential protective agent against certain types of inflammatory pain. Further histopathological and radiological studies are required to confirm the possibility of developing novel therapeutic vaccines against some forms of arthritis.

  6. Fungal arthritis

    MedlinePlus

    Mycotic arthritis; Infectious arthritis - fungal ... Marquez J, Espinoza LR. Infectious arthritis II: mycobacterial, brucellar, fungal, and parasitic arthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Rheumatology . ...

  7. Vulnerability and Resilience in Women with Arthritis: Test of a Two-Factor Model

    ERIC Educational Resources Information Center

    Smith, Bruce W.; Zautra, Alex J.

    2008-01-01

    The purpose of this study was to test a 2-factor model of affective health in women with rheumatoid arthritis (RA; n = 82) or osteoarthritis (OA; n = 88). Positive and negative social interactions and affect were assessed for 11 consecutive weeks. For each participant, Vulnerability and Resilience factors were created from factor analyses of…

  8. Enigma of IL-17 and Th17 Cells in Rheumatoid Arthritis and in Autoimmune Animal Models of Arthritis

    PubMed Central

    Kugyelka, Reka; Kohl, Zoltan; Olasz, Katalin; Mikecz, Katalin; Rauch, Tibor A.; Glant, Tibor T.; Boldizsar, Ferenc

    2016-01-01

    Rheumatoid arthritis (RA) is one of the most common autoimmune disorders characterized by the chronic and progressive inflammation of various organs, most notably the synovia of joints leading to joint destruction, a shorter life expectancy, and reduced quality of life. Although we have substantial information about the pathophysiology of the disease with various groups of immune cells and soluble mediators identified to participate in the pathogenesis, several aspects of the altered immune functions and regulation in RA remain controversial. Animal models are especially useful in such scenarios. Recently research focused on IL-17 and IL-17 producing cells in various inflammatory diseases such as in RA and in different rodent models of RA. These studies provided occasionally contradictory results with IL-17 being more prominent in some of the models than in others; the findings of such experimental setups were sometimes inconclusive compared to the human data. The aim of this review is to summarize briefly the recent advancements on the role of IL-17, particularly in the different rodent models of RA. PMID:26903711

  9. Activation of nucleotide oligomerization domain 2 exacerbates a murine model of proteoglycan-induced arthritis

    PubMed Central

    Rosenzweig, H. L.; Jann, M. M.; Glant, T. T.; Martin, T. M.; Planck, S. R.; van Eden, W.; van Kooten, P. J. S.; Flavell, R. A.; Kobayashi, K. S.; Rosenbaum, J. T.; Davey, M. P.

    2009-01-01

    In addition to its role in innate immunity, nucleotide oligomerization domain 2 (NOD2) has been shown to play a suppressive role in models of colitis. Notably, mutations in NOD2 cause the inherited granulomatous disease of the joints called Blau syndrome, thereby linking NOD2 with joint disease as well. However, the role of NOD2 in joint inflammation has not been clarified. We demonstrate here that NOD2 is functional within the mouse joint and promotes inflammation, as locally or systemically administered muramyl dipeptide (MDP; the NOD2 agonist) resulted in significant joint inflammation that was abolished in NOD2-deficient mice. We then sought to investigate the role of NOD2 in a mouse model of inflammatory arthritis dependent on adaptive immunity using TCR-transgenic mice whose T cells recognized the dominant epitope of proteoglycan (PG). Mice immunized with PG in the presence of MDP developed a more severe inflammatory arthritis and histopathology within the joints. Antigen-specific activation of splenocytes was enhanced by MDP with respect to IFN-γ production, which would be consistent with the Th1-mediated disease in vivo. Intriguingly, NOD2 deficiency did not alter the PG-induced arthritis, indicating that NOD2 does not play an essential role in this model of joint disease when it is not activated by MDP. In conclusion, we demonstrate that in a model of inflammatory arthritis dependent on T and B cell priming, NOD2 activation potentiates disease. However, the absence of NOD2 does not alter the course of inflammatory arthritis, in contrast to models of intestinal inflammation. PMID:19129483

  10. Continuous monitoring of arthritis in animal models using optical imaging modalities

    NASA Astrophysics Data System (ADS)

    Son, Taeyoon; Yoon, Hyung-Ju; Lee, Saseong; Jang, Won Seuk; Jung, Byungjo; Kim, Wan-Uk

    2014-10-01

    Given the several difficulties associated with histology, including difficulty in continuous monitoring, this study aimed to investigate the feasibility of optical imaging modalities-cross-polarization color (CPC) imaging, erythema index (EI) imaging, and laser speckle contrast (LSC) imaging-for continuous evaluation and monitoring of arthritis in animal models. C57BL/6 mice, used for the evaluation of arthritis, were divided into three groups: arthritic mice group (AMG), positive control mice group (PCMG), and negative control mice group (NCMG). Complete Freund's adjuvant, mineral oil, and saline were injected into the footpad for AMG, PCMG, and NCMG, respectively. LSC and CPC images were acquired from 0 through 144 h after injection for all groups. EI images were calculated from CPC images. Variations in feet area, EI, and speckle index for each mice group over time were calculated for quantitative evaluation of arthritis. Histological examinations were performed, and the results were found to be consistent with those from optical imaging analysis. Thus, optical imaging modalities may be successfully applied for continuous evaluation and monitoring of arthritis in animal models.

  11. Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory Arthritis.

    PubMed

    Qi, Rong; Majoros, Istvan; Misra, Asish C; Koch, Alisa E; Campbell, Phil; Marotte, Hubert; Bergin, Ingrid L; Cao, Zhengyi; Goonewardena, Sascha; Morry, Jingga; Zhang, Shuai; Beer, Michael; Makidon, Paul; Kotlyar, Alina; Thomas, Thommey P; Baker, James R

    2015-08-01

    Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 μmol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.

  12. Optimization of pulsed electromagnetic field therapy for management of arthritis in rats.

    PubMed

    Kumar, Venkatachalam Senthil; Kumar, Dilly Ashok; Kalaivani, Kalyanasundaram; Gangadharan, Akkalayi Chandrapuram; Raju, K V S Narayana; Thejomoorthy, Pammi; Manohar, Bhakthavatchalam Murali; Puvanakrishnan, Rengarajulu

    2005-09-01

    Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.

  13. Interleukin 1 or tumor necrosis factor-alpha: which is the real target in rheumatoid arthritis?

    PubMed

    Dayer, Jean-Michel

    2002-09-01

    Much debate has focused on the relative importance of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of rheumatoid arthritis (RA). The production of these cytokines by synovial macrophages is tightly regulated by cell-cell contact with T cells. During this contact, several surface molecules are implicated in contact mediated cytokine production, including CD40 ligand, CD11b/c, and CD69. Apolipoprotein A-I, an acute phase reactant (APR) that declines during systemic inflammation (reverse APR), inhibits cytokine production by interfering in the T cell-monocyte interaction. Although the effects of IL-1 and TNF-alpha overlap, they have somewhat differing roles in RA on the basis of evidence from several animal models. TNF-alpha appears to play a more important role in triggering events leading to inflammation both locally and systemically, whereas IL-1 is more involved at the local level in processes leading to cartilage and bone destruction and in impeding cartilage repair. However, IL-1 and TNF-alpha strongly synergize in numerous biological functions, both in vitro and in vivo. Blockade of IL-1 and TNF-alpha simultaneously provides favorable effects in collagen and adjuvant induced arthritis, illustrating the importance of both cytokines.

  14. Tinospora cordifolia inhibits autoimmune arthritis by regulating key immune mediators of inflammation and bone damage.

    PubMed

    Sannegowda, K M; Venkatesha, S H; Moudgil, K D

    2015-12-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints leading to tissue damage. Despite the availability of potent drugs including the biologics, many patients fail to respond to them, whereas others suffer adverse effects following long-term use of these drugs. Accordingly, the use of natural herbal products by RA patients has been increasing over the years. However, limited information about the mechanism of action of these natural products is a major shortcoming that prevents the widespread acceptance of herbal therapy by professionals and patients alike. In this study, we demonstrated the anti-arthritic activity of Tinospora cordifolia extract (TCE) using the rat adjuvant-induced arthritis model of human RA and elaborated the immune mechanisms underlying this effect. TCE treatment suppressed arthritic inflammation and bone and cartilage damage. The anti-inflammatory effect of TCE was mediated via reduction of the pro-inflammatory cytokines such as: IL-1β, TNF-α, IL-6, and IL-17; the frequency of IL-17-producing T cells; and the production of chemokines such as RANTES. Furthermore, TCE treatment limited bone damage by shifting the balance of mediators of bone remodeling (e.g., receptor activator of nuclear factor-kB ligand [RANKL] and MMP-9) in favor of anti-osteoclastic activity. Our results suggest that TCE and its bioactive components should be evaluated for their utility as therapeutic adjuncts to conventional drugs against RA. PMID:26467057

  15. Antiarthritic effects of Ajuga bracteosa Wall ex Benth. in acute and chronic models of arthritis in albino rats

    PubMed Central

    Kaithwas, Gaurav; Gautam, Raju; Jachak, Sanjay M; Saklani, Arvind

    2012-01-01

    Objective To evaluate the antiarthritic activity of Ajuga bracteosa using albino rats. Methods The antiarthritic activity of 70% ethanolic extract of Ajuga bracteosa (EEAB) was evaluated against turpentine oil- and formaldehyde- induced acute non immunological and complete freund's adjuvant (CFA)-induced chronic immunological arthritis in albino rats. Results EEAB showed a significant (P<0.05) and dose dependent inhibitory effect against acute and chronic models of arthritis. EEAB exhibited better antiarthritic activity than the standard aspirin. Conclusions EEAB exhibits a significant and promising antiarthritic activity against acute and chronic arthritis and supports the traditional use of Ajuga bracteosa for rheumatism and other inflammatory diseases. PMID:23569895

  16. Rheumatoid Arthritis

    MedlinePlus

    Rheumatoid arthritis (RA) is a form of arthritis that causes pain, swelling, stiffness and loss of function in ... wrist and fingers. More women than men get rheumatoid arthritis. It often starts in middle age and is ...

  17. Juvenile Arthritis

    MedlinePlus

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss ... common type of JA that children get is juvenile idiopathic arthritis. There are several other forms of ...

  18. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

    SciTech Connect

    Choi, Chang-Hyuk; Kim, Hong-Tae; Choe, Jung-Yoon; Kim, Jong Ki; Youn, Hwa Shik

    2007-01-19

    This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a x 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.

  19. Application of Synchrotron Radiation Imaging for Non-destructive Monitoring of Mouse Rheumatoid Arthritis Model

    NASA Astrophysics Data System (ADS)

    Choi, Chang-Hyuk; Kim, Hong-Tae; Choe, Jung-Yoon; Kim, Jong Ki; Youn, Hwa Shik

    2007-01-01

    This study was performed to observe microstructures of the rheumatoid arthritis induced mouse feet using a synchrotron radiation beam and to compare findings with histological observations. X-ray refraction images from ex-vivo rheumatoid arthritis induced mouse feet were obtained with an 8KeV white (unmonochromatic) beam and 20 micron thick CsI(Tl) scintillation crystal. The visual image was magnified using a × 10 microscope objective and captured using digital CCD camera. Experiments were performed at 1B2 bending magnet beamline of the Pohang Accelerator Laboratory (PAL) in Korea. Obtained images were compared with histopathologic findings from same sample. Cartilage destruction and thickened joint capsule with joint space narrowing were clearly identified at each grade of rheumatoid model with spatial resolution of as much as 1.2 micron and these findings were directly correlated with histopathologic findings. The results suggest that x-ray microscopy study of the rheumatoid arthritis model using synchrotron radiation demonstrates the potential for clinically relevant micro structure of mouse feet without sectioning and fixation.

  20. Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis

    PubMed Central

    2014-01-01

    Introduction Early diagnosis of and subsequent monitoring of therapy for rheumatoid arthritis (RA) could benefit from detection of (sub)clinical synovitis. Imaging of (sub)clinical arthritis by targeting the translocator protein (TSPO) on activated macrophages is feasible using (R)-[11C] PK11195-based positron emission tomography (PET), but clinical applications are limited by background uptake in peri-articular bone/bone marrow. The purpose of the present study was to evaluate two other TSPO ligands with potentially lower background uptake in neurological studies, [11C]DPA-713 and [18F]DPA-714, in a rat model of arthritis. Methods TSPO binding of DPA-713, DPA-714 and PK11195 were assessed by in vitro competition studies with [3H]DPA-713 using human macrophage THP-1 cells and CD14+ monocytes from healthy volunteers. In vivo studies were performed in rats with methylated bovine serum albumin-induced knee arthritis. Immunohistochemistry with anti-TSPO antibody was performed on paraffin-embedded sections. Rats were imaged with [11C]DPA-713 or [18F]DPA-714 PET, followed by ex vivo tissue distribution studies. Results were compared with those obtained with the tracer (R)-[11C]PK11195, the established ligand for TSPO. Results In THP-1 cells, relative TSPO binding of DPA-713 and DPA-714 were 7-fold and 25-fold higher, respectively, than in PK11195. Comparable results were observed in CD14+ monocytes from healthy volunteers. In the arthritis rat model, immunohistochemistry confirmed the presence of TSPO-positive inflammatory cells in the arthritic knee. PET images showed that uptake of [11C]DPA-713 and [18F]DPA-714 in arthritic knees was significantly increased compared with contralateral knees and knees of normal rats. Uptake in arthritic knees could be largely blocked by an excess of PK11195. [11C]DPA-713 and [18F]DPA-714 provided improved contrast compared with (R)-[11C]PK11195, as was shown by significantly higher arthritic knee-to-bone ratios of [11C]DPA-713 (1.60

  1. Defining immunological impact and therapeutic benefit of mild heating in a murine model of arthritis.

    PubMed

    Lee, Chen-Ting; Kokolus, Kathleen M; Leigh, Nicholas D; Capitano, Maegan; Hylander, Bonnie L; Repasky, Elizabeth A

    2015-01-01

    Traditional treatments, including a variety of thermal therapies have been known since ancient times to provide relief from rheumatoid arthritis (RA) symptoms. However, a general absence of information on how heating affects molecular or immunological targets relevant to RA has limited heat treatment (HT) to the category of treatments known as "alternative therapies". In this study, we evaluated the effectiveness of mild HT in a collagen-induced arthritis (CIA) model which has been used in many previous studies to evaluate newer pharmacological approaches for the treatment of RA, and tested whether inflammatory immune activity was altered. We also compared the effect of HT to methotrexate, a well characterized pharmacological treatment for RA. CIA mice were treated with either a single HT for several hours or daily 30 minute HT. Disease progression and macrophage infiltration were evaluated. We found that both HT regimens significantly reduced arthritis disease severity and macrophage infiltration into inflamed joints. Surprisingly, HT was as efficient as methotrexate in controlling disease progression. At the molecular level, HT suppressed TNF-α while increasing production of IL-10. We also observed an induction of HSP70 and a reduction in both NF-κB and HIF-1α in inflamed tissues. Additionally, using activated macrophages in vitro, we found that HT reduced production of pro-inflammatory cytokines, an effect which is correlated to induction of HSF-1 and HSP70 and inhibition of NF-κB and STAT activation. Our findings demonstrate a significant therapeutic benefit of HT in controlling arthritis progression in a clinically relevant mouse model, with an efficacy similar to methotrexate. Mechanistically, HT targets highly relevant anti-inflammatory pathways which strongly support its increased study for use in clinical trials for RA. PMID:25793532

  2. Arthritis Induces Early Bone High Turnover, Structural Degradation and Mechanical Weakness

    PubMed Central

    Vidal, Bruno; Cascão, Rita; Vale, Ana Catarina; Cavaleiro, Inês; Vaz, Maria Fátima; Brito, José Américo Almeida; Canhão, Helena; Fonseca, João Eurico

    2015-01-01

    Background We have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone. Methods Twenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers. Results AIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group. Conclusions We have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness. PMID:25617902

  3. Temporal cytokine expression and the target organ attributes unravel novel aspects of autoimmune arthritis

    PubMed Central

    Astry, Brian; Venkatesha, Shivaprasad H.; Moudgil, Kamal D.

    2013-01-01

    Susceptibility to autoimmunity is determined by multiple factors. Defining the contribution of the quantitative versus qualitative aspects of antigen-directed immune responses as well as the factors influencing target organ susceptibility is vital to advancing the understanding of the pathogenesis of autoimmunity. In a series of studies, we have addressed these issues using the adjuvant-induced arthritis (AA) model of human rheumatoid arthritis (RA). Lewis rats are susceptible to AA following immunization with heat-killed Mycobacterium tuberculosis H37Ra, whereas Wistar-Kyoto (WKY) rats of the same MHC (major histocompatibility complex) haplotype are resistant. Comparative studies on these and other susceptible/resistant rodent strains have offered interesting insights into differential cytokine responses in the face of comparable T cell proliferative response to the disease relevant antigens. Study of the cytokine kinetics have also permitted validation of the disease-protective versus disease-aggravating effects of specific cytokines by treatment of rats/mice with those cytokines at different phases of the disease. In regard to the target organ attributes, the migration of arthritogenic leukocytes into the joints; the expression of mediators of inflammation, angiogenesis, and tissue damage; the role of vascular permeability; and the characteristics of vascular endothelial cells have been examined. Further, various inhibitors of angiogenesis are effective in suppressing arthritis. Taken together, the differential cytokine responses and unique attributes of the target organ have revealed novel aspects of disease susceptibility and joint damage in AA. The translation of this basic research in animal models to RA patients would not only advance our understanding of the disease process, but also offer novel avenues for immunomodulation of this disease. PMID:24434324

  4. 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

  5. CD4+ cell-derived interleukin-17 in a model of dysregulated, Borrelia-induced arthritis.

    PubMed

    Hansen, Emily S; Johnson, Megan E; Schell, Ronald F; Nardelli, Dean T

    2016-10-01

    Lyme borreliosis, which is caused in the United States by the spirochete Borrelia burgdorferi, may manifest as different arrays of signs, symptoms and severities between infected individuals. Recent studies have indicated that particularly severe forms of Lyme borreliosis in humans are associated with an increased Th17 response. Here, we hypothesized that a murine model combining the dysregulated immune response of an environment lacking interleukin-10 (IL-10) with a robust T-cell-driven inflammatory response would reflect arthritis associated with the production of IL-17 by CD4+ cells. We demonstrate that IL-10 regulates the production of IL-17 by Borrelia-primed CD4+ cells early after interaction with Lyme spirochetes in vitro and that infection of Borrelia-primed mice with B. burgdorferi leads to significant production of IL-17 that contributes to the development of severe arthritis. These results extend our previous findings by demonstrating that a dysregulated adaptive immune response to Lyme spirochetes can contribute to severe, Th17-associated arthritis. These findings may lead to therapeutic measures for individuals with particularly severe symptoms of Lyme borreliosis. PMID:27549424

  6. Nanomedicines for Inflammatory Arthritis: Head-To-Head Comparison of Glucocorticoid-Containing Polymers, Micelles and Liposomes

    PubMed Central

    Crielaard, Bart J.; Dusad, Anand; Lele, Subodh M.; Rijcken, Cristianne J. F.; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R.; Hennink, Wim E.; Storm, Gert; Lammers, Twan; Wang, Dong

    2014-01-01

    As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research. PMID:24341611

  7. Psoriatic arthritis

    SciTech Connect

    Gerber, L.H.; Espinoza, L.R.

    1985-01-01

    This book contains 11 chapters. Some of the titles are: The history and epidemiologic definition of psoriatic arthritis as a distinct entity; Psoriatic arthritis: Further epidemiologic and genetic considerations; The radiologic features of psoriatic arthritis; and Laboratory findings and pathology of psoriatic arthritis.

  8. Majoon ushba, a polyherbal compound, suppresses pro-inflammatory mediators and RANKL expression via modulating NFкB and MAPKs signaling pathways in fibroblast-like synoviocytes from adjuvant-induced arthritic rats.

    PubMed

    Ganesan, Ramamoorthi; Doss, Hari Madhuri; Rasool, Mahaboobkhan

    2016-08-01

    Fibroblast-like synoviocytes (FLS) are inhabitant mesenchymal cells of synovial joints and have been recognized to play an imperative role in the immunopathogenesis of rheumatoid arthritis (RA). Blocking these pathological roles of FLS provides a potentially important therapeutic strategy for the treatment for RA. A recent study had confirmed that majoon ushba (MU), a polyherbal unani compound, possesses anti-arthritic effects in in vivo. Toward this direction, an effort has been made to understand the effect of MU on FLS derived from adjuvant-induced arthritis (AIA) rats. Here, we observed that MU administration (100-300 µg/ml) significantly inhibited the expression and phosphorylation of NFкB-p65 protein similar to that of the Bay 11-7082 (NFкB inhibitor) in NFкB signaling pathway and suppressed the protein expression of ERK1/2 and JNK1/2 in MAPKs signaling pathway in AIA-FLS. In addition, the protein expression of TNF-α, IL-17, RANKL, and iNOS was also found reduced. MU treatment significantly inhibited the mRNA expression of pro-inflammatory mediators (TNF-α, IL-1β, IL-6, MCP-1, IL-17, iNOS, and COX-2), transcription factors (NFкB-p65 and AP-1), and RANKL and attenuated the overproduction of TNF-α, IL-1β, IL-6, and MCP-1 (ELISA) in AIA-FLS. Furthermore, MU treatment significantly inhibited the level of lipid peroxidation, lysosomal enzymes release, and glycoproteins and increased antioxidant status (superoxide dismutase and catalase) in AIA-FLS. In conclusion, the results of this study provide evidence that MU possesses anti-inflammatory effect against AIA-FLS through the decrease in pro-inflammatory mediators expression by suppressing NFкB and MAPKs signaling pathways. PMID:27067226

  9. Activation of NALP1 inflammasomes in rats with adjuvant arthritis; a novel therapeutic target of carboxyamidotriazole in a model of rheumatoid arthritis

    PubMed Central

    Zhu, Lei; Li, Juan; Guo, Lei; Yu, Xiaoli; Wu, Danwei; Luo, Lifeng; Zhu, Lingzhi; Chen, Wei; Chen, Chen; Ye, Caiying; Zhang, Dechang

    2015-01-01

    Background and Purpose Pro-inflammatory cytokines are important in rheumatoid arthritis (RA) and their production is mainly regulated by NF-κB and inflammasomes. Carboxyamidotriazole (CAI) exhibits potent anti-inflammatory activities by decreasing cytokines. Here, we have investigated NACHT, LRR and PYD domains-containing protein (NALP) inflammasomes in a rat model of RA and explored the therapeutic effects of CAI in this model and the involvement of NF-κB and inflammasomes in the actions of CAI. Experimental Approach The anti-arthritic effects of CAI were assessed in the adjuvant arthritis (AA) model in rats, using radiological and histological techniques. NALP1 and NALP3 inflammasomes, NF-κB pathway and pro-inflammatory cytokines levels were measured with Western blots, immunohistochemistry and elisa. Key Results CAI decreased the arthritis index, improved radiological and histological changes, and reduced synovial IL-1β, IL-6, IL-18 and TNF-α levels in rats with AA. Compared with normal rats, the 70 kDa NALP1 isoform was up-regulated, NALP3 was down-regulated, and levels of the 165 kDa NALP1 isoform and the adaptor protein ASC were unchanged in synovial tissue from AA rats. CAI reduced the 70 kDa NALP1 isoform and restored NALP3 levels in AA rats; CAI inhibited caspase-1 activation in AA synovial tissue, but not its enzymic activity in vitro. In addition, CAI reduced expression of p65 NF-κB subunit and IκBα phosphorylation and degradation in AA rats. Conclusion and Implications NALP1 inflammasomes were activated in synovial tissues from AA rats and appeared to be a novel therapeutic target for RA. CAI could have therapeutic value in RA by inhibiting activation of NF-κB and NALP1 inflammasomes and by decreasing pro-inflammatory cytokines. PMID:25799914

  10. IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in a mouse model of autoimmune arthritis.

    PubMed

    Merlo, Lauren M F; Pigott, Elizabeth; DuHadaway, James B; Grabler, Samantha; Metz, Richard; Prendergast, George C; Mandik-Nayak, Laura

    2014-03-01

    Rheumatoid arthritis and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme IDO. However, the precise contributions of IDO function to autoimmunity remain unclear. In this article, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of rheumatoid arthritis. We find that IDO2, not IDO1, is critical for arthritis development, providing direct evidence of separate in vivo functions for IDO1 and IDO2. Mice null for Ido2 display decreased joint inflammation relative to wild-type mice owing to a reduction in pathogenic autoantibodies and Ab-secreting cells. Notably, IDO2 appears to specifically mediate autoreactive responses, but not normal B cell responses, as total serum Ig levels are not altered and IDO2 knockout mice are able to mount productive Ab responses to model Ags in vitro and in vivo. Reciprocal adoptive transfer studies confirm that autoantibody production and arthritis are modulated by IDO2 expression in a cell type extrinsic to the T cell. Taken together, our results, provide important insights into IDO2 function by defining its pathogenic contributions to autoantibody-mediated autoimmunity.

  11. Mandibulofacial adaptations in a juvenile animal model of temporomandibular joint arthritis.

    PubMed

    Tavakkoli-Jou, M; Miller, A J; Kapila, S

    1999-08-01

    Juvenile rheumatoid arthritis (JRA) is a chronic systemic disease of childhood that affects synovial joints including the temporomandibular joint (TMJ). Individuals with JRA of the TMJ frequently show aberrations in mandibulofacial development. Since the basis for these developmental perturbations is poorly understood, they remain a perplexing clinical problem to manage. To begin dissecting the mechanisms for altered craniofacial development in JRA of the TMJ, we characterized the gross morphologic adaptations in the facial skeleton in a juvenile animal model of TMJ arthritis. Arthritis was induced in ten 87-day-old male rabbits by intra-articular challenge with ovalbumin. Eight sham-challenged and 4 unchallenged rabbits were used as controls. Serial lateral head cephalograms, taken at 73 (T1), 87 (T2), 108 (T3), 129 (T4), and 150 (T5) days of age, were evaluated by linear measures of maxillary, mandibular, and posterior dental height dimensions. Differences in the absolute dimensions and relative percent incremental changes were compared by ANOVA and Fisher's test. The body weights, as well as the absolute measures and incremental changes in maxillary and posterior dental height dimensions, were not significantly different between the antigen-challenged and control groups. In contrast, absolute measures of posterior mandibular height, condylar neck height, and total mandibular length were significantly smaller (P < 0.05) in antigen-challenged rabbits than in both control groups at T5. Furthermore, the antigen-challenged rabbits demonstrated significantly smaller (P < 0.05) relative increases in all measures of mandibular length, and in total posterior mandibular and condylar neck heights. Cephalometric superimpositions on the cranial base and tantalum implants confirmed these quantitative observations. This investigation demonstrates mandibulofacial developmental aberrations in experimental JRA-like disease of the TMJ that are similar to those observed in humans

  12. Semiphysiologically Based Pharmacokinetic Model of Leflunomide Disposition in Rheumatoid Arthritis Patients.

    PubMed

    Hopkins, A M; Wiese, M D; Proudman, S M; O'Doherty, C E; Foster, Djr; Upton, R N

    2015-06-01

    A semiphysiologically based pharmacokinetic (semi-PBPK) population model was used to evaluate the influence of enterohepatic recycling and protein binding, as well as the effect of genetic variability in CYP1A2, CYP2C19, and ABCG2, on the large interindividual variability of teriflunomide (active metabolite) concentrations following leflunomide administration in rheumatoid arthritis (RA) patients. The model was developed with total and free teriflunomide concentrations determined in RA patients taking leflunomide, as well as mean teriflunomide concentrations following the administration of leflunomide or teriflunomide extracted from the literature. Once developed, the 15-compartment model was able to predict total and free teriflunomide concentrations and was used to screen demographic and genotypic covariates, of which only fat-free mass and liver function (ALT) improved prediction. This approach effectively evaluated the effects of multiple covariates on both total and free teriflunomide concentrations, which have only been explored previously through simplistic one-compartment models for total teriflunomide. PMID:26225264

  13. Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis.

    PubMed

    Rioja, Inmaculada; Clayton, Chris L; Graham, Simon J; Life, Paul F; Dickson, Marion C

    2005-01-01

    Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena. Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis. In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A). After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis. Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis. Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression. The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling. Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease. The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development. In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat. These findings improve our understanding of

  14. Septic arthritis

    MedlinePlus

    ... acute septic arthritis are caused by Staphylococcus or Streptococcus bacteria . Chronic septic arthritis (which is less common) ... cases are caused by the bacteria group B streptococcus. Another common cause is Haemophilus influenza , especially if ...

  15. Psoriatic Arthritis

    MedlinePlus

    ... your body. Some people with psoriasis have psoriatic arthritis. It causes pain, stiffness, and swelling of the ... physical exam and imaging tests to diagnose psoriatic arthritis. There is no cure, but medicines can help ...

  16. Viral arthritis

    MedlinePlus

    Infectious arthritis - viral ... Ohl CA, Forster D. Infectious arthritis of native joints. In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious ...

  17. Infectious Arthritis

    MedlinePlus

    ... bones meet, such as your elbow or knee. Infectious arthritis is an infection in the joint. The infection ... from another part of the body. Symptoms of infectious arthritis include Intense pain in the joint Joint redness ...

  18. Reactive arthritis

    PubMed Central

    Hind, C. R. K.

    1982-01-01

    Reactive arthritis is a rare complication of certain infections. The similar features and HLA associations with the seronegative arthropathies have raised the possibility that the latter may be forms of reactive arthritis. This review describes the clinical and epidemiological features, and the recent advances in our understanding of the underlying pathogenesis of reactive arthritis. PMID:7100033

  19. Integration of gene ontology pathways with North American Rheumatoid Arthritis Consortium genome-wide association data via linear modeling.

    PubMed

    Lebrec, Jérémie Jp; Huizinga, Tom Wj; Toes, René Em; Houwing-Duistermaat, Jeanine J; van Houwelingen, Hans C

    2009-01-01

    We describe an empirical Bayesian linear model for integration of functional gene annotation data with genome-wide association data. Using case-control study data from the North American Rheumatoid Arthritis Consortium and gene annotation data from the Gene Ontology, we illustrate how the method can be used to prioritize candidate genes for further investigation.

  20. Integration of gene ontology pathways with North American Rheumatoid Arthritis Consortium genome-wide association data via linear modeling

    PubMed Central

    2009-01-01

    We describe an empirical Bayesian linear model for integration of functional gene annotation data with genome-wide association data. Using case-control study data from the North American Rheumatoid Arthritis Consortium and gene annotation data from the Gene Ontology, we illustrate how the method can be used to prioritize candidate genes for further investigation. PMID:20018091

  1. Bacterial arthritis.

    PubMed

    Ho, G

    2001-07-01

    The septic arthritis literature of 2000 revisited several topics previously examined in some detail. These include septic arthritis in rheumatoid arthritis, rheumatic manifestations of bacterial endocarditis, and infectious complications of prosthetic joints. The trend in antibiotic prophylaxis to prevent late infections in total joint replacement is to narrow the targeted hosts to those most at risk, to define the procedures associated with the greatest risk of bacteremia, and to simplify the antibiotic regimen. The diagnoses of septic arthritis of the lumbar facet joint and septic arthritis caused by direct inoculation of bacteria by a foreign object penetrating the joint are facilitated by noninvasive imaging technologies. Septic arthritis caused by uncommon microorganisms and septic arthritis in immunocompromised hosts are other noteworthy topics in this year's literature. PMID:11555734

  2. Unmasking of a Protective TNFR1 Mediated Signal in the Collagen Arthritis Model

    PubMed Central

    Williams-Skipp, Cheryll; Raman, Thiagarajan; Valuck, Robert J.; Watkins, Herschel; Palmer, Brent E.; Scheinman, Robert I.

    2009-01-01

    OBJECTIVE: TNFR1 plays a major role in rheumatoid arthritis (RA). Here we explore the relative importance of TNFR1 signaling in the hematopoietic tissue compartment for disease progression. METHODS: DBA/1 mice were lethally irradiated and rescued with bone marrow derived from either DBA/1 or TNFR1−/− animals. The mice were then input into the collagen induced arthritis (CIA) model and disease progression characterized. RESULTS: Surprisingly, TNFR1−/− transplant mice input into the CIA model develop increased disease as compared to controls. This could not be attributed to either an increased primary response to collagen or to the contribution of a non-DBA genetic background. Histological markers of advanced disease were evident in TNFR1−/− transplant mice shortly after initiation of the immune response to collagen and long before clinical evidence of disease. Serum TNFα was undetectable while serum IL-12p40 levels were increased in TNFR1−/− transplant mice at the end point of the study. CONCLUSION: These data raise the intriguing possibility of the existence of an anti-inflammatory TNFR1 mediated circuit in the hematopoietic compartment. This circuit bears a resemblance to emerging data delineating a switch in TNFα function observed in the resolution of bacterial infections. These data suggest that TNFR1 mediated signals in the radio-resistant tissues contributes to disease progression while TNFR1 mediated signals in the radio-sensitive tissues can contribute to protection from disease. We thus put forward the hypothesis that the degree of responce to TNFα blockade in RA is dependent, in part, on the relative genetic strengths of these two pathways. PMID:19180511

  3. Effects of Libby amphibole exposure on two models of arthritis in the Lewis rat

    EPA Science Inventory

    Epidemiological data suggest that occupational exposure to the amphibole-containing venniculite in Libby, MT was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). The collagen induced arthriti...

  4. What Is Reactive Arthritis?

    MedlinePlus

    ... Arthritis PDF Version Size: 69 KB November 2014 What is Reactive Arthritis? Fast Facts: An Easy-to- ... Information About Reactive Arthritis and Other Related Conditions What Causes Reactive Arthritis? Sometimes, reactive arthritis is set ...

  5. Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: boron biodistribution study in a model of antigen-induced arthritis in rabbits.

    PubMed

    Trivillin, Verónica A; Abramson, David B; Bumaguin, Gaston E; Bruno, Leandro J; Garabalino, Marcela A; Monti Hughes, Andrea; Heber, Elisa M; Feldman, Sara; Schwint, Amanda E

    2014-11-01

    Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.

  6. B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

    PubMed

    Dunussi-Joannopoulos, Kyri; Hancock, Gerald E; Kunz, Arthur; Hegen, Martin; Zhou, Xiaochuan X; Sheppard, Barbara J; Lamothe, Jennifer; Li, Evelyn; Ma, Hak-Ling; Hamann, Philip R; Damle, Nitin K; Collins, Mary

    2005-10-01

    We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

  7. Development of a framework for reporting health service models for managing rheumatoid arthritis.

    PubMed

    O'Donnell, Siobhan; Li, Linda C; King, Judy; Lauzon, Chantal; Finn, Heather; Vliet Vlieland, Theodora P M

    2010-02-01

    The purpose of this study was to develop a framework for reporting health service models for managing rheumatoid arthritis (RA). We conducted a search of the health sciences literature for primary studies that described interventions which aimed to improve the implementation of health services in adults with RA. Thereafter, a nominal group consensus process was used to synthesize the evidence for the development of the reporting framework. Of the 2,033 citations screened, 68 primary studies were included which described 93 health service models for RA. The origin and meaning of the labels given to these health service delivery models varied widely and, in general, the reporting of their components lacked detail or was absent. The six dimensions underlying the framework for reporting RA health service delivery models are: (1) Why was it founded? (2) Who was involved? (3) What were the roles of those participating? (4) When were the services provided? (5) Where were the services provided/received? (6) How were the services/interventions accessed and implemented, how long was the intervention, how did individuals involved communicate, and how was the model supported/sustained? The proposed framework has the potential to facilitate knowledge exchange among clinicians, researchers, and decision makers in the area of health service delivery. Future work includes the validation of the framework with national and international stakeholders such as clinicians, health care administrators, and health services researchers. PMID:19865842

  8. Differential Regulatory Role of Pituitary Adenylate Cyclase–Activating Polypeptide in the Serum-Transfer Arthritis Model

    PubMed Central

    Botz, Bálint; Bölcskei, Kata; Kereskai, László; Kovács, Miklós; Németh, Tamás; Szigeti, Krisztián; Horváth, Ildikó; Máthé, Domokos; Kovács, Noémi; Hashimoto, Hitoshi; Reglődi, Dóra; Szolcsányi, János; Pintér, Erika; Mócsai, Attila; Helyes, Zsuzsanna

    2014-01-01

    Objective Pituitary adenylate cyclase–activating polypeptide (PACAP) expressed in capsaicin-sensitive sensory neurons and immune cells has divergent functions in inflammatory and pain processes. This study was undertaken to investigate the involvement of PACAP in a mouse model of rheumatoid arthritis. Methods Arthritis was induced in PACAP−/− and wild-type (PACAP+/+) mice by K/BxN serum transfer. General features of the disease were investigated by semiquantitative scoring, plethysmometry, and histopathologic analysis. Mechano- and thermonociceptive thresholds and motor functions were also evaluated. Metabolic activity was assessed by positron emission tomography. Bone morphology was measured by in vivo micro–computed tomography, myeloperoxidase activity and superoxide production by bioluminescence imaging with luminol and lucigenin, respectively, and vascular permeability by fluorescent indocyanine green dye study. Results PACAP+/+ mice developed notable joint swelling, reduced grasping ability, and mechanical (but not thermal) hyperalgesia after K/BxN serum transfer. In PACAP−/− mice clinical scores and edema were significantly reduced, and mechanical hyperalgesia and motor impairment were absent, throughout the 2-week period of observation. Metabolic activity and superoxide production increased in the tibiotarsal joints of wild-type mice but were significantly lower in PACAP−/− animals. Myeloperoxidase activity in the ankle joints of PACAP−/− mice was significantly reduced in the early phase of arthritis, but increased in the late phase. Synovial hyperplasia was also significantly increased, and progressive bone spur formation was observed in PACAP-deficient mice only. Conclusion In PACAP-deficient mice with serum-transfer arthritis, joint swelling, vascular leakage, hyperalgesia, and early inflammatory cell accumulation are reduced; in the later phase of the disease, immune cell function and bone neoformation are increased. Elucidation of

  9. Paeoniflorin ameliorates rheumatoid arthritis in rat models through oxidative stress, inflammation and cyclooxygenase 2

    PubMed Central

    JIA, ZHILIN; HE, JIAO

    2016-01-01

    Paeoniflorin has anti-inflammatory, anti-allergy, immune regulatory and pain-relieving effects, amongst other roles. However, the mechanisms underlying the protective effects of paeoniflorin on rheumatoid arthritis (RA) remain under investigation; the objective of the current study was to evaluate these protective effects in the context of an RA model. Rats were randomly divided into 5 groups, as follows: The control group, the RA rat model group, and the paeoniflorin groups, in which paeoniflorin was administered at concentrations of 5, 10 and 20 mg/kg for 3 weeks. The pain thresholds and arthritic symptoms of the RA rats were measured. Oxidative stress and inflammatory cytokines were also analyzed and western blot analysis was used to evaluate cyclooxygenase-2 (COX-2) protein expression levels. Paeoniflorin significantly increased the pain threshold and decreased the arthritic symptoms in the RA rat model. Notably, paeoniflorin reduced the malondialdehyde concentration and increased the activity of superoxide dismutase, catalase and glutathione peroxidase. Furthermore, paeoniflorin attenuated the activity of nuclear factor-κB p65 unit, tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and reduced the COX-2 protein expression level. The present study indicates that paeoniflorin ameliorates disease in rat models of RA through oxidative stress, inflammation and alterations to COX-2 expression. PMID:26893662

  10. Dose response effect of Paracoccidioides brasiliensis in an experimental model of arthritis.

    PubMed

    Loth, Eduardo Alexandre; Biazim, Samia Khalil; Dos Santos, José Henrique Fermino Ferreira; Puccia, Rosana; Brancalhão, Rosimeire Costa; Chasco, Lucinéia de Fátima; Gandra, Rinaldo Ferreira; Simão, Rita de Cássia Garcia; de Franco, Marcello Fabiano

    2014-01-01

    Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model.

  11. DOSE RESPONSE EFFECT OF Paracoccidioides brasiliensis IN AN EXPERIMENTAL MODEL OF ARTHRITIS

    PubMed Central

    Loth, Eduardo Alexandre; Biazim, Samia Khalil; dos Santos, José Henrique Fermino Ferreira; Puccia, Rosana; Brancalhão, Rosimeire Costa; Chasco, Lucinéia de Fátima; Gandra, Rinaldo Ferreira; Simão, Rita de Cássia Garcia; de Franco, Marcello Fabiano

    2014-01-01

    Paracoccidioidomycosis (PCM) is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb) and corresponds to prevalent systemic mycosis in Latin America. The aim of the present work was to evaluate the dose response effect of the fungal yeast phase for the standardization of an experimental model of septic arthritis. The experiments were performed with groups of 14 rats that received doses of 103, 104 or 105 P. brasiliensis (Pb18) cells. The fungi were injected in 50 µL of phosphate-buffered saline (PBS) directly into the knee joints of the animals. The following parameters were analyzed in this work: the formation of swelling in knees infused with yeast cells and the radiological and anatomopathological alterations, besides antibody titer by ELISA. After 15 days of infection, signs of inflammation were evident. At 45 days, some features of damage and necrosis were observed in the articular cartilage. The systemic dissemination of the fungus was observed in 11% of the inoculated animals, and it was concluded that the experimental model is able to mimic articular PCM in humans and that the dose of 105 yeast cells can be used as standard in this model. PMID:24879005

  12. Quantification of joint inflammation in rheumatoid arthritis by time-resolved diffuse optical spectroscopy and tracer kinetic modeling

    NASA Astrophysics Data System (ADS)

    Ioussoufovitch, Seva; Morrison, Laura B.; Lee, Ting-Yim; St. Lawrence, Keith; Diop, Mamadou

    2015-03-01

    Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation, which can cause progressive joint damage and disability. Diffuse optical spectroscopy (DOS) and imaging have the potential to become potent monitoring tools for RA. We devised a method that combined time-resolved DOS and tracer kinetics modeling to rapidly and reliably quantify blood flow in the joint. Preliminary results obtained from two animals show that the technique can detect joint inflammation as early as 5 days after onset.

  13. Psoriatic Arthritis

    MedlinePlus

    ... physical exam as well as x rays or magnetic resonance imaging (MRI) of the affected joints. Although there is no lab test to diagnose psoriatic arthritis, your doctor may order tests on blood or joint fluid to rule out other forms of arthritis with ...

  14. Modeling best practices in chronic disease management: the Arthritis Program at Southlake Regional Health Centre.

    PubMed

    Bain, Lorna; Mierdel, Sandra; Thorne, Carter

    2012-01-01

    Researchers, hospital administrators and governments are striving to define competencies in interprofessional care and education, as well as to identify effective models in chronic disease management. For more than 25 years The Arthritis Program (TAP) at Southlake Regional Health Centre in Newmarket, Ontario, has actively practiced within these two interrelated priorities, which are now at the top of the healthcare agenda in Ontario and Canada. The approximately 135 different rheumatic conditions are the primary cause of long-term disability in Canada, affecting those from youth to the senior years, with an economic burden estimated at $4.4 billion (CAD$) annually, and growing. For the benefit of healthcare managers and their clients with chronic conditions, this article discusses TAP's history and demonstrable success, predicated on an educational model of patient self-management and self-efficacy. Also outlined are TAP's contributions in supporting evidence-based best practices in interprofessional collaboration and chronic disease management; approaches that are arguably understudied and under-practiced. Next steps for TAP include a larger role in empirical research in chronic-disease management and integration of a formal training program to benefit health professionals launching or expanding their interprofessional programs using TAP as the dynamic clinical example. PMID:23224289

  15. Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC.

    PubMed

    Yan, Li; Hu, Rui; Tu, Song; Cheng, Wen-Jun; Zheng, Qiong; Wang, Jun-Wen; Kan, Wu-Sheng; Ren, Yi-Jun

    2015-01-01

    TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay.

