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Sample records for adjuvant arthritis aa

  1. Effects and mechanisms of Geniposide on rats with adjuvant arthritis.

    PubMed

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

    2014-05-01

    Geniposide (GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis (GJ) fruit which has anti-inflammatory and other important therapeutic activities. The aim of this study was to investigate the effects of GE on adjuvant arthritis (AA) rats and its possible mechanisms. AA was induced by injecting with Freund's complete adjuvant (FCA). Male SD rats were subjected to treatment with GE at 30, 60 and 120mg/kg from days 18 to 24 after immunization. Lymphocyte proliferation was assessed by MTT. Interleukin (IL)-6, IL-17, IL-4 and transforming growth factor-beta 1 (TGF-β1) were determined by ELISA. c-Jun N-terminal kinase (JNK) and phospho-JNK (p-JNK) were detected by Western blot. GE (60, 120mg/kg) significantly relieved the secondary hind paw swelling and arthritis index, along with decreased Th17-cells cytokines and increased Treg-cell cytokines in mesenteric lymph node lymphocytes (MLNL) and peripheral blood lymphocytes (PBL) of AA rats. In addition, GE decreased the expression of p-JNK in MLNL and PBL of AA rats. In vivo study, it was also observed that GE attenuated histopathologic changes of MLN in AA rats. Collectively, GE might exert its anti-inflammatory and immunoregulatory effects through inducing Th17 cell immune tolerance and enhancing Treg cell-mediated activities by down-regulating the expression of p-JNK. The mechanisms of GE on JNK signaling in MLNL and PBL may play critical roles in the pathogenesis of rheumatoid arthritis. PMID:24583144

  2. Decreased hepatobiliary transport of methotrexate in adjuvant arthritis rats.

    PubMed

    Achira, M; Totsuka, R; Fujimura, H; Kume, T

    2002-12-01

    1. We investigated the difference in hepatobiliary transport of methotrexate in normal and adjuvant arthritis (AA) rats and substantiated the expression level of multidrug resistance-associated protein 2 (MRP2) in the liver. 2. Biliary clearance of methotrexate in normal and AA rats was calculated from plasma concentrations and biliary excretion following intravenous infusion and hepatic uptake clearance was estimated from an integration plot using methotrexate concentrations in plasma and liver. 3. Biliary clearance of methotrexate in AA rats was 2.30 +/- 0.23 ml min(-1) kg(-1) (mean SD) and significantly lower than in normal rats (8.42 +/- 0.81 ml min(-1) kg(-1)). The uptake clearance of methotrexate in AA rats was also lower than in normal rats (0.138 versus 0.278 ml min(-1) g liver(-1)). 4. MRP2 in the liver was detected by fluorescein isothiocyanate-labelled antibody and visualized using a confocal laser microscope system. The expression level of MRP2 in AA rats was very low compared with normal rats, indicating a down-regulation in AA rats. 5. In conclusion, biliary clearance of methotrexate was decreased due to the lower activities in both uptake and canalicular secretion, suggesting that several active transporters in the liver, including MRP2, are down-regulated in AA rats. PMID:12593762

  3. Thalidomide analogue CC1069 inhibits development of rat adjuvant arthritis

    PubMed Central

    Oliver, S J; Freeman, S L; Corral, L G; Ocampo, C J; Kaplan, G

    1999-01-01

    The cytokine tumour necrosis factor-alpha (TNF-α) has been implicated in the aetiology of rheumatoid arthritis in humans as well as of experimental arthritis in rodents. Thalidomide, and to a greater extent the new thalidomide analogue CC1069, inhibit monocyte TNF-α production both in vitro and in vivo. The aim of the present study is to establish whether these drugs block production of TNF-α as well as IL-2 by rat leucocytes and whether this inhibition affects the development of rat adjuvant arthritis (AA). Cultured splenocytes were stimulated with either lipopolysaccharide (LPS) or concanavalin A (Con A) in the presence of thalidomide, CC1069, or solvent, and the production of TNF-α and IL-2 were compared. Next, adjuvant was injected into the base of the tail of rats without or with daily intraperitoneal injections with 100–200 mg/kg per day thalidomide or 50–200 mg/kg per day CC1069. Disease activity, including ankle swelling, hind limb radiographic and histological changes, weight gain, and ankle joint cytokine mRNA levels, were monitored. CC1069, but not the parent drug thalidomide, inhibited in vitro production of TNF-α and IL-2 by stimulated splenocytes in a dose-dependent manner. In vivo, a dose-dependent suppression of AA disease activity occurred in the CC1069-treated animals. In contrast, thalidomide-treated rats experienced comparable arthritis severity to placebo-treated animals. There was also a reduction in TNF-α and IL-2 mRNA levels in the ankle joints of CC1069-treated rats compared with thalidomide- and placebo-treated arthritic rats. Early initiation of CC1069 treatment suppressed AA inflammation more efficiently than delayed treatment. We conclude that thalidomide, which did not suppress TNF-α or IL-2 production in vitro by Lewis rat cells, did not suppress development of rat AA. However, the development of rat AA can be blocked by the thalidomide analogue CC1069, which is an efficient inhibitor of TNF-α production and IL-2 in vitro

  4. Tissue-specific regulation of expression and activity of P-glycoprotein in adjuvant arthritis rats.

    PubMed

    Achira, Meguru; Totsuka, Ryuichi; Fujimura, Hisako; Kume, Toshiyuki

    2002-07-01

    Cyclosporine A and steroids are effective against rheumatoid arthritis and also known as substrates of P-glycoprotein (P-gp). We investigated the effect of arthritis on the hepatic and intestinal P-gp activity in rats, and substantiated the expression level of the hepatic P-gp. Doxorubicin was used as a P-gp substrate. Cumulative biliary excretion and intestinal exsorption of doxorubicin following intravenous administration were compared between adjuvant arthritis (AA) and normal rats. Intestinal P-gp activity was also investigated by intestinal everted sac method, and hepatic P-gp was detected by FITC-labeled antibody and visualized using a confocal laser microscope system. Biliary clearance of doxorubicin in AA rats was significantly decreased from that in normal rats. The expression level of the hepatic P-gp in AA rats was very low compared to normal rats, indicating down-regulation. Intestinal exsorption clearance was not different between AA and normal rats. Permeability of doxorubicin across intestinal everted sac was comparable between AA and normal rats, corresponding to in vivo study. In AA rats, hepatic P-gp activity was decreased due to the reduction of expression level, but intestinal P-gp activity was not changed. Different regulation systems may be involved in liver and intestine. PMID:12113888

  5. 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

  6. Modulation of Adjuvant Arthritis by Cellular and Humoral Immunity to Hsp65

    PubMed Central

    Kim, Eugene Y.; Durai, Malarvizhi; Mia, Younus; Kim, Hong R.; Moudgil, Kamal D.

    2016-01-01

    Heat shock proteins (Hsps) are highly conserved, and their expression is upregulated in cells by heat and other stressful stimuli. These proteins play a vital role in preserving the structural and functional integrity of cells under stress. Despite the ubiquitous expression of Hsps in an individual, the immune system is not fully tolerant to them. In fact, Hsps are highly immunogenic in nature, and immune response to these proteins is observed in various inflammatory and autoimmune diseases. Studies on the immunopathogenesis of autoimmune arthritis in the rat adjuvant arthritis (AA) model of human rheumatoid arthritis (RA) as well as observations in patients with RA and juvenile idiopathic arthritis (JIA) have unraveled immunoregulatory attributes of self-Hsp65-directed immunity. Notable features of Hsp65 immunity in AA include protection rather than disease induction following immunization of Lewis rats with self (rat)-Hsp65; the diversification of T cell response to mycobacterial Hsp65 during the course of AA and its association with spontaneous induction of response to self-Hsp65; the cross-reactive T cells recognizing foreign and self homologs of Hsp65 and their role in disease suppression in rats; the suppressive effect of antibodies to Hsp65 in AA; and the use of Hsp65, its peptides, or altered peptide ligands in controlling autoimmune pathology. The results of studies in the AA model have relevance to RA and JIA. We believe that these insights into Hsp65 immunity would not only advance our understanding of the disease process in RA/JIA, but also lead to the development of novel therapeutic approaches for autoimmune arthritis. PMID:27379088

  7. Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

    PubMed Central

    van Bilsen, Jolanda HM; Wagenaar-Hilbers, Josée PA; van der Cammen, Maarten JF; van Dijk, Mariska EA; van Eden, Willem; Wauben, Marca HM

    2002-01-01

    We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies. PMID:12106501

  8. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    SciTech Connect

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B. )

    1991-09-01

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.

  9. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol

    PubMed Central

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  10. Autophagy and mitochondrial dysfunction in adjuvant-arthritis rats treatment with resveratrol.

    PubMed

    Zhang, Junqiang; Song, Xianbin; Cao, Wei; Lu, Jinseng; Wang, Xiaoqing; Wang, Gaoyuan; Wang, Zhicheng; Chen, Xiaoyu

    2016-01-01

    Resveratrol is a polyphenol derivatives which exhibits a pro-apoptotic effect in a variety of human cancers by triggering mitochondria apoptosis pathway and autophagy. However, there are scarcely reports on its apoptosis-promoting effect in abnormal proliferation fibroblast-like synoviocytes (FLSs). In this study, we investigated the underlying mechanism and apoptosis-inducing effects of resveratrol on the abnormal proliferation of FLSs in adjuvant-arthritis (AA) rats. Since using resveratrol for 12 days resulted in a significant decreasing the swelling degree of the paw, reducing malondialdehyde (MDA) content and enhancing superoxide dismutase (SOD) activity, antioxidant capacity, glutathione peroxidase and glutathione reductase ratio in AA rats. Moreover, we found that 5 μMH2O2 could increase cells viability, Beclin1, LC3A/B, MnSOD, SIRT3 protein expression in FLSs. But, resveratrol could reverse these effects by changing mitochondrial membrane potential (Δψm) to promote mitochondrial reactive oxygen species (mtROS) generation in 5 μMH2O2-treatment FLSs. These results suggest that oxidative stress existed in AA rats. Resveratrol could suppress oxidative stress in AA rats and increase mtROS production by reducing autophagy protein Beclin1, LC3A/B and oxidative stress protein MnSOD to promoted the apoptosis of FLSs. Thus, targeting of mtROS may be a crucial mechanism of resveratrol confers patients with rheumatoid arthritis. PMID:27611176

  11. Establishment of a Rat Adjuvant Arthritis-Interstitial Lung Disease Model

    PubMed Central

    Song, Liu-nan; Kong, Xiao-dan; Wang, Hong-jiang; Zhan, Li-bin

    2016-01-01

    Introduction. Development of an animal model of rheumatoid arthritis-interstitial lung disease (RA-ILD) and improved knowledge of the pathogenesis of RA-ILD may facilitate earlier diagnosis and the development of more effective targeted therapies. Methods. Adult male Wistar rats were studied in an adjuvant arthritis (AA) model induced by the injection of Freund's complete adjuvant (FCA). Rats were sacrificed on days 7, 14, 21, and 28 after FCA injection. Lung tissue was obtained for histopathological examination and evaluation of Caveolin-1 (Cav-1) and transforming growth factor-β (TGF-β1) protein expression levels. Results. Pulmonary inflammation was evident in lung tissue from day 21 after FCA injection. Inflammation and mild fibrosis were observed in lung tissue on day 28 after FCA injection. Cav-1 protein expression was significantly decreased from day 7 through day 28 and TGF-β1 protein expression was significantly increased on day 28 after FCA injection compared to control (P < 0.05). Conclusion. We established an AA rat model that exhibited the extra-articular complication of RA-ILD. We identified Cav-1 and TGF-β1 as protein biomarkers of RA-ILD in this model and propose their signaling pathway as a possible target for therapeutic intervention. PMID:26881215

  12. Modulation of SERCA in the chronic phase of adjuvant arthritis as a possible adaptation mechanism of redox imbalance.

    PubMed

    Strosova, Miriam; Karlovska, Jana; Spickett, Corinne M; Orszagova, Zuzana; Ponist, Silvester; Bauerova, Katarina; Mihalova, Danica; Horakova, Lubica

    2009-09-01

    Adjuvant arthritis (AA) is a condition that involves systemic oxidative stress. Unexpectedly, it was found that sarcoplasmic reticulum Ca(2 +)-ATPase (SERCA) activity was elevated in muscles of rats with AA compared to controls, suggesting possible conformational changes in the enzyme. There was no alteration in the nucleotide binding site but rather in the transmembrane domain according to the tryptophan polar/non-polar fluorescence ratio. Higher relative expression of SERCA, higher content of nitrotyrosine but no increase in phospholipid oxidation in AA SR was found. In vitro treatments of SR with HOCl showed that in AA animals SERCA activity was more susceptible to oxidative stress, but SR phospholipids were more resistant and SERCA could also be activated by phosphatidic acid. It was concluded that increased SERCA activity in AA was due to increased levels of SERCA protein and structural changes to the protein, probably induced by direct and specific oxidation involving reactive nitrogen species. PMID:19591012

  13. 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

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

    PubMed

    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

  15. 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

  16. 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

  17. 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

  18. Effect of iron complexes on adjuvant arthritis in rats.

    PubMed Central

    Dabbagh, A J; Blake, D R; Morris, C J

    1992-01-01

    When a total dose infusion of iron dextran is given to anaemic rheumatoid patients an exacerbation of inflammatory synovitis in previously affected joints is observed. The adjuvant arthritis model of inflammation in rats has been used to investigate the mechanism of iron promoted synovitis. Either iron dextran (5 mg injected intravenously) with a dextran C control, or iron sorbitol (7.5 mg injected intramuscularly) with a sorbitol citrate complex control was given at the onset of clinical joint inflammation. Iron dextran significantly increased joint inflammation (assessed by joint scoring) at days 12, 13, 14, and 16 after injection. Similarly, iron sorbitol produced a significant increase in the joint score at days 17, 18, 19, and 21. In addition, extensive osteoporosis was observed in the rats treated with iron sorbitol. These pro-inflammatory effects of iron coincide with the presence of positive results for synovial iron (III) using Perl's test and neutrophil infiltration. The results of this study suggest that the iron induced increase in synovitis in adjuvant arthritis is a result of iron promoted oxidative damage and is not likely to be due to the dextran C or the sorbitol citric acid components. It is suggested that a similar mechanism may occur in rheumatoid patients given iron supplements. Images PMID:1586252

  19. 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

  20. 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

  1. Effect of total flavonoids of Chrysanthemum indicum on the apoptosis of synoviocytes in joint of adjuvant arthritis rats.

    PubMed

    Chen, Xiao-Yu; Li, Jun; Cheng, Wen-Ming; Jiang, Hui; Xie, Xue-Feng; Hu, Rong

    2008-01-01

    Chrysanthemum is a traditional Chinese medicine used in China to treat inflammatory diseases. The total flavonoids Chrysanthemum indicum (TFC) were extracted from the dried bud of Chrysanthemum indicum. Our previous study had demonstrated that TFC was a new class of effective anti-inflammation, analgesia and immunoloregulation agents. In this study, we established an adjuvant arthritis (AA) model by injection of Freund's Complete Adjuvant (FCA) to investigate the effect of TFC on the apoptosis of synoviocytes in AA Rats. Synoviocytes isolated from knee joint of rats were treated with different doses of TFC in vitro. Synoviocytes proliferation was measured by MTT assay, and DNA fragmentations were evaluated on agarose gel electrophoresis. The levels of caspase-3 cleaved fragments were analyzed by Western blot. The annexin V stain assay was used to explore the inhibition of caspase-3 on the amelioration of synoviocytes apoptosis. The results showed that TFC inhibited the proliferation of synoviocytes. Electrophoresis showed higher ladders of DNA bands in the TFC group. Cleaved fragments of caspase-3 were increased significantly. Furthermore, the apoptotic synoviocytes were markedly decreased by the caspase-3 specific inhibitor. These results suggest that TFC could induce synoviocytes apoptosis and suppress proliferation of synoviocytes in adjuvant-induced arthritis rats. PMID:18711767

  2. Pharmacological influence on processes of adjuvant arthritis: Effect of the combination of an antioxidant active substance with methotrexate.

    PubMed

    Drafi, Frantisek; Bauerova, Katarina; Kuncirova, Viera; Ponist, Silvester; Mihalova, Danica; Fedorova, Tatiana; Harmatha, Juraj; Nosal, Radomir

    2012-06-01

    Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe(2+)-induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of

  3. Anti-arthritic activity of luteolin in Freund's complete adjuvant-induced arthritis in rats by suppressing P2X4 pathway.

    PubMed

    Shi, Fengchao; Zhou, Dun; Ji, Zhongqiu; Xu, Zhaofeng; Yang, Huilin

    2015-01-25

    To investigate anti-arthritic activity of luteolin (Lut) in Freund's complete adjuvant (FCA)-induced arthritis (AA) in rats. AA was induced by injecting with Freund's complete adjuvant (FCA). Male rats were randomly divided into five groups with 10 mice in each group: (1) control group (saline), (2) AA group, (3) AA+Diclofenac Sodium (AA+DS, 5 mg/kg), (4) AA+Lut (20 mg/kg), (5) AA+Lut (40 mg/kg). Male SD rats were subjected to treatment with Lut at 10 and 20 mg/kg from days 18 to 24 after immunization. Arthritic scores, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-17 (IL-17), paw histopathology and the proteins of P2X4 pathway were assessed at the end of the experiment. Lut reduced the severity of arthritic scores during the experimental period as compared with positive control (RA). Lut significantly suppressed TNF-α, IL-6, IL-1β and IL-17 as compared with RA group. Histopathological examination indicated that Lut alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Lut significantly suppressed P2X4, NLRP1, ASC, and Caspase-1p10. Lut may be a potential preventive or therapeutic candidate for the treatment of inflammation and arthritis. PMID:25450234

  4. Identification and distribution of four metabolites of geniposide in rats with adjuvant arthritis.

    PubMed

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

    2014-09-01

    Geniposide (GE), also called Jasminoidin, is the major active ingredient of Gardenia jasminoides Ellis (GJ) fruit, which has long been used in traditional Chinese medicine (TCM). Growing evidences suggested that GE has a great potentiality for treating rheumatoid arthritis (RA). However, GE is rapidly metabolized, and we know little about its availability or metabolites in tissues. To elucidate the distribution of GE and its metabolites in tissues, three groups of adjuvant arthritis (AA) rats were given GE (33, 66 and 120 mg/kg) from days 18 to 24, and the biotransformation of GE in plasma, liver, spleen, synovium, urine and mesenteric lymph node (MLN) of rats was investigated by a novel approach named Information-Dependent Acquisition (IDA)-Mediated LC-MS/MS method. As a result, GE and its four major metabolites were detected as follows: GE, G1, G2 in plasma; GE, G2 in MLNs; only GE in liver and synovium; GE, G2, G3 and G4 in spleen; and GE, G1, G2 and G4 in urine. In total four metabolites (G1-G4) involved in the in vivo metabolism processes were identified. The results of this work have demonstrated the IDA-Mediated LC-MS/MS could screen rapidly and reliably the characterization of metabolites from iridoid compounds. PMID:24910002

  5. 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

  6. 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. PMID:24989003

  7. Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis.

    PubMed

    Strosova, Miriam K; Karlovska, Janka; Zizkova, Petronela; Kwolek-Mirek, Magdalena; Ponist, Silvester; Spickett, Corinne M; Horakova, Lubica

    2011-07-01

    Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part. These events were associated with an increased level of protein carbonyls, a decrease in cysteine SH groups, and alterations in SR membrane fluidity. There was no alteration in the nucleotide binding site at any time point of AA, as detected by a FITC fluorescence marker. Some changes observed on day 21 appeared to be reversible, as indicated by SERCA activity, cysteine SH groups, SR membrane fluidity, protein carbonyl content and fluorescence of an NCD-4 marker specific for the calcium binding site. The reversibility may represent adaptive mechanisms of AA, induced by higher relative expression of SERCA, oxidation of cysteine, nitration of tyrosine and presence of acidic phospholipids such as phosphatidic acid. Nitric oxide may regulate cytoplasmic Ca(2+) level through conformational alterations of SERCA, and decreasing levels of calsequestrin in SR may also play regulatory role in SERCA activity and expression. PMID:21531199

  8. Suppression and augmentation of rat adjuvant arthritis with monoclonal anti-interferon-gamma antibody.

    PubMed Central

    Wiesenberg, I; Van der Meide, P H; Schellekens, H; Alkan, S

    1989-01-01

    The effects of a monoclonal antibody (MoAb DB-1), which neutralized rat interferon-gamma (IFN-gamma), on the induction and progression of adjuvant arthritis in Lewis rats induced by intraplantar injection of Freund's complete adjuvant was studied. The animals were treated intraperitoneally with MoAb DB-1 (0.3-5 mg) for various times. Prophylactic treatment with MoAb DB-1, starting 2 days prior to arthritis induction, inhibited oedema in both the injected and non-injected hind paws and delayed joint destruction as shown by radiography. However, despite continued MoAb treatment, the disease progressed. High doses of MoAb DB-1 exacerbated the disease. A control MoAb of the same isotype did not have significant effects on adjuvant arthritis. Therapeutic treatment with the MoAb DB-1 starting 8 days after arthritis induction caused only slight and short-lived inhibitory effects. IFN-gamma appears to be a critical lymphokine for the development of adjuvant arthritis. PMID:12412757

  9. Decreased activity of hepatic P-glycoprotein in the isolated perfused liver of the adjuvant arthritis rat.

    PubMed

    Achira, M; Totsuka, R; Kume, T

    2002-11-01

    1. We investigated the hepatobiliary transport of doxorubicin in the isolated perfused liver prepared from the adjuvant arthritis rat, an animal model for rheumatoid arthritis, to examine the hepatic P-glycoprotein activity in the adjuvant arthritis rat. 2. Liver was isolated from the normal and the adjuvant arthritis rat and perfused for 60 min with recirculating buffer and the perfusate and bile samples were collected at timed interval. 3. The elimination of doxorubicin in the adjuvant arthritis rat tended to be reduced, but it was not significantly different from the normal rat. Biliary clearance (CL(bile)) in the normal rat was 1.93 +/- 0.48 ml min(-1), whereas, CL(bile) in the adjuvant arthritis rat was significantly decreased to 0.40 +/- 0.13 ml min(-1). 4. CL(bile) was markedly decreased to about 0.15 ml min(-1) in the presence of 100 microM verapamil in both types of rat. Methotrexate treatment had no effect on CL(bile) in both the normal and adjuvant arthritis rat (2.18 +/- 0.22 and 0.47 +/- 0.22 ml min(-1), respectively). 5. The results suggest that the hepatic P-glycoprotein activity was markedly decreased in the adjuvant arthritis rat and the effect of methotrexate on the hepatic P-glycoprotein activity did not corresponded to its anti-inflammatory effect. PMID:12487726

  10. Differences in pharmacokinetics and hepatobiliary transport of a novel anti-inflammatory agent between normal and adjuvant arthritis rats.

    PubMed

    Achira, M; Totsuka, R; Kume, T

    2002-12-01

    1. The pharmacokinetics, particularly the hepatobiliary transport of T-5557 ((3-methyl-2-oxo-piperadin-3-yl)-acetic acid N'-(3-thieophen-2-yl-8-methoxy-quinazolin-1-yl)-hydrazide), a novel anti-inflammatory agent, has been examined in normal and adjuvant arthritis (AA) rats. 2. Following oral administration of T-5557, the absolute bioavailability in AA rats was increased by sixfold compared with normal rats. The extent of binding T-5557 to plasma proteins obtained from AA rats was markedly greater than in normal rats (97.0 versus 88.2%). The biliary clearance in AA rats was significantly lower than that in normal rats (1.186 versus 5.621 ml min(-1) kg(-1)), and lower intrinsic biliary clearance was also observed in AA rats (40.33 versus 69.83 ml min(-1) kg(-1)). 3. Concomitant administration of T-5557 with quinidine, a potent P-glycoprotein inhibitor, to normal rats caused a significant decrease in the biliary clearance of T-5557 by 37.9%. Moreover, the transport of T-5557 for the apical-to-basal compartment in a Caco-2 cells' monolayer was fourfold lower than that for the opposite direction, and was increased in the presence of quinidine and verapamil. 4. These results suggest that P-glycoprotein is involved in the biliary excretion of T-5557 and the decrease in the transport activity as well as the increase in plasma protein binding caused the elevated plasma concentration and bioavailability of T-5557 in AA rats. PMID:12593761

  11. Arthritis associated with adjuvant mycobacterial treatment for carcinoma of the bladder.

    PubMed Central

    Hughes, R A; Allard, S A; Maini, R N

    1989-01-01

    A patient who developed an inflammatory polyarthritis following intravesical administration of bacillus Calmette-Guérin (BCG) used in the treatment of bladder cancer is described. An inflammatory synovitis comprising predominantly T lymphocytes was demonstrated on synovial biopsy. The synovitis resolved spontaneously within 14 days in this 'human model' of adjuvant arthritis. Images PMID:2786389

  12. 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

  13. Protective effect of apigenin on Freund's complete adjuvant-induced arthritis in rats via inhibiting P2X7/NF-κB pathway.

    PubMed

    Chang, Xiayun; He, He; Zhu, Lingpeng; Gao, Jin; Wei, Tingting; Ma, Zhanqian; Yan, Tianhua

    2015-07-01

    To evaluate the effect of apigenin (AP) on arthritis in rats stimulated by Freund's complete adjuvant (FCA) was the main purpose of the investigation. Arthritis model was established by the administration of 0.1 ml FCA in the palmar surface. AP and diclofenac sodium (DS) were administered to explore and evidence the protective effects against adjuvant-induced arthritis (AA). Cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) were detected to assess the anti-inflammatory effect of AP. Besides, pathological conditions were examined in rat paws. Related-proteins of nuclear factor kappa B (NF-κB) signal pathway activated by P2X7 were investigated to determine the molecular mechanism of AP and their expressions were measured by western blot. The data showed that AP significantly suppressed the expressions of P2X7/NF-κB signal-related proteins and alleviated inflammatory reactions. Therefore, it was assumed that AP might be a potential therapeutic candidate to treat arthritis. PMID:25935278

  14. Paradoxical effects of tumour necrosis factor-α in adjuvant-induced arthritis

    PubMed Central

    Williams, Richard O

    2008-01-01

    Anti-tumour necrosis factor (TNF)α therapy is highly effective in rheumatoid arthritis and it is surprising, therefore, that a recent study showed that intraperitoneal administration of recombinant TNFα reduced the severity of adjuvant-induced arthritis and decreased IFNγ expression in cultured draining lymph node cells. Furthermore, in untreated arthritic rats, maximal TNFα expression in draining lymph node cells coincided with spontaneous disease remission, suggesting a role for endogenous TNFα in recovery from arthritis. If confirmed in further studies, these findings suggest that, in addition to its well-established pro-inflammatory properties, TNFα may also play a disease-limiting role in this model of rheumatoid arthritis by suppressing effector T cell responses. PMID:18564403

  15. Norisoboldine, an alkaloid compound isolated from Radix Linderae, inhibits synovial angiogenesis in adjuvant-induced arthritis rats by moderating Notch1 pathway-related endothelial tip cell phenotype.

    PubMed

    Lu, Qian; Lu, Shuai; Gao, Xinghua; Luo, Yubin; Tong, Bei; Wei, Zhifeng; Lu, Tao; Xia, Yufeng; Chou, Guixin; Wang, Zhengtao; Dai, Yue

    2012-08-01

    Synovial angiogenesis is well recognized as participating in the pathogenesis of rheumatoid arthritis (RA) and has been regarded as a potential target for RA therapy. Previously, we have shown that norisoboldine (NOR) can protect joints from destruction in mice with collagen II-induced arthritis (CIA). Here, we investigate the effect of NOR on synovial angiogenesis in adjuvant-induced arthritis (AA) rats, and clarify the mechanisms in vitro. NOR, administered orally, significantly reduced the number of blood vessels and expression of growth factors in the synovium of AA rats. In vitro, it markedly prevented the migration and sprouting of endothelial cells. Notably, the endothelial tip cell phenotype, which is essential for the migration of endothelial cells and subsequent angiogenesis, was significantly inhibited by NOR. This inhibitory effect was attenuated by pretreatment with N-{N-[2-(3,5-difluorophenyl) acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester, a Notch1 inhibitor, suggesting that the action of NOR was related to the Notch1 pathway. A molecular docking study further confirmed that NOR was able to promote Notch1 activation by binding the Notch1 transcription complex. In conclusion, NOR was able to prevent synovial angiogenesis in AA rats, which is a putatively new mechanism responsible for its anti-rheumatoid effect. The anti-angiogenesis action of NOR was likely achieved by moderating the Notch1 pathway-related endothelial tip cell phenotype with a potential action target of the Notch1 transcription complex. PMID:22875342

  16. Inhibition of oxidative stress in brain during rat adjuvant arthritis by carnosine, trolox and novel trolox-carnosine.

    PubMed

    Poništ, S; Slovák, L; Kuncírová, V; Fedorova, T; Logvinenko, A; Muzychuk, O; Mihalová, D; Bauerová, K

    2015-01-01

    Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain. PMID:26681078

  17. Role of Sinomenine on Complete Freund's Adjuvant-Induced Arthritis in Rats.

    PubMed

    Lan, Zhou; Wei, Meng; Chen, Lvyi; Xie, Guangjing; Liu, Xiao; Zhang, Xiuqiao

    2016-06-01

    The investigation was undertaken to evaluate the effect of sinomenine (Sin) on experimental adjuvant arthritis rats stimulated by Freund's complete adjuvant and explore the corresponding potential molecular mechanism. The content of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6 were detected. Besides, canonical nuclear factor kappa B (NF-κB) pathway was also assessed to evaluate the antiarthritic potential of sinomenine. Pathological sections of rat paws showed sinomenine and diclofenac sodium significantly alleviated articular cartilage lesion, cellular infiltration, epithelial cell degeneration, synovial tissue vasodilation and congestion. The phosphorylations of inhibitor of kappaB alpha and NF-κB subunit p65 were downregulated with the treatment of sinomenine in dose dependent manners, as well as proinflammatory cytokines. Therefore, it was assumed that sinomenine might be a new therapeutic candidate to treat arthritis. © 2016 IUBMB Life, 68(6):429-435, 2016. PMID:27079983

  18. Quercetin: a potential natural drug for adjuvant treatment of rheumatoid arthritis.

    PubMed

    Ji, Jian-Jun; Lin, Yuan; Huang, Shan-Shan; Zhang, Hou-Li; Diao, Yun-Peng; Li, Kun

    2013-01-01

    Rheumatoid arthritis (RA) is the rheumatism mainly manifested as disabling joint disease and mainly involves hands, wrists, feet and other small joints. Recurrent arthritis attacks, synovial cell hypertrophy and hyperplasia and bone and cartilage damages eventually lead to joint dysfunction and other complications, and there is no cure. Quercetin (QU) is a kind of natural flavonoids, with lipid-lowering, anti-inflammatory and other pharmacological activities, and minor toxic side effects. Thus, we assume that QU may be an adjuvant natural drug for treatment of RA. The possible mechanism is through regulation of NF-κB, to inhibit the transcription of joint synovitis factors, hinder the generation of inflammatory factors, and inhibit the inflammatory reaction; through inhibiting the activities of VEGF, bFGF, MMP-2 and other cytokines, to inhibit angiogenesis in multiple links and inhibit synovial pannus formation. QU may be an adjuvant natural drug for treatment of RA. PMID:24146468

  19. Protective effects of L-carnitine and alpha-lipoic acid in rats with adjuvant arthritis.

    PubMed

    Tastekin, Nurettin; Aydogdu, Nurettin; Dokmeci, Dikmen; Usta, Ufuk; Birtane, Murat; Erbas, Hakan; Ture, Mevlut

    2007-10-01

    Free radicals play an important role in the pathophysiology of adjuvant arthritis. The purpose of this study was to assess the efficacy of L-carnitine (LC) and alpha-lipoic acid (alpha-LA) which are known to have antioxidant effects, in the treatment of adjuvant arthritis. Arthritis model was created by the administration of complete Freund's adjuvant (CFA) in 32 of 40 male Sprague-Dawley rats. The rats were divided into five groups. Rats in Group I served as controls and received 0.1 ml kg(-1) saline. Group II received only 0.1 ml of CFA and served as the CFA-control for the other groups. Groups III-V, after being injected with CFA, were treated with LC, alpha-LA or diclofenac, respectively. Levels of malondialdehyde (MDA) and glutathione (GSH) were measured in plasma samples. Enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The paws of rats were evaluated histopathologically to investigate the anti-inflammatory effects. TNF-alpha levels were measured for the evaluation of inflammation. In Group II plasma MDA increased, levels of glutathione decreased, enzyme activities of SOD and GPx decreased. Histopathological damage increased in the paws of the rats in this group. MDA levels decreased in Groups III-V when compared with Group II. GSH levels significantly increased in Group III and IV than Group V. SOD activity of Group IV was higher than Group III and V. TNF-alpha levels were significantly lower in Group IV and V. LC and alpha-LA seemed to have protective effects against oxidative damage in adjuvant arthritis model. PMID:17826175

  20. Cytokine expression and synovial pathology in the initiation and spontaneous resolution phases of adjuvant arthritis: Interleukin-17 expression is upregulated in early disease

    PubMed Central

    Bush, K A; Walker, J S; Lee, C S; Kirkham, B W

    2001-01-01

    The aim of this study was to understand the immune processes controlling the initiation and spontaneous resolution of adjuvant arthritis (AA). We investigated synovial T-cell recruitment and mRNA expression of IL-17 and other important disease related cytokines, IFN-γ, IL-2, IL-4, TNF and TGF-β in inguinal lymph node (ILN) and synovial membrane (SM). Arthritis severity was assessed by a numerical rating score and rats were sacrificed every 3–4 days postadjuvant induction. Further assessment involved quantitative radiology and histology of the ankle joints on each day, and the ILN and SM were removed for RNA extraction. Cytokine mRNA expression was measured using RT-PCR and densitometry. Paraffin sections of rat ankle joints were stained for T-cells (CD3) by immunohistochemistry. In the ILN, there was an increase in IL-17, TNF and IFN-γ expression in the early stages of disease, with a secondary sustained increase in IFN-γ expression. In the SM, there was expression of T-cell cytokines in early arthritis (day 13), and prolonged TNF and TGF-β expression, which reflected disease progression. IL-4 mRNA expression increased in the later stages of AA. Synovial T-cell numbers transiently increased at day 6, and remained high from days 13–28. Increased pro-inflammatory cytokine expression, including IL-17, in the ILN reflects the initiating events in the early stage of disease. IL-17 may therefore play an important role in the pathogenesis of AA. The increase in IL-4 (an anti-inflammatory cytokine) in the SM in the later stages of AA suggests that IL-4 is involved in the spontaneous resolution of AA. The initial increase in IFN-γ in the ILN may reflect a pro-inflammatory response, while the prolonged secondary increase may indicate activation of regulatory T-cells. PMID:11298138

  1. Effect of methotrexate on inflammatory cells redistribution in experimental adjuvant arthritis.

    PubMed

    Feketeová, Lucia; Jančová, Petra; Moravcová, Petra; Janegová, Andrea; Bauerová, Katarína; Poništ, Silvester; Mihalová, Danica; Janega, Pavol; Babál, Pavel

    2012-11-01

    The aim of this study was to evaluate the morphological changes in the spleen, the thymus and the knee joints of rats with experimental adjuvant arthritis induced by Mycobacterium butyricum in the incomplete Freund's adjuvant and the effect of treatment with methotrexate (MTX). Particular attention was aimed on the redistribution of granulocytes in the tissues during the inflammatory process. Clinical parameters, e.g., joint edema, body weight and of gamma glutamyl transferase (GGT) activity as an inflammatory marker, have also been determined. Induction of adjuvant arthritis caused a significant decrease in granulocyte number in the spleen and vice versa a significant increase in the knee joints, but without significant changes in the thymus. Treatment with methotrexate reversed this phenomenon by increasing the granulocyte number in the spleen and decreasing it in knee joints. MTX decreased the joint edema as well as the activity of GGT in the spleen, modified the size of the white pulp of the spleen and increased the cortex/medulla ratio in the thymus. The observed changes support the anti-inflammatory and immunomodulatory properties of MTX supporting its use as the first-line medication in patients with rheumatoid arthritis. PMID:22083611

  2. 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. PMID:23037783

  3. 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

  4. Adjuvant oestrogen therapy does not improve disease activity in postmenopausal patients with rheumatoid arthritis.

    PubMed Central

    van den Brink, H R; van Everdingen, A A; van Wijk, M J; Jacobs, J W; Bijlsma, J W

    1993-01-01

    OBJECTIVE--To investigate whether oestrogens can be used as treatment to diminish disease activity in women with rheumatoid arthritis. METHODS--Forty postmenopausal female patients with active rheumatoid arthritis participated in a placebo-controlled, double-blind study on the possible beneficial effect of adjuvant treatment of oestradiol on disease activity. RESULTS--Thirty three patients completed 52 weeks of treatment with 2 mg oestradiol-valerate or placebo. No statistically significant difference was found in and between both treatment groups with regard to articular indices, pain score by visual analogue scale, erythrocyte sedimentation rate and health questionnaire on daily activities before, during and at the end of the study. CONCLUSION--This first randomised prospective placebo-controlled study shows no beneficial effect of oestrogens on disease activity in postmenopausal female patients with rheumatoid arthritis. PMID:8311536

  5. 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.