  16. Establishment of a cell model for screening antibody drugs against rheumatoid arthritis with ADCC and CDC.

    PubMed

    Yan, Li; Hu, Rui; Tu, Song; Cheng, Wen-Jun; Zheng, Qiong; Wang, Jun-Wen; Kan, Wu-Sheng; Ren, Yi-Jun

    2015-01-01

    TNFα played a dominant role in the development and progression of rheumatoid arthritis (RA). Clinical trials proved the efficacies of anti-TNFα agents for curing RA. However, most researchers were concentrating on their abilities of neutralizing TNFα, the potencies of different anti-TNFα agents varied a lot due to the antibody-dependent cell-mediated cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC). For better understanding and differentiating the potentiality of various candidate anti-TNF reagents at the stage of new drug research and development, present study established a cell model expressing the transmembrane TNFα for usage in in vitro ADCC or CDC assay, meanwhile, the assay protocol described here could provide guidelines for screening macromolecular antibody drugs. A stable cell subline bearing transmembrane TNFα was first established by conventional transfection method, the expression of transmembrane TNFα was approved by flow cytometer, and the performance of the stable subline in ADCC and CDC assay was evaluated, using human peripheral blood mononuclear cells as effector cells, and Adalimumab as the anti-TNFα reagent. The stable cell subline demonstrated high level of surface expression of transmembrane TNFα, and Adalimumab exerted both ADCC and CDC effects on this cell model. In conclusion, the stable cell line we established in present research could be used in ADCC or CDC assay for screening antibody drugs, which would provide in-depth understanding of the potencies of candidate antibody drugs in addition to the traditional TNFα neutralizing assay. PMID:26884918

  17. Standardization of an experimental model suitable for studies on the effect of exercise on arthritis

    PubMed Central

    Gomes, Raquel Pinheiro; Bressan, Elisangela; da Silva, Tatiane Morgana; Gevaerd, Monique da Silva; Tonussi, Carlos Rogério; Domenech, Susana Cristina

    2013-01-01

    ABSTRACT Objective: To standardize an experimental model of chronic monoarthritis induced by complete Freund's adjuvant appropriate for the analysis of the effect of walking on nociception and on joint edema. Methods: The following factors were evaluated as to monoarthritis induction: route and site of administration, number and interval of inoculations, Mycobacterium species, and animal gender. Wistar male and female rats (200 to 250g) received two injections of complete Freund's adjuvant containing Mycobacterium tuberculosis (1.0mg/mL; 50μL) or Mycobacterium butyricum (0.5mg/mL; 50μL) intra-articularly in the tibiotarsal or tibiofemoral joints, or an injection of complete Freund's adjuvant (Mycobacterium butyricum or tuberculosis) intradermally at the base of the tail and another intra-articularly (tibiotarsal or tibiofemoral). The animals were submitted to evaluations of articular disability and edema. Articular disability was assessed by paw elevation time (in seconds) during the one-minute walk test. Edema of the tibiofemoral joint was assessed by variation of joint diameter (cm). Tibiotarsal joint edema was measured by the volume of the paw (mL). Results: Administration of complete Freund's adjuvant containing Mycobacterium butyricum increased paw elevation time and edema in both joints. Conclusion: These data allow standardization of an animal model of chronic monoarthritis adequate for analysis of the effects of exercise on treatment of rheumatoid arthritis. PMID:23579748

  18. A causal model of coping and well-being in elderly people with arthritis.

    PubMed

    Downe-Wamboldt, B L; Melanson, P M

    1998-06-01

    The purpose of this longitudinal study was to test a model of the relationships among social economic status, gender, severity of impairment, stress emotions, coping strategies and psychological well-being. A sample of 78 elderly women and men, 60 years old or over, and diagnosed as having rheumatoid arthritis since mid-life, volunteered to participate in the study. Twelve months later, 64 of these elderly people were re-interviewed. Path analysis was used to examine the empirical import of the Lazarus and Folkman theory of stress and coping. Analysis of variance for repeated measures was used to test for changes over time among the study variable. A consistent relationship between severity of impairment, emotions, coping strategies and psychological well-being emerged from the data at time one and time two. Choice of coping strategies and psychological well-being were primarily influenced by emotions. The best predictor of psychological well-being at both time periods was the stress emotion of challenge. At both time periods, optimistic and self-reliant coping strategies were used most often and evasive and emotive strategies the least.

  19. Anti-inflammatory effect and low ulcerogenic activity of etodolac, a cyclooxygenase-2 selective non-steroidal anti-inflammatory drug, on adjuvant-induced arthritis in rats.

    PubMed

    Tachibana, Masaki; Inoue, Naoki; Yoshida, Eri; Matsui, Masami; Ukai, Yojiro; Yano, Junichi

    2003-06-01

    Adjuvant arthritic rats are known to be more susceptible to gastric damage induced by non-steroidal anti-inflammatory drugs (NSAIDs) than are normal rats. We compared the relative gastric safety profile of etodolac with those of meloxicam, diclofenac sodium and indometacin in adjuvant arthritic rats and normal rats or mice. As a measure of the safety profiles of NSAIDs, we used the safety index, the ratio of the dose that elicits gastric mucosal lesions to the effective dose as an anti-inflammatory or analgesic compound. The anti-inflammatory or analgesic effects of NSAIDs were assessed by paw swelling in adjuvant arthritic rats, and either carrageenin-induced paw edema or brewer's yeast-induced hyperalgesia, as well as acetic acid-induced writhing, in normal rats or mice. In addition, we also investigated the effects of these NSAIDs on human COX-1 and COX-2 activity. Etodolac and other NSAIDs inhibited paw swelling and caused gastric mucosal lesions in adjuvant arthritic rats in a dose-dependent manner. Etodolac showed the highest UD(50) value and safety index among these NSAIDs in arthritic rats. In normal rats, etodolac also showed the highest UD(50) value and safety index, except when its effects were assessed by acetic acid-induced writhing. Etodolac and meloxicam showed selectivity for human COX-2 over COX-1. In contrast, diclofenac sodium and indometacin were selective for COX-1. These results suggest that etodolac, a COX-2 selective NSAID, has anti-inflammatory effects with a better safety profile for the stomach than do non-selective NSAIDs, including diclofenac sodium and indometacin, in adjuvant arthritic as well as normal rats.

  20. Forms of Arthritis

    MedlinePlus

    ... It typically begins during the early-adult years. Juvenile arthritisarthritis that is diagnosed before age 16. The most common form of juvenile arthritis, juvenile rheumatoid arthritis, affects between 30,000 and ...

  1. Calcium pyrophosphate arthritis

    MedlinePlus

    ... disease that can cause attacks of arthritis. Like gout, crystals form in the joints. But in this ... CPPD arthritis can be confused with: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis Exams and Tests Most arthritic ...

  2. 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.

  3. 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. PMID:25620693

  4. Gonococcal arthritis

    MedlinePlus

    ... people who have gonorrhea caused by the bacteria Neisseria gonorrhoeae . Gonococcal arthritis affects women more often than ... Saunders; 2013:chap 109. Marrazzo JM, Apicella MA. Neisseria gonorrhoeae (gonnorrhea). In: Bennett JE, Dolin R, Blaser ...

  5. High-Methionine Diet Attenuates Severity of Arthritis and Modulates IGF-I Related Gene Expressions in an Adjuvant Arthritis Rats Model

    PubMed Central

    2016-01-01

    Rheumatoid arthritis, a synthesized form of adjuvant arthritis exhibited throughout many animal species, inhibits liver function and circulation of IGF-I and contributes to the degradation of skeletal muscle mass. One of the primary goals of the present study is determining whether a high-Methionine (high-Met) diet is capable of reducing the adverse effects of arthritis, namely, loss of body mass. Following adjuvant injection, forty arthritic rats were randomly assigned to either a control group with a basal diet or a high-Met group with the same basal diet + 0.5% Methionine. After 14 days all rats were terminated. The high-Met group exhibited an increase in body weight and food intake in comparison with the control group (P < 0.05). High-Met diet debilitated arthritis-induced surges in the gastrocnemius in both atrogin-1 and the MuRF1 expressions; however, it was observed to have little to no effect on atrogin-1 and MuRF1 gene expression in soleus. At the same time, high-Met diet rats experienced a rise in IGF-I, with lowering of IGFBP-3 gene expression in the gastrocnemius and the soleus. These data suggest that arthritis severity can be partly attenuated by high-Met diet. PMID:27738392

  6. CZ415, a Highly Selective mTOR Inhibitor Showing in Vivo Efficacy in a Collagen Induced Arthritis Model.

    PubMed

    Cansfield, Andrew D; Ladduwahetty, Tammy; Sunose, Mihiro; Ellard, Katie; Lynch, Rosemary; Newton, Anthea L; Lewis, Ann; Bennett, Gavin; Zinn, Nico; Thomson, Douglas W; Rüger, Anne J; Feutrill, John T; Rausch, Oliver; Watt, Alan P; Bergamini, Giovanna

    2016-08-11

    CZ415, a potent ATP-competitive mTOR inhibitor with unprecedented selectivity over any other kinase is described. In addition to a comprehensive characterization of its activities in vitro, in vitro ADME, and in vivo pharmacokinetic data are reported. The suitability of this inhibitor for studying in vivo mTOR biology is demonstrated in a mechanistic mouse model monitoring mTOR proximal downstream phosphorylation signaling. Furthermore, the compound reported here is the first ATP-competitive mTOR inhibitor described to show efficacy in a semitherapeutic collagen induced arthritis (CIA) mouse model. PMID:27563401

  7. 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

  8. Anti-inflammatory Effect of Isaria sinclairii Glycosaminoglycan in an Adjuvant-treated Arthritis Rat Model

    PubMed Central

    Jee, Sang Duck; Hwang, Jae Sam; Yun, Eun Young; Ahn, Kwang Seok; Kim, Yeong Shik

    2013-01-01

    The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund’s adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin® as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-κB activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin E2-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-α production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin® (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future. PMID:24386520

  9. Effects of Libby amphibole asbestos exposure on two rat models of rheumatoid arthritis

    EPA Science Inventory

    Epidemiological data suggests that occupational exposure to the amphibole-containing vermiculite in Libby, MT was associated with increased risk for developing autoimmune diseases and had an odds ratio of 3.23 for developing rheumatoid arthritis (RA). Our goal was to determine wh...

  10. KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates rat models of rheumatoid arthritis

    PubMed Central

    Tanner, Mark R.; Hu, Xueyou; Huq, Redwan; Tajhya, Rajeev B.; Sun, Liang; Khan, Fatima S.; Laragione, Teresina; Horrigan, Frank T.; Gulko, Pércio S.; Beeton, Christine

    2014-01-01

    Objective Fibroblast-like synoviocytes (FLS) participate in joint inflammation and damage during rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi-K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy. Methods We compared KCa1.1 expression levels in FLS from rats with the pristane-induced arthritis (PIA) model of RA and in FLS from healthy rats. We then used ex vivo functional assays combined with siRNA-induced knock-down, over-expression, and functional modulation of KCa1.1 in PIA-FLS. Finally, we determined the effectiveness of modulating KCa1.1 in two rat models of RA, moderate PIA and severe complete Freund’s adjuvant collagen-induced arthritis (CFA-CIA). Results We found that PIA-FLS express the KCa1.1 channel as their major potassium channel, as do FLS from patients with RA. In contrast, FLS from healthy rats expressed fewer of these channels. Inhibiting the function or expression of KCa1.1 ex vivo reduced the proliferation, production of proteases, and invasive properties of PIA-FLS whereas opening native KCa1.1 or over-expressing the channel enhanced the invasiveness of both PIA-FLS and FLS isolated from healthy rats. Treatment with a KCa1.1 channel blocker starting at onset of clinical signs stopped disease progression in both PIA and CFA-CIA, reduced joint and bone damage, and inhibited FLS invasiveness and proliferation. Conclusion Our results demonstrate a critical role for KCa1.1 channels in the regulation of FLS invasiveness and suggest they represent a potential therapeutic target for RA. PMID:25252152

  11. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    PubMed

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups

  12. Rheumatoid arthritis.

    PubMed

    Scott, David L; Wolfe, Frederick; Huizinga, Tom W J

    2010-09-25

    Rheumatoid arthritis is characterised by persistent synovitis, systemic inflammation, and autoantibodies (particularly to rheumatoid factor and citrullinated peptide). 50% of the risk for development of rheumatoid arthritis is attributable to genetic factors. Smoking is the main environmental risk. In industrialised countries, rheumatoid arthritis affects 0·5-1·0% of adults, with 5-50 per 100 000 new cases annually. The disorder is most typical in women and elderly people. Uncontrolled active rheumatoid arthritis causes joint damage, disability, decreased quality of life, and cardiovascular and other comorbidities. Disease-modifying antirheumatic drugs (DMARDs), the key therapeutic agents, reduce synovitis and systemic inflammation and improve function. The leading DMARD is methotrexate, which can be combined with other drugs of this type. Biological agents are used when arthritis is uncontrolled or toxic effects arise with DMARDs. Tumour necrosis factor inhibitors were the first biological agents, followed by abatacept, rituximab, and tocilizumab. Infections and high costs restrict prescription of biological agents. Long-term remission induced by intensive, short-term treatment selected by biomarker profiles is the ultimate goal.

  13. [Mechanisms involved in the regulation of immune response in animal model of rheumatoid arthritis in mice (CIA)].

    PubMed

    Marcińska, Katarzyna; Szczepanik, Marian

    2010-08-04

    Rheumatoid arthritis (RA) represents an example of the autoimmune disease. With a prevalence of 1% worldwide, the pathogenesis of RA is not clear yet. At present it is thought that the pathogenesis of RA results from an inflammatory response mediated by CD4+ Th1 cells that recognize unidentified antigens present in bone joints. Recently, there is a growing evidence for a role for Th17 lymphocytes in autoimmunity, including RA, suggesting that this population of helper cells may be more important in the pathogenesis of RA than Th1 cells. Thus far, treatment modalities for RA are limited, with the prevailing one acting nonspecifically on the immune system. However, such an approach results in a general immunosuppression and is accompanied by severe side-effects. There is a large demand for developing RA therapy that particularly targets pathogenic antigen-specific T cells. Research on pathogenesis of the autoimmune diseases, and development of new drugs is now possible thanks to experimental animal models that mimic human diseases. Collagen-induced arthritis (CIA) in genetically susceptible strains of mice, rats, rabbits or rhesus monkeys has been used as an experimental model of RA, as it shares many histological and immunological features. The knowledge gained using this model allows to better understand the pathogenesis of RA and, consequently, to manipulate particular components of the immune system to develop efficient therapies.

  14. 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.

  15. Haemophilic arthritis.

    PubMed

    Steven, M M; Yogarajah, S; Madhok, R; Forbes, C D; Sturrock, R D

    1986-02-01

    A detailed clinical and radiological examination of the joints and laboratory studies were carried out on 139 haemophiliacs attending a single centre. The group included more patients with mild and moderate haemophilia (factor levels 6 to 60 per cent) than in previous studies. Haemarthrosis, the most common bleeding manifestation, had affected more than two-thirds of patients including many with mild or moderate disease. Restriction and contracture of the knees and elbows were the most common clinical features and, with the ankles, these joints were most frequently affected both clinically and radiologically. Using a combination of clinical and radiological features, 42 per cent of the patients could be classed as having 'definite' and a further 14 per cent 'possible' haemophilic arthritis. Although haemarthroses were equally prevalent in patients with classical haemophilia and Christmas disease, arthritis was more frequently present in the former. Haemarthrosis and joint disease were exceptional in von Willebrand's disease. The prevalence of arthritis generally related to disease severity as measured by factor level but, in contrast to earlier studies, definite arthritis was seen in some patients with factor levels up to 20 per cent of normal although the number of affected joints was less in these patients with milder disease. Laboratory test abnormalities including circulating immune complexes and hypocomplementaemia were noted in some patients but the abnormalities correlated poorly with clinical features. The present results suggest a recent slight reduction in the prevalence or severity of haemophilic arthritis, possibly attributable to recent improvements in factor replacement treatment. Longer-term studies are required to show whether arthritis is indeed lessening or whether the onset is merely being delayed.

  16. Effect of green tea extract and vitamin C on oxidant or antioxidant status of rheumatoid arthritis rat model.

    PubMed

    Meki, Abdel-Raheim M A; Hamed, Enas Ahmed; Ezam, Khaled A

    2009-07-01

    Elevated free radical generation in inflamed joints and impaired antioxidant system has been implicated in rheumatoid arthritis (RA). Green tea extracts (GTE) have been shown to reduce inflammation in inflammatory arthritis murine model. This study investigates possible mechanisms by which vitamin C and GTE protect joints in RA rat model. This study included forty adult male rats that were divided into four groups (10 rats each); control group, collagen II induced RA group (CII), CII treated with vitamin C (CII + Vit C) and CII treated with GTE (CII + GTE) in physiology laboratory, Assiut University, Egypt. After 45 days of treatment, plasma levels of lipid peroxides (LPO), nitric oxide (NO), ceruloplasmin (CP), superoxide dismutase (SOD), uric acid (UA) and glutathione (GSH) were detected using colorimetric methods, PGE(2) using ELISA and copper (Cu) and zinc (Zn) using spectrometer. In CII group, levels of LPO, NO, PGE(2), UA, CP, Cu were higher while SOD, GSH, Zn were lower than controls. In groups treated with vitamin C and GTE, levels of SOD, GSH were increased while levels of LPO, NO, PGE(2), Cu, CP were decreased compared with CII group. Levels of UA were decreased and Zn increased in GTE treated group compared with CII group. GTE treated group showed higher Zn and low Cu levels compared with vitamin C treated group. This study suggests proper GTE and vitamin C intake may effectively normalize the impaired oxidant/antioxidant system and delaying complication of RA.

  17. Enhanced excitability and suppression of A-type K+ currents in joint sensory neurons in a murine model of antigen-induced arthritis

    PubMed Central

    Qu, Lintao; Caterina, Michael J.

    2016-01-01

    Pain is a dominant symptom of rheumatoid arthritis (RA) and its adequate treatment represents a major unmet need. However, the cellular mechanisms that drive arthritis pain are largely unexplored. Here, we examined the changes in the activity of joint sensory neurons and the associated ionic mechanisms using an animal model of antigen-induced arthritis (AIA). Methylated-bovine serum albumin (mBSA), but not vehicle challenge, in the ankle of previously immunized mice produced time-dependent symptoms of arthritis, including joint inflammation, primary mechanical hyperalgesia in the ipsilateral ankle, and secondary mechanical and heat hyperalgesia in the ipsilateral hindpaw. In vivo electrophysiological recordings revealed that Dil-labeled joint sensory neurons in AIA mice exhibited a greater incidence of spontaneous activity, mechanically evoked after-discharges, and/or increased responses to mechanical stimulation of their receptive fields, compared to control animals. Whole-cell recordings in vitro showed that AIA enhanced the excitability of joint sensory neurons. These signs of neuronal hyperexcitability were associated with a significant reduction in the density of A-type K+ currents. Thus, our data suggest that neuronal hyperexcitability, brought about in part by reduced A-type K+ currents, may contribute to pain-related behaviors that accompany antigen-induced arthritis and/or other antigen-mediated diseases. PMID:27363579

  18. Grammatical Arthritis.

    ERIC Educational Resources Information Center

    Bush, Don

    1994-01-01

    Discusses grammatical arthritis (an internal buildup of rules that hinders writing flexibility); four new "rules" (concerning "data is,""none are,""hopefully," and the restrictive "which"); attitudes toward English grammar; how to be a helpful editor; and where to learn about grammar. (SR)

  19. Raman spectroscopy detects deterioration in biomechanical properties of bone in a glucocorticoid-treated mouse model of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Maher, Jason R.; Takahata, Masahiko; Awad, Hani A.; Berger, Andrew J.

    2011-08-01

    Although glucocorticoids are frequently prescribed for the symptomatic management of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid exposure is the leading cause of physician-induced osteoporosis and leaves patients at a high risk of fracture. To study the biochemical effects of glucocorticoid exposure and how they might affect biomechanical properties of the bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and placebo-treated wild-type mice and a transgenic mouse model of rheumatoid arthritis. Statistically significant spectral differences were observed due to both treatment regimen and mouse genotype. These differences are attributed to changes in the overall bone mineral composition, as well as the degree of phosphate mineralization in tibial cortical bone. In addition, partial least squares regression was used to generate a Raman-based prediction of each tibia's biomechanical strength as quantified by a torsion test. The Raman-based predictions were as accurate as those produced by microcomputed tomography derived parameters, and more accurate than the clinically-used parameter of bone mineral density. These results suggest that Raman spectroscopy could be a valuable tool for monitoring bone biochemistry in studies of bone diseases such as osteoporosis, including tests of drugs being developed to combat these diseases.

  20. Preventing and curing citrulline-induced autoimmune arthritis in a humanized mouse model using a Th2-polarizing iNKT cell agonist.

    PubMed

    Walker, Kyle M; Rytelewski, Mateusz; Mazzuca, Delfina M; Meilleur, Shannon A; Mannik, Lisa A; Yue, David; Brintnell, William C; Welch, Ian; Cairns, Ewa; Haeryfar, S M Mansour

    2012-07-01

    Invariant natural killer T (iNKT) cells are innate lymphocytes with unique reactivity to glycolipid antigens bound to non-polymorphic CD1d molecules. They are capable of rapidly releasing pro- and/or anti-inflammatory cytokines and constitute attractive targets for immunotherapy of a wide range of diseases including autoimmune disorders. In this study, we have explored the beneficial effects of OCH, a Th2-polarizing glycolipid agonist of iNKT cells, in a humanized mouse model of rheumatoid arthritis (RA) in which citrullinated human proteins are targeted by autoaggressive immune responses in mice expressing an RA susceptibility human leukocyte antigen (HLA) DR4 molecule. We found for the first time that treatment with OCH both prevents and cures citrulline-induced autoimmune arthritis as evidenced by resolved ankle swelling and reversed histopathological changes associated with arthritis. Also importantly, OCH treatment blocked the arthritogenic capacity of citrullinated antigen-experienced splenocytes without compromising their global responsiveness or altering the proportion of splenic naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells. Interestingly, administering the Th1-promoting iNKT cell glycolipid ligand α-C-galactosylceramide into HLA-DR4 transgenic mice increased the incidence of arthritis in these animals and exacerbated their clinical symptoms, strongly suggesting a role for Th1 responses in the pathogenesis of citrulline-induced arthritis. Therefore, our findings indicate a role for Th1-mediated immunopathology in citrulline-induced arthritis and provide the first evidence that iNKT cell manipulation by Th2-skewing glycolipids may be of therapeutic value in this clinically relevant model, a finding that is potentially translatable to human RA. PMID:21912419

  1. Arthritis of the Wrist

    MedlinePlus

    ... is caused by just two types: osteoarthritis and rheumatoid arthritis. Osteoarthritis Osteoarthritis (OA) is a progressive condition that ... other, it results in pain, stiffness, and weakness. Rheumatoid Arthritis Rheumatoid arthritis (RA) is a chronic disease that ...

  2. What Is Rheumatoid Arthritis?

    MedlinePlus

    ... Information Arthritis Find a Clinical Trial Journal Articles Rheumatoid Arthritis PDF Version Size: 57 KB Audio Version Time: ... Size: 9.7 MB November 2014 What Is Rheumatoid Arthritis? Fast Facts: An Easy-to-Read Series of ...

  3. Arthritis and Rheumatic Diseases

    MedlinePlus

    ... Bursitis and Tendinitis, Q&A Fibromyalgia, Q&A Gout, Q&A Juvenile Arthritis, Q&A Childhood Arthritis ( ... Many people also experience fatigue and sleep disturbances. Gout. A type of arthritis resulting from deposits of ...

  4. Improvement in latent variable indirect response joint modeling of a continuous and a categorical clinical endpoint in rheumatoid arthritis.

    PubMed

    Hu, Chuanpu; Zhou, Honghui

    2016-02-01

    Improving the quality of exposure-response modeling is important in clinical drug development. The general joint modeling of multiple endpoints is made possible in part by recent progress on the latent variable indirect response (IDR) modeling for ordered categorical endpoints. This manuscript aims to investigate, when modeling a continuous and a categorical clinical endpoint, the level of improvement achievable by joint modeling in the latent variable IDR modeling framework through the sharing of model parameters for the individual endpoints, guided by the appropriate representation of drug and placebo mechanism. This was illustrated with data from two phase III clinical trials of intravenously administered mAb X for the treatment of rheumatoid arthritis, with the 28-joint disease activity score (DAS28) and 20, 50, and 70% improvement in the American College of Rheumatology (ACR20, ACR50, and ACR70) disease severity criteria were used as efficacy endpoints. The joint modeling framework led to a parsimonious final model with reasonable performance, evaluated by visual predictive check. The results showed that, compared with the more common approach of separately modeling the endpoints, it is possible for the joint model to be more parsimonious and yet better describe the individual endpoints. In particular, the joint model may better describe one endpoint through subject-specific random effects that would not have been estimable from data of this endpoint alone.

  5. The Effect of Treatment with Resiniferatoxin and Capsaicin on Dynamic Weight Bearing Measures and Evoked Pain Responses in a Chronic Inflammatory Arthritis Murine Model

    PubMed Central

    Bert, Joseph; Mahowald, Maren L.; Frizelle, Sandra; Dorman, Christopher W.; Funkenbusch, Sonia C.; Krug, Hollis E.

    2016-01-01

    Objective Capsaicin (CAP) and Resiniferatoxin (RTX) are vanilloid receptor agonists that can normalize Evoked Pain Scores (EPS) and Automated Dynamic Weight Bearing (ADWB) measures in murine acute inflammatory arthritis when given by intra-articular (IA) injection. To determine whether these vanilloid receptor agonists have benefit in Complete Freund’s Adjuvant (CFA) induced chronic inflammatory arthritis pain, we measured changes in ADWB and EPS in arthritic mice with and without treatment with IA CAP and RTX. Methods and materials Chronic inflammatory arthritis was produced by IA injection of 30 µl of Complete Freund’s Adjuvant (CFA) into the left knee of C57BL6 male mice 3 weeks prior to pain behavior testing. Mice were injected with either low or high dose IA RTX (10µl of 0.001 or 0.003%), or IA CAP (10 µL of 0.01%) 7 days prior to pain behavior testing. Results Chronic Inflammatory arthritis pain produced increased EPS and reduced ADWB measures for weight bearing in the affected limb of arthritic mice compared to naïve mice. ADWB measurements for time in CFA when compared with Naive were not significantly different, but suggested off-loading the arthritic limb to the normal limb. Treatment with IA CAP or RTX 7 days prior to pain behavior testing produced significant improvement in EPS but no improvement in ADWB measures. Neither IA CAP nor IA RTX had any impact on EPS or ADWB measurements in non-arthritic mice when given 7 days prior to pain behavioral testing. Conclusion Using ADWB and EPS, we quantified pain in a murine chronic inflammatory arthritis model. IA CFA caused a significant increase in EPS and decreased ADWB measures in the affected limb. Treatment with IA RTX and CAP produced significant improvement in EPS in mice with mono-articular inflammatory arthritis. IA vanilloid treatment produced no improvement in ADWB measurements for weight and for time.

  6. Efficacy of Mitochondrial Antioxidant Plastoquinonyl-decyl-triphenylphosphonium Bromide (SkQ1) in the Rat Model of Autoimmune Arthritis

    PubMed Central

    Andreev-Andrievskiy, Alexander A.; Kolosova, Nataliya G.; Stefanova, Natalia A.; Lovat, Maxim V.; Egorov, Maxim V.; Manskikh, Vasily N.; Zinovkin, Roman A.; Galkin, Ivan I.; Prikhodko, Anastasia S.; Skulachev, Maxim V.; Lukashev, Alexander N.

    2016-01-01

    Rheumatoid arthritis is one of the most common autoimmune diseases. Many antioxidants have been tested in arthritis, but their efficacy was, at best, marginal. In this study, a novel mitochondria-targeted antioxidant, plastoquinonyl-decyl-triphenylphosphonium bromide (SkQ1), was tested in vivo to prevent and cure experimental autoimmune arthritis. In conventional Wistar rats, SkQ1 completely prevented the development of clinical signs of arthritis if administered with food before induction. Further, SkQ1 significantly reduced the fraction of animals that developed clinical signs of arthritis and severity of pathological lesions if administration began immediately after induction of arthritis or at the onset of first symptoms (day 14 after induction). In specific pathogen-free Wistar rats, SkQ1 administered via gavage after induction of arthritis did not reduce the fraction of animals with arthritis but decreased the severity of lesions upon pathology examination in a dose-dependent manner. Efficacious doses of SkQ1 were in the range of 0.25–1.25 nmol/kg/day (0.13–0.7 μg/kg/day), which is much lower than doses commonly used for conventional antioxidants. SkQ1 promoted apoptosis of neutrophils in vitro, which may be one of the mechanisms underlying its pharmacological activity. Considering its low toxicity and the wide therapeutic window, SkQ1 may be a valuable additional therapy for rheumatoid arthritis. PMID:27293517

  7. Icariin Prevents Cartilage and Bone Degradation in Experimental Models of Arthritis

    PubMed Central

    Chao Wei, Chen; Qi Ping, Dai; Tian You, Fan; Yong Qiang, Chen; Tao, Che

    2016-01-01

    Background. Icariin (ICA) is an active compound extracted from Epimedium brevicornum Maxim. Previous reports have shown that icariin has a clinically significant therapeutic effect on rheumatoid arthritis. However, little is known about the mechanism by which icariin inhibits cartilage and bone degradation. Methods. New Zealand rabbits were immunized with antigen-induced arthritis (AIA) and treated with icariin. Joint tissues from rabbits were studied by histological analysis, transmission electron microscopy (TEM), and micro-CT. The expression levels of receptor activator of nuclear factor-B ligand (RANKL) and osteoprotegerin (OPG) in joint tissues were determined using immunohistochemistry and real-time PCR analysis. Results. Histological analysis and TEM sections of cartilage in the ICA treated group showed a low level of chondrocyte destruction. Micro-CT analysis showed that the bone mineral density value and bone structural level in ICA treated rabbits were significantly higher compared with those in the AIA group. Immunohistochemistry and real-time PCR analysis showed that icariin treatment reduced RANKL expression and enhanced OPG expression levels, as compared to the AIA group. Conclusion. These data indicate that ICA suppresses articular bone loss and prevents joint destruction. This study also determined that ICA regulated articular bone loss in part by regulating RANKL and OPG expression. PMID:27199510

  8. Conditional pharmacology/toxicology V: ambivalent effects of thiocyanate upon the development and the inhibition of experimental arthritis in rats by aurothiomalate (Myocrysin®) and metallic silver.

    PubMed

    Whitehouse, Michael; Butters, Desley; Vernon-Roberts, Barrie

    2013-08-01

    This article discusses the bizarre and contrary effects of thiocyanate, the major detoxication product of hydrogen cyanide inhaled from tobacco smoke or liberated from cyanogenic foods, e.g. cassava. Thiocyanate both (1) promotes inflammatory disease in rats and (2) facilitates the anti-inflammatory action of historic metal therapies based on gold (Au) or silver (Ag) in three models of chronic polyarthritis in rats. Low doses of nanoparticulate metallic silver (NMS) preparations, i.e. zerovalent silver (Ag°) administered orally, suppressed the mycobacterial ('adjuvant')-induced arthritis (MIA) in rats. Similar doses of cationic silver, Ag(I), administered orally as silver oxide or soluble silver salts were inactive. By contrast, NMS only inhibited the development of the collagen-induced arthritis (CIA) and pristane-induced arthritis (PIA) in rats when thiocyanate was also co-administered in drinking water. These (a) arthritis-selective and (b) thiocyanate-inducible effects of Ag° were also observed in some previous, and now extended, studies with the classic anti-arthritic drug, sodium aurothiomalate (ATM, Myocrisin(®)) and its silver analogue (STM), administered subcutaneously to rats developing the same three forms of polyarthritis. In the absence of either Ag° or ATM, thiocyanate considerably increased the severity of the MIA, CIA and PIA, i.e. acting as a pro-pathogen. Hitherto, thiocyanate was considered relatively harmless. This may not be true in rats/people with immuno-inflammatory stress and concomitant leukocyte activation. Collectively, these findings show how the drug action of a xenobiotic might be determined by the nature (and severity) of the experimental inflammation, as an example of conditional pharmacology. They also suggest that an incipient toxicity, even of normobiotics such as thiocyanate, might likewise be modulated beneficially by well-chosen xenobiotics (drugs, nutritional supplements, etc.), i.e. conditional toxicology (Powanda 1995

  9. Nociceptive sensitivity and opioid antinociception and antihyperalgesia in Freund's adjuvant-induced arthritic male and female rats.

    PubMed

    Cook, Charles D; Nickerson, Michael D

    2005-04-01

    The present study was designed to examine sex differences in complete Freund's adjuvant (CFA)-induced mechanical hyperalgesia and sex differences in opioid antinociception and anti-hyperalgesia. Female rats developed inflammation and hyperalgesia faster and exhibited greater peak hyperalgesia than male rats. In arthritic (CFA-treated) rats, lower thresholds were observed during estrus and proestrus, and in nonarthritic (vehicle-treated) rats, lower thresholds were observed during proestrus. Morphine and oxycodone were more potent in male than female arthritic rats, and butorphanol was more potent and effective in male than female arthritic rats. The potency of morphine was increased in arthritic rats, although to a greater magnitude in males. The potency of oxycodone was increased in male but not female arthritic rats. The potency of butorphanol was increased in arthritic male rats and the maximal antinociceptive effect of butorphanol was increased in arthritic female rats, but it did not result in greater than 20% antinociception. Morphine, oxycodone, and butorphanol all produced antihyperalgesic effects (returning thresholds of arthritic rats to the thresholds of nonarthritic rats) with greater potency in males than females. The peripherally acting opioid agonist loperamide produced intermediate levels of antinociception in male and female arthritic rats and no antinociception in nonarthritic rats. Loperamide was more potent in male than female arthritic rats at producing antihyperalgesia. These data demonstrate sex differences in arthritis-induced hyperalgesia and responsiveness to opioid analgesics. In arthritic rats, the antinociceptive effects of opioid agonists are most probably mediated by both central and peripheral opioid receptors, whereas their antihyperalgesic effects are mediated primarily by actions at peripheral opioid receptors. PMID:15608071

  10. A threshold hazard model for estimating serious infection risk following anti-tumor necrosis factor therapy in rheumatoid arthritis patients.

    PubMed

    Fu, Bo; Lunt, Mark; Galloway, James; Dixon, Will; Hyrich, Kimme; Symmons, Deborah

    2013-03-11

    Over recent years novel biologic agents have been developed for the treatment of rheumatoid arthritis. The most common type of biologic agent in use in the United Kingdom is the anti-tumor necrosis factor inhibitor class. To fully appreciate the potential risks of anti-tumor necrosis factor therapy in patients, knowledge about the baseline hazard (risk pattern) and the characteristics of patients associated with serious infection is important. We propose a nonproportional hazard model for estimating the infection risk, by including the drug exposure history information into the baseline hazard. We found that the infection risk reaches a peak within 1 month after drug exposure starts and then declines steadily for nearly 2 years before stabilizing out.

  11. Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment.

    PubMed

    Rioja, I; Bush, K A; Buckton, J B; Dickson, M C; Life, P F

    2004-07-01

    Biomarker quantification in disease tissues from animal models of rheumatoid arthritis (RA) can help to provide insights into the mechanisms of action of novel therapeutic agents. In this study we validated the kinetics of IL-1beta, TNF-alpha and IL-6 mRNA and protein expression levels in joints from DBA/1OlaHsd murine collagen-induced arthritis (CIA) and Lewis rat Streptococcal cell wall (SCW)-induced arthritis by real-time polymerase chain reaction (PCR) TaqMan and Enzyme-linked immunosorbent assay (ELISA). Prednisolone was used as a reference to investigate any correlation between clinical response and cytokine levels at selected time-points. To our knowledge this is the first report showing a close pattern of expression between mRNA and protein for IL-1beta and IL-6, but not for TNF-alpha, in these two models of RA. The kinetics of expression for these biomarkers suggested that the optimal sampling time-points to study the effect of compounds on both inflammation and cytokine levels were day 4 postonset in CIA and day 3 after i.v challenge in SCW-induced arthritis. Prednisolone reduced joint swelling through a mechanism associated with a reduction in IL-1beta and IL-6 protein and mRNA expression levels. At the investigated time points, protein levels for TNF-alpha in arthritic joints were lower than the lower limit of detection of the ELISA, whereas mRNA levels for this cytokine were reliably detected. These observations suggest that RT-PCR TaqMan is a sensitive technique that can be successfully applied to the quantification of mRNA levels in rodent joints from experimental arthritis models providing insights into mechanisms of action of novel anti-inflammatory drugs.

  12. Establishing serological classification tree model in rheumatoid arthritis using combination of MALDI-TOF-MS and magnetic beads.

    PubMed

    Yan, Zhang; Chaojun, Hu; Chuiwen, Deng; Xiaomei, Leng; Xin, Zhang; Yongzhe, Li; Fengchun, Zhang

    2015-02-01

    To establish a serological classification tree model for rheumatoid arthritis (RA), protein/peptide profiles of serum were detected by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF-MS) combined with weak cationic exchange (WCX) from Cohort 1, including 65 patients with RA and 41 healthy controls (HC). The samples were randomly divided into a training set and a test set. Twenty-four differentially expressed peaks (P < 0.05) were identified in the training set and 4 of them, namely m/z 3,939, 5,906, 8,146, and 8,569 were chosen to set up our model. This model exhibited a sensitivity of 100.0% and a specificity of 96.0% for differentiating RA patients from HC. The test set reproduced these high levels of sensitivity and specificity, which were 100.0 and 81.2%, respectively. Cohort 2, which include 228 RA patients, was used to further verify the classification efficiency of this model. It came out that 97.4% of them were classified as RA by this model. In conclusion, MALDI-TOF-MS combined with WCX magnetic beads was a powerful method for constructing a classification tree model for RA, and the model we established was useful in recognizing RA.

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

    PubMed

    Matsuo, Yusuke; Mizoguchi, Fumitaka; Saito, Tetsuya; Kawahata, Kimito; Ueha, Satoshi; Matsushima, Kouji; Inagaki, Yutaka; Miyasaka, Nobuyuki; Kohsaka, Hitoshi

    2016-02-12

    Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA. PMID:26806309

  14. 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

  15. Challenges faced in Latin America for the implementation of an ideal health-care model for rheumatoid arthritis patients: are we ready?

    PubMed

    Rodríguez Jaillier, Juan Carlos; Posada Arango, Ana María; Martínez Pérez, David Antonio

    2015-03-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory, progressive disease characterized by inflammation of the synovial tissue. It results in the severe functional deterioration of the joints involved and the incapacity to work. Our main aim is to determine the characteristics of the current health-care models used in treating rheumatoid arthritis patients in Latin America. We want to analyze the details, using them as the foundation to create an ideal health-care model that is focused on the patient. We have revised documents, including guides to clinical practice, monitoring models and health-care models according to the current policies and resources available in various Latin American countries. Based on this information, the qualities and deficiencies of the current models will be analyzed, in order to use this as a basis on which to construct a proposed health-care model that covers the specific needs of rheumatoid arthritis patients, considering the resources of each population. Despite the collapse seen in many health systems throughout history, we can learn from them and should develop a new model starting from the path pursued, capitalizing on our experiences, teachings, and errors committed. However, in most cases, the obstacles to the success of the systems do not lie in the fundamental structure or the "spirit of the legislator" but rather in the day-to-day development within the community and the special interest of each agent in a system. PMID:26255188

  16. Challenges faced in Latin America for the implementation of an ideal health-care model for rheumatoid arthritis patients: are we ready?

    PubMed

    Rodríguez Jaillier, Juan Carlos; Posada Arango, Ana María; Martínez Pérez, David Antonio

    2015-03-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory, progressive disease characterized by inflammation of the synovial tissue. It results in the severe functional deterioration of the joints involved and the incapacity to work. Our main aim is to determine the characteristics of the current health-care models used in treating rheumatoid arthritis patients in Latin America. We want to analyze the details, using them as the foundation to create an ideal health-care model that is focused on the patient. We have revised documents, including guides to clinical practice, monitoring models and health-care models according to the current policies and resources available in various Latin American countries. Based on this information, the qualities and deficiencies of the current models will be analyzed, in order to use this as a basis on which to construct a proposed health-care model that covers the specific needs of rheumatoid arthritis patients, considering the resources of each population. Despite the collapse seen in many health systems throughout history, we can learn from them and should develop a new model starting from the path pursued, capitalizing on our experiences, teachings, and errors committed. However, in most cases, the obstacles to the success of the systems do not lie in the fundamental structure or the "spirit of the legislator" but rather in the day-to-day development within the community and the special interest of each agent in a system.

  17. A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

    PubMed

    Prinold, Joe A I; Mazzà, Claudia; Di Marco, Roberto; Hannah, Iain; Malattia, Clara; Magni-Manzoni, Silvia; Petrarca, Maurizio; Ronchetti, Anna B; Tanturri de Horatio, Laura; van Dijkhuizen, E H Pieter; Wesarg, Stefan; Viceconti, Marco

    2016-01-01

    Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important.

  18. A Patient-Specific Foot Model for the Estimate of Ankle Joint Forces in Patients with Juvenile Idiopathic Arthritis.

    PubMed

    Prinold, Joe A I; Mazzà, Claudia; Di Marco, Roberto; Hannah, Iain; Malattia, Clara; Magni-Manzoni, Silvia; Petrarca, Maurizio; Ronchetti, Anna B; Tanturri de Horatio, Laura; van Dijkhuizen, E H Pieter; Wesarg, Stefan; Viceconti, Marco

    2016-01-01

    Juvenile idiopathic arthritis (JIA) is the leading cause of childhood disability from a musculoskeletal disorder. It generally affects large joints such as the knee and the ankle, often causing structural damage. Different factors contribute to the damage onset, including altered joint loading and other mechanical factors, associated with pain and inflammation. The prediction of patients' joint loading can hence be a valuable tool in understanding the disease mechanisms involved in structural damage progression. A number of lower-limb musculoskeletal models have been proposed to analyse the hip and knee joints, but juvenile models of the foot are still lacking. This paper presents a modelling pipeline that allows the creation of juvenile patient-specific models starting from lower limb kinematics and foot and ankle MRI data. This pipeline has been applied to data from three children with JIA and the importance of patient-specific parameters and modelling assumptions has been tested in a sensitivity analysis focused on the variation of the joint reaction forces. This analysis highlighted the criticality of patient-specific definition of the ankle joint axes and location of the Achilles tendon insertions. Patient-specific detection of the Tibialis Anterior, Tibialis Posterior, and Peroneus Longus origins and insertions were also shown to be important. PMID:26374518

  19. Protective effects of isolated polyphenolic and alkaloid fractions of Ruta graveolens L. on acute and chronic models of inflammation.

    PubMed

    Ratheesh, M; Shyni, G L; Sindhu, G; Helen, A

    2010-02-01

    Ruta graveolens L. (Rutaceae) are traditionally used for the treatment of rheumatism, arthritis and other inflammatory conditions in the traditional medicine of India, were evaluated for their protective effect in acute and chronic models of inflammation. Carrageenan induced rat paw edema and adjuvant induced arthritis were employed as the experimental models of acute and chronic inflammation respectively. Isolated polyphenolic and alkaloid fraction (AFR) from Ruta graveolens and evaluated its anti inflammatory activity in carrageenan induced acute model. AFR with a dose 10 mg/kg showed higher anti inflammatory effect than polyphenols and standard drug diclofenec. AFR significantly decreased the paw edema in arthritic rats. TBARS, COX-2, 5-LOX and MPO level were decreased and the levels of antioxidant enzymes and GSH level were increased on treatment with AFR. The increment in CRP level and ceruloplasmin level observed in arthritic animals were also found to be significantly restored in AFR treated rats. The results demonstrated the potential beneficiary effect of isolated polyphenolic and alkaloid fraction of Ruta graveolens L. on acute and chronic models of inflammation in rats.

  20. A semi-mechanistic model of CP-690,550-induced reduction in neutrophil counts in patients with rheumatoid arthritis.

    PubMed

    Gupta, Pankaj; Friberg, Lena E; Karlsson, Mats O; Krishnaswami, Sriram; French, Jonathan

    2010-06-01

    CP-690,550, a selective inhibitor of the Janus kinase family, is being developed as an oral disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). A semi-mechanistic model was developed to characterize the time course of drug-induced absolute neutrophil count (ANC) reduction in a phase 2a study. Data from 264 RA patients receiving 6-week treatment (placebo, 5, 15, 30 mg bid) followed by a 6-week off-treatment period were analyzed. The model included a progenitor cell pool, a maturation chain comprising transit compartments, a circulation pool, and a feedback mechanism. The model was adequately described by system parameters (BASE(h), ktr(h), gamma, and k(circ)), disease effect parameters (DIS), and drug effect parameters (k(off) and k(D)). The disease manifested as an increase in baseline ANC and reduced maturation time due to increased demand from the inflammation site. The drug restored the perturbed system parameters to their normal values via an indirect mechanism. ANC reduction due to a direct myelosuppressive drug effect was not supported. The final model successfully described the dose- and time-dependent changes in ANC and predicted the incidence of neutropenia at different doses reasonably well.