  6. 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

  7. Liposomal encapsulation enhances and prolongs the anti-inflammatory effects of water-soluble dexamethasone phosphate in experimental adjuvant arthritis

    PubMed Central

    2010-01-01

    Introduction The objective of this study was to evaluate the efficacy of intravenous (i.v.) injection of liposomally encapsulated dexamethasone phosphate (DxM-P) in comparison to free DxM-P in rats with established adjuvant arthritis (AA). This study focused on polyethylene glycol (PEG)-free liposomes, to minimize known allergic reactions caused by neutral PEG-modified (PEG-ylated) liposomes. Methods Efficacy was assessed clinically and histologically using standard scores. Non-specific and specific immune parameters were monitored. Activation of peritoneal macrophages was analyzed via cytokine profiling. Pharmacokinetics/biodistribution of DxM in plasma, synovial membrane, spleen and liver were assessed via mass spectrometry. Results Liposomal DxM-P (3 × 1 mg/kg body weight; administered intravenously (i.v.) on Days 14, 15 and 16 of AA) suppressed established AA, including histological signs, erythrocyte sedimentation rate, white blood cell count, circulating anti-mycobacterial IgG, and production of interleukin-1beta (IL-1β) and IL-6 by peritoneal macrophages. The suppression was strong and long-lasting. The clinical effects of liposomal DxM-P were dose-dependent for dosages between 0.01 and 1.0 mg/kg. Single administration of 1 mg/kg liposomal DxM-P and 3 × 1 mg/kg of free DxM-P showed comparable effects consisting of a partial and transient suppression. Moreover, the effects of medium-dose liposomal DxM-P (3 × 0.1 mg/kg) were equal (in the short term) or superior (in the long term) to those of high-dose free DxM-P (3 × 1 mg/kg), suggesting a potential dose reduction by a factor between 3 and 10 by liposomal encapsulation. For at least 48 hours after the last injection, the liposomal drug achieved significantly higher levels in plasma, synovial membrane, spleen and liver than the free drug. Conclusions This new PEG-free formulation of macrophage-targeting liposomal DxM-P considerably reduces the dose and/or frequency required to treat AA, with a potential

  8. Developments in the rat adjuvant arthritis model and its use in therapeutic evaluation of novel non-invasive treatment by SOD in Transfersomes.

    PubMed

    Simões, S I; Delgado, T C; Lopes, R M; Jesus, S; Ferreira, A A; Morais, J A; Cruz, M E M; Corvo, M L; Martins, M B F

    2005-03-21

    The aim of this study was firstly to refine a rat model of arthritis, the adjuvant arthritis (AA) model, by studying the time course of the disease, introducing new evaluation methods such as haematological and biochemical parameters in order to identify the main stages of the disease. An optimisation of treatment schedule and evaluation criteria was developed. This refinement provided novel non-invasive anti-inflammatory treatment of the AA with SOD by using mixed lipid vesicles specially developed for transdermal delivery, Transfersomes (Tfs), this being the second major aim. The time course of AA includes a first stage: 1 day after the disease induction, the induced paw volume more than doubled and the paw circumference increased by approx. 50%. Two weeks later, another stage occurred where the disease shifted from the local arthritis form towards polyarthritis: an additional increase of volume and circumference of the induced and non-induced paws, occurred. The animals also started to loose weight around day 14 after the disease induction. Radiographic observable lesions increased correspondingly. Treatment of animals, started at day 1 after induction, by epicutaneous application of SOD-Tfs showed that 1 mg SOD/kg body weight is more efficient than 0.66 mg SOD /kg body weight. As a positive control, SOD liposomes intravenously injected were used for comparison and confirmed the biological efficiency of epicutaneously applied SOD in Tfs. SOD solution and empty Tfs epicutaneously applied exerted no effect. In addition, epicutaneous application of SOD-Tfs used prophylactically was able to suppress the induced rat paw oedema. Radiographic images showed less joint lesions in SOD-Tfs treated animals in comparison with control and placebo treated rats. It was shown for the first time that SOD incorporated into Tfs and applied onto a skin area not necessarily close to the inflamed tissue is able to promote non-invasive treatment of induced arthritis. PMID:15763624

  9. Adjuvant oils induce arthritis in the DA rat. I. Characterization of the disease and evidence for an immunological involvement.

    PubMed

    Kleinau, S; Erlandsson, H; Holmdahl, R; Klareskog, L

    1991-12-01

    An intradermal injection of Freund's incomplete adjuvant oil (FIA) without further additives was shown to induce erosive polyarthritis in dark Agouti (DA) rats, but not in Lewis rats. Histological examination revealed joint inflammation, first with polymorphonuclear cells and synovial hyperplasia, and subsequently, with multinucleated giant cells. Both constituents of FIA, mineral oil and Arlacel A, as well as Pristane oil were arthritogenic, whereas vegetable oil were not. Re-administration of adjuvant oil after recovery failed to induce arthritis, thus making possible a role of specific immunity in this new form of arthritis in rats. PMID:1812893

  10. Therapeutic Vaccination against Adjuvant Arthritis Using Autoimmune T Cells Treated with Hydrostatic Pressure

    NASA Astrophysics Data System (ADS)

    Lider, Ofer; Karin, Nathan; Shinitzky, Meir; Cohen, Irun R.

    1987-07-01

    An ideal treatment for autoimmune diseases would be a nontoxic means of specifically neutralizing the autoreactive lymphocytes responsible for the disease. This goal has been realized in experimental autoimmunity models by immunizing rats or mice against their own autoimmune cells such that the animals generate an immune response specifically repressive to the disease-producing lymphocytes. This maneuver, termed lymphocyte vaccination, was demonstrated to be effective using some, but not all, autoimmune helper T-lymphocyte lines. We now report that T lymphocytes, otherwise incapable of triggering an immune response, can be transformed into effective immunogens by treating the cells in vitro with hydrostatic pressure. Clone A2b, as effector clone that recognized cartilage proteoglycan and caused adjuvant arthritis in Lewis rats, is such a cell. Untreated A2b could not trigger an immune response, but inoculating rats with pressure-treated A2b induced early remission of established adjuvant arthritis as well as resistance to subsequent disease. Specific resistance to arthritis was associated with anti-idiotypic T-cell reactivity to clone A2b and could be transferred from vaccinated rats to naive recipients using donor lymphoid cells. Aggregation of T-lymphocyte membrane components appeared to be important for an immune response because the effects of hydrostatic pressure could be reproduced by treatment of A2b with chemical cross-linkers or with agents disrupting the cytoskeleton. Populations of lymph node cells from antigen-primed rats, when treated with hydrostatic pressure, could also induce suppression of disease. Thus, effective vaccines can be developed without having to isolate the autoimmune T lymphocytes as lines or clones. These results demonstrate that effector T lymphocytes suitably treated may serve as agents for specifically controlling the immune system.

  11. 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

  12. 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

  13. Specific accumulation of cholesterol-rich liposomes in the inflammatory tissue of rats with adjuvant arthritis.

    PubMed Central

    Love, W G; Amos, N; Kellaway, I W; Williams, B D

    1990-01-01

    High performance liquid chromatography has shown that after intravenous injection cholesterol-poor liposomes (100 nm) are unstable and their phospholipid is redistributed. Under identical conditions cholesterol-rich liposomes remain structurally intact within the circulation. When injected intravenously cholesterol-rich liposomes accumulate within the inflamed paws of rats with adjuvant induced arthritis to the same extent as cholesterol-poor liposomes. Uptake in inflamed tissue of three cholesterol-rich liposome preparations was always significantly greater than the uptake noted in normal tissue. The degree of accumulation in inflamed tissue was found to depend on the size of the liposome, with the greatest uptake, 7% of the injected dose, achieved by the smallest vesicle (100 nm). These results indicate that intact liposomes accumulate at inflamed joint tissue sites. Therefore the passive targeting of anti-inflammatory drugs encapsulated within these liposomes could be contemplated. PMID:2396866

  14. Intraarticular gene transfer of SPRY2 suppresses adjuvant-induced arthritis in rats.

    PubMed

    Zhang, Wei; Zhu, Jingying; Du, Zhiyan; Yu, Jiyun; Xu, Yuanji; Wang, Fang

    2015-08-01

    AKT and ERK pathways have been implicated as therapeutic targets for human rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) inhibition, and thus RA treatment. Sprouty2 (SPRY2) has been known as a tumor suppressor by blocking both ERK and AKT signaling cascades. Whether SPRY2 can function as a suppressor of tumor-like inflammatory FLS and RA through negatively regulating AKT and ERK activation has not been reported. The purpose of this study was to determine whether SPRY2 might have antiarthritic effects in experimental animal model of RA. We first determined that expression of SPRY2 mRNA was decreased in FLS from patients with RA compared with patients with osteoarthritis (OA). Further studies demonstrated that intraarticular gene transfer with AdSPRY2, the recombinant adenovirus containing SPRY2 complementary DNA, resulted in a significant suppression of rat adjuvant-induced arthritis (AIA) compared with the control AdGFP, the adenoviral vector encoding green fluorescent protein, as reflected in both clinical and histological observations. AdSPRY2 suppressed the production of proinflammatory cytokines and matrix metalloproteinases (MMPs), and the activation of ERK and AKT signals in AIA ankle joints. These results suggest that using SPRY2 to block the AKT and ERK pathways effectively reduces the inflammatory responses and arthritic progression in AIA. Thus, the development of an immunoregulatory strategy based on SPRY2 may therefore have therapeutic potential in the treatment of RA. PMID:25935347

  15. 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.

  16. Increase in sensory neuropeptides surrounding the Achilles tendon in rats with adjuvant arthritis.

    PubMed

    Bring, Daniel K-I; Heidgren, Marie-Louise; Kreicbergs, Andris; Ackermann, Paul W

    2005-03-01

    The Achilles tendon in rats with adjuvant arthritis was analyzed by radioimmunoassay (RIA) and semi-quantitative immunohistochemistry for the occurrence of two sensory neuropeptides, substance P (SP) and calcitonin gene related peptide (CGRP), and a sensory modulating peptide, galanin (GAL). The tissue concentration of SP and CGRP in the Achilles tendon and its envelope, i.e. the paratenon and bony insertion, as assessed by RIA was increased by 22% and 71%, respectively, compared to normal controls, whereas the level of GAL was unchanged. Semi-quantitative immunohistochemistry applied to different regions of the tendon in arthritic rats disclosed an increased occurrence of SP and CGRP positive nerve fibers in the paratenon and bone tendinous junction, whereas GAL fibers were only increased at the bone tendinous junction. Notably, neither neuropeptides nor inflammatory cells were seen in the tendon proper. The increased occurrence of SP and CGRP in the tendon envelope presumably reflects inflammatory actions, whereas that of GAL implies an endogenous anti-inflammatory response. The observed SP and CGRP upregulation in the paratenon and bony insertion suggests a pathophysiological role in paratenonitis and enthesitis often seen in patients with rheumatoid arthritis. Presumably Achillodynia originates in the tendon envelope rather than the tendon proper. The observations could be used to define new pharmacological targets for mitigating symptoms from tendons in rheumatoid arthritis and possibly also in other disorders. Whether a neuronal pathogenic mechanism underlies tendon overuse disorders in non-arthritic tendinopathies and the development of degeneration, i.e. tendinosis, remains to be studied. PMID:15734239

  17. 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). PMID:26349791

  18. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis.

    PubMed

    Cicala, C; Ianaro, A; Fiorucci, S; Calignano, A; Bucci, M; Gerli, R; Santucci, L; Wallace, J L; Cirino, G

    2000-07-01

    1. Anti-inflammatory non steroidal drugs releasing NO (NO-NSAIDs) are a new class of anti-inflammatory drugs to which has been added an NO-releasing moiety. These compounds have been shown to retain the anti-inflammatory, analgesic and antipyretic activity of the parent compound but to be devoid of gastrointestinal (GI) toxicity. 2. Freund's adjuvant (FA) arthritis was induced in rats by a single intraplantar injection into the right hindpaw of 100 microl of mycobacterium butirricum (6 mg ml(-1)). The effect of equimolar doses of naproxen (1, 3 and 10 mg kg(-1)) and NO-naproxen (1.5, 4.5 and 16 mg kg(-1)) was evaluated using two dosage regimen protocols: (i) preventive, starting oral administration of the drugs at the time of induction of arthritis and for the following 21 days (day 1 - 21); (ii) therapeutic, starting oral administration of the drugs 7 days after adjuvant injection and for the following 14 days (day 7 - 21). 3. Hindpaw swelling (days 3, 7, 11, 14, 17, 21) and nociception (days 15 and 21) were measured. On day 22 rats were sacrificed, draining lymph nodes were removed and T cells isolated. In vitro proliferation of T cells following stimulation with concanavalin A (0.5 - 5 microg ml(-1)) was measured using a tritiated thymidine incorporation assay. IL-2 receptor expression on T cells was measured by FACS analysis. 4. Naproxen and NO-naproxen showed similar activity in reducing oedema formation in the non-injected (controlateral) hindpaw. Both drugs showed anti-nociceptive effect. NO-naproxen was anti-nociceptive at a dose of 4.5 mg kg(-1) while naproxen showed the same extent of inhibition only at a dose of 10 mg kg(-1). 5. T cells were isolated and characterized by FACS analysis. Stimulation of isolated T cells with concanavallin A in vitro caused a significant increase in thymidine uptake. NO-naproxen at a dose of 4.5 mg kg(-1) inhibited T cell proliferation to the same extent as 10 mg kg(-1) of naproxen. 6. Inhibition of T cell proliferation was

  19. NO-naproxen modulates inflammation, nociception and downregulates T cell response in rat Freund's adjuvant arthritis

    PubMed Central

    Cicala, Carla; Ianaro, Angela; Fiorucci, Stefano; Calignano, Antonio; Bucci, Mariarosaria; Gerli, Roberto; Santucci, Luca; Wallace, John L; Cirino, Giuseppe

    2000-01-01

    Anti-inflammatory non steroidal drugs releasing NO (NO-NSAIDs) are a new class of anti-inflammatory drugs to which has been added an NO-releasing moiety. These compounds have been shown to retain the anti-inflammatory, analgesic and antipyretic activity of the parent compound but to be devoid of gastrointestinal (GI) toxicity.Freund's adjuvant (FA) arthritis was induced in rats by a single intraplantar injection into the right hindpaw of 100 μl of mycobacterium butirricum (6 mg ml−1). The effect of equimolar doses of naproxen (1, 3 and 10 mg kg−1) and NO-naproxen (1.5, 4.5 and 16 mg kg−1) was evaluated using two dosage regimen protocols: (i) preventive, starting oral administration of the drugs at the time of induction of arthritis and for the following 21 days (day 1–21); (ii) therapeutic, starting oral administration of the drugs 7 days after adjuvant injection and for the following 14 days (day 7–21).Hindpaw swelling (days 3, 7, 11, 14, 17, 21) and nociception (days 15 and 21) were measured. On day 22 rats were sacrificed, draining lymph nodes were removed and T cells isolated. In vitro proliferation of T cells following stimulation with concanavalin A (0.5–5 μg ml−1) was measured using a tritiated thymidine incorporation assay. IL-2 receptor expression on T cells was measured by FACS analysis.Naproxen and NO-naproxen showed similar activity in reducing oedema formation in the non-injected (controlateral) hindpaw. Both drugs showed anti-nociceptive effect. NO-naproxen was anti-nociceptive at a dose of 4.5 mg kg−1 while naproxen showed the same extent of inhibition only at a dose of 10 mg kg−1.T cells were isolated and characterized by FACS analysis. Stimulation of isolated T cells with concanavallin A in vitro caused a significant increase in thymidine uptake. NO-naproxen at a dose of 4.5 mg kg−1 inhibited T cell proliferation to the same extent as 10 mg kg−1 of naproxen.Inhibition of T cell proliferation

  20. Extract of the Chinese herbal formula Huo Luo Xiao Ling Dan inhibited adjuvant arthritis in rats

    PubMed Central

    Zhang, Rui-Xin; Fan, Arthur Yin; Zhou, An-Nan; Moudgil, Kamal D.; Ma, Zhong-Ze; Lee, David Yue-Wei; Fong, Harry HS; Berman, Brian M.; Lao, Lixing

    2010-01-01

    Ethnopharmacological relevance The herbal formula Huo Luo Xiao Ling Dan (HLXL) and its modifications have been used in traditional Chinese medicine for about one hundred years to alleviate pain and inflammation. Aim To investigate the effects of HLXL on complete Freund’s adjuvant (CFA)-induced multiple-joint arthritis in rats. Materials and Methods Male Lewis rats, 190–210g, were immunized subcutaneously at the base of the tail with 200 µl of heat-killed M. tuberculosis in mineral oil (5 mg/ml). HLXL (2.30g/kg and 4.60g/kg) or vehicle control (n=8 per group) was administered orally (i.g.) once a day between days 16–25 post-CFA injection. The rats were observed for signs of arthritis with arthritic changes (erythema, edema, induration) being scored on a scale of 0 to 4 of increasing severity using a standard scoring system. The maximum arthritis score per rat was 16. A plethysmometer was used to measure edema volume in each paw. Adverse effects of HLXL were monitored by closely observing the animals for unusual behavioral changes. Levels of tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β) in local tissue were measured by enzyme-linked immunosorbent assay on day 25 post-CFA. Results HLXL significantly decreased arthritis scores between days 23–25 in the 2.30g/kg group and 21–25 in the 4.60g/kg group (p<0.05). It reduced paw edema on days 22 and 24 in the 2.30g/kg group and on days 20, 22 and 24 in the 4.60g/kg group compared to control (p<0.05). Local tissue TNF-α and IL-1β levels on day 25 post-CFA injection were significantly (p<0.05) lower in rats treated with HLXL than in control rats. No observable adverse effects were found. Conclusion The data suggest that HLXL produces significant anti-arthritic effects that may be mediated by suppressing pro-inflammatory cytokines, and it appears to be safe. PMID:19100323

  1. 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

  2. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  3. Glucocorticoids in nano-liposomes administered intravenously and subcutaneously to adjuvant arthritis rats are superior to the free drugs in suppressing arthritis and inflammatory cytokines.

    PubMed

    Ulmansky, Rina; Turjeman, Keren; Baru, Moshe; Katzavian, Galia; Harel, Michal; Sigal, Alex; Naparstek, Yaakov; Barenholz, Yechezkel

    2012-06-10

    We have previously shown that intravenous (i.v.) treatment with sterically stabilized nano-liposomes (NSSL) actively remote-loaded with the glucocorticoid (GC) methylprednisolone hemisuccinate (NSSL-MPS) or betamethasone hemisuccinate (NSSL-BMS) significantly decreased severity of adjuvant arthritis in Lewis rats (a model of human rheumatoid arthritis) throughout all disease stages. Here, we compared i.v. or subcutaneous (s.c.) weekly treatment with each of the two NSSL-GC to weekly or daily treatment with the free drugs or with the TNF-α antagonists Infliximab and Etanercept. Therapeutic efficacy and effects on the profile of pro-inflammatory (IL-6, TNF-α, and INF-γ) and anti-inflammatory (IL-10 and TGF-β) cytokines in rat sera and splenocyte tissue culture supernatants were compared to those of the liposomal and free drugs. Both s.c. and i.v. NSSL-GC suppressed arthritis significantly, compared to higher doses of the free drugs or to TNF-α antagonists. NSSL-GC also suppressed the secretion of pro-inflammatory cytokines, but did not change the levels of TGF- β. The highly efficacious anti-inflammatory therapeutic feature of these nano-drugs makes them candidates for treatment of human rheumatoid arthritis. PMID:22226777

  4. AA-negative and Kappa-positive Amyloidosis in a Patient with Rheumatoid Arthritis.

    PubMed

    Ueno, Toshiharu; Sumida, Keiichi; Hoshino, Junichi; Suwabe, Tatsuya; Mise, Koki; Hazue, Ryo; Hayami, Noriko; Hiramatsu, Rikako; Kawada, Masahiro; Imafuku, Aya; Hasegawa, Eiko; Sawa, Naoki; Takaichi, Kenmei; Kinowaki, Keiichi; Ohashi, Kenichi; Fujii, Takeshi; Nishida, Aya; Ubara, Yoshifumi

    2016-01-01

    A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient. PMID:27580556

  5. Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

    PubMed

    Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

    2011-10-01

    Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. PMID:21693118

  6. 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

  7. 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

  8. In vivo and in vitro effects of dexamethasone on leukocyte migration in the rat adjuvant arthritis model

    SciTech Connect

    Thieme, T.R.; Mirkovich, A.; Maloney, P.; Goodwin, D.A.

    1982-12-01

    When polymorphonuclear leukocytes (PMNs) and mononuclear cells were isolated from the blood of dexamethasone-treated normal rats, in vitro mononuclear cell migration was inhibited and PMN migration was stimulated in comparison to controls. Inflammogen-induced PMNs showed inhibited cell migration due to dexamethasone treatment. Gamma camera imaging was then used to detect cells in vivo after labeling with /sup 111/In. When the dexamethasone-treated blood cells were injected into adjuvant arthritis diseased rats, mononuclear cells showed depressed migration into the inflamed paws, while PMNs showed stimulated migration into the inflamed paws in comparison to controls. When the recipient adjuvant arthritic animals were treated with dexamethasone, both normal mononuclear cell and normal PMN migration to the inflamed paws were inhibited.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Comparative antigen-induced gene expression profiles unveil novel aspects of susceptibility/resistance to adjuvant arthritis in rats.

    PubMed

    Yu, Hua; Lu, Changwan; Tan, Ming T; Moudgil, Kamal D

    2013-12-01

    Lewis (LEW) and Wistar Kyoto (WKY) rats of the same major histocompatibility complex (MHC) haplotype (RT.1(l)) display differential susceptibility to adjuvant-induced arthritis (AIA). LEW are susceptible while WKY are resistant to AIA. To gain insights into the mechanistic basis of these disparate outcomes, we compared the gene expression profiles of the draining lymph node cells (LNC) of these two rat strains early (day 7) following a potentially arthritogenic challenge. LNC were tested both ex vivo and after restimulation with the disease-related antigen, mycobacterial heat-shock protein 65. Biotin-labeled fragment cRNA was generated from RNA of LNC and then hybridized with an oligonucleotide-based DNA microarray chip. The differentially expressed genes (DEG) were compared by limiting the false discovery rate to <5% and fold change ≥2.0, and their association with quantitative trait loci (QTL) was analyzed. This analysis revealed overall a more active immune response in WKY than LEW rats. Important differences were observed in the association of DEG with QTL in LEW vs. WKY rats. Both the number of upregulated DEG associated with rat arthritis-QTL and their level of expression were relatively higher in LEW when compared to WKY rat; however, the number of downregulated DEG-associated with rat arthritis-QTL as well as AIA-QTL were found to be higher in WKY than in LEW rats. In conclusion, distinct gene expression profiles define arthritis-susceptible versus resistant phenotype of MHC-compatible inbred rats. These results would advance our understanding of the pathogenesis of autoimmune arthritis and might also offer potential novel targets for therapeutic purposes. PMID:23911410

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

    PubMed Central

    Gupta, Mradu; Sasmal, Saumyakanti; Mukherjee, Arup

    2014-01-01

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

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

    PubMed

    Gupta, Mradu; Sasmal, Saumyakanti; Mukherjee, Arup

    2014-01-01

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

  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. Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.

    PubMed

    Fahim, A T; Abd-el Fattah, A A; Agha, A M; Gad, M Z

    1995-01-01

    Pumpkin-seed oil (PSO), a natural supplement rich with antioxidant ingredients, was given to rats in which arthritis was induced using Freund's complete adjuvant. Its effect was compared with that of indomethacin, as a classical anti-inflammatory agent. Two experimental patterns were studied, an acute phase that was applied only with PSO and a chronic phase applied for both PSO and indomethacin. Compared to normal untreated rats, it was shown that the induction of arthritis caused a decrease in serum sulphhydryl groups, with an increase in serum ceruloplasmin in both phases. Blood glutathione was first elevated in the acute phase, then its level was reduced in the chronic phase. Serum N-acetyl-beta-D-glucosaminidase activity was elevated only at the acute phase, while plasma total proteins and albumin were reduced at the chronic phase. Liver glucose-6-phosphate dehydrogenase activity was markedly increased, while no changes were observed in the levels of liver lipid peroxides and glutathione. These changes in the studied parameters were attributed to the superoxides and free radicals during arthritic inflammation. Administration of PSO succeeded in modulating most of the altered parameters affected during arthritis, especially at the chronic phase. Also, a remarkable inhibition of paw oedema was observed. A similar pattern was obtained upon treatment with indomethacin except that indomethacin markedly elevated liver lipid peroxides levels. Concurrent administration of PSO with indomethacin caused no changes in the parameters studied compared to that induced by treatment with indomethacin alone. PMID:7784309

  18. Determination of geniposide in adjuvant arthritis rat plasma by ultra-high performance liquid chromatography tandem mass spectrometry method and its application to oral bioavailability and plasma protein binding ability studies.

    PubMed

    Chen, Jian; Wu, Hong; Xu, Guo-Bing; Dai, Miao-Miao; Hu, Shun-Li; Sun, Liang-Liang; Wang, Wei; Wang, Rong; Li, Shu-Pin; Li, Guo-Qiang

    2015-04-10

    A specific, sensitive and high throughput ultra-high performance liquid chromatography-electrospray ionization tandem mass spectrometric method (UHPLC-ESI-MS/MS) was established and validated to assay geniposide (GE), a promising anti-inflammatory drug, in adjuvant arthritis rat plasma: application to pharmacokinetic and oral bioavailability studies and plasma protein binding ability. Plasma samples were processed by de-proteinised with ice-cold methanol and separated on an ACQUITY UPLC™ HSS C18 column (100 mm × 2.1mm i.d., 1.8 μm particle size) at a gradient flow rate of 0.2 mL/min using acetonitrile-0.1% formic acid in water as mobile phase, and the total run time was 9 min. Mass detection was performed in selected reaction monitoring (SRM) mode with negative electro-spray ionization includes the addition of paeoniflorin (Pae) as an internal standard (IS). The mass transition ion-pair was followed as m/z 387.4 → 122.4 for GE and m/z 479.4 → 449.0 for IS. The calibration curves were linear over the concentration range of 2-50,000 ng/mL with lower limit of quantification of 2 ng/mL. The intra-day and inter-day precisions (RSD, %) of the assay were less than 8.4%, and the accuracy was within ± 6.4% in terms of relative error (RE). Extraction recovery, matrix effect and stability were satisfactory in adjuvant arthritis rat plasma. The UHPLC-ESI-MS/MS method was successfully applied to a pharmacokinetic study of GE after oral administration of depurated GE at 33, 66, 132 mg/kg and intravenous injection at 33, 66, 132 mg/kg in adjuvant arthritis (AA) rats. In addition, it was found that GE has rapid absorption and elimination, low absolute bioavailability, high plasma protein binding ability in AA rats after oral administration within the tested dosage range. It suggested that GE showed slow distribution into the intra- and extracellular space, and the binding rate was not proportionally dependent on plasma concentration of GE when the concentration of GE was

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

    PubMed

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

    1997-01-01

    Besides a superior protection of the pentadecapeptide BPC 157 (an essential fragment of an organoprotective gastric juice peptide BPC) against different gastrointestinal and liver lesions, an acute anti-inflammatory and analgetic activity was also noted. Consequently, its effect on chronic inflammation lesions, such as adjuvant arthritis, and non-steroidal anti-inflammatory agents (NSAIAs)-induced gastrointestinal lesions was simultaneously studied in rats. In gastrointestinal lesions (indomethacin (30 mg/kg s.c.), aspirin (400 mg/kg i.g.) and diclofenac (125 mg/kg i.p.) studies, BPC 157 (10 micrograms or 10 ng/kg i.p.) was regularly given simultaneously and/or 1 h prior to drug application (indomethacin). In the adjuvant arthritis (tail-application of 0.2 mL of Freund's adjuvant) studies (14 days, 30 days, 1 year) BPC 157 (10 micrograms or 10 ng/kg i.p.), it was given as a single application (at 1 h either before or following the application of Freund's adjuvant) or in a once daily regimen (0-14th day, 14-30th day, 14th day-1 year). Given with the investigated NSAIAs, BPC 157 consistently reduced the otherwise prominent lesions in the stomach of the control rats, as well as the lesions in the small intestine in the indomethacin groups. In the adjuvant arthritis studies, the lesion's development seems to be considerably reduced after single pentadecapeptide medication, and even more attenuated in rats daily treated with BPC 157. As a therapy of already established adjuvant arthritis, its salutary effect consistently appeared already after 2 weeks of medication and it could be clearly seen also after 1 year of application. Taking together all these results, the data likely point to a special anti-inflammatory and mucosal integrity protective effect. PMID:9403784

  20. Modulation of Th1 cytokines and inflammatory mediators by Euphorbia hirta in animal model of adjuvant-induced arthritis.

    PubMed

    Fayaz Ahmad, Sheikh; Sultan, Phalisteen; Ashour, Abdelkader E; Khan, Tajdar Husain; Attia, Sabry M; Bakheet, Saleh A; Abd-Allah, Adel R A

    2013-10-01

    Euphorbia hirta L. (Euphorbiaceae) (E. hirta) is a tree locally used as a traditional medicine in Africa and Australia to treat numerous diseases such as hypertension, respiratory ailments, tumors, antipyretic, anti-inflammatory activities. In the present study, we investigated the anti-arthritic activity of fresh leaves of E. hirta ethanol extract that was found to inhibit the production of inflammatory mediators and cytokines of adjuvant arthritis in rats. Adjuvant arthritis was induced in rats (Wistar) by the subplantar injection of 0.05 ml freshly prepared suspension (5.0 mg/ml) of steam killed Mycobacterium tuberculli in liquid paraffin. Animals were treated with graded doses of 25, 50, 100 and 200 mg/kg of E. hirta ethanol extract, p.o. E. hirta significantly inhibited the swelling of the adjuvant-induced arthritis. Moreover, E. hirta at higher dose (200 mg/kg) showed 40.54 ± 1.09 % of CD3+, 15.1 ± 0.76 % of CD4+, 12.2 ± 1.18 % of CD8+ T cell receptor and 17.6 ± 1.11 % gated of CD19+ B cell receptor revealing a down regulation of adjuvant-induced arthritis as compared to the corresponding valves of the arthritic control rats. According to the results shown in Tables 1, 2, the production of IL-1β, TNF-α, IL-2 and IFN-γ were increased in splenocytes of arthritic rats and this increased level was reduced by E. hirta. Also, E. hirta significantly down regulated lipopolysaccharide (LPS)-induced production of nitric oxide production in peritoneal macrophages. These results suggest that E. hirta exhibits an improvement in adjuvant-induced arthritis through down regulation of activated macrophages and T lymphocytes functions. Such unique effects of E. hirta shown on adjuvant arthritis rat model may be advantageous to the long-term treatment of clinical rheumatoid arthritis. Table 1 Effect of E. hirta and prednisolone (Pred) on LPS-induced IL-1β and TNF-α productions from splenocytes in Mycobacterium tuberculli-induced inflammatory arthritic rats Treatment

  1. Cytochemical demonstration of constitutive H2O2 production by macrophages in synovial tissue from rats with adjuvant arthritis.

    PubMed Central

    Hoffstein, S. T.; Gennaro, D. E.; Meunier, P. C.

    1988-01-01

    Generation of toxic oxygen metabolites by inflammatory cells is considered to be one of the mechanisms by which inflammation produces tissue injury. This concept is based on in vitro studies of purified leukocyte populations because it has not been possible to assess production of these metabolites in tissues. In order to determine whether or not inflammatory cells in tissue generate H2O2, the authors modified an earlier cytochemical method for the localization of H2O2. The incubation medium consists of 0.5 mM CeCl3 in a Hepes-buffered balanced salt solution with Cl- as the only anion. Synovial tissue from the knees of normal and 16-day adjuvant arthritic rats was incubated in this medium for 30 minutes and then fixed and processed for electron microscopy. No H2O2 reaction product was visible in normal synovium. In contrast, patchy deposits of H2O2 reaction product were seen adjacent to a subpopulation of synovial lining macrophages in synovium from inflamed knee joints. These data show that rat synovial macrophages are capable of generating H2O2 when appropriately stimulated and that such a stimulus is present in adjuvant arthritis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3257356

  2. Application of a radiometric ear assay for studies of adjuvant arthritis in rats

    SciTech Connect

    Gans, K.R.; Heyner, S.; Orzechowski, R.F.

    1980-06-01

    A radioisotopic method, originally developed for measuring the cellular response in delayed hypersensitivity lesions in mice, has been evaluated in adjuvant arthritic rats. Focal accumulation of 5-iodo-2'-deoxyuridine-/sup 125/I (/sup 125/IUdR) at a site of antigen challenge (left pinna) was measured and expressed as increased radioactivity in the challenged (left) over the unchallenged (right) ear (L/R ear ratio). A significant negative correlation was observed between the /sup 125/IUdR ear ratios and subjective arthritic scores in established adjuvant disease. The results of this study support the utility of the /sup 125/IUdR ear assay to quantify cellular accumulation at a site of antigen challenge in adjuvant arthritic rats and possibly other antigenic systems in this species.

  3. Penetration and effect of topically applied dimethylsulfoxide or indomethacin on adjuvant arthritis in the rat

    SciTech Connect

    Francis, M.D.; Horn, P.A.; McCreary, L.D.

    1983-07-01

    The present study, using /sup 14/C-DMSO, established the systemic and local load and distribution of topically applied DMSO in adjuvant arthritic rats. Under equivalent conditions, the antiinflammatory effects (systemic and local) of topical DMSO treatments were compared with a topical treatment of a control vehicle or of indomethacin, a known effective antiinflammatory agent. No significant systemic or local antiinflammatory effect of topical DMSO was seen in the adjuvant arthritic rats. Indomethacin, applied topically, had a significant systemic antiinflammatory effect; however, no significant local antiinflammatory effect of indomethacin was observed.

  4. Arthritis

    MedlinePlus

    ... when taking arthritis medicines . Over-the-counter medicines: Acetaminophen (Tylenol) is often the first medicine tried. Take up to 4000 mg a day (two arthritis-strength Tylenol every 8 hours). To prevent damage to your ...

  5. Imaging of Carrageenan-Induced Local Inflammation and Adjuvant-Induced Systemic Arthritis with [11C]PBR28 PET

    PubMed Central

    Shao, Xia; Wang, Xueding; English, Sean J; Desmond, Timothy; Sherman, Phillip S; Quesada, Carole A; Piert, Morand R

    2013-01-01

    Introduction [11C]PBR28 binding to translocator protein (TSPO) was evaluated for imaging of acute and chronic inflammation using two established rat models. Methods Acute inflammation was induced by local Carrageenan-injection into the paw of Fisher 344 rats (model A). T-cell mediated adjuvant arthritis was induced by heat-inactivated Mycobacterium butyricum injection in Lewis rats (model B). Micro-PET scan was performed after injection of approximately 35 MBq [11C]PBR28. In model A, volumes of interest (VOIs) were defined in the paw of Fisher 344 rats (n=6) with contralateral sham treatment as control. For model B, VOIs were defined in the tail, sacroiliac joints, hips, knees and thigh muscles of M. butyricum treated animals (n=8) and compared with sham-treated controls (n=4). The peak 11C-PBR28 SUV (SUVpeak) and area under the curve (AUCSUV) of 60-minute time-activity data were calculated. Immunohistochemistry for CD68, a macrophage stain, was performed from paw tissues. In addition, the [11C]PBR28 cell uptake was measured in lipopolysaccharide (LPS)-stimulated and non-stimulated macrophage cultures. Results LPS-stimulated macrophages displayed dose-dependent increased [11C]PBR28 uptake, which was blocked by non-labeled PBR28. In both models, radiotracer uptake of treated lesions increased rapidly within minutes and displayed overall accumulative kinetics. The SUVpeak and AUCSUV of Carrageenan-treated paws was significantly increased compared to controls. Also, the [11C]PBR28 uptake ratio of Carrageenan-treated vs. sham-treated paw correlated significantly with CD68 staining ratios of the same animals. In adjuvant arthritis, significantly increased [11C]PBR28 SUVpeak and AUCSUV values were identified at the tail, knees, and sacroiliac joints, while no significant differences were identified in the lumbar spine and hips. Conclusions Based on our initial data, [11C]PBR28 PET appears to have potential for imaging of various inflammatory processes involving

  6. A role for mast cells in the development of adjuvant-induced vasculitis and arthritis.

    PubMed Central

    Johnston, B.; Burns, A. R.; Kubes, P.

    1998-01-01

    The objective of this study was to characterize the role of mast cells in the development of vasculitis and joint swelling in adjuvant-immunized rats. Leukocyte trafficking within mesenteric venules (rolling and adhesion) and mast cell activation (ruthenium red uptake) were examined in vivo. Elevated leukocyte trafficking was observed by 4 days after immunization, whereas joint swelling developed between days 10 and 12. Perivascular mast cells took up ruthenium red and appeared activated by electron microscopy at 4 but not 12 days after immunization. Treatment with the mast cell stabilizer cromolyn on days 1 to 4 after immunization blocked ruthenium red uptake at day 4 and reduced leukocyte rolling and adhesion by approximately 50%. This treatment also reduced rolling, adhesion, and joint swelling at day 12 by approximately 50%. Cromolyn treatment over days 9 to 12 reduced joint swelling but increased leukocyte emigration into the mesentery. Peritoneal mast cells isolated 4 days after immunization elicited significant neutrophil chemotaxis in vitro, whereas day 12 mast cells did not. Mast cell activation and vasculitis were absent in adjuvant-resistant Fisher/344 rats. These data suggest that mast cells play an early role in the initiation of vasculitis and may function by day 12 to limit infiltration of leukocytes from the vasculature. In the joint, however, mast cells appear to contribute to inflammation at early as well as later time points. Images Figure 2 PMID:9466582

  7. 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

  8. Differences in osteoclast formation between proximal and distal tibial osteoporosis in rats with adjuvant arthritis: inhibitory effects of bisphosphonates on osteoclasts.

    PubMed

    Shu, Goukei; Yamamoto, Kaname; Nagashima, Masakazu

    2006-01-01

    Patients with rheumatoid arthritis commonly suffer both systemic and periarticular osteoporosis. Bisphosphonates (BPs) are inhibitors of bone resorption, and several derivatives have been developed for treatment of enhanced bone resorption. We aimed to characterize osteoclast formation in two different sites, the proximal tibial and distal tibial areas, in rats with adjuvant arthritis, and to investigate the impact of amino or non-amino types of bisphosphonate. Adjuvant arthritis was initiated in rats while administering daily injections of either etidronate, a non-amino BP, or alendronate, an amino BP, for 3 weeks. On the day following the last injection, bone mineral density (BMD) was measured in the proximal tibia to assess systemic osteoporosis and in the distal tibia for periarticular osteoporosis using dual-energy X-ray absorptiometry. Subsequently, bone marrow cells from either end of the tibia were collected and incubated for 7 days before staining and counting tartrate-resistant acid phosphatase positive cells. In the rats with adjuvant arthritis, BMD of either end of the tibia was lower than in normal rats. Although etidronate prevented bone mineral loss at both ends, distal loss was significantly less than proximal. In contrast, alendronate significantly inhibited mineral loss primarily in the proximal area. Large osteoclasts, defined as having five or more nuclei, formed preferentially in the proximal tibia, while small osteoclasts with fewer than four nuclei were found mainly distally. The suppressive effect of alendronate was greater on the large osteoclasts, while etidronate had a greater effect on the small osteoclasts. These results show that the size and multinuclearity of osteoclasts and the number of osteoclasts formed are different in the distal and proximal areas of the tibia, and that alendronate and etidronate may suppress different types of osteoclasts as discriminated by the number of nuclei. PMID:17164994

  9. Arthritis

    MedlinePlus

    ... Difficulty moving a joint (called "limited range of motion") Some types of arthritis may cause joint deformity. ... exercise). Walking is a good example. Range of motion exercises for flexibility. Strength training for muscle tone. ...

  10. 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

  11. An Important Role for N-Acylethanolamine Acid Amidase in the Complete Freund's Adjuvant Rat Model of Arthritis.

    PubMed

    Bonezzi, F T; Sasso, O; Pontis, S; Realini, N; Romeo, E; Ponzano, S; Nuzzi, A; Fiasella, A; Bertozzi, F; Piomelli, D

    2016-03-01

    The endogenous lipid amides, palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), exert marked antinociceptive and anti-inflammatory effects in animal models by engaging nuclear peroxisome proliferator-activated receptor-α. PEA and OEA are produced by macrophages and other host-defense cells and are deactivated by the cysteine amidase, N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and B-lymphocytes. In the present study, we examined whether a) NAAA might be involved in the inflammatory reaction triggered by injection of complete Freund's adjuvant (CFA) into the rat paw and b) administration of 4-cyclohexylbutyl-N-[(S)-2-oxoazetidin-3-yl]-carbamate (ARN726), a novel systemically active NAAA inhibitor, attenuates such reaction. Injection of CFA into the paw produced local edema and heat hyperalgesia, which were accompanied by decreased PEA and OEA content (assessed by liquid chromatography/mass spectrometry) and increased NAAA levels (assessed by Western blot and ex vivo enzyme activity measurements) in paw tissue. Administration of undec-10-ynyl-N-[(3S)-2-oxoazetidin-3-yl] carbamate (ARN14686), a NAAA-preferring activity-based probe, revealed that NAAA was catalytically active in CFA-treated paws. Administration of ARN726 reduced NAAA activity and restored PEA and OEA levels in inflamed tissues, and significantly decreased CFA-induced inflammatory symptoms, including pus production and myeloperoxidase activity. The results confirm the usefulness of ARN726 as a probe to investigate the functions of NAAA in health and disease and suggest that this enzyme may provide a new molecular target for the treatment of arthritis. PMID:26769918

  12. 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. PMID:24664592

  13. The A3 adenosine receptor agonist CF502 inhibits the PI3K, PKB/Akt and NF-kappaB signaling pathway in synoviocytes from rheumatoid arthritis patients and in adjuvant-induced arthritis rats.

    PubMed

    Ochaion, A; Bar-Yehuda, S; Cohen, S; Amital, H; Jacobson, K A; Joshi, B V; Gao, Z G; Barer, F; Patoka, R; Del Valle, L; Perez-Liz, G; Fishman, P

    2008-08-15

    The A(3) adenosine receptor (A(3)AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant- and collagen-induced arthritis. In this study we present a novel A(3)AR agonist, CF502, with high affinity and selectivity at the human A(3)AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-kappaB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of adjuvant-induced arthritis (AIA) in a rat experimental model when given orally at a low dose (100 microg/kg). As is typical of other G-protein coupled receptors, the A(3)AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of protein kinase B/Akt (PKB/Akt), IkappaB kinase (IKK), I kappa B (IkappaB), NF-kappaB and tumor necrosis factor-alpha (TNF-alpha) took place. In addition, the expression levels of glycogen synthase kinase-3 beta (GSK-3beta), beta-catenin, and poly(ADP-ribose)polymerase (PARP), known to control the level and activity of NF-kappaB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A(3)AR agonists for the treatment of rheumatoid arthritis. PMID:18602896

  14. The A3 Adenosine Receptor Agonist CF502 Inhibits the PI3K, PKB/Akt and NF-κB Signaling Pathway in Synoviocytes from Rheumatoid Arthritis Patients and in Adjuvant Induced Arthritis Rats

    PubMed Central

    Ochaion, A.; Bar-Yehuda, S.; Cohen, S.; Amital, H.; Jacobson, K.A.; Joshi, B.V.; Gao, Z.G.; Barer, F.; Patoka, R.; Del Valle, L.; Perez-Liz, G.; Fishman, P.

    2009-01-01

    The A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells and was defined as a target to combat inflammation. Synthetic agonists to this receptor, such as IB-MECA and Cl-IB-MECA, exert an anti-inflammatory effect in experimental animal models of adjuvant and collagen induced arthritis. In this study we present a novel A3AR agonist, CF502, with high affinity and selectivity at the human A3AR. CF502 induced a dose dependent inhibitory effect on the proliferation of fibroblast-like synoviocytes (FLS) via de-regulation of the nuclear factor-kappa B (NF-κB) signaling pathway. Furthermore, CF502 markedly suppressed the clinical and pathological manifestations of Adjuvant Induced Arthritis (AIA) in a rat experimental model when given orally at a low dose (100 μg/kg). As is typical of other G-protein coupled receptors, the A3AR expression level was down-regulated shortly after treatment with agonist CF502 in paw and in peripheral blood mononuclear cells (PBMCs) derived from treated AIA animals. Subsequently, a decrease in the expression levels of Protein Kinase B/Akt (PKB/Akt), IκB kinase (IKK), (I kappa B) IκB, NF-κB and tumor necrosis factor-alpha (TNF-α) took place. In addition, the expression levels of Glycogen synthase kinase-3 beta (GSK-3β), β-catenin, and Poly (ADP-ribose) polymerase (PARP), known to control the level and activity of NF-κB, were down-regulated upon treatment with CF502. Taken together, CF502 inhibits FLS growth and the inflammatory manifestations of arthritis, supporting the development of A3AR agonists for the treatment of rheumatoid arthritis. PMID:18602896

  15. Perturbations of hypothalamic-pituitary-gonadal (HPG) axis and adrenal androgen (AA) functions in rheumatoid arthritis.

    PubMed

    Masi, A T; Da Silva, J A; Cutolo, M

    1996-05-01

    The available evidence reviewed does not allow definitive response to the question of a primary versus secondary role of sex hormone perturbations in RA. However, this conclusion should not be discouraging in view of the relatively recent focus upon this facet of the physiopathogenesis of RA and the enormous complexities of sex hormone biology and this disease. Specifically, data on the incidence of RA as well as life cycle changes in serum androgenic-anabolic (A-A) and sex hormone levels suggest important risk correlations. Furthermore, HLA-susceptibility markers for RA, gender, menopause and older age are all factors which significantly relate to the risk of developing RA and each has been shown to associate with sex hormone status. Whether or not HPG-AA hormonal status may modulate RA risk (or its course) primarily and independently or merely be predictive markers of other biological mechanisms was critically considered and requires further study. Sex hormone influences on cellular and humoral immunological reactivity and vascular pathogenetic mechanisms in RA were summarized. Androgens generally suppress immunoreactivity and cartilage responses to inflammation-mediated injury processes and may enhance synovial macrophage-like lining cell apoptosis. Oestrogens generally enhance immunoreactivity, offer some protection to inflammation-mediated cartilage damage (but less than androgens) and may inhibit apoptosis in certain in vitro cell models. Scant information is available on the balance of sex hormones (and glucocorticoids) in RA or its presumed pathogenetic mechanisms. Data were reviewed which support the concept of a spectrum of androgenicity in the normal population, particularly among women. A simplified schema of trophic and tropic steroidogenic mechanisms was proposed which could influence androgenic-anabolic (A-A) status and might relate to RA. Serum concentrations of DHAS (mumol/l), T (nmol/l) and O2 (pmol/l) span several orders of magnitude in normal

  16. 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

  17. Safety and immunogenicity of co-administered MF59-adjuvanted 2009 pandemic and plain 2009–10 seasonal influenza vaccines in rheumatoid arthritis patients on biologicals

    PubMed Central

    Milanetti, F; Germano, V; Nisini, R; Donatelli, I; Di Martino, A; Facchini, M; Ferlito, C; Cappella, A; Crialesi, D; Caporuscio, S; Biselli, R; Rossi, F; Salemi, S; D'Amelio, R

    2014-01-01

    Rheumatoid arthritis (RA) patients under immunosuppressive therapy are particularly susceptible to infections, mainly of the respiratory tract, thus vaccination may represent a strategy to reduce their incidence in this vulnerable population. In the 2009–10 influenza season, the safety and immunogenicity of co-administered non-adjuvanted seasonal and MF59-adjuvanted pandemic influenza vaccines were evaluated in this study in 30 RA patients under therapy with anti-tumour necrosis factor (TNF)-α agents or Abatacept and in 13 healthy controls (HC). Patients and HC underwent clinical and laboratory evaluation before (T0), 1 (T1) and 6 months (T2) after vaccinations. No severe adverse reactions, but a significant increase in total mild side effects in patients versus HC were observed. Both influenza vaccines fulfilled the three criteria of the Committee for Proprietary Medicinal Products (CPMP). Seroconversion rate for any viral strain in patients and HC was, respectively, 68 versus 45 for H1-A/Brisbane/59/07, 72 versus 81 for H3-A/Brisbane/10/07, 68 versus 54 for B/Brisbane/60/08 and 81 versus 54 for A/California/7/2009. A slight increase in activated interferon (IFN)-γ-, TNF-α- or interleukin (IL)-17A-secreting T cells at T1 compared to T0, followed by a reduction at T2 in both patients and HC, was registered. In conclusion, simultaneous administration of adjuvanted pandemic and non-adjuvanted seasonal influenza vaccines is safe and highly immunogenic. The largely overlapping results between patients and HC, in terms of antibody response and cytokine-producing T cells, may represent further evidence for vaccine safety and immunogenicity in RA patients on biologicals. PMID:24666311

  18. Evaluation of Protective Efficacy of Avicennia marina (Forssk.) Vierh Leaves against Complete Freund᾽s Adjuvant-induced Arthritis in Wistar

    PubMed Central

    Zamani Gandomani, Mahdi; Forouzandeh Malati, Elaheh

    2014-01-01

    Aviecennia marina (Avicenniaceae) is an endemic plant that widely distributed in the Southern parts of Iran. This plant has been used as treatment of rheumatism arthritis among the inhabitants of Southern parts of Iran. The Avicennia marina hydroalcoholic extract was prepared and its protective efficacy was investigated using measurement of ankle diameter, total WBC and RBC count, ESR, and Pro-inflammatory cytokines levels in the complete Freund᾽s adjuvant (CFA)-induced arthritic rat. The increment in ESR and total WBC, reduction in RBC count and hemoglobin levels observed in the arthritic animals were also found to be significantly restored in HEA treated rats. A. marina at 400 mg/Kg significantly decreases the serum pro-inflammatory cytokines as well as normalizes ankle diameter of CFA rats. A. marina (400 mg/Kg) significantly normalizes changes observed in arthritic rats to near normal conditions, indicates that A. marina has promising protective efficacy against arthritic rats. PMID:25276195

  19. 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

  20. Anti-arthritic Activity of Dashanga Ghana (An Ayurvedic Compound Formulation) Against Freund's Adjuvant Induced Arthritis in Charles Foster Albino Rats

    PubMed Central

    Ruknuddin, Galib; Patgiri, B. J.; Prajapati, P. K.; Ashok, B. K.; Ravishankar, B.

    2015-01-01

    Introduction: Arthritis is the most common cause of disability, limiting the activities of adults throughout the world. Apart from the conventional treatment strategies using non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs, and glucocorticoids, newer and safer drugs are continuously being searched, as long-term usage of these drugs have resulted in adverse effects. Besides this, currently a number of medicinal plants are under scientific evaluation to develop a promising remedy in these cases. There is a need to investigate the complete therapeutic potential of these herbals for providing newer and safer treatment options with minimum side effects. Considering this, a polyherbal Ayurvedic compound formulation (Dashanga Ghana) has been studied in experimental animals to evaluate anti-arthritic activity. Materials and Methods: Dashanga Ghana has been prepared in the laboratory by following standard guidelines. Charles Foster albino rats were used to evaluate the activity through Freund's adjuvant induced arthritis model. Results and Conclusions: Dashanga Ghana is found to possess significant anti-arthritic activity. Further studies are required to identify and characterize exact active phyto-constituents and to elucidate the exact mechanism of action, which is responsible for the observed pharmacological profile. PMID:26862275

  1. 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

  2. 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. PMID:27294302

  3. Swertiamarin attenuates inflammation mediators via modulating NF-κB/I κB and JAK2/STAT3 transcription factors in adjuvant induced arthritis.

    PubMed

    Saravanan, S; Islam, V I Hairul; Babu, N Prakash; Pandikumar, P; Thirugnanasambantham, K; Chellappandian, M; Raj, C Simon Durai; Paulraj, M Gabriel; Ignacimuthu, S

    2014-06-01

    Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that leads to pannus formation followed by severe joint destruction, characterized by synovial hyperplasia, inflammation and angiogenesis. Swertiamarin is a secoiridoid glycoside that is used as an anti-inflammatory compound, mainly found in Enicostema axillare (Lam) A. Raynal, a medicinal plant used in Indian system of traditional medicine. In the present study, the effect of swertiamarin was evlauated in experimental adjuvant arthritis animal model by the estimation of biochemical (paw thickness, lysosomal enzymes, and urinary degradative products) parameters, proinflammatory cytokines and enzymes along with histopathological and radiographic observations. The proteins of phosphorylated NF-κB/IκB and JAK2/STAT3 transcription factors were also quantified from experimental animals as well as LPS induced RAW 264.7 macrophage cells. In in silico analysis, swertiamarin was docked with proinflammatory enzymes to confirm its potential. The administration of swertiamarin (2, 5, 10mg/kg bw) significantly (P⩽0.05) inhibited the levels of paw thickness, lysosomal enzymes and increased the body weight of experimental animals in a dose dependent manner. In molecular analysis, the treatment decreased the release of proinflammatory cytokines (IL1, TNF, IL-6) and proangiogenic enzymes (MMPs, iNOS, PGE2, PPARγ and COX-2); and also significantly (P⩽0.05) increased the levels of antiinflammatory proteins (IL-10, IL-4) when compared to the disease groups. The swertiamarin treatment significantly (P⩽0.05) inhibited the release of NF-κB p65, p-IκBα, p-JAK2 and p-STAT3 signaling proteins levels on both experimental animals and LPS induced cells. Histopathological and radiological analysis evidenced the curative effect of swertiamarin on bone destruction. The docking studies of swertiamarin on proinflammatory enzymes supported the results from the in vivo experiments. Thus the swertiamarin inhibited

  4. Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.

    PubMed

    Tang, Quan Yong; Kukita, Toshio; Ushijima, Yuki; Kukita, Akiko; Nagata, Kengo; Sandra, Ferry; Watanabe, Toshiyuki; Toh, Kazuko; Okuma, Yutaka; Kawasaki, Sadamichi; Rasubala, Linda; Teramachi, Junpei; Miyamoto, Ichiko; Wu, Zhou; Iijima, Tadahiko

    2006-03-01

    Simon extracts are vitamin K(1)-rich food materials extracted from the leaves of the Simon sweet potato. Although vitamin K is known to stimulate bone formation, we postulated that Simon extracts also contain unknown biological compounds having the ability to regulate bone resorption. Here we prepared the vitamin K-free fraction from the Simon extracts and investigated the ability of this fraction on the differentiation of osteoclasts. A remarkable inhibitory effect of osteoclastogenesis was observed when osteoclast precursors were treated with this fraction in rat bone marrow culture systems as well as in a pure differentiation system using murine osteoclast precursor cell line. The vitamin K-free Simon extracts markedly suppressed severe bone destruction mediated by abundant osteoclasts associated with adjuvant-induced arthritis in rats. High performance liquid chromatography (HPLC) analysis revealed that the vitamin K-free Simon extracts contained three types of low molecular weight inhibitors for osteoclastogenesis; caffeic acid, chlorogenic acids and isochlorogenic acids. Among these substances, caffeic acid showed the most powerful inhibitory effects on osteoclastogenesis. Caffeic acid significantly suppressed expression of NFATc1, a key transcription factor for the induction of osteoclastogenesis. Our current study enlightened a high utility of the Simon extracts and their chemical components as effective regulators for bone resorption accompanied with inflammation and metabolic bone diseases. PMID:16205940

  5. 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. PMID:27241582

  6. 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

  7. Anti-inflammatory effect of glycosaminoglycan derived from Gryllus bimaculatus (a type of cricket, insect) on adjuvant-treated chronic arthritis rat model.

    PubMed

    Ahn, Mi Young; Han, Jea Woong; Hwang, Jae Sam; Yun, Eun Young; Lee, Byung Mu

    2014-01-01

    Anti-inflammatory effects of glycosaminoglycan (GAG) derived from cricket (Gryllus bimaculatus, Gb) were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritic rat model. This GAG produced a significant anti-edema effect as evidenced by inhibition of C-reactive protein (CRP) and rheumatoid factor, and interfered with atherogenesis by reducing proinflammatory cytokine levels of (1) vascular endothelial growth factor (VEGF) production in human umbilical vein endothelial cells (HUVEC), (2) interleukin-6, (3) prostaglandin E2-stimulated lipopolysaccharide in RAW 264.7 cells, and (4) tumor necrosis factor (TNF)-α production in normal splenocytes, in a dose-dependent manner. This GAG was also found to induce nitric oxide (NO) production in HUVEC cells and elevated endothelial nitric oxide synthase (eNOS) activity levels. Histological findings demonstrated the fifth lumbar vertebrae (LV) dorsal root ganglion, which was linked to the paw treated with Gb GAG, was repaired against CFA-induced cartilage destruction. Further, combined indomethacin (5 mg/kg)-Gb GAG (10 mg/kg) inhibited more effectively CFA-induced paw edema at 3 h and 2 or 3 d after treatment to levels comparable to only the anti-inflammatory drug indomethacin. Ultraviolet (UV)-irritated skin inflammation also downregulated nuclear factor κB (NFκB) activity in transfected HaCaT cells. Data suggest that the anti-inflammatory effects of GAG obtained from cricket (Gb) may be useful for treatment of inflammatory diseases including chronic arthritis. PMID:25343284

  8. Effects of central administration of oxytocin-saporin cytotoxin on chronic inflammation and feeding/drinking behaviors in adjuvant arthritic rats.

    PubMed

    Matsuura, Takanori; Kawasaki, Makoto; Hashimoto, Hirofumi; Yoshimura, Mitsuhiro; Motojima, Yasuhito; Saito, Reiko; Ueno, Hiromichi; Maruyama, Takashi; Sabanai, Ken; Mori, Toshiharu; Ohnishi, Hideo; Sakai, Akinori; Ueta, Yoichi

    2016-05-16

    An increase in the arthritis index as a marker of chronic inflammation and suppression of food intake are observed in adjuvant arthritic (AA) rats. Our previous study demonstrated that central oxytocin (OXT)-ergic pathways were activated potently in AA rats. In the present study, OXT-saporin (SAP) cytotoxin, which chemically disrupts OXT signaling was administered centrally to determine whether central OXT may be involved in the developments of chronic inflammation and alteration of feeding/drinking behavior in AA rats. The arthritis index was significantly enhanced in AA rats pretreated with OXT-SAP administered intrathecally (i.t.) but not intracerebroventricularly (i.c.v.). Suppression of food intake was significantly attenuated transiently in AA rats pretreated with OXT-SAP administered i.c.v. but not i.t. Suppression of drinking behavior was not affected by i.t. or i.c.v. administration of OXT-SAP in AA rats. In addition, intraperitoneal administration of an OXT receptor antagonist did not change the arthritis index or feeding/drinking behavior in AA rats. These results suggest that central OXT-ergic pathways may be involved in anti-inflammation at the spinal level and suppression of feeding behavior at the forebrain-brainstem level in AA rats. PMID:27060190

  9. Paederia foetida Linn. inhibits adjuvant induced arthritis by suppression of PGE(2) and COX-2 expression via nuclear factor-κB.

    PubMed

    Kumar, Vikas; Al-Abbasi, F A; Ahmed, Danish; Verma, Amita; Mujeeb, Mohd; Anwar, Firoz

    2015-05-01

    The current investigation was undertaken to determine the anti-inflammatory and antioxidant effects of Paederia foetida Linn. (PF) along with its mechanism of action when implemented in tissue protection. HPTLC was used in the identification of the compound quercetin, while in vitro analysis confirmed the significance of the antioxidant and anti-inflammatory action of PF. We initially demonstrated the in vivo anti-inflammatory effect of PF, evaluating it against a variety of phlogistic agents as well as turpentine oil, prostaglandin and arachidonic acid. Groups of rats, fasted overnight, were treated as follows: Group I: normal control (vehicle), Group II: PF (100 mg kg(-1)), Group III: arthritic control (CFA only, 0.05 ml), Group IV, V, VI: CFA (0.05 ml) + PF (25, 50 and 100 mg kg(-1)) and Group VII: CFA (0.05 ml) + indomethacin (10 mg per kg b.w.). PF significantly protected against paw edema, arthritic index and body weight alteration induced by Complete Fruend's Adjuvant (CFA). Other observations, like histological and macroscopic changes, were observed in CFA induced inflammation in knee joints. Subcutaneous administration of CFA was accompanied by proinflammatory cytokine status, as appraised by the amplification of interleukin-2 (IL-2), interleukin-1β (IL-1β) and tumor necrosis factor (TNF-α); oxidative stress status was estimated by the enhancement of the level of lipid peroxidation (LPO) and the depletion of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH). Pre-treatment with PF significantly (P < 0.001) protected against CFA induced oxidative stress and proinflammatory cytokines. More prominently, CFA administration augmented tissue and plasma superoxide (O2) and hydrogen peroxide (H2O2) levels, while the PF pre-treatment significantly (P < 0.001) reversed all CFA induced intracellular interruption. Following CFA induced arthritis, PF was tested for its free radical scavenging activity against the DPPH and ABTS radicals

  10. 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

  11. Effects of one minute and ten minutes of walking activity in rats with arthritis induced by complete Freund's adjuvant on pain and edema symptoms.

    PubMed

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

    2014-01-01

    This study evaluated the effects of two protocols of exercise on nociception, edema and cell migration in rats with CFA-induced arthritis. Female Wistar rats (200 - 250 g, n = 50) was monoarthritis-induced by complete Freund's adjuvant (CFA; Mycobacterium butyricum, 0.5 mg/mL; 50 μL) into the right knee joint (TF; n = 24) or right ankle joint (TT; n = 26). Incapacitation was measured by the paw elevation time (TEP; s) in 1-min periods of observation. The edema of the knee or ankle joints was evaluated by the variation of the articular diameter (DA, cm) and by the paw volume variation (EP, mL), respectively. Both were measured during 10 consecutive days. Two protocols of exercise were performed: (a) in the constant exercise group (TF, n = 6; TT, n = 6) performing 1 minute of daily exercise on the cylinder; (b) variable exercise group (TF, n = 6; TT, n = 7), the exercise increased by 1 minute per day. The control groups (TF, n = 12; TT, n = 13) didn't perform the exercise. After 10 days, the animals were euthanized for total (CT; cells/mm3) and differential leukocyte counts (mononuclear - MON, and polymorphonuclear - PMN, cells/mm3) of the articular inflammatory exudate. The variable exercise protocol inhibited incapacitation and edema for both joints. However, cell migration decreased only in the TF.The constant exercise reduced edema in both joints, and cell migration was decreased in the TT. However, the incapacitation was not reduced. Variable exercise seemed to be more effective in reducing the inflammatory parameters than constant exercise. PMID:24878853

  12. Comparative evaluation of low-level laser and systemic steroid therapy in adjuvant-enhanced arthritis of rat temporomandibular joint: A histological study

    PubMed Central

    Khozeimeh, Faezeh; Moghareabed, Ahmad; Allameh, Maryam; Baradaran, Shahrzad

    2015-01-01

    Background: Low-level laser therapy (LLLT) has shown a promising effect in ameliorating symptoms of rheumatoid arthritis (RA). The aim of this investigation was to compare the early and late anti-inflammatory effects of LLLT and betamethasone in RA. Materials and Methods: In this animal experimental study, after inducing a model of RA in temporomandibular joint (TMJ) of 37 Wistar rats using adjuvant injection, they were randomly distributed into three experimental groups of 12 animals each: (1) LLLT group; (2) steroid group which received a single dose of betamethasone systemically; and (3) positive control group, which did not receive any treatment. One rat served as the negative control. Half of the animals in all the experimental groups were sacrificed on the 21st day after RA induction (early phase), and the other half were sacrificed 2 weeks later (late phase). Then, the severity of TMJ inflammation was assessed histologically in each group on a semi-quantitative scale. Kruskal-Wallis and Mann-Whitney tests were used to compare differences (α = 0.05). Results: The LLLT and steroid groups showed significantly (P < 0.05) lower inflammation mean scores in both early (5.66 [±1.86] and 1.66 [±1.21], respectively) and late phases of evaluation (1.16 [±1.47] and 6.50 [±1.04], respectively) compared to positive control group in early and late stages of assessment (11.66 [±3.50] and 8.66 [±1.36], respectively). However, the best results (P < 0.005) were achieved in early phase of the steroid group as well as late phase of the LLLT group. Conclusion: Within limitations of this study, it may be concluded that LLLT method has a long-term promising effect on reducing inflammation severity of TMJ similar to betamethasone in earlier stages. PMID:26005460

  13. 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

  14. 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

  15. Effect and mechanism of AR-6 in experimental rheumatoid arthritis.

    PubMed

    Sun, Shi-xue; Li, Yun-man; Fang, Wei-rong; Cheng, Peng; Liu, Lifang; Li, Fengwen

    2010-06-01

    The root of Clematis chinensis Osbeck has been used widely in rheumatoid arthritis in Chinese traditional medicine and AR-6 is a triterpene saponin isolated from it. In this present study, we investigated in vivo effects of oral AR-6 in chronic rat adjuvant-induced arthritis (AA) and in vitro effect in macrophage and synoviocytes cells. Arthritic scores and serum inflammatory mediators were evaluated 19 days after AA induction by endermic injection of Freund's complete adjuvant in Sprague-Dawley(S-D) rats. Oral administration of AR-6 to arthritic rats resulted in a clear decrease of clinical signs compared to untreated controls. The synoviocyte and macrophage response ex vivo were then analyzed. Anti-arthritic effects of AR-6 correlated with significant decrease of NO and TNF-alpha produced by peritoneal macrophages, ex vivo and in vitro. AR-6 also significant decreased the proliferation of synoviocyte. These data indicate that AR-6 is a potential anti-inflammatory therapeutic and preventive agent. PMID:19842015

  16. Distinct serum proteome profiles associated with collagen-induced arthritis and complete Freund's adjuvant-induced inflammation in CD38⁻/⁻ mice: The discriminative power of protein species or proteoforms.