  1. [Rheumatoid arthritis].

    PubMed

    Strunk, J; Lange, U; Müller-Ladner, U

    2005-07-29

    The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.

  2. Rheumatoid Arthritis Educational Video Series

    MedlinePlus

    ... Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed to help you ... Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic Arthritis 101 2010 E.S.C.A.P. ...

  3. From the model of integral attention to the creation of centers of excellence in rheumatoid arthritis.

    PubMed

    Santos-Moreno, Pedro; Castañeda, Oswaldo; Garro, Boris; Flores, Dennis; Sánchez, Guillermo; Castro, Carlos

    2015-03-01

    For the Pan American Health Organization (PAHO), the care of patients with chronic diseases currently experiences fragmentation in attention, generating poor performance of health services. Thus, comprehensive health care strategies arise to mitigate these problems; one of them are Centers of Excellence (CoEs), which aim to obtain high quality results in health from the adequate and minimum use of resources. The objective of this study was to describe the history and current context of the CoE in comprehensive care in patients with rheumatoid arthritis (RA). A systematic search of the literature terms (MeSH) was performed. The bases used were PubMed, Ebsco Host, Lilacs, Science Direct, Ovid, and Google (gray literature). The source of the information was evaluated to determine its quality. International standards focus the CoEs starting from comprehensive management of patients with RA and patient volume, continuous improvement, and quality of health care, constituting an interdisciplinary team. The REAL-PANLAR group suggested that the inclusion of the strategy "Treat to Target", and patient education improves patient conditions and understanding of the disease. RA is a prevalent and costly disease. The creation of comprehensive care centers of the CoE type is an initiative that improves the prognosis of RA. This document aims to encourage rheumatologists and scientific societies to structure CoE in an interdisciplinary endeavor.

  4. Clinical and histopathological evaluation of MDP/collagen induced arthritis rat model (MCIA) after treatment with Urtica dioica, plantago major and Hypericum perforatum L herbal mixture.

    PubMed

    Khalifeh, Mohammad S; Hananeh, Wael; Al-Rukibat, Raida; Okour, Omar; Boumezrag, Assia

    2008-04-01

    This study was done to assess the effects of Urtica dioica, Plantago major and Hypericum perforatum L herbal mixture in the MCIA rat model. In addition, a new pathological and clinical arthritis lesion assessment was developed. Sprague-Dawley (SD) rats were immunized with bovine type II collagen and muramyl dipeptide (MDP). Commercial herbal extracts were administered daily to the rats after the immunization for the course of experiment (90 days). Rats were boosted with a second collagen-MDP emulsion 60 days after the first immunization. Paws were daily evaluated macroscopically for redness, swelling, distortion, or ankylosis of the joints. On the day of sacrifice, rat paws were assessed for histopathologic changes. Herbal mixture administration decreased the clinical lesion manifestation in the MCIA rat model and led to development of similar or slightly more severe histopathological lesions compared to rats that did not receive the treatment. The clinical arthritis signs appeared as early as 13 days after the first MDP/collagen injection and with peak incidence at 20 days post-immunization. Histopathologically, animals showed changes ranging from mild to very severe. Administration of the herbal mixture used in this study had a clinical therapeutic effect on the course of the clinical manifestations in the MCIA model, but the herbal treatment had no such effect on the histopathological lesion development and even led to slightly more severe lesions. Rats in the MCIA model developed prominent clinical and histopathological changes that were comparable to rheumatoid arthritis (RA) lesions in humans. PMID:18421172

  5. Clinical and histopathological evaluation of MDP/collagen induced arthritis rat model (MCIA) after treatment with Urtica dioica, plantago major and Hypericum perforatum L herbal mixture.

    PubMed

    Khalifeh, Mohammad S; Hananeh, Wael; Al-Rukibat, Raida; Okour, Omar; Boumezrag, Assia

    2008-04-01

    This study was done to assess the effects of Urtica dioica, Plantago major and Hypericum perforatum L herbal mixture in the MCIA rat model. In addition, a new pathological and clinical arthritis lesion assessment was developed. Sprague-Dawley (SD) rats were immunized with bovine type II collagen and muramyl dipeptide (MDP). Commercial herbal extracts were administered daily to the rats after the immunization for the course of experiment (90 days). Rats were boosted with a second collagen-MDP emulsion 60 days after the first immunization. Paws were daily evaluated macroscopically for redness, swelling, distortion, or ankylosis of the joints. On the day of sacrifice, rat paws were assessed for histopathologic changes. Herbal mixture administration decreased the clinical lesion manifestation in the MCIA rat model and led to development of similar or slightly more severe histopathological lesions compared to rats that did not receive the treatment. The clinical arthritis signs appeared as early as 13 days after the first MDP/collagen injection and with peak incidence at 20 days post-immunization. Histopathologically, animals showed changes ranging from mild to very severe. Administration of the herbal mixture used in this study had a clinical therapeutic effect on the course of the clinical manifestations in the MCIA model, but the herbal treatment had no such effect on the histopathological lesion development and even led to slightly more severe lesions. Rats in the MCIA model developed prominent clinical and histopathological changes that were comparable to rheumatoid arthritis (RA) lesions in humans.

  6. New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice.

    PubMed

    Kimura, I; Yoshikawa, M; Kobayashi, S; Sugihara, Y; Suzuki, M; Oominami, H; Murakami, T; Matsuda, H; Doiphode, V V

    2001-04-23

    Myrrhanol A, a new triterpene isolated from guggul (Balsamodendron or Commiphora mukul Hook.)-gum resin, displays a potent anti-inflammatory effect on exudative pouch fluid, angiogenesis, and granuloma weights in adjuvant-induced air-pouch granuloma of mice. Its effects were more marked than those of hydrocortisone and the 50% aqueous methanolic extract of the crude drug. Myrrhanol A is a plausible candidate for a potent anti-inflammatory agent. PMID:11327606

  7. Predicting the risk of rheumatoid arthritis and its age of onset through modelling genetic risk variants with smoking.

    PubMed

    Scott, Ian C; Seegobin, Seth D; Steer, Sophia; Tan, Rachael; Forabosco, Paola; Hinks, Anne; Eyre, Stephen; Morgan, Ann W; Wilson, Anthony G; Hocking, Lynne J; Wordsworth, Paul; Barton, Anne; Worthington, Jane; Cope, Andrew P; Lewis, Cathryn M

    2013-01-01

    The improved characterisation of risk factors for rheumatoid arthritis (RA) suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA). Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs) and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA)-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls); UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls). HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC) value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG). Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001); ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively. PMID:24068971

  8. Predicting the risk of rheumatoid arthritis and its age of onset through modelling genetic risk variants with smoking.

    PubMed

    Scott, Ian C; Seegobin, Seth D; Steer, Sophia; Tan, Rachael; Forabosco, Paola; Hinks, Anne; Eyre, Stephen; Morgan, Ann W; Wilson, Anthony G; Hocking, Lynne J; Wordsworth, Paul; Barton, Anne; Worthington, Jane; Cope, Andrew P; Lewis, Cathryn M

    2013-01-01

    The improved characterisation of risk factors for rheumatoid arthritis (RA) suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA). Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs) and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA)-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls); UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls). HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC) value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG). Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001); ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively.

  9. Predicting the Risk of Rheumatoid Arthritis and Its Age of Onset through Modelling Genetic Risk Variants with Smoking

    PubMed Central

    Scott, Ian C.; Seegobin, Seth D.; Steer, Sophia; Tan, Rachael; Forabosco, Paola; Hinks, Anne; Eyre, Stephen; Morgan, Ann W.; Wilson, Anthony G.; Hocking, Lynne J.; Wordsworth, Paul; Barton, Anne; Worthington, Jane; Cope, Andrew P.; Lewis, Cathryn M.

    2013-01-01

    The improved characterisation of risk factors for rheumatoid arthritis (RA) suggests they could be combined to identify individuals at increased disease risks in whom preventive strategies may be evaluated. We aimed to develop an RA prediction model capable of generating clinically relevant predictive data and to determine if it better predicted younger onset RA (YORA). Our novel modelling approach combined odds ratios for 15 four-digit/10 two-digit HLA-DRB1 alleles, 31 single nucleotide polymorphisms (SNPs) and ever-smoking status in males to determine risk using computer simulation and confidence interval based risk categorisation. Only males were evaluated in our models incorporating smoking as ever-smoking is a significant risk factor for RA in men but not women. We developed multiple models to evaluate each risk factor's impact on prediction. Each model's ability to discriminate anti-citrullinated protein antibody (ACPA)-positive RA from controls was evaluated in two cohorts: Wellcome Trust Case Control Consortium (WTCCC: 1,516 cases; 1,647 controls); UK RA Genetics Group Consortium (UKRAGG: 2,623 cases; 1,500 controls). HLA and smoking provided strongest prediction with good discrimination evidenced by an HLA-smoking model area under the curve (AUC) value of 0.813 in both WTCCC and UKRAGG. SNPs provided minimal prediction (AUC 0.660 WTCCC/0.617 UKRAGG). Whilst high individual risks were identified, with some cases having estimated lifetime risks of 86%, only a minority overall had substantially increased odds for RA. High risks from the HLA model were associated with YORA (P<0.0001); ever-smoking associated with older onset disease. This latter finding suggests smoking's impact on RA risk manifests later in life. Our modelling demonstrates that combining risk factors provides clinically informative RA prediction; additionally HLA and smoking status can be used to predict the risk of younger and older onset RA, respectively. PMID:24068971

  10. Logistic regression models for predicting physical and mental health-related quality of life in rheumatoid arthritis patients.

    PubMed

    Alishiri, Gholam Hossein; Bayat, Noushin; Fathi Ashtiani, Ali; Tavallaii, Seyed Abbas; Assari, Shervin; Moharamzad, Yashar

    2008-01-01

    The aim of this work was to develop two logistic regression models capable of predicting physical and mental health related quality of life (HRQOL) among rheumatoid arthritis (RA) patients. In this cross-sectional study which was conducted during 2006 in the outpatient rheumatology clinic of our university hospital, Short Form 36 (SF-36) was used for HRQOL measurements in 411 RA patients. A cutoff point to define poor versus good HRQOL was calculated using the first quartiles of SF-36 physical and mental component scores (33.4 and 36.8, respectively). Two distinct logistic regression models were used to derive predictive variables including demographic, clinical, and psychological factors. The sensitivity, specificity, and accuracy of each model were calculated. Poor physical HRQOL was positively associated with pain score, disease duration, monthly family income below 300 US$, comorbidity, patient global assessment of disease activity or PGA, and depression (odds ratios: 1.1; 1.004; 15.5; 1.1; 1.02; 2.08, respectively). The variables that entered into the poor mental HRQOL prediction model were monthly family income below 300 US$, comorbidity, PGA, and bodily pain (odds ratios: 6.7; 1.1; 1.01; 1.01, respectively). Optimal sensitivity and specificity were achieved at a cutoff point of 0.39 for the estimated probability of poor physical HRQOL and 0.18 for mental HRQOL. Sensitivity, specificity, and accuracy of the physical and mental models were 73.8, 87, 83.7% and 90.38, 70.36, 75.43%, respectively. The results show that the suggested models can be used to predict poor physical and mental HRQOL separately among RA patients using simple variables with acceptable accuracy. These models can be of use in the clinical decision-making of RA patients and to recognize patients with poor physical or mental HRQOL in advance, for better management.

  11. Menstrual arthritis.

    PubMed Central

    McDonagh, J E; Singh, M M; Griffiths, I D

    1993-01-01

    The menstrual cycle is characterised by variations in the absolute and relative concentrations of the hormones of the hypothalamic pituitary ovarian axis, which in turn affect cell function and cytokine and heat shock protein production. Menstruation involves the shedding of the secretory endometrium, which is part of the mucosal associated lymphoid tissue and hence is rich in immunologically competent cells such as CD8 T cells and macrophages. The case is reported here of a patient presenting with a recurrent but transient symmetrical inflammatory polyarthritis which only occurred at menstruation with no residual damage. The disease was suppressed by danazol. Endometrial degradation products are suggested as the trigger of this 'menstrual arthritis'. PMID:8427519

  12. Don’t let up: implementing and sustaining change in a new post-licensure education model for developing extended role practitioners involved in arthritis care

    PubMed Central

    Lundon, Katie; Shupak, Rachel; Canzian, Sonya; Ziesmann, Ed; Schneider, Rayfel

    2015-01-01

    Key message Across a 9-year period, the Advanced Clinician Practitioner in Arthritis Care program has achieved a set of short-term “wins” giving direction and momentum to the development of new roles for health care practitioners providing arthritis care. Implication This is a viable model for post-licensure training offered to multiple allied health professionals to support the development of competent extended role practitioners (extended scope practice). Challenges at this critical juncture include: retain focus, drive, and commitment; develop academic and financial partnerships transferring short-term success to long-term sustainability; advanced, context-driven, system-level evaluation including fiscal outcome; health care policy adaptation to new human health resource development. Supporting evidence Success includes: completed 2-year health services research evaluating 37 graduates; leadership, innovation, educational excellence, and human health resource benefit awards; influential publications/presentations addressing post-licensure education/outcome, interprofessional collaboration, and improved patient care. PMID:26347223

  13. 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.

  14. Treating Psoriatic Arthritis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  15. Classification of Psoriatic Arthritis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  16. Diagnosing Psoriatic Arthritis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  17. Rheumatoid arthritis (image)

    MedlinePlus

    Rheumatoid arthritis is an autoimmune disease in which the body's immune system attacks itself. The pattern of joints ... other joints and is worse in the morning. Rheumatoid arthritis is also a systemic disease, involving other body ...

  18. Juvenile idiopathic arthritis

    MedlinePlus

    Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ... The cause of juvenile idiopathic arthritis (JIA) is not known. It is thought to be an autoimmune illness . This means the body attacks ...

  19. 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. PMID:23895160

  20. [99mTc]diphosphonate uptake and hemodynamics in experimental arthritis: effect of naproxen in the canine carrageenan injection model.

    PubMed

    Hansen, E S; He, S Z; Søballe, K; Kjølseth, D; Henriksen, T B; Hjortdal, V E; Bünger, C

    1992-09-01

    The impact of naproxen treatment on juxta-articular hemodynamics and bone metabolism in experimental juvenile arthritis was studied in the articular carrageenan injection model. Unilateral gonarthritis was induced for 12 weeks in eight dogs receiving naproxen (dosage, 2 mg/kg) and eight controls. Regional blood flow was assessed by the microsphere method, plasma volume by the distribution space of [125I]fibrinogen, and bone metabolism by the 2-h uptake of [99mTc]diphosphonate ([99mTc]DPD). Synovial effusion was less prominent with naproxen treatment as judged by joint fluid volume and pressure. Naproxen reduced the arthritic capsular hyperemia, almost normalized a severe blood flow increase in patella and both juxta-articular epiphyses, ameliorated an expansion of plasma volume in the patella and the distal femoral epiphysis, and normalized an increased [99mTc]DPD uptake in subchondral femoral bone and the tibial cortex. Significantly increased arteriovenous shunting in the arthritic extremity was unaffected by naproxen. The study suggests that long-term cyclooxygenase inhibition offers protection against hemodynamic and metabolic changes in juxta-articular bone secondary to synovial inflammation. PMID:1500978

  1. Enzymosomes with surface-exposed superoxide dismutase: in vivo behaviour and therapeutic activity in a model of adjuvant arthritis.

    PubMed

    Gaspar, Maria Manuela; Boerman, Otto C; Laverman, Peter; Corvo, Maria Luísa; Storm, Gert; Cruz, Maria Eugénia Meirinhos

    2007-02-12

    Acylated Superoxide Dismutase (Ac-SOD) enzymosomes, liposomal enzymatic systems expressing catalytic activity in the intact form, were previously characterized. The main scope of the present work was to investigate the biological behaviour of Ac-SOD inserted in the lipid bilayer of liposomes, in comparison with SOD located in the aqueous compartment of liposomes. Two types of liposomes were used: conventional liposomes presenting an unmodified external surface and long circulating liposomes coated with poly (ethylene glycol) (PEG). Liposomal formulations of Ac-SOD and SOD were prepared and labelled with indium-111 and their in vivo fate compared. Data obtained led us to the conclusion that, for liposomes coated with PEG the in vivo fate was not influenced by the insertion of Ac-SOD in the lipid bilayers. The potential therapeutic effect of Ac-SOD enzymosomes was compared with SOD liposomes in a rat model of adjuvant arthritis. A faster anti-inflammatory effect was observed for Ac-SOD enzymosomes by monitoring the volume of the inflamed paws. The present results allowed us to conclude that Ac-SOD enzymosomes are nano-carriers combining the advantages of expressing enzymatic activity in intact form and thus being able to exert therapeutic effect even before liposomes disruption, as well as acting as a sustained release of the enzyme. PMID:17169460

  2. Evaluation of [(89)Zr]-Oxalate as a PET Tracer in Inflammation, Tumor, and Rheumatoid Arthritis Models.

    PubMed

    Park, Ji-Ae; Lee, Yong Jin; Lee, Ji Woong; Yoo, Ran Ji; Shin, Un Chol; Lee, Kyo Chul; Kim, Byung Il; Kim, Kyeong Min; Kim, Jung Young

    2016-07-01

    To obtain an additional pharmacological agent for the diagnosis of inflammation, we investigated the medical use of (89)Zr-oxalate as a positron emission tomography (PET) probe for the in vivo imaging of inflammation and compared its efficacy to that of 2-deoxy-2-[(18)F]fluoro-d-glucose ([(18)F]FDG) and sodium [(18)F]fluoride. (89)Zr-oxalate exhibited observable higher uptake in a macrophage cell line than in tumor cells. The inflammatory lesions and tumors were clearly visualized by PET imaging and autoradiography using (89)Zr-oxalate. Compared to [(18)F]FDG and sodium [(18)F]fluoride, (89)Zr-oxalate demonstrated a high selectivity index to the tumor at an early time point after injection and to inflammation at a delayed time point after injection (24 h). Through histological examination, large numbers of macrophages and neutrophils were observed in the tumor lesions with the highest (89)Zr-oxalate uptake. In a rheumatoid arthritis (RA) mouse model, (89)Zr-oxalate demonstrated a high level of accumulation in inflammatory lesions. (89)Zr-oxalate is a new strategic tool for tumor imaging and inflammatory processes. PMID:27243098

  3. Development of a high-throughput screening assay based on the 3-dimensional pannus model for rheumatoid arthritis.

    PubMed

    Ibold, Yvonne; Frauenschuh, Simone; Kaps, Christian; Sittinger, Michael; Ringe, Jochen; Goetz, Peter M

    2007-10-01

    The 3-dimensional (3-D) pannus model for rheumatoid arthritis (RA) is based on the interactive co-culture of cartilage and synovial fibroblasts (SFs). Besides the investigation of the pathogenesis of RA, it can be used to analyze the active profiles of antirheumatic pharmaceuticals and other bioactive substances under in vitro conditions. For a potential application in the industrial drug-screening process as a transitional step between 2-dimensional (2-D) cell-based assays and in vivo animal studies, the pannus model was developed into an in vitro high-throughput screening (HTS) assay. Using the CyBitrade mark-Disk workstation for parallel liquid handling, the main cell culture steps of cell seeding and cultivation were automated. Chondrocytes were isolated from articular cartilage and seeded directly into 96-well microplates in high-density pellets to ensure formation of cartilage-specific extracellular matrix (ECM). Cell seeding was performed automatically and manually to compare both processes regarding accuracy, reproducibility, consistency, and handling time. For automated cultivation of the chondrocyte pellet cultures, a sequential program was developed using the CyBio Control software to minimize shear forces and handling time. After 14 days of cultivation, the pannus model was completed by coating the cartilage pellets with a layer of human SFs. The effects due to automation in comparison to manual handling were analyzed by optical analysis of the pellets, histological and immunohistochemical staining, and real-time PCR. Automation of this in vitro model was successfully achieved and resulted in an improved quality of the generated pannus cultures by enhancing the formation of cartilage-specific ECM. In addition, automated cell seeding and media exchange increased the efficiency due to a reduction of labor intensity and handling time.

  4. Immunoliposome co-delivery of bufalin and anti-CD40 antibody adjuvant induces synergetic therapeutic efficacy against melanoma

    PubMed Central

    Li, Ying; Yuan, Jiani; Yang, Qian; Cao, Wei; Zhou, Xuanxuan; Xie, Yanhua; Tu, Honghai; Zhang, Ya; Wang, Siwang

    2014-01-01

    Liposomes constitute one of the most popular nanocarriers for improving the delivery and efficacy of agents in cancer patients. The purpose of this study was to design and evaluate immunoliposome co-delivery of bufalin and anti-CD40 to induce synergetic therapeutic efficacy while eliminating systemic side effects. Bufalin liposomes (BFL) conjugated with anti-CD40 antibody (anti-CD40-BFL) showed enhanced cytotoxicity compared with bufalin alone. In a mouse B16 melanoma model, intravenous injection of anti-CD40-BFL achieved smaller tumor volume than did treatment with BFL (average: 117 mm3 versus 270 mm3, respectively); the enhanced therapeutic efficacy through a caspase-dependent pathway induced apoptosis, which was confirmed using terminal deoxynucleotidyl transferase-mediated dUTP-Fluorescein nick end labeling and Western blot assay. Meanwhile, anti-CD40-BFL elicited unapparent body-weight changes and a significant reduction in serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ, and hepatic enzyme alanine transaminase, suggesting minimized systemic side effects. This may be attributed to the mechanism by which liposomes are retained within the tumor site for an extended period of time, which is supported by the following biodistribution and flow cytometric analyses. Taken together, the results demonstrated a highly promising strategy for liposomal vehicle transport of anti-CD40 plus bufalin that can be used to enhance antitumor effects via synergetic systemic immunity while blocking systemic toxicity. PMID:25506218

  5. TIGIT overexpression diminishes the function of CD4 T cells and ameliorates the severity of rheumatoid arthritis in mouse models.

    PubMed

    Zhao, Weigong; Dong, Yanying; Wu, Caijun; Ma, Yunfeng; Jin, Yaofeng; Ji, Yanhong

    2016-01-01

    Rheumatoid arthritis (RA) is an immune-mediated disease with a pathogenesis that involves CD4 T cell activation. Multiple immune regulatory molecules expressed on CD4(+) T cells were involved in RA pathogenesis. In this study, we investigated the role of T cell immunoglobulin and ITIM (immunoreceptor tyrosine-based inhibition motif) domain (TIGIT) in RA. The frequency of TIGIT-positive CD4(+) T cells in the synovial fluid (SF) of active RA patients was lower than that of inactive RA patients. And a negative correlation between RA disease activity and TIGIT expression was found. In CD4(+) T cells isolated from SF of active RA patients, TIGIT upregulation significantly decreased cell proliferation, as shown by MTT assay. TIGIT overexpression also significantly decreased the production of IFN-γ and IL-17, and increased that of IL-10, as determined by ELISA and qRT-PCR. In CD4(+) T cells isolated from SF of inactive RA patients, TIGIT was silenced by siRNA transfection. As expected, TIGIT knockdown resulted in an opposite effect on cell proliferation and the production of cytokines, including IFN-γ, IL-17 and IL-10. A RA mouse model was established using type II collagen induction. TIGIT was upregulated in RA mouse by lentivector infection. As expected, TIGIT overexpression in vivo significantly alleviated the disease severity and deceased the levels of anti-collagen II antibodies. TIGIT upregulation in the early stage was more effective to alleviate disease severity. Our data suggested the potential therapeutic role of TIGIT in RA patients.

  6. Inhibition of LPS-induced TNF-α and NO production in mouse macrophage and inflammatory response in rat animal models by a novel Ayurvedic formulation, BV-9238.

    PubMed

    Dey, Debendranath; Chaskar, Sunetra; Athavale, Nitin; Chitre, Deepa

    2014-10-01

    Rheumatoid arthritis is a chronic crippling disease, where protein-based tumor necrosis factor-alpha (TNF-α) inhibitors show significant relief, but with potentially fatal side effects. A need for a safe, oral, cost-effective small molecule or phyto-pharmaceutical is warranted. BV-9238 is an Ayurvedic poly-herbal formulation containing specialized standardized extracts of Withania somnifera, Boswellia serrata, Zingiber officinale and Curcuma longa. The anti-inflammatory and anti-arthritic effects of BV-9238 were evaluated for inhibition of TNF-α and nitric oxide (NO) production, in lipopolysaccharide-stimulated, RAW 264.7, mouse macrophage cell line. BV-9238 reduced TNF-α and NO production, without any cytotoxic effects. Subsequently, the formulation was tested in adjuvant-induced arthritis (AIA) and carrageenan-induced paw edema (CPE) rat animal models. AIA was induced in rats by injecting Freund's complete adjuvant intra-dermally in the paw, and BV-9238 and controls were administered orally for 21 days. Arthritic scores in AIA study and inflamed paw volume in CPE study were significantly reduced upon treatment with BV-9238. These results suggest that the anti-inflammatory and anti-arthritic effects of BV-9238 are due to its inhibition of TNF-α, and NO, and this formulation shows promise as an alternate therapy for inflammatory disorders where TNF-α and NO play important roles. PMID:24706581

  7. Arthritis: joints inflamed.

    PubMed

    Casey, Georgina

    2015-06-01

    ARTHRITIS IS a generic term for inflammatory joint disease. There are various forms of arthritis, including osteoarthritis, rheumatoid arthritis and spondyloarthritis. Arthritis can be a chronic debilitating condition or a transient effect of bacterial or viral infections. As a chronic condition, arthritis can cause loss of quality of life, disability and, with rheumatoid disease, early death. The economic burden of arthritis, in terms of management and loss of productivity due to disability, is high and set to increase with the ageing population. Recent advances in our understanding of the causes and progression of a number of forms of arthritis have raised hopes of better management and possible remission. Pharmacotherapy has moved from symptom management to addressing underlying disease processes. However, therapies that prevent or cure arthritis remain elusive. Current care for people with arthritis relies on a multidisciplinary approach and substantial pharmacological intervention. Nurses have a key role to play in guiding patients through treatment, ensuring they receive optimal therapy to reduce the impact of arthritis and its management on their lives.

  8. Rheumatoid Arthritis Educational Video Series

    MedlinePlus

    ... Rheumatoid Arthritis Educational Video Series Rheumatoid Arthritis Educational Video Series This series of five videos was designed ... Activity Role of Body Weight in Osteoarthritis Educational Videos for Patients Rheumatoid Arthritis Educational Video Series Psoriatic ...

  9. Infectious arthritis in patients with rheumatoid arthritis.

    PubMed Central

    Mateo Soria, L; Miquel Nolla Solé, J; Rozadilla Sacanell, A; Valverde García, J; Roig Escofet, D

    1992-01-01

    Eleven cases of infectious arthritis occurring in patients with rheumatoid arthritis are reported. Staphylococcus aureus was the causative organism in eight patients. Streptococcus anginosus and Streptococcus agalactiae in one patient each, and Mycobacterium tuberculosis in two patients. The mean duration of symptoms before diagnosis was 16 days in patients with pyogenic arthritis. The diagnosis of joint infection caused by Mycobacterium tuberculosis was especially delayed (57 days). Four patients died; they were found to have a longer time to diagnosis and two of them had multiple joint infection. Although Staphylococcus aureus is the microorganism most often affecting patients with rheumatoid arthritis, infection caused by Mycobacterium tuberculosis must also be considered in such patients. PMID:1575593

  10. Enthesitis-related arthritis.

    PubMed

    Aggarwal, Amita; Misra, Durga Prasanna

    2015-11-01

    Juvenile idiopathic arthritis (JIA) is the most common chronic arthritis of childhood. Currently, it is characterized by seven categories. The enthesitis-related arthritis (ERA) category usually affects boys older than 6 years and presents with lower limb asymmetrical arthritis associated with enthesitis. Later, these children can develop inflammatory lumbosacral pain (IBP). These children are at risk of developing acute anterior uveitis. A recently devised disease activity index, Juvenile Spondyloarthropathy Disease Activity Index (JSpADA), has been validated in retrospective cohorts. The corner stone of treatment is NSAIDs, local corticosteroid injections, and exercise. Methotrexate and sulfasalazine can be used for peripheral arthritis while anti-tumor necrosis factor (TNF) agents are sometimes used to treat refractory enthesitis and sacroiliitis. Almost two third of patients with ERA have persistent disease and often have impairments in their quality of life. The presence of hip or ankle arthritis and a family history of spondyloarthropathy or polyarticular joint involvement at onset are associated with poorer prognosis.

  11. Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses.

    PubMed

    Lloyd, K C; Stover, S M; Pascoe, J R; Adams, P

    1990-09-01

    Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

    PubMed Central

    Song, X Y; Gu, M; Jin, W W; Klinman, D M; Wahl, S M

    1998-01-01

    Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. PMID:9637694

  13. Macrophage Migration Inhibitory Factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

    PubMed Central

    Gu, Ran; Santos, Leilani L.; Ngo, Devi; Fan, HuaPeng; Singh, Preetinder P.; Fingerle-Rowson, Gunter; Bucala, Richard; Xu, Jiake; Quinn, Julian M. W.; Morand, Eric F.

    2015-01-01

    Macrophage migration inhibitory factor (MIF) enhances activation of leukocytes, endothelial cells and fibroblast-like synoviocytes (FLS), thereby contributing to the pathogenesis of rheumatoid arthritis (RA). A MIF promoter polymorphism in RA patients resulted in higher serum MIF concentration and worsens bone erosion; controversially current literature reported an inhibitory role of MIF in osteoclast formation. The controversial suggested that the precise role of MIF and its putative receptor CD74 in osteoclastogenesis and RA bone erosion, mediated by locally formed osteoclasts in response to receptor activator of NF-κB ligand (RANKL), is unclear. We reported that in an in vivo K/BxN serum transfer arthritis, reduced clinical and histological arthritis in MIF-/- and CD74-/- mice were accompanied by a virtual absence of osteoclasts at the synovium-bone interface and reduced osteoclast-related gene expression. Furthermore, in vitro osteoclast formation and osteoclast-related gene expression were significantly reduced in MIF-/- cells via decreasing RANKL-induced phosphorylation of NF-κB-p65 and ERK1/2. This was supported by a similar reduction of osteoclastogenesis observed in CD74-/- cells. Furthermore, a MIF blockade reduced RANKL-induced osteoclastogenesis via deregulating RANKL-mediated NF-κB and NFATc1 transcription factor activation. These data indicate that MIF and CD74 facilitate RANKL-induced osteoclastogenesis, and suggest that MIF contributes directly to bone erosion, as well as inflammation, in RA. PMID:25647268

  14. Chemical characterization of a red raspberry fruit extract and evaluation of its pharmacological effects in experimental models of acute inflammation and collagen-induced arthritis.

    PubMed

    Figueira, M E; Câmara, M B; Direito, R; Rocha, J; Serra, A T; Duarte, C M M; Fernandes, A; Freitas, M; Fernandes, E; Marques, M C; Bronze, M R; Sepodes, B

    2014-12-01

    Berries are an important dietary source of fibres, vitamins, minerals and some biologically active non-nutrients. A red raspberry fruit extract was characterized in terms of phenolic content and the anti-inflammatory properties and protective effects were evaluated in two experimental models of inflammation. The antioxidant potential of the extract, the cellular antioxidant activity and the effects over neutrophils' oxidative burst were also studied to provide a mechanistic insight for the anti-inflammatory effects observed. The extract was administered in a dose of 15 mg kg(-1), i.p. and significantly inhibited paw oedema formation in the rat. The same dose was administered via i.p. and p.o. routes in the collagen-induced arthritis model in the rat. The extract showed pharmacological activity and was able to significantly reduce the development of clinical signs of arthritis and markedly reduce the degree of bone resorption, soft tissue swelling and osteophyte formation, preventing articular destruction in treated animals.

  15. 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

  16. Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model

    PubMed Central

    Li, Xue; Wei, Yi; Chen, Meng; Zhou, Jingwei; Dong, Bin; Zhu, Lingqun

    2016-01-01

    In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA.

  17. Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model.

    PubMed

    Nie, Bo; Li, Xue; Wei, Yi; Chen, Meng; Zhou, Jingwei; Lou, Lixia; Dong, Bin; Wu, Aiming; Zhang, Dongmei; Zhu, Lingqun; Zhao, Jiuli; Chai, Limin

    2016-01-01

    In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA. PMID:27656238

  18. Inhibitory effects of anti-rheumatic drugs containing magnosalin, a compound from 'Shin-i' (Flos magnoliae), on the proliferation of synovial cells in rheumatoid arthritis models.

    PubMed

    Kobayashi, S; Kobayashi, H; Matsuno, H; Kimura, I; Kimura, M

    1998-05-01

    This study was undertaken to examine the effects of magnosalin, a compound isolated from 'Shin-i' (Flos magnoliae) on proliferation of synovial cells isolated from MRL/1pr and collagen-induced arthritis (CIA) mice, and rheumatoid arthritis (RA) patients. Magnosalin (2.39-23.9 microM) inhibited 5% fetal bovine serum (FBS)-stimulated [3H]-thymidine incorporation into the synovial cells in the MRL/1pr mice. The effect of magnosalin was greater than that of hydrocortisone, bucillamine and magnoshinin (another compound from 'Shin-i'), but weaker than that of corticosterone. The effects of magnosalin for FBS-induced thymidine incorporation into the cells of the CIA mice and the RA patients were significantly greater than those in the corresponding control mice and osteoarthritis patients. Interleukin (IL)-1alpha increased the incorporation of thymidine into the synovial cells in the C57BL/6J mice to a greater degree than did basic fibroblast growth factor (bFGF) or platelet-derived growth factor BB-homodimer (PDGF-BB). The inhibitory effect of magnosalin on the submaximal action of IL-1alpha was significantly greater than that of bFGF, PDGF-BB or FBS. These results offer evidence that magnosalin suppresses the proliferation of synovial cells in RA models by inhibiting IL-1alpha-stimulated action.

  19. Xianfanghuomingyin, a Chinese Compound Medicine, Modulates the Proliferation and Differentiation of T Lymphocyte in a Collagen-Induced Arthritis Mouse Model

    PubMed Central

    Li, Xue; Wei, Yi; Chen, Meng; Zhou, Jingwei; Dong, Bin; Zhu, Lingqun

    2016-01-01

    In traditional Chinese medicine (TCM), xianfanghuomingyin (XFHM) is used to treat autoimmune diseases, including rheumatoid arthritis (RA). Here, we studied the mechanisms underlying its treatment effects, especially its anti-inflammatory effects in a collagen-induced arthritis (CIA) mouse model. We found that cartilage destruction and pannus formation were alleviated by treatment with XFHM. The abnormal differentiation of Th1 and Th17 cells was downregulated significantly by XFHM, and Th2 and Treg cells were upregulated. Moreover, the expression levels of specific cytokines and transcription factors related to Th1 cells (interferon γ [IFNγ], T-bet) and Th17 cells (interleukin- [IL-] 17) and the nuclear receptor retinoic acid receptor-related orphan receptor-gamma (RORγ) were downregulated. Serum IL-4 and GATA-3, which contribute to Th2 cells differentiation, increased significantly after XFHM administration. These results indicate that XFHM can restore the balance of T lymphocytes and reestablish the immunological tolerance to inhibit autoinflammatory disorder of RA. Taken together, XFHM can be used as a complementary or alternative traditional medicine to treat RA. PMID:27656238

  20. Anti-inflammatory effects and pharmacokinetics study of geniposide on rats with adjuvant arthritis.

    PubMed

    Chen, Jin-Yun; Wu, Hong; Li, Hui; Hu, Shun-Li; Dai, Miao-miao; Chen, Jian

    2015-01-01

    The aim of this study was to explore the anti-inflammatory effects of Geniposide (GE), an iridoid glycoside compound extracted from Gardenia jasminoides Ellis (GJ) fruit in adjuvant-induced arthritis (AA) rats and its pharmacokinetic (PK) basis. AA was induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were subjected to treatment with GE (30, 60 and 120mg/kg) from day 17 to 24 after immunization. Fibroblast-like synoviocyte (FLS) proliferation was assessed by MTT. Interleukin (IL)-1, IL-6, TNF-α and IL-10 were determined using double-sandwich enzyme-linked immunosorbent assay (ELISA). Expression of p38 mitogen-activated protein kinases (p38MAPKs) related proteins in FLS was detected by Western blotting. PK profiles were simultaneously detected by ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) in AA rat plasma after oral administration of GE on day 17 after immunization. As a result, GE promoted the recovery of arthritis and inhibited the colonic inflammation damage in AA rats by decreasing the expression level of TNF-α, IL-1 and IL-6, increasing the production of IL-10 and inhibiting the expression of phospho-p38 (p-p38) related proteins in FLS. PK parameters (AUC, Cmax and t1/2) tended to be associated with dosage-related decreasing of efficacy index. PMID:25434608

  1. Postinfectious Arthritis in Pediatric Practice

    PubMed Central

    PLESCA, Doina Anca; LUMINOS, Monica; SPATARIU, Luminita; STEFANESCU, Mihaela; CINTEZA, Eliza; BALGRADEAN, Mihaela

    2013-01-01

    ABSTRACT Postinfectious arthritis is a relatively often encountered in pediatric practice. The authors present the most important data concerneing this pathology, with up to date informations exemplifying with case presentations. Clinical cases bring to attention the most common forms of postinfectious arthritis (reactive arthritis, postinfectious arthritis bacterial, viral, spirochete, and so on). Although highly studied and commonly found in current pediatric practice, arthritis occurring after infections remains controversial entities, especially regarding terminology. While, according to some authors, postinfectious arthritis belongs to the large group of reactive arthritis, by other authors, these joint events are independent entities. PMID:24371480

  2. Microbial Infection and Rheumatoid Arthritis

    PubMed Central

    Li, Song; Yu, Yangsheng; Yue, Yinshi; Zhang, Zhixin; Su, Kaihong

    2014-01-01

    Rheumatoid arthritis (RA) is a complex autoimmune disease affecting 1–2% of general worldwide population. The etiopathogenesis of RA involves the interplay of multiple genetic risk factors and environmental triggers. Microbial infections are believed to play an important role in the initiation and perpetuation of RA. Recent clinical studies have shown the association of microbial infections with RA. Accumulated studies using animal models have also found that microbial infections can induce and/or exaggerate the symptoms of experimental arthritis. In this review, we have identified the most common microbial infections associated with RA in the literature and summarized the current evidence supporting their pathogenic role in RA. We also discussed the potential mechanisms whereby infection may promote the development of RA, such as generation of neo-autoantigens, induction of loss of tolerance by molecular mimicry, and bystander activation of the immune system. PMID:25133066

  3. Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models

    PubMed Central

    Kuwabara, Harumi

    2016-01-01

    Prostaglandin E2 (PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2 synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin-4-yl]carbonyl amino)cyclohexyl] propanoic acid, in rat yeast-induced acute and adjuvant-induced chronic inflammatory pain models. Although this compound suppressed the synthesis of PGE2 selectively, no analgesic effect was shown in both inflammatory pain models. Prostacyclin (PGI2) also plays crucial roles in inflammatory pain, so we evaluated the involvement of PGI2 signaling in rat inflammatory pain models using prostacyclin receptor (IP) antagonist, RO3244019. RO3244019 showed no analgesic effect in inflammatory pain models, but concomitant administration of compound I and RO3244019 showed analgesic effects comparable to celecoxib, a specific cyclooxygenase- (COX-) 2 inhibitor. Furthermore, coadministration of PGE2 receptor 4 (EP4) antagonist, CJ-023423, and RO3244019 also showed an analgesic effect. These findings suggest that both PGE2 signaling, especially through the EP4 receptor, and PGI2 signaling play critical roles in inflammatory pain and concurrent inhibition of both signals is important for suppression of inflammatory hyperalgesia. PMID:27478311

  4. Simultaneous Inhibition of PGE2 and PGI2 Signals Is Necessary to Suppress Hyperalgesia in Rat Inflammatory Pain Models.

    PubMed

    Sugita, Ryusuke; Kuwabara, Harumi; Kubota, Kazufumi; Sugimoto, Kotaro; Kiho, Toshihiro; Tengeiji, Atsushi; Kawakami, Katsuhiro; Shimada, Kohei

    2016-01-01

    Prostaglandin E2 (PGE2) is well known as a mediator of inflammatory symptoms such as fever, arthritis, and inflammatory pain. In the present study, we evaluated the analgesic effect of our selective PGE2 synthesis inhibitor, compound I, 2-methyl-2-[cis-4-([1-(6-methyl-3-phenylquinolin-2-yl)piperidin-4-yl]carbonyl amino)cyclohexyl] propanoic acid, in rat yeast-induced acute and adjuvant-induced chronic inflammatory pain models. Although this compound suppressed the synthesis of PGE2 selectively, no analgesic effect was shown in both inflammatory pain models. Prostacyclin (PGI2) also plays crucial roles in inflammatory pain, so we evaluated the involvement of PGI2 signaling in rat inflammatory pain models using prostacyclin receptor (IP) antagonist, RO3244019. RO3244019 showed no analgesic effect in inflammatory pain models, but concomitant administration of compound I and RO3244019 showed analgesic effects comparable to celecoxib, a specific cyclooxygenase- (COX-) 2 inhibitor. Furthermore, coadministration of PGE2 receptor 4 (EP4) antagonist, CJ-023423, and RO3244019 also showed an analgesic effect. These findings suggest that both PGE2 signaling, especially through the EP4 receptor, and PGI2 signaling play critical roles in inflammatory pain and concurrent inhibition of both signals is important for suppression of inflammatory hyperalgesia. PMID:27478311

  5. Techniques for assessing knee joint pain in arthritis.

    PubMed

    Neugebauer, Volker; Han, Jeong S; Adwanikar, Hita; Fu, Yu; Ji, Guangchen

    2007-03-28

    The assessment of pain is of critical importance for mechanistic studies as well as for the validation of drug targets. This review will focus on knee joint pain associated with arthritis. Different animal models have been developed for the study of knee joint arthritis. Behavioral tests in animal models of knee joint arthritis typically measure knee joint pain rather indirectly. In recent years, however, progress has been made in the development of tests that actually evaluate the sensitivity of the knee joint in arthritis models. They include measurements of the knee extension angle struggle threshold, hind limb withdrawal reflex threshold of knee compression force, and vocalizations in response to stimulation of the knee. A discussion of pain assessment in humans with arthritis pain conditions concludes this review.

  6. [Septic arthritis and spondylitis].

    PubMed

    Fujikawa, Yosuke

    2014-10-01

    Septic arthritis and spondylitis in elderly adult are uncommon disease. But symptoms and signs of septic arthritis and spondylitis are an important medical emergency, with high mortality and morbidity. Delayed or inadequate treatment can result in irreversible joint destruction and neurological condition. Early diagnoses as well as prompt and effective treatment are essential for avoiding severe outcomes. In spite of advances in diagnostic imaging techniques, the incidence of septic arthritis and spondylitis appears to have been increased. The aging of the population, the widespread use of immunosuppressant therapies, including systemic corticosteroids, cytokines and anticytokines, and growing resistance to conventional antibiotics seem to be the major cause.

  7. Arthritis and IBD

    MedlinePlus

    ... Events Search: What are Crohn's & Colitis? What is Crohn's Disease What is Ulcerative Colitis Types of Medications What’s ... affect as many as 25% of people with Crohn’s disease or ulcerative colitis. Although arthritis is typically associated ...

  8. Juvenile Idiopathic Arthritis

    MedlinePlus

    ... vein that are done regularly at the hospital. Physical Therapy An appropriate physical therapy program is essential to the management of any type of arthritis. A physical therapist will explain the importance of certain activities ...

  9. Living with Psoriatic Arthritis

    MedlinePlus

    ... effects. Learn more about biologic treatments . Reducing your sensitivity to pain When the pain of psoriatic arthritis ... your doctor about medication that helps reduce your sensitivity to pain. Prescription pain medications such as Gabapentin ...

  10. Arthritis of the Hand

    MedlinePlus

    ... of hand and wrist arthritis. (Note: The U.S. Food and Drug Administration does not test dietary supplements. These compounds may cause negative interactions with other medications. Always consult your doctor before taking dietary supplements.) ...