    PubMed

    Rosal-Vela, Antonio; García-Rodríguez, Sonia; Postigo, Jorge; Iglesias, Marcos; Longobardo, Victoria; Lario, Antonio; Merino, Jesús; Merino, Ramón; Zubiaur, Mercedes; Sancho, Jaime

    2015-10-01

    Collagen-type-II-induced arthritis (CIA) is an autoimmune disease, which involves a complex host systemic response including inflammatory and autoimmune reactions. CIA is milder in CD38(-/-) than in wild-type (WT) mice. ProteoMiner-equalized serum samples were subjected to 2D-DiGE and MS-MALDI-TOF/TOF analyses to identify proteins that changed in their relative abundances in CD38(-/-) versus WT mice either with arthritis (CIA(+) ), with no arthritis (CIA(-) ), or with inflammation (complete Freund's adjuvant (CFA)-treated mice). Multivariate analyses revealed that a multiprotein signature (n = 28) was able to discriminate CIA(+) from CIA(-) mice, and WT from CD38(-/-) mice within each condition. Likewise, a distinct multiprotein signature (n = 16) was identified which differentiated CIA(+) CD38(-/-) mice from CIA(+) WT mice, and lastly, a third multiprotein signature (n = 18) indicated that CD38(-/-) and WT mice could be segregated in response to CFA treatment. Further analyses showed that the discriminative power to distinguish these groups was reached at protein species level and not at the protein level. Hence, the need to identify and quantify proteins at protein species level to better correlate proteome changes with disease processes. It is crucial for plasma proteomics at the low-abundance protein species level to apply the ProteoMiner enrichment. All MS data have been deposited in the ProteomeXchange with identifiers PXD001788, PXD001799 and PXD002071 (http://proteomecentral.proteomexchange.org/dataset/PXD001788, http://proteomecentral.proteomexchange.org/dataset/PXD001799 and http://proteomecentral.proteomexchange.org/dataset/PXD002071). PMID:26175002

  17. β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory response in adjuvant-induced arthritic rats

    PubMed Central

    Wu, Huaxun; Chen, Jingyu; Song, Shasha; Yuan, Pingfan; Liu, Lihua; Zhang, Yunfang; Zhou, Aiwu; Chang, Yan; Zhang, Lingling; Wei, Wei

    2016-01-01

    Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, which leads to the progressive destruction of cartilage and bone. Adrenoreceptor (AR) signaling may play an important role in modulating dendritic cell (DC), which may be involved in the pathogenesis of RA. We examined the effect of the β-AR agonist isoprenaline (ISO) on DC function, the impact of the β2-AR agonist salbutamol on adjuvant-induced arthritic (AA) rats, and changes in β2-AR signaling in DCs during the course of AA. ISO inhibited the expression of the surface molecules CD86 and MHC-II, inhibited the stimulation of T lymphocyte proliferation by DC and TNF-α secretion, and promoted DC antigen uptake and IL-10 secretion. The effects of ISO on MHC-II expression, DC stimulation of T lymphocyte proliferation, and DC antigen uptake were mediated by β2-AR. Treatment with salbutamol ameliorated the severity of AA and histopathology of the joints and inhibited proliferation of thymus lymphocytes and FLS in vivo. β2-AR signaling was weaker in AA rats compared to the control. Elevated GRK2 and decreased β2-AR expression in DC cytomembranes were observed in AA and may have decreased the anti-inflammatory effect of β2-AR signaling. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation. PMID:27079168

  18. 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. ...

  19. 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

  20. 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

  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

    2015-01-01

    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

  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. Rheumatoid Arthritis

    MedlinePlus

    ... Rheumatoid Arthritis What Is Rheumatoid Arthritis? An Inflammatory, Autoimmune Disease Rheumatoid arthritis is an inflammatory disease that causes ... sometimes feverish. Rheumatoid arthritis is classified as an autoimmune disease. An autoimmune disease occurs when the immune system ...

  4. 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

  5. Transfer of spleen cells expanded by T cell growth factor suppresses arthritis induced in rats.

    PubMed Central

    Ogawa, H; Tsunematsu, T

    1987-01-01

    The effects of transfer of T cell growth factor (TCGF)-expanded spleen cells after concanavalin A (Con A) stimulation into syngeneic Lewis rats were studied. The recipient rats were immunized with complete Freund's adjuvant for induction of adjuvant arthritis (AA) or chick type II collagen in incomplete Freund's adjuvant for induction of collagen-induced arthritis (CIA) on day 0. Each of 5 X 10(7) cultured cells without mitogenic stimulation, 2 X 10(7) Con A-stimulated cells, or 1 X 10(7) TCGF-expanded cells cultured for 8 days (4 days X 2 culture cycles) after Con A stimulation was given on days 0 and 7. Both transfers of the cultured cells without stimulation and TCGF-expanded cells markedly diminished the severity of AA and CIA. On the contrary, transfer of Con A-stimulated cells led to no suppressive activity. In addition, transfer to TCGF-expanded cells significantly lowered the titre of anti-type II collagen antibody compared to that of control rats. The transfer of 1 X 10(7) TCGF-expanded cells was optimal for suppressing AA, in terms of cell number. This observation suggests that these cells were much more effective than were the unstimulated cultured cells, for which more than five times the number was required for the same suppressive activity. As far as the phenotypic proportion of helper (W3/13) and suppressor (OX-8) cells is concerned, we found no significant differences between the cultured cell groups and the freshly separated spleen cell group. The precise mechanism of these suppressive effects is the subject of further study. The transfer of TCGF-expanded cells appears to have a potent immunomodulatory effect. PMID:3497743

  6. 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 ...

  7. Viral arthritis

    MedlinePlus

    Infectious arthritis - viral ... Arthritis may be a symptom of many virus-related illnesses. It usually disappears on its own without ... the rubella vaccine, only a few people develop arthritis. No risk factors are known.

  8. Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp)60 and hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA)

    PubMed Central

    BLOEMENDAL, A; VAN DER ZEE, R; RUTTEN, V P M G; VAN KOOTEN, P J S; FARINE, J C; VAN EDEN, W

    1997-01-01

    OM-89 is a bacterial (Escherichia coli) extract used for oral administration in the treatment of RA. Given the evidence that immunity to bacterial heat shock antigens plays a critical role in the immunomodulation of arthritis and possibly inflammation in general, the purpose of the present studies was to evaluate the presence and immunogenicity of hsp in OM-89. Furthermore, we studied the effects of OM-89 in an experimental arthritis, where hsp are known to have a critical significance in disease development. In rats immunization with OM-89 was found to lead to proliferative T cell responses to hsp60 and hsp70 of both E. coli and mycobacterial origin. Conversely, immunization with hsp antigens was also found to induce T cell reactivity specific for OM-89. Based on this and the antigen specificity analysis of specific T cell lines, hsp70 (DnaK) turned out to be one of the major immunogenic constituents of OM-89. Parenteral immunization with OM-89 was found to reduce resistance to adjuvant arthritis (AA), whereas oral administration was found to protect against AA. Given the arthritis-inhibitory effect of oral OM-89 in AA, it is possible that peripheral tolerance is induced at the level of regulatory T cells with specificity for hsp. This may also constitute a mode of action for OM-89 as an arthritis-suppressive oral drug. PMID:9353151

  9. 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

  10. Juvenile Arthritis

    MedlinePlus

    Juvenile arthritis (JA) is arthritis that happens in children. It causes joint swelling, pain, stiffness, and loss of motion. It can affect any joint, but ... of JA that children get is juvenile idiopathic arthritis. There are several other forms of arthritis affecting ...

  11. 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.

  12. 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

    2016-01-01

    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

  13. 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

  14. Adjuvant treatment

    PubMed Central

    Sultana, Asma; Neoptolemos, John

    2006-01-01

    Exocrine pancreatic cancer (pancreatic ductal adenocarcinoma) is one of the leading causes of cancer deaths in the western world, accounting for 5% of all cancer-related deaths. Only a small percentage of patients with pancreatic cancer are able to undergo potentially curative resection, even in specialized centres, and prognosis remains poor after successful surgery. Over the last few years efforts have been directed towards the development of adjuvant therapies in attempts to improve outcome. The main trials of adjuvant chemotherapy, chemoradiotherapy and chemoradiotherapy with follow-on chemotherapy are described in this paper, followed by the results of the ESPAC-1 trial and the status of ESPAC-2 and -3 trials. PMID:18333088

  15. Infectious Arthritis

    MedlinePlus

    Most kinds of arthritis cause pain and swelling in your joints. Joints are places where two bones meet, such as your elbow or knee. Infectious arthritis is an infection in the joint. The infection ...

  16. 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 ...

  17. Arthritis Foundation

    MedlinePlus

    ... hour massage will be donated to the Arthritis Foundation! Jingle Bell Run Join us for the nation's ... a cure! Answers When You Need Them Arthritis Foundation licensed social workers provide 24/7 assistance on ...

  18. Fungal arthritis

    MedlinePlus

    ... and irritation (inflammation) of a joint by a fungal infection. It is also called mycotic arthritis. Causes Fungal ... symptoms of fungal arthritis. Prevention Thorough treatment of fungal infections elsewhere in the body may help prevent fungal ...

  19. Opioid and adjuvant analgesics: compared and contrasted.

    PubMed

    Khan, Mohammed Ilyas Ahmed; Walsh, Declan; Brito-Dellan, Norman

    2011-08-01

    An adjuvant (or co-analgesic) is a drug that in its pharmacological characteristic is not necessarily primarily identified as an analgesic in nature but that has been found in clinical practice to have either an independent analgesic effect or additive analgesic properties when used with opioids. The therapeutic role of adjuvant analgesics (AAs) is to increase the therapeutic index of opioids by a dose-sparing effect, add a unique analgesic action in opioid-resistant pain, or reduce opioid side effects. A notable difference between opioids and AAs is that unlike opioids some AAs are associated with permanent organ toxicity, for example, nonsteroidal anti-inflammatory drugs (NSAIDs) and renal failure. It is impossible to predict in advance in a given individual what opioid dose they may require to control cancer pain. Most AAs have a ceiling effect for their analgesic actions, but often with continued dose-related toxicities and side effects (with the exception of glucocorticoids). The blood levels of opioids (and their metabolites) can be measured with great precision and accuracy. There is sometimes a role for drug blood levels of certain AAs, like tricyclic antidepressants or anticonvulsants when used for neuropathic pain. Age affects metabolism of most opioids. The therapeutic window of opioids is wide, with no ceiling effect. Most AAs (except corticosteroids) have a narrow therapeutic window. Naloxone is a pure opioid antagonist that competes and displaces opioids from their receptor sites. All clinically useful opioids are mu opioid receptor agonists. Not all routes of administration are available to all opioids. Adjuvant analgesics lack the versatility in routes of administration that opioids possess. Dosing flexibility is a major advantage when treating cancer-related pain with opioids. Dose flexibility is much less with AAs than opioids. Unlike opioids, the analgesic response is usually observed within hours to days of attaining an adequate dose with most

  20. Common commercial cosmetic products induce arthritis in the DA rat.

    PubMed Central

    Sverdrup, B; Klareskog, L; Kleinau, S

    1998-01-01

    Many different agents, including mineral oil and silicone, have the capacity to act as immunological adjuvants, i.e., they can contribute to the activation of the immune system. Some adjuvants, including mineral oil, are known to induce arthritis in certain strains of rats after intradermal injection or percutaneous application. The aim of this study was to determine if common commercial cosmetic products containing mineral oil could induce arthritis in the highly susceptible DA (Dark Agouti) rat. Intradermal injection of five out of eight assayed cosmetic products without further additives resulted in arthritis with synovitis. One of the products induced a very aggressive arthritis, which had declined after 5-9 weeks. When this product was also assayed for arthritogenicity upon percutaneous administration, it induced a mild and transient arthritis in 5 out of 10 DA rats, whereas control animals showed no clinical signs of joint involvement. No arthritic reaction was seen in rats after peroral feeding with the most arthritogenic product or by intravaginal application of Freund's adjuvants. Silicone gel implants in DA rats did not cause arthritis. We conclude that mineral oils included in common commercially available products retain their adjuvant properties and are arthritogenic in the presently investigated arthritis-prone rat strain. There is yet no evidence that mineral oils present in cosmetics may contribute to arthritis in humans, but we suggest that this question should be subject to further investigation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:9417771

  1. 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

  2. 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

  3. 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 ...

  4. 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

  5. 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 ...

  6. Infectious Arthritis

    MedlinePlus

    ... Another form of reactive arthritis starts with eating food or handling something that has bacteria on it. To diagnose infectious arthritis, your health care provider may do tests of your blood, urine, and joint fluid. Treatment includes medicines and sometimes surgery.

  7. Reactive arthritis

    MedlinePlus

    Reactive arthritis is a group of conditions that may involve the joints, eyes, and urinary and genital systems. ... The exact cause of reactive arthritis is unknown. It occurs most often in men younger than age 40. It may follow an infection in the urethra ...

  8. [Adjuvants--essential components of new generation vaccines].

    PubMed

    Dzierzbicka, Krystyna; Kołodziejczyk, Aleksander M

    2006-01-01

    Adjuvants are essential components of vaccines that augment an immunological reaction of organism. New vaccines based on recombinant proteins and DNA, are more save than traditional vaccines but they are less immunogenic. Therefore, there is an urgent need for the development of new, improved vaccine adjuvants. There are two classes of adjuvants: vaccine delivery systems (e.g. emulsions, microparticles, immune-stimulating complexes ISCOMs, liposomes) and immunostimulatory adjuvants (e.g. lipopolysaccharide, monophosphoryl lipid A, CpG DNA, or muramylpeptides). The discovery of more potent and safer adjuvants may allow to development better prophylactic and therapeutic vaccines against chronic infectious (e.g., HSV, HIV, HCV, HBV, HPV, or Helicobacter pylori) and noninfectious diseases as multiple sclerosis, insulin-dependent diabetes, rheumatoid arthritis, allergy and tumors (e.g., melanoma, breast, or colon cancer). PMID:17078510

  9. Reactive arthritis.

    PubMed

    Keat, A

    1999-01-01

    Reactive arthritis is one of the spondyloarthropathy family of clinical syndromes. The clinical features are those shared by other members of the spondyloarthritis family, though it is distinguished by a clear relationship with a precipitating infection. Susceptibility to reactive arthritis is closely linked with the class 1 HLA allele B27; it is likely that all sub-types pre-dispose to this condition. The link between HLA B27 and infection is mirrored by the development of arthritis in HLA B27-transgenic rats. In this model, arthritis does not develop in animals maintained in a germ-free environment. Infections of the gastrointestinal, genitourinary and respiratory tract appear to provoke reactive arthritis and a wide range of pathogens has now been implicated. Although mechanistic parallels may exist, reactive arthritis is distinguished from Lyme disease, rheumatic fever and Whipple's disease by virtue of the distinct clinical features and the link with HLA B27. As in these conditions both antigens and DNA of several micro-organisms have been detected in joint material from patients with reactive arthritis. The role of such disseminated microbial elements in the provocation or maintenance of arthritis remains unclear. HLA B27-restricted T-cell responses to microbial antigens have been demonstrated and these may be important in disease pathogenesis. The importance of dissemination of bacteria from sites of mucosal infection and their deposition in joints has yet to be fully understood. The role of antibiotic therapy in the treatment of reactive arthritis is being explored; in some circumstances, both the anti-inflammatory and anti-microbial effects of certain antibiotics appear to be valuable. The term reactive arthritis should be seen as a transitory one, reflecting a concept which may itself be on the verge of replacement, as our understanding of the condition develops. Nevertheless it appropriately describes arthritis that is associated with demonstrable

  10. 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 ...

  11. Calcium pyrophosphate arthritis

    MedlinePlus

    ... that can cause attacks of arthritis. Like with gout, crystals form in the joints. But in calcium ... pyrophosphate arthritis can be misdiagnosed as: Gouty arthritis (gout) Osteoarthritis Rheumatoid arthritis

  12. Juvenile Idiopathic Arthritis

    MedlinePlus

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

  13. Rheumatoid arthritis

    MedlinePlus

    ... rheumatoid arthritis drugs. However, because they are very expensive, insurance approval is generally required. Most of them ... rich in fish oils (omega-3 fatty acids). Smoking cigarettes should be stopped. Excessive alcohol should also ...

  14. Enteropathic Arthritis

    MedlinePlus

    ... as well. Those who test positive for the HLA-B27 genetic marker are much more likely to have spinal involvement with enteropathic arthritis than those who test negative. Disease Course/Prognosis ...

  15. Septic arthritis

    MedlinePlus

    ... 2013:chap 109. Krogstad P. Septic arthritis. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Feigin and Cherry's Textbook of Pediatric Infectious Diseases . 7th ed. Philadelphia, ...

  16. Gonococcal arthritis

    MedlinePlus

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

  17. Psoriatic arthritis

    MedlinePlus

    ... that often occurs with a skin condition called psoriasis . ... inflammatory condition. About 1 in 20 people with psoriasis may develop arthritis with the skin condition. In most cases, psoriasis ...

  18. Reactive Arthritis

    MedlinePlus

    ... with treatment and may cause joint damage. What Research Is Being Conducted on Reactive Arthritis? Researchers continue ... such as methotrexate and sulfasalazine. More information on research is available from the following websites: National Institutes ...

  19. Psoriatic arthritis

    MedlinePlus

    ... that often occurs with a skin condition called psoriasis . Causes Psoriasis is a common skin problem that causes red ... inflammatory condition. About 1 in 20 people with psoriasis may develop arthritis with the skin condition. In ...

  20. Interleukin-1β and Interleukin-6 in Arthritis Animal Models: Roles in the Early Phase of Transition from Acute to Chronic Inflammation and Relevance for Human Rheumatoid Arthritis

    PubMed Central

    Ferraccioli, Gianfranco; Bracci-Laudiero, Luisa; Alivernini, Stefano; Gremese, Elisa; Tolusso, Barbara; De Benedetti, Fabrizio

    2010-01-01

    Tumor necrosis factor-α (TNF-α) is the major target of the therapeutic approach in rheumatoid arthritis. A key issue in the approach to chronic arthritis is the understanding of the crucial molecules driving the transition from the acute phase to the chronic irreversible phase of the disease. In this review we analyzed five experimental arthritis animal models (antigen-induced arthritis, adjuvant-induced arthritis, streptococcal cell wall arthritis, collagen-induced arthritis and SKG) considered as possible scenarios to facilitate interpretation of the biology of human rheumatoid arthritis. The SKG model is strictly dependent on interleukin (IL)-6. In the other models, IL-1β and IL-6, more than TNF-α, appear to be relevant in driving the transition, which suggests that these should be the targets of an early intervention to stop the course toward the chronic form of the disease. PMID:20683549

  1. Bacterial arthritis.

    PubMed

    Ho, G

    1991-08-01

    In this review of the 1990 septic arthritis literature, we revisit synovial fluid leukocytosis, examine the utility of synovial fluid glucose and protein measurements, and look at the levels of two cytokines, tumor necrosis factor and interleukin-1, in infected joint fluids. We see the many faces of gonococcal arthritis and the ravages of septic arthritis when the host has rheumatoid arthritis. Should we recommend antibiotic prophylaxis for the rheumatoid patient with a prosthetic joint who is undergoing a procedure that leads to transient bacteremia? What are some of the salient features of septic arthritis when it involves the sternoclavicular or sacroiliac joints? We also look at some unusual microorganisms, eg, group C Streptococcus, Streptococcus viridans, Listeria monocytogenes, Pseudomonas cepacia, Pseudomonas maltophilia, and Neisseria sicca. In patients with acquired immunodeficiency syndrome, we encounter reports of septic arthritis, osteomyelitis, and spinal epidural abscess caused by opportunistic microorganisms. Two unusual sites of infection include the C1-2 lateral facet joint and subacromial bursa without involvement of the glenohumeral joint. Finally, we examine how to drain a septic knee: the orthopedic point of view. PMID:1911055

  2. Viral arthritis.

    PubMed

    Marks, Michael; Marks, Jonathan L

    2016-04-01

    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

  3. Therapeutic effect of an altered peptide ligand derived from heat-shock protein 60 by suppressing of inflammatory cytokines secretion in two animal models of rheumatoid arthritis.

    PubMed

    Lorenzo, N; Barberá, A; Domínguez, M C; Torres, A M; Hernandez, M V; Hernandez, I; Gil, R; Ancizar, J; Garay, H; Reyes, O; Altruda, F; Silengo, L; Padrón, G

    2012-09-01

    Rheumatoid arthritis is a systemic autoimmune disease mediated by T cells. Productive engagement of T cell receptors by major histocompatibility complex-peptide leads to proliferation, differentiation and the definition of effector functions. Altered peptide ligands (APL) generated by amino acid substitutions in the antigenic peptide have diverse effects on T cell response. We predicted a novel T cell epitope from human heat-shock protein 60, an autoantigen involved in the pathogenesis of rheumatoid arthritis. Three APLs were designed from this epitope and it was demonstrated that these peptides induce the activation of T cells through their ability to modify cell cycle phase's distribution of CD4+T cells from RA patients. Also, IL-17, TNF-α and IL-10 levels were determined in PBMC from these patients. Unlike the wild-type peptide and the other two APLs, APL2 increased the IL-10 level and suppressed IL-17 secretion in these assays. Therapeutic effect of this APL in adjuvant arthritis (AA) and collagen-induced arthritis (CIA) models was also evaluated. Clinical score, histopathology, inflammatory and regulatory cytokine concentration were monitored in the animals. APL2 efficiently inhibited the progression of AA and CIA with a significant reduction of the clinical and histopathologic score. Therapeutic effect of APL2 on CIA was similar to that obtained with MTX; the standard treatment for RA. This effect was associated with a decrease of TNF-α and IL-17 levels. These results suggest that the therapeutic effect of APL2 is mediated in part by down-regulation of inflammatory cytokines and support the potential use of APL2 as a therapeutic drug in RA patients. PMID:22686732

  4. Bidirectional effects of serum TNF alpha level and spinal p38MAPK phosphorylation on hyperalgesia variation during CFA-induced arthritis

    PubMed Central

    Akhtari, Zeinab; Zaringhalam, Jalal; Eidi, Akram; Manaheji, Homa; Tekieh, Elaheh

    2012-01-01

    Regarding the role of TNFα in the induction of hyperalgesia, the dual suggested roles of the Pp38 MAPK intracellular pathway in the emergence of symptomatic inflammation, we aimed to investigate the bidirectional effects of serum TNFα level and p38 MAPK phosphorylation on hyperalgesia variation during different stages of adjuvant-induced arthritis. Hyperalgesia and edema were assessed at 0, 3, 7, 14, and 21 days of study after arthritis induction by CFA. Anti-TNFα and Pp38 inhibitor were administered during the 21 days of study. Receptor and intra-cellular enzyme expression were detected by western blotting. Anti-TNFα administration in the AA group decreased paw volume and hyperalgesia until the 14th day of study; on the 21st day, those symptoms increased. Daily administration of anti-TNFα antibody caused significant decrease in spinal mOR protein and Pp38/p38 MAPK enzyme level expression on the 14th and 21st days compared to the AA control group. Our data suggested that phosphorylation of spinal p38 MAPK enzyme played an important role in bidirectional effects of serum TNFα on inflammatory symptoms via spinal mOR expression variation.

  5. 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)

  6. Trends in vaccine adjuvants.

    PubMed

    Schijns, Virgil E J C; Lavelle, Ed C

    2011-04-01

    Adjuvants are essential components of most clinically used vaccines. This is because the majority of nonliving vaccines are relatively poor inducers of adaptive immunity unless effective adjuvants are co-administered. Aluminum salts (alum) have been used as adjuvants with great success for almost a century and have been particularly effective at promoting protective humoral immunity. However, alum is not optimally effective for diseases where cell-mediated immunity is required for protection. Furthermore, adjuvants including oil-in-water emulsions have shown improved efficacy for avian influenza protection suggesting that even for diseases where humoral immunity can confer protection, there is scope for developing improved adjuvants. There have been major developments in antigen discovery over the past decade, which has accelerated the vaccine development process for new indications and this demands a new generation of adjuvants that can drive and specifically direct the desired immune responses. A number of systems are under investigation that combine different types of adjuvants into specific formulations with greater activity. Additionally, targeting of vaccines to specific immune cells shows great promise. In the case of cancer and chronic infectious diseases, it may be difficult to develop effective vaccines without blocking immune regulatory pathways, which impede cell-mediated responses. However, increased understanding of immunology and particularly the innate immune system is informing vaccine adjuvant research and consequently driving the development of novel and specifically directed vaccine adjuvant strategies. In this article we address the importance of adjuvants in vaccine development, the known mode of action of specific adjuvants and recent developments in this important field. PMID:21506650

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. Forms of Arthritis

    MedlinePlus

    ... stiffness, inflammation, swelling and, sometimes, destruction of joints. Gout — a form of arthritis that occurs when uric ... the joints. Some 2.1 million Americans have gout. Lupus — a form of arthritis, like rheumatoid arthritis, ...

  11. Reactive Arthritis Diagnosis

    MedlinePlus

    ... Of Spondylitis The Heart In Spondyloarthritis Inflammatory vs. Mechanical Back ... Arthritis Symptoms Because there is no specific laboratory test for reactive arthritis, doctors sometimes find it difficult ...

  12. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  13. Midfoot arthritis.

    PubMed

    Patel, Amar; Rao, Smita; Nawoczenski, Deborah; Flemister, Adolf S; DiGiovanni, Benedict; Baumhauer, Judith F

    2010-07-01

    Midfoot arthritis is a common cause of significant pain and disability. Although the medial tarsometatarsal (TMT) joints provide < 7 degrees of sagittal plane motion, the more mobile lateral fourth and fifth TMT joints provide balance and accommodation on uneven ground. These small constrained TMT joints also provide stability and translate the forward propulsion motion of the hindfoot and ankle joint to the forefoot metatarsophalangeal joints from heel rise to toe-off. Posttraumatic degeneration is the primary cause of midfoot arthritis, although primary degeneration and inflammatory conditions can also affect this area. The result is a painful midfoot that can no longer effectively transmit load from the hindfoot to the forefoot. Shoe modifications and orthotic inserts are the mainstay of nonsurgical management. Successful management of midfoot arthritis with orthoses is predicated on achieving adequate joint stabilization while still allowing function. Surgical intervention typically involves arthrodesis of the medial midfoot, although the best treatment of the more mobile lateral column is a subject of debate. PMID:20595134

  14. 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

  15. Mechanisms of Action of Adjuvants

    PubMed Central

    Awate, Sunita; Babiuk, Lorne A.; Mutwiri, George

    2013-01-01

    Adjuvants are used in many vaccines, but their mechanisms of action are not fully understood. Studies from the past decade on adjuvant mechanisms are slowly revealing the secrets of adjuvant activity. In this review, we have summarized the recent progress in our understanding of the mechanisms of action of adjuvants. Adjuvants may act by a combination of various mechanisms including formation of depot, induction of cytokines and chemokines, recruitment of immune cells, enhancement of antigen uptake and presentation, and promoting antigen transport to draining lymph nodes. It appears that adjuvants activate innate immune responses to create a local immuno-competent environment at the injection site. Depending on the type of innate responses activated, adjuvants can alter the quality and quantity of adaptive immune responses. Understanding the mechanisms of action of adjuvants will provide critical information on how innate immunity influences the development of adaptive immunity, help in rational design of vaccines against various diseases, and can inform on adjuvant safety. PMID:23720661

  16. 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

  17. Novel adjuvant systems.

    PubMed

    McCluskie, M J; Weeratna, R D

    2001-11-01

    Vaccination remains the single most valuable tool in the prevention of infectious disease. Nevertheless, there exists a need to improve the performance of existing vaccines such that fewer boosts are needed or to develop novel vaccines. For the development of effective vaccines for humans, a great need exists for safe and effective adjuvants. A number of novel adjuvants have been reported in recent years including: i) bacterial toxins such as cholera toxin, CT, and the Escherichia coli heat-labile enterotoxin, LT; ii) less toxic derivatives of CT and LT; iii) endogenous human immunomodulators, such as IL-2, IL-12, GM-CSF; iv) hormones; v) lipopeptides; vi) saponins, such as QS-21; vii) synthetic oligonucleotides containing CpG motifs (CpG ODN); viii) lipid 'A derivatives, such as monophosphoryl lipid A, MPL, and ix) muramyl dipeptide (MDP) derivatives. Herein, we will review recent findings using these novel adjuvant systems. PMID:12455400

  18. 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 ...

  19. Juvenile rheumatoid arthritis

    MedlinePlus

    ... joints. This form of JIA may turn into rheumatoid arthritis. It may involve five or more large and ... no known prevention for JIA. Alternative Names Juvenile rheumatoid arthritis (JRA); Juvenile chronic polyarthritis; Still disease; Juvenile spondyloarthritis ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ... illness . This means the body attacks and destroys healthy body ...

  4. Forms of Arthritis

    MedlinePlus

    ... this page please turn Javascript on. Forms of Arthritis Past Issues / Fall 2006 Table of Contents Today, ... of Linda Saisselin Osteoarthritis (OA) — the form of arthritis typically occurring during middle or old age, this ...

  5. Adjuvant Therapy for Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad A.

    2012-01-01

    Estimates from the U.S. Surveillance, Epidemiology, and End Results (SEER) registry suggest that melanoma incidence will reach 70,230 in 2011, of which 8,790 will die. The rising incidence and predilection for young individuals makes this tumor a leading source of lost productive years in the society. High-dose interferon-α2b is the only agent approved for adjuvant therapy of melanoma; the improvement in relapse-free survival has been observed across nearly all published studies and meta-analyses. However toxicity affects compliance and current research is focusing upon biomarkers that may allow selection of patients with greater likelihood of response, and exploring new agents either singly or in combination that may improve upon the benefit of IFN. In this article, we review the data for the adjuvant therapy of malignant melanoma - focusing on the results obtained with various regimens testing the several formulations of interferon-α2, and the adjuvant studies of vaccines and radiotherapy. Recent advances in the treatment of metastatic disease have established a role for CTLA-4 blockade and BRAF-inhibition, and raising hopes that these agents may have a role in the adjuvant setting. At present, several trials investigating combinations of novel agents with existing immunomodulators are underway. PMID:22453021

  6. What Is Juvenile Arthritis?

    MedlinePlus

    ... children with arthritis Preventing anemia in children with chronic inflammatory diseases such as arthritis Whether daily calcium supplements ... density in children with arthritis The impact of chronic and recurrent pain on ... role of an inflammatory chemical called interleukin-15 (IL-15). For More ...

  7. Laser vaccine adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

    2014-01-01

    Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines. PMID:25424797

  8. Macrophage-derived reactive oxygen species protects against autoimmune priming with a defined polymeric adjuvant.

    PubMed

    Shakya, Akhilesh Kumar; Kumar, Ashok; Holmdahl, Rikard; Nandakumar, Kutty Selva

    2016-01-01

    Understanding the nature of adjuvants and the immune priming events in autoimmune diseases, such as rheumatoid arthritis, is a key challenge to identify their aetiology. Adjuvants are, however, complex structures with inflammatory and immune priming properties. Synthetic polymers provide a possibility to separate these functions and allow studies of the priming mechanisms in vivo. A well-balanced polymer, poly-N-isopropyl acrylamide (PNiPAAm) mixed with collagen type II (CII) induced relatively stronger autoimmunity and arthritis compared with more hydrophilic (polyacrylamide) or hydrophobic (poly-N-isopropylacrylamide-co-poly-N-tertbutylacrylamide and poly-N-tertbutylacrylamide) polymers. Clearly, all the synthesized polymers except the more hydrophobic poly-N-tertbutylacrylamide induced arthritis, especially in Ncf1-deficient mice, which are deficient in reactive oxygen species (ROS) production. We identified macrophages as the major infiltrating cells present at PNiPAAm-CII injection sites and demonstrate that ROS produced by the macrophages attenuated the immune response and the development of arthritis. Our results reveal that thermo-responsive polymers with high immune priming capacity could trigger an autoimmune response to CII and the subsequent arthritis development, in particular in the absence of NOX2 derived ROS. Importantly, ROS from macrophages protected against the autoimmune priming, demonstrating a critical regulatory role of macrophages in immune priming events. PMID:26455429

  9. Infections and arthritis.

    PubMed

    Mathew, Ashish Jacob; Ravindran, Vinod

    2014-12-01

    Bacteria, viruses, fungi, and parasites can all cause arthritis of either acute or chronic nature, which can be divided into infective/septic, reactive, or inflammatory. Considerable advances have occurred in diagnostic techniques in the recent decades resulting in better treatment outcomes in patients with infective arthritis. Detection of emerging arthritogenic viruses has changed the epidemiology of infection-related arthritis. The role of viruses in the pathogenesis of chronic inflammatory arthritides such as rheumatoid arthritis is increasingly being recognized. We discuss the various causative agents of infective arthritis and emphasize on the approach to each type of arthritis, highlighting the diagnostic tests, along with their statistical accuracy. Various investigations including newer methods such as nucleic acid amplification using polymerase chain reaction are discussed along with the pitfalls in interpreting the tests. PMID:26096095

  10. When is arthritis reactive?

    PubMed

    Hamdulay, S S; Glynne, S J; Keat, A

    2006-07-01

    Reactive arthritis is an important cause of lower limb oligoarthritis, mainly in young adults. It is one of the spondyloarthropathy family; it is distinguishable from other forms of inflammatory arthritis by virtue of the distribution of affected sites and the high prevalence of characteristic extra-articular lesions. Many terms have been used to refer to this and related forms of arthritis leading to some confusion. Reactive arthritis is precipitated by an infection at a distant site and genetic susceptibility is marked by possession of the HLA-B27 gene, although the mechanism remains uncertain. Diagnosis is a two stage process and requires demonstration of a temporal link with a recognised "trigger" infection. The identification and management of "sexually acquired" and "enteric" forms of reactive arthritis are considered. Putative links with HIV infection are also discussed. The clinical features, approach to investigation, diagnosis, and management of reactive arthritis are reviewed. PMID:16822921

  11. When is arthritis reactive?

    PubMed Central

    Hamdulay, S S; Glynne, S J; Keat, A

    2006-01-01

    Reactive arthritis is an important cause of lower limb oligoarthritis, mainly in young adults. It is one of the spondyloarthropathy family; it is distinguishable from other forms of inflammatory arthritis by virtue of the distribution of affected sites and the high prevalence of characteristic extra‐articular lesions. Many terms have been used to refer to this and related forms of arthritis leading to some confusion. Reactive arthritis is precipitated by an infection at a distant site and genetic susceptibility is marked by possession of the HLA‐B27 gene, although the mechanism remains uncertain. Diagnosis is a two stage process and requires demonstration of a temporal link with a recognised “trigger” infection. The identification and management of “sexually acquired” and “enteric” forms of reactive arthritis are considered. Putative links with HIV infection are also discussed. The clinical features, approach to investigation, diagnosis, and management of reactive arthritis are reviewed. PMID:16822921

  12. Hallux metatarsophalangeal arthritis.

    PubMed

    Weinfeld, S B; Schon, L C

    1998-04-01

    Arthritis of the hallux metatarsophalangeal joint is a common disorder that affects shoewear, ambulation, and other activities of daily living. Etiologies include degenerative arthritis (hallux rigidus), crystal induced arthropathy (gout, pseudogout), rheumatoid arthritis, the seronegative spondyloathropathies, posttraumatic degeneration, and advanced hallux valgus. Accurate diagnosis and selection of the appropriate intervention depends on recognition of pertinent clinical and radiographic features. This study presents a synopsis of the senior author's (LCS) experience with 439 surgically treated patients with hallux metatarsophalangeal arthritis, focusing on origin and treatment. PMID:9584362

  13. Adjuvant Therapy Trials.

    PubMed

    Ursem, Carling; Van Loon, Katherine; Venook, Alan

    2016-01-01

    In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598

  14. Carbohydrate-based immune adjuvants

    PubMed Central

    Petrovsky, Nikolai; Cooper, Peter D

    2011-01-01

    The role for adjuvants in human vaccines has been a matter of vigorous scientific debate, with the field hindered by the fact that for over 80 years, aluminum salts were the only adjuvants approved for human use. To this day, alum-based adjuvants, alone or combined with additional immune activators, remain the only adjuvants approved for use in the USA. This situation has not been helped by the fact that the mechanism of action of most adjuvants has been poorly understood. A relative lack of resources and funding for adjuvant development has only helped to maintain alum’s relative monopoly. To seriously challenge alum’s supremacy a new adjuvant has many major hurdles to overcome, not least being alum’s simplicity, tolerability, safety record and minimal cost. Carbohydrate structures play critical roles in immune system function and carbohydrates also have the virtue of a strong safety and tolerability record. A number of carbohydrate compounds from plant, bacterial, yeast and synthetic sources have emerged as promising vaccine adjuvant candidates. Carbohydrates are readily biodegradable and therefore unlikely to cause problems of long-term tissue deposits seen with alum adjuvants. Above all, the Holy Grail of human adjuvant development is to identify a compound that combines potent vaccine enhancement with maximum tolerability and safety. This has proved to be a tough challenge for many adjuvant contenders. Nevertheless, carbohydrate-based compounds have many favorable properties that could place them in a unique position to challenge alum’s monopoly over human vaccine usage. PMID:21506649

  15. Adjuvant Therapy: Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad; Kirkwood, John M.

    2011-01-01

    With an incidence that is increasing at 2–5% per year, cutaneous melanoma is an international scourge that disproportionately targets young individuals. Despite much research, the treatment of advanced disease is still quite challenging. Immunotherapy with high-dose interferon-α2b or interleukin-2 benefits a select group of patients in the adjuvant and metastatic settings, respectively, with significant attendant toxicity. Advances in the biology of malignant melanoma and the role of immunomodulatory therapy have produced advances that have stunned the field. In this paper, we review the data for the use of interferon-α2b in various dosing ranges, vaccine therapy, and the role of radiotherapy in the adjuvant setting for malignant melanoma. Recent trials in the metastatic setting using anticytoxic T-lymphocyte antigen-4 (anti-CTLA-4) monoclonal antibody therapy and BRAF inhibitor therapy have demonstrated clear benefit with prolongation of survival. Trials investigating combinations of these novel agents with existing immunomodulators are at present underway. PMID:22220281

  16. The surgical management of atlanto-axial subluxation in juvenile rheumatoid arthritis.

    PubMed

    Salem, Khalid M I; Radhakrishnan, Ajay; Behrbalk, Eyal; Boszczyk, B M

    2016-07-01

    Juvenile idiopathic arthritis (JIA) is a chronic condition affecting patients <16 years of age and can be associated with substantial morbidity. Atlanto-axial subluxation (AAS) is a known complication of JIA and can result in pain, reduced neck motion and neurological compromise. In this paper, we present the case of a 10-year old suffering with JIA and significant AAS; we discuss the management options and present the approach and outcome of treatment for this case. PMID:25427669

  17. Section AA Pre2004 Fire, Section AA 2009, Section AA, South ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Section A-A Pre-2004 Fire, Section A-A 2009, Section A-A, South Elevation - Boston & Maine Railroad, Berlin Branch Bridge #148.81, Formerly spanning Moose Brook at former Boston & Maine Railroad, Gorham, Coos County, NH

  18. The adjuvanted influenza vaccines with novel adjuvants: experience with the MF59-adjuvanted vaccine.

    PubMed

    Podda, A

    2001-03-21

    Elderly people and subjects with underlying chronic diseases are at increased risk for influenza and related complications. Conventional influenza vaccines provide only limited protection in the elderly population. In order to enhance the immune response to influenza vaccines, several adjuvants have been evaluated. Among these, an oil in water adjuvant emulsion containing squalene, MF59, has been combined with subunit influenza antigens and tested in clinical trials in comparison with non-adjuvanted conventional vaccines. Data from a clinical database of over 10000 elderly subjects immunised with this adjuvanted vaccine (Fluad, Chiron Vaccines, Siena, Italy) demonstrate that, although common postimmunisation reactions are more frequent in recipients of the adjuvanted vaccine, this vaccine is well tolerated, also after re-immunisation in subsequent influenza seasons. Immunogenicity analyses demonstrate a consistently higher immune response with statistically significant increases of postimmunisation geometric mean titres, and of seroconversion and seroprotection rates compared to non-adjuvanted subunit and split influenza vaccines, particularly for the A/H3N2 and the B strains. The higher immunogenicity profile of the MF59-adjuvanted vaccine is maintained also after subsequent immunisations. An even higher adjuvant effect was shown in subjects with low pre-immunisation titre and in those affected by chronic underlying diseases. In conclusion, the addition of MF59 to subunit influenza vaccines enhances significantly the immune response in elderly subjects without causing clinically important changes in the safety profile of the influenza vaccine. PMID:11257408

  19. Varicella arthritis in a child.

    PubMed Central

    Shuper, A; Mimouni, M; Mukamel, M; Varsano, I

    1980-01-01

    A 2 1/2-year-old girl developed arthritis in a metatarsophalangeal joint concomitantly with varicella. As she recovered within 2 days without antimicrobial treatment, it was considered that the arthritis was directly due to the viral infection. The importance of differentiating viral arthritis from septic arthritis, a well-known complication of varicella, is stressed. PMID:7436508

  20. 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

  1. The AAS Workforce Survey

    NASA Astrophysics Data System (ADS)

    Postman, Marc; Norman, D. J.; Evans, N. R.; Ivie, R.

    2014-01-01

    The AAS Demographics Committee, on behalf of the AAS, was tasked with initiating a biennial survey to improve the Society's ability to serve its members and to inform the community about changes in the community's demographics. A survey, based in part on similar surveys for other scientific societies, was developed in the summer of 2012 and was publicly launched in January 2013. The survey randomly targeted 2500 astronomers who are members of the AAS. The survey was closed 4 months later (April 2013). The response rate was excellent - 63% (1583 people) completed the survey. I will summarize the results from this survey, highlighting key results and plans for their broad dissemination.

  2. The adjuvant effect of stearyl tyrosine on a recombinant subunit hepatitis B surface antigen.

    PubMed

    Nixon-George, A; Moran, T; Dionne, G; Penney, C L; Lafleur, D; Bona, C A

    1990-06-15

    We describe the enhancement of the antibody response against hepatitis B surface Ag by octadecyl L-tyrosine, a synthetic adjuvant designed to exert its adjuvant effect in a manner similar to that of alum because it binds soluble Ag and releases it slowly from the site of injection. Our data demonstrate that octadecyl L-tyrosine showed a significant enhancement of the antihepatitis B surface Ag response compared to that of alum in the secondary response. The most striking difference between octadecyl L-tyrosine and alum in the antihepatitis B surface Ag antibody response was the absence of IgE-specific antibodies subsequent to immunization of the Ag in octadecyl L-tyrosine. Both the optical isomers of the octadecyl esters of tyrosine were adjuvant active, however, the racemic mixture showed a significantly lowe adjuvant activity. This adjuvant has great potential to be used in humans because it is devoid of side effects as assessed by the lack of acute and chronic toxicity in mice and rats, pyrogenicity in rabbits, formation of granuloma in cats, and adjuvant arthritis in rats. PMID:2351829

  3. 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

  4. AAS 227: Welcome!

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Greetings from the 227th American Astronomical Society meeting in Kissimmee, Florida! This week, along with several fellow authors from astrobites, Iwill bewritingupdates on selectedevents at themeeting and posting at the end of each day. You can follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.If youre an author or referee (or plan to be!) and youre here at the meeting, consider joining us at our Author and Referee Workshop on Wednesday in the Tallahassee room, where well be sharingsome of the exciting new features of the AAS journals. You can drop intoeither of the two-hour sessions(10 AM 12 PM or 1 PM 3 PM), and there will be afree buffet lunch at noon.Heres the agenda:Morning SessionTopic Speaker10:00 am 10:05 amIntroductionsJulie Steffen10:05 am 10:35 amChanges at AAS Journals; How to Be a Successful AAS AuthorEthan Vishniac10:35 am 11:00 amThe Peer Review ProcessButler Burton11:00 am 11:15 amAAS Nova: Sharing AAS Authors Research with the Broader CommunitySusanna Kohler11:15 am 11:30 amFixing Software and Instrumentation Publishing: New Paper Styles in AAS JournalsChris Lintott11:30 am 11:45 amMaking Article Writing Easier with the New AASTeX v6.0Greg Schwarz11:45 am 12:00 pmBringing JavaScript and Interactivity to Your AAS Journal FiguresGus MuenchLunch SessionTopic Speaker12:00 pm 12:15 pmUnified Astronomy ThesaurusKatie Frey12:15 pm 12:30 pmAAS/ADS ORCID Integration ToolAlberto Accomazzi12:30 pm 12:45 pmWorldWide Telescope and Video AbstractsJosh Peek12:45 pm 01:00 pmArizona Astronomical Data Hub (AADH)Bryan HeidornAfternoon SessionTopic Speaker01:00 pm 01:05 pmIntroductionsJulie Steffen01:05 pm 01:35 pmChanges at AAS Journals; How to Be a Successful AAS AuthorEthan Vishniac01:35 pm 02:00 pmThe Peer Review ProcessButler Burton02:00 pm 02:15 pmAAS Nova: Sharing AAS Authors Research with the Broader CommunitySusanna Kohler02:15 pm 02:30 pm

  5. AAS 228: Welcome!

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Greetings from the 228th American Astronomical Society meeting in San Diego, California! This week, along with a team of fellow authorsfrom astrobites, Iwill bewritingupdates on selectedevents at themeeting and posting twiceeach day. You can follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.If youre at the meeting, come stop by the AAS booth (Booth #211-213) to learn about the newly-announced partnership between AAS and astrobites and pick up some swag.And dont forget to visit the IOP booth in the Exhibit Hall (Booth #223) to learn more about the new corridors for AAS Journals and to pick up a badge pin to representyour corridor!

  6. 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 ...

  7. 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.) ...

  8. 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 ...

  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 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 ...

  11. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  12. Innate immunity and adjuvants

    PubMed Central

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536

  13. 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

  14. 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 ...

  15. Rheumatoid Arthritis Educational Video Series

    MedlinePlus Videos and Cool Tools

    ... to take a more active role in your care. The information in these videos should not take ... She is a critical member of our patient care team. Managing Your Arthritis Managing Your Arthritis Managing ...

  16. Classification of Laser Vaccine Adjuvants

    PubMed Central

    Kashiwagi, Satoshi; Brauns, Timothy; Poznansky, Mark C

    2016-01-01

    An immunologic adjuvant, which enhances the magnitude and quality of immune responses to vaccine antigens, has become an essential part of modern vaccine practice. Chemicals and biologicals have been typically used for this purpose, but there are an increasing number of studies that are being conducted on the vaccine adjuvant effect of laser light on the skin. Currently, four different types or classes of laser devices have been shown to systemically enhance immune responses to intradermal vaccination: ultra-short pulsed lasers, non-pulsed lasers, non-ablative fractional lasers and ablative fractional lasers. Aside from involving the application of laser light to the skin in a manner that minimizes discomfort and damage, each type of laser vaccine adjuvant involves emission parameters, modes of action and immunologic adjuvant effects that are quite distinct from each other. This review provides a summary of the four major classes of “laser vaccine adjuvant” and clarifies and resolves their characteristics as immunologic adjuvants. These aspects of each adjuvant’s properties will ultimately help define which laser would be most efficacious in delivering a specific clinical benefit with a specific vaccine. PMID:27104047

  17. Arthritis in mice induced by a single immunisation with collagen.

    PubMed Central

    Kato, F; Nomura, M; Nakamura, K

    1996-01-01

    OBJECTIVE: To determine whether collagen induced arthritis (CIA) in mice can be satisfactorily induced by a single immunisation and whether this model has some advantages compared with conventional CIA, which is induced by two immunisations. METHODS: The incidence of arthritis was observed under different immunisation conditions (variation of species of Mycobacterium included in complete Freund's adjuvant and the method of emulsification) and immunological, histopathological, and pharmacological features were examined. RESULTS: Under optimum immunisation conditions, joint inflammation developed two to three weeks after the primary immunisation with an incidence of 100% at four to five weeks. The progression of the arthritis was mild and was associated with moderate increases in concentrations of serum IgG against type II collagen. This CIA model was similar to the conventional model in histopathological and pharmacological features. CONCLUSIONS: Murine CIA could be successfully induced by a single immunisation. An important feature of this model was a mild progression of joint inflammation. This feature seems to be of benefit for monitoring the development of arthritis from an early stage in the disease and for the development of novel antirheumatic drugs for such early stage patients. Images PMID:8774181

  18. AAS Career Services

    NASA Astrophysics Data System (ADS)

    Marvel, Kevin B.

    2012-08-01

    The American Astronomical Society provides substantial programs in the area of Career Services.Motivated by the Society's mission to enhance and share humanity's understanding of the Universe, the AAS provides a central resource for advertising positions, interviewing opportunities at its annual winter meeting and information, workshops and networks to enable astronomers to find employment.The programs of the Society in this area are overseen by an active committee on employment and the AAS Council itself.Additional resources that help characterize the field, its growth and facts about employment such as salaries and type of jobs available are regularly summarized and reported on by the American Institute of Physics.

  19. Freund's adjuvants: relationship of arthritogenicity and adjuvanticity in rats to vehicle composition

    PubMed Central

    Whitehouse, M. W.; Orr, K. J.; Beck, Frances W. J.; Pearson, C. M.

    1974-01-01

    Over a hundred compounds and natural materials were examined for their ability to induce arthritis in rats when mixed with heat-killed delipidated Mycobacteria tuberculosis. Many of these materials were also assessed for (CMI) adjuvant activity by their ability to induce allergic encephalomyelitis (EAE) in rats when mixed with guinea-pig spinal cord, both with and without added M. tuberculosis. Cyclization and/or the presence of oxygen atoms, or double bonds reduced (or abolished) the arthritogenic potential and adjuvanticity of alkanes>C10. Esters/triglycerides of fatty acids >C12, retinol acetate (not palmitate) and vitamins E and K showed co-arthritogenic and adjuvant activity. Other active lipids included squalene and cholesterol oleate, which are both present in human sebum. Sebaceous lipids may therefore perhaps function as natural adjuvants if resorbed during abrasion and infection. Squalane (perhydrosqualene), pristane and hexadecane were excellent substitutes for mineral oil in preparing arthritogenic adjuvants from various mycobacteria, C. rubrum and N. asteroides. These oily compounds were also very effective adjuvants per se, in the absence of bacterial material or emulsifier, for inducing EAE in Lewis rats. PMID:4214125

  20. Acute Septic Arthritis

    PubMed Central

    Shirtliff, Mark E.; Mader, Jon T.

    2002-01-01

    Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection. PMID:12364368

  1. Adjuvant treatment for pancreatic cancer.

    PubMed

    Daoud, Vladimir; Saif, Muhammad Wasif; Goodman, Martin

    2014-07-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women. Surgical resection has been shown to be the only curable treatment available. Unfortunately only 20% of all patients diagnosed with pancreatic cancer are surgical candidates due to the aggressive biology of this disease. There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. The survival of these patients, even status post resection and adjuvant therapy, remains poor and therefore the need for alternative adjuvant therapies is needed. We will therefore discuss Abstracts #4124, #TPS4162, #4120 and #E15191 in this paper which are relevant to the issues described above. PMID:25076340

  2. AAS Oral History Project

    NASA Astrophysics Data System (ADS)

    Buxner, Sanlyn; Holbrook, Jarita; AAS Oral History Team

    2016-06-01

    Now in its fourth year, the AAS Oral History Project has interviewed over 80 astronomers from all over the world. Led by the AAS Historical Astronomy Division (HAD) and partially funded by the American Institute of Physics Niels Bohr Library and ongoing support from the AAS, volunteers have collected oral histories from astronomers at professional meetings starting in 2015, including AAS, DPS, and the IAU general assembly. Each interview lasts one and a half to two hours and focuses on interviewees’ personal and professional lives. Questions include those about one’s family, childhood, strong influences on one’s scientific career, career path, successes and challenges, perspectives on how astronomy is changing as a field, and advice to the next generation. Each interview is audio recorded and transcribed, the content of which is checked with each interviewee. Once complete, interview transcripts are posted online as part of a larger oral history library at https://www.aip.org/history-programs/niels-bohr-library/oral-histories. Future analysis will reveal a rich story of astronomers and will help the community address issues of diversity, controversies, and the changing landscape of science. We are still recruiting individuals to be interviewed from all stages of career from undergraduate students to retired and emeritus astronomers. Contact Jarita Holbrook to schedule an interview or to find out more information about the project (astroholbrook@gmail.com). Also, contact Jarita Holbrook if you would like to become an interviewer for the project.

  3. American Astronomical Society (AAS)

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    Founded in 1899, the AAS is a non-profit scientific society created to promote the advancement of astronomy and closely related branches of science. Its membership consists primarily of professional researchers in the astronomical sciences, but also includes educators, students and others interested in the advancement of astronomical research. About 85% of the membership is drawn from North Ame...

  4. Chemokines as Cancer Vaccine Adjuvants

    PubMed Central

    Bobanga, Iuliana D.; Petrosiute, Agne; Huang, Alex Y.

    2013-01-01

    We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs) and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants. PMID:24967094

  5. 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

  6. Arthritis-associated syndromes.

    PubMed

    Osial, T A; Cash, J M; Eisenbeis, C H

    1993-12-01

    There are a number of diseases characterized by inflammatory arthropathy that, although not as commonly seen as rheumatoid arthritis, often present to the family physician as difficult diagnostic problems. The diagnosis is frequently most difficult during the early course of these diseases. During recent years, new and altered concepts have arisen regarding both diagnostic and therapeutic management of this challenging group of arthropathies. This article presents a review of the more common arthritis-associated syndromes with emphasis on the differential diagnosis and medicinal therapeutics. PMID:8310085

  7. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  8. Spray drift mitigation with spray mix adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  9. Drift reduction with drift control adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Four new drift control adjuvants were sele...

  10. QS-21: a potent vaccine adjuvant

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QS-21 is an potent adjuvant derived from the bark of a Chilean tree, Quillaja saponaria. One of the advantages of this adjuvant is that it promotes a balanced humoral and cell-mediaed immune response and can be widely applicable to a variety of vaccines. This adjuvant has used for some veterinary va...

  11. Therapeutic Effect of Ficus lacor Aerial Roots of Various Fractions on Adjuvant-Induced Arthritic Rats

    PubMed Central

    Sindhu, Rakesh K.; Arora, Sandeep

    2013-01-01

    The present study was carried out to evaluate antiarthritic potential and phytochemical screening of various extracts of Ficus lacor aerial roots. The antiarthritic activity was evaluated by adjuvant-induced arthritis at the dose of 50 and 100 mg/kg body weight and the standard drug used was indomethacin. The extracts administered in higher doses reduced the lesions to a greater extent showing a dose-dependent decrease in lesions comparable with standard drug indomethacin. The extracts of FLPE and FLET showed significant increase in body weight as compared to arthritic control group as well as an increase in liver weight, a decrease in liver weight, and an increase in spleen weight in arthritis control. The extracts of FLPE and FLET showed significant decrease in WBC count, increase in hemoglobin contents, and RBC count as compared to control group. FLEA and FLCF were not able to produce a significant effect. There was significant reduction in production of IL-1 and TNF-α level between model group and control group in serum. In conclusion, we demonstrate that, at 100 mg/kg body weight, doses of FLPE and PLET extracts were highly effective in preventing and suppressing the development of adjuvant-induced arthritis. PMID:24167737

  12. 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

  13. Leflunomide in psoriatic arthritis.

    PubMed

    Kaltwasser, Joachim Peter

    2007-09-01

    Psoriatic arthritis (PsA) is a common unique form of inflammatory arthritis associated with psoriasis. Its exact prevalence is unknown but 5-30% of the 2-3% of subjects of the general population affected with psoriasis are developing PsA. Typically PsA presents as an oligoarticular asymmetrical arthritis with predominant distal finger joint pattern, presence of spinal involvement enthesitis and dactylitis. There is evidence that T-cells play a key role in the immunopathology of PsA as well as Psoriasis. Leflunomide, a selective pyrimidine synthesis inhibitor with the property to inhibit T-cell activation and proliferation has been shown to improve both joint and skin symptoms in patients with PsA. Significant response rates have been observed for Psoriatic Arthritis Response Criteria (PsARC), modified ACR20 and PASI 50 after 24 weeks of treatment with 20 mg/d Leflunomide orally in a randomised, placebo controlled multicenter trial (TOPAS Study). Leflunomide treatment also improved quality of life and showed a favourable safety profile. It is therefore concluded that Leflunomide offers an efficacious, well tolerated, safe, and relatively inexpensive therapeutic option for the treatment of actively inflamed joints and psoriatic skin lesions in patients with PsA. PMID:17854740

  14. [Arthritis and palmoplantar pustulosis].

    PubMed

    Bauduceau, B; Hanny, P; Chanudet, X; Celton, H; Doury, P; Larroque, P

    1987-01-01

    Pustulosis palmaris et plantaris may be associated with a number of articular diseases. Known to be present in Fiessinger-Leroy-Reiter syndrome and psoriasis arthropatica, this skin disease has been classified by Japanese authors as a new nosological entity: pustular osteo-arthritis. Pustulosis palmaris et plantaris seems to represent a meeting point for axial rheumatisms close to ankylozing spondylitis. PMID:3563169

  15. Effect of nabumetone treatment on vascular responses of the thoracic aorta in rat experimental arthritis.

    PubMed

    Ulker, S; Onal, A; Hatip, F B; Sürücü, A; Alkanat, M; Koşay, S; Evinç, A

    2000-04-01

    Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg x kg(-1) x day(-1), orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects. PMID:10754450

  16. Vaccine adjuvants as potential cancer immunotherapeutics.

    PubMed

    Temizoz, Burcu; Kuroda, Etsushi; Ishii, Ken J

    2016-07-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  17. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  18. Vaccine adjuvants as potential cancer immunotherapeutics

    PubMed Central

    Temizoz, Burcu; Kuroda, Etsushi

    2016-01-01

    Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund’s adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy. PMID:27006304

  19. A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression.

    PubMed

    Wang, Qiuhong; Shu, Zunpeng; Xing, Na; Xu, Bingqing; Wang, Changfu; Sun, Guibo; Sun, Xiaobo; Kuang, Haixue

    2016-05-01

    In our previous study, we found that the acidic polysaccharides of Ephedra sinica had immunosuppressive effect to treat rheumatoid arthritis and the pure polysaccharide ESP-B4 was the main composition of the acidic polysaccharides. At present, the exact molecular mechanism of ESP-B4 on treating arthritis is unclear. We are thus evaluating the properties of ESP-B4 on LPS-induced THP-1 pro-monocytic cells and adjuvant-induced arthritis in Wistar rats via TLR4. In vitro, ESP-B4 decreased the production of cytokines induced by LPS. In addition, ESP-B4 reduced the LPS-stimulated nuclear translocation of p65 subunit of NF-κB. Pretreatment with ESP-B4 significantly down-regulated the phosphorylation of MAPKs induced by LPS. Furthermore, in vivo, after 12 days of disease induced by adjuvant, rats were treated with ESP-B4 for 16 days. ESP-B4 significantly improved all parameters of inflammation. ESP-B4 reduced the release of inflammatory factors and cytokines by inhibiting the TLR4 signaling pathway to treat rheumatoid arthritis. PMID:26835987

  20. Reactive arthritis or post-infective arthritis?

    PubMed

    Keat, Andrew

    2002-09-01

    Infective mechanisms probably underlie a wide range of inflammatory arthropathies. There appears to be a spectrum of mechanisms ranging from the frankly septic, through low-grade infection with very small numbers of microorganisms in the joint to arthritides in which no hard evidence for an infective cause exists. In the midst of the spectrum lie 'post-infective' and 'reactive' arthritides, characterized clinically, genetically and by epidemiological links with infection. Identification of bacterial components within joint material from such patients suggested that the causes of the arthritis had been found. It is now clear that many bacteria are present in inflamed joints; establishing their significance will be of crucial importance, but not easy. PMID:12406424

  1. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  2. Adjuvant therapy for endometrial cancer

    PubMed Central

    DeLeon, Maria C.; Ammakkanavar, Natraj R.

    2014-01-01

    Endometrial cancer is a common gynecologic malignancy typically diagnosed at early stage and cured with surgery alone. Adjuvant therapy is tailored according to the risk of recurrence, estimated based on the International Federation of Gynecology and Obstetrics (FIGO) stage and other histological factors. The objective of this manuscript is to review the evidence guiding adjuvant therapy for early stage and locally advanced uterine cancer. For patients with early stage disease, minimizing toxicity, while preserving outstanding cure rates remains the major goal. For patients with locally advanced endometrial cancer optimal combined regimens are being defined. Risk stratification based on molecular traits is under development and may aid refine the current risk prediction model and permit personalized approaches for women with endometrial cancer. PMID:24761218

  3. 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

  4. Polysaccharides: Candidates of promising vaccine adjuvants.

    PubMed

    Li, Pingli; Wang, Fengshan

    2015-04-01

    Aluminium-based adjuvants remain the only adjuvants approved for human use in the USA for over 80 years because of alum's simplicity, tolerability, safety and cost-efficiency. Recent development of vaccines, especially the increasing applications of recombinant subunit and synthetic vaccines, makes aluminium adjuvants cannot stimulate enough immunity to the antigens, since aluminium adjuvants can only induce Th2 type immune responses. So, novel adjuvants are urgent to make up the disadvantages of aluminium adjuvants. However, some major hurdles need to be overcome, not only the scientific knowledge of adjuvants but also unacceptable side-effects and toxicity. A number of carbohydrate-based polysaccharides from plant, bacterial, yeast and synthetic sources can act as pathogen-associated molecular patterns (PAMPs) and recognize pattern recognition receptors (PRRs) on immune cells, followed by triggering innate immunity and regulating adaptive immunity. What is more, polysaccharides are safe and biodegradable without tissue deposits as observed in aluminium adjuvants. Therefore, polysaccharide-based compounds and formulations are potential vaccine adjuvant candidates. Here, we mainly review polysaccharide-based adjuvants investigated in recent years. PMID:25994059

  5. [Psoriatic arthritis and etanercept].

    PubMed

    Pedraz, J; Daudén, E

    2010-05-01

    Psoriatic arthritis (PA) is a chronic inflammatory condition whose symptoms generally appear after the skin symptoms. Making an early diagnosis and treatment of the disease is of vital importance because of the potential development of mutilating and deforming arthritis. Classical treatments of PA include the use of non-steroid anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARD) such as methotrexate, sulfasalazine, or gold, and finally, leflunomide. Research on the pathophysiology of psoriasis and of the PA has led to the incorporation of biological treatments, specifically anti-TNF drugs. The three treatments used most in PA are etanercept, infliximab and adalimumab. Of all these, we are going to make a systematic review of the principal studies available on etanercept for the treatment of PA. PMID:20492877

  6. [Pauciarticular juvenile chronic arthritis].

    PubMed

    Hertzberger-ten Cate, R; Fiselier, T

    1991-10-01

    On basis of clinical and immunogenetic factors most children with pauciarticular juvenile chronic arthritis can be included in one of the subtypes: type 1 and type 2 pauciarticular JCA. Type 1 occurs in young children, mainly girls, with involvement of knees, ankles or elbows. In the majority of children antinuclear antibodies can be detected. The presence of these autoantibodies is associated with chronic anterior uveitis. Type 2 or the juvenile spondylarthropathies include morbus Bechterew, the reactive arthritides and arthritis associated with psoriasis and inflammatory bowel diseases. Large joints of the lower extremities are involved, back pain is unusual at onset, but enthesitis is frequently present. There is a strong association with HLA-B27. Treatment of both subsets consists of non-steroidal anti-inflammatory drugs, application of intra-articular steroids, physio- and hydrotherapy and splinting. In children with a polyarticular course of type 1, or a prolonged course of type 2 disease modifying drugs are often needed. PMID:1957301

  7. [Juvenile psoriatic arthritis].

    PubMed

    Lu, Shan; Zhou, Wei; Zhang, Qian; Yu, Xin-Ying; Liu, Dong-Ming; Liu, Xiang-Yuan

    2007-08-01

    A case of juvenile psoriatic arthritis in a 12 year-old boy was reported. The patient had a history of one and half a year of bilateral heel pain, followed by pain in the right knee and ankle and right hip joint. He developed psoriatic lesions affecting his nails and skin. He had increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) contents. Human leukocyte antigen (HLA) B27 was detected but serum rheumatoid factor was not in the patient. A skin biopsy revealed psoriasis and ultrasonography demonstrated synovitis in right knee and ankle. Juvenile psoriatic arthritis was diagnosed based on his physical, laboratory and skin biopsy findings. A treatment with nonsteroidal anti-inflammatory drugs and sulfasalazine produced no effect. Leflunomide in conjunction with anti-TNF biologic agents (Etanercept) was administered, followed by symptomatic improvement 2 weeks later. PMID:17706035

  8. Lack of Galanin 3 Receptor Aggravates Murine Autoimmune Arthritis.

    PubMed

    Botz, Bálint; Kemény, Ágnes; Brunner, Susanne M; Locker, Felix; Csepregi, Janka; Mócsai, Attila; Pintér, Erika; McDougall, Jason J; Kofler, Barbara; Helyes, Zsuzsanna

    2016-06-01

    Neurogenic inflammation mediated by peptidergic sensory nerves has a crucial impact on the pathogenesis of various joint diseases. Galanin is a regulatory sensory neuropeptide, which has been shown to attenuate neurogenic inflammation, modulate neutrophil activation, and be involved in the development of adjuvant arthritis, but our current understanding about its targets and physiological importance is incomplete. Among the receptors of galanin (GAL1-3), GAL3 has been found to be the most abundantly expressed in the vasculature and on the surface of some immune cells. However, since there are minimal in vivo data on the role of GAL3 in joint diseases, we analyzed its involvement in different inflammatory mechanisms of the K/BxN serum transfer-model of autoimmune arthritis employing GAL 3 gene-deficient mice. After arthritis induction, GAL3 knockouts demonstrated increased clinical disease severity and earlier hindlimb edema than wild types. Vascular hyperpermeability determined by in vivo fluorescence imaging was also elevated compared to the wild-type controls. However, neutrophil accumulation detected by in vivo luminescence imaging or arthritic mechanical hyperalgesia was not altered by the lack of the GAL3 receptor. Our findings suggest that GAL3 has anti-inflammatory properties in joints by inhibiting vascular hyperpermeability and consequent edema formation. PMID:26941032

  9. AAS 227: Day 1

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or at astrobites.com, or catch ourlive-tweeted updates from the @astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto have so many people tell us that they already know about and useastrobites, and we were excited to introduce a new cohort of students at AAS to astrobites for the first time.Tuesday morning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended today.Opening Address (by Becky Smethurst)The President of the AAS, aka our fearless leader Meg Urry kicked off the meeting this morning at the purely coffee powered hour of 8am this morning. She spoke about the importance of young astronomers at the meeting (heres looking at you reader!) and also the importance of the new Working Group for Accessibility and Disabilities (aka WGAD pronounced like wicked) at the AAS. The Society has made extra effort this year to make the conference accessible to all,a message which was very well received by everyone in attendance.Kavli Lecture: New Horizons Alan Stern (by Becky Smethurst)We were definitely spoilt with the first Plenary lecture at this years conference Alan Stern gave us a a review of the New Horizons mission of the Pluto Fly By (astrobites covered the mission back in July with this post). We were treated to beautiful images, wonderful results and a foray into geology.Before (Hubble) and after #NewHorizons. #thatisall #science #astro alanstern #aas227 pic.twitter.com/kkMt6RsSIR Science News (@topsciencething) January 5, 2016Some awesome facts from the lecture that blew my mind:New Horizons is now 2AU (!) beyond Pluto

  10. Adjuvant progestagens for endometrial cancer

    PubMed Central

    Martin-Hirsch, Pierre PL; Bryant, Andrew; Keep, Sarah L; Kitchener, Henry C; Lilford, Richard

    2014-01-01

    Background Endometrial cancer is the most common genital tract carcinoma among women in developed countries, with most women presenting with stage 1 disease. Adjuvant progestagen therapy has been advocated following primary surgery to reduce the risk of recurrence of disease. Objectives To evaluate the effectiveness and safety of adjuvant progestagen therapy for the treatment of endometrial cancer. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Specilaised Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 2, 2009. MEDLINE and EMBASE up to April 2009. Selection criteria Randomised controlled trials (RCTs) of progestagen therapy in women who have had surgery for endometrial cancer. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Risk ratios (RRs) comparing survival in women who did and did not receive progestagen were pooled in random effects meta-analyses.. Main results Seven trials assessing 4556 women were identified. Three trials included women with stage one disease only, whereas four included women with more advanced disease. Meta-analysis of four trials showed that there was no significant difference in the risk of death at five years between adjuvant progestagen therapy and no further treatment (RR = 1.00, 95% CI 0.85 to 1.18). This conclusion is also robust to single trial analyses at 4 and 7 years and in one trial across all points in time using a hazard ratio (HR). There was also no significant difference between progestagen therapy and control in terms of the risk of death from endometrial cancer, cardiovascular disease and intercurrent disease. Relapse of disease appeared to be reduced by progestagen therapy in one trial (HR = 0.71, 95% CI 0.52 to 0.97 and 5 year RR = 0.74, 95% CI 0.58 to 0.96), but there was no evidence of a difference in disease recurrence in another trial at 7 years (RR = 1.34, 95% CI 0.79 to 2.27). Authors’ conclusions There

  11. Adalimumab in psoriatic arthritis.

    PubMed

    Salvarani, Carlo; Pipitone, Nicolò; Catanoso, Mariagrazia; Chiarolanza, Ilaria; Boiardi, Luigi; Caruso, Andrea; Pazzola, Giulia; Macchioni, Pierluigi; Di Lernia, Vito; Albertini, Giuseppe

    2012-07-01

    Open prospective studies and randomized controlled trials (RCT) have shown the short-term efficacy of adalimumab (ADA) in psoriatic arthritis (PsA) and psoriasis. ADA effectively treated all varied musculoskeletal manifestations characteristic of PsA, including peripheral arthritis, spinal disease, enthesitis, and dactylitis. ADA significantly inhibited structural changes on radiographs, lessened disability, and improved quality of life in patients with active PsA. One study showed the efficacy of 24-week ADA therapy on bone marrow edema and erosions, as measured by magnetic resonance imaging. The clinical and radiographic efficacy of ADA demonstrated during short-term treatment was sustained during longterm treatment. ADA was generally well tolerated and its safety profile was similar to that reported in studies of ADA in rheumatoid arthritis. Overall, ADA has a favorable risk-benefit profile in PsA. The combination of ADA and cyclosporine seems to be more effective than ADA monotherapy in patients with active PsA and inadequate response to methotrexate; however, this observation must be confirmed in RCT. PMID:22751600

  12. Arthritis, a complex connective and synovial joint destructive autoimmune disease: animal models of arthritis with varied etiopathology and their significance.