  11. Arthritis and the Feet

    MedlinePlus

    ... for months, or years, then abate, sometimes permanently. Gout (gouty arthritis) : Gout is a condition caused by a buildup of ... sauces, shellfish, and brandy is popularly associated with gout, there are other protein compounds in foods such ...

  12. Juvenile idiopathic arthritis.

    PubMed

    Gowdie, Peter J; Tse, Shirley M L

    2012-04-01

    Juvenile idiopathic arthritis (JIA) encompasses a complex group of disorders with arthritis as a common feature. This article provides the pediatrician with a review of the epidemiology, classification, clinical manifestations, and complications of JIA. It also provides an update on the current understanding of the cause of JIA and recent developments in management and a recent review of the long-term outcome in JIA.

  13. Avenues to autoimmune arthritis triggered by diverse remote inflammatory challenges.

    PubMed

    Chevalier, Nina; Tan, Jian K; Mason, Linda J; Robert, Remy; McKenzie, Craig I; Lim, Florence; Wong, Connie H; Macia, Laurence; Thorburn, Alison N; Russ, Brendan E; Masters, Seth L; Mackay, Charles R

    2016-09-01

    Environmental factors contribute to development of autoimmune diseases. For instance, human autoimmune arthritis can associate with intestinal inflammation, cigarette smoking, periodontal disease, and various infections. The cellular and, molecular pathways whereby such remote challenges might precipitate arthritis or flares remain unclear. Here, we used a transfer model of self-reactive arthritis-inducing CD4(+) cells from KRNtg mice that, upon transfer, induce a very mild form of autoinflammatory arthritis in recipient animals. This model enabled us to identify external factors that greatly aggravated disease. We show that several distinct challenges precipitated full-blown arthritis, including intestinal inflammation through DSS-induced colitis, and bronchial stress through Influenza infection. Both triggers induced strong IL-17 expression primarily in self-reactive CD4(+) cells in lymph nodes draining the site of inflammation. Moreover, treatment of mice with IL-1β greatly exacerbated arthritis, while transfer of KRNtg CD4(+) cells lacking IL-1R significantly reduced disease and IL-17 expression. Thus, IL-1β enhances the autoaggressive potential of self-reactive CD4(+) cells, through increased Th17 differentiation, and this influences inflammatory events in the joints. We propose that diverse challenges that cause remote inflammation (lung infection or colitis, etc.) result in IL-1β-driven Th17 differentiation, and this precipitates arthritis in genetically susceptible individuals. Thus the etiology of autoimmune inflammatory arthritis likely relates to diverse triggers that converge to a common pathway involving IL-1β production and Th17 cell distribution. PMID:27427404

  14. Avenues to autoimmune arthritis triggered by diverse remote inflammatory challenges.

    PubMed

    Chevalier, Nina; Tan, Jian K; Mason, Linda J; Robert, Remy; McKenzie, Craig I; Lim, Florence; Wong, Connie H; Macia, Laurence; Thorburn, Alison N; Russ, Brendan E; Masters, Seth L; Mackay, Charles R

    2016-09-01

    Environmental factors contribute to development of autoimmune diseases. For instance, human autoimmune arthritis can associate with intestinal inflammation, cigarette smoking, periodontal disease, and various infections. The cellular and, molecular pathways whereby such remote challenges might precipitate arthritis or flares remain unclear. Here, we used a transfer model of self-reactive arthritis-inducing CD4(+) cells from KRNtg mice that, upon transfer, induce a very mild form of autoinflammatory arthritis in recipient animals. This model enabled us to identify external factors that greatly aggravated disease. We show that several distinct challenges precipitated full-blown arthritis, including intestinal inflammation through DSS-induced colitis, and bronchial stress through Influenza infection. Both triggers induced strong IL-17 expression primarily in self-reactive CD4(+) cells in lymph nodes draining the site of inflammation. Moreover, treatment of mice with IL-1β greatly exacerbated arthritis, while transfer of KRNtg CD4(+) cells lacking IL-1R significantly reduced disease and IL-17 expression. Thus, IL-1β enhances the autoaggressive potential of self-reactive CD4(+) cells, through increased Th17 differentiation, and this influences inflammatory events in the joints. We propose that diverse challenges that cause remote inflammation (lung infection or colitis, etc.) result in IL-1β-driven Th17 differentiation, and this precipitates arthritis in genetically susceptible individuals. Thus the etiology of autoimmune inflammatory arthritis likely relates to diverse triggers that converge to a common pathway involving IL-1β production and Th17 cell distribution.

  15. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR. PMID:26640276

  16. Tetrandrine ameliorates collagen-induced arthritis in mice by restoring the balance between Th17 and Treg cells via the aryl hydrocarbon receptor.

    PubMed

    Yuan, Xusheng; Tong, Bei; Dou, Yannong; Wu, Xin; Wei, Zhifeng; Dai, Yue

    2016-02-01

    Tetrandrine is an alkaloid constituent of the root of Stephania tetrandra S. Moore. The long-term clinical uses of tetrandrine for treatments of rheumatalgia and arthralgia as well as the inhibition of rat adjuvant-induced arthritis imply that tetrandrine may have therapeutic potential in rheumatoid arthritis (RA). Here, we explored its anti-RA mechanism in collagen-induced arthritis (CIA) in relation to the balance between T helper (Th) 17 cells and regulatory T (Treg) cells. DBA/1 mice were immunized with chicken type II collagen and were orally administered tetrandrine for 14 consecutive days. Then, the mice were sacrificed, their joints were removed for histological analysis, and spleens and mesenteric lymph nodes (MLNs) were removed to examine the Th17 and Treg cells. Tetrandrine markedly alleviated the severity of arthritis, reduced the serum levels of pro-inflammatory cytokines, and restored the Th17/Treg balance, as demonstrated by the serum levels of their related cytokines (IL-17 and IL-10) and the proportion of each cell type. Tetrandrine inhibited Th17 cell differentiation and induced Treg cell differentiation in vitro . Notably, aryl hydrocarbon receptor (AhR) was proven to play a crucial role in tetrandrine-mediated T cell differentiation. The correlation between AhR activation, regulation of Th17/Treg and amelioration of arthritis by tetrandrine was verified in the CIA mice. Moreover, tetrandrine might be a ligand of AhR because it facilitated the expression of the AhR target gene cytochrome P450 1A1 (CYP1A1) and the activation of its downstream signaling pathways. Taken together, tetrandrine exerts its anti-arthritis efficacy by restoring Th17/Treg balance via AhR.

  17. Lysosomal β-glucuronidase regulates Lyme and rheumatoid arthritis severity

    PubMed Central

    Bramwell, Kenneth K.C.; Ma, Ying; Weis, John H.; Chen, Xinjian; Zachary, James F.; Teuscher, Cory; Weis, Janis J.

    2013-01-01

    Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most prevalent arthropod-borne illness in the United States and remains a clinical and social challenge. The spectrum of disease severity among infected patients suggests that host genetics contribute to pathogenic outcomes, particularly in patients who develop arthritis. Using a forward genetics approach, we identified the lysosomal enzyme β-glucuronidase (GUSB), a member of a large family of coregulated lysosomal enzymes, as a key regulator of Lyme-associated arthritis severity. Severely arthritic C3H mice possessed a naturally occurring hypomorphic allele, Gusbh. C57BL/6 mice congenic for the C3H Gusb allele were prone to increased Lyme-associated arthritis severity. Radiation chimera experiments revealed that resident joint cells drive arthritis susceptibility. C3H mice expressing WT Gusb as a transgene were protected from severe Lyme arthritis. Importantly, the Gusbh allele also exacerbated disease in a serum transfer model of rheumatoid arthritis. A known GUSB function is the prevention of lysosomal accumulation of glycosaminoglycans (GAGs). Development of Lyme and rheumatoid arthritis in Gusbh-expressing mice was associated with heightened accumulation of GAGs in joint tissue. We propose that GUSB modulates arthritis pathogenesis by preventing accumulation of proinflammatory GAGs within inflamed joint tissue, a trait that may be shared by other lysosomal exoglycosidases. PMID:24334460

  18. Physical Activity and Psoriatic Arthritis

    MedlinePlus

    ... Psoriatic Arthritis Info Kit Resources Community icon: Link text: Post your questions in our online community and ... psoriasis and psoriatic arthritis. Talk Psoriasis icon: Link text: Contact our Patient Navigators for free and confidential ...

  19. Imaging reactive oxygen species in arthritis.

    PubMed

    Chen, Wei-Tsung; Tung, Ching-Hsuan; Weissleder, Ralph

    2004-07-01

    Reactive oxygen species (ROS) have been shown to play a role in the pathogenesis of arthritides. Luminol was used as the primary reporter of ROS and photons resulting from the chemiluminescence reaction were detected using a super-cooled CCD photon counting system. Luminol was injected intravenously into groups of animals with different models of arthritis. Imaging signal correlated well with the severity of arthritis in focal and pan-arthritis as determined by histological measurement of ROS by formazan. Measurements were highly reproducible, sensitive, and repeatable. In vivo chemiluminescence imaging is expected to become a useful modality to elucidate the role of ROS in the pathogenesis of arthritides and in determining therapeutic efficacy of protective therapies.

  20. Arthritis in Flemish paintings (1400-1700).

    PubMed Central

    Dequeker, J

    1977-01-01

    A close examination of the hands of people depicted in paintings of the Flemish school showed that in five paintings there were figures with hand lesions resembling those of rhematoid arthritis. Although none of the deformities or swellings are indisputable examples of rheumatoid arthritis, they do at least suggest that the painters must have been confronted with rheumatoid-like lesions in their models. In two other paintings there were signs of rheumatic fever and of temporal arteritis. No arthritic lesions were found in the works of painters of the Italian Renaissance, probably because they are less detailed. The finding of rheumatoid deformities in the Flemish paintings does, however, question the general belief that rheumatoid arthritis is a condition that has arisen relatively recently. Images FIGS 1-2 FIG 3 FIG 4 FIG 5 FIG 6 FIG 7 PMID:324568

  1. Simultaneous Exposure–Response Modeling of ACR20, ACR50, and ACR70 Improvement Scores in Rheumatoid Arthritis Patients Treated With Certolizumab Pegol

    PubMed Central

    Lacroix, B D; Karlsson, M O; Friberg, L E

    2014-01-01

    The Markovian approach has been proposed to model American College of Rheumatology's (ACR) response (ACR20, ACR50, or ACR70) reported in rheumatoid arthritis clinical trials to account for the dependency of the scores over time. However, dichotomizing the composite ACR assessment discards much information. Here, we propose a new approach for modeling together the three thresholds: a continuous-time Markov exposure–response model was developed, based on data from five placebo-controlled certolizumab pegol clinical trials. This approach allows adequate prediction of individual ACR20/50/70 time-response, even for non-periodic observations. An exposure–response was established over a large range of licensed and unlicensed doses including phase II dose-ranging data. Simulations from the model (50–400 mg every other week) illustrated the range and sustainability of response (ACR20: 56–68%, ACR50: 27–42%, ACR70: 11–22% at week 24) with maximum clinical effect achieved at the recommended maintenance dose of 200 mg every other week. PMID:25353186

  2. Aeromonas hydrophila septic arthritis.

    PubMed

    Danaher, Patrick J; Mueller, William P

    2011-12-01

    Septic arthritis is a serious, life and limb threatening infection. If suspected, empiric treatment must begin immediately and account for the most likely pathogens. Eight days following left knee arthroscopic surgery, a 51-year-old active duty male spent approximately 1 hour driving a personal watercraft on Okaloosa Bay near the Gulf of Mexico. Eight days later, he presented to the emergency room with septic arthritis of that knee. Fluid aspirated from the joint yielded Aeromonas hydrophila. The infection resolved with surgical drainage and 21 days of levofloxacin. A. hydrophila is a rare cause of septic arthritis, and reported cases have involved exposure to water after trauma to the affected joint. Many U.S. military bases are located in coastal areas and military members frequently participate in activities which compromise skin integrity and place them at increased risk for contracting waterborne infections. We present the ninth case of A. hydrophila septic arthritis described in the English language literature, highlight the importance of considering this pathogen in at-risk populations, and review the diagnosis and management of septic arthritis.

  3. Chemical changes demonstrated in cartilage by synchrotron infrared microspectroscopy in an antibody-induced murine model of rheumatoid arthritis

    NASA Astrophysics Data System (ADS)

    Croxford, Allyson M.; Selva Nandakumar, Kutty; Holmdahl, Rikard; Tobin, Mark J.; McNaughton, Don; Rowley, Merrill J.

    2011-06-01

    Collagen antibody-induced arthritis develops in mice following passive transfer of monoclonal antibodies (mAbs) to type II collagen (CII) and is attributed to effects of proinflammatory immune complexes, but transferred mAbs may react directly and damagingly with CII. To determine whether such mAbs cause cartilage damage in vivo in the absence of inflammation, mice lacking complement factor 5 that do not develop joint inflammation were injected intravenously with two arthritogenic mAbs to CII, M2139 and CIIC1. Paws were collected at day 3, decalcified, paraffin embedded, and 5-μm sections were examined using standard histology and synchrotron Fourier-transform infrared microspectroscopy (FTIRM). None of the mice injected with mAb showed visual or histological evidence of inflammation but there were histological changes in the articular cartilage including loss of proteoglycan and altered chondrocyte morphology. Findings using FTIRM at high lateral resolution revealed loss of collagen and the appearance of a new peak at 1635 cm-1 at the surface of the cartilage interpreted as cellular activation. Thus, we demonstrate the utility of synchrotron FTIRM for examining chemical changes in diseased cartilage at the microscopic level and establish that arthritogenic mAbs to CII do cause cartilage damage in vivo in the absence of inflammation.

  4. IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis.

    PubMed

    Lee, Seon-Yeong; Jung, Young Ok; Kim, Doo-Jin; Kang, Chang-Min; Moon, Young-Mee; Heo, Yu-Jung; Oh, Hye-Jwa; Park, Seong-Jeong; Yang, Se-Hwan; Kwok, Seung Ki; Ju, Ji-Hyeon; Park, Sung-Hwan; Sung, Young Chul; Kim, Ho-Youn; Cho, Mi-La

    2015-10-01

    IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist-knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)2 model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)2 inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4(+)CD25(+)Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor-related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2 suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling. PMID:26324771

  5. IL-12p40 Homodimer Ameliorates Experimental Autoimmune Arthritis

    PubMed Central

    Lee, Seon-Yeong; Jung, Young Ok; Kim, Doo-Jin; Kang, Chang-Min; Moon, Young-Mee; Heo, Yu-Jung; Oh, Hye-Jwa; Park, Seong-Jeong; Yang, Se-Hwan; Kwok, Seung Ki; Ju, Ji-Hyeon; Park, Sung-Hwan; Sung, Young Chul

    2015-01-01

    IL-23 is the key cytokine that induces the expansion of Th17 cells. It is composed of p19 and p40 subunits of IL-12. The p40 subunit binds competitively to the receptor of IL-23 and blocks its activity. Our aim was to assess the preventive and therapeutic effect of the IL-12p40 homodimer (p40)2 subunit in autoimmune arthritis animal models. In the current study, using IL-1R antagonist–knockout mice and a collagen-induced arthritis model, we investigated the suppressive effect of (p40)2 on inflammatory arthritis. We demonstrated that the recombinant adenovirus-expressing mouse (p40)2 model prevented the development of arthritis when given before the onset of arthritis. It also decreased the arthritis index and joint erosions in the mouse model if transferred after arthritis was established. (p40)2 inhibited the production of inflammatory cytokines and Ag-specific T cell proliferation. It also induced CD4+CD25+Foxp3 regulatory T (Treg) cells in vitro and in vivo, whereas the generation of retinoic acid receptor–related organ receptor γt and Th17 cells was suppressed. The induction of Treg cells and the suppression of Th17 cells were mediated via activated STAT5 and suppressed STAT3. Our data suggest that (p40)2 suppressed inflammatory arthritis successfully. This could be a useful therapeutic approach in autoimmune arthritis to regulate the Th17/Treg balance and IL-23 signaling. PMID:26324771

  6. Dermatoglyphics in rheumatoid arthritis.

    PubMed

    Ravindranath, Roopa; Shubha, R; Nagesh, H V; Johnson, Job; Rajangam, Sayee

    2003-10-01

    Patients with rheumatoid arthritis have been referred to Division of Human Genetics for counselling. Qualitative dermatoglyphics comprising of finger print pattern, interdigital pattern, hypothenar pattern and palmar crease were studied on 26 female and 11 male rheumatoid arthritis patients. Comparison between patient male and control male; and patient female and control female has been done. 'Chi' square test was performed. In male patients, with hands together, arches were increased, loops/ whorls were decreased. Partial Simian crease was significantly increased. In the right hand, patterns were increased in the 3rd interdigital area. On the other hand, in female patients there was a significant increase in whorls and decrease in loops on the first finger on both the hands, increase in arches on the 3rd finger; both arches and whorls on the 4th finger of left hand. Present study has emphasized that dermatoglyphics could be applied as a diagnostic tool to patients with rheumatoid arthritis.

  7. Glucocorticoids and Rheumatoid Arthritis.

    PubMed

    Ferreira, Joana Fonseca; Ahmed Mohamed, Alaa Abdelkhalik; Emery, Paul

    2016-02-01

    Glucocorticoids (GCs) were discovered in the 1940s and were administered for the first time to patients with rheumatoid arthritis in 1948. However, side effects were subsequently reported. In the last 7 decades, the mechanisms of action for both therapeutic properties and side effects have been elucidated. Mechanisms for minimizing side effects were also developed. GCs are the most frequently used class of drugs in the treatment of rheumatoid arthritis because of their efficacy in relieving symptoms and their low cost. A review of clinical applications, side effects, and drug interactions is presented. PMID:26611549

  8. Psoriatic Arthritis Registries.

    PubMed

    Sarzi-Puttini, Piercarlo; Varisco, Valentina; Ditto, Maria Chiara; Benucci, Maurizio; Atzeni, Fabiola

    2015-11-01

    The introduction of new biological drugs for the treatment of rheumatoid arthritis and spondyloarthritis has led to the creation of a number of registries in Europe and the United States. Most of them are sponsored by national rheumatology societies, and provide information that is useful in clinical practice concerning the clinical characteristics, efficacy, and safety of all licensed biological drugs. Their findings also help to improve our understanding of the quality of life and working ability of patients receiving biological drugs, and suggest methods for allocating resources. However, there are only a few registries for psoriatic arthritis, and efforts should be made to increase their number to obtain further reliable and useful data.

  9. Newer drugs for arthritis.

    PubMed

    McGillivray, D C

    1977-01-01

    The major area of new drug discoveries for the treatment of arthritis is in non-steroidal anti-inflammatory agents (NSAIA). Unfortunately, as yet no new and safe drug of major significance has appeared. Aspirin still ranks high beside the newcomers. Indomethacin, ibuprofen, naproxen, fenoprofen and tolmetin are described and their roles in therapy are discussed. A further group of older drugs receiving new application in the treatment of arthritis is presented. These include penicillamine and the immunosuppressive drugs. Gold and chloroquin are also discussed to put these agents in their proper perspective.

  10. Arthritis severity and spirochete burden are determined by serotype in the Borrelia turicatae-mouse model of Lyme disease.

    PubMed Central

    Pennington, P M; Allred, C D; West, C S; Alvarez, R; Barbour, A G

    1997-01-01

    Immunodeficient mice infected with Borrelia turicatae, a relapsing fever agent, have a disorder that resembles disseminated Lyme disease. Two serotypes, A and B, differed in their arthritogenicity in both CB-17 SCID and C3H SCID mice. In CB-17 SCID mice infected with serotype A or B, arthritis was assessed by measurement of tibiotarsal diameter, functional ability on a beam walk test, and microscopic assessment of joint inflammation. Serotype B-infected mice had greater joint swelling, functional disability, and leukocytic infiltration in the joints than serotype A-infected mice. Joint swelling and disability peaked at 2 weeks of infection and then decreased, while leukocyte infiltration in the joints persisted. To investigate the basis for the differences in arthritogenicity of serotypes A and B, spirochete burdens in infected mice were measured by quantitative PCR of spirochete DNA in joints, direct immunofluorescence of spirochetes in joints, and counts of spirochetes in the blood. At 2 weeks of infection there were seven times more spirochetes in the joints of serotype B-infected mice than in those of serotype A-infected mice, measured by both quantitative PCR and direct enumeration. Although serotypes A and B had the same infectivity and growth rate in vivo, serotype B spirochetes were eightfold more abundant in the blood than serotype A spirochetes and produced greater fatality in newborn mice. These findings indicate that differences in disease severity in mice infected with serotype A or B are attributable to differences in the spirochete burden in the joints and blood. PMID:8975925

  11. Role of Leukotriene B4 Receptors in Rheumatoid Arthritis

    PubMed Central

    Mathis, Steven; Jala, Venkatakrishna R.; Haribabu, Bodduluri

    2007-01-01

    The purpose of this review is to summarize the role that murine models of arthritis are playing in the understanding of human rheumatoid arthritis and how leukotriene B4 (LTB4) is emerging as an important target in this field. Both the collagen-induced arthritis (CIA) model and the K/BxN serum transfer arthritis model have contributed to outline the potential mechanisms involved in inflammatory arthritis. Indeed, the CIA model has contributed to the development of effective anti-TNF and anti-IL-1β based treatments for RA that are currently in the clinic. Many recent studies in mouse models have suggested a critical role for LTB4 and its receptors in the development of inflammatory arthritis. Inhibitors of LTB4 biosynthesis as well as LTB4 receptors are protective in mouse models of RA and mice deficient in the LTB4 biosynthetic enzymes or LTB4 receptors are resistant to disease development suggesting several promising targets for RA in this pathway. PMID:17967719

  12. Growth disturbances in experimental juvenile arthritis of the dog knee.

    PubMed

    Bunger, C; Bunger, E H; Harving, S; Djurhuus, J C; Jensen, O M

    1984-06-01

    In the study of pathophysiological mechanisms in growth abnormalities of the juvenile knee in arthritis an animal model in dogs was developed. Arthritis was induced by intra-articular injections of Carrageenan. Prominent growth changes were enlargement of the distal femoral epiphysis, patellar squaring and decreased endochondral and appositional growth of the distal femur. Generalized osteoporosis of the arthritic limb was present. The induced growth disturbances bear resemblance to the growth abnormalities in juvenile chronic arthritis and hemophilic arthropathy of the knee. PMID:6467860

  13. Linezolid and vancomycin decrease the therapeutic effect of methylene blue-photodynamic therapy in a mouse model of MRSA bacterial arthritis.

    PubMed

    Tanaka, Masamitsu; Mroz, Pawel; Dai, Tianhong; Huang, Liyi; Morimoto, Yuji; Kinoshita, Manabu; Yoshihara, Yasuo; Shinomiya, Nariyoshi; Seki, Shuhji; Nemoto, Koichi; Hamblin, Michael R

    2013-01-01

    We previously reported that photodynamic therapy (PDT) using intra-articular methylene blue (MB) could be used to treat arthritis in mice caused by bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) either in a therapeutic or in a preventative mode. PDT accumulated neutrophils into the mouse knee via activation of chemoattractants such as inflammatory cytokines or chemokines. In this study, we asked whether PDT combined with antibiotics used for MRSA could provide added benefit in controlling the infection. We compared MB-PDT alone, systemic administration of either linezolid (LZD) alone or vancomycin (VCM) alone or the combination of PDT with either LZD or VCM. Real-time noninvasive imaging was used to serially follow the progress of the infection. PDT alone was the most effective, whereas LZD alone was ineffective and VCM alone showed some benefit. Surprisingly the addition of LZD or VCM reduced the therapeutic effect of PDT alone (P < 0.05). Considering that PDT in this mouse model stimulates neutrophils to be antibacterial rather than actively killing the bacteria, we propose that LZD and VCM might inhibit the activation of inflammatory cytokines without eradicating the bacteria, and thereby reduce the therapeutic effect of PDT.

  14. Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration.

    PubMed

    Vugmeyster, Yulia; Wang, Qin; Xu, Xin; Harrold, John; Daugusta, Daren; Li, Jian; Zollner, Richard; Flannery, Carl R; Rivera-Bermúdez, Moisés A

    2012-03-01

    We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

  15. Effect of pine pollen extract on experimental chronic arthritis.

    PubMed

    Lee, Kyung-Hee; Choi, Eun-Mi

    2009-05-01

    The effects of pine pollen extract (PE) on Freund's complete adjuvant (FCA)-induced arthritis and collagen-induced arthritis (CIA) were investigated. The oral administration of PE (100 and 200 mg/kg per day) for 21 days after subcutaneous immunization with FCA, significantly reduced hindpaw swelling and the production of inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) compared with the FCA-induced arthritis group. Treatment with the PE (100 mg/kg) also decreased the serum levels of LDL-cholesterol and increased HDL-cholesterol contents compared with those of the arthritis group. Since CIA is a model of some types of human autoimmune rheumatoid arthritis (RA), the study examined whether PE is efficacious against CIA in mice and investigated the possible antioxidant potential of PE on CIA. Arthritis in DBA/1J mice was induced by subcutaneous immunization with bovine type II collagen. PE (100 and 200 mg/kg) was orally administered once daily for 49 days after initial immunization with type II collagen. The arthritis score and paw edema were markedly suppressed in the groups treated with PE. Moreover, administration of PE (100 mg/kg) for 49 days reduced the serum levels of rheumatoid factor, anti-type II collagen antibody, TNF-alpha, IL-1beta, IL-6, protein carbonyl, advanced glycation endproducts, malondialdehyde and LDL-cholesterol compared with that of CIA mice. These results suggest that the pine pollen might be beneficial in the treatment of chronic inflammatory disorders.

  16. Enhanced Topical Delivery of Tetrandrine by Ethosomes for Treatment of Arthritis

    PubMed Central

    Fan, Chao; Li, Xinru; Zhou, Yanxia; Zhao, Yong; Ma, Shujin; Li, Wenjing; Liu, Yan; Li, Guiling

    2013-01-01

    The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pKa = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin. PMID:24062995

  17. Enhanced topical delivery of tetrandrine by ethosomes for treatment of arthritis.

    PubMed

    Fan, Chao; Li, Xinru; Zhou, Yanxia; Zhao, Yong; Ma, Shujin; Li, Wenjing; Liu, Yan; Li, Guiling

    2013-01-01

    The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pK(a) = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin.

  18. Enhanced topical delivery of tetrandrine by ethosomes for treatment of arthritis.

    PubMed

    Fan, Chao; Li, Xinru; Zhou, Yanxia; Zhao, Yong; Ma, Shujin; Li, Wenjing; Liu, Yan; Li, Guiling

    2013-01-01

    The purpose of this work was to explore the feasibility of ethosomes for improving the antiarthritic efficacy of tetrandrine by topical application. It was found that tetrandrine was a weak base (pK(a) = 7.06) with pH-dependent partition coefficient. The spherical-shaped ethosomes were prepared by pH gradient loading method. Ex vivo permeation and deposition behavior demonstrated that the drug flux across rat skin and deposition of the drug in rat skin for ethosomes was 2.1- and 1.7-fold higher than that of liposomes, respectively. Confocal laser scanning microscopy confirmed that ethosomes could enhance the topical delivery of the drug in terms of depth and quantity compared with liposomes. The ethosomes were shown to generate substantial enhancement of therapeutic efficacy of tetrandrine on Freund's complete adjuvant-induced arthritis with regard to liposomes. These results indicated that ethosomes would be a promising carrier for topical delivery of tetrandrine into and across the skin. PMID:24062995

  19. Clinical management of septic arthritis.

    PubMed

    Sharff, Katie A; Richards, Eric P; Townes, John M

    2013-06-01

    Septic arthritis is a rheumatologic emergency as joint destruction occurs rapidly and can lead to significant morbidity and mortality. Accurate diagnosis can be particularly challenging in patients with underlying inflammatory joint disease. This review outlines the risk factors for septic arthritis and summarizes the causative bacterial organisms. We highlight advances in antibiotic management with a focus on new drugs for methicillin-resistant Staphylococcus aureus (MRSA) and discuss the use of adjunctive therapies for treatment of septic arthritis in adults.

  20. Arthritis associated with hidradenitis suppurativa.

    PubMed Central

    Bhalla, R; Sequeira, W

    1994-01-01

    OBJECTIVE--To review the presentation and clinical findings of arthritis associated with hidradenitis suppurativa. METHOD--Medical records from the rheumatology clinics of two major teaching hospitals were reviewed for arthritis and hidradenitis suppurativa. The nine patient records fulfilling these criteria were reviewed and compared with 20 previous reports. RESULTS AND CONCLUSION--The arthritis associated with hidradenitis suppurativa is rare and most commonly affects the peripheral joints. The axial skeleton is less frequently involved and is often asymptomatic. Images PMID:8311560

  1. Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats.

    PubMed

    Fahmy Wahba, Mariam Gamal; Shehata Messiha, Basim Anwar; Abo-Saif, Ali Ahmed

    2015-10-15

    Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials.

  2. Analgesic Effect of the Newly Developed S(+)‐Flurbiprofen Plaster on Inflammatory Pain in a Rat Adjuvant‐Induced Arthritis Model

    PubMed Central

    Toda, Yoshihisa; Hori, Miyuki; Mitani, Akiko; Ichihara, Takahiro; Sekine, Shingo; Hirose, Takuya; Endo, Hiromi; Futaki, Nobuko; Kaku, Shinsuke; Otsuka, Noboru; Matsumoto, Hideo

    2016-01-01

    ABSTRACT Preclinical Research This article describes the properties of a novel topical NSAID (Nonsteroidal anti‐inflammatory drug) patch, SFPP (S(+)‐flurbiprofen plaster), containing the potent cyclooxygenase (COX) inhibitor, S(+)‐flurbiprofen (SFP). The present studies were conducted to confirm human COX inhibition and absorption of SFP and to evaluate the analgesic efficacy of SFPP in a rat adjuvant‐induced arthritis (AIA) model. COX inhibition by SFP, ketoprofen and loxoprofen was evaluated using human recombinant COX proteins. Absorption of SFPP, ketoprofen and loxoprofen from patches through rat skin was assessed 24 h after application. The AIA model was induced by injecting Mycobacterium tuberculosis followed 20 days later by the evaluation of the prostaglandin PGE2 content of the inflamed paw and the pain threshold. SFP exhibited more potent inhibitory activity against COX‐1 (IC50 = 8.97 nM) and COX‐2 (IC50 = 2.94 nM) than the other NSAIDs evaluated. Absorption of SFP was 92.9%, greater than that of ketoprofen and loxoprofen from their respective patches. Application of SFPP decreased PGE2 content from 15 min to 6 h and reduced paw hyperalgesia compared with the control, ketoprofen and loxoprofen patches. SFPP showed analgesic efficacy, and was superior to the ketoprofen and loxoprofen patches, which could be through the potent COX inhibitory activity of SFP and greater skin absorption. The results suggested SFPP can be expected to exert analgesic effect clinically. Drug Dev Res 76 : 20–28, 2016. © 2016 Wiley Periodicals, Inc. PMID:26763139

  3. Arthritis in myasthenia gravis.

    PubMed

    Aarli, J A; Milde, E J; Thunold, S

    1975-11-01

    Seven patients with myasthenia gravis developed clinical signs of arthropathy. In two patients, the symptoms were due to a deforming rheumatoid arthritis and the myasthenic symptoms appeared as a transitory phase during the course of the disease. Muscle antibodies of IgG class were demonstrated with sera from both patients. Autoreactivity between muscle antibodies and rheumatoid factor was detected in one patient. Both patients died from sudden cardiac failure. Necropsy was performed in one and revealed a spotty myocardial necrosis. One patient had juvenile rheumatoid arthritis. Two patients had mild articular symptoms with indices of multivisceral disease and serological findings indicating a systemic lupus erythematous. One patient had classical ankylosing spondylitis, and one, unspecified arthropathy.

  4. Staphylococcal peptidoglycans induce arthritis

    PubMed Central

    Liu, Zai-Qing; Deng, Guo-Min; Foster, Simon; Tarkowski, Andrej

    2001-01-01

    Staphylococcus aureus is one of the most important pathogens in septic arthritis. To analyse the arthritogenic properties of staphylococcal peptidoglycan (PGN), highly purified PGN from S. aureus was intra-articularly injected into murine joints. The results demonstrate that PGN will trigger arthritis in a dose-dependent manner. A single injection of this compound leads to massive infiltration of predominantly macrophages and polymorphonuclear cells with occasional signs of cartilage and/or bone destruction, lasting for at least 14 days. Further studies showed that this condition is mediated by the combined impact of acquired and innate immune systems. Our results indicate that PGN exerts a central role in joint inflammation triggered by S. aureus. PMID:11714392

  5. [Reactive arthritis. A review].

    PubMed

    Gutiérrez, F; Espinoza, L R

    1990-07-01

    The arthritides that meet the definition or reactive arthritis include the so-called seronegative spondyloarthropathies. Patients are usually aged less than thirty-two. Preceding infection is generally intestinal or venereal, although the involved agent may remain unknown. Enteric forms occur in small epidemics, whereas venereal forms correlate with a recent new sexual partner. The clinical picture varies in severity, with manifestations overlapping between disorders, and often the first complaint is extra-articular. Highly suggestive of reactive arthritis is "sausage" deformity of fingers and toes, pain and stiffness about multiple joints accompanied by radiating lower back discomfort, and enthesitis, particularly at the Achilles tendon. One out of six or seven patients becomes disabled; therapy aimed at preventing disability is vital since medication has little effect on spinal involvement. Antibiotic therapy may be effective in cases in which specific etiologic agents are well defined.

  6. Determinants of exercise and aerobic fitness in outpatients with arthritis.

    PubMed

    Neuberger, G B; Kasal, S; Smith, K V; Hassanein, R; DeViney, S

    1994-01-01

    Factors that influenced exercise behaviors and aerobic fitness were identified in 100 outpatients with rheumatoid arthritis or osteoarthritis. Data included perceived health status, benefits of and barriers to exercise, and impact of arthritis on health; demographic and biologic characteristics; and past exercise behavior. Exercise measures included range-of-motion and strengthening exercises, 7-day activity recall, and the exercise subscale of the Health-Promoting Lifestyle Profile. An aerobic fitness level was obtained on each subject by bicycle ergometer testing. The theoretical model predicted 20% of the variance in composite exercise scores but none of the variance in aerobic fitness levels. Perceived benefits of exercise was a significant predictor of exercise participation. Subjects with less formal education, longer duration of arthritis, and higher impact of arthritis scores perceived fewer benefits of exercise, while subjects who reported exercising in their youth perceived more benefits of exercise.

  7. Rheumatoid arthritis: vocational rehabilitation.

    PubMed

    Cochrane, G M

    1982-01-01

    The consequences of inflation and accelerating introduction of automation and microprocessors into industry are a shift from unskilled to skilled work, the lessening of opportunities for the unskilled worker, and growing unemployment. If disabled people are competing for employment they must take every opportunity to extend education and acquire skills. Juvenile chronic arthritis presents one set of problems in vocational rehabilitation at the beginning of a working career and adult rheumatoid arthritis another, commonly in those over 45 years old and previously established in work. The prevalence of severe disability in juvenile chronic arthritis is about 1 in 20 000 of the population, females are affected twice as often as males and 1 in 10 has defective vision or blindness due to chronic iridocyclitis. At school, besides education, there must be emphasis on encouraging independence, self-confidence, mobility and determination. A School Leavers' Conference early in the last year at school gives the adolescent the best chance of choosing a career. Rheumatoid arthritis is three times more common in women and increasingly, over the last 40 years, women are working besides home-making. Morning stiffness, fatigue, immobility and pain are the common symptoms of widespread involvement of joints and systemic disturbance. The principal determinant in the success of vocational rehabilitation is personality, and the social and environmental factors are more significant than the degree of disability. The Disablement Resettlement Officer can assure continuity of rehabilitation between the health and employment services: a favourable outcome is work, self-derived income independence and freedom of movement using whatever technical aids are required to achieve this.

  8. Chronic arthritis in children.

    PubMed

    Prieur, A M

    1994-09-01

    Chronic inflammatory arthritides in children include a wide range of various diseases. One of the main concerns of physicians who treat these disorders is the risk of permanent physical disability resulting from joint damage. Actual classification relies mainly on clinical features, particularly the number of joints affected at onset, although the general feeling is that chronic childhood arthritis exists in many different entities gathered together under the common names juvenile chronic arthritis or juvenile rheumatoid arthritis. The past 2 years were rather fertile in debates for proposing a progression for more objectivity in nomenclature, which was the theme of the Pediatric Rheumatology Study Group session at the American College of Rheumatology annual meeting held in Atlanta in 1992. The viewpoints from North America and Europe addressed at this meeting were published in a supplement of the Journal of Rheumatology in 1993. A debate on this topic was also organized at the International League Against Rheumatism Congress held in Barcelona in 1993. At present, the main criteria rely on clinical experience and natural history of the diseases and on biology and immunogenetics. Another important concern among pediatric rheumatologists is efficacy of treatment. Questions include, "Are we doing enough?" and "How safe are the therapeutic strategies?" In this review some of the recent studies that may be important for classification and nomenclature and therapy and management are discussed.

  9. Proteomics in Rheumatoid Arthritis Research

    PubMed Central

    Park, Yune-Jung; Chung, Min Kyung; Hwang, Daehee

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common chronic inflammatory autoimmune disease, diagnosis of RA is currently based on clinical manifestations, and there is no simple, practical assessment tool in the clinical field to assess disease activity and severity. Recently, there has been increasing interest in the discovery of new diagnostic RA biomarkers that can assist in evaluating disease activity, severity, and treatment response. Proteomics, the large-scale study of the proteome, has emerged as a powerful technique for protein identification and characterization. For the past 10 years, proteomic techniques have been applied to different biological samples (synovial tissue/fluid, blood, and urine) from RA patients and experimental animal models. In this review, we summarize the current state of the application of proteomics in RA and its importance in identifying biomarkers and treatment targets. PMID:26330803

  10. Induction of lyme arthritis in LSH hamsters

    SciTech Connect

    Schmitz, J.L.; Schell, R.F.; Hejka, A.; England, D.M.; Konick, L.

    1988-09-01

    In studies of experimental Lyme disease, a major obstacle has been the unavailability of a suitable animal model. We found that irradiated LSH/Ss Lak hamsters developed arthritis after injection of Borrelia burgdorferi in the hind paws. When nonirradiated hamsters were injected in the hind paws with B. burgdorferi, acute transient synovitis was present. A diffuse neutrophilic infiltrate involved the synovia and periarticular structures. The inflammation was associated with edema, hyperemia, and granulation tissue. Numerous spirochetes were seen in the synovial and subsynovial tissues. The histopathologic changes were enhanced in irradiated hamsters. The onset and duration of the induced swelling were dependent on the dose of radiation and the inoculum of spirochetes. Inoculation of irradiated hamsters with Formalin-killed spirochetes or medium in which B. burgdorferi had grown for 7 days failed to induce swelling. This animal model should prove useful for studies of the immune response to B. burgdorferi and the pathogenesis of Lyme arthritis.

  11. Septic arthritis in adult horses.

    PubMed

    Carstanjen, B; Boehart, S; Cislakova, M

    2010-01-01

    Septic arthritis in horses is a serious disease which can become life-threatening. In case the infection can be eliminated before irreversible joint damage occurs, complete recovery is possible. This article gives an overview of the literature concerning etiology, diagnosis and strategies of therapy in cases of septic arthritis in adult horses, with special reference to novel options of treatment.

  12. Synthetic Toll-Like Receptor 4 (TLR4) and TLR7 Ligands as Influenza Virus Vaccine Adjuvants Induce Rapid, Sustained, and Broadly Protective Responses

    PubMed Central

    Goff, Peter H.; Hayashi, Tomoko; Martínez-Gil, Luis; Corr, Maripat; Crain, Brian; Yao, Shiyin; Cottam, Howard B.; Chan, Michael; Ramos, Irene; Eggink, Dirk; Heshmati, Mitra; Krammer, Florian; Messer, Karen; Pu, Minya; Fernandez-Sesma, Ana

    2015-01-01

    ABSTRACT Current vaccines against influenza virus infection rely on the induction of neutralizing antibodies targeting the globular head of the viral hemagglutinin (HA). Protection against seasonal antigenic drift or sporadic pandemic outbreaks requires further vaccine development to induce cross-protective humoral responses, potentially to the more conserved HA stalk region. Here, we present a novel viral vaccine adjuvant comprised of two synthetic ligands for Toll-like receptor 4 (TLR4) and TLR7. 1Z105 is a substituted pyrimido[5,4-b]indole specific for the TLR4-MD2 complex, and 1V270 is a phospholipid-conjugated TLR7 agonist. Separately, 1Z105 induces rapid Th2-associated IgG1 responses, and 1V270 potently generates Th1 cellular immunity. 1Z105 and 1V270 in combination with recombinant HA from the A/Puerto Rico/8/1934 strain (rPR/8 HA) effectively induces rapid and sustained humoral immunity that is protective against lethal challenge with a homologous virus. More importantly, immunization with the combined adjuvant and rPR/8 HA, a commercially available split vaccine, or chimeric rHA antigens significantly improves protection against both heterologous and heterosubtypic challenge viruses. Heterosubtypic protection is associated with broadly reactive antibodies to HA stalk epitopes. Histological examination and cytokine profiling reveal that intramuscular (i.m.) administration of 1Z105 and 1V270 is less reactogenic than a squalene-based adjuvant, AddaVax. In summary, the combination of 1Z105 and 1V270 with a recombinant HA induces rapid, long-lasting, and balanced Th1- and Th2-type immunity; demonstrates efficacy in a variety of murine influenza virus vaccine models assaying homologous, heterologous, and heterosubtypic challenge viruses; and has an excellent safety profile. IMPORTANCE Novel adjuvants are needed to enhance immunogenicity and increase the protective breadth of influenza virus vaccines to reduce the seasonal disease burden and ensure pandemic

  13. Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis.

    PubMed

    Steere, A C; Gross, D; Meyer, A L; Huber, B T

    2001-05-01

    In about 10% of patients with Lyme arthritis in the United States, joint inflammation persists for months or even several years after the apparent eradication of the spirochete, Borrelia burgdorferi, from the joint with antibiotic treatment. We propose a model of molecular mimicry affecting genetically susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1*0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface protein A OspA) of the spirochete. Using an algorithm, the immunodominant epitope of OspA presented by the DRB1*0401 molecule was predicted to be located at aa 165-173. In a search of the Genetics Computer Group gene bank, only one human protein was identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence homology with OspA(165-173)and predicted binding in the DRB1*0401 molecule. Synovial fluid T cells from most patients with treatment-resistant arthritis responded to both OspA and hLFA-1, whereas those from patients with other forms of chronic inflammatory arthritis did not. Molecular mimicry between a dominant T cell epitope of OspA and hLFA-1 may be an important factor in the persistence of joint inflammation in genetically susceptible patients with treatment-resistant Lyme arthritis.

  14. 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.

  15. Effects of a mixture of fatty acids from sugar cane (Saccharum officinarum L.) wax oil in two models of inflammation: zymosan-induced arthritis and mice tail test of psoriasis.

    PubMed

    Ledón, N; Casacó, A; Remirez, D; González, A; Cruz, J; González, R; Capote, A; Tolón, Z; Rojas, E; Rodríguez, V J; Merino, N; Rodríguez, S; Ancheta, O; Cano, M C

    2007-10-01

    A mixture of fatty acids obtained from sugar cane (Saccharum officinarum L.) wax oil (FAM), in which the main constituents are palmitic, oleic, linoleic, and linolenic acids, was evaluated in two models of inflammation: zymosan-induced arthritis and in the tail test for psoriasis, both on mice. In the first model, FAM significantly reduced zymozan-induced increase of beta glucuronidase (DE(50) 90+/-7 mg/kg). Histopathological studies showed inhibition in cellular infiltration and reduction of synovial hyperplasia and synovitis, whereas in the second test, histopathological and ultrastructural studies showed that topical application of FAM induced orthokeratosis with the presence of keratohyalin granules in the previously parakeratotic adult mouse tail, and without effects on epidermal thickness. The ED(50) of FAM in this model was 155+/-10 mg. The results of our studies showed that topical application of FAM exerts an important anti-inflammatory activity in both tests without evidence of irritant effects. The anti-inflamatory effects exerted by FAM may be due to its inhibitory effects on arachidonic acid metabolism. To our knowledge, this is the first report on the anti-inflammatory effect of sugar cane by-products in experimental models of arthritis and psoriasis.

  16. Multifunctional nanoparticles co-delivering Trp2 peptide and CpG adjuvant induce potent cytotoxic T-lymphocyte response against melanoma and its lung metastasis.

    PubMed

    Xu, Zhenghong; Ramishetti, Srinivas; Tseng, Yu-Cheng; Guo, Shutao; Wang, Yuhua; Huang, Leaf

    2013-11-28

    Immunotherapy has shown the potential to become an essential component of the successful treatment of various malignancies. In many cases, such as in melanoma, however, induction of a potent and specific T-cell response against the endogenous antigen or self-antigen still remains a major challenge. To induce a potent MHC I-restricted cytotoxic T-lymphocyte (CTL) response, cytosol delivery of an exogenous antigen into dendritic cells is preferred, if not required. Lipid-calcium-phosphate (LCP) nanoparticles represent a new class of intracellular delivery systems for impermeable drugs. We are interested in exploring the potential of LCP NPs for use as a peptide vaccine delivery system for cancer therapy. To increase the encapsulation of Trp2 peptide into the calcium phosphate precipitate core of LCP, two phosphor-serine residues were added to the N-terminal of the peptide (p-Trp2). CpG ODN was also co-encapsulated with p-Trp2 as an adjuvant. The NPs were further modified with mannose to enhance and prolong the cargo deposit into the lymph nodes (LNs), which ensured persistent antigen loading and stimulation. Compared with free Trp2 peptide/CpG, vaccination with LCP encapsulating p-Trp2 and CpG resulted in superior inhibition of tumor growth in both B16F10 subcutaneous and lung metastasis models. An IFN-γ production assay and in vivo CTL response study revealed that the improved efficacy was a result of a Trp2-specific immune response. Thus, encapsulation of phospho-peptide antigens into LCP may be a promising strategy for enhancing the immunogenicity of poorly immunogenic self-antigens for cancer therapy.

  17. Autoantibodies in inflammatory arthritis.

    PubMed

    Conigliaro, P; Chimenti, M S; Triggianese, P; Sunzini, F; Novelli, L; Perricone, C; Perricone, R

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

  18. Automation of arthritis measures in hand radiographs

    NASA Astrophysics Data System (ADS)

    Levitt, Tod S.; Hedgcock, Marcus W.; Dye, John; Johnston, Scott E.

    1990-07-01

    Hand radiographs provide a valuable index of disease in arthritis and other generalized diseases such as secondary hyperparathyroidism and osteoporosis. Measures such as cortical volume intercortical width average and periarticular demineralization provide diagnostic indicators for these diseases. However visual analysis of hand radiographs is not quantitative and is compromised by both interobserver and intraobserver variation. Automation of these measures would provide repeatable comparable quantities to assist in diagnosis and disease and therapy monitoring. The computer calculations to perform these measures are straightforward. The key problem is automatic segmentation of the hand anatomy that is recognizing the pixels that correspond to specific imaged bones and joints. Our approach incorporates computer-represented hand models in addition to more traditional image processing algorithms. We describe our techniques for using a combination of predictive models and image processing evidence to automatically fmd bone and tissue boundaries and identify specific bone and joints. 2. COMPUTING ARTHRITIS MEASURES Digital scanners and radiograph digitizers make the radiograph available as a data source for computer algorithms that analyze medical imagery. This is significant because radiographs comprise more than 80 of all medical imagery at this time and they are considerably quicker and less costly than other digital modalities such as CT and Mill. Quantitative measures from digital radiographs can aid physicians in diagnosis tracking disease progress and in therapy planning and evaluation. We have begun studying diagnostic measures in arthritis

  19. The involvement of heat-shock proteins in the pathogenesis of autoimmune arthritis: a critical appraisal

    PubMed Central

    Huang, Min-Nung; Yu, Hua; Moudgil, Kamal D.

    2012-01-01

    Objectives To review the literature on the role of heat-shock proteins (HSPs) in the pathogenesis of autoimmune arthritis in animal models ans patients with rheumatoid arthritis (RA). Methods The published literature in Medline (PubMed), including our published work on the cell-mediated as well as humoral immune response to various HSPs was reviewed. Studies in both the pre-clinical animal models of arthritis as well as RA were examined critically and the data presented. Results In experimental arthritis, disease induction by different arthritogenic stimuli, including an adjuvant, led to immune response to mycobacterial HSP65 (BHSP65). However, attempts to induce arthritis by a purified HSP have not met with success. There are several reports of a significant immune response to HSP65 in RA patients. But, the issue of cause and effect is difficult to address. Nevertheless, several studies in animal models and a couple of clinical trials in RA patients have shown the beneficial effect of HSPs against autoimmune arthritis. Conclusions There is a clear association between immune response to HSPs, particularly HSP65, and the initiation and propagation of autoimmune arthritis in experimental models. The correlation is relatively less convincing in RA patients. In both cases, the ability of HSPs to modulate arthritis offers support, albeit an indirect one, for the involvement of these antigens in the disease process. PMID:19969325

  20. Management of septic arthritis.

    PubMed

    Shetty, Avinash K; Gedalia, Abraham

    2004-09-01

    Septic arthritis in children remains a serious disease with the potential for significant systemic and musculoskeletal morbidity. Staphlococcus aureus is the most common cause of bone and joint infections in all age groups. Microbial invasion of the synovial space occurs typically results from hematogenous seeding. Diagnosis in neonates and young infants can be difficult since the clinical signs are much less specific in these age groups. Early diagnosis by needle aspiration of the affected joint and prompt initiation of appropriate antimicrobial therapy in conjunction with drainage of the affected joint is critical to avoid destruction of the articular cartilage and prevent disability. Septic arthritis in infants and children should always be managed by a pediatrician in close consultation with an orthopedic surgeon. Empiric antibiotic regimens should always include adequate anti-staphylococcal coverage. Antibiotic treatment should be started with appropriate doses of intravenous antibiotics. Switch to oral antibiotic therapy can be made when patient demonstrates clinical improvement. A minimum of 3-4 weeks of therapy is recommended. Close follow-up is warranted to monitor the growth of the affected limb until skeletal maturity.

  1. Role of NMDA receptors in the trigeminal pathway, and the modulatory effect of magnesium in a model of rat temporomandibular joint arthritis.

    PubMed

    Cavalcante, André L C; Siqueira, Rafaelly M P; Araujo, Joana C B; Gondim, Delane V; Ribeiro, Ronaldo A; Quetz, Josiane S; Havt, Alexandre; Lima, Aldo A M; Vale, Mariana L

    2013-12-01

    Temporomandibular joint (TMJ) arthritis is a common cause of orofacial pain. In the present study, the modulatory effects of N-methyl-d-aspartate receptors (NMDA-Rs) and magnesium were investigated in TMJ arthritis hypernociception. Male Wistar rats received an intra-articular injection of carrageenan (Cg) in the TMJ, and mechanical hypernociception was measured. The NMDA-R antagonist, MK-801, and magnesium chloride (MgCl₂ ) were administered before arthritis induction. Magnesium deficiency was promoted by feeding rats a synthetic magnesium-free diet for 9 d before injection of Cg. The Cg induced mechanical hypernociception that lasted for 120 h. MK-801 inhibited this hypernociceptive state. MgCl₂ pretreatment prevented Cg-induced hypernociception and altered the nociceptive threshold in the absence of Cg. Magnesium deficiency increased hypernociception and induced spontaneous hypernociceptive behavior. TMJ arthritis increased the expression of mRNA for all NMDA-R subunits and immunostaining of phosphorylated NR1 (phospho-NR1). MgCl₂ inhibited expression of NR2B mRNA and phospho-NR1 immunostaining and increased expression of NR3 mRNA. Magnesium deficiency increased expression of both NR1 and NR3 mRNAs and phospho-NR1 immunostaining in the trigeminal subnucleus caudalis. We found that magnesium modulates nociceptive behavior and induces NMDA-R subunit rearrangement in the subnucleus caudalis. The present results may lead to a better understanding of central processing in the nociceptive trigeminal pathway and the development of new approaches to treat orofacial pain with a TMJ origin.

  2. Anti-proliferative effects of Salacia reticulata leaves hot-water extract on interleukin-1β-activated cells derived from the synovium of rheumatoid arthritis model mice

    PubMed Central

    2012-01-01

    Background Salacia reticulata (SR) is a plant native to Sri Lanka. In ayurvedic medicine, SR bark preparations, taken orally, are considered effective in the treatment of rheumatism and diabetes. We investigated the ability of SR leaves (SRL) to inhibit in vitro the interleukin-1β (IL-1β)-activated proliferation of synoviocyte-like cells derived from rheumatoid arthritis model mice. Findings Inflammatory synovial tissues were harvested from type II collagen antibody-induced arthritic mice. From these tissues, a synoviocyte-like cell line was established and named MTS-C H7. To determine whether SRL can suppress cell proliferation and gene expression in MTS-C H7 cells, fractionation of the SRL hot-water extract was performed by high-performance liquid chromatography (HPLC), liquid-liquid extraction, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), and protease digestion. The 50% inhibitory concentration of the SRL hot-water extract against MTS-C H7 cells proliferation was ~850 μg/mL. Treatment with a low dose (25 μg dry matter per millilitre) of the extract inhibited IL-1β-induced cell proliferation and suppressed the expression of the matrix metalloproteinase (MMP) genes in MTS-C H7 cells. Various polyphenolic fractions obtained from HPLC and the fractions from liquid-liquid extraction did not affect cell proliferation. Only the residual water sample from liquid-liquid extraction significantly affected cell proliferation and the expression of MMP genes. The results of SDS-PAGE and protease digestion experiment showed that low molecular weight proteins present in SRL inhibited the IL-1β-activated cell proliferation. Conclusions We surmised that the residual water fraction of the SRL extract was involved in the inhibition of IL-1β-activated cell proliferation and regulation of mRNA expression in MTS-C H7 cells. In addition, we believe that the active ingredients in the extract are low molecular weight proteins. PMID:22537486

  3. Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis.

    PubMed

    Song, Jialin; Chen, Yinghui; Jiang, Shichao; Yang, Kejia; Li, Xiaoming; Zhao, Xiaotian; Ouyang, Yuanming; Fan, Cunyi; Yuan, Weien

    2016-01-01

    Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. PMID:27594856

  4. Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis

    PubMed Central

    Song, Jialin; Chen, Yinghui; Jiang, Shichao; Yang, Kejia; Li, Xiaoming; Zhao, Xiaotian; Ouyang, Yuanming; Fan, Cunyi; Yuan, Weien

    2016-01-01

    Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA. PMID:27594856

  5. Efficient and Non-Toxic Biological Response Carrier Delivering TNF-α shRNA for Gene Silencing in a Murine Model of Rheumatoid Arthritis

    PubMed Central

    Song, Jialin; Chen, Yinghui; Jiang, Shichao; Yang, Kejia; Li, Xiaoming; Zhao, Xiaotian; Ouyang, Yuanming; Fan, Cunyi; Yuan, Weien

    2016-01-01

    Small interfering RNA (siRNA) is an effective and specific method for silencing genes. However, an efficient and non-toxic carrier is needed to deliver the siRNA into the target cells. Tumor necrosis factor α (TNF-α) plays a central role in the occurrence and progression of rheumatoid arthritis (RA). In this study, we pre-synthetized a degradable cationic polymer (PDAPEI) from 2,6-pyridinedicarboxaldehyde and low-molecular-weight polyethyleneimine (PEI, Mw = 1.8 kDa) as a gene vector for the delivery of TNF-α shRNA. The PDAPEI/pDNA complex showed a suitable particle size and stable zeta potential for transfection. In vitro study of the PDAPEI/pDNA complex revealed a lower cytotoxicity and higher transfection efficiency when transfecting TNF-α shRNA to macrophages by significantly down-regulating the expression of TNF-α. Moreover, the complex was extremely efficient in decreasing the severity of arthritis in mice with collagen-induced arthritis. PDAPEI delivered TNF-α shRNA has great potential in the treatment of RA.

  6. Pregnancy amelioration of arthritis in SKG mice corresponds with alterations in serum amyloid A3 levels

    PubMed Central

    Shaw, Laura A; Stefanski, Adrianne L; Peterson, Lisa K; Rumer, Kristen K; Vondracek, Andrea; Phang, Tzu L; Sakaguchi, Shimon; Winn, Virginia D; Dragone, Leonard L

    2012-01-01

    Objectives: Pregnancy leads to rheumatoid arthritis remission in humans. The objective of this study was to determine if the SKG mouse could serve as a model for pregnancy-associated inflammatory arthritis amelioration. In addition, the maternal peripheral blood mononuclear cell (PBMC) transcriptome was assessed to define a biomarker associated with remission. Methods: Cohorts of zymosan-treated pregnant SKG mice and controls were monitored for arthritis progression. Microarray analysis evaluated alterations in gene expression in maternal PBMCs at embryonic day 14.5 (E14.5) between arthritic and pregnancy-remitted mice. A selected target, serum amyloid A3 (SAA3), was further investigated using quantitative reverse transcriptase PCR (qRT-PCR) and an enzyme-linked immunosorbent assay (ELISA). Results: Pregnancy resulted in complete or partial remission in the majority of the zymosan-treated SKG mice. Twenty-seven transcripts were differentially expressed in the PBMCs between arthritic and pregnancy-remitted mice. Expression and plasma SAA3 levels decreased with pregnancy-induced arthritis amelioration and plasma SAA3 levels correlated with arthritis severity. Conclusions: These results establish the SKG mouse as a model system to study pregnancy-induced amelioration of arthritis. These studies also establish SAA3 as a biomarker of arthritis amelioration in SKG mice. This model can be used to elucidate the molecular and cellular mechanisms underlying the impact of pregnancy on the maternal immune system that results in arthritis amelioration. PMID:23097751

  7. Immunomodulation of Autoimmune Arthritis by Herbal CAM

    PubMed Central

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

    2011-01-01

    Rheumatoid arthritis (RA) is a debilitating autoimmune disease of global prevalence. The disease is characterized by synovial inflammation leading to cartilage and bone damage. Most of the conventional drugs used for the treatment of RA have severe adverse reactions and are quite expensive. Over the years, increasing proportion of patients with RA and other immune disorders are resorting to complementary and alternative medicine (CAM) for their health needs. Natural plant products comprise one of the most popular CAM for inflammatory and immune disorders. These herbal CAM belong to diverse traditional systems of medicine, including traditional Chinese medicine, Kampo, and Ayurvedic medicine. In this paper, we have outlined the major immunological pathways involved in the induction and regulation of autoimmune arthritis and described various herbal CAM that can effectively modulate these immune pathways. Most of the information about the mechanisms of action of herbal products in the experimental models of RA is relevant to arthritis patients as well. The study of immunological pathways coupled with the emerging application of genomics and proteomics in CAM research is likely to provide novel insights into the mechanisms of action of different CAM modalities. PMID:21234398

  8. CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage

    PubMed Central

    Chang, Yan; Jia, Xiaoyi; Wei, Fang; Wang, Chun; Sun, Xiaojing; Xu, Shu; Yang, Xuezhi; Zhao, Yingjie; Chen, Jingyu; Wu, Huaxun; Zhang, Lingling; Wei, Wei

    2016-01-01

    Paeoniflorin-6′-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin (Pae), was evaluated in rats with adjuvant-induced arthritis (AA) to study its potential anti-arthritic activity. AA rats were treated with CP-25 (25, 50, or 100 mg/kg) from days 17 to 29 after immunization. CP-25 effectively reduced clinical and histopathological scores compared with the AA groups. CP-25-treated rats exhibited decreases in pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) coupled with an increase in the anti-inflammatory cytokine TGF-β1 in the serum. CP-25 treatment inhibited M1 macrophage activation and enhanced M2 macrophage activation by influencing cytokine production. Decreases in Th17-IL-17 and the Th17-associated transcription factor RAR-related orphan receptor gamma (ROR-γt) dramatically demonstrated the immunomodulatory effects of CP-25 on abnormal immune dysfunction. In addition, CP-25 suppressed the production of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase (MMP) 9, which supported its anti-osteoclastic effects. The data presented here demonstrated that CP-25 significantly inhibited the progression of rat AA by reducing inflammation, immunity and bone damage. The protective effects of CP-25 in AA highlight its potential as an ideal new anti-arthritic agent for human RA. PMID:27184722

  9. CP-25, a novel compound, protects against autoimmune arthritis by modulating immune mediators of inflammation and bone damage.

    PubMed

    Chang, Yan; Jia, Xiaoyi; Wei, Fang; Wang, Chun; Sun, Xiaojing; Xu, Shu; Yang, Xuezhi; Zhao, Yingjie; Chen, Jingyu; Wu, Huaxun; Zhang, Lingling; Wei, Wei

    2016-05-17

    Paeoniflorin-6'-O-benzene sulfonate (code: CP-25), a novel ester derivative of paeoniflorin (Pae), was evaluated in rats with adjuvant-induced arthritis (AA) to study its potential anti-arthritic activity. AA rats were treated with CP-25 (25, 50, or 100 mg/kg) from days 17 to 29 after immunization. CP-25 effectively reduced clinical and histopathological scores compared with the AA groups. CP-25-treated rats exhibited decreases in pro-inflammatory cytokines (IL-1β, IL-6, IL-17 and TNF-α) coupled with an increase in the anti-inflammatory cytokine TGF-β1 in the serum. CP-25 treatment inhibited M1 macrophage activation and enhanced M2 macrophage activation by influencing cytokine production. Decreases in Th17-IL-17 and the Th17-associated transcription factor RAR-related orphan receptor gamma (ROR-γt) dramatically demonstrated the immunomodulatory effects of CP-25 on abnormal immune dysfunction. In addition, CP-25 suppressed the production of receptor activator of nuclear factor kappa B ligand (RANKL) and matrix metalloproteinase (MMP) 9, which supported its anti-osteoclastic effects. The data presented here demonstrated that CP-25 significantly inhibited the progression of rat AA by reducing inflammation, immunity and bone damage. The protective effects of CP-25 in AA highlight its potential as an ideal new anti-arthritic agent for human RA.

  10. Rheumatoid arthritis and ocular involvement.

    PubMed

    Shaw, Chittaranjan; Banik, Sujoy; Islam, Md Nazarul; Biswas, Mukul Chandra; Biswas, Gautam; Biswas, Sobhan

    2003-09-01

    To study the occurrence and incidence of different ocular manifestations in rheumatoid arthritis a random cross-sectional study was carried out among 54 patients with active rheumatoid arthritis. The patients were examined thoroughly to detect any ocular disease associated with rheumatoid arthritis. Complete ocular examination with special emphasis on anterior segment evaluation and tearfilm study was done. Two-thirds of the patients examined had some kind of visual problem at presentation. Three patients (5.55%) had marked dry eye with another 20 (37.03%) having borderline tear deficiency. Two cases ( 3.70% ) of episcleritis were also seen. No cases of scleritis or retinopathy were found. The most common ocular association with rheumatoid arthritis was secondary Sjogren's syndrome. Other conditions include episcleritis and marginal keratitis.

  11. Stay active and exercise - arthritis

    MedlinePlus

    ... your overall health and sense of well-being. Exercise keeps your muscles strong and increases your range ... Water exercises may be the best exercise for your arthritis. Swimming laps, water aerobics, or even just walking in ...

  12. Therapy strategies in psoriatic arthritis.

    PubMed

    Coates, Laura C

    2015-01-01

    Psoriatic arthritis (PsA) is a heterogeneous condition with a myriad of different clinical presentations. It commonly affects the skin and musculoskeletal system causing psoriasis, peripheral arthritis, axial arthritis, enthesitis and dactylitis. Many patients also have related conditions, such as those within the metabolic syndrome and associated spondyloarthritis (SpA) conditions including inflammatory bowel disease and uveitis. Any therapeutic strategy must be tailored to the individual patient, taking into account her/his complete clinical presentation and comorbidities. New treatment recommendations from the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) provide evidence based recommendations on effective therapies for the management of each different manifestation of PsA, and how treatment may be affected by comorbidities (1). However, the limited evidence comparing different treatment strategies in PsA is recognised as a limitation in these recommendations and further information is detailed below.

  13. Alternative for Anti-TNF Antibodies for Arthritis Treatment

    PubMed Central

    Paquet, Joseph; Henrionnet, Christel; Pinzano, Astrid; Vincourt, Jean-Baptiste; Gillet, Pierre; Netter, Patrick; Chary-Valckenaere, Isabelle; Loeuille, Damien; Pourel, Jacques; Grossin, Laurent

    2011-01-01

    Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α remain refractory or become nonresponder to these treatments. In this context, there is a need for new or complementary therapeutic strategies. In this study, we investigated in vitro and in vivo anti-inflammatory potentialities of an anti-TNF-α triplex-forming oligonucleotide (TFO), as judged from effects on two rat arthritis models. The inhibitory activity of this TFO on articular cells (synoviocytes and chondrocytes) was verified and compared to that of small interfering RNA (siRNA) in vitro. The use of the anti-TNF-α TFO as a preventive and local treatment in both acute and chronic arthritis models significantly reduced disease development. Furthermore, the TFO efficiently blocked synovitis and cartilage and bone destruction in the joints. The results presented here provide the first evidence that gene targeting by anti-TNF-α TFO modulates arthritis in vivo, thus providing proof-of-concept that it could be used as therapeutic tool for TNF-α-dependent inflammatory disorders. PMID:21811249

  14. Alternative for anti-TNF antibodies for arthritis treatment.

    PubMed

    Paquet, Joseph; Henrionnet, Christel; Pinzano, Astrid; Vincourt, Jean-Baptiste; Gillet, Pierre; Netter, Patrick; Chary-Valckenaere, Isabelle; Loeuille, Damien; Pourel, Jacques; Grossin, Laurent

    2011-10-01

    Tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, plays a key role in the pathogenesis of many inflammatory diseases, including arthritis. Neutralization of this cytokine by anti-TNF-α antibodies has shown its efficacy in rheumatoid arthritis (RA) and is now widely used. Nevertheless, some patients currently treated with anti-TNF-α remain refractory or become nonresponder to these treatments. In this context, there is a need for new or complementary therapeutic strategies. In this study, we investigated in vitro and in vivo anti-inflammatory potentialities of an anti-TNF-α triplex-forming oligonucleotide (TFO), as judged from effects on two rat arthritis models. The inhibitory activity of this TFO on articular cells (synoviocytes and chondrocytes) was verified and compared to that of small interfering RNA (siRNA) in vitro. The use of the anti-TNF-α TFO as a preventive and local treatment in both acute and chronic arthritis models significantly reduced disease development. Furthermore, the TFO efficiently blocked synovitis and cartilage and bone destruction in the joints. The results presented here provide the first evidence that gene targeting by anti-TNF-α TFO modulates arthritis in vivo, thus providing proof-of-concept that it could be used as therapeutic tool for TNF-α-dependent inflammatory disorders.

  15. Photoacoustic imaging: a potential new tool for arthritis

    NASA Astrophysics Data System (ADS)

    Wang, Xueding

    2012-12-01

    The potential application of photoacoustic imaging (PAI) technology to diagnostic imaging and therapeutic monitoring of inflammatory arthritis has been explored. The feasibility of our bench-top joint imaging systems in delineating soft articular tissue structures in a noninvasive manner was validated first on rat models and then on human peripheral joints. Based on the study on commonly used arthritis rat models, the capability of PAI to differentiate arthritic joints from the normal was also examined. With sufficient imaging depth, PAI can realize tomographic imaging of a human peripheral joint or a small-animal joint as a whole organ noninvasively. By presenting additional optical contrast and tissue functional information such as blood volume and blood oxygen saturation, PAI may provide an opportunity for early diagnosis of inflammatory joint disorders, e.g. rheumatoid arthritis, and for monitoring of therapeutic outcomes with improved sensitivity and accuracy.

  16. T Regulatory Cell Numbers and Function in Patients with Antibiotic-Refractory or Antibiotic-Responsive Lyme Arthritis

    PubMed Central

    Shen, Shiqian; Shin, Junghee J.; Strle, Klemen; McHugh, Gail; Li, Xin; Glickstein, Lisa J.; Drouin, Elise E.; Steere, Allen C.

    2010-01-01

    Objective In a murine model of antibiotic-refractory Lyme arthritis, the numbers of T regulatory cells (Treg) are dramatically reduced. Our goal was to examine Treg numbers and function in human patients with antibiotic-refractory Lyme arthritis. Methods CD4+ T cell subsets were enumerated in peripheral blood (PB) and synovial fluid (SF) in 12 patients with antibiotic-refractory arthritis and 6 with antibiotic-responsive arthritis. Treg function was examined using Borrelia-specific and non-specific Treg proliferation assays. Results In both patient groups, IFN-γ+ TH1 cells in SF were abundant and enriched (~50% of CD4+ T cells). In patients with antibiotic-refractory arthritis, the median percentages of FoxP3+ Treg were significantly higher in SF than PB (12% versus 6%) (P<0.01) or in SF in patients with antibiotic-responsive arthritis (12% versus 5%) (P=0.04). Moreover, in the refractory group, a higher percentage of Treg in SF correlated with a shorter duration to resolution of arthritis (r = −0.74, P = 0.006). In contrast, patients with fewer Treg had suboptimal responses to DMARDs and longer duration of arthritis after antibiotics, and they often required synovectomies for arthritis resolution. In each group, Treg in SF dampened B. burgdorferi-specific proliferative responses, and in 2 patients with refractory arthritis, Treg were functional in non-specific suppression assays. Conclusions Treg were functional in patients with antibiotic-refractory arthritis, and in some patients, large numbers of these cells in SF appeared to participate in arthritis resolution. However, as in the murine model, patients with refractory arthritis and low numbers of Treg seemed unable to resolve synovial inflammation. PMID:20506317

  17. [Rheumatoid arthritis and cytokines].

    PubMed

    Kaneko, Shunta; Kondo, Yuya; Yokosawa, Masahiro; Sumida, Takayuki

    2016-06-01

    The cytokines are an important substance involved in the immune reaction and maintenance of homeostasis. An imbalance in the cytokine network may lead to inflammation and autoimmune diseases such as rheumatoid arthritis (RA). RA is an autoimmune and systemic inflammatory disorder characterized by synovial inflammation, destruction of cartilage and bone and systemic manifestations. The pro-inflammatory cytokines such as tumor necrosis factor α (TNFα), interleukin-1 (IL-1), IL-6 and IL-17 induce the inflammation of the joints and destruction of bone and cartilage via activation of macrophages, fibroblast like synoviocytes (FLS), helper T (Th) cells and osteoclasts. Recently, the available therapeutic agents that target these cytokines have excellent clinical effects in RA patients.

  18. Physiotherapy in rheumatoid arthritis.

    PubMed

    Kavuncu, Vural; Evcik, Deniz

    2004-01-01

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented. PMID:15266230

  19. [Septic arthritis in adults].

    PubMed

    Loock, J; Haustedt, N; Wollenhaupt, J

    2014-09-01

    Septic arthritis is a true rheumatological emergency requiring immediate and thoughtful effort for rapid diagnosis establishment and treatment initiation. Children and elderly persons as well as immunocompromised individuals, patients with pre-existing joint damage and with inflammatory rheumatic joint diseases are preferentially affected. Bacteremia, joint surgery and intra-articular injections pose risk situations for the development of joint infections. The most frequent causative organism is Staphylococcus aureus but other relevant pathogens include coagulase-negative staphylococci, streptococci and mycobacteria. Synovial fluid analysis (e.g. appearance, cell count and microbiological examination) is the most important step to establish the diagnosis. The two main components of therapy consist of joint drainage and antibiotic treatment. The approach to periprosthetic joint infections depends on the duration of symptoms, causative organism and individual factors.

  20. Physiotherapy in rheumatoid arthritis.

    PubMed

    Kavuncu, Vural; Evcik, Deniz

    2004-05-17

    Rheumatoid arthritis (RA) is a chronic and painful clinical condition that leads to progressive joint damage, disability, deterioration in quality of life, and shortened life expectancy. Even mild inflammation may result in irreversible damage and permanent disability. The clinical course according to symptoms may be either intermittent or progressive in patients with RA. In most patients, the clinical course is progressive, and structural damage develops in the first 2 years. The aim of RA management is to achieve pain relief and prevent joint damage and functional loss. Physiotherapy and rehabilitation applications significantly augment medical therapy by improving the management of RA and reducing handicaps in daily living for patients with RA. In this review, the application of physiotherapy modalities is examined, including the use of cold/heat applications, electrical stimulation, and hydrotherapy. Rehabilitation treatment techniques for patients with RA such as joint protection strategies, massage, exercise, and patient education are also presented.

  1. Juvenile idiopathic arthritis.

    PubMed

    Espinosa, Maria; Gottlieb, Beth S

    2012-07-01

    Juvenile idiopathic arthrithis (JIA) is the most common rheumatic disease of childhood.JIA is a chronic disease that is associated with periods of disease flares and periods of disease inactivity.Early, aggressive treatment with nonsteroidal anti-inflammatory drugs, intra-articular corticosteroid injections, or methotrexate, has significantly improved the outcome of most children who have JIA. Biologics have been shown to be both safe and effective for the treatment of more aggressive forms of arthritis and for uveitis. Long-term safety data of biologics is still uncertain. In the near future, it is hoped that genetic testing will allow earlier diagnosis of JIA as well as help predict the disease course of children who have JIA. Genetic analysis also may allow physicians to target therapies more effectively. It is hoped that development of more specific therapies will decrease overall immunosuppression and other associated toxicities.

  2. HLA-linked rheumatoid arthritis

    SciTech Connect

    Hasstedt, S.J.; Clegg, D.O.; Ingles, L.; Ward, R.H.

    1994-10-01

    Twenty-eight pedigrees were ascertained through pairs of first-degree relatives diagnosed with rheumatoid arthritis (RA). RA was confirmed in 77 pedigree members including probands; the absence of disease was verified in an additional 261 pedigree members. Pedigree members were serologically typed for HLA. We used likelihood analysis to statistically characterize the HLA-linked RA susceptibility locus. The genetic model assumed tight linkage to HLA. The analysis supported the existence of an HLA-linked RA susceptibility locus, estimated the lifetime penetrance as 41% in male homozygotes and as 48% in female homozygotes. Inheritance was recessive in males and was nearly recessive in females. In addition, the analysis attributed 78% of the variance within genotypes to genetic or environmental effects shared by siblings. The genetic model inferred in this analysis is consistent with previous association, linkage, and familial aggregation studies of RA. The inferred HLA-linked RA susceptibility locus accounts for approximately one-fifth of the RA in the population. Although other genes may account for the remaining familial RA, a large portion of RA cases may occur sporadically. 79 refs., 9 tabs.

  3. [Personalized Medicine in Rheumatoid Arthritis].

    PubMed

    Kumagai, Shunichi

    2015-10-01

    Medical strategy for rheumatoid arthritis (RA) has markedly advanced in recent years. The introductions of biologics and methotrexate as an anchor drug have made it possible to not only suppress pain and inflammation (clinical remission), but also to inhibit joint destruction (structural remission), leading to cure of the disease. In order to achieve this target, it is the most important to diagnose RA early and promote disease remission. However, since the condition and pathology are diverse among patients, optimal treatment for each patient is desired (personalized medicine). Treatment should be performed under consideration of the disease state such as activity, prognosis regarding joint destruction, and complications. It is also important to clarify the patient characteristics, such as responsiveness to the drugs and risk of adverse effects. Biomarkers, such as proteomics and pharmacogenomics (genetic polymorphism, etc.), are indispensable for personalized medicine. We have established a predictive model for methotrexate hepatotoxicity, consisting of 13 SNPs with a sensitivity of 100% and specificity of 89%, although the model should be validated with a larger-scale prospective study. RA is a multifactorial disorder with clinically heterogeneous features. Gene-environment interaction is closely involved in the production of anti-CCP antibodies (ACPA); thereafter, secondary stimuli of joints may lead to symptoms of RA. Joint injury, emotional stress, and infections often trigger the onset of RA. Cure can be achieved through complete remission by early aggressive treatment and returning to the pre-clinical state of RA with environmental improvement.

  4. Efficacy of ultrasound mediated microbubbles in diclofenac gel to enhance transdermal permeation in rheumatoid arthritis induced rat.

    PubMed

    Liao, A H; Chuang, H C; Chung, H Y

    2015-08-01

    In previous study in the literature, the effect of ultrasound on the transdermal permeation of the nonsteroidal anti-inflammatory drug, diclofenac has been investigated. Therapeutic ultrasound can increase circulation in the inflamed joint and decrease arthritic pain. Recently, transdermal drug delivery has been demonstrated by ultrasound (US) combining with microbubbles (MBs) contrast agent. In this study, the efficiency of US-MBs mediated diclofenac delivery for adjuvant-induced rheumatoid arthritis (RA) in rats was evaluated. RA was induced by injection of 100 μl Freund's complete adjuvant into the ankle joint in SD male rats (250-300g) and were randomly divided into five groups: (1) control group (C); (2) penetrating diclofenac alone (D); (3) US alone (U); (4) US combined with penetrating diclofenac (DU); (5) US combined with MBs and penetrating diclofenac (DUB). The evaluations of ankle width were performed for 10 days by high frequency (40MHz) US B-mode and color Doppler mode imaging before and after treatment. Longitudinal US images of arthritis induced show synovitis and neovascularity. After treatment, only a little neovascularity has been observed. The recovery rate at 10th day in the group DUB (97.7±2.7 %) was significantly higher than in the group C (1.0±2.7 %), group D (37.5±4.6 %), group U (75.5±4.2 %) and group DU (87.3±5.2 %) (p <; 0.05). Our results investigated that the treatments of US and MBs can increase skin permeability to enhance diclofenac sodium delivery and inhibit inflammation of the tissues surrounded the arthritic ankle. In color Doppler imaging, after the combination treatment, the synovial neoangiogenesis in the arthritic area was reduced quickly.

  5. Alternative complement pathway activation is essential for inflammation and joint destruction in the passive transfer model of collagen-induced arthritis.

    PubMed

    Banda, Nirmal K; Thurman, Joshua M; Kraus, Damian; Wood, Allyson; Carroll, Michael C; Arend, William P; Holers, V Michael

    2006-08-01

    Activation of each complement initiation pathway (classical, alternative, and lectin) can lead to the generation of bioactive fragments with resulting inflammation in target organs. The objective of the current study was to determine the role of specific complement activation pathways in the pathogenesis of experimental anti-type II collagen mAb-passive transfer arthritis. C57BL/6 mice were used that were genetically deficient in either the alternative pathway protein factor B (Bf(-/-)) or in the classical pathway component C4 (C4(-/-)). Clinical disease activity was markedly decreased in Bf(-/-) compared with wild-type (WT) mice (0.5 +/- 0.22 (n = 6) in Bf(-/-) vs 8.83 +/- 0.41 (n = 6) in WT mice (p < 0.0001)). Disease activity scores were not different between C4(-/-) and WT mice. Analyses of joints showed that C3 deposition, inflammation, pannus, cartilage, and bone damage scores were all significantly less in Bf(-/-) as compared with WT mice. There were significant decreases in mRNA levels of C3, C4, CR2, CR3, C3aR, and C5aR in the knees of Bf(-/-) as compared with C4(-/-) and WT mice with arthritis; mRNA levels for complement regulatory proteins did not differ between the three strains. These results indicate that the alternative pathway is absolutely required for the induction of arthritis following injection of anti-collagen Abs. The mechanisms by which these target organ-specific mAbs bypass the requirements for engagement of the classical pathway remain to be defined but do not appear to involve a lack of alternative pathway regulatory proteins. PMID:16849503

  6. Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model

    PubMed Central

    Andersson, C; Wenander, C S; Usher, P A; Hebsgaard, J B; Sondergaard, B-C; Rønø, B; Mackay, C; Friedrichsen, B; Chang, C; Tang, R; Hornum, L

    2014-01-01

    Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR. PMID:24665841

  7. Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model.

    PubMed

    Andersson, C; Wenander, C S; Usher, P A; Hebsgaard, J B; Sondergaard, B-C; Rønø, B; Mackay, C; Friedrichsen, B; Chang, C; Tang, R; Hornum, L

    2014-07-01

    Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.

  8. Borrelia burgdorferi arthritis-associated locus Bbaa1 regulates Lyme arthritis and K/B×N serum transfer arthritis through intrinsic control of type I IFN production.

    PubMed

    Ma, Ying; Bramwell, Kenneth K C; Lochhead, Robert B; Paquette, Jackie K; Zachary, James F; Weis, John H; Teuscher, Cory; Weis, Janis J

    2014-12-15

    Localized upregulation of type I IFN was previously implicated in development of Borrelia burgdorferi-induced arthritis in C3H mice, and was remarkable due to its absence in the mildly arthritic C57BL/6 (B6) mice. Independently, forward genetics analysis identified a quantitative trait locus on Chr4, termed B. burgdorferi-associated locus 1 (Bbaa1), that regulates Lyme arthritis severity and includes the 15 type I IFN genes. Involvement of Bbaa1 in arthritis development was confirmed in B6 mice congenic for the C3H allele of Bbaa1 (B6.C3-Bbaa1), which developed more severe Lyme arthritis and K/B×N model of rheumatoid arthritis (RA) than did parental B6 mice. Administration of a type I IFN receptor blocking mAb reduced the severity of both Lyme arthritis and RA in B6.C3-Bbaa1 mice, formally linking genetic elements within Bbaa1 to pathological production of type I IFN. Bone marrow-derived macrophages from Bbaa1 congenic mice implicated this locus as a regulator of type I IFN induction and downstream target gene expression. Bbaa1-mediated regulation of IFN-inducible genes was upstream of IFN receptor-dependent amplification; however, the overall magnitude of the response was dependent on autocrine/paracrine responses to IFN-β. In addition, the Bbaa1 locus modulated the functional phenotype ascribed to bone marrow-derived macrophages: the B6 allele promoted expression of M2 markers, whereas the C3H allele promoted induction of M1 responses. This report identifies a genetic locus physically and functionally linked to type I IFN that contributes to the pathogenesis of both Lyme and RA.

  9. Methotrexate-loaded lipid-core nanocapsules are highly effective in the control of inflammation in synovial cells and a chronic arthritis model

    PubMed Central

    Boechat, Antônio Luiz; de Oliveira, Catiúscia Padilha; Tarragô, Andrea Monteiro; da Costa, Allyson Guimarães; Malheiro, Adriana; Guterres, Silvia Stanisçuaski; Pohlmann, Adriana Raffin

    2015-01-01

    Background Rheumatoid arthritis (RA) is the most common autoimmune disease in the word, affecting 1% of the population. Long-term prognosis in RA was greatly improved following the introduction of highly effective medications such as methotrexate (MTX). Despite the importance of this drug in RA, 8%–16% of patients must discontinue the treatment because of adverse effects. Last decade, we developed a promising new nanocarrier as a drug-delivery system, lipid-core nanocapsules. Objective The aim of the investigation reported here was to evaluate if methotrexate-loaded lipid-core nanocapsules (MTX-LNC) reduce proinflammatory and T-cell-derived cytokines in activated mononuclear cells derived from RA patients and even in functional MTX-resistant conditions. We also aimed to find out if MTX-LNC would reduce inflammation in experimentally inflammatory arthritis at lower doses than MTX solution. Methods Formulations were prepared by self-assembling methodology. The adjuvant arthritis was induced in Lewis rats (AIA) and the effect on edema formation, TNF-α levels, and interleukin-1 beta levels after treatment was evaluated. Mononuclear cells obtained from the synovial fluid of RA patients during articular infiltration procedures were treated with MTX solution and MTX-LNC. For in vitro experiments, the same dose of MTX was used in comparing MTX and MTX-LNC, while the dose of MTX in the MTX-LNC was 75% lower than the drug in solution in in vivo experiments. Results Formulations presented nanometric and unimodal size distribution profiles, with D[4.3] of 175±17 nm and span of 1.6±0.2. Experimental results showed that MTX-LNC had the same effect as MTX on arthritis inhibition on day 28 of the experiment (P<0.0001); however, this effect was achieved earlier, on day 21 (P<0.0001), by MTX-LNC, and this formulation had reduced both TNF-α (P=0.001) and IL-1α (P=0.0002) serum levels by the last day of the experiment. Further, the MTX-LNC were more effective at reducing the

  10. Arthritis Mechanisms May Vary by Joint

    MedlinePlus

    ... Molecular differences between knee and hip joints with rheumatoid arthritis may inform more personal treatment strategies. Sebastian Kaulitzki/Hemera/Thinkstock Knee and hip joints with rheumatoid arthritis have differing genetic markers linked to inflammation, suggesting ...

  11. New Treatments Helping Kids with Juvenile Arthritis

    MedlinePlus

    ... 159984.html New Treatments Helping Kids With Juvenile Arthritis Several biologics have been approved by the FDA ... 20, 2016 (HealthDay News) -- New treatments for juvenile arthritis offer hope to children with the chronic autoimmune ...

  12. [Juvenile idiopathic arthritis: Definition and classification].

    PubMed

    Deslandre, C

    2016-04-01

    Juvenile idiopathic arthritis (JIA) is a group of diseases defined by the presence of arthritis of more than 6 weeks duration in patients aged less than 16 years and with unknown etiology. The international classification based on clinical and biological criteria define each type of JIA: systemic, oligoarticular, polyarticular with and without rheumatoid factor, enthesitis-related arthritis, and psoriatic arthritis. However, some discussions persist concerning systemic-onset juvenile idiopathic arthritis, whose clinical symptoms and pathogenic mechanisms are quite similar to those observed in autoinflammatory diseases, arthritis with antinuclear factors (poly- and oligoarticular) that could be considered as a homogenous group, and a family history of psoriasis that frequently led to unclassified arthritis. Better knowledge of the pathogenic mechanisms should improve the initial clinical classification with more homogeneous groups of patients and reduce the number of unclassified cases of arthritis. PMID:26968301

  13. Role of the complement system in rheumatoid arthritis and psoriatic arthritis: relationship with anti-TNF inhibitors.

    PubMed

    Ballanti, Eleonora; Perricone, Carlo; di Muzio, Gioia; Kroegler, Barbara; Chimenti, Maria Sole; Graceffa, Dario; Perricone, Roberto

    2011-08-01

    The complement system is an essential component of innate immunity and also plays an important role in modulating adaptive immunity. It comprises more than 30 plasma and membrane-bound proteins and can be activated through three pathways: the classical, the alternative and the lectin pathways. Its activation contributes to the pathogenesis of several autoimmune and inflammatory conditions. The evidence of complement activation in synovial fluid of Rheumatoid Arthritis (RA) patients is abundant, while few data exist in Psoriatic Arthritis (PsA) patients. Levels of complement proteins are generally depressed in the synovial fluid of patients with RA, reflecting consumption of complement. On the other hand, elevated levels of several complement cleavage products have been observed in synovial fluid. Involvement of complement in the pathogenesis of RA was also confirmed in animal models of arthritis: mice deficient for complement proteins are protected against the development of collagen-induced arthritis and administration of the anti-C5 monoclonal antibody prevents the onset of this arthritis. In the last decade anti-tumor necrosis factor agents have shown to be effective for the treatment of both RA and PsA and some studies suggest that the interaction between TNFα and complement system may contribute to the pathogenesis of these diseases. Reduction of the complement activation could be one of the mechanism by which TNFα-inhibitors exert their effectiveness in inflammatory arthritides. Because of these findings, complement could be an attractive therapeutic target both in RA and in PsA.

  14. 9 CFR 311.7 - Arthritis.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Arthritis. 311.7 Section 311.7 Animals... CERTIFICATION DISPOSAL OF DISEASED OR OTHERWISE ADULTERATED CARCASSES AND PARTS § 311.7 Arthritis. (a) Carcasses affected with arthritis which is localized and not associated with systemic change may be passed for...

  15. Immunomodulation in human and experimental arthritis: including vitamin D, helminths and heat-shock proteins.

    PubMed

    Ishikawa, L L W; Shoenfeld, Y; Sartori, A

    2014-05-01

    Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that is mainly directed to the joints, affecting the synovial membrane, the cartilage and also the bone. This disease affects 1% to 2% of the world population and is associated with significant morbidity and increased mortality. RA experimental models have allowed a great deal of information to be translated to the corresponding human disease. This review summarizes some of the most relevant findings targeting immunomodulation in arthritis. Some general guidelines to choose an adequate experimental model and also our experience with arthritis are supplied.