    PubMed

    Naik, S R; Wala, S M

    2014-01-01

    Animal models play a vital role in simplifying the complexity of pathogenesis and understanding the indefinable processes and diverse mechanisms involved in the progression of disease, and in providing new knowledge that may facilitate the drug development program. Selection of the animal models has to be carefully done, so that there is morphologic similarity to human arthritic conditions that may predict as well as augment the effective screening of novel antiarthritic agents. The review describes exclusively animal models of rheumatoid arthritis (RA) and osteoarthritis (OA). The development of RA has been vividly described using a wide variety of animal models with diverse insults (viz. collagen, Freund's adjuvant, proteoglycan, pristane, avridine, formaldehyde, etc.) that are able to simulate/trigger the cellular, biochemical, immunological, and histologic alterations, which perhaps mimic, to a great extent, the pathologic conditions of human RA. Similarly, numerous methods of inducing animal models with OA have also been described (such as spontaneous, surgical, chemical, and physical methods including genetically manipulated animals) which may give an insight into the events of alteration in connective tissues and their metabolism (synovial membrane/tissues along with cartilage) and bone erosion. The development of such arthritic animal models may throw light for better understanding of the etiopathogenic mechanisms of human arthritis and give new impetus for the drug development program on arthritis, a crippling disease. PMID:25121375

  13. Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

    PubMed Central

    2013-01-01

    Introduction Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model. Methods DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund’s adjuvant (CFA) or incomplete Freund’s adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression. Results Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA

  14. Autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination in Colombians: a call for personalised medicine.

    PubMed

    Anaya, Juan-Manuel; Reyes, Benjamin; Perdomo-Arciniegas, Ana M; Camacho-Rodríguez, Bernardo; Rojas-Villarraga, Adriana

    2015-01-01

    This was a case study in which 3 patients with autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA) after quadrivalent human papillomavirus vaccination (HPV) were evaluated and described. All the patients were women. Diagnosis consisted of HLA-B27 enthesitis related arthritis, rheumatoid arthritis and systemic lupus erythematous, respectively. Our results highlight the risk of developing ASIA after HPV vaccination and may serve to increase the awareness of such a complication. Factors that are predictive of developing autoimmune diseases should be examined at the population level in order to establish preventive measures in at-risk individuals for whom healthcare should be personalized and participatory. PMID:25962455

  15. The Impact of Adjuvant Radiation Therapy for High-Grade Gliomas by Histology in the United States Population

    SciTech Connect

    Rusthoven, Chad G.; Carlson, Julie A.; Waxweiler, Timothy V.; Dally, Miranda J.; Barón, Anna E.; Yeh, Norman; Gaspar, Laurie E.; Liu, Arthur K.; Ney, Douglas E.; Damek, Denise M.; Lillehei, Kevin O.; Kavanagh, Brian D.

    2014-11-15

    Purpose: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. Results: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were

  16. Strategic Change in AAS Publishing

    NASA Astrophysics Data System (ADS)

    Steffen, Julie

    2015-08-01

    The American Astronomical Society has embarked on a process of strategic change in its publishing program. The process has incuded authors, AAS leaders, editors, publishing experts, librarians, and data scientists. This session will outline the still ongoing process and present some both upcoming and already available new AAS Publishing features and services to the global astronomy community.

  17. Subchondral pseudocysts in rheumatoid arthritis.

    PubMed

    Rennell, C; Mainzer, F; Multz, C V; Genant, H K

    1977-12-01

    Subchondral cyst formation (geode) is a not uncommon manifestation of rheumatoid arthritis which may at times impede correct radiologic interpretation. Four patients with rheumatoid arthritis who demonstrated striking subarticular cystic erosive disease are described. These cases emphasize the nature and appearance of this interesting finding. PMID:413361

  18. 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. PMID:26063174

  19. AAS 227: Day 2

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 2 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Plenary Session: Black Hole Physics with the Event Horizon Telescope (by Susanna Kohler)If anyone needed motivation to wake up early this morning, they got it in the form of Feryal Ozel (University of Arizona) enthralling us all with exciting pictures, videos, and words about black holes and the Event Horizon Telescope. Ozel spoke to a packed room (at 8:30am!) about where the project currently stands, and where its heading in the future.The EHT has pretty much the coolest goal ever: actually image the event horizons of black holes in our universe. The problem is that the largest black hole we can look at (Sgr A*, in the center of our galaxy) has an event horizon size of 50 as. For this kind of resolution roughly equivalent to trying to image a DVD on the Moon! wed need an Earth-sized telescope. EHT has solved this problem by linking telescopes around the world, creating one giant, mm-wavelength effective telescope with a baseline the size of Earth.Besides producing awesome images, the EHT will be able to test properties of black-hole spacetime, the no-hair theorem, and general relativity (GR) in new regimes.Ozel walked us through some of the theory prep work we need to do now in order to get the most science out of the EHT, including devising new

  20. [Novel immunodiagnostics for inflammatory arthritis].

    PubMed

    Wahle, M; Kling, E

    2016-05-01

    Immunodiagnostics play an important role in the differential diagnostics of arthritis but the test results must be interpreted with respect to the clinical context. The detection of antibodies against citrullinated proteins has significantly improved the immunodiagnostics of arthritis, whereas the importance of testing for rheumatoid factor has decreased due to the low specificity. Antibodies against carbamylated or oxidized proteins will expand the immunodiagnostics of arthritis (especially rheumatoid arthritis) in the future. In contrast, the determination of cytokine concentrations in plasma or synovial fluid plays a subordinate role in the differential diagnostics of arthritis. Indirect immunofluorescence continues to be the gold standard in the detection of antinuclear antibodies (ANA) and in the case of positive results further testing for antigen specificity should be carried out. The presence of ANA is not necessarily associated with autoimmune diseases. An example of a non-pathogenic ANA is anti-DFS70 antibodies. PMID:27142378

  1. AAS 227: Day 2

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 2 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Plenary Session: Black Hole Physics with the Event Horizon Telescope (by Susanna Kohler)If anyone needed motivation to wake up early this morning, they got it in the form of Feryal Ozel (University of Arizona) enthralling us all with exciting pictures, videos, and words about black holes and the Event Horizon Telescope. Ozel spoke to a packed room (at 8:30am!) about where the project currently stands, and where its heading in the future.The EHT has pretty much the coolest goal ever: actually image the event horizons of black holes in our universe. The problem is that the largest black hole we can look at (Sgr A*, in the center of our galaxy) has an event horizon size of 50 as. For this kind of resolution roughly equivalent to trying to image a DVD on the Moon! wed need an Earth-sized telescope. EHT has solved this problem by linking telescopes around the world, creating one giant, mm-wavelength effective telescope with a baseline the size of Earth.Besides producing awesome images, the EHT will be able to test properties of black-hole spacetime, the no-hair theorem, and general relativity (GR) in new regimes.Ozel walked us through some of the theory prep work we need to do now in order to get the most science out of the EHT, including devising new

  2. AAS 227: Day 1

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or at astrobites.com, or catch ourlive-tweeted updates from the @astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto have so many people tell us that they already know about and useastrobites, and we were excited to introduce a new cohort of students at AAS to astrobites for the first time.Tuesday morning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended today.Opening Address (by Becky Smethurst)The President of the AAS, aka our fearless leader Meg Urry kicked off the meeting this morning at the purely coffee powered hour of 8am this morning. She spoke about the importance of young astronomers at the meeting (heres looking at you reader!) and also the importance of the new Working Group for Accessibility and Disabilities (aka WGAD pronounced like wicked) at the AAS. The Society has made extra effort this year to make the conference accessible to all,a message which was very well received by everyone in attendance.Kavli Lecture: New Horizons Alan Stern (by Becky Smethurst)We were definitely spoilt with the first Plenary lecture at this years conference Alan Stern gave us a a review of the New Horizons mission of the Pluto Fly By (astrobites covered the mission back in July with this post). We were treated to beautiful images, wonderful results and a foray into geology.Before (Hubble) and after #NewHorizons. #thatisall #science #astro alanstern #aas227 pic.twitter.com/kkMt6RsSIR Science News (@topsciencething) January 5, 2016Some awesome facts from the lecture that blew my mind:New Horizons is now 2AU (!) beyond Pluto

  3. Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway.

    PubMed

    Zhu, Lingpeng; Chen, Tong; Chang, Xiayun; Zhou, Rui; Luo, Fen; Liu, Jingyan; Zhang, Kai; Wang, Yue; Yang, Ying; Long, Hongyan; Liu, Yu; Yan, Tianhua; Ma, Chunhua

    2016-04-01

    The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling. PMID:26690894

  4. Psoriatic arthritis: a systematic review.

    PubMed

    Cantini, Fabrizio; Niccoli, Laura; Nannini, Carlotta; Kaloudi, Olga; Bertoni, Michele; Cassarà, Emanuele

    2010-10-01

    Psoriatic arthritis is an inflammatory rheumatic disorder of unknown etiology occurring in patients with psoriasis. The Classification Criteria for Psoriatic Arthritis study group has recently developed a validated set of classification criteria for psoriatic arthritis with a sensitivity of 91.4% and a specificity of 98.7%. Three main clinical patterns have been identified: oligoarticular (≤ 4 involved joints) or polyarticular (≥ 5 involved joints) peripheral disease and axial disease with or without associated peripheral arthritis. In this context distal interphalangeal arthritis and arthritis mutilans may occur. According to other reports, also in our centre, asymmetric oligoarthritis is the most frequent pattern at onset. Axial disease has been estimated between 5% and 36% of patients. It is characterized by an irregular involvement of the axial skeleton with a predilection for the cervical spine. Recurrent episodes of enthesitis and dactylitis represent a hallmark of psoriatic arthritis. In around 20% of cases distal extremity swelling with pitting edema of the hands or feet is observed. Unilateral acute iridocyclitis, usually recurrent in alternate fashion, is the most frequent extra-articular manifestation, and accelerated atherosclerosis is the prominent comorbidity. The clinical course of peripheral and axial psoriatic arthritis is usually less severe than rheumatoid arthritis and ankylosing spondylitis, respectively. Local corticosteroid injections and non-steroidal anti-inflammatory drugs are recommended in milder forms. Sulphasalazine and methotrexate are effective in peripheral psoriatic arthritis. Recent studies have provided evidence on the efficacy of anti-tumor necrosis factor-α drugs to control symptoms and to slow or arrest radiological disease progression. PMID:21199465

  5. Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma.

    PubMed Central

    Williams, R O; Williams, D G; Feldmann, M; Maini, R N

    1993-01-01

    We have tested the effect of administering H22, a hamster neutralizing MoAb to murine interferon-gamma (IFN-gamma) in collagen-induced arthritis. Mice were immunized with human type II collagen in adjuvant on day 1 and boosted with soluble collagen on day 21. H22 was administered (250 micrograms, intraperitoneally) either during the induction of arthritis (on days 0, 6, 13 and 20) or around the time of disease manifestation (on days 21, 28, 35 and 42). Control mice received either an isotype-matched non-neutralizing MoAb or saline. Both treatment regimes gave similar results. Treatment with H22 did not significantly affect the incidence of arthritis, time of onset, degree of oedema, histopathological severity, or level of anti-type II collagen IgG. However, a highly significant increase (P < 0.01) in the number of limbs affected by arthritis was observed in the H22-treated group, irrespective of whether the antibody was administered during the induction of arthritis, or during the time of clinical manifestation of disease. From these results it was concluded that anti-IFN-gamma treatment caused an increase in the number of arthritic lesions, but did not affect the severity of each individual lesion. PMID:8485917

  6. Gene expression profile and synovial microcirculation at early stages of collagen-induced arthritis

    PubMed Central

    Gierer, Philip; Ibrahim, Saleh; Mittlmeier, Thomas; Koczan, Dirk; Moeller, Steffen; Landes, Jürgen; Gradl, Georg; Vollmar, Brigitte

    2005-01-01

    A better understanding of the initial mechanisms that lead to arthritic disease could facilitate development of improved therapeutic strategies. We characterized the synovial microcirculation of knee joints in susceptible mouse strains undergoing intradermal immunization with bovine collagen II in complete Freund's adjuvant to induce arthritis (i.e. collagen-induced arthritis [CIA]). Susceptible DBA1/J and collagen II T-cell receptor transgenic mice were compared with CIA-resistant FVB/NJ mice. Before onset of clinical symptoms of arthritis, in vivo fluorescence microscopy of knee joints revealed marked leucocyte activation and interaction with the endothelial lining of synovial microvessels. This initial inflammatory cell response correlated with the gene expression profile at this disease stage. The majority of the 655 differentially expressed genes belonged to classes of genes that are involved in cell movement and structure, cell cycle and signal transduction, as well as transcription, protein synthesis and metabolism. However, 24 adhesion molecules and chemokine/cytokine genes were identified, some of which are known to contribute to arthritis (e.g. CD44 and neutrophil cytosolic factor 1) and some of which are novel in this respect (e.g. CC chemokine ligand-27 and IL-13 receptor α1). Online in vivo data on synovial tissue microcirculation, together with gene expression profiling, emphasize the potential role played by early inflammatory events in the development of arthritis. PMID:15987489

  7. Metabolomics analysis of collagen-induced arthritis in rats and interventional effects of oral tolerance.

    PubMed

    Ding, Xinghong; Hu, Jinbo; Li, Jinfeng; Zhang, Yan; Shui, Bingjie; Ding, Zhishan; Yao, Li; Fan, Yongsheng

    2014-08-01

    A serum metabolomics method based on rapid resolution liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (RRLC-Q-TOF-MS) was performed for a holistic evaluation of the metabolic changes of collagen-induced arthritis (CIA) in rats and to assess the interventional effects of type II collagen (CII) in this model. Partial least-squares-discriminant analysis (PLS-DA) was employed to study the metabolic profiling of CIA rats and control rats. Ten metabolites, namely, 12(S)-HHTrE, 12(S)-HEPE, PGE2, TXB2, 12(S)-HETE, LysoPE(16:0), PE(O-18:0/0:0), Lyso-PE(18:2), Lyso-PE(20:4), and Lyso-PC(22:5) were identified as differential metabolites associated with the pathogenesis of CIA. These results suggested that dysregulation of the arachidonic acid (AA) and phospholipid metabolic networks is involved in the pathomechanism of CIA. Differential metabolomics and histopathological analyses demonstrated that CII inhibits the progress of arthritis. Furthermore, the therapeutic effects of CII on CIA may involve regulation of the disordered AA and phospholipid metabolic networks. This metabolomics study provides new insights into the pathogenesis of arthritis and, furthermore, indicates the potential mechanism underlying the significantly increased prevalence of metabolic syndrome, defined as a clustering of cardiovascular disease (CVD) risk factors, in arthritis patients. PMID:24814225

  8. 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. PMID:26970491

  9. AAS 227: Day 3

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 3 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Henry Norris Russell Lecture: Viewing the Universe with Infrared Eyes: The Spitzer Space Telescope (by Erika Nesvold)The Henry Norris Russell Award is the highest honor given by the AAS, for a lifetime of eminence in astronomy research. This years award went to Giovanni Fazio of the Harvard-Smithsonian Center for Astrophysics. Fazio became a leader in gamma ray astronomy before switching mid-career to the study of infrared astronomy, and he gave his award lecture on the latter subject, specifically on the Spitzer Space Telescope, one of the most successful infrared telescopes of all time.Artists rendering of the Spitzer space telescope. [NASA/JPL-Caltech]Spitzer has been operating for more than twelve years, and has resulted in over six thousand papers in refereed journals in that time. The telescope sits in an Earth-trailing orbit around the Sun, and is now farther from the Earth (1.4 AU) than the Earth is from the Sun. Fazio gave the audience a fascinating overview of the science done by Spitzer over more than a decade. One of the most productive areas of research for Spitzer is the study of exoplanets, which hadnt even been discovered when the Spitzer Telescope was first conceived. Spitzers high sensitivity and ability to observe exoplanets over

  10. [Early rheumatoid arthritis].

    PubMed

    Babić-Naglić, Durdica

    2008-01-01

    Rheumatoid arthritis (RA) is chronic joint disease which if untreated leads to permanent structural damage and disability. Early diagnosis and therapy are the main requests for good clinical practice. Early diagnosis tools include specific clinical assesment, serological, immunogenetic and radiological evaluation. Disease activity score is cornerstone in clinical assesment, rheumatoid factor and anti-cyclic citrullinated peptide antibodies (anti-CCP) are very specific serological parameters. The shared epitope containing HLA-DRB1* alleles represent the most significant genetic risk for RA. Magnetic resonance and ultrasound imaging are very sensitive methods in early phase of disease. PMID:19024271

  11. 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

  12. AAS 227: Day 3

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 3 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Henry Norris Russell Lecture: Viewing the Universe with Infrared Eyes: The Spitzer Space Telescope (by Erika Nesvold)The Henry Norris Russell Award is the highest honor given by the AAS, for a lifetime of eminence in astronomy research. This years award went to Giovanni Fazio of the Harvard-Smithsonian Center for Astrophysics. Fazio became a leader in gamma ray astronomy before switching mid-career to the study of infrared astronomy, and he gave his award lecture on the latter subject, specifically on the Spitzer Space Telescope, one of the most successful infrared telescopes of all time.Artists rendering of the Spitzer space telescope. [NASA/JPL-Caltech]Spitzer has been operating for more than twelve years, and has resulted in over six thousand papers in refereed journals in that time. The telescope sits in an Earth-trailing orbit around the Sun, and is now farther from the Earth (1.4 AU) than the Earth is from the Sun. Fazio gave the audience a fascinating overview of the science done by Spitzer over more than a decade. One of the most productive areas of research for Spitzer is the study of exoplanets, which hadnt even been discovered when the Spitzer Telescope was first conceived. Spitzers high sensitivity and ability to observe exoplanets over

  13. Adjuvants: Classification, Modus Operandi, and Licensing

    PubMed Central

    Apostólico, Juliana de Souza

    2016-01-01

    Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations. PMID:27274998

  14. AAS 228: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note: Lastweek we were at the 228th AAS Meeting in San Diego, CA. Here is a final post aboutselectedevents on the last day of the meeting, written by authors fromastrobites.com, a grad-student collaborative project with which we recently announced a new partnership! Starting in July,keep an eye out for astrobites postsat AAS Nova in between Highlights(i.e., on Tuesdays and Thursdays).Were excited to be working together to bring you more recent astronomy research from AAS journals!Extrasolar Planets: Detection (by Leonardo dos Santos)Thursdays first session on exoplanets was about detecting these distant worlds, and the opening talk was given by Robert Siverd (Las Cumbres Observatory). He describes the NRES, a network of spectrographs that will look for exoplanets using the radial velocity method. One of the coolest aspects of this instrument is that it will feature an on the fly scheduling system that will perform observations as efficiently as possible. The spectrograph is still being tested, but a unit will be deployed at CTIO later this year.@lcogt contracted by @NASA_TESS for follow up of their candidates. #aas228 Jessie Christiansen (@aussiastronomer) June 16, 2016Measuring the depths of transits and eclipses in Spitzer has been problematic in the past, since the Spitzer instrument IRAC (InfraRed Array Camera) has a non-uniform response in its detectors pixels. But, as reported by James Ingalls (Spitzer Science Center, Caltech), observers are circumventing this issue by using what they call the staring mode (avoiding large pointing jumps) and an algorithm to pick sweet spot pixels. Moreover, the results from the IRAC Data Challenge are helping to better understand its behavior. Giuseppe Morello (University College London), on the other hand, explained how his research group gets rid of instrumental effects from IRAC using machine learning. This method removes systematics from exoplanet transit data no matter if the noise source is from an instrument or

  15. AA9 and AA10: from enigmatic to essential enzymes.

    PubMed

    Corrêa, Thamy Lívia Ribeiro; dos Santos, Leandro Vieira; Pereira, Gonçalo Amarante Guimarães

    2016-01-01

    The lignocellulosic biomass, comprised mainly of cellulose, hemicellulose, and lignin, is a strong competitor for petroleum to obtain fuels and other products because of its renewable nature, low cost, and non-competitiveness with food production when obtained from agricultural waste. Due to its recalcitrance, lignocellulosic material requires an arsenal of enzymes for its deconstruction and the consequent release of fermentable sugars. In this context, enzymes currently classified as auxiliary activity 9 (AA9/formerly GH61) and 10 (AA10/formerly CBM 33) or lytic polysaccharide monooxygenases (LPMO) have emerged as cellulase boosting enzymes. AA9 and AA10 are the new paradigm for deconstruction of lignocellulosic biomass by enhancing the activity and decreasing the loading of classical enzymes to the reaction and, consequently, reducing costs of the hydrolysis step in the second-generation ethanol production chain. In view of that disclosed above, the goal of this work is to review experimental data that supports the relevance of AA9 and AA10 for the biomass deconstruction field. PMID:26476647

  16. 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

  17. AAS 227: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 4 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Helen B. Warner Prize: Origins of Structure in Planetary Systems (by Erika Nesvold)Another excellent prize lecture started off todays sessions. The Helen B. Warner Prize is awarded for achievement in observational or theoretical astrophysics by a young researcher (no more than eight years after their Ph.D.). This years Warner Prize was presented to Ruth Murray-Clay of UC Santa Barbara. For her award lecture, Murray-Clay told us all about planetary system architecture: the number, masses, and orbits of planets in a given system.Ruth Murray-Clay [photo from http://web.physics.ucsb.edu/ ~murray/biocv.html]The underlying question motivating this type of research is: How rare is the Solar System? In other words, how likely is it that a given planetary system will have rocky planets close to their star, gas giants farther out, and ice giants at the outer reaches of the system? Answering this question will help us solve the physics problem of how and where planets form, and will also help us on our search for other planets like Earth.The data on exoplanet population from transit and radial velocity observations and from direct imaging tell us that our Solar System is not common (many systems we observe have much more eccentric gas giants), but that doesnt

  18. AAS 228: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note: Lastweek we were at the 228th AAS Meeting in San Diego, CA. Here is a final post aboutselectedevents on the last day of the meeting, written by authors fromastrobites.com, a grad-student collaborative project with which we recently announced a new partnership! Starting in July,keep an eye out for astrobites postsat AAS Nova in between Highlights(i.e., on Tuesdays and Thursdays).Were excited to be working together to bring you more recent astronomy research from AAS journals!Extrasolar Planets: Detection (by Leonardo dos Santos)Thursdays first session on exoplanets was about detecting these distant worlds, and the opening talk was given by Robert Siverd (Las Cumbres Observatory). He describes the NRES, a network of spectrographs that will look for exoplanets using the radial velocity method. One of the coolest aspects of this instrument is that it will feature an on the fly scheduling system that will perform observations as efficiently as possible. The spectrograph is still being tested, but a unit will be deployed at CTIO later this year.@lcogt contracted by @NASA_TESS for follow up of their candidates. #aas228 Jessie Christiansen (@aussiastronomer) June 16, 2016Measuring the depths of transits and eclipses in Spitzer has been problematic in the past, since the Spitzer instrument IRAC (InfraRed Array Camera) has a non-uniform response in its detectors pixels. But, as reported by James Ingalls (Spitzer Science Center, Caltech), observers are circumventing this issue by using what they call the staring mode (avoiding large pointing jumps) and an algorithm to pick sweet spot pixels. Moreover, the results from the IRAC Data Challenge are helping to better understand its behavior. Giuseppe Morello (University College London), on the other hand, explained how his research group gets rid of instrumental effects from IRAC using machine learning. This method removes systematics from exoplanet transit data no matter if the noise source is from an instrument or

  19. 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 ...

  20. MedlinePlus: Psoriatic Arthritis

    MedlinePlus

    ... an Expert For You Women Patient Handouts Summary Psoriasis is a skin disease that causes itchy or ... other parts of your body. Some people with psoriasis have psoriatic arthritis. It causes pain, stiffness, and ...

  1. 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. PMID:22111586

  2. Leflunomide for rheumatoid arthritis.

    PubMed

    2000-07-01

    Disease-modifying antirheumatic drugs (DMARDs) are given to patients with rheumatoid arthritis (RA) to prevent synovitis, slow destruction of articular cartilage and bone, preserve function and control systemic manifestations of the disease. Recognition that irreversible joint damage often occurs early in RA has led to much prompter use of DMARDs, with sulfasalazine or methotrexate commonly considered the treatment of first choice. Leflunomide (Arava-Aventis) is a new DMARD, licensed for the treatment of adults with active RA. The manufacturer claims that leflunomide has "comparable efficacy to methotrexate and sulphasalazine", with a "faster onset of action", and an "acceptable tolerability profile". Here, we consider the place of leflunomide in the management of patients with RA. PMID:11027115

  3. Smoking and Rheumatoid Arthritis

    PubMed Central

    Chang, Kathleen; Yang, So Min; Kim, Seong Heon; Han, Kyoung Hee; Park, Se Jin; Shin, Jae Il

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper. PMID:25479074

  4. Physiotherapy in Rheumatoid Arthritis

    PubMed Central

    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

  5. [Rheumatoid arthritis and malignancy].

    PubMed

    Kameda, Tomohiro; Dobashi, Hiroaki

    2016-06-01

    Rheumatoid arthritis (RA) is associated with excess mortality. Especially, malignancy is a major cause of mortality. According to previous reports, the overall incidence of malignancies in RA patients has been reported to be comparable or slightly higher than that in general population. The increased incidence of malignant lymphoma and lung cancer has been reported to be consistent in most studies. The use of some csDMARD was also reported as risk factors for malignancy. Recently, MTX associated lymphoproliferative disorder(MTX-LPD) is one of the important complications in RA treatment. We revealed the mean MTX dose was demonstrated to be an independent risk factor regarding MTX-LPD onset in RA patients. This data suggest that the treatment with higher MTX dose promotes LPD onset in Japanese RA patients. PMID:27311195

  6. 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

  7. Juvenile idiopathic arthritis

    PubMed Central

    Bhatt, Krupa H; Karjodkar, Freny R; Sansare, Kaustubh; Patil, Darshana

    2014-01-01

    Juvenile Idiopathic Arthritis (JIA) is the most chronic musculoskeletal disease of pediatric population. The chronic course of disease has a great impact on oral health. Temporomandibular joint is involved in JIA causing limited mouth opening with progressive open bite, retrognathia, microgenia and bird like appearance. Joints of upper and lower extremities are also involved. Effect on upper limb function leads to difficulty with fine motor movements required for brushing and flossing. This increases incidence of caries and periodontal disease in children. The cause of JIA is still poorly understood and none of the available drugs for JIA can cure the disease. However, prognosis has improved as a result of progress in disease classification and management. The dental practitioner should be familiar with the symptoms and oral manifestations of JIA to help manage as multidisciplinary management is essential. PMID:24808703

  8. AAS 227: Day 4

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-01-01

    Editors Note:This week were at the 227th AAS Meeting in Kissimmee, FL. Along with several fellow authors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting at the end of each day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Welcome to Day 4 of the winter American Astronomical Society (AAS) meeting in Kissimmee! Several of us are attending the conference this year, and we will report highlights from each day here on astrobites. If youd like to see more timely updates during the day, we encourage you to follow @astrobites on twitter or search the #aas227 hashtag.Helen B. Warner Prize: Origins of Structure in Planetary Systems (by Erika Nesvold)Another excellent prize lecture started off todays sessions. The Helen B. Warner Prize is awarded for achievement in observational or theoretical astrophysics by a young researcher (no more than eight years after their Ph.D.). This years Warner Prize was presented to Ruth Murray-Clay of UC Santa Barbara. For her award lecture, Murray-Clay told us all about planetary system architecture: the number, masses, and orbits of planets in a given system.Ruth Murray-Clay [photo from http://web.physics.ucsb.edu/ ~murray/biocv.html]The underlying question motivating this type of research is: How rare is the Solar System? In other words, how likely is it that a given planetary system will have rocky planets close to their star, gas giants farther out, and ice giants at the outer reaches of the system? Answering this question will help us solve the physics problem of how and where planets form, and will also help us on our search for other planets like Earth.The data on exoplanet population from transit and radial velocity observations and from direct imaging tell us that our Solar System is not common (many systems we observe have much more eccentric gas giants), but that doesnt

  9. [Reactive arthritis: inflammation or true infection?].

    PubMed

    Finckh, Axel

    2016-03-01

    Reactive arthritis has been classically defined as an aseptic arthritis induced by a bacterial infection in another organ. If the classical form of reactive arthritis is in fact a spondyloarthritis triggered by a urogenital or intestinal bacterial infection, it is not necessarily sterile, and in some cases it may be worthwhile to treat a chronic infection with long-term antibiotherapy. In a broader definition, the concept of reactive arthritis is widened to other post-infectious rheumatism, such as post-streptococcal arthritis or post-viral arthritis. PMID:27089639

  10. Extended Adjuvant Therapy for Breast Cancer

    Cancer.gov

    An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

  11. Adjuvant Bisphosphonates for Postmenopausal Breast Cancer

    Cancer.gov

    A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.

  12. [Rectal cancer and adjuvant chemotherapy: which conclusions?].

    PubMed

    Bachet, J-B; Rougier, P; de Gramont, A; André, T

    2010-01-01

    Adenocarcinoma of the rectum represents about a third of cases of colorectal cancer, with an annual incidence of 12,000 cases in France. On the contrary of colon cancer, the benefice of adjuvant chemotherapy in rectal cancer has not been definitively proved, more because this question was assessed in few recent studies than because negative results. Preoperative radiochemotherapy is now the reference treatment for mid and lower rectal cancers, and allow to increase the local control without improvement of progression free survival and overall survival. The data of the "historical studies" of adjuvant treatment in rectal cancer published before 1990, of the meta-analysis of adjuvant trials in rectal cancer and of the QUASAR study suggest that adjuvant chemotherapy with fluoropyrimidines (intravenous or oral), in absence of pre-operative treatment, decrease the risk of metastatic relapse after curative surgery for a rectal cancer of stage II or III. This benefice seems similar to the one observed in colon cancer. In the EORTC radiotherapy group trial 22921, an adjuvant chemotherapy with 5-fluorouracil and low dose of leucovorin was not associated with a significantly improvement of overall survival but, despite the fact that only 42.9% of patients received all planed cycles, the progression free survival was increased (not significantly) in groups receiving adjuvant chemotherapy. The French recommendations are to discuss the indication of adjuvant chemotherapy by fluoropyrimidines in cases of stage III rectal cancer on histopathologic reports and no chemotherapy in case of stade II. Despite the fact that none study have assessed a combination of fluoropyrimidines and oxaliplatin in adjuvant setting in rectal cancer, like in colon cancer, the Folfox4, modified Folfox6 or Xelox regimens are valid options in stage III (experts opinion). In cases of pathologic complete remission or in absence of involved nodes, the benefice of adjuvant chemotherapy is not assessed. In

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

    PubMed Central

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

    2013-01-01

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

  14. Applications of nanomaterials as vaccine adjuvants

    PubMed Central

    Zhu, Motao; Wang, Rongfu; Nie, Guangjun

    2014-01-01

    Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

  15. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  16. 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 ...

  17. Experimental Drug for Rheumatoid Arthritis Shows Promise

    MedlinePlus

    ... news/fullstory_158076.html Experimental Drug for Rheumatoid Arthritis Shows Promise Baricitinib helped patients who failed other ... HealthDay News) -- An experimental drug to treat rheumatoid arthritis showed promise in a new six-month trial. ...

  18. 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 ...

  19. Arthritis - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arthritis URL of this page: https://medlineplus.gov/languages/arthritis.html Other topics A-Z A B ...

  20. [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 6weeks duration in patients aged less than 16years 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

  1. Arthritis - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Arthritis URL of this page: https://www.nlm.nih.gov/medlineplus/languages/arthritis.html Other topics A-Z A B ...

  2. Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

    SciTech Connect

    Darwish, Hebatallah A.; Arab, Hany H.; Abdelsalam, Rania M.

    2014-09-01

    Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy to celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved spermatogenesis

  3. 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.

  4. 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.

  5. 9 CFR 311.7 - Arthritis.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 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...

  6. 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...

  7. 9 CFR 311.7 - Arthritis.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 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...

  8. 9 CFR 311.7 - Arthritis.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 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...

  9. 9 CFR 311.7 - Arthritis.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 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...

  10. Vaccinations for Rheumatoid Arthritis

    PubMed Central

    Perry, Lisa M.; Winthrop, Kevin L.; Curtis, Jeffrey R.

    2014-01-01

    Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients. PMID:24925587

  11. [Vasculitis in rheumatoid arthritis].

    PubMed

    Bély, M; Apáthy, A

    1996-07-21

    The frequency and histopathological characteristics of systemic vasculitis were studied in the autopsy material of 161 patients with rheumatoid arthritis. Systemic vasculitis was observed in 36 case (22.4%). In percentage of all cases with systemic vasculitis, the most frequently involved organs were the heart (66.7%), skeletal muscles (54.8%), and peripheral nerves (52%). The skin was involved only in about one third of 36 cases (36%). In most cases the arterioles and the small arteries were affected by vasculitis. Three types of vasculitis (non specific, fibrinoid necrotic, granulomatous) could be observed simultaneously in different vessels or combined in the same vessel. Different stages of inflammation could be found simultaneously, reflecting the relapsing nature of vasculitis. The frequency, the severity, and the recurrence of vasculitis are different aspects of the same phenomenon running usually parallel to each other in different organs and on different vessels. Vasculitis lead to local ischaemia and regressive changes depend on the number and size of the involved vessels. Systemic vasculitis led to death in 19 of 36 cases. Vasculitis was detected clinically in 7 of 36 cases. Exitus lethalis depend on the localization of the involved vessels. Vasculitis in the heart and brain are more life threatening, than that of localized to the skin. PMID:8757068

  12. Rheumatoid arthritis and pregnancy.

    PubMed

    Klipple, G L; Cecere, F A

    1989-05-01

    The activity of RA is significantly altered by pregnancy with approximately 70 per cent of patients experiencing substantial improvement in symptoms, signs and sometimes extra-articular manifestations. This lessening of disease activity occurs in association with an almost complete cessation of medications. However, whether partial or complete this remission is short-lived with more than 90 per cent of women who improved relapsing by 6 to 8 months postpartum. Further, in approximately 30 per cent of RA patients the course remains unchanged or worsens during gestation and indeed the first symptoms of RA may develop during pregnancy or shortly thereafter. Conversely active rheumatoid arthritis seems to little influence the maternal course or fetal outcome of pregnancy. The multiple and complex immunologic alterations of the pregnant state are designed to ensure survival of the fetal allograft in a foreign host. A number of these alterations particularly involving modulation of cell-mediated immunity, immunoglobulin composition, immune complex generation, or the inflammatory response have the potential to interfere with the pathophysiology of RA. In short, although the specific mechanism remains an enigma, the reason for the amelioration of RA during pregnancy is probably an incidental and fortuitous reaction to one or more of these immunomodulatory factors. PMID:2657889

  13. A case of emphysematous pyelonephritis in a patient with rheumatoid arthritis taking corticosteroid and low-dose methotrexate.