  16. Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

    PubMed Central

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

    2016-01-01

    Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

  17. Ultrasound in rheumatoid arthritis.

    PubMed

    Rizzo, Chiara; Ceccarelli, Fulvia; Gattamelata, Angelica; Vavala, Caterina; Valesini, Guido; Iagnocco, Annamaria

    2013-09-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation that can lead to structural damage of cartilage, bone and tendons. Assessing the inflammatory activity and the severity is essential in RA to help rheumatologists in adopting proper therapeutic strategies and in evaluating disease outcome and response to treatment. In the last years musculoskeletal (MS) ultrasonography (US) underwent tremendous technological development of equipment with increased sensitivity in detecting a wide set of joint and soft tissues abnormalities. In RA MSUS with the use of Doppler modalities is a useful imaging tool to depict inflammatory abnormalities (i.e. synovitis, tenosynovitis and bursitis) and structural changes (i.e. bone erosions, cartilage damage and tendon lesions). In addition, MSUS has been demonstrated to be able to monitor the response to different therapies in RA to guide local diagnostic and therapeutic procedures such as biopsy, fluid aspirations and injections. Future applications based on the development of new tools may improve the role of MSUS in RA.

  18. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltán

    2013-10-01

    The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics. PMID:23288628

  19. Genetics of rheumatoid arthritis - a comprehensive review.

    PubMed

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T; Mikecz, Katalin; Szekanecz, Zoltán

    2013-10-01

    The "Bermuda triangle" of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11-37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci - Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, respectively - have been identified. Finally, pharmacogenomics identified SNPs or multiple genetic signatures that may be associated with responses to traditional disease-modifying drugs and biologics.

  20. The Impact of Arthritis on Life Satisfaction of Older Adults.

    ERIC Educational Resources Information Center

    Burckhardt, Carol S.

    Poor health has been implicated as a suppressor of the life satisfaction of older adults. To clarify the contribution of arthritis to this process, functional disability, negative affect, pain, current severity of the disease, self-esteem, perception of general health, and internal health locus of control, were placed within a causal model as…

  1. [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. PMID:12794379

  2. Childhood arthritis: classification and radiology.

    PubMed

    Johnson, Karl; Gardner-Medwin, Janet

    2002-01-01

    Childhood arthritis has now been reclassified into a single internationally recognized entity of juvenile idiopathic arthritis (JIA). Radiology provides an important role in the management of JIA, in helping in the differential diagnosis, monitoring disease progression and detecting complications. Traditionally, plain radiographs have been the imaging investigation of choice but magnetic resonance imaging (MRI) and ultrasound are now providing a more effective and safer alternative. The appropriate use of sequences in MR imaging is important in the early detection of joint abnormalities in JIA. PMID:11798203

  3. Septic arthritis involving Capnocytophaga ochracea.

    PubMed Central

    Winn, R E; Chase, W F; Lauderdale, P W; McCleskey, F K

    1984-01-01

    Septic arthritis of the knee developed in a 21-month-old child. The causative organism, isolated from two separate arthrocenteses, was identified as Capnocytophaga ochracea morphologically and by biochemical reactions. Previous human infections (bacteremias) have occurred in granulocytopenic hosts with concomitant oral pathology including periodontitis and gingivitis. No abnormalities of oral hygiene were present in this patient, and granulocyte numbers were normal or elevated. Eradication of the infection was accomplished with 8 weeks of antibiotic therapy combined with surgical drainage. Septic arthritis expands the spectrum of infections reported to be caused by Capnocytophaga spp. PMID:6715520

  4. How co-morbidities magnify the effect of arthritis on labour force participation and economic status: a costs of illness study in Australia.

    PubMed

    Schofield, Deborah J; Callander, Emily J; Shrestha, Rupendra N; Passey, Megan E; Percival, Richard; Kelly, Simon J

    2014-04-01

    Few studies have assessed the impact of co-morbid conditions amongst patients with arthritis. This study will quantify the impact co-morbid health conditions have on the labour force status and economic circumstances of people with arthritis. This study uses a microsimulation model, Health&WealthMOD, to quantify the impact of co-morbidities on the labour force participation and economic circumstances of 45- to 64-year-old Australians with arthritis. The results show that the probability of being out of the labour force increases with increasing number of co-morbidities. However, there was no statistically significant difference in the amount of weekly private income received by people with arthritis and no co-morbidities, and people with arthritis and one or two co-morbidities. However, those with arthritis and three or more co-morbidities received a weekly private income 72 % lower than people with arthritis alone (95 % CI -82, -57). People with arthritis and co-morbidities paid less in tax and received more in government transfer payments. As such, it is important to consider the co-morbid conditions an individual has when assessing the impact of arthritis on labour force participation and economic circumstances. People with arthritis that have multiple co-morbid conditions are likely to have their labour force participation and economic circumstances interrupted much more than those with arthritis only. PMID:24562914

  5. How co-morbidities magnify the effect of arthritis on labour force participation and economic status: a costs of illness study in Australia.

    PubMed

    Schofield, Deborah J; Callander, Emily J; Shrestha, Rupendra N; Passey, Megan E; Percival, Richard; Kelly, Simon J

    2014-04-01

    Few studies have assessed the impact of co-morbid conditions amongst patients with arthritis. This study will quantify the impact co-morbid health conditions have on the labour force status and economic circumstances of people with arthritis. This study uses a microsimulation model, Health&WealthMOD, to quantify the impact of co-morbidities on the labour force participation and economic circumstances of 45- to 64-year-old Australians with arthritis. The results show that the probability of being out of the labour force increases with increasing number of co-morbidities. However, there was no statistically significant difference in the amount of weekly private income received by people with arthritis and no co-morbidities, and people with arthritis and one or two co-morbidities. However, those with arthritis and three or more co-morbidities received a weekly private income 72 % lower than people with arthritis alone (95 % CI -82, -57). People with arthritis and co-morbidities paid less in tax and received more in government transfer payments. As such, it is important to consider the co-morbid conditions an individual has when assessing the impact of arthritis on labour force participation and economic circumstances. People with arthritis that have multiple co-morbid conditions are likely to have their labour force participation and economic circumstances interrupted much more than those with arthritis only.

  6. Treatment of arthritis, including rheumatoid arthritis, with radioactive isotopes

    SciTech Connect

    Lieberman, E.; Bordoni, M.E.; Thornton, A.K.

    1988-06-21

    A radioactive composition is described for the treatment of arthritis comprising, in combination, a ferric hydroxide or aluminum hydroxide aggregate suspension having a particle size of 3 to 20 microns, wherein a radionuclide is entrapped, the radionuclide being /sup 166/Holmium.

  7. [Pathogenesis of rheumatoid arthritis].

    PubMed

    Branimir Anić; Miroslav Mayer

    2014-01-01

    Rheumatoid arthritis (RA) is an autoimmune systemic disease that primarily affects joints. Etiology and the pathogenesis of RA are complex, involving many types of cells, among others macrophages, T and B cells, fibro- blasts, chondrocytes and dendritic cells. Despite well documented role of many genes and epigenetic modifications in the development and evolution of the disease, in most RA patients there is no clear predisposing factor present. Environmental factors involved in RA pathogenesis are cigarette smoke, industrial pollutants like silica crystals, disturbances of intestinal, lung, and oral microbiota and some specific bacterial and viral infectious agents and their components. In the initial disease stage there are qualitative and quantitative disturbances ofpeptide citrulination as well as other protein modifications, followed by antigen presenting cell (APC) (macrophages and dendritic cells) and fibroblast like synoviocytes (FLS) activation. Some microbes foster this processes by APC and FLS direct and indirect activation. In the second stage APC's elicit specific humoral B cell re- sponse resulting in specific antibodies production and T cell autoreactivity. Inherited and acquired defects in T and B cell responses caused by repeated activation of innate immunity as well as loss of tolerance, elicit chronic autoimmune inflammation, primarily of synovial membranes, and development of cellular panus. Pathologic activation of the osteoclasts and release of the immune system effector molecules and the proteolytic enzymes damage the cartilage, bone and tendons composition and structure. Persistent inflammation through its complex mechanisms results in many systemic and extraarticular RA manifestations of almost all organ systems, resulting in severe complications and comorbidities such as rheumatoid lung, carditis, vasculitis, cahexia, anemia, accelerated atherosclerosis, myocardial and cerebrovascular vascular disease, lymphoma, osteoporosis, depression etc

  8. Relationship between angiogenesis and inflammation in experimental arthritis.

    PubMed

    Clavel, Gaelle; Valvason, Chiara; Yamaoka, Kunio; Lemeiter, Delphine; Laroche, Liliane; Boissier, Marie-Christophe; Bessis, Natacha

    2006-09-01

    Background. Angiogenesis is involved in rheumatoid arthritis (RA) leading to leucocyte recruitment and inflammation in the synovium. Furthermore, synovial inflammation itself further potentiates endothelial proliferation and angiogenesis. In this study, we aimed at evaluating the reciprocical relationship between synovial inflammation and angiogenesis in a RA model, namely collagen-induced arthritis (CIA). Methods. CIA was induced by immunization of DBA/1 mice with collagen type II in adjuvant. Endothelial cells were detected using a GSL-1 lectin-specific immunohistochemical staining on knee joint sections. Angiogenesis, clinical scores and histological signs of arthritis were evaluated from the induction of CIA until the end of the experiment. Angiogenesis was quantified by counting both the isolated endothelial cells and vessels stained on each section. To evaluate the effect of increased angiogenesis on CIA, VEGF gene transfer was performed using an adeno-associated virus encoding VEGF (AAV-VEGF), by intra-muscular or intra-articular injection in mice with CIA. Results. We showed an increase in synovial angiogenesis from day 6 to day 55 after CIA induction, and, moreover, joint vascularization and clinical scores of arthritis were correlated (p < 0.0001, r = 0.61). Vascularization and histological scores were also correlated (p = 0.0006, r = 0.51). Systemic VEGF overexpression in mice with CIA was followed by an aggravation of arthritis as compared to AAV-lacZ control group (p < 0.0001). In contrast, there was no difference in clinical scores between control mice and mice injected within the knee with AAV-VEGF, even if joint vascularization was higher in this group than in all other groups (p = 0,05 versus non-injected group). Intra-articular AAV-VEGF injections induced more severe signs of histological inflammation and bone destruction than AAV-Lac Z or no injection. Conclusion. Angiogenesis and joint inflammation evolve in parallel during collagen

  9. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis.

    PubMed

    Gonzalo-Gil, Elena; Galindo-Izquierdo, María

    2014-01-01

    Transforming growth factor-beta (TGF-β) is a cytokine with pleiotropic functions in hematopoiesis, angiogenesis, cell proliferation, differentiation, migration and apoptosis. Although its role in rheumatoid arthritis is not well defined, TGF-β activation leads to functional immunomodulatory effects according to environmental conditions. The function of TGF-β in the development of arthritis in murine models has been extensively studied with controversial results. Recent findings point to a non-relevant role for TGF-β in a mice model of collagen-induced arthritis. The study of TGF-β on T-cell responses has shown controversial results as an inhibitor or promoter of the inflammatory response. This paper presents a review of the role of TGF-β in animal models of arthritis.

  10. Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat correlates with higher production of epinephrine in mesenteric adipocytes in rat model of cachectic rheumatoid arthritis.

    PubMed

    Stofkova, Andrea; Krskova, Katarina; Vaculin, Simon; Jurcovicova, Jana

    2016-06-01

    Cachectic rheumatoid arthritis, the less frequent form of the disease, is associated with loss of fat mass and often more severe course of the disease. Its experimental model represents rat adjuvant arthritis (AA) characterized by edema, lack of appetite, sharp body weight and fat loss. As individual fat depots display functional differences, here we studied lipolytic activity and sensitivity to lipolytic stimuli of nodeless epididymal fat (eWAT) and perinodal mesenteric fat (mWAT) depots at the peak of AA. We also examined changes in catecholamine and cytokine levels involved in lipolysis in plasma and/or isolated adipocytes from both WATs to identify the contribution of local, adipocyte-based processes and/or systemic events to adiposity loss in cachectic rheumatoid arthritis. AA was induced to male Lewis rats by complete Freund's adjuvant. Groups of ad libitum-fed and pair-fed controls were used to distinguish the effects of food restriction from inflammation-induced cachexia. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and its phosphorylated form (pHSL) were analyzed by western blot. CRP and catecholamine levels in plasma or adipocyte lysates were determined using ELISA kits. Cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1), monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-1β, IL-6, IL-10 and leptin in adipocyte lysate were analyzed by quantitative protein microarray. Plasma glycerol and FFA were measured spectrophotometrically. AA rats developed severe cachexia, with lower adiposity in mWAT compared to normal and pair-fed controls, whereas in eWAT the adiposity was similarly reduced in AA and pair-fed groups. ATGL levels in both WATs were not affected by AA or pair feeding. AA upregulated levels of HSL, pHSL and pHSL/HSL ratio in mWAT, whereas none of these parameters has changed in eWAT of AA rats or in either WATs of pair-fed rats. In AA rats plasma glycerol was elevated, whereas FFA concentration was reduced. Plasma

  11. [Early diagnosis of rheumatoid arthritis].

    PubMed

    Badot, V

    2014-09-01

    Rheumatoid arthritis is the most common chronic inflammatory rheumatic disorder, and is characterized by inflammation of the joint, which can lead to irreversible bone damage, joint deformity and disability, if not diagnosed timely or treated adequately. New classification criteria were developed in 2010 in order to identify patients at risk of developing persistent or erosive arthritis, and requiring early therapy. In order to detect early arthritis or bone erosions before their appearance on X-rays, ultrasound and magnetic resonance imaging are now routinely used by clinicians, and also seem to deliver prognostic information about the disease. Synovial biopsies are potentially interesting in case of early arthritis to identify markers of diagnosis, prognosis or therapeutic response. Genetic or environmental risk factors were described to play a role in the development or maintenance of the disease; they could also help to screen early RA. A rapid diagnosis is eventually based on the right information and a tight collaboration between the primary care physician and the rheumatology care specialist. PMID:25675622

  12. Genetics Home Reference: rheumatoid arthritis

    MedlinePlus

    ... risk factors for rheumatoid arthritis are variations in human leukocyte antigen (HLA) genes , especially the HLA-DRB1 gene. The proteins produced from HLA genes help the immune system distinguish the body's own proteins from proteins made by foreign invaders ( ...

  13. Medicines to Treat Rheumatoid Arthritis

    MedlinePlus

    ... and 55, but it can happen at any age. Rheumatoid arthritis affects women more than men. Visit your doctor to talk about your health and the medicines you may need. This factsheet will give you information about a type of medicine. You will learn ...

  14. Effect of cadmium chloride exposure during the induction of collagen induced arthritis.

    PubMed

    Ansari, Md Meraj; Neha; Khan, Haider A

    2015-08-01

    The precise cause of autoimmune diseases such as rheumatoid arthritis remains uncertain. Collagen induced arthritis (CIA) in animals is the most commonly used model of human rheumatoid arthritis (RA). Exposure of humans and animals to toxic metals is widespread. Cadmium is one of the most prevalent nephrotoxic heavy metal, but it may cause other systemic toxicity as well. Cadmium may cause adverse health effects by impairment of the immune systems and induction of reactive oxygen species. Since rheumatoid arthritis pathogenesis involve immune system disorder and chronic inflammation, the present study has been designed to find out the effect of cadmium chloride exposure on clinical manifestation of development of collagen induced rheumatoid arthritis. Arthritis was induced in rats by intradermal injection of emulsion of type II collagen in Complete Freund's Adjuvant. Rats were treated with cadmium chloride dissolved in drinking water at concentrations of 5ppm and 50ppm for 21 days from day of immunization. The effects of cadmium in the rats were assessed by biochemical parameters (articular elastase, articular nitrite, lipid peroxidation, reduced glutathione, catalase and superoxide dismutase) histopathological analysis and immunohistochemical expression of pro-inflammatory cytokines in rat joint tissue. Histopathological changes further confirmed the biochemical and immunohistochemical results. Our results suggest that exposure to cadmium chloride during the induction phase of collagen induced arthritis abrogate disease development at lower dose whereas exacerbates at higher dose in Wistar rats. PMID:26070417

  15. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice

    PubMed Central

    Wang, Xuewen; Zhong, Wei

    2015-01-01

    Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA. PMID:26629181

  16. Isorhamnetin attenuates collagen-induced arthritis via modulating cytokines and oxidative stress in mice.

    PubMed

    Wang, Xuewen; Zhong, Wei

    2015-01-01

    Inflammation and oxidative stress were involved in the development and progression of rheumatoid arthritis (RA). Isorhamnetin has anti-inflammatory and anti-oxidative activities, but its effects on RA have not been investigated. In order to observe the possible therapeutic effects of isorhamnetin on RA, we established a collagen-induced arthritis mouse model and treated the animal with isorhamnetin for 3 weeks. Besides, fibroblast-like synoviocytes (FLS) were treated with lipopolysaccharide (LPS) and isorhamnetin. The severity of arthritis was assessed by arthritis score, joint destruction score and inflammation score. Levels of cytokines TNF-α, IL-1β, IL-6, IL-17A, IL-17F, IL-10 and IL-35 in the joint tissue homogenate and cell culture medium as well as anti-type II collagen antibody in serum were measured using ELISA. Contents of H2O2 and malondialdehyde (MDA) in joint tissue homogenate were measured using assay kits. We found collagen immunization induced significant arthritis in mice and isorhamnetin at the dose of 10 and 20 mg/kg/day could significantly attenuate the collagen-induced arthritis. Isorhamnetin also modulated the production of cytokines and suppressed the oxidative stress in the mice with collagen-induced arthritis at the dose of 10 and 20 mg/kg/day. These data suggested that isorhamnetin might be a potential agent for the management of RA. PMID:26629181

  17. Lyme arthritis of the pediatric ankle.

    PubMed

    Aiyer, Amiethab; Walrath, Jessica; Hennrikus, William

    2014-10-01

    Lyme arthritis results from acute inflammation caused by the spirochete Borrelia burgdorferi. The number of cases per year has been rising since 2006, with a majority of patients being affected in the northeastern United States. Development of Lyme arthritis is of particular importance to the orthopedic surgeon because Lyme arthritis often presents as an acute episode of joint swelling and tenderness and may be confused with bacterial septic arthritis. Considering the vast difference in treatment management between these 2 pathologies, differentiating between them is of critical importance. Septic arthritis often needs to be addressed surgically, whereas Lyme arthritis can be treated with oral antibiotics alone. Laboratory testing for Lyme disease often results in a delay in diagnosis because many laboratories batch-test Lyme specimens only a few times per week because of increased expense. The authors present a case of Lyme arthritis in the pediatric ankle in an endemic region. No clear algorithm exists to delineate between septic arthritis and Lyme arthritis of the joint. Improved clinical guidelines for the identification and diagnosis of Lyme arthritis of the ankle are important so that appropriate antibiotics can be used and surgery can be avoided.

  18. Standardized ethyl acetate fraction from the roots of Brassica rapa attenuates the experimental arthritis by down regulating inflammatory responses and inhibiting NF-κB activation.

    PubMed

    Shin, Ji-Sun; Yun, Chang Hyeon; Chung, Kyung-Sook; Bang, Myun-Ho; Baek, Nam-In; Chung, Hae-Gon; Cho, Young-Wuk; Lee, Kyung-Tae

    2014-04-01

    This study was undertaken to investigate the anti-arthritic potential of a standardized ethyl acetate fraction from the roots of Brassica rapa (EABR) and to explore the molecular mechanisms in adjuvant-induced arthritic rats and macrophages. In AIA-induced arthritic rats, EABR significantly reduced paw swelling, an arthritic index, serum rheumatoid factor, and tissue expression ratio of RANKL/OPG versus vehicle-administered group. This was found to be well correlated with significant suppressions in productions of PGE2, NO, and pro-inflammatory cytokines and in activations of NF-κB in AIA-induced paw tissues and LPS-induced macrophages. EABR attenuated NF-κB activation by reducing the nuclear translocation and phosphorylation of the p65 NF-κB, which were accompanied by parallel reductions in the degradation and phosphorylation of IκBα after blocking the phosphorylation mediated IKK activation. The findings suggest EABR exerts its anti-arthritic and anti-inflammatory properties via NF-κB inactivation in vitro and in vivo, and that EABR is a potential therapeutic for the treatment of arthritis and inflammation-associated disorders.

  19. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis

    NASA Astrophysics Data System (ADS)

    Trentham, David E.; Dynesius-Trentham, Roselynn A.; Orav, E. John; Combitchi, Daniel; Lorenzo, Carlos; Sewell, Kathryn Lea; Hafler, David A.; Weiner, Howard L.

    1993-09-01

    Rheumatoid arthritis is an inflammatory synovial disease thought to involve T cells reacting to an antigen within the joint. Type II collagen is the major protein in articular cartilage and is a potential autoantigen in this disease. Oral tolerization to autoantigens suppresses animal models of T cell-mediated autoimmune disease, including two models of rheumatoid arthritis. In this randomized, double-blind trial involving 60 patients with severe, active rheumatoid arthritis, a decrease in the number of swollen joints and tender joints occurred in subjects fed chicken type II collagen for 3 months but not in those that received a placebo. Four patients in the collagen group had complete remission of the disease. No side effects were evident. These data demonstrate clinical efficacy of an oral tolerization approach for rheumatoid arthritis.

  20. Craniomandibular disorders in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. A clinical study.

    PubMed

    Könönen, M; Wenneberg, B; Kallenberg, A

    1992-10-01

    Sixty-one subjects with rheumatoid arthritis, 61 with psoriatic arthritis, 61 with ankylosing spondylitis, and 61 healthy controls were examined with regard to subjective symptoms and clinical signs of craniomandibular disorders (CMD). The frequencies of most subjective and clinical variables were higher in all three disease groups than in the control group. Subjects with rheumatoid arthritis and psoriatic arthritis showed more frequent and severe signs and symptoms than subjects with ankylosing spondylitis. It is concluded that subjective symptoms and clinical signs of CMD are common in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis and are mainly caused by the respective general joint disease. None of the signs and symptoms is pathognomonic for rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis.

  1. Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You?

    MedlinePlus

    Treating Rheumatoid Arthritis: Are Biologic Drugs Right for You? What is rheumatoid arthritis (RA)? Rheumatoid arthritis (RA) is a serious condition. The body’s immune system attacks the lining of ...

  2. Hyperspectral imaging for detection of arthritis: feasibility and prospects

    NASA Astrophysics Data System (ADS)

    Milanic, Matija; Paluchowski, Lukasz A.; Randeberg, Lise L.

    2015-09-01

    Rheumatoid arthritis (RA) is a disease that frequently leads to joint destruction. It has a high incidence rate worldwide, and the disease significantly reduces patients' quality of life. Detecting and treating inflammatory arthritis before structural damage to the joint has occurred is known to be essential for preventing patient disability and pain. Existing diagnostic technologies are expensive, time consuming, and require trained personnel to collect and interpret data. Optical techniques might be a fast, noninvasive alternative. Hyperspectral imaging (HSI) is a noncontact optical technique which provides both spectral and spatial information in one measurement. In this study, the feasibility of HSI in arthritis diagnostics was explored by numerical simulations and optimal imaging parameters were identified. Hyperspectral reflectance and transmission images of RA and normal human joint models were simulated using the Monte Carlo method. The spectral range was 600 to 1100 nm. Characteristic spatial patterns for RA joints and two spectral windows with transmission were identified. The study demonstrated that transmittance images of human joints could be used as one parameter for discrimination between arthritic and unaffected joints. The presented work shows that HSI is a promising imaging modality for the diagnostics and follow-up monitoring of arthritis in small joints.

  3. Protective effect of Asarum extract in rats with adjuvant arthritis

    PubMed Central

    ZHANG, WENQIANG; ZHANG, JUAN; ZHANG, MING; NIE, LIN

    2014-01-01

    The aim of the present study was to investigate the protective effect of Asarum extract on rats with adjuvant arthritis (AA) and to determine the underlying mechanism. An AA model was established by injecting Freund’s complete adjuvant into the rats. The degree of toe swelling, arthritis index, spleen index, and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were measured. In addition, the underlying molecular mechanism was investigated using murine macrophage-derived RAW 264.7 cells. Asarum extract was found to significantly reduce the severity of arthritis by decreasing hind paw swelling, the arthritis index, the spleen index, and TNF-α, IL-1β and IL-6 expression levels in plasma. In vitro, Asarum extract inhibited the nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling pathways. These results indicate that Asarum extract may be a therapeutic agent for AA and may exert an anti-inflammatory effect by mediating the NF-κB and MAPK signaling pathways. PMID:25289073

  4. Polyarticular septic arthritis in an immunocompetent patient.

    PubMed

    Clements, J; Dinneen, A; Heilpern, G

    2013-03-01

    Septic arthritis is an uncommon condition with an incidence of 2-3/100,000. It is clinically notable, however, as it is a rapidly destructive joint disease with significant associated morbidity and mortality. Polyarticular septic arthritis has an estimated incidence of 15% of all cases of infectious arthritis. We report a case of polyarticular septic arthritis with involvement of bilateral shoulders and wrist to highlight the importance of early diagnosis and treatment as well as the high mortality rates associated with this condition. Bilateral septic shoulder arthritis poses a challenge to treat, and its significance should not be underestimated as even with early surgical intervention and aggressive antibiotic and fluid resuscitation death is a sad but perhaps not uncommon outcome. It is therefore imperative that the diagnosis of polyarticular septic arthritis is kept prominent in the physician's mind when confronted with a patient with symptomatic polyarthralgia.

  5. Psoriatic arthritis: Epidemiology, diagnosis, and treatment

    PubMed Central

    Liu, Jung-Tai; Yeh, Horng-Ming; Liu, Shyun-Yeu; Chen, Kow-Tong

    2014-01-01

    Our understanding of psoriatic arthritis has evolved as new knowledge of the disease has emerged. However, the exact prevalence of psoriatic arthritis is unknown, and its pathogenesis has not been fully elucidated. Genetic, environmental, and immunologic factors have all been implicated in disease development. Early diagnosis and treatment have become primary objectives in clinical rheumatology. Psoriatic arthritis not only causes functional impairment, but also increases mortality risk of patients. The advent of new therapeutic agents capable of arresting the progression of joint damage is expected. However, early psoriatic arthritis assessment remains limited. The objectives of this article are to outline the epidemiology, diagnosis, and treatment of psoriatic arthritis and to suggest a paradigm for identifying early psoriatic arthritis patients. PMID:25232529

  6. Acromioclavicular septic arthritis and sternoclavicular septic arthritis with contiguous pyomyositis.

    PubMed

    Corey, Sally A; Agger, William A; Saterbak, Andrew T

    2015-03-01

    Acromioclavicular (AC) and sternoclavicular (SC) septic arthritis with contiguous pyomyositis are rare, especially in immunocompetent individuals. We report a case of septic AC joint with pyomyositis of the deltoid and supraspinatus muscles and a separate case with septic SC joint with pyomysitis of the sternocleidomastoid muscle. Both patients had similar presentations of infections with Staphylococcus aureus and were successfully treated with surgical incision and drainage followed by prolonged antibiotic therapy.

  7. Septic arthritis in immunocompetent and immunosuppressed hosts.

    PubMed

    Wang, Dingyuan Alvin; Tambyah, Paul Anantharajah

    2015-04-01

    Septic arthritis has long been considered an orthopedic emergency. Historically, Neisseria gonorrhoeae and Staphylococcus aureus have been the most common causes of septic arthritis worldwide but in the modern era of biological therapy and extensive use of prosthetic joint replacements, the spectrum of microbiological causes of septic arthritis has widened considerably. There are also new approaches to diagnosis but therapy remains a challenge, with a need for careful consideration of a combined medical and surgical approach in most cases.

  8. Combination therapy of dexamethasone with epigallocatechin enhances tibiotarsal bone articulation and modulates oxidative status correlates with cartilage cytokines expression in the early phase of experimental arthritis.

    PubMed

    Roy, Souvik; Sannigrahi, Santanu; Ghosh, Balaram; Pusp, Priyanka; Roy, Tathagata

    2013-01-01

    The inclusion of antioxidant for the treatment of arthritis, especially under the therapy with immunosuppressant, is motivated because antioxidant plays an essential role in disease progression and moreover, immunosuppressive treatment suffers redox homeostasis balance of the organism. The aim of the present study was to evaluate the enhancement of anti-arthritic effect of dexamethasone in combination with epigallocatechin on the progression of adjuvant-induced arthritis in rats. Adjuvant arthritic rats were treated with dexamethasone (0.2mg/kg), epigallocatechin (100mg/kg) and combination of dexamethasone (0.1mg/kg) with epigallocatechin (100mg/kg) daily for a period of 28 days. Paw swelling changes, estimation of serum albumin level, alteration of bone mineral density, histopathological, and radiographical analysis were assessed to evaluate the anti-arthritic effect. Lipid peroxidation and antioxidant enzyme activities in joint tissue homogenate were performed along with the expression of different pro-inflammatory cartilage cytokines like TNF-α and IL-6. Dexamethasone and epigallocatechin combination potentiated both the antiarthritic (decrease of hind paw volume) and the antioxidant effect (lipid peroxidation, superoxide dismutase, glutathione reductase and catalase). In combination with dexamethasone, epigallocatechin markedly potentiated the beneficial effect of dexamethasone which resulted in more significant increment of serum albumin and bone mineral density. Improvement of anti-arthritic effect of combination therapy was supported by histopathological, radiographical alterations, and attenuation of over-expression of cartilage cytokines. Epigallocatechin act as potent antioxidant and combined administration of dexamethasone with epigallocatechin increased the anti-arthritic efficacy of basal dexamethasone therapy and suppressed the development phase of arthritic progression in rats.

  9. Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver

    PubMed Central

    Poništ, Silvester; Mihálová, Danica; Nosáľ, Radomír; Harmatha, Juraj; Hrádková, Iveta; Šišková, Katarína; Bezáková, Lýdia

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX. PMID:27556049

  10. Effect of N-Feruloylserotonin and Methotrexate on Severity of Experimental Arthritis and on Messenger RNA Expression of Key Proinflammatory Markers in Liver.

    PubMed

    Pašková, Ľudmila; Kuncírová, Viera; Poništ, Silvester; Mihálová, Danica; Nosáľ, Radomír; Harmatha, Juraj; Hrádková, Iveta; Čavojský, Tomáš; Bilka, František; Šišková, Katarína; Paulíková, Ingrid; Bezáková, Lýdia; Bauerová, Katarína

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX. PMID:27556049

  11. Diagnosis and treatment of Lyme arthritis.

    PubMed

    Arvikar, Sheila L; Steere, Allen C

    2015-06-01

    In the United States, Lyme arthritis is the most common feature of late-stage Borrelia burgdorferi infection, usually beginning months after the initial bite. In some, earlier phases are asymptomatic and arthritis is the presenting manifestation. Patients with Lyme arthritis have intermittent or persistent attacks of joint swelling and pain in 1 or a few large joints. Serologic testing is the mainstay of diagnosis. Synovial fluid polymerase chain reaction for B burgdorferi DNA is often positive before treatment, but is not a reliable marker of spirochetal eradication after therapy. This article reviews the clinical manifestations, diagnosis, and management of Lyme arthritis.

  12. Fungal osteomyelitis and septic arthritis.

    PubMed

    Bariteau, Jason T; Waryasz, Gregory R; McDonnell, Matthew; Fischer, Staci A; Hayda, Roman A; Born, Christopher T

    2014-06-01

    Management of fungal osteomyelitis and fungal septic arthritis is challenging, especially in the setting of immunodeficiency and conditions that require immunosuppression. Because fungal osteomyelitis and fungal septic arthritis are rare conditions, study of their pathophysiology and treatment has been limited. In the literature, evidence-based treatment is lacking and, historically, outcomes have been poor. The most common offending organisms are Candida and Aspergillus, which are widely distributed in humans and soil. However, some fungal pathogens, such as Histoplasma, Blastomyces, Coccidioides, Cryptococcus, and Sporothrix, have more focal areas of endemicity. Fungal bone and joint infections result from direct inoculation, contiguous infection spread, or hematogenous seeding of organisms. These infections may be difficult to diagnose and eradicate, especially in the setting of total joint arthroplasty. Although there is no clear consensus on treatment, guidelines are available for management of many of these pathogens.

  13. Interaction between extracellular matrix molecules and microbial pathogens: evidence for the missing link in autoimmunity with rheumatoid arthritis as a disease model

    PubMed Central

    Sofat, Nidhi; Wait, Robin; Robertson, Saralili D.; Baines, Deborah L.; Baker, Emma H.

    2015-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation followed by tissue rebuilding or fibrosis. A failure by the body to regulate inflammation effectively is one of the hallmarks of RA. The interaction between the external environment and the human host plays an important role in the development of autoimmunity. In RA, the observation of anti-cyclic citrullinated peptide antibodies (ACPA) to autoantigens is well recognized. Citrullination is a post-translational modification mediated by peptidyl arginine deiminases, which exist in both mammalian and bacterial forms. Previous studies have shown how proteins expressed in the human extracellular matrix (ECM) acquire properties of damage-associated molecular patterns (DAMPs) in RA and include collagens, tenascin-C, and fibronectin (FN). ECM DAMPs can further potentiate tissue damage in RA. Recent work has shown that citrullination in RA occurs at mucosal sites, including the oral cavity and lung. Mucosal sites have been linked with bacterial infection, e.g., periodontal disease, where exogenous pathogens are implicated in the development of autoimmunity via an infectious trigger. Proteases produced at mucosal sites, both by bacteria and the human host, can induce the release of ECM DAMPs, thereby revealing neoepitopes which can be citrullinated and lead to an autoantibody response with further production of ACPA. In this perspectives article, the evidence for the interplay between the ECM and bacteria at human mucosal surfaces, which can become a focus for citrullination and the development of autoimmunity, is explored. Specific examples, with reference to collagen, fibrinogen, and FN, are discussed. PMID:25642219

  14. Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response

    PubMed Central

    Kragstrup, Tue Wenzel; Jalilian, Babak; Keller, Kresten Krarup; Zhang, Xianwei; Laustsen, Julie Kristine; Stengaard-Pedersen, Kristian; Hetland, Merete Lund; Hørslev-Petersen, Kim; Junker, Peter; Østergaard, Mikkel; Hauge, Ellen-Margrethe; Hvid, Malene; Vorup-Jensen, Thomas; Deleuran, Bent

    2016-01-01

    Introduction In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis. Methods The level of sCD18 was analyzed with a time-resolved immunoflourometric assay in 1) plasma from early treatment naïve RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFα or adalimumab. Results Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFα and decreased by adalimumab. Conclusions The plasma sCD18 levels were altered

  15. NLRP3 Inflammasome Plays an Important Role in the Pathogenesis of Collagen-Induced Arthritis

    PubMed Central

    Zhang, Yongfeng; Zheng, Yi; Li, Hongbin

    2016-01-01

    Objective. To investigate the relationship between NLRP3 and the pathogenesis of collagen-induced arthritis. Methods. We used the collagen-induced arthritis (CIA) mouse model. The mice were divided into two groups: the model group (CIA, n = 16) and the control group (Normal, n = 8). The mice were sacrificed seven weeks after immunization. The arthritis score and imaging evaluation (X-rays, Micro-CT, and MRI) were performed. Synovial tissue NLRP3 expression and peripheral blood cytokine levels were analyzed. Results. The arthritis score (6.00 ± 2.52), imaging score (4.63 ± 0.92), and synovial tissue NLRP3 expression (4.00 ± 2.03) significantly increased in the CIA mice. The expression of synovial NLRP3 was positively correlated with arthritis clinical and radiographic scores (r = 0.792 and r = 0.669, resp.). Conclusions. The synovial NLRP3 expression increased at the early onset of RA. Synovial NLRP3 expression level was correlated with the clinical arthritis severity and extent of radiological destruction, suggesting that NLRP3 is involved in the pathogenesis of RA. PMID:27034595

  16. Report - Recurrent hip arthritis diagnosed as juvenile idiopathic arthritis: A case report.

    PubMed

    Chang, Tung-Ming; Yang, Kuender D; Yong, Su-Boon

    2016-05-01

    Juvenile idiopathic arthritis is the most common rheumatic disease in childhood. It is a chronic inflammatory disease associated with arthritis of unknown etiology that begins before the age of 16 and persists for longer than 6 weeks. In this report, the case of a child who suffered recurrent alternative hip arthritis with bilateral hip arthritis is examined, in which he was finally diagnosed as suffering from Juvenile idiopathic arthritis. A 14-year-old boy of Taiwanese origin presented with a normal birth and developmental history. At the age of 10, right-side hip joint pain was experienced, which later migrated to the left side. On further inspection, synovium hypertrophy, cartilage erosion and hip turbid fluid accumulation were found and aseptic arthritis was presumed to be the primary cause. However, after re-examining both his clinical history and presentation, Juvenile idiopathic arthritis was the final diagnosis. Any child presenting with repeat joint swelling are at risk of Juvenile idiopathic arthritis. This is still to be the case if symptoms recede or heal and no initial diagnosis is made. Therefore, a better understanding of the risk of recurrent arthritis is needed. It cannot be emphasized strongly enough that Juvenile idiopathic arthritis should be suspected at all times when a child suffers from recurrent aseptic arthritis of the hip joint.

  17. The potential use of microcalorimetry in rapid differentiation between septic arthritis and other causes of arthritis.

    PubMed

    Yusuf, E; Hügle, T; Daikeler, T; Voide, C; Borens, O; Trampuz, A

    2015-03-01

    Current diagnostic methods in differentiating septic from non-septic arthritis are time-consuming (culture) or have limited sensitivity (Gram stain). Microcalorimetry is a novel method that can rapidly detect microorganisms by their heat production. We investigated the accuracy and time to detection of septic arthritis by using microcalorimetry. Patients older than 18 years of age with acute arthritis of native joints were prospectively included. Synovial fluid was aspirated and investigated by Gram stain, culture and microcalorimetry. The diagnosis of septic arthritis and non-septic arthritis were made by experienced rheumatologists or orthopaedic surgeons. Septic arthritis was diagnosed by considering the finding of acute arthritis together with findings such as positive Gram stain or positive culture of synovial fluid or positive blood culture. The sensitivity and specificity for diagnosing septic arthritis and the time to positivity of microcalorimetry were determined. Of 90 patients (mean age 64 years), nine had septic arthritis, of whom four (44 %) had positive Gram stain, six (67 %) positive synovial fluid culture and four (44 %) had positive blood culture. The sensitivity of microcalorimetry was 89 %, the specificity was 99 % and the mean detection time was 5.0 h (range, 2.2-8.0 h). Microcalorimetry is an accurate and rapid method for the diagnosis of septic arthritis. It has potential to be used in clinical practice in diagnosing septic arthritis.

  18. Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory Reaction and Protects Against Inflammatory Arthritis in Mice.

    PubMed

    Wang, Wenhan; Li, Zhong; Meng, Qingjuan; Zhang, Pei; Yan, Pengcheng; Zhang, Zhenbiao; Zhang, Hao; Pan, Jingrui; Zhai, Yujia; Liu, Yaoge; Wang, Xiaokai; Li, Weiwei; Zhao, Yunpeng

    2016-10-01

    It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown. To investigate the role of verapamil in antagonizing TNF-α-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-α, in the presence or absence of verapamil. Inflammation-associated cytokines, including IL-1, IL-6, inducible nitric oxide synthase 2 (NOS-2), and cyclooxygenase-2 (COX-2), were assessed, and verapamil suppressed TNF-α-induced expression of inflammatory cytokines. Furthermore, collagen-induced arthritis (CIA) mice models were established, and arthritis progression was evaluated by clinical and histological signs of arthritis. Treatment of verapamil attenuated inflammation as well as joint destruction in arthritis models. In addition, activity of NF-kB signaling pathway was determined both in vitro and in mice arthritis models, and verapamil inhibited TNF-α-induced activation of NF-kB signaling both in vitro and in mice models. Collectively, chronic calcium channel blocker verapamil may shed light on treatment of inflammatory arthritis and provide a potential therapeutic instrument for RA in the future. PMID:27438468

  19. Light scattering study of rheumatoid arthritis

    SciTech Connect

    Beuthan, J; Netz, U; Minet, O; Mueller, G; Scheel, A; Henniger, J

    2002-11-30

    The distribution of light scattered by finger joints is studied in the near-IR region. It is shown that variations in the optical parameters of the tissue (scattering coefficient {mu}{sub s}, absorption coefficient {mu}{sub a}, and anisotropy factor g) depend on the presence of the rheumatoid arthritis (RA). At the first stage, the distribution of scattered light was measured in diaphanoscopic experiments. The convolution of a Gaussian error function with the scattering phase function proved to be a good approximation of the data obtained. Then, a new method was developed for the reconstruction of distribution of optical parameters in the finger cross section. Model tests of the quality of this reconstruction method show good results. (laser biology and medicine)

  20. Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis.

    PubMed

    Stahl, Eli A; Wegmann, Daniel; Trynka, Gosia; Gutierrez-Achury, Javier; Do, Ron; Voight, Benjamin F; Kraft, Peter; Chen, Robert; Kallberg, Henrik J; Kurreeman, Fina A S; Kathiresan, Sekar; Wijmenga, Cisca; Gregersen, Peter K; Alfredsson, Lars; Siminovitch, Katherine A; Worthington, Jane; de Bakker, Paul I W; Raychaudhuri, Soumya; Plenge, Robert M

    2012-05-01

    The genetic architectures of common, complex diseases are largely uncharacterized. We modeled the genetic architecture underlying genome-wide association study (GWAS) data for rheumatoid arthritis and developed a new method using polygenic risk-score analyses to infer the total liability-scale variance explained by associated GWAS SNPs. Using this method, we estimated that, together, thousands of SNPs from rheumatoid arthritis GWAS explain an additional 20% of disease risk (excluding known associated loci). We further tested this method on datasets for three additional diseases and obtained comparable estimates for celiac disease (43% excluding the major histocompatibility complex), myocardial infarction and coronary artery disease (48%) and type 2 diabetes (49%). Our results are consistent with simulated genetic models in which hundreds of associated loci harbor common causal variants and a smaller number of loci harbor multiple rare causal variants. These analyses suggest that GWAS will continue to be highly productive for the discovery of additional susceptibility loci for common diseases. PMID:22446960

  1. Enhanced therapeutic anti-inflammatory effect of betamethasone upon topical administration with low frequency, low intensity (20 kHz, 100 mW/cm2) ultrasound exposure on carrageenan-induced arthritis in mice model

    PubMed Central

    Cohen, Gadi; Natsheh, Hiba; Sunny, Youhan; Bawiec, Christopher R.; Touitou, Elka; Lerman, Melissa A.; Lazarovici, Philip; Lewin, Peter A.

    2015-01-01

    The purpose of this work was to investigate whether low frequency, low intensity (LFLI, 20 kHz, <100 mW/cm2, spatial-peak, temporal-peak) ultrasound (US), delivered by a light-weight (<100g), tether-free, fully wearable, battery powered applicator is capable of reducing inflammation in a mouse model of Rheumatoid Arthritis (RA). The therapeutic, acute, anti-inflammatory effect was estimated by the relative swelling induced in mice hind limb paws. In an independent, indirect approach, the inflammation was bio-imaged by measuring glycolytic activity with near infrared labeled 2-deoxy-glucose (2DG). The outcome of the experiments indicated that the combination of US exposure with topical application of 0.1% w/w betamethasone gel, exhibited statistically significant (p<0.05) enhanced anti-inflammatory properties in comparison with the drug or US treatment alone. The present study underscores the potential benefits of LFLI US assisted drug delivery. However, the proof of concept presented indicates the need for additional experiments to systematically evaluate and optimize the potential of, and the conditions for, safe, LFLI ultrasound promoted non-invasive drug delivery. PMID:26003010

  2. Psoriatic Arthritis with Annular Pustular Psoriasis.

    PubMed

    Nagafuchi, Hiroko; Watanabe, Kyoko; Mikage, Hidenori; Ozaki, Shoichi

    2016-01-01

    We herein present the case of a 56-year-old woman who presented with symptoms of psoriatic arthritis (PsA) with erythema that progressed to annular pustular psoriasis. The patient had a 15-year history of polyarthritis. Annular pustular psoriasis is not typically observed in cases of arthritis. This is the first reported case of PsA with annular pustular psoriasis.

  3. [Non-pharmacologic treatment of rheumatoid arthritis].

    PubMed

    Curković, Bozidar

    2010-01-01

    Non-pharmacologic interventions are the part of comprehensive therapy of rheumatoid arthritis, proposed by all guidelines and recommendations. Patients with rheumatoid arthritis have pain, limited joint mobility, and impaired quality of life. Physical modalities are prescribed exactly with idea to diminish pain, iprove joint mobility and quality of life. Physical procedures are generally safe and well tolerated.

  4. Therapeutic exercise for rheumatoid arthritis and osteoarthritis.

    PubMed

    Semble, E L; Loeser, R F; Wise, C M

    1990-08-01

    Therapeutic exercise in rheumatoid arthritis and osteoarthritis may be useful in improving aerobic capacity, strengthening muscles, improving endurance and increasing flexibility. This article reviews the major studies of exercise in these conditions and summarizes the authors recommendations regarding the use of therapeutic exercise in the treatment of rheumatoid arthritis osteoarthritis.

  5. A Comparison of Disease Burden in Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis

    PubMed Central

    Michelsen, Brigitte; Fiane, Ragnhild; Diamantopoulos, Andreas P.; Soldal, Dag Magnar; Hansen, Inger Johanne W.; Sokka, Tuulikki; Kavanaugh, Arthur; Haugeberg, Glenn

    2015-01-01

    Objective The main objective of this study was to compare disease burden in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (ax-SpA). Methods In this cross-sectional study, all the RA (1093), PsA (365) and ax-SpA (333) patients who visited the out-patient clinic of the Hospital of Southern Norway Trust during the year 2013 were included; the RA patients all had a RA diagnosis verified by the treating rheumatologist, the PsA patients all fulfilled the ClASsification for Psoriatic ARthritis (CASPAR) criteria and the ax-SpA patients all fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for ax-SpA. Patient-reported health status, demographic variables, medications, and composite scores of disease activity were assessed. The main analyses were performed using General Linear Models adjusted for age, sex and multiple comparisons. Correlation analyses were performed using Spearman’s rho. Results The reported pain, joint pain, patient’s global assessment and fatigue were similar in PsA and ax-SpA, but significantly lower in RA. The 28-joint Disease Activity Score (DAS28) (0.3±0.1, p = 0.003), Clinical Disease Activity Index (CDAI) (1.0±0.4, p = 0.028) and Routine Assessment of Patient Index Data 3 (RAPID3) (0.4±0.1, p = 0.004) were all significantly higher in PsA vs. RA. RAPID3 showed moderate to high correlation with DAS28 (rho = 0.521, p<0.001) and CDAI (rho = 0.768, p<0.001) in RA and PsA, and with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (rho = 0.902, p<0.001) and Bath Ankylosing Spondylitis Functional Index (BASFI) (0.865, p<0.001) in ax-SpA and PsA. Conclusion In conclusion, patient- reported outcome measures were similar in our population of PsA and ax-SpA patients, but significantly lower for the RA patients. Composite disease activity measures were lower in RA than in PsA and ax-SpA, but the magnitude of these differences was small and probably not of

  6. Childhood Psychosocial Stressors and Adult Onset Arthritis: Broad Spectrum Risk Factors and Allostatic Load

    PubMed Central

    Von Korff, Michael; Alonso, Jordi; Ormel, Johan; Angermeyer, Matthais; Bruffaerts, Ronny; Fleiz, Clara; de Girolamo, Giovanni; Kessler, Ronald C.; Kovess-Masfety, Viviane; Posada-Villa, José; Scott, Kate M.; Uda, Hidenori

    2009-01-01

    Neural, endocrine and immune stress mediators are hypothesized to increase risks of diverse chronic diseases, including arthritis. Retrospective data from the World Mental Health Surveys (N=18,309) were employed to assess whether adult onset of arthritis was associated with childhood adversities and early onset psychological disorder. Cox proportional hazard models assessed the association of number of childhood adversities and the presence of early onset psychological disorder with arthritis age of onset. Controlling for age, sex and early onset mental disorder, relative to persons with no childhood adversities, persons with two adversities had increased risk of adult onset arthritis (Hazard ratio=1.27, 95% CI= 1.08, 1.50), while persons with three or more adversities had higher risk (HR=1.44, CI=1.24,1.67). Early onset depressive and/or anxiety disorder was associated with increased risk of adult-onset arthritis after controlling for childhood adversities (HR=1.43, CI=1.28, 1.61). Since psychosocial stressors may be broad spectrum risk factors that increase risks of diverse chronic conditions in later life (e.g., arthritis, heart disease, diabetes, asthma, chronic pain), prospective studies of childhood psychosocial stressors may be most productive if multiple disease outcomes are assessed in the same study. Results from this study provide methodological guidance for future prospective studies of the relationship between childhood psychosocial stressors and subsequent risk of adult onset arthritis. PERSPECTIVE Retrospective reports of early onset mood-anxiety disorder and multiple childhood adversities were independently associated with increased risk of adult onset arthritis. Carrying out prospective studies of these relationships entails significant challenges. Since childhood psychosocial stressors may be broad spectrum risk factors for diverse chronic conditions, multiple disease outcomes should be assessed in prospective studies assessing health consequences

  7. Supplementation of diet with krill oil protects against experimental rheumatoid arthritis

    PubMed Central

    2010-01-01

    Background Although the efficacy of standard fish oil has been the subject of research in arthritis, the effect of krill oil in this disease has yet to be investigated. The objective of the present study was to evaluate a standardised preparation of krill oil and fish oil in an animal model for arthritis. Methods Collagen-induced arthritis susceptible DBA/1 mice were provided ad libitum access to a control diet or diets supplemented with either krill oil or fish oil throughout the study. There were 14 mice in each of the 3 treatment groups. The level of EPA + DHA was 0.44 g/100 g in the krill oil diet and 0.47 g/100 g in the fish oil diet. Severity of arthritis was determined using a clinical scoring system. Arthritis joints were analysed by histopathology and graded. Serum samples were obtained at the end of the study and the levels of IL-1α, IL-1β, IL-7, IL-10, IL-12p70, IL-13, IL-15, IL-17 and TGF-β were determined by a Luminex™ assay system. Results Consumption of krill oil and supplemented diet significantly reduced the arthritis scores and hind paw swelling when compared to a control diet not supplemented with EPA and DHA. However, the arthritis score during the late phase of the study was only significantly reduced after krill oil administration. Furthermore, mice fed the krill oil diet demonstrated lower infiltration of inflammatory cells into the joint and synovial layer hyperplasia, when compared to control. Inclusion of fish oil and krill oil in the diets led to a significant reduction in hyperplasia and total histology score. Krill oil did not modulate the levels of serum cytokines whereas consumption of fish oil increased the levels of IL-1α and IL-13. Conclusions The study suggests that krill oil may be a useful intervention strategy against the clinical and histopathological signs of inflammatory arthritis. PMID:20587038

  8. Improving physical activity in arthritis clinical trial (IMPAACT): study design, rationale, recruitment, and baseline data.

    PubMed

    Chang, Rowland W; Semanik, Pamela A; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D

    2014-11-01

    Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and Physical Function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change.

  9. IMPROVING PHYSICAL ACTIVITY IN ARTHRITIS CLINICAL TRIAL (IMPAACT): STUDY DESIGN, RATIONALE, RECRUITMENT, AND BASELINE DATA

    PubMed Central

    Chang, Rowland W.; Semanik, Pamela A.; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D.

    2014-01-01

    Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and physical function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. PMID:25183043

  10. Biomarkers for rheumatoid and psoriatic arthritis.

    PubMed

    Verheul, M K; Fearon, U; Trouw, L A; Veale, D J

    2015-11-01

    Rheumatic diseases, such as rheumatoid and psoriatic arthritis are systemic inflammatory conditions characterized by a chronic form of arthritis, often leading to irreversible joint damage. Early treatment for patients with rheumatic diseases is required to reduce or prevent joint injury. However, early diagnosis can be difficult and currently it is not possible to predict which individual patient will develop progressive erosive disease or who may benefit from a specific treatment according to their clinical features at presentation. Biomarkers are therefore required to enable earlier diagnosis and predict prognosis in both rheumatoid arthritis and psoriatic arthritis. In this review we will examine the evidence and current status of established and experimental biomarkers in rheumatoid and psoriatic arthritis for three important purposes; disease diagnosis, prognosis and prediction of response to therapy.

  11. Exploitation of the IDO Pathway in the Therapy of Rheumatoid Arthritis.

    PubMed

    Williams, Richard O

    2013-01-01

    Indoleamine 2,3-dioxygenase (IDO) is the first and rate-limiting step along the kynurenine pathway and is thought to play a key role in immune homeostasis through depletion of tryptophan and accumulation of kynurenines. In this review we summarize recent research into the possibility of harnessing the IDO pathway for the therapy of rheumatoid arthritis. Inhibition of IDO activity, or knockout of the gene encoding IDO, was shown to cause an increase in the severity of collagen-induced arthritis, an animal model of rheumatoid arthritis. The increased severity of disease was associated with elevated numbers of pathogenic Th1 and Th17 cells in the joints and draining lymph nodes. In another study, analysis of the kinetics of expression of downstream kynurenine pathway enzymes during the course of arthritis revealed a potential role for tryptophan metabolites in resolution of arthritis. Furthermore, the therapeutic administration of L-kynurenine or [3,4-dimethoxycinnamonyl]-anthranilic acid (a synthetic derivative of 3-hydroxy-anthranilic acid) significantly reduced both clinical and histological progression of experimental arthritis. These findings raise the possibility of exploiting the IDO pathway for the therapy of autoimmune disease.

  12. 38 CFR 4.58 - Arthritis due to strain.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... arthritis in the joints directly subject to strain. Amputation, or injury to an upper extremity, is not..., arthritis in the injured extremity, including also arthritis of the lumbosacral joints and lumbar spine, if..., that arthritis affecting joints not directly subject to strain as a result of the service...

  13. 38 CFR 4.58 - Arthritis due to strain.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... arthritis in the joints directly subject to strain. Amputation, or injury to an upper extremity, is not..., arthritis in the injured extremity, including also arthritis of the lumbosacral joints and lumbar spine, if..., that arthritis affecting joints not directly subject to strain as a result of the service...

  14. 38 CFR 4.58 - Arthritis due to strain.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... arthritis in the joints directly subject to strain. Amputation, or injury to an upper extremity, is not..., arthritis in the injured extremity, including also arthritis of the lumbosacral joints and lumbar spine, if..., that arthritis affecting joints not directly subject to strain as a result of the service...

  15. 38 CFR 4.58 - Arthritis due to strain.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... arthritis in the joints directly subject to strain. Amputation, or injury to an upper extremity, is not..., arthritis in the injured extremity, including also arthritis of the lumbosacral joints and lumbar spine, if..., that arthritis affecting joints not directly subject to strain as a result of the service...

  16. MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis

    PubMed Central

    Xian, Pei-Feng; Yang, Lu; Wang, Sheng-Xu

    2016-01-01

    MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway. PMID:27429986

  17. MicroRNA-21 Promotes Proliferation of Fibroblast-Like Synoviocytes through Mediation of NF-κB Nuclear Translocation in a Rat Model of Collagen-Induced Rheumatoid Arthritis.

    PubMed

    Chen, Ying; Xian, Pei-Feng; Yang, Lu; Wang, Sheng-Xu

    2016-01-01

    MicroRNA-21 (miR-21) is overexpressed in patients with rheumatoid arthritis (RA). This study was designed to investigate the effect and mechanism of miR-21 on cell proliferation in fibroblast-like synoviocytes (FLS) of RA. FLS were primary-cultured from a rat RA model. RA-FLS and normal FLS were infected with lentivirus (anti-miR-21 or pro-miR-21) for overexpression or downregulation of miR-21, respectively. The effects of miR-21 overexpression or inhibition on nucleoprotein NF-κB levels and FLS cell proliferation were evaluated by western blotting and MTT assays. The effects of an inhibitor of NF-κB nuclear translocation (BAY 11-7082) were also evaluated. The results showed that the levels of miR-21 and nucleoprotein NF-κB were increased in FLS of RA model rats compared to the control group. Downregulation of miR-21 in RA FLS led to a significant decrease in nucleoprotein NF-κB levels and cell proliferation rates compared to the antinegative control (NC) group. However, miR-21 overexpression in normal FLS resulted in a significant increase of nucleoprotein NF-κB levels and cell proliferation rates compared to the pro-NC group. The effects of miR-21 overexpression were reversed by BAY 11-7082. We concluded that upregulated miR-21 in FLS in RA model rats may promote cell proliferation by facilitating NF-κB nuclear translocation, thus affecting the NF-κB pathway.

  18. Circadian rhythms: glucocorticoids and arthritis.

    PubMed

    Cutolo, Maurizio; Sulli, Alberto; Pizzorni, Carmen; Secchi, Maria Elena; Soldano, Stefano; Seriolo, Bruno; Straub, Rainer H; Otsa, Kati; Maestroni, Georges J

    2006-06-01

    Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol. Interestingly, cortisol and MLT show an opposite response to the light. The light conditions in the early morning have a strong impact on the morning cortisol peak, whereas MLT is synthesized in a strictly nocturnal pattern. Recently, a diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and MLT. The interferon (IFN)-gamma/interleukin (IL)-10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma MLT. Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a "relative adrenal insufficiency" in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms. PMID:16855156

  19. Aryl hydrocarbon receptor antagonism and its role in rheumatoid arthritis

    PubMed Central

    Nguyen, Nam Trung; Nakahama, Taisuke; Nguyen, Chi Hung; Tran, Trang Thu; Le, Van Son; Chu, Hoang Ha; Kishimoto, Tadamitsu

    2015-01-01

    Although rheumatoid arthritis (RA) is the most common autoimmune disease, affecting approximately 1% of the population worldwide, its pathogenic mechanisms are poorly understood. Tobacco smoke, an environmental risk factor for RA, contains several ligands of aryl hydrocarbon receptor (Ahr), also known as dioxin receptor. Ahr plays critical roles in the immune system. We previously demonstrated that Ahr in helper T-cells contributes to development of collagen-induced arthritis, a mouse model of RA. Other studies have shown that cigarette smoke condensate and pure Ahr ligands exacerbate RA by altering bone metabolism and inducing proinflammatory responses in fibroblast-like synoviocytes. Consistent with these findings, several Ahr antagonists such as α-naphthoflavone, resveratrol, and GNF351 reverse the effect of Ahr ligands in RA pathogenesis. In this review, we summarize the current knowledge of Ahr function in the immune system and the potential clinical benefits of Ahr antagonism in treating RA. PMID:27186143

  20. Clinical and histological assessment of collagen-induced arthritis progression in the diabetes-resistant BB/Wor rat.

    PubMed

    Knoerzer, D B; Donovan, M G; Schwartz, B D; Mengle-Gaw, L J

    1997-01-01

    Collagen-induced arthritis in the diabetes-resistant BB (DR BB)/Wor rat is a severe, aggressive disease initiated by immunization with heterologous native Type II collagen. Onset of clinical symptoms reproducibly occurs in 100% of animals between days 10 and 12 following collagen immunization. Hypertrophy of the synovial lining is the first histological manifestation of the early inflammatory arthritis. A mild inflammatory infiltrate in the synovium rapidly becomes a fibrovascular pannus eroding articular cartilage and subchondral bone. Beginning at the joint margins, an active synovitis is present. Light microscopy and immunohistochemical staining show the infiltrate to be comprised of mononuclear (lymphocytes, macrophages) and polymorphonuclear inflammatory cells. In addition, there is histological evidence for chronic inflammatory nodules and necrotizing vasculitis in connective tissue from diseased joints, both morphologic features associated with rheumatoid arthritis in humans. Subchondral bone erosion appears to be mediated largely by the resorptive action of activated osteoclasts. These histological parameters of disease progression in the DR BB/Wor rat are similar to human rheumatoid arthritis. The extensive degree of similarity in the pathology of DR BB/Wor rat collagen-induced arthritis and human rheumatoid arthritis supports the role of this model as an in vivo disease model for human rheumatoid arthritis. PMID:9061845

  1. [Cardiovascular diseases in rheumatoid arthritis].

    PubMed

    Nakajima, Ayako

    2016-06-01

    Cardiovascular diseases (CVD) are serious complications in patients with rheumatoid arthritis (RA) in its high morbidity and mortality. The risk of coronary artery disease (CAD)has been reported to relate to RA disease activity. By improvement of treatment agents and treatment strategy aiming remission or low disease activity of RA, the incidence of CAD can be decreasing. The cardiovascular morbidity may be attributed to other types of CVD such as large vessel diseases, microvascular myocardial dysfunction or arrhythmia in addition to CAD. To improve quality of life and mortality of RA patients, physicians should treat patients to prevent cardiovascular morbidity through RA disease control. PMID:27311194

  2. Glucocorticoids in juvenile idiopathic arthritis.

    PubMed

    Malattia, Clara; Martini, Alberto

    2014-05-01

    Although the use of corticosteroids in juvenile idiopathic arthritis (JIA) is now much more limited owing to the availability of methotrexate and biological agents, there are clinical scenarios where it is still indicated. For example, corticosteroids may be indicated for intraarticular injections to prevent joint deformities, as a "bridge" drug to relieve symptoms in polyarticular disease while waiting for methotrexate and biologics to exert their full therapeutic effects, and in the treatment of chronic iridocyclitis, macrophage activation syndrome, and systemic JIA, although the advent of interleukin (IL)-1 and IL-6 blockers has greatly reduced the latter indication.

  3. Lung disease in rheumatoid arthritis.

    PubMed

    Yunt, Zulma X; Solomon, Joshua J

    2015-05-01

    Rheumatoid arthritis (RA) affects approximately 1% of the US population frequently has extra-articular manifestations. Most compartments of the lung are susceptible to disease. Interstitial lung disease (ILD) and airways disease are the most common forms of RA-related lung disease. RA-ILD carries the worst prognosis and most often manifests in a histologic pattern of usual interstitial pneumonia or nonspecific interstitial pneumonia. There have been no large, well-controlled prospective studies investigating therapies for RA-ILD. Treatment usually entails immunomodulatory agents. Further studies are needed to better understand pathogenic mechanisms of disease that lead to lung involvement in these patients.

  4. Biologic Therapy for Psoriatic Arthritis.

    PubMed

    Mease, Philip J

    2015-11-01

    Biologic medications, therapeutic proteins that inhibit or modulate proinflammatory immune cells and cytokines, have significantly altered clinicians' ability to effectively treat psoriatic arthritis (PsA). The first widely used biologics have been those targeting tumor necrosis factor alpha. Five agents (etanercept, infliximab, adalimumab, golimumab, and certolizumab) have shown significant benefit in all clinical domains of PsA as well as inhibiting progressive joint destruction. Treatment strategies such as treating PsA early in the disease course, treating to target and tight control, use of background methotrexate to reduce immunogenicity, and various cost-saving strategies are all being tested with biologic medicines for PsA.

  5. Treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis

    PubMed Central

    Machado, Marina Amaral de Ávila; de Moura, Cristiano Soares; Ferré, Felipe; Bernatsky, Sasha; Rahme, Elham; Acurcio, Francisco de Assis

    2016-01-01

    ABSTRACT OBJECTIVE To evaluate treatment persistence in patients with rheumatoid arthritis and ankylosing spondylitis who started therapies with disease-modifying antirheumatic drugs (DMARD) and tumor necrosis factor blockers (anti-TNF drugs). METHODS This retrospective cohort study from July 2008 to September 2013 evaluated therapy persistence, which is defined as the period between the start of treatment until it is discontinued, allowing for an interval of up to 30 days between the prescription end and the start of the next prescription. Odds ratio (OR) with 95% confidence intervals (95%CI) were calculated by logistic regression models to estimate the patients’ chances of persisting in their therapies after the first and after the two first years of follow-up. RESULTS The study included 11,642 patients with rheumatoid arthritis – 2,241 of these started on anti-TNF drugs (+/-DMARD) and 9,401 patients started on DMARD – and 1,251 patients with ankylosing spondylitis – 976 of them were started on anti-TNF drugs (+/-DMARD) and 275 were started on DMARD. In the first year of follow-up, 63.5% of the patients persisted in their therapies with anti-TNF drugs (+/-DMARD) and 54.1% remained using DMARD in the group with rheumatoid arthritis. In regards to ankylosing spondylitis, 79.0% of the subjects in anti-TNF (+/-DMARD) group and 41.1% of the subjects in the DMARD group persisted with their treatments. The OR (95%CI) for therapy persistence was 1.50 (1.34-1.67) for the anti-TNF (+/-DMARD) group as compared with the DMARD group in the first year for the patients with rheumatoid arthritis, and 2.33 (1.74-3.11) for the patients with ankylosing spondylitis. A similar trend was observed at the end of the second year. CONCLUSIONS A general trend of higher rates of therapy persistence with anti-TNF drugs (+/-DMARD) was observed as compared to DMARD in the study period. We observed higher persistence rates for anti-TNF drugs (+/-DMARD) in patients with ankylosing

  6. Epidemiology of Rheumatoid Arthritis in Tirana, Albania

    PubMed Central

    Duraj, Valbona; Tafaj, Argjent; Backa, Teuta

    2013-01-01

    Conflict of interest: none declared. Aim Rheumatoid arthritis is considered a clinical syndrome across several disease subsets characterized by systemic inflammation, persistent synovitis, and autoantibodies. Our aim was to assess the distribution of risk factors among people diagnosed with rheumatoid arthritis in the adult population of Tirana, the capital city of Albania. Methods All individuals diagnosed with rheumatoid arthritis in primary health care services of Tirana city during the period 2009-2012 were included in this study. The diagnosis of rheumatoid arthritis was based on the clinical signs and symptoms and laboratory tests including measurement of the rheumatoid factor. Results Overall, there were identified 817 cases with rheumatoid arthritis in all primary health care centers of Tirana for the period 2009-2012. Of these, 529 (65%) were women and 288 (35%) were men. Genetic factors accounted for 60% of the diseases in women and 45% in men (P<0.001). In both sexes, the proportion of older individuals was higher compared with younger adults. Most of the individuals with rheumatoid were from urban areas of Tirana. Conclusion Our study provides new evidence about the distribution of risk factors of rheumatoid arthritis in transitional Albania where valid and reliable data about this disease were scarce. Future studies in Albania should assess the prevalence of rheumatoid arthritis in population-based samples. PMID:24082831

  7. Diagnosis and management of rheumatoid arthritis.

    PubMed

    Wasserman, Amy M

    2011-12-01

    Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management.

  8. Immunopathological features of rat Staphylococcus aureus arthritis.

    PubMed Central

    Bremell, T; Lange, S; Holmdahl, R; Rydén, C; Hansson, G K; Tarkowski, A

    1994-01-01

    Staphylococcus aureus is the most common bacterial species found in nongonococcal bacterial arthritis in humans. We present the first description, to our knowledge, of an outbreak of spontaneous staphylococcal arthritis in a rat colony. In a group of 10 rats, 9 displayed arthritis. Clinically, the most obvious findings were arthritis of one or both hindpaws and malaise. Bacteriophage typing showed the common phage type 85 in isolates recovered from the joints, blood, and bedding of rats and from the nose and cheeks of one person from the staff of the animal facility. The S. aureus strain proved to produce staphylococcal enterotoxin A and exhibited strong binding to collagen types I and II and bone sialoprotein, which are potentially important virulence factors. When the recovered S. aureus strain was injected intravenously into healthy rats, severe septic arthritis was induced in almost all of the animals. The arthritic lesions were characterized by infiltration of phagocytic cells and T lymphocytes into the synovium. Many of the synovial cells strongly expressed major histocompatibility complex class II molecules. Increased levels of interleukin 6 in serum as well as a prominent polyclonal B-cell activation were noted throughout the disease course. Pretreatment of S. aureus-injected rats in vivo with an antibody to the alpha beta T-cell receptor significantly decreased the severity of the arthritis. Our results indicate that alpha beta + T lymphocytes contribute to an erosive and persistent course of S. aureus arthritis. Images PMID:8188356

  9. Diagnosis and management of rheumatoid arthritis.

    PubMed

    Wasserman, Amy M

    2011-12-01

    Rheumatoid arthritis is the most commonly diagnosed systemic inflammatory arthritis. Women, smokers, and those with a family history of the disease are most often affected. Criteria for diagnosis include having at least one joint with definite swelling that is not explained by another disease. The likelihood of a rheumatoid arthritis diagnosis increases with the number of small joints involved. In a patient with inflammatory arthritis, the presence of a rheumatoid factor or anti-citrullinated protein antibody, or elevated C-reactive protein level or erythrocyte sedimentation rate suggests a diagnosis of rheumatoid arthritis. Initial laboratory evaluation should also include complete blood count with differential and assessment of renal and hepatic function. Patients taking biologic agents should be tested for hepatitis B, hepatitis C, and tuberculosis. Earlier diagnosis of rheumatoid arthritis allows for earlier treatment with disease-modifying antirheumatic agents. Combinations of medications are often used to control the disease. Methotrexate is typically the first-line drug for rheumatoid arthritis. Biologic agents, such as tumor necrosis factor inhibitors, are generally considered second-line agents or can be added for dual therapy. The goals of treatment include minimization of joint pain and swelling, prevention of radiographic damage and visible deformity, and continuation of work and personal activities. Joint replacement is indicated for patients with severe joint damage whose symptoms are poorly controlled by medical management. PMID:22150658

  10. 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.

  11. 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

  12. [Current treatment of rheumatoid arthritis].

    PubMed

    Carli, P; Landais, C; Aletti, M; Cournac, J-M; Poisnel, E; Paris, J-F

    2009-12-01

    Over the past 10 years, the management of rheumatoid arthritis has been revolutionized. Early diagnosis is essential and should allow an early initiation of disease modifying anti-rheumatic drugs (DMARD), if possible within the first 3 three months after disease onset, aiming at disease remission and the best long-term prognosis. Recommendations for the prescription of synthetic and biologic DMARD (mainly anti-TNFalpha agents) are available since September 2007 [6] by HAS in France. The great efficacy of these drugs has been established from many clinical trials including tens of thousands of patients. However, severe adverse side effects may occur (allergy, tuberculosis, opportunistic infections, demyelination) and rheumatologists should remain vigilant. Global care of the patient includes prescription of pharmacologic and non-pharmacologic treatments (education, physical treatment, ergotherapy, psychotherapy, surgery). A good coordination between all specialists is required. Screening and treatment of extra-articular manifestations, prevention of infections, osteoporosis and cardiovascular complications are essential to allow a better long-term prognosis, and reduce disability and mortality of rheumatoid arthritis.

  13. Chronic Lyme disease arthritis: review of the literature and report of a case of wrist arthritis.

    PubMed

    Scerpella, T A; Engber, W D

    1992-05-01

    A case of Lyme arthritis with advanced degenerative changes localized to the midcarpal joint was treated with a limited wrist arthrodesis with relief of pain and improved function. Chronic Lyme arthritis occurs as the third stage of Lyme disease. Serologic testing and a history of a characteristic rash may be helpful in the diagnosis. Radiographic and histopathologic findings are nonspecific, with both degenerative and inflammatory characteristics. Intravenous antibiotics provide an effective treatment of chronic Lyme arthritis.

  14. Antigen-specific tolerogenic and immunomodulatory strategies for the treatment of autoimmune arthritis

    PubMed Central

    Satpute, Shailesh R.; Durai, Malarvizhi; Moudgil, Kamal D.

    2008-01-01

    Objectives To review various antigen-specific tolerogenic and immunomodulatory approaches for arthritis in animal models and patients in regard to their efficacy, mechanisms of action and limitations. Methods We reviewed the published literature in Medline (PubMed) on the induction of antigen-specific tolerance and its effect on autoimmune arthritis, as well as the recent work on B cell-mediated tolerance from our laboratory. The prominent key words used in different combinations included arthritis, autoimmunity, immunotherapy, innate immunity, tolerance, treatment, and rheumatoid arthritis (RA). Although this search spanned the years 1975 to 2007, the majority of the short-listed articles belonged to the period 1990 to 2007. The relevant primary as well as cross-referenced articles were then collected from links within PubMed and reviewed. Results Antigen-specific tolerance has been successful in the prevention and/or treatment of arthritis in animal models. The administration of soluble native antigen or an altered peptide ligand intravenously, orally, or nasally, and the delivery of the DNA encoding a particular antigen by gene therapy have been the mainstay of immunomodulation. Recently, the methods for in vitro-expansion of CD4+CD25+ regulatory T cells have been optimized. Furthermore, interleukin-17 has emerged as a promising new therapeutic target in arthritis. However, in RA patients, non-antigen-specific therapeutic approaches have been much more successful than antigen-specific tolerogenic regimens. Conclusion An antigen-specific treatment against autoimmune arthritis is still elusive. However, insights into newly emerging mechanisms of disease pathogenesis provide hope for the development of effective and safe immunotherapeutic strategies in the near future. PMID:18177689

  15. Inhibition by Artocarpus tonkinensis of the development of collagen-induced arthritis in rats.

    PubMed

    Ngoc, D D T; Catrina, A I; Lundberg, K; Harris, H E; Ha, N T; Anh, P T; Larsson, P

    2005-03-01

    Extracts of the leaves and roots from the tree Artocarpus tonkinensis A Cheval (family Moraceae) are used in traditional Vietnamese medicine in order to treat backache as well as rheumatic joint diseases. We prepared an ethyl acetate (EtOAc) extract from this plant and tested its anti-inflammatory properties in an experimental arthritis model, collagen-induced arthritis (CIA). CIA was induced in Dark Agouti rats by means of immunization with collagen type II (CII) emulsified in incomplete Freund's adjuvant. Starting at the day of immunization, the rats were treated daily with intraperitoneal injections of Artocarpus extract. Arthritis progression was measured by means of clinical scoring of paws and anti-CII antibody titres were measured by means of ELISA. In vitro, lymph node (LN) cell cultures were treated with Artocarpus extract and the apoptosis-inducing effect was determined with FACS staining by using annexin V and propidium iodide as well as the TUNEL method. Treatment of the rats with Artocarpus extract decreased arthritis incidence and severity and delayed disease onset. When treatment was started after the onset of arthritis, a tendency towards arthritis amelioration was observed. In vitro, Artocarpus extract acted as a T-cell modulator, inhibiting mitogen-induced T-cell proliferation and inducing apoptosis of activated LN-derived lymphocytes. Thus, we have demonstrated that an EtOAc extract of Artocarpus, a plant traditionally used in Vietnamese folk medicine for treating arthritic conditions, has beneficial effects in an experimental arthritis model. This effect is likely to be T cell-dependent and mediated through apoptosis induction in activated cells.

  16. My treatment approach to rheumatoid arthritis.

    PubMed

    Davis, John M; Matteson, Eric L

    2012-07-01

    The past decade has brought important advances in the understanding of rheumatoid arthritis and its management and treatment. New classification criteria for rheumatoid arthritis, better definitions of treatment outcome and remission, and the introduction of biologic response-modifying drugs designed to inhibit the inflammatory process have greatly altered the approach to managing this disease. More aggressive management of rheumatoid arthritis early after diagnosis and throughout the course of the disease has resulted in improvement in patient functioning and quality of life, reduction in comorbid conditions, and enhanced survival.

  17. Specificity Evaluation and Disease Monitoring in Arthritis Imaging with Complement Receptor of the Ig superfamily targeting Nanobodies

    PubMed Central

    Zheng, Fang; Perlman, Harris; Matthys, Patrick; Wen, Yurong; Lahoutte, Tony; Muyldermans, Serge; Lu, Shemin; De Baetselier, Patrick; Schoonooghe, Steve; Devoogdt, Nick; Raes, Geert

    2016-01-01

    Single-photon emission computed tomography combined with micro-CT (SPECT/μCT) imaging using Nanobodies against complement receptor of the Ig superfamily (CRIg), found on tissue macrophages such as synovial macrophages, has promising potential to visualize joint inflammation in experimental arthritis. Here, we further addressed the specificity and assessed the potential for arthritis monitoring. Signals obtained with 99mTc-labelled NbV4m119 Nanobody were compared in joints of wild type (WT) versus CRIg−/− mice with collagen-induced arthritis (CIA) or K/BxN serum transfer-induced arthritis (STIA). In addition, SPECT/μCT imaging was used to investigate arthritis development in STIA and in CIA under dexamethasone treatment. 99mTc-NbV4m119 accumulated in inflamed joints of WT, but not CRIg−/− mice with CIA and STIA. Development and spontaneous recovery of symptoms in STIA was reflected in initially increased and subsequently reduced joint accumulation of 99mTc-NbV4m119. Dexamethasone treatment of CIA mice reduced 99mTc-NbV4m119 accumulation as compared to saline control in most joints except knees. SPECT/μCT imaging with 99mTc-NbV4m119 allows specific assessment of inflammation in different arthritis models and provides complementary information to clinical scoring for quantitatively and non-invasively monitoring the pathological process and the efficacy of arthritis treatment. PMID:27779240

  18. Successful induction of severe destructive arthritis by the transfer of in vitro-activated synovial fluid T cells from patients with rheumatoid arthritis (RA) in severe combined immunodeficient (SCID) mice.

    PubMed

    Sakata, A; Sakata, K; Ping, H; Ohmura, T; Tsukano, M; Kakimoto, K

    1996-05-01

    In order to investigate the role of pathogenic T cells in RA, the establishment of an RA model using patients' T cells is thought to be essential. In this study, multiple and severe destructive arthritis was established by transferring in vitro-stimulated synovial fluid T (SFT) cells from patients with RA through simultaneous injection into knee joint and peritoneal cavity of SCID mice without causing xenogeneic graft-versus-host disease (GVHD). Neither the transfer of unstimulated SFT cells nor sole i.p. injection was sufficient to induce severe arthritis. Interestingly, in contrast with SFT cells, in vitro-activated peripheral blood lymphocytes from RA patients failed to trigger such arthritis, suggesting that pathogenic T cells might be concentrated in synovial fluid of RA patients. This, the first severe arthritis model mimicking RA induced by RA patients' T cells, is expected to provide important information about RA pathogenesis and a possible therapeutic approach.

  19. Antibody-mediated modulation of arthritis induced by Chlamydia.

    PubMed Central

    Rank, R. G.; Ramsey, K. H.; Hough, A. J.

    1988-01-01

    The purpose of this investigation was to determine the role of the humoral immune response in the production of arthritis in mice immunized with the chlamydial agent of mouse pneumonitis (MoPn) (Chlamydia trachomatis biovar). Mice were made B cell deficient (BCD) by treatment with rabbit antiserum to murine IgM. Control mice included animals treated similarly with normal rabbit serum or phosphate-buffered saline. Male mice were immunized with MoPn inactivated with ultraviolet irradiation while female mice were immunized by genital tract infection with viable chlamydiae. Arthritis was elicited in all mice by intra-articular inoculation of inactivated MoPn. When knee joints were examined for pathologic changes at varying times after challenge, a marked enhancement of the arthritis was observed in both male and female BCD mice when compared with controls at all time points. These data indicated that the humoral immune response is not essential for the production of arthritic disease in this model but may have some role in the modulation of the process in immunologically intact animals. Persistence of chlamydial antigen in joint tissue of BCD mice suggested that antibody may play a role in the elimination of antigen, thus decreasing the stimulus for the development of cell-mediated immunologic injury. Regulatory role for T suppressor cells cannot be ruled out however, because B cell deficient mice have been shown to lack certain T suppressor cell subsets. Images Figure 3 Figure 4 Figure 6 Figure 7 Figure 9 PMID:3400779

  20. Altered composition of gut microbiota in rheumatoid arthritis patients.

    PubMed

    Maeda, Yuichi; Kumanogoh, Atsushi; Takeda, Kiyoshi

    2016-01-01

      Manifestation of rheumatoid arthritis (RA) can be attributed to both genetic and environmental factors. Some researchers have been focusing on intestinal microbiota which is thought to be one of the environmental factors that may enhance the development of RA. The advancement of culture-independent, high throughput microbial DNA sequencing had enabled us to understand the interplay between intestinal microbiota and host immune systems. In this study, we have reviewed the previous findings in animal and human studies with respect to the role of intestinal microbiota in RA. Mouse models of arthritis have demonstrated that gut microbiota plays a critical role in the disease development. K/BxN and IL-1 receptor-antagonist knock-out mice did not develop disease in germ free condition, however, colonization of particular intestinal bacteria was sufficient to induce arthritis. Moreover, the dysbiosis was observed in the human RA patients from United States, China and Finland. Thus, we believe that endeavors to improve the dysbiosis would serve as a novel therapeutic or preventive strategy in RA patients. PMID:27181236

  1. Haemodynamics in acute arthritis of the knee in puppies.

    PubMed

    Bünger, C; Hjermind, J; Bach, P; Bünger, E H; Myhre-Jensen, O

    1984-04-01

    In order to study the haemodynamic changes of the juvenile knee in acute arthritis, an experimental model was developed in puppies by unilateral intra-articular injections of Carragheenin solution into the knee. Tissue blood flow was studied by the tracer microsphere technique in eight dogs and simultaneous intra-articular and intraosseous pressure recordings were performed in seven other dogs. The intra-articular pressure was elevated in all arthritic knees. Hyperaemia was found in the knee-joint capsule and distal femoral metaphysis, whereas juxta-articular epiphyseal blood flow rates were not significantly changed. A decrease of femoral muscle blood flow was encountered. Intraosseous pressure recordings during venous tamponade of the knee-joint capsules suggested a qualitative change of bone vasculature in acute arthritis. The juxta-articular bone blood flow in arthritis appears to be influenced by synovial hyperaemia, synovial effusion pressure, an "inflammatory resistance factor" and the anatomical relationship of the epiphyseal vessels to the knee-joint capsule. PMID:6711289

  2. Verna Wright Lecture: Psoriatic Arthritis: The Need for Early Intervention.

    PubMed

    McHugh, Neil J

    2015-11-01

    About 30% of individuals with skin psoriasis will develop an inflammatory disease of the peripheral or axial skeleton involving synovial and/or entheseal tissue termed psoriatic arthritis (PsA). In most cases psoriasis will precede PsA by several years. Hence skin psoriasis provides an opportune model to investigate genetic and environmental factors that interact and contribute to the development of a common form of inflammatory arthritis. Further, the preexisting presence of psoriasis represents a unique opportunity for the early detection of arthritis and the potential for more effective intervention. However, despite the presence of psoriasis, there may be delay in the diagnosis of PsA that is associated with adverse longterm outcome. Undiagnosed disease is not uncommon, as demonstrated by studies applying screening questionnaires to primary care and dermatology clinic populations. Other potential risk factors, such as obesity and smoking, the presence of certain genetic and biomarker profiles, combined with accurate imaging modalities, offer the potential for more targeted screening. So in future it should be possible to detect PsA at a much earlier stage and prevent significant joint damage and associated disability before it happens.

  3. 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

    2016-09-01

    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.

  4. Golimumab for the treatment of psoriatic arthritis.

    PubMed

    Yang, H; Epstein, D; Bojke, L; Craig, D; Light, K; Bruce, I; Sculpher, M; Woolacott, N

    2011-05-01

    from controlled studies in other conditions, such as rheumatoid arthritis and ankylosing spondylitis. Although the adverse effect profile of golimumab appears similar to other anti-tumour necrosis factor (TNF) agents, the longer-term safety profile of golimumab remains uncertain. The manufacturer's submission presented a decision model to compare etanercept, infliximab, golimumab and adalimumab versus palliative care for patients with PsA. In the base-case model, 73% of the cohort of patients were assumed to have significant psoriasis (> 3% of body surface area). Estimates of the effectiveness of anti-TNF agents in terms of PsARC, HAQ change and PASI change were obtained from an MTC analysis of RCT data. The manufacturer failed to calculate incremental cost-effectiveness ratios (ICERs) correctly by comparing golimumab with palliative care instead of the most cost-effective alternative (etanercept). Despite the manufacturer's claim that golimumab is a cost-effective treatment option, the manufacturer's own model showed that golimumab is not cost-effective compared with other biologics when the ICERs are correctly calculated. None of the sensitivity analyses carried out by the manufacturer or the ERG regarding uncertainty in the estimates of clinical effectiveness, the acquisition and administration cost of drugs, the cost of treating psoriasis and the utility functions estimated to generate health outcomes changed this conclusion. However, a key area in determining the cost-effectiveness of anti-TNF agents is whether they should be treated as a class. If all anti-TNF agents are considered equally effective then etanercept, adalimumab and golimumab have very nearly equal costs and equal quality-adjusted life-years (QALYs), and all have an ICER of about £ 15,000 per QALY versus palliative care, whereas infliximab with a higher acquisition cost is dominated by the other biologics.

  5. Risk of Major Cardiovascular Events in Patients with Psoriatic Arthritis, Psoriasis and Rheumatoid Arthritis: A population-based cohort study

    PubMed Central

    Yu, YiDing; Haynes, Kevin; Love, Thorvardur Jon; Maliha, Samantha; Jiang, Yihui; Troxel, Andrea B.; Hennessy, Sean; Kimmel, Stephen E.; Margolis, David J.; Choi, Hyon; Mehta, Nehal N.; Gelfand, Joel M.

    2015-01-01

    Objectives We aimed to quantify the risk of major adverse cardiovascular events (MACE) among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and psoriasis without known PsA compared to the general population after adjusting for traditional cardiovascular risk factors. Methods A population-based longitudinal cohort study from 1994–2010 was performed in The Health Improvement Network (THIN), a primary care medical record database in the United Kingdom. Patients aged 18–89 with PsA, RA, or psoriasis were included. Up to 10 unexposed controls matched on practice and index date were selected for each patient with PsA. Outcomes included cardiovascular death, myocardial infarction, cerebrovascular accidents, and the composite outcome (MACE). Cox proportional hazards models were used to calculate the hazard ratios (HR) for each outcome adjusted for traditional risk factors. A priori we hypothesized an interaction between disease status and disease modifying anti-rheumatic drug (DMARD) use. Results Patients with PsA (N=8,706), RA (N=41,752), psoriasis (N=138,424) and unexposed controls (N=81,573) were identified. After adjustment for traditional risk factors, the risk of MACE was higher in PsA patients not prescribed a DMARD (HR 1.24, 95%CI: 1.03 to 1.49), patients with RA (No DMARD: HR 1.39, 95%CI: 1.28 to 1.50, DMARD: HR 1.58, 95%CI: 1.46 to 1.70), patients with psoriasis not prescribed a DMARD (HR 1.08, 95%CI: 1.02 to 1.15) and patients with severe psoriasis (DMARD users: HR 1.42, 95%CI: 1.17 to 1.73). Conclusions Cardiovascular risk should be addressed with all patients affected by psoriasis, psoriatic arthritis or rheumatoid arthritis. PMID:25351522

  6. ASTROMEDICINE IN THE TREATMENT OF RHEUMATOID ARTHRITIS

    PubMed Central

    Janai, Sudhakar; Biviji, A. T.; Naik, D. G.; Lakhe, R. T.; Rao, V. Bhaskar

    1991-01-01

    One patient of rheumatoid arthritis was treated according to astromedicine. Wearing of Coral beads had remarkable effect on the disease. The interesting finding are reported in this paper. PMID:22556538

  7. Vocational Rehabilitation for Persons with Rheumatoid Arthritis.

    ERIC Educational Resources Information Center

    Allaire, Saralynn H.

    1998-01-01

    Useful vocational rehabilitation strategies for persons with rheumatoid arthritis include (1) management of symptoms and reduction of energy demand; (2) reasonable job accommodations; (3) identification of suitable jobs and necessary training; and (4) enhancement of self-advocacy skills. (SK)

  8. Management of melioidosis osteomyelitis and septic arthritis.

    PubMed

    Shetty, R P; Mathew, M; Smith, J; Morse, L P; Mehta, J A; Currie, B J

    2015-02-01

    Little information is available about several important aspects of the treatment of melioidosis osteomyelitis and septic arthritis. We undertook a retrospective review of 50 patients with these conditions in an attempt to determine the effect of location of the disease, type of surgical intervention and duration of antibiotic treatment on outcome, particularly complications and relapse. We found that there was a 27.5% risk of osteomyelitis of the adjacent bone in patients with septic arthritis in the lower limb. Patients with septic arthritis and osteomyelitis of an adjacent bone were in hospital significantly longer (p = 0.001), needed more operations (p = 0.031) and had a significantly higher rate of complications and re-presentation (p = 0.048). More than half the patients (61%), most particularly those with multifocal bone and joint involvement, and those with septic arthritis and osteomyelitis of an adjacent bone who were treated operatively, needed more visits to theatre.

  9. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    PubMed

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA. PMID:26603475

  10. Factors secreted from dental pulp stem cells show multifaceted benefits for treating experimental rheumatoid arthritis.