    PubMed

    Watanabe, Hiroshi; Suzuki, Ryoma; Asano, Tomoyuki; Shio, Kiori; Iwadate, Haruyo; Kobayashi, Hiroko; Matsuoka, Toshimitsu; Aikawa, Ken; Ohira, Hiromasa

    2010-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease that is characterized by chronic synovial inflammation. Patients with RA have increased risk of infection; this is related to RA itself or the adverse effects of medication. In this report, we describe a case of emphysematous pyelonephritis in a patient with RA associated with AA amyloidosis and steroid-induced diabetes mellitus who was taking corticosteroid and low-dose methotrexate. PMID:20536605

  14. Adjuvant effects of saponins on animal immune responses*

    PubMed Central

    Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

  15. Polyarticular psoriatic arthritis is more like oligoarticular psoriatic arthritis, than rheumatoid arthritis

    PubMed Central

    Helliwell, P S; Porter, G; Taylor, W J

    2007-01-01

    Background and objective Since the original description of psoriatic arthritis (PsA) subgroups by Moll and Wright, there has been some discrepancy in the precise prevalence of the different subgroups and in particular the proportion of patients with polyarthritis. The higher prevalence of the polyarthritis subgroup may be due to the inclusion of patients with seronegative rheumatoid arthritis with coincidental psoriasis. The classification of psoriatic arthritis (CASPAR) study database provided an opportunity to examine this question. Methods The CASPAR study collected clinical, radiological and laboratory data on 588 patients with physician‐diagnosed PsA and 525 controls with other inflammatory arthritis, 70% of whom had rheumatoid arthritis. Patients with PsA were divided into two groups: polyarthritis and non‐polyarthritis (which included the Moll and Wright subgroups of spinal disease, distal interphalangeal predominant and arthritis mutilans) and were compared with patients with rheumatoid arthritis. Comparisons were made between all three groups and, if a significant difference occurred, between the two groups with PsA. Results The three groups differed significantly with regard to all clinical and laboratory variables except duration of disease. Significant differences were also found between the two groups of PsA in terms of age, sex, total number of involved joints, disability score and symmetry. However, no differences were found between the groups of patients with PsA in terms of seropositivity for rheumatoid factor and antibodies to cyclic citrullinated peptide, enthesitis, and spinal pain and stiffness. Further, dactylitis was commonly seen in patients with PsA (57% in the polyarticular group and 45% in non‐polyarticular group), and uncommonly found in patients with rheumatoid arthritis (5%). With the exception of entheseal changes, syndesmophytes and osteolysis, typical radiological features of PsA could not be used to distinguish between the Ps

  16. Finemapping of the arthritis QTL Pia7 reveals co-localization with Oia2 and the APLEC locus.

    PubMed

    Rintisch, C; Kelkka, T; Norin, U; Lorentzen, J C; Olofsson, P; Holmdahl, R

    2010-04-01

    In this study, we sought to determine the effect of the quantitative trait locus Pia7 on arthritis severity. The regulatory locus derived from the arthritis-resistant E3 rat strain was introgressed into the arthritis-susceptibility DA strain through continuous backcrossing. Congenic rats were studied for their susceptibility to experimental arthritis using pristane and adjuvant oil. In addition, cell number and function of various leukocyte populations were analyzed either under naive or stimulated conditions. We found that the minimal congenic fragment of DA.E3-Pia7 rats overlapped with the minimal fragment in DA.PVG-Oia2 congenic rats, which has been positionally cloned to the antigen-presenting lectin-like receptor complex (APLEC) genes. DA.E3-Pia7 congenic rats were protected from both PIA and OIA, but the protection was more pronounced in OIA. In adoptive transfer experiments we observed that the Pia7 locus controlled the priming of arthritogenic T cells and not the effector phase. In addition, Pia7 congenic rats had a significant higher frequency of B cells and granulocytes as well as TNFalpha production after stimulation, indicating a higher activation state of cells of the innate immune system. In conclusion, this study shows that the APLEC locus is a major locus regulating the severity of experimentally induced arthritis in rats. PMID:20200546

  17. Pyogenic infection and rheumatoid arthritis.

    PubMed Central

    Rowe, I. F.; Deans, A. C.; Keat, A. C.

    1987-01-01

    Ten episodes of severe pyogenic infection occurring in nine patients with rheumatoid arthritis are reported. There was a wide range of presenting features including pyoarthrosis in 7 episodes. Three cases presented with meningitis, bacterial endocarditis and probable multiple abscesses respectively. Infection was caused by Staphylococcus aureus in 7 episodes and by Staphylococcus epidermidis, Streptococcus pneumoniae and beta-haemolytic Streptococcus in each of one episode. Three infective episodes were fatal. Pyogenic, especially staphylococcal, infection should be considered in patients with rheumatoid arthritis with unexplained illness with or without sudden deterioration in joint symptoms. It is important to recognize and treat infection rapidly. Images Figure 1 Figure 2 PMID:3671222

  18. 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

  19. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  20. Beyond antigens and adjuvants: formulating future vaccines.

    PubMed

    Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J

    2016-03-01

    The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033

  1. Systemic adjuvant therapies in renal cell carcinoma.

    PubMed

    Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea

    2012-10-01

    Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216

  2. CpG DNA as mucosal adjuvant.

    PubMed

    McCluskie, M J; Davis, H L

    1999-09-01

    We have previously found synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs to be a potent adjuvant to protein administered by intramuscular injection or intranasal inhalation to BALB/c mice. Herein we have further evaluated the potential of CpG ODN as a mucosal adjuvant to purified hepatitis B surface antigen (HBsAg) when administered alone or with cholera toxin (CT). CpG ODN and CT both augmented systemic (humoral and cellular) and mucosal immune responses against HBsAg, and these could be further enhanced with higher doses of adjuvant or boosting. Overall, antibody isotypes with CT alone were predominantly IgG1 (Th2-like) whereas they were predominantly IgG2a (Th1-like) with CpG ODN alone or in combination with CT. Results from this study indicate that stimulatory CpG ODN are promising new adjuvants for mucosal vaccination strategies, whether used alone or in combination with other mucosal adjuvants. PMID:10506647

  3. 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.

  4. Adjuvant radiation for soft tissue sarcomas.

    PubMed

    Dickie, Colleen I; Haas, Rick; O'Sullivan, Brian

    2015-01-01

    Over recent decades, limb-preservation surgery in combination with radiotherapy achieves local control rates exceeding 90% for extremity soft tissue sarcoma (STS). Local control is not as successful for retroperitoneal sarcoma (approximately 60%) despite aggressive surgical approaches including en bloc resection of uninvolved adjacent organs combined with intensity modulated radiotherapy (IMRT). This review will discuss the indications for adjuvant radiation therapy (RT) for primary presentation of soft tissue sarcoma: "What," referring to the type and manner of planning and delivery of RT; "When," referring to the timing and scheduling of RT; and "Why," referring to the rationale for the use of RT will be addressed. From a practical stand point, this Educational Chapter on "adjuvant RT" will focus on pre- and postoperative RT in the context of gross total resection for extremity and retroperitoneal soft tissue sarcoma, the two most frequent paradigms for the use of adjuvant RT. PMID:25993234

  5. Systemic immunotoxicity reactions induced by adjuvanted vaccines.

    PubMed

    Batista-Duharte, Alexander; Portuondo, Deivys; Pérez, O; Carlos, Iracilda Zeppone

    2014-05-01

    Vaccine safety is a topic of concern for the treated individual, the family, the health care personnel, and the others involved in vaccination programs as recipients or providers. Adjuvants are necessary components to warrant the efficacy of vaccines, however the overstimulation of the immune system is also associated with adverse effects. Local reactions are the most frequent manifestation of toxicity induced by adjuvanted vaccines and, with the exception of the acute phase response (APR), much less is known about the systemic reactions that follow vaccination. Their low frequency or subclinical expression meant that this matter has been neglected. In this review, various systemic reactions associated with immune stimulation will be addressed, including: APR, hypersensitivity, induction or worsening of autoimmune diseases, modification of hepatic metabolism and vascular leak syndrome (VLS), with an emphasis on the mechanism involved. Finally, the authors analyze the current focus of discussion about vaccine safety and opportunities to improve the design of new adjuvanted vaccines in the future. PMID:24607449

  6. 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 ( ...

  7. 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 ...

  8. [Adjuvant chemotherapy of adults soft tissue sarcomas].

    PubMed

    Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M

    2010-06-01

    The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481

  9. Hydrodynamic Delivery of Chitosan-Folate-DNA Nanoparticles in Rats with Adjuvant-Induced Arthritis

    PubMed Central

    Shi, Qin; Wang, Huijie; Tran, Covi; Qiu, Xingping; Winnik, Françoise M.; Zhang, Xiaoling; Dai, Kerong; Benderdour, Mohamed; Fernandes, Julio C.

    2011-01-01

    50 kDa chitosan was conjugated with folate, a specific tissue-targeting ligand. Nanoparticles such as chitosan-DNA and folate-chitosan-DNA were prepared by coacervation process. The hydrodynamic intravenous injection of nanoparticles was performed in the right posterior paw in normal and arthritic rats. Our results demonstrated that the fluorescence intensity of DsRed detected was 5 to 12 times more in the right soleus muscle and in the right gastro muscle than other tissue sections. β-galactosidase gene expression with X-gal substrate and folate-chitosan-plasmid nanoparticles showed best coloration in the soleus muscle. Treated arthritic animals also showed a significant decrease in paw swelling and IL-1β and PGE2 concentration in serum compared to untreated rats. This study demonstrated that a nonviral gene therapeutic approach using hydrodynamic delivery could help transfect more efficiently folate-chitosan-DNA nanoparticles in vitro/in vivo and could decrease inflammation in arthritic rats. PMID:21274258

  10. [ADJUVANTED INFLUENZA VACCINES: DATA FROM DIRECT COMPARATIVE STUDIES].

    PubMed

    Chernikova, M I; Vasiliev, Yu M

    2015-01-01

    Vaccines are the cornerstone of influenza control, however available vaccines are subject to certain limitations. Adjuvanted vaccines are a promising approach, however available adjuvants have a suboptimal effectiveness and safety profile. Data from direct comparative trials are necessary for selection of optimal adjuvants among currently available and search for novel safe and effective adjuvants for next generation influenza vaccines. Data from published direct comparative studies of adjuvants for influenza vaccines are summarized, a lack of such studies is noted, especially those using adequate methods and designs and comparing adjuvants of major groups (nature/source and mechanism of action). Several promising approaches of adjuvant research and development could be identified: chitosan-based adjuvants, oil-in-water emulsions and multi-component formulations (depot + immune modulating components). PMID:26829860

  11. The impact of concurrent temozolomide with adjuvant radiation and IDH mutation status among patients with anaplastic astrocytoma

    PubMed Central

    Giannini, Caterina; Voss, Jesse S.; Decker, Paul A.; Jenkins, Robert B.; Hardie, John; Laack, Nadia N.; Parney, Ian F.; Uhm, Joon H.; Buckner, Jan C.

    2014-01-01

    This study assesses the controversial role of temozolomide (TMZ) concurrent with adjuvant radiation (RT) in patients with anaplastic astrocytoma (AA). The impact of isocitrate dehydrogenase (IDH) status on therapy and outcomes is also examined. All adult patients diagnosed with AA from 2001 to 2011 and treated with standard doses of adjuvant RT were identified retrospectively for clinical data extraction. IDH status was determined by IDH1-R132H immunostain and sequencing for other mutations in IDH1/IDH2. Cumulative survival probabilities were estimated using the Kaplan-Meier method. Cox proportional hazards regression models were fit for univariable/multivariable analyses. 136 patients had received concurrent TMZ while 29 had not. Of these, IDH status was determined on 114 and 27 patients, respectively. On univariable analysis, improved five-year survival was independently associated with concurrent TMZ (46.2 vs. 29.3 %, p = 0.02) and IDH mutation (78.9 vs. 22.0 %, p < 0.001). IDH mutation was additionally associated with a greater likelihood of extensive resection possibly secondary to a more favorable tumor location. Gross total/subtotal resections also led to improved survival when compared to biopsy alone on univariable analysis. On multivariable analysis, the association with five-year survival persisted for both concurrent TMZ and IDH mutation, but not with extent of surgery. Both IDH mutation and concurrent TMZ are associated with improved five-year survival in patients with AA who are receiving adjuvant RT. Secondarily, the association between five-year survival and extent of resection is lost on multivariable analysis. This suggests a possible association between IDH mutation, tumor location and consequent resectability. PMID:24993250

  12. Phenotypic characterization of type II collagen-induced arthritis in Wistar rats

    PubMed Central

    SONG, HOU-PAN; LI, XIN; YU, RONG; ZENG, GUANG; YUAN, ZHEN-YI; WANG, WEI; HUANG, HUI-YONG; CAI, XIONG

    2015-01-01

    The aim of the present study was to determine a more specific, efficient and simple method for the induction of collagen-induced arthritis (CIA) in rats. Different strains of rats were injected at the base of the tail with bovine type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA). The onset and severity of arthritis were evaluated by clinical assessment. The established CIA model was analyzed using a comprehensive examination of clinical, hematological, histological and radiological parameters. The results demonstrated that Wistar rats were the most susceptible strain to CIA followed by Wistar Furth rats, with Sprague Dawley rats being the least susceptible. Following primary and booster immunization, female Wistar rats developed severe arthritis, with an incidence of >83% and low variability in clinical signs. The development of arthritis was accompanied by a significantly elevated erythrocyte sedimentation rate compared with that in the control rats. The radiographic examination revealed bone matrix resorption, considerable soft tissue swelling, periosteal new bone formation and bone erosion in the arthritic joints of the CIA rats. Histopathologically, the synovial joints of CIA rats were characterized by synovial hyperplasia, pannus formation, marked cellular infiltration, bone and cartilage erosion and narrowing of the joint space. The administration of an intradermal injection of only 200 µg bovine CII emulsified in IFA at the base of the tail therefore leads to the successful development of a CIA rat model. This well-characterized CIA rat model could be specifically used to study the pathophysiology of human rheumatoid arthritis as well as to test and develop anti-arthritic agents for humans. PMID:26622511

  13. The role of lipopolysaccharide injected systemically in the reactivation of collagen-induced arthritis in mice

    PubMed Central

    Yoshino, Shin; Ohsawa, Motoyasu

    2000-01-01

    We investigated the role of bacterial lipopolysaccharide (LPS) in the reactivation of autoimmune disease by using collagen-induced arthritis (CIA) in mice in which autoimmunity to the joint cartilage component type II collagen (CII) was involved.CIA was induced by immunization with CII emulsified with complete Freund's adjuvant at the base of the tail (day 0) followed by a booster injection on day 21. Varying doses of LPS from E. coli were i.p. injected on day 50.Arthritis began to develop on day 25 after immunization with CII and reached a peak on day 35. Thereafter, arthritis subsided gradually but moderate joint inflammation was still observed on day 50. An i.p. injection of LPS on day 50 markedly reactivated arthritis on a dose-related fashion. Histologically, on day 55, there were marked oedema of synovium which had proliferated by the day of LPS injection, new formation of fibrin, and intense infiltration of neutrophils accompanied with a large number of mononuclear cells. The reactivation of CIA by LPS was associated with increases in anti-CII IgG and IgG2a antibodies as well as various cytokines including IL-12, IFN-γ, IL-1β, and TNF-α. LPS from S. enteritidis, S. typhimurium, and K. neumoniae and its component, lipid A from E. coli also reactivated the disease. Polymyxin B sulphate suppressed LPS- or lipid A-induced reactivation of CIA.These results suggest that LPS may play an important role in the reactivation of autoimmune joint inflammatory diseases such as rheumatoid arthritis in humans. PMID:10742285

  14. Age-Related Differences in Collagen-Induced Arthritis: Clinical and Imaging Correlations

    PubMed Central

    Wilson-Gerwing, Tracy D; Pratt, Isaac V; Cooper, David M L; Silver, Tawni I; Rosenberg, Alan M

    2013-01-01

    Arthritis is among the most common chronic diseases in both children and adults. Although intraarticular inflammation is the feature common among all patients with chronic arthritis there are, in addition to age at onset, clinical characteristics that further distinguish the disease in pediatric and adult populations. In this study, we aimed to demonstrate the utility of microCT (µCT) and ultrasonography in characterizing pathologic age-related differences in a collagen-induced arthritis (CIA) rat model. Juvenile (35 d old) and young adult (91 d old) male Wistar rats were immunized with bovine type II collagen and incomplete Freund adjuvant to induce polyarthritis. Naïve male Wistar rats served as controls. All paws were scored on a scale of 0 (normal paw) to 4 (disuse of paw). Rats were euthanized at 14 d after the onset of arthritis and the hindpaws imaged by µCT and ultrasonography. Young adult rats had more severe signs of arthritis than did their juvenile counterparts. Imaging demonstrated that young adult CIA rats exhibited more widespread and severe skeletal lesions of the phalanges, metatarsals, and tarsal bones, whereas juvenile CIA rats had more localized and less proliferative and osteolytic damage that was confined predominantly to the phalanges and metatarsals. This report demonstrates the utility of imaging modalities to compare juvenile and young adult rats with CIA and provides evidence that disease characteristics and progression differ between the 2 age groups. Our observations indicate that the CIA model could help discern age-related pathologic processes in inflammatory joint diseases. PMID:24326225

  15. 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. PMID:25275987

  16. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 582.99...

  17. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 582.99...

  18. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide chemicals. 182.99...

  19. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  20. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 182.99...

  1. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Adjuvants for pesticide chemicals. 582.99...

  2. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 582.99...

  3. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  4. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide use dilutions. 172.710... Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower or applicant prior to application to...

  5. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Adjuvants for pesticide chemicals. 182.99...

  6. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  7. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) SUBSTANCES GENERALLY RECOGNIZED AS SAFE General Provisions § 182.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.910 and 40 CFR 180.920, which are added to... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Adjuvants for pesticide chemicals. 182.99...

  8. Effectiveness of spray adjuvants on reduction of spray drift

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...

  9. 21 CFR 172.710 - Adjuvants for pesticide use dilutions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide use dilutions. 172.710... HUMAN CONSUMPTION Other Specific Usage Additives § 172.710 Adjuvants for pesticide use dilutions. The following surfactants and related adjuvants may be safely added to pesticide use dilutions by a grower...

  10. 21 CFR 582.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99...

  11. 21 CFR 182.99 - Adjuvants for pesticide chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99...

  12. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    PubMed Central

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  13. Evolution of collagen arthritis in mice is arrested by treatment with anti-tumour necrosis factor (TNF) antibody or a recombinant soluble TNF receptor.

    PubMed Central

    Piguet, P F; Grau, G E; Vesin, C; Loetscher, H; Gentz, R; Lesslauer, W

    1992-01-01

    Immunization of DBA/1 mice with type II collagen within complete Freund's adjuvant leads to arthritis, lasting more than 3 months. Injection of anti-tumour necrosis factor (TNF) IgG, 2 and 3 weeks after immunization prevented the development of arthritis in the following months. This treatment had no effect when started 2 months after induction of the disease. A soluble form of the human recombinant TNF receptor type-beta (rsTNFR-beta), continuously infused at a rate of 20 micrograms/day during the second and third week after immunization, also had a long-term protective effect. Anti-TNF antibody had no effect upon the production of anti-type II collagen antibodies. These results indicate that TNF is critically involved in an early phase of this arthritis. Images Figure 1 Figure 2 PMID:1337334

  14. Induction of lupus autoantibodies by adjuvants

    USGS Publications Warehouse

    Satoh, M.; Kuroda, Y.; Yoshida, H.; Behney, K.M.; Mizutani, A.; Akaogi, J.; Nacionales, D.C.; Lorenson, T.D.; Rosenbauer, R.J.; Reeves, W.H.

    2003-01-01

    Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNF?? production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines. ?? 2003 Elsevier Ltd. All rights reserved.

  15. Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

    SciTech Connect

    Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

    2011-08-01

    Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

  16. Adjuvant steroids and relapse of typhoid fever.

    PubMed

    Cooles, P

    1986-10-01

    In a retrospective study, relapse after non-severe acute typhoid fever was highly significantly related to the use of adjuvant steroid in the initial illness. The steroid was given late and in small doses when compared with other studies. Caution should be observed when using steroids in this way as relapse though often mild may be a severe illness. PMID:3795323

  17. Aluminum vaccine adjuvants: are they safe?

    PubMed

    Tomljenovic, L; Shaw, C A

    2011-01-01

    Aluminum is an experimentally demonstrated neurotoxin and the most commonly used vaccine adjuvant. Despite almost 90 years of widespread use of aluminum adjuvants, medical science's understanding about their mechanisms of action is still remarkably poor. There is also a concerning scarcity of data on toxicology and pharmacokinetics of these compounds. In spite of this, the notion that aluminum in vaccines is safe appears to be widely accepted. Experimental research, however, clearly shows that aluminum adjuvants have a potential to induce serious immunological disorders in humans. In particular, aluminum in adjuvant form carries a risk for autoimmunity, long-term brain inflammation and associated neurological complications and may thus have profound and widespread adverse health consequences. In our opinion, the possibility that vaccine benefits may have been overrated and the risk of potential adverse effects underestimated, has not been rigorously evaluated in the medical and scientific community. We hope that the present paper will provide a framework for a much needed and long overdue assessment of this highly contentious medical issue. PMID:21568886

  18. 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 ...

  19. Genetics of psoriatic arthritis.

    PubMed

    O'Rielly, Darren D; Rahman, Proton

    2014-10-01

    Spondyloarthritis (SpA) represents a group of inflammatory rheumatic diseases that cluster within families and possess overlapping clinical features. The pathogenesis of SpA encompasses a complex array of genetic, immunological and environmental factors. In this article, we will briefly review the genetics of PsA, and then focus on the genes that may be potentially linked either directly or indirectly to the immunopathology of the Th-17 pathway. The most consistent and dominant genetic effect of PsV and PsA is located on chromosome 6p21.3 within the major histocompatibility complex (MHC) region, which accounts for approximately one-third of the genetic contribution of PsV and PsA. To date, 36 genes have reached genome-wide significance, accounting for approximately 22% of psoriasis (PsV) heritability. Prominent genes identified via GWAS include HLA-Cw6, IL12B, IL23R, IL23A, TNIP1, TNFAIP3, LCE3B-LCE3C, TRAF3IP2, NFkBIA, FBXL19, TYK2, IFIH1, REL, and ERAP1. Genes identified in psoriatic arthritis (PsA) has largely echoed those in PsV and include HLA-B/C, HLA-B, IL-12B, IL-23R, TNIP1, TRAF3IP2, FBXL19, and REL. The lack of identified genetic susceptibility loci is largely attributed to the much smaller number of PsA patients and the greater clinical heterogeneity of PsA. Searching for different types of genetic variants such as small CNVs and/or insertions/deletions has also led to the identification of several genes with a function relative to PsV in particular including DEFB4, LCE3C_LCE3B, and IL-22 gene (exon 1). The candidate genes identified in PsV/PsA have highlighted pathways of critical importance to psoriatic disease including distinct signaling pathways comprised of barrier integrity, innate immune response and adaptive immune response, mediated primarily by Th-17 and Th-1 signalling. While GWAS studies have yielded great insights into the genes that contribute to the pathogenesis of PsV and PsA, replication in large cohorts, fine-mapping and resequencing

  20. Laboratory Astrophysics Division of The AAS (LAD)

    NASA Astrophysics Data System (ADS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-10-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  1. Laboratory Astrophysics Division of the AAS (LAD)

    NASA Technical Reports Server (NTRS)

    Salama, Farid; Drake, R. P.; Federman, S. R.; Haxton, W. C.; Savin, D. W.

    2012-01-01

    The purpose of the Laboratory Astrophysics Division (LAD) is to advance our understanding of the Universe through the promotion of fundamental theoretical and experimental research into the underlying processes that drive the Cosmos. LAD represents all areas of astrophysics and planetary sciences. The first new AAS Division in more than 30 years, the LAD traces its history back to the recommendation from the scientific community via the White Paper from the 2006 NASA-sponsored Laboratory Astrophysics Workshop. This recommendation was endorsed by the Astronomy and Astrophysics Advisory Committee (AAAC), which advises the National Science Foundation (NSF), the National Aeronautics and Space Administration (NASA), and the U.S. Department of Energy (DOE) on selected issues within the fields of astronomy and astrophysics that are of mutual interest and concern to the agencies. In January 2007, at the 209th AAS meeting, the AAS Council set up a Steering Committee to formulate Bylaws for a Working Group on Laboratory Astrophysics (WGLA). The AAS Council formally established the WGLA with a five-year mandate in May 2007, at the 210th AAS meeting. From 2008 through 2012, the WGLA annually sponsored Meetings in-a-Meeting at the AAS Summer Meetings. In May 2011, at the 218th AAS meeting, the AAS Council voted to convert the WGLA, at the end of its mandate, into a Division of the AAS and requested draft Bylaws from the Steering Committee. In January 2012, at the 219th AAS Meeting, the AAS Council formally approved the Bylaws and the creation of the LAD. The inaugural gathering and the first business meeting of the LAD were held at the 220th AAS meeting in Anchorage in June 2012. You can learn more about LAD by visiting its website at http://lad.aas.org/ and by subscribing to its mailing list.

  2. 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

  3. Vitamins as influenza vaccine adjuvant components.

    PubMed

    Quintilio, Wagner; de Freitas, Fábio Alessandro; Rodriguez, Dunia; Kubrusly, Flavia Saldanha; Yourtov, Dimitri; Miyaki, Cosue; de Cerqueira Leite, Luciana Cezar; Raw, Isaias

    2016-10-01

    A number of adjuvant formulations were assayed in mice immunized with 3.75 µg of A/California/7/2009 (H1N1) pdm09 influenza vaccine with vitamins A, D and/or E in emulsions or B2 and/or B9 combined with Bordetella pertussis MPLA and/or alum as adjuvants. Squalene was used as positive control, as well as MPLA with alum. The immune response was evaluated by a panel of tests, including a hemagglutination inhibition (HAI) test, ELISA for IgG, IgG1, and IgG2a and IFN-γ, IL-2, IL-6 and IL-10 quantification in splenocyte culture supernatant after stimulus with influenza antigen. Immunological memory was evaluated using a 1/10 dose booster 60 days after the first immunization followed by assessment of the response by HAI, IgG ELISA, and determination of the antibody affinity index. The highest increases in HAI, IgG1 and IgG2a titers were obtained with the adjuvant combinations containing vitamin E, or the hydrophilic combinations containing MPLA and alum or B2 and alum. The IgG1/IgG2a ratio indicates that the response to the combination of B2 with alum would have more Th2 character than the combination of MPLA with alum. In an assay to investigate the memory response, a significant increase in HAI titer was observed with a booster vaccine dose at 60 days after immunization with vaccines containing MPLA with alum or B2 with alum. Overall, of the 27 adjuvant combinations, MPLA with alum and B2 with alum were the most promising adjuvants to be evaluated in humans. PMID:27449155

  4. Constitutive behavior of as-cast AA1050, AA3104, and AA5182

    NASA Astrophysics Data System (ADS)

    van Haaften, W. M.; Magnin, B.; Kool, W. H.; Katgerman, L.

    2002-07-01

    Recent thermomechanical modeling to calculate the stress field in industrially direct-chill (DC) cast-aluminum slabs has been successful, but lack of material data limits the accuracy of these calculations. Therefore, the constitutive behavior of three aluminum alloys (AA1050, AA3104, and AA5182) was determined in the as-cast condition using tensile tests at low strain rates and from room temperature to solidus temperature. The parameters of two constitutive equations, the extended Ludwik equation and a combination of the Sellars-Tegart equation with a hardening law, were determined. In order to study the effect of recovery, the constitutive behavior after prestraining at higher temperatures was also investigated. To evaluate the quantified constitutive equations, tensile tests were performed simulating the deformation and cooling history experienced by the material during casting. It is concluded that both constitutive equations perform well, but the combined hardening-Sellars-Tegart (HST) equation has temperature-independent parameters, which makes it easier to implement in a DC casting model. Further, the deformation history of the ingot should be taken into account for accurate stress calculations.

  5. 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

  6. 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

  7. Immune modulation of rheumatoid arthritis.

    PubMed

    Pappas, Dimitrios A; Geraldino-Pardilla, Laura; Bathon, Joan M

    2011-12-01

    The approval - several years ago - of the first tumour necrosis factor-α (TNF-α) inhibitor for the management of rheumatoid arthritis launched a new era in the therapeutics of rheumatology. Since then an almost cataclysmic discovery of new treatment targets and corresponding biologic agents ensued. Nowadays, the rheumatologist and the rheumatologic patient have the luxury of several immune modulators available to successfully treat the majority of patients with RA or other inflammatory arthritides and conditions. In this review we focus on a discussion of the approved immune modulators/biologic agents available for the treatment of rheumatoid arthritis. We also present an overview of agents under development. For the immune modulators discussed, we describe their mechanism of action and summarise initial data and recent updates on efficacy and safety. PMID:22265267

  8. 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

  9. AAS 228: Day 1 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Come visit astrobites at the AAS booth we have swag!Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto hear from undergrads who already know and love the site, educators who want to use it in their classrooms, and students who had not yet been introduced to astrobites and were excited about a new resource!For the rest of the meeting we will be stationed at theAAS booth in the exhibit hall (booth #211-213), so drop by if you want to learn more (or pick up swag: weve got lots of stickers and sunglasses)!Mondaymorning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended this morning.Opening Address(by Susanna Kohler)AAS President Meg Urry kicked off the meeting this morning at 8am with an overview of some of the great endeavors AAS is supporting. We astrobiters had personal motivation to drag ourselves out of bed that early: during this session, Urryannounced the new partnership between AAS and astrobites!Urry touched on some difficult topics in her welcome, including yesterdays tragedy in Orlando. Shereiteratedthe AASs support fortheCommittee for Sexual-Orientation and Gender Minorities in Astronomy (SGMA). She also reminded meeting attendees about the importance ofkeeping conference interactions professional, and pointed to the meetings anti-harassment policy.Partnership Announcement (by Michael Zevin)This morning, the American Astronomical Society announced the new partnership that it will have with Astrobites! We are beyond excited to embark on this new partnership with the

  10. Emerging immunotherapies for rheumatoid arthritis

    PubMed Central

    Reynolds, Gary; Cooles, Faye AH; Isaacs, John D; Hilkens, Catharien MU

    2014-01-01

    Novel treatments in development for rheumatoid arthritis target 3 broad areas: cytokines, cells, and signaling pathways. Therapies from each domain share common advantages (for example previously demonstrated efficacy, potential long-term immunomodulation, and oral administration respectively) that have stimulated research in each area but also common obstacles to their development. In this review recent progress in each area will be discussed alongside the factors that have impeded their path to clinical use. PMID:24535556

  11. [Interstitial granulomatous dermatitis with arthritis].

    PubMed

    Ebschner, U; Hartschuh, W; Petzoldt, D

    2000-02-01

    Interstitial granulomatous dermatitis with arthritis is a rare dermatologic disorder seen in patients suffering from diseases in which circulating immune complexes occur. The typical cutaneous signs are linear cords usually located on the lateral aspect of the trunk. The characteristic, although not specific, histology reveals a dense diffuse infiltrate composed mostly of histiocytes, accompanied by neutrophils and eosinophils, and degenerated collagen surrounded by palisades of histiocytes. We discuss this disorder and its differential diagnosis. PMID:10743580

  12. Transmission of systemic AA amyloidosis in animals.

    PubMed

    Murakami, T; Ishiguro, N; Higuchi, K

    2014-03-01

    Amyloidoses are a group of protein-misfolding disorders that are characterized by the deposition of amyloid fibrils in organs and/or tissues. In reactive amyloid A (AA) amyloidosis, serum AA (SAA) protein forms deposits in mice, domestic and wild animals, and humans that experience chronic inflammation. AA amyloid fibrils are abnormal β-sheet-rich forms of the serum precursor SAA, with conformational changes that promote fibril formation. Extracellular deposition of amyloid fibrils causes disease in affected animals. Recent findings suggest that AA amyloidosis could be transmissible. Similar to the pathogenesis of transmissible prion diseases, amyloid fibrils induce a seeding-nucleation process that may lead to development of AA amyloidosis. We review studies of possible transmission in bovine, avian, mouse, and cheetah AA amyloidosis. PMID:24280941

  13. Systemic Administration of Proteoglycan Protects BALB/c Retired Breeder Mice from Experimental Arthritis

    PubMed Central

    Ishikawa, Larissa Lumi Watanabe; Colavite, Priscila Maria; Fraga-Silva, Thais Fernanda de Campos; Mimura, Luiza Ayumi Nishiyama; França, Thais Graziela Donegá; Zorzella-Pezavento, Sofia Fernanda Gonçalves; Chiuso-Minicucci, Fernanda; Marcolino, Larissa Doddi; Marques, Camila; Ikoma, Maura Rosane Valerio; Sartori, Alexandrina

    2016-01-01

    This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γ and IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulated in vitro with PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3+ T cells. Lower TNF-α and IL-6 levels and higher expression of ROR-γ and GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis. PMID:27294161

  14. 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

  15. New generation adjuvants--from empiricism to rational design.

    PubMed

    O'Hagan, Derek T; Fox, Christopher B

    2015-06-01

    Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. PMID:26022561

  16. Combined treatment with low dose prednisone and escin improves the anti-arthritic effect in experimental arthritis.

    PubMed

    Du, Yuan; Song, Yanqin; Zhang, Leiming; Zhang, Menglin; Fu, Fenghua

    2016-02-01

    The present study was aimed at investigating whether low dose oral prednisone combined with escin could inhibit the progression of adjuvant-induced arthritis (AIA) in rats. Adjuvant arthritis was induced in SD rats began day 1 for 28 days. Prednisone at doses of 2, 10 mg/kg/day alone or escin at doses of 5, 10 mg/kg/day alone, or prednisone at dose of 2 mg/kg/day with escin at doses of 5 or 10 mg/kg/day were given to different groups of rats intragastrically from day 13 to 28 respectively. Paw swelling, arthritic index, histological and radiographic changes were assessed to evaluate the anti-arthritic effect. Weight growth, spleen and thymus indexes were also calculated. Serum samples were collected for estimation of pro-inflammatory cytokines. Rats developed erosive arthritis of the hind paw when immunized with adjuvant. Prednisone 2 mg/kg combined with escin 5 or 10 mg/kg significantly inhibited the paw swelling. Histopathological and radiographic analysis showed a marked decrease of synovial inflammatory infiltration, synovial hyperplasia and bone erosion by combination therapy, which also markedly suppressed the expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). No significant changes were found in monotherapy group except prednisone 10 mg/kg group. Furthermore, combined treatment rescued some of GCs' adverse effects evidenced by increase in body weight and decrease in index of spleen compared with untreated AIA rats. In conclusion, the combination therapy possessed synergistic anti-arthritic efficacy and reduced adverse effect, which may play a role in the management of human RA. PMID:26773773

  17. Recurrence of cervical spine instability in rheumatoid arthritis following previous fusion: can disease progression be prevented by early surgery?