    PubMed

    Ishikawa, Jun; Takahashi, Nobunori; Matsumoto, Takuya; Yoshioka, Yutaka; Yamamoto, Noriyuki; Nishikawa, Masaya; Hibi, Hideharu; Ishigro, Naoki; Ueda, Minoru; Furukawa, Koichi; Yamamoto, Akihito

    2016-02-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and chronic inflammation, which lead to the progressive destruction of cartilage and bone in the joints. Numerous studies have reported that administrations of various types of MSCs improve arthritis symptoms in animal models, by paracrine mechanisms. However, the therapeutic effects of the secreted factors alone, without the cell graft, have been uncertain. Here, we show that a single intravenous administration of serum-free conditioned medium (CM) from human deciduous dental pulp stem cells (SHED-CM) into anti-collagen type II antibody-induced arthritis (CAIA), a mouse model of rheumatoid arthritis (RA), markedly improved the arthritis symptoms and joint destruction. The therapeutic efficacy of SHED-CM was associated with an induction of anti-inflammatory M2 macrophages in the CAIA joints and the abrogation of RANKL expression. SHED-CM specifically depleted of an M2 macrophage inducer, the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9), exhibited a reduced ability to induce M2-related gene expression and attenuate CAIA. SHED-CM also inhibited the RANKL-induced osteoclastogenesis in vitro. Collectively, our findings suggest that SHED-CM provides multifaceted therapeutic effects for treating CAIA, including the ED-Siglec-9-dependent induction of M2 macrophage polarization and inhibition of osteoclastogenesis. Thus, SHED-CM may represent a novel anti-inflammatory and reparative therapy for RA.

  11. Synergistic benefit in inflammatory arthritis by targeting IκB kinase ε and interferon β

    PubMed Central

    Corr, M; Boyle, D L; Ronacher, L; Flores, N; Firestein, G S

    2009-01-01

    Objectives The IκB kinase (IKK)-related kinase IKKε regulates type I interferon expression and responses as well as proinflammatory mediator production. We examined the role of IKKε in arthritis and its ability to enhance the therapeutic response to systemic interferon (IFN) β therapy in passive murine K/BxN arthritis. Methods IKKε−/−, IFNα~βR−/− and wild type mice were given K/BxN serum and treated with polyinosinic polycytidylic acid (poly(I:C)), IFNβ, or normal saline. Clinical response and histological scores were assessed. Gene expression in the paws was measured by quantitative PCR. Serum interleukin 1a receptor agonist (IL1Ra) and IL10 were measured by ELISA and multiplex bead array. Results Arthritis was almost completely blocked in wild type mice if arthritogenic K/BxN serum and the Toll-like receptor (TLR)3 ligand, poly(I:C), were coadministered at the onset of the model, but not in established disease. Mice deficient in IFNα~βR had an accelerated course of arthritis, and did not respond to poly(I:C). IKKε null mice had a modest decrease in clinical arthritis compared with heterozygous mice. Low doses of IFNβ that were ineffective in wild type mice significantly decreased clinical arthritis in IKKε null mice. Articular chemokine gene expression was reduced in the IKKε−/− mice with arthritis and secreted IL1Ra (sIL1Ra) mRNA was significantly increased. Serum levels of IL1Ra were increased in low dose IFNβ-treated IKKε−/− mice. Conclusions Subtherapeutic doses of IFNβ enhance the anti-inflammatory effects of IKKε deficiency, possibly by increasing production of IL1Ra and unmasking the antichemokine effects. Combination therapy with low dose IFNβ and an IKKε inhibitor might improve efficacy of either agent alone and offers a novel approach to RA. PMID:18653628

  12. αvβ3-Targeted nanotherapy suppresses inflammatory arthritis in mice

    PubMed Central

    Zhou, Hui-fang; Chan, Happy W.; Wickline, Samuel A.; Lanza, Gregory M.; Pham, Christine T. N.

    2009-01-01

    The purpose of this study was to assess whether an alternative treatment approach that targets angiogenesis, delivered through ligand-targeted nanotherapy, would ameliorate inflammatory arthritis. Arthritis was induced using the K/BxN mouse model of inflammatory arthritis. After arthritis was clearly established, mice received three consecutive daily doses of αvβ3-targeted fumagillin nanoparticles. Control groups received no treatment or αvβ3-targeted nanoparticles without drugs. Disease score and paw thickness were measured daily. Mice that received αvβ3-targeted fumagillin nanoparticles showed a significantly lower disease activity score (mean score of 1.4±0.4; P<0.001) and change in ankle thickness (mean increase of 0.17±0.05 mm; P<0.001) 7 d after arthritis induction, whereas the group that received αvβ3-targeted nanoparticles without drugs exhibited a mean arthritic score of 9.0 ± 0.3 and mean change in ankle thickness of 1.01 ± 0.09 mm. Meanwhile, the group that received no treatment showed a mean arthritic score of 9.8 ± 0.5 and mean change in ankle thickness of 1.05 ± 0.10 mm. Synovial tissues from animals treated with targeted fumagillin nanoparticles also showed significant decrease in inflammation and angiogenesis and preserved proteoglycan integrity. Ligand-targeted nanotherapy to deliver antiangiogenic agents may represent an effective way to treat inflammatory arthritis.—Zhou, H.-F., Chan, H. W., Wickline, S. A., Lanza, G. M., Pham, C. T. N. αvβ3-Targeted nanotherapy suppresses inflammatory arthritis in mice. PMID:19376816

  13. Clinical management of septic arthritis in cattle.

    PubMed

    Desrochers, André; Francoz, David

    2014-03-01

    Synovial fluid, ultrasound, and radiographic imaging are common diagnostic tools for septic arthritis. Mycoplasma septic arthritis is suspected in calves with clinical signs of otitis and pneumonia. Commonly affected joints are carpus, stifle, and tarsus. Treatment strategy must include long-term antibiotics, anti-inflammatories, and joint lavage. Knowledge of communication and boundaries for commonly affected joints is essential to perform joint lavage and arthrotomy.

  14. [Septic arthritis of thoracic facet joint].

    PubMed

    Ben Abdelghani, K; Gérard-Dran, D; Combe, B

    2009-08-01

    Septic arthritis of the facet joint is a rare condition. We report a case of septic arthritis of both a thoracic facet joint and a wrist. Clinical manifestations were consistent with a spondylodiscitis. Magnetic resonance imaging of the spine demonstrated infection of facet joints of T1 and T2. A surgical biopsy of the wrist isolated a type B streptococcus. The same organism was found in urine culture. The patient had an uneventful recovery on antibiotics.

  15. Anti cytokine therapy in chronic inflammatory arthritis.

    PubMed

    Thompson, Charlotte; Davies, Ruth; Choy, Ernest

    2016-10-01

    This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17. PMID:27497159

  16. Psoriatic Arthritis with Annular Pustular Psoriasis.

    PubMed

    Nagafuchi, Hiroko; Watanabe, Kyoko; Mikage, Hidenori; Ozaki, Shoichi

    2016-01-01

    We herein present the case of a 56-year-old woman who presented with symptoms of psoriatic arthritis (PsA) with erythema that progressed to annular pustular psoriasis. The patient had a 15-year history of polyarthritis. Annular pustular psoriasis is not typically observed in cases of arthritis. This is the first reported case of PsA with annular pustular psoriasis. PMID:26935375

  17. Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew/SSN rat.

    PubMed

    Volker, D; Bate, M; Gentle, R; Garg, M

    2000-10-01

    This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew/SSN rats. Forty weanling rats lin 2 groups) were trained to accept disks of jelly as part of their dietary regimen. At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were incorporated into the jelly disks to alleviate the pain of acute arthritis, which developed 24 h post-induction. Group A rats received buprenorphine at a rate of 1 mg/kg 12 hourly. Group B rats received buprenorphine at a rate of 2 mg/kg 12 hourly. Both groups of rats were monitored for symptoms of distress using an adaptation of the Morton and Griffin scale of adverse reactions. Group A rats with severe arthritis required additional subcutaneous (s.c.) injections of buprenorphine to alleviate the adverse effects of arthritis. Group B rats, with twice the dose of buprenorphine did not require additional s.c. injections of buprenorphine. Histological sections of rat hocks indicated that the inflammation was suppressed in Group B rats. We concluded that oral administration of buprenorphine is an effective method of pain management in the pathogenesis of SCW-induced arthritis in Lew/SSN rats. In this model of arthritis, oral buprenorphine has a significant anti-inflammatory effect and appears to modulate the destructive arthritic phase in joints in this animal model of arthritis.

  18. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

    PubMed

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  19. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

    PubMed Central

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  20. Tuberculous arthritis of the elbow joint: A case report

    PubMed Central

    Yazıcı, Ayten; Kayan, Gökçen; Yaylacı, Selçuk; Demir, Mustafa Volkan; Karakeçe, Engin; Tamer, Ali; Karabay, Oğuz

    2016-01-01

    Tuberculous arthritis of the elbow joint is rare. A 57-year-old male patient presented with swelling, pain, and redness of the elbow. The symptoms first appeared one month ago; he was given antibiotic treatment after the diagnosis of septic arthritis at another center. The patient who did not improve with treatment was diagnosed with tuberculous arthritis according to the culture and was started on antituberculosis treatment. Tuberculous arthritis usually presents with chronic arthritis. However, it can also present in patients with septic arthritis. PMID:27733947

  1. [New therapies for rheumatoid arthritis].

    PubMed

    Salgado, Eva; Maneiro, José Ramón

    2014-11-18

    Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterized by inflammation of the synovial membrane and progressive destruction of the articular cartilage and bone. Advances in the knowledge of disease pathogenesis allowed the identification of novel therapeutic targets such as tumor necrosis factor (TNF), interleukin (IL)-1, IL-6 or the system JAK/STAT phosphorylation. At present there are 5 TNF antagonists approved for RA. Tocilizumab blocks the pathway of IL-6 and is the only biological with proven efficacy in monotherapy. Rituximab modulates B cell response in RA. Abatacept provided new data on T cell involvement in the pathogenesis of RA. Tofacitinib is the first kinase inhibitor approved for this disease. Biologic drugs have proven efficacy, almost always in combination with methotrexate, and even halt radiographic progression. Monitoring infection is the main precaution in handling these patients.

  2. Hypercalcaemia in rheumatoid arthritis revisited.

    PubMed Central

    Ralston, S H; Fraser, W D; Jankowski, J; Richards, I M; Cowan, R A; Capell, H A; Sturrock, R D

    1990-01-01

    The prevalence and mechanisms of hypercalcaemia were studied in a series of patients attending a regional referral centre for rheumatic diseases. In a prospective study one case of hypercalcaemia due to primary hyperparathyroidism was found in 251 consecutive patients who were screened over a three month period. In a retrospective study of 39 patients who had been discovered to be hypercalcaemic during the preceding 12 months known cases of hypercalcaemia were found in 38 (97%) cases. Primary hyperparathyroidism was the most common cause (n = 24; 62%), followed by thiazide treatment in five (13%), cancer in three (8%), immobility in three (8%), vitamin D toxicity in two (5%), and chronic liver disease in one (3%). In one case the diagnosis remained unclear after full investigation. This study shows that the causes of hypercalcaemia in rheumatological patients are similar to those in the general population. These observations contrast with previous reports, which suggested that hypercalcaemia may be a complication of rheumatoid arthritis itself. PMID:2310223

  3. [Team management of rheumatoid arthritis].

    PubMed

    Le Loët, X; Vittecoq, O

    2001-12-01

    The main objectives of team management of rheumatoid arthritis are to stop structural damage of joints and to reduce functional, psychological, socioprofessional and economic consequences. Team management requires the collaboration, around the patient, of a rheumatologist, a nurse, a psychologist, a physiotherapist, an occupational therapist, an orthopaedic surgeon at the same time, in the same place. More and more patients wish to manage their disease by themselves. Team care should not be proposed to every patient; it must be reserved to patients whose condition required such an approach because of the severity of the disease, comorbidity, psychological or socioprofessionnal difficulties. Team management should be personalized. Utility of team management is now accepted; out-patient administration is as effective as in-patient one. A good educational program is very important. However, search is still needed to define optimal modalities of team management and tools to measure the efficiency of this approach.

  4. Pulmonary involvement in rheumatoid arthritis.

    PubMed

    Bilgici, Ayhan; Ulusoy, H; Kuru, O; Celenk, C; Unsal, M; Danaci, M

    2005-08-01

    The primary objective of this investigation was to assess the relationships between clinical characteristics, lung involvement, and frequency of pulmonary involvement in rheumatoid arthritis (RA). Using high-resolution computed tomography (HRCT) and pulmonary function tests (PFT), we prospectively evaluated 52 patients with RA (eight males and 44 females, mean age 53.6 years). The HRCT was abnormal in 35 patients (67.3%), the most frequent abnormalities being reticulonodular patterns, which were found in 22 patients (62.9%), ground-glass attenuation (20%), and bronchiectasis (17%). In this group of patients, PFT results were normal in 13 patients (37%). Titers of rheumatoid factor and erythrocyte sedimentation rate were significantly higher in abnormal HRCT presence. Higher Larsen's score, advanced age, and severe disease were significant risk factors for lung involvement (p<0.001, p<0.01, and p<0.01, respectively) and are suggested by our data to be statistically significant predictors of lung involvement in RA.

  5. [Pulmonary manifestations in rheumatoid arthritis].

    PubMed

    Morawska, Justyna; Domysławska, Izabela; Bagrowska, Magdalena; Sierakowski, Stanislaw

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by destructive cartilages, bones and other structures formed joints. RA belongs to connective tissue diseases represented by systemic nature, internal illness, extra-articular features and rapidly progress of atherosceirosis. The extra-articular complications cause the reduction of patient longevity. The frequency of symptoms in patient with RA and respiratory disorders occur in 10-20% of cases. Pulmonary complications are the second most common cause of premature of patient deaths. Respiratory disorders associated with RA are devided into 3 groups: infection, lung disease caused by drugs and pulmonary manifestation connected by RA. These last affect interstitial tissue, bronchioli, pulmonary vessels, pleura, also are presented by pulmonary rheumatoid nodules and pulmonary hypertension.

  6. Emerging biomarkers in psoriatic arthritis.

    PubMed

    Paek, So Yeon; Han, Ling; Weiland, Matthew; Lu, Chuan-Jian; McKinnon, Kathleen; Zhou, Li; Lim, Henry W; Elder, James T; Mi, Qing-Sheng

    2015-12-01

    Psoriasis is an immune-mediated skin disease which affects 2-4% of the worldwide population. Approximately 20-30% of patients with psoriasis develop psoriatic arthritis (PsA), a frequently destructive and disabling condition. As skin manifestations precede joint symptoms in nearly all patients with PsA, identification of biomarkers for early prediction of joint damage is an important clinical need. Because not all patients with PsA respond to treatment in the same fashion, identification of biomarkers capable of predicting therapeutic response is also imperative. Here, we review existing literature and discuss current investigations to identify potential biomarkers for PsA disease activity, with particular emphasis on microRNAs as novel markers of interest. Serum (soluble) biomarkers, peripheral osteoclast precursor as cellular biomarkers, and genetic loci associated with skin and joint disease are also reviewed. PMID:26602058

  7. Rheumatoid arthritis in Saudi Arabia

    PubMed Central

    Almoallim, Hani M.; Alharbi, Laila A.

    2014-01-01

    The status of rheumatoid arthritis (RA) in Saudi Arabia (SA) was examined from various perspectives based on a systematic literature review and the authors’ personal experiences. In this regard, database and journal search were conducted to identify studies on RA in SA, yielding a total of 43 articles. Although efforts have been made to promote RA research in SA, current studies mostly represent only a few centers and may not accurately portray the national status of RA care. Notably, biological therapies were introduced early for almost all practicing rheumatologists in SA (government and private). However, no national guidelines regarding the management of RA have been developed based on local needs and regulations. Also, while efforts were made to establish RA data registries, they have not been successful. Taken together, this analysis can contribute to the planning of future guidelines and directives for RA care in SA. PMID:25491208

  8. Rheumatoid arthritis: MR imaging manifestations.

    PubMed

    Beltran, J; Caudill, J L; Herman, L A; Kantor, S M; Hudson, P N; Noto, A M; Baran, A S

    1987-10-01

    Radiologic assessment of the stage and treatment response of rheumatoid arthritis (RA) is based on the presence of bone erosions, joint-space narrowing, and osteoporosis. Most radiologic methods for staging RA lack interobserver correlation and are time consuming. Magnetic resonance (MR) imaging provides excellent depiction of soft-tissue abnormalities of the joints affected by RA, which allows detection of early changes. Nineteen joints of 17 patients with RA were studied with surface-coil MR imaging. Measurable abnormalities demonstrated by MR imaging but not clearly seen on plain radiographs included bone erosions, joint effusion, synovial sheath effusion, and cartilage irregularity and thinning. Seven patients of this group underwent MR imaging before and after 6 months of gold therapy. Four patients had significant interval changes on MR images that were not seen on plain radiographs. MR imaging may become a sensitive and objective method for quantitative assessment of the joint changes of RA. PMID:3628762

  9. [Physiotherapy for juvenile idiopathic arthritis].

    PubMed

    Spamer, M; Georgi, M; Häfner, R; Händel, H; König, M; Haas, J-P

    2012-07-01

    Control of disease activity and recovery of function are major issues in the treatment of children and adolescents suffering from juvenile idiopathic arthritis (JIA). Functional therapies including physiotherapy are important components in the multidisciplinary teamwork and each phase of the disease requires different strategies. While in the active phase of the disease pain alleviation is the main focus, the inactive phase requires strategies for improving motility and function. During remission the aim is to regain general fitness by sports activities. These phase adapted strategies must be individually designed and usually require a combination of different measures including physiotherapy, occupational therapy, massage as well as other physical procedures and sport therapy. There are only few controlled studies investigating the effectiveness of physical therapies in JIA and many strategies are derived from long-standing experience. New results from physiology and sport sciences have contributed to the development in recent years. This report summarizes the basics and main strategies of physical therapy in JIA.

  10. The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is dependent on vascular endothelial growth factor.

    PubMed

    Biscetti, F; Flex, A; Pecorini, G; Angelini, F; Arena, V; Stigliano, E; Gremese, E; Tolusso, B; Ferraccioli, G

    2016-04-01

    High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme-linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL-17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model. PMID:26671547

  11. [Animal models for bone and joint disease. CIA, CAIA model].

    PubMed

    Hirose, Jun; Tanaka, Sakae

    2011-02-01

    The collagen-induced arthritis (collagen-induced arthritis, CIA) is an autoimmune arthritis that resembles rheumatoid arthritis (RA) in many ways, therefore it has been used most commonly as a model of RA. CIA is induced by immunization with an emulsion of complete Freund's adjuvant (CFA) and type II collagen (C II ) . Collagen antibody-induced arthritis (CAIA) is induced by the administration of a cocktail of monoclonal antibodies recognizing conserved epitopes located within the CB11 fragment. CAIA offers several advantages over CIA, including rapid disease onset, high uptake rate, and the capacity to use genetically modified mice, such as transgenics and knockouts.

  12. Critical Roles for Interleukin 1 and Tumor Necrosis Factor α in Antibody-induced Arthritis

    PubMed Central

    Ji, Hong; Pettit, Allison; Ohmura, Koichiro; Ortiz-Lopez, Adriana; Duchatelle, Veronique; Degott, Claude; Gravallese, Ellen; Mathis, Diane; Benoist, Christophe

    2002-01-01

    In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)–α was also required, although seemingly less critically than IL-1, because a proportion of TNF-α–deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFα for bone destruction. The variability in the requirement for TNF-α, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes. PMID:12093872

  13. Critical roles for interleukin 1 and tumor necrosis factor alpha in antibody-induced arthritis.

    PubMed

    Ji, Hong; Pettit, Allison; Ohmura, Koichiro; Ortiz-Lopez, Adriana; Duchatelle, Veronique; Degott, Claude; Gravallese, Ellen; Mathis, Diane; Benoist, Christophe

    2002-07-01

    In spontaneous inflammatory arthritis of K/BxN T cell receptor transgenic mice, the effector phase of the disease is provoked by binding of immunoglobulins (Igs) to joint surfaces. Inflammatory cytokines are known to be involved in human inflammatory arthritis, in particular rheumatoid arthritis, although, overall, the pathogenetic mechanisms of the human affliction remain unclear. To explore the analogy between the K/BxN model and human patients, we assessed the role and relative importance of inflammatory cytokines in K/BxN joint inflammation by transferring arthritogenic serum into a panel of genetically deficient recipients. Interleukin (IL)-1 proved absolutely necessary. Tumor necrosis factor (TNF)-alpha was also required, although seemingly less critically than IL-1, because a proportion of TNF-alpha-deficient mice developed robust disease. There was no evidence for an important role for IL-6. Bone destruction and reconstruction were also examined. We found that all mice with strong inflammation exhibited the bone erosion and reconstruction phenomena typical of K/BxN arthritis, with no evidence of any particular requirement for TNFalpha for bone destruction. The variability in the requirement for TNF-alpha, reminiscent of that observed in treated rheumatoid arthritis patients, did not appear genetically programmed but related instead to subtle environmental changes.

  14. 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.

  15. A Cytokine-Centric View of the Pathogenesis and Treatment of Autoimmune Arthritis

    PubMed Central

    Astry, Brian; Harberts, Erin

    2011-01-01

    Cytokines are immune mediators that play an important role in the pathogenesis of rheumatoid arthritis (RA), an autoimmune disease that targets the synovial joints. The cytokine environment in the peripheral lymphoid tissues and the target organ (the joint) has a strong influence on the outcome of the initial events that trigger autoimmune inflammation. In susceptible individuals, these events drive inflammation and tissue damage in the joints. However, in resistant individuals, the inflammatory events are controlled effectively with minimal or no overt signs of arthritis. Animal models of human RA have permitted comprehensive investigations into the role of cytokines in the initiation, progression, and recovery phases of autoimmune arthritis. The discovery of interleukin-17 (IL-17) and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of arthritis, which previously was based on a simplistic T helper 1 (Th1)-Th2 paradigm. This review discusses the role of the newer cytokines, particularly those associated with the IL-17/IL-23 axis in arthritis. Also presented herein is the emerging information on IL-32, IL-33, and IL-35. Ongoing studies examining the role of the newer cytokines in the disease process would improve understanding of RA as well as the development of novel cytokine inhibitors that might be more efficacious than the currently available options. PMID:22149412

  16. Patient Disease Perceptions and Coping Strategies for Arthritis in a Developing Nation: A Qualitative Study

    PubMed Central

    2011-01-01

    Background There is little prior research on the burden of arthritis in the developing world. We sought to document how patients with advanced arthritis living in the Dominican Republic are affected by and cope with their disease. Methods We conducted semi-structured, one-to-one interviews with economically disadvantaged Dominican patients with advanced knee and/or hip arthritis in the Dominican Republic. The interviews, conducted in Spanish, followed a moderator's guide that included topics such as the patients' understanding of disease etiology, their support networks, and their coping mechanisms. The interviews were audiotaped, transcribed verbatim in Spanish, and systematically analyzed using content analysis. We assessed agreement in coding between two investigators. Results 18 patients were interviewed (mean age 60 years, median age 62 years, 72% women, 100% response rate). Patients invoked religious and environmental theories of disease etiology, stating that their illness had been caused by God's will or through contact with water. While all patients experienced pain and functional limitation, the social effects of arthritis were gender-specific: women noted interference with homemaking and churchgoing activities, while men experienced disruption with occupational roles. The coping strategies used by patients appeared to reflect their beliefs about disease causation and included prayer and avoidance of water. Conclusions Patients' explanatory models of arthritis influenced the psychosocial effects of the disease and coping mechanisms used. Given the increasing reach of global health programs, understanding these culturally influenced perceptions of disease will be crucial in successfully treating chronic diseases in the developing world. PMID:21985605

  17. Antibody-based delivery of IL4 to the neovasculature cures mice with arthritis

    PubMed Central

    Hemmerle, Teresa; Doll, Fabia; Neri, Dario

    2014-01-01

    Antibody–cytokine fusion proteins (immunocytokines) are innovative biopharmaceutical agents, which are being considered for the therapy of cancer and chronic inflammatory conditions. Immunomodulatory fusion proteins capable of selective localization at the sites of rheumatoid arthritis (RA) are of particular interest, as they may increase the therapeutic index of the cytokine payload. The F8 antibody recognizes the alternatively spliced extra domain A of fibronectin, a marker of angiogenesis, which is strongly overexpressed at sites of arthritis. In this study, we investigated the targeting and therapeutic activity of the immunocytokine F8-IL4 in the mouse model of collagen-induced arthritis. Different combination regimes were tested and evaluated by the analysis of serum and tissue cytokine levels. We show that F8-IL4 selectively localizes to neovascular structures at sites of rheumatoid arthritis in the mouse, leading to high local concentrations of IL4. When used in combination with dexamethasone, F8-IL4 was able to cure mice with established collagen-induced arthritis. Response to treatment was associated with an elevation of IL13 levels and decreased IL6 plasma concentrations. A fully human version of F8-IL4 is currently being developed for clinical investigations. PMID:25092334

  18. Differentially expressed epigenome modifiers, including Aurora kinase A and B, in immune cells of rheumatoid arthritis

    PubMed Central

    Glant, Tibor T.; Besenyei, Timea; Kádár, András; Kurkó, Júlia; Tryniszewska, Beata; Gál, János; Soós, Györgyi; Szekanecz, Zoltán; Hoffmann, Gyula; Block, Joel A.; Katz, Robert S.; Mikecz, Katalin; Rauch, Tibor A.

    2014-01-01

    Objective The aim of this study was to identify epigenetic factors that are implicated in the pathogenesis of rheumatoid arthritis (RA) and to explore the therapeutic potential of the targeted inhibition of these factors. Methods PCR arrays were utilized to investigate the expression profile of genes that encod key epigenetic regulator enzymes. Mononuclear cells from RA patients and mice were monitored for gene expression changes, in association with arthritis development in murine models of RA. Selected genes were further characterized by quantitative real-time PCR, Western blot and flow cytometry methods. The targeted inhibition of the upregulated enzymes was studied in arthritic mice. Results A set of genes with arthritis-specific expression was identified by the PCR arrays. Aurora kinase A and B, both of which were highly expressed in arthritic mice and treatment naïve RA patients, were selected for detailed analysis. Elevated Aurora kinase expression was accompanied with an increased phosphorylation of histone H3, which promotes proliferation of T lymphocytes. Treatment with VX-680, a pan-Aurora kinase inhibitor, promoted B cell apoptosis, provided significant protection against the onset, and attenuated the inflammatory reactions in arthritic mice. Conclusions Arthritis development is accompanied the changes in the expression of a number of epigenome-modifying enzymes. Drug-induced downregulation of the Aurora kinases, among other targets, seems to be sufficient to treat experimental arthritis. Development of new therapeutics that target the Aurora kinases can potentially improve RA management. PMID:23653330

  19. Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis.

    PubMed

    Denys, Anne; Clavel, Gaëlle; Lemeiter, Delphine; Schischmanoff, Olivier; Boissier, Marie-Christophe; Semerano, Luca

    2016-05-01

    Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. PMID:26859834

  20. A retrospective study of septic arthritis in a tertiary hospital in West Texas with high rates of methicillin-resistant Staphylococcus aureus infection.

    PubMed

    Lim, Sian Yik; Pannikath, Deepa; Nugent, Kenneth

    2015-07-01

    Septic arthritis is an important concern for rheumatologists in the evaluation of joint disease. Very few studies have addressed the microbiologic epidemiology and outcomes of septic arthritis in the USA since the year 2000. We performed a retrospective study of septic arthritis in a tertiary hospital in West Texas from the year 2000 to 2013. We recorded data on patient demographics, microbiologic etiology, treatment patterns, and outcomes. The most common causative organisms were Staphylococcus aureus and Streptococcus spp. Methicillin-resistant Staphylococcus aureus (MRSA) caused septic arthritis in 22.6 % of the cases. MRSA septic arthritis was associated with low rates of adequate empiric antimicrobial therapy. The mortality due to sepsis in our study was 5.5 %. Patients with septic arthritis had a mean length of stay of 13.5 ± 12.1 days and required 2.1 ± 1.4 joint operations. Many patients (29.2 %) had readmissions due to complications, and these patients had high rates of home health utilization and transfers to other facilities post hospital discharge. In our logistic regression analysis model, factors associated with poor outcomes in septic arthritis were MRSA, older age, and prosthetic joint infection. Septic arthritis is associated with significant mortality, morbidity, and health care costs, and more studies are needed to improve outcomes, especially considering the increasing rates of MRSA as the pathogen.

  1. A retrospective study of septic arthritis in a tertiary hospital in West Texas with high rates of methicillin-resistant Staphylococcus aureus infection.

    PubMed

    Lim, Sian Yik; Pannikath, Deepa; Nugent, Kenneth

    2015-07-01

    Septic arthritis is an important concern for rheumatologists in the evaluation of joint disease. Very few studies have addressed the microbiologic epidemiology and outcomes of septic arthritis in the USA since the year 2000. We performed a retrospective study of septic arthritis in a tertiary hospital in West Texas from the year 2000 to 2013. We recorded data on patient demographics, microbiologic etiology, treatment patterns, and outcomes. The most common causative organisms were Staphylococcus aureus and Streptococcus spp. Methicillin-resistant Staphylococcus aureus (MRSA) caused septic arthritis in 22.6 % of the cases. MRSA septic arthritis was associated with low rates of adequate empiric antimicrobial therapy. The mortality due to sepsis in our study was 5.5 %. Patients with septic arthritis had a mean length of stay of 13.5 ± 12.1 days and required 2.1 ± 1.4 joint operations. Many patients (29.2 %) had readmissions due to complications, and these patients had high rates of home health utilization and transfers to other facilities post hospital discharge. In our logistic regression analysis model, factors associated with poor outcomes in septic arthritis were MRSA, older age, and prosthetic joint infection. Septic arthritis is associated with significant mortality, morbidity, and health care costs, and more studies are needed to improve outcomes, especially considering the increasing rates of MRSA as the pathogen. PMID:25572838

  2. Nerve Zap Eased Rheumatoid Arthritis in Small Study

    MedlinePlus

    ... news/fullstory_159838.html Nerve Zap Eased Rheumatoid Arthritis in Small Study Treatment worked some for patients ... gut may help ease stubborn symptoms of rheumatoid arthritis, preliminary research suggests. The study, of 17 adults ...

  3. Arthritis Education: Opportunities and State of the Art.

    ERIC Educational Resources Information Center

    Daltroy, Lawren H.; Liang, Matthew H.

    1993-01-01

    A variety of programs have produced changes in knowledge, behavior, and health for arthritis patients. National dissemination of patient education programs is in progress. Research needs center on new populations, delivery methods, and arthritis-specific applications of theory. (SK)

  4. Relationship between Immunity to Borrelia burgdorferi Outer-surface Protein A (OspA) and Lyme Arthritis

    PubMed Central

    Drouin, Elise E.; Glickstein, Lisa J.

    2011-01-01

    Antibiotic-refractory Lyme arthritis may result from Borrelia burgdorferi–induced autoimmunity in affected joints. Such patients usually have certain HLA-DRB1 molecules that bind an epitope of B. burgdorferi outer-surface protein A (OspA163–175), and cellular and humoral immune responses to OspA are greater in patients with antibiotic-refractory arthritis than in those with antibiotic-responsive arthritis. Recent work in a mouse model suggests that, during B. burgdorferi infection, OspA in genetically susceptible individuals stimulates a particularly strong TH1 response, which may be one of several factors that can help set the stage for a putative autoimmune response in affected joints. However, vaccination with OspA did not induce arthritis in this mouse model, and case and control comparisons in human vaccine trials did not show an increased frequency of arthritis among OspA-vaccinated individuals. Thus, a vaccine-induced immune response to OspA does not replicate the sequence of events needed in the natural infection to induce antibiotic-refractory Lyme arthritis. PMID:21217173

  5. Relationship between immunity to Borrelia burgdorferi outer-surface protein A (OspA) and Lyme arthritis.

    PubMed

    Steere, Allen C; Drouin, Elise E; Glickstein, Lisa J

    2011-02-01

    Antibiotic-refractory Lyme arthritis may result from Borrelia burgdorferi-induced autoimmunity in affected joints. Such patients usually have certain HLA-DRB1 molecules that bind an epitope of B. burgdorferi outer-surface protein A (OspA₁₆₃₋₁₇₅), and cellular and humoral immune responses to OspA are greater in patients with antibiotic-refractory arthritis than in those with antibiotic-responsive arthritis. Recent work in a mouse model suggests that, during B. burgdorferi infection, OspA in genetically susceptible individuals stimulates a particularly strong T(H)1 response, which may be one of several factors that can help set the stage for a putative autoimmune response in affected joints. However, vaccination with OspA did not induce arthritis in this mouse model, and case and control comparisons in human vaccine trials did not show an increased frequency of arthritis among OspA-vaccinated individuals. Thus, a vaccine-induced immune response to OspA does not replicate the sequence of events needed in the natural infection to induce antibiotic-refractory Lyme arthritis.

  6. Arthritis susceptibility and the Gut Microbiome

    PubMed Central

    Taneja, Veena

    2014-01-01

    Summary Rheumatoid arthritis (RA) is an autoimmune disease with unknown etiology though both genetic and environmental factors have been suggested to be involved in its pathogenesis. While infections and other environmental factors like smoking have been studies extensively and show some association, a direct link between all the factors has been difficult to prove. With the recent advances in technology, it has become possible to sequence the commensals that are residing in our gut. The gut microbiome may provide the missing link to this puzzle and help solve the mystery of many leaky gut syndromes. The gut commensals are involved in maintaining host immune homeostasis and function suggesting that they might be critical in altering the immune system that leads to autoimmune diseases like RA. Mouse models support the role of the gut microbiota in predisposition to RA. If that is true, the power of gut-derived commensal can be harnessed to our benefit by generating a biomarker profile along with genetic factors to define individuals at risk and by altering the gut microbial composition using various means. PMID:24873878

  7. 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

  8. 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.

  9. Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis.

    PubMed

    Pasi, Shweta; Kant, Ravi; Gupta, Sarika; Surolia, Avadhesha

    2015-02-01

    Protein therapeutics targeting inflammatory mediators have shown great promise for the treatment of autoimmunities such as rheumatoid arthritis (RA). However, a significant challenge in this area has been their low in vivo stability and consequently their severely compromised therapeutic efficacy. One such therapeutic molecule IL-1 receptor antagonist (IL-1ra), used in the treatment of rheumatoid arthritis, has displayed only modest efficacy in human clinical trials owing to its short biological half-life. Herein, we report a novel approach to conglomerate individual protein entities into a drug depot by incorporation of an amyloidogenic motif Lys-Phe-Phe-Glu (KFFE) thereby dramatically improving their systemic persistence and in turn their therapeutic efficacy in a mice model of autoimmune arthritis.

  10. Fluorescence imaging of experimental rheumatoid arthritis in vivo using a fast flying-spot scanner

    NASA Astrophysics Data System (ADS)

    Berger, J.; Voigt, J.; Seifert, F.; Ebert, B.; Macdonald, R.; Gemeinhardt, I.; Gemeinhardt, O.; Schnorr, J.; Taupitz, M.; Vater, A.; Vollmer, S.; Licha, K.; Schirner, M.

    2007-07-01

    We have developed a flying-spot scanner for fluorescence imaging of rheumatoid arthritis in the near infrared (NIR) spectral range following intravenous administration of contrast agents. The new imaging system has been characterized with respect to linearity, dynamic range and spatial resolution with the help of fluorescent phantoms. In vivo experiments were performed on an animal model of rheumatoid arthritis. Finally, NIR-fluorescence images of early stages of joint inflammation have been compared with findings from contrast enhanced MR imaging and histology.

  11. Juvenile rheumatoid arthritis: therapeutic perspectives.

    PubMed

    Chikanza, Ian C

    2002-01-01

    Juvenile rheumatoid arthritis (JRA) is the most common childhood chronic systemic autoimmune inflammatory disease. The therapeutic approach to JRA has, to date, been casual and based on extensions of clinical experiences gained in the management of adult rheumatoid arthritis (RA). The physiology of inflammation has been systemically studied and this has led to the identification of specific therapeutic targets and the development of novel approaches to the management of JRA. The classical treatments of the disease such as methotrexate, sodium aurothiomalate and sulfasalazine, are not always effective in controlling RA and JRA. This has necessitated the development of novel agents for treating RA, most of which are biological in nature and are targeted at specific sites of the inflammatory cascades. These biological therapeutic strategies in RA have proved successful and are being applied in the management of JRA. These developments have been facilitated by the advances in molecular biology which have heralded the advent of biodrugs (recombinant proteins) and gene therapy, in which specific genes can be introduced locally to enhance in vivo gene expression or suppress gene(s) of interest with a view to down-regulating inflammation. Some of these biodrugs, such as anti-tumor necrosis factor alpha (anti-TNFalpha), monoclonal antibodies (infliximab, adalimumab), TNF soluble receptor constructs (etanercept) and interleukin-1 receptor antagonist (IL-1Ra) have been tested and shown to be effective in RA. Etanercept has now been licensed for JRA. Clinical trials of infliximab in JRA are planned. Studies show that the clinical effects are transient, necessitating repeated treatments and the risk of vaccination effects. Anti-inflammatory cytokines such as IL-4, IL-10, transforming growth factor-beta and interferon-beta (IFN-beta) are undergoing clinical trials. Many of these agents have to be administered parenterally and production costs are very high; thus, there is a need

  12. 77 FR 14529 - Arthritis Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-12

    ... moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice...

  13. Molecular targets in arthritis and recent trends in nanotherapy

    PubMed Central

    Roy, Kislay; Kanwar, Rupinder Kaur; Kanwar, Jagat Rakesh

    2015-01-01

    Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy. PMID:26345140

  14. 76 FR 29767 - Arthritis Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-23

    ... HUMAN SERVICES Food and Drug Administration Arthritis Advisory Committee; Notice of Meeting AGENCY: Food... of Committee: Arthritis Advisory Committee. General Function of the Committee: To provide advice and... arthritis attacks. ILARIS has also been shown to extend the time to the next attack and reduce the...

  15. Infliximab in psoriasis and psoriatic arthritis.

    PubMed

    Papoutsaki, Marina; Osório, Filipa; Morais, Paulo; Torres, Tiago; Magina, Sofia; Chimenti, Sergio; Costanzo, Antonio

    2013-01-01

    Psoriasis is a chronic inflammatory disorder of the skin and joints. Although rarely life threatening, psoriasis can significantly impair quality of life (QOL) and cause considerable physical and psychological distress. Between 6 and 42% of patients with psoriasis develop psoriatic arthritis, which is characterized by stiffness, pain, swelling and tenderness of the joints. Nail psoriasis is highly prevalent in both plaque-type psoriasis and psoriatic arthritis and is found in approximately 50% of patients with psoriasis and in 80% of patients with psoriatic arthritis. Infliximab, a chimeric human-murine monoclonal antibody directed against tumour necrosis factor α, is approved in the USA and EU for the treatment of plaque psoriasis and psoriatic arthritis at a recommended dosage of 5 mg/kg administered by intravenous infusion at 0,2 and 6 weeks, then every 8 weeks thereafter. The EXPRESS and EXPRESS II trials demonstrated that infliximab is efficacious as induction and maintenance therapy in the treatment of moderate to severe plaque psoriasis and also improved health-related QOL. Infliximab is also efficacious in the treatment of psoriatic arthritis, as shown in the IMPACT and IMPACT II studies. Infliximab is generally well tolerated, with a similar adverse event profile in both psoriasis and psoriatic arthritis. The use of infliximab in three case reports is presented. The patients are similar to those normally seen by clinicians, and include a male patient with plaque psoriasis and a history of severe psoriatic arthritis who was corticosteroid dependent and in whom other systemic treatments were not effective or were not able to be used. This patient showed a rapid response to infliximab with no skin lesions or arthritis after 7 weeks' treatment. Infliximab was also safe and effective in the treatment of a female patient with plaque and nail psoriasis and a history of psoriatic arthritis. Importantly, this case report supports the efficacy of infliximab in

  16. 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.

  17. Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow’s Milk Proteins

    PubMed Central

    Ibañez, Andrés E.; Smaldini, Paola; Coria, Lorena M.; Delpino, María V.; Pacífico, Lucila G. G.; Oliveira, Sergio C.; Risso, Gabriela S.; Pasquevich, Karina A.; Fossati, Carlos Alberto; Giambartolomei, Guillermo H.; Docena, Guillermo H.; Cassataro, Juliana

    2013-01-01

    The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow’s Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations. PMID:23861971

  18. The microbiome and rheumatoid arthritis

    PubMed Central

    Scher, Jose U.; Abramson, Steven B.

    2012-01-01

    Humans are not (and have never been) alone. From the moment we are born, millions of micro-organisms populate our bodies and coexist with us rather peacefully for the rest of our lives. This microbiome represents the totality of micro-organisms (and their genomes) that we necessarily acquire from the environment. Micro-organisms living in or on us have evolved to extract the energy they require to survive, and in exchange they support the physiological, metabolic and immune capacities that have contributed to our evolutionary success. Although currently categorized as an autoimmune disorder and regarded as a complex genetic disease, the ultimate cause of rheumatoid arthritis (RA) remains elusive. It seems that interplay between predisposing genetic factors and environmental triggers is required for disease manifestation. New insights from DNA sequence-based analyses of gut microbial communities and a renewed interest in mucosal immunology suggest that the microbiome represents an important environmental factor that can influence autoimmune disease manifestation. This Review summarizes the historical clues that suggest a possible role for the microbiota in the pathogenesis of RA, and will focus on new technologies that might provide scientific evidence to support this hypothesis. PMID:21862983

  19. Rheumatoid arthritis: Disease or syndrome?

    PubMed Central

    Stanich, Jessica A; Carter, John D; Whittum-Hudson, Judith; Hudson, Alan P

    2009-01-01

    Rheumatoid arthritis (RA) has been described in the medical literature for over two hundred years, but its etiology remains unknown. RA displays phenotypic heterogeneity, and it is a relatively prevalent clinical entity: it affects approximately 1% of the population, resulting in enormous pathologic sequelae. Earlier studies targeting the cause(s) of RA suggested potential infectious involvement, whereas more recent reports have focused on a genetic origin of the disease. However, neither infection nor genetics, nor any other single factor is currently accepted as causative of RA. In this article we review studies relating to the etiology of RA, and those of several related matters, and we conclude that the literature indeed does provide insight into the causes underlying the initiation of RA pathogenesis. Briefly, given the remarkable phenotypic variation of RA, especially in its early stages, as well as a number of other characteristics of the condition, we contend that RA is not a discrete clinical entity with a single etiological source. Rather, we argue that it represents a common clinical endpoint for various starting points, each of which is largely guided by as yet poorly understood aspects of the genetic background of the affected individual. Adoption of this alternative view of the origin of RA will have significant consequences for future research and for development of new therapeutic interventions for this burdensome condition.

  20. Genetics of Rheumatoid Arthritis — A Comprehensive Review

    PubMed Central

    Kurkó, Júlia; Besenyei, Timea; Laki, Judit; Glant, Tibor T.; Mikecz, Katalin

    2013-01-01

    The “Bermuda triangle” of genetics, environment and autoimmunity is involved in the pathogenesis of rheumatoid arthritis (RA). Various aspects of genetic contribution to the etiology, pathogenesis and outcome of RA are discussed in this review. The heritability of RA has been estimated to be about 60 %, while the contribution of HLA to heritability has been estimated to be 11–37 %. Apart from known shared epitope (SE) alleles, such as HLA-DRB1*01 and DRB1*04, other HLA alleles, such as HLA-DRB1*13 and DRB1*15 have been linked to RA susceptibility. A novel SE classification divides SE alleles into S1, S2, S3P and S3D groups, where primarily S2 and S3P groups have been associated with predisposition to seropositive RA. The most relevant non-HLA gene single nucleotide polymorphisms (SNPs) associated with RA include PTPN22, IL23R, TRAF1, CTLA4, IRF5, STAT4, CCR6, PADI4. Large genome-wide association studies (GWAS) have identified more than 30 loci involved in RA pathogenesis. HLA and some non-HLA genes may differentiate between anti-citrullinated protein antibody (ACPA) seropositive and seronegative RA. Genetic susceptibility has also been associated with environmental factors, primarily smoking. Some GWAS studies carried out in rodent models of arthritis have confirmed the role of human genes. For example, in the collagen-induced (CIA) and proteoglycan-induced arthritis (PgIA) models, two important loci — Pgia26/Cia5 and Pgia2/Cia2/Cia3, corresponding the human PTPN22/CD2 and TRAF1/C5 loci, resp