    PubMed

    Agarwal, A K; Peppelman, W C; Kraus, D R; Pollock, B H; Stolzer, B L; Eisenbeis, C H; Donaldson, W F

    1992-09-01

    In a retrospective study, 110 patients with rheumatoid arthritis who had cervical spine fusion were evaluated for recurrence of cervical spine instability and resultant need for further surgery. Recurrence of cervical instability was correlated with initial radiographic abnormality, primary surgical procedure and interval between the 2 surgeries. There were 55 patients who had atlantoaxial subluxation (AAS) and required C1-C2 fusion as primary surgery. Three of these patients (5.5%) developed subaxial subluxation (SAS) and had a second procedure after a mean interval of 9 years. Twenty-two patients had AAS with superior migration of the odontoid (AAS-SMO) and had initial surgery of occiput-C3 fusion. Eight of these patients (36%) developed SAS and had a second surgery after a mean interval of 2.6 years. Of the 19 patients with primary radiographic deformity of SAS, one required further surgery for subluxation of an adjacent superior vertebra after a period of 6 years. Fourteen patients had combined deformity of AAS-SMO-SAS, and one required further surgery for SAS after an interval of 22 months. Recurrence of cervical instability following a previous fusion occurred in 15% of these 110 patients. It was seen in 5.5% of patients with initial deformity of AAS vs 36% of patients with AAS-SMO. No patients with C1-C2 fusion for AAS progressed to develop superior migration of the odontoid. We conclude that early C1-C2 fusion for AAS before development of SMO decreases the risk of further progression of cervical spine instability. The pattern of progression of cervical spine involvement, as discussed in the literature, is reviewed. PMID:1433002

  18. Hesperidin inhibits collagen-induced arthritis possibly through suppression of free radical load and reduction in neutrophil activation and infiltration.

    PubMed

    Umar, Sadiq; Kumar, Anubhav; Sajad, Mir; Zargan, Jamil; Ansari, Meraj; Ahmad, Sayeed; Katiyar, Chandra Kant; Khan, Haider A

    2013-03-01

    Rheumatoid arthritis is a chronic inflammatory disease characterized by the destruction of articular cartilage and bone in a chronic phase. Pathology of rheumatoid arthritis suggests autoimmunity linked to inflammation. In our study, rheumatoid arthritis was induced in Wistar rats by intradermal injections of 100 μl of emulsion containing bovine type II collagen in complete Freund's adjuvant at the base of the tail. Disease developed about 13 ± 1 days after immunization and treatment with hesperidin (HES) at a dose of 160 mg kg(-1) body weight was given after onset of disease daily until 20th day. The effect of treatment in the rats was monitored by clinical scoring, biochemical parameters and histological evaluations in joints. A steady increase in the articular elastase, nitric oxide and lipid peroxidation was observed in joints of arthritic rats as compared to control, whereas a significant decrease in reduced glutathione, superoxide dismutase activity and catalase was observed in collagen-induced arthritis rats as compared to control group. The results from the present work indicate that the treatment with hesperidin was effective in bringing about significant changes on all the parameters studied in collagen-induced arthritis rats. These data confirm that erosive destruction of the joint cartilage in collagen-induced arthritis is due free radicals released by activated neutrophils and produced by other biochemical pathways. In the present study, an attempt has been made to amelioration of the disease process by a natural product. These results suggest that oral administration of HES could be effective for treating human RA patients. PMID:22527139

  19. Potential of Vigna radiata (L.) sprouts in the management of inflammation and arthritis in rats: Possible biochemical alterations.

    PubMed

    Venkateshwarlu, E; Reddy, K Purnima; Dilip, D

    2016-01-01

    Vigna radiata (Fabaceae) is an important pulse crop widespread throughout the tropics and warm temperature regions. In this study, we evaluated the in vitro anti-inflammatory and in vivo antiarthritic activity of Vigna radiata sprouts in rats. The in vitro anti-inflammatory activity was determined by membrane stabilization and protein denaturation method. Whereas, the antiarthritic activity of the ethanolic extract of the sprouts was evaluated by complete Freund's adjuvant model with diclofenac sodium as the standard drug. Body weights, paw volume, biochemical parameters such as lipid peroxidation, total reduced glutathione, myeloperoxidase and lysosomal enzymes like cathepsin-D, N-acetyl β-D-glucosamindase and β-D-glucuronidase were estimated. Treatment with ethanolic extract of V. radiata exhibited significant membrane stabilization activity and protein denaturation activity, and significantly attenuated the biochemical changes induced by administration of complete Freund's adjuvant. The findings of the present study suggest the possible role of Vigna radiata in the therapeutics of arthritis. PMID:26891551

  20. The A3 adenosine receptor (A3AR): therapeutic target and predictive biological marker in rheumatoid arthritis.

    PubMed

    Fishman, Pnina; Cohen, Shira

    2016-09-01

    The Gi protein-associated A3 adenosine receptor (A3AR) is over-expressed in inflammatory cells, and this high expression is also reflected in the peripheral blood mononuclear cells of patients with autoimmune inflammatory diseases such as rheumatoid arthritis, psoriasis, and Crohn's disease. CF101, a selective agonist with high affinity to the A3AR, is known to induce robust anti-inflammatory effect in experimental animal models of adjuvant-, collagen-, and tropomyosin-induced arthritis. The effect is mediated via a definitive molecular mechanism entailing deregulation of the nuclear factor-κB (NF-κB) and the Wnt signal transduction pathways resulting in apoptosis of inflammatory cells. CF101 was found to be safe and well tolerated in all preclinical, phase I, and phase II human clinical studies. In two phase II clinical studies where CF101 was administered to rheumatoid arthritis (RA) patients as a stand-alone drug, a significant anti-rheumatic effect and a direct significant correlation were found between receptor expression at baseline and patients' response to the drug, suggesting that A3AR may be utilized as a predictive biomarker. The A3AR is a promising therapeutic target in rheumatoid arthritis and can be used also as a biological marker to predict patients' response to CF101. This is a unique type of a personalized medicine approach which may pave the way for a safe and efficacious treatment for this patient population. PMID:26886128

  1. Effects of Wutou Decoction on DNA Methylation and Histone Modifications in Rats with Collagen-Induced Arthritis

    PubMed Central

    Wen, Cai-Yu-Zhu; Chen, Zhe; Wang, Yu; Huang, Ying; Hu, Yong-Hong; Tu, Sheng-Hao

    2016-01-01

    Background. Wutou decoction (WTD) has been wildly applied in the treatment of rheumatoid arthritis and experimental arthritis in rats for many years. Epigenetic deregulation is associated with the aetiology of rheumatoid arthritis; however, the effects of WTD on epigenetic changes are unclear. This study is set to explore the effects of WTD on DNA methylation and histone modifications in rats with collagen-induced arthritis (CIA). Methods. The CIA model was established by the stimulation of collagen and adjuvant. The knee synovium was stained with hematoxylin and eosin. The DNA methyltransferase 1 (DNMT1) and methylated CpG binding domain 2 (MBD2) expression of peripheral blood mononuclear cells (PBMCs) were determined by Real-Time PCR. The global DNA histone H3-K4/H3-K27 methylation and total histones H3 and H4 acetylation of PBMCs were detected. Results. Our data demonstrated that the DNMT1 mRNA expression was significantly lowered in group WTD compared to that in group CIA (P < 0.05). The DNA methylation level was significantly reduced in group WTD compared to that in group CIA (P < 0.05). Moreover, H3 acetylation of PBMCs was overexpressed in WTD compared with CIA (P < 0.05). Conclusions. WTD may modulate DNA methylation and histone modifications, functioning as anti-inflammatory potential. PMID:27042192

  2. Immunosuppressive activity of deer antler extracts of Cervus korean TEMMINCK var. mantchuricus Swinhoe, on type II collagen-induced arthritis.

    PubMed

    Kang, Sung-Koo; Kim, Kap-Sung; Kim, Sung-Il; Chung, Kang-Hyun; Lee, In-Seon; Kim, Cheorl-Ho

    2006-01-01

    Unossified horn or pilose antler cut from deer, which belong to the Cervidae generally is termed Nokyong. Nokyong is one of the most famous Korean traditional medicines and has been considered to possess sexual-reinforcing and antiaging actions. In this study, water extract of deer antler extract (DAA) prepared from the growing antler of Cervus korean TEMMINCK var. mantchuricus Swinhoe was used to investigate the efficacy of the DAA on the development of type II collagen (CII)-induced arthritis (CIA) in rats. Male rats were immunized with an emulsion of 200 microg of CII and complete Freund's adjuvant (CFA). The rats then were administered by injection a suspension of DAA or phosphate-buffered saline. The effect of DAA on cellular responses to CII was examined. The injection of DAA suppressed the CII-specific secretion of interferon (IFN)-gamma from splenocytes ex vivo. The influence of DAA also was evaluated on the incidence and development of arthritis in rat CIA. Rats were immunized twice at a 3-wk interval with bovine CII, with DAA being given by injection once a d for 14 d with four different regimens. A 14-d course of DAA treatment at a daily dose of 100 microg/kg, which began on the d of the first CII immunization, suppressed the development of arthritis, as well as antibody formation and delayed-type hypersensitivity to CII. Treatment with DAA resulted in inhibition of development of arthritis and immune responses to CII. PMID:16759146

  3. Effects of Wutou Decoction on DNA Methylation and Histone Modifications in Rats with Collagen-Induced Arthritis.

    PubMed

    Liu, Ya-Fei; Wen, Cai-Yu-Zhu; Chen, Zhe; Wang, Yu; Huang, Ying; Hu, Yong-Hong; Tu, Sheng-Hao

    2016-01-01

    Background. Wutou decoction (WTD) has been wildly applied in the treatment of rheumatoid arthritis and experimental arthritis in rats for many years. Epigenetic deregulation is associated with the aetiology of rheumatoid arthritis; however, the effects of WTD on epigenetic changes are unclear. This study is set to explore the effects of WTD on DNA methylation and histone modifications in rats with collagen-induced arthritis (CIA). Methods. The CIA model was established by the stimulation of collagen and adjuvant. The knee synovium was stained with hematoxylin and eosin. The DNA methyltransferase 1 (DNMT1) and methylated CpG binding domain 2 (MBD2) expression of peripheral blood mononuclear cells (PBMCs) were determined by Real-Time PCR. The global DNA histone H3-K4/H3-K27 methylation and total histones H3 and H4 acetylation of PBMCs were detected. Results. Our data demonstrated that the DNMT1 mRNA expression was significantly lowered in group WTD compared to that in group CIA (P < 0.05). The DNA methylation level was significantly reduced in group WTD compared to that in group CIA (P < 0.05). Moreover, H3 acetylation of PBMCs was overexpressed in WTD compared with CIA (P < 0.05). Conclusions. WTD may modulate DNA methylation and histone modifications, functioning as anti-inflammatory potential. PMID:27042192

  4. Polyclonal Th1 cells transfer oil-induced arthritis.

    PubMed Central

    Svelander, L; Müssener, A; Erlandsson-Harris, H; Kleinau, S

    1997-01-01

    T-cells play a critical role in oil-induced arthritis (OIA) in DA rats. The present study focuses on the involvement of CD4/CD8 T cells in OIA by using adoptive transfer. Mitogen-activated T cells from DA rats previously injected with incomplete Freund's adjuvant (IFA) were depleted of CD4+ T cells or CD8+ T cells before transfer to irradiated naive receipients. The results indicate that CD4+ T cells are essential for the induction of passively induced OIA. However, in vitro blocking experiments with monoclonal antibodies (mAb) to the CD4 molecule of the T cells before transfer did not affect the passive OIA. Neither was passive OIA inhibited by treating the CD4+ T cells with mAb to intracellular adhesion molecule-1 (ICAM-1) in order to block cell-cell interactions or migration. The arthritogenic CD4+ T cells were sensitive, however, to in vitro treatment with mAb to the interleukin-2 receptor, which inhibited the disease or delayed the onset of passive OIA in recipients. The arthritogenic CD4+ T cells were also analysed for expression of specific T-cell receptor (TCR) variable (V) beta chains, critical for recognition of autoantigen, by utilizing V beta gene-specific polymerase chain reaction (PCR). The results show a heterogeneous expression of V beta segments of the TCR, indicating a polyclonal origin of the pathogenic cells. Moreover, an investigation of the T helper (Th)1/Th2 status of the CD4+ T cells, defined by cytokine expression, was made at the mRNA level by using in situ hybridization. High numbers of interleukin-2 (IL-2) mRNA expressing cells and also interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha)-expressing cells could be identified. We conclude from this study that non-immunogenic IFA triggers polyclonal, IL-2-dependent Th1 cells which induce arthritis. The contribution of the CD4 or ICAM-1 molecules for arthritis induction seem to be of minor importance. PMID:9227326

  5. The adjuvancy of silicones: dependency on compartmentalization.

    PubMed

    Klykken, P C; White, K L

    1996-01-01

    Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response. PMID:8565549

  6. Psychosocial and Physical Effects of Adjuvant Chemotherapy

    PubMed Central

    Hislop, Thomas Gregory; Elwood, J. Mark; Waxler-Morrison, Nancy; Ragaz, Joseph; Skippen, Diane Hazel; Turner, I.D.

    1991-01-01

    Breast cancer patients younger than 55 completed a questionnaire on psychosocial factors and physical side effects shortly after diagnosis and 9 to 15 months after diagnosis. Those who had used adjuvant chemotherapy were more likely than those who had not to report physical side effects; there was little difference in psychosocial factors. Recent users were more likely than ex-users to report physical side effects, difficulties with domestic chores, and improvement in psychosocial factors. PMID:21229020

  7. AAS 228: Day 3 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Wikipedia Year of Science Editathon (by Meredith Rawls)Whats your first go-to source for an unfamiliar topic on the internet? If you said Wikipedia, youre not alone. For many people, Wikipedia is the primary source of information about astronomy and science. However, many Wikipedia articles about science topics are incomplete or missing, and women are underrepresented among scientists with biographies.To address this, the AAS Astronomy Education Board teamed up with the Wiki Education Foundation to host an edit-a-thon as part of the Wikipedia Year of Science. More than forty attendees spent the better part of three hours working through tutorials, creating new articles, and editing existing ones. The session was generously sponsored by the Simons Foundation.The Year of Science initiative seeks to bring Wikipedia editing skills to the classroom and help new editors find sustainable ways to contribute to Wikipedia in the long term. Anybody can create a free account and start editing!As a first-time Wikipedia contributor, I took the time to go through nearly all the tutorial exercises and familiarize myself with the process of editing a page. I decided to flesh out one section in an existing page about asteroseismology. Others created biography pages from scratch or selected various astronomical topics to write about. To me, the editing process felt like a cross between writing a blog post and a journal article, in a hack day type environment. Working through the tutorial and some examples renewed my empathy for learners who are tackling a new skill set for the first time. A full summary of our

  8. Bacillus thuringiensis subsp. israelensis Cyt1Aa synergizes Cry11Aa toxin by functioning as a membrane-bound receptor.

    PubMed

    Pérez, Claudia; Fernandez, Luisa E; Sun, Jianguang; Folch, Jorge Luis; Gill, Sarjeet S; Soberón, Mario; Bravo, Alejandra

    2005-12-20

    Bacillus thuringiensis subsp. israelensis produces crystal proteins, Cry (4Aa, 4Ba, 10Aa, and 11Aa) and Cyt (1Aa and 2Ba) proteins, toxic to mosquito vectors of human diseases. Cyt1Aa overcomes insect resistance to Cry11Aa and Cry4 toxins and synergizes the toxicity of these toxins. However, the molecular mechanism of synergism remains unsolved. Here, we provide evidence that Cyt1Aa functions as a receptor of Cry11Aa. Sequential-binding analysis of Cyt1Aa and Cry11Aa revealed that Cyt1Aa binding to Aedes aegypti brush border membrane vesicles enhanced the binding of biotinylated-Cry11Aa. The Cyt1Aa- and Cry11Aa-binding epitopes were mapped by means of the yeast two-hybrid system, peptide arrays, and heterologous competition assays with synthetic peptides. Two exposed regions in Cyt1Aa, loop beta6-alphaE and part of beta7, bind Cry11Aa. On the other side, Cry11Aa binds Cyt1Aa proteins by means of domain II-loop alpha8 and beta-4, which are also involved in midgut receptor interaction. Characterization of single-point mutations in Cry11Aa and Cyt1Aa revealed key Cry11Aa (S259 and E266) and Cyt1Aa (K198, E204 and K225) residues involved in the interaction of both proteins and in synergism. Additionally, a Cyt1Aa loop beta6-alphaE mutant (K198A) with enhanced synergism to Cry11Aa was isolated. Data provided here strongly indicates that Cyt1Aa synergizes or suppresses resistance to Cry11Aa toxin by functioning as a membrane-bound receptor. Bacillus thuringiensis subsp. israelensis is a highly effective pathogenic bacterium because it produces a toxin and also its functional receptor, promoting toxin binding to the target membrane and causing toxicity. PMID:16339907

  9. AAS 228: Day 3 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Wikipedia Year of Science Editathon (by Meredith Rawls)Whats your first go-to source for an unfamiliar topic on the internet? If you said Wikipedia, youre not alone. For many people, Wikipedia is the primary source of information about astronomy and science. However, many Wikipedia articles about science topics are incomplete or missing, and women are underrepresented among scientists with biographies.To address this, the AAS Astronomy Education Board teamed up with the Wiki Education Foundation to host an edit-a-thon as part of the Wikipedia Year of Science. More than forty attendees spent the better part of three hours working through tutorials, creating new articles, and editing existing ones. The session was generously sponsored by the Simons Foundation.The Year of Science initiative seeks to bring Wikipedia editing skills to the classroom and help new editors find sustainable ways to contribute to Wikipedia in the long term. Anybody can create a free account and start editing!As a first-time Wikipedia contributor, I took the time to go through nearly all the tutorial exercises and familiarize myself with the process of editing a page. I decided to flesh out one section in an existing page about asteroseismology. Others created biography pages from scratch or selected various astronomical topics to write about. To me, the editing process felt like a cross between writing a blog post and a journal article, in a hack day type environment. Working through the tutorial and some examples renewed my empathy for learners who are tackling a new skill set for the first time. A full summary of our

  10. Melanoma and IFN alpha: potential adjuvant therapy.

    PubMed

    Bottoni, U; Clerico, R; Paolino, G; Corsetti, P; Ambrifi, M; Brachini, A; Richetta, A; Nisticò, S; Pranteda, G; Calvieri, S

    2014-01-01

    Interferon alpha (IFNalpha) is the most used adjuvant treatment in clinical practice for melanoma (MEL) high-medium risk patients; however, the use of IFNalpha has yielded conflicting data on Overall Survival (OS) and disease free survival (DFS) rates. Starting from these considerations, we carried out an analysis on our MEL patients who received adjuvant IFNalpha therapy, in order to identify possible predictors for their outcome. A total of 140 patients were included in our analysis. Patients with Breslow thickness ≤2.00 mm presented a significantly longer mean DFS than patients with Breslow ≥2.01 mm (p = 0.01). Using non- parametric Spearman’s Coefficient test we found association between DFS and Breslow thickness (p < 0.001) and between DFS and ulceration (p = 0.03). Performing Multiple Regression test, Breslow thickness (p < 0.001) remained the only statistically significant predictor. From the OS analysis we found that patients with lower Breslow values ≤ 2.00 mm (p < 0.0001), and absence of ulceration (p <0.004) showed a significantly better long-term survival. From the current analysis we found that the use of low dose IFNalpha is justified only for cutaneous melanoma ≤ 4.01 mm that was not ulcerated; patients with Breslow ≥ 4.01 mm, in our opinion, should not carry out adjuvant treatment with low dose IFNalpha, because its side effects could be higher than the its benefits. PMID:25001659

  11. Utility of adjuvant systemic therapy in melanoma

    PubMed Central

    Eggermont, A. M. M.; Testori, A.; Marsden, J.; Hersey, P.; Quirt, I.; Petrella, T.; Gogas, H.; MacKie, R. M.; Hauschild, A.

    2009-01-01

    The lack of effective drugs in stage IV melanoma has impacted the effectiveness of adjuvant therapies in stage II/III disease. To date, chemotherapy, immunostimulants and vaccines have been used with minimal success. Interferon (IFN) has shown an effect on relapse-free survival (RFS) in several clinical trials; however, without a clinically significant effect on overall survival (OS). A recently conducted meta-analysis demonstrated prolongation of disease-free survival (DFS) in 7% and OS benefit in 3% of IFN-treated patients when compared with observation-only patients. There were no clear differences for the dose and duration of treatment observed. Observation is still an appropriate control arm in adjuvant clinical trials. Regional differences exist in Europe in the adjuvant use of IFN. In Northwest Europe, IFN is infrequently prescribed. In Central and Mediterranean Europe, dermatologists commonly prescribe low-dose IFN therapy for AJCC stage II and III disease. High-dose IFN regimens are not commonly used. The population of patients that may benefit from IFN needs to be further characterised, potentially by finding biomarkers that can predict response. Such studies are ongoing. PMID:19617295

  12. Adjuvant and neoadjuvant treatment in pancreatic cancer

    PubMed Central

    Herreros-Villanueva, Marta; Hijona, Elizabeth; Cosme, Angel; Bujanda, Luis

    2012-01-01

    Pancreatic adenocarcinoma is one of the most aggressive human malignancies, ranking 4th among causes for cancer-related death in the Western world including the United States. Surgical resection offers the only chance of cure, but only 15 to 20 percent of cases are potentially resectable at presentation. Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy. Currently there is no consensus around the world on what constitutes “standard” adjuvant therapy for pancreatic cancer. This controversy derives from several studies, each fraught with its own limitations. Standards of care also vary somewhat with regard to geography and economy, for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe. Regardless of the efforts in adjuvant and neoadjuvant improved therapy, the major goal to combat pancreatic cancer is to find diagnostic markers, identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients. In this review, authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients. PMID:22529684

  13. Efficacy of live adjuvanted mesogenic Newcastle disease vaccine in chickens.

    PubMed

    Roy, P; Venugopalan, A T; Koteeswaran, A

    1999-06-01

    120 white leghorn chickens primed with a lentogenic Newcastle disease (ND) live vaccine at 7 days of age were divided into three equal groups of 8 weeks of age and vaccinated with a live mesogenic ND vaccine (NDV). One group received only Newcastle disease mesogenic vaccine (RDVK) in normal saline, the second group received RDVK with groundnut oil as adjuvant and the third group received RDVK with liquid paraffin as adjuvant. Sera were collected at different time points for the assessment of antibody level against ND virus (NDV) by the haemagglutination inhibition (HI) test. The commonly used non-adjuvanted RDVK could not evince 100% protective HI titre beyond 11 weeks of age but in both the adjuvanted groups 100% protective HI titre was evident up to 20 weeks of age. On challenge at 20 weeks of age both the adjuvanted groups withstood challenge but in the non-adjuvanted group 80% of chickens withstood the challenge. A significant difference in immune response between the adjuvanted and non-adjuvanted groups was seen but not between both the adjuvanted groups. The advantage of vegetable oil (groundnut oil) as an adjuvant for live mesogenic ND vaccine has been discussed. PMID:10418918

  14. Recent Advances of Vaccine Adjuvants for Infectious Diseases

    PubMed Central

    Nguyen, Minh Trang

    2015-01-01

    Vaccines are the most effective and cost-efficient method for preventing diseases caused by infectious pathogens. Despite the great success of vaccines, development of safe and strong vaccines is still required for emerging new pathogens, re-emerging old pathogens, and in order to improve the inadequate protection conferred by existing vaccines. One of the most important strategies for the development of effective new vaccines is the selection and usage of a suitable adjuvant. Immunologic adjuvants are essential for enhancing vaccine potency by improvement of the humoral and/or cell-mediated immune response to vaccine antigens. Thus, formulation of vaccines with appropriate adjuvants is an attractive approach towards eliciting protective and long-lasting immunity in humans. However, only a limited number of adjuvants is licensed for human vaccines due to concerns about safety and toxicity. We summarize current knowledge about the potential benefits of adjuvants, the characteristics of adjuvants and the mechanisms of adjuvants in human vaccines. Adjuvants have diverse modes of action and should be selected for use on the basis of the type of immune response that is desired for a particular vaccine. Better understanding of current adjuvants will help exploring new adjuvant formulations and facilitate rational design of vaccines against infectious diseases. PMID:25922593

  15. Intraarticular corticosteroids in refractory childhood Lyme arthritis.

    PubMed

    Nimmrich, S; Becker, I; Horneff, G

    2014-07-01

    Lyme arthritis caused by infection with Borrelia burgdorferi is a common late manifestation of Lyme borreliosis. Current treatment recommendations include at least one oral or intravenous antibiotic course, followed by antirheumatic therapy in case of refractory arthritis. We reviewed the course of 31 children with Lyme arthritis who had received antibiotic treatment and assessed outcome and requirement of antirheumatic therapy. Of a total of 31 patients, 23 (74%) showed complete resolution of arthritis after one or two courses of antibiotics, whereas in 8 patients (28%), steroid injections had been performed due to relapsing or remaining symptoms. All of these 8 patients showed immediate resolution of symptoms after intraarticular steroid injections. Four of them (50%) remained asymptomatic so far with a follow-up period between five up to 40 months. In two cases, multiple intraarticular corticosteroid injections were required; three patients received additional or consecutive treatment with systemic antirheumatic treatment. Patients with antibiotic refractory arthritis showed a higher rate of positivity of the IgG p58 and OspC immunoblot bands (p = 0.05) at presentation. Antibodies against OspA, an indicator of later stage infection, occurred more frequently in the refractory group without reaching significant level. No clinical marker as indicator for severe or prolonged course of Lyme arthritis was identifiable. A quarter of childhood Lyme arthritis patients were refractory to antibiotics and required antirheumatic treatment. Intraarticular steroid injections in childhood Lyme arthritis refractory to antibiotics can lead to marked clinical improvement. PMID:24390634

  16. Adjuvant chemotherapy for early-stage cervical cancer

    PubMed Central

    Asano, Hiroshi; Todo, Yukiharu; Watari, Hidemichi

    2016-01-01

    The aim of this review is to address the current status of adjuvant chemotherapy alone in early-stage cervical cancer treatments in the literature. At present, the therapeutic effect of adjuvant chemotherapy alone after radical surgery (RS) has not yet been established, and radiation therapy (RT) or concurrent chemoradiotherapy (CCRT) is recommended as the standard adjuvant therapy after RS for early-stage cervical cancer in various guidelines. The main purpose of adjuvant therapy after RS, however, should be to reduce extrapelvic recurrence rather than local recurrence, although adjuvant RT or CCRT has survival benefits for patients with intermediate- or high-risk factors for recurrence. Moreover, several studies reported that adjuvant therapies including RT were associated with a higher incidence of complications, such as lymphedema, bowel obstruction and urinary disturbance, and a lower grade of long-term quality of life (QOL) or sexual functioning than adjuvant chemotherapy alone. The effect of adjuvant chemotherapy alone for early-stage cervical cancer with intermediate- or high-risk factors for recurrence were not fully investigated in prospective studies, but several retrospective studies suggest that the adjuvant effects of chemotherapy alone are at least similar to that of RT or CCRT in terms of recurrence rate, disease-free survival, or overall survival (OS) with lower incidence of complications. Whereas cisplatin based combination regimens were used in these studies, paclitaxel/cisplatin (TP) regimen, which is currently recognized as a standard chemotherapy regimen for patients with metastatic, recurrent or persistent cervical cancer by Gynecologic Oncology Group (GOG), had also survival benefit as an adjuvant therapy. Therefore, it may be worth considering a prospective randomized controlled trial (RCT) of adjuvant chemotherapy alone using TP regimen versus adjuvant RT as an alternative adjuvant therapy. Because early-stage cervical cancer is a curable

  17. Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer

    PubMed Central

    2011-01-01

    Background Several studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women. Methods To establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated. Results A significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor

  18. Brucellar sternoclavicular arthritis, the forgotten complication.

    PubMed

    Mousa, A M; Muhtaseb, S A; Al-Mudallal, D S; Marafie, A A; Habib, F M

    1988-06-01

    Of 511 cases of brucellosis studied between December 1983 and February 1986, four (0.8%) had sternoclavicular (STCL) arthritis. Two were male and two female, and only one was younger than 50 years old. All four cases had significantly high specific IgG antibody titres (1 of 1280), measured by the indirect immunofluorescent (IIF) test, and two had Brucella melitensis isolated from their blood. In two cases, STCL arthritis was the presenting problem, and it was associated in one with ankle arthritis, hepatitis, renal impairment, orogenital ulcers and a haematological picture of myelodysplasia; in the other it was a relapsing STCL arthritis. In the remaining two cases, STCL arthritis was part of an extensive osteoarticular disease, which was associated in one with cachexia, liver cirrhosis, heart failure and prostatitis with urine retention, and in the other with severe thrombocytopenia. Excellent results were obtained from six to eight weeks' therapy with streptomycin, rifampicin and cotrimoxazole or tetracycline. PMID:3250341

  19. 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.

  20. 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. PMID:15887257

  1. Interface Formation During Fusion™ Casting of AA3003/AA4045 Aluminum Alloy Ingots

    NASA Astrophysics Data System (ADS)

    Di Ciano, Massimo; Caron, E. J. F. R.; Weckman, D. C.; Wells, M. A.

    2015-12-01

    Fusion™ casting is a unique Direct Chill continuous casting process whereby two different alloys can be cast simultaneously, producing a laminated ingot for rolling into clad sheet metal such as AA3003/AA4045 brazing sheet. Better understanding of the wetting and interface formation process during Fusion™ casting is required to further improve process yields and also explore use of other alloy systems for new applications. In this research, AA3003-core/AA4045-clad ingots were cast using a well-instrumented lab-scale Fusion™ casting system. As-cast Fusion™ interfaces were examined metallurgically and by mechanical testing. Computational fluid dynamic analyses of the FusionTM casts were also performed. It was shown that the liquid AA4045-clad alloy was able to successfully wet and create an oxide-free, metallurgical, and mechanically sound interface with the lightly oxidized AA3003-core shell material. Based on the results of this study, it is proposed that the bond formation process at the alloys interface during casting is a result of discrete penetration of AA4045 liquid at defects in the preexisting AA3003 oxide, dissolution of underlying AA3003 by liquid AA4045, and subsequent bridging between penetration sites. Spot exudation on the AA3003 chill cast surface due to remelting and inverse segregation may also improve the wetting and bonding process.

  2. 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

  3. AAS 228: Day 1 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Come visit astrobites at the AAS booth we have swag!Things kicked off last night at our undergraduate reception booth. Thanks to all of you who stopped by we were delightedto hear from undergrads who already know and love the site, educators who want to use it in their classrooms, and students who had not yet been introduced to astrobites and were excited about a new resource!For the rest of the meeting we will be stationed at theAAS booth in the exhibit hall (booth #211-213), so drop by if you want to learn more (or pick up swag: weve got lots of stickers and sunglasses)!Mondaymorning was the official start of the meeting. Here are just a few of the talks and workshops astrobiters attended this morning.Opening Address(by Susanna Kohler)AAS President Meg Urry kicked off the meeting this morning at 8am with an overview of some of the great endeavors AAS is supporting. We astrobiters had personal motivation to drag ourselves out of bed that early: during this session, Urryannounced the new partnership between AAS and astrobites!Urry touched on some difficult topics in her welcome, including yesterdays tragedy in Orlando. Shereiteratedthe AASs support fortheCommittee for Sexual-Orientation and Gender Minorities in Astronomy (SGMA). She also reminded meeting attendees about the importance ofkeeping conference interactions professional, and pointed to the meetings anti-harassment policy.Partnership Announcement (by Michael Zevin)This morning, the American Astronomical Society announced the new partnership that it will have with Astrobites! We are beyond excited to embark on this new partnership with the

  4. Food-induced (allergic) arthritis. Inflammatory arthritis exacerbated by milk.

    PubMed

    Panush, R S; Stroud, R M; Webster, E M

    1986-02-01

    Suggestive, but largely unproven, observations have associated arthritis with environmental antigens, including foods. We studied a patient with inflammatory arthritis in a prospective, "blinded," controlled fashion to determine whether her symptoms were associated with food sensitivities. This 52-year-old white woman with 11 years of class I, stage I, active disease, had symptomatic exacerbations allegedly associated with meat, milk, and beans. We observed an increase in symptoms following an unblinded food challenge and then studied her in our clinical research unit. On her normal diet for 6 days, she averaged 30 minutes of morning stiffness, 9 tender joints, 3 swollen joints, 87% subjective assessment (100% = best possible), and 89% examiner assessment. While she was fasting (3 days) or taking Vivonex (2 days), we noted no morning stiffness, tender joint score of 1, swollen joint score of 0, and assessments of 100% (P less than 0.05 versus normal diet). She was then nourished with Vivonex for 33 days without difficulty and challenged in a blinded fashion at mealtimes with lyophilized foods placed into opaque capsules. Four milk challenges (equivalent to greater than or equal to 8 ounces per meal) produced up to 30 minutes of morning stiffness, 14 tender joints, 4 swollen joints, subjective assessment of 85%, and objective assessment of 80% (P less than 0.05 versus fasting-Vivonex), peaking 24-48 hours postchallenge. Placebo and other foods (lettuce and carrots) were without effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3513771

  5. Working together: interactions between vaccine antigens and adjuvants

    PubMed Central

    Kramer, Ryan M.; Barnes V, Lucien; Dowling, Quinton M.; Vedvick, Thomas S.

    2013-01-01

    The development of vaccines containing adjuvants has the potential to enhance antibody and cellular immune responses, broaden protective immunity against heterogeneous pathogen strains, enable antigen dose sparing, and facilitate efficacy in immunocompromised populations. Nevertheless, the structural interplay between antigen and adjuvant components is often not taken into account in the published literature. Interactions between antigen and adjuvant formulations should be well characterized to enable optimum vaccine stability and efficacy. This review focuses on the importance of characterizing antigen–adjuvant interactions by summarizing findings involving widely used adjuvant formulation platforms, such as aluminum salts, emulsions, lipid vesicles, and polymer-based particles. Emphasis is placed on the physicochemical basis of antigen–adjuvant associations and the appropriate analytical tools for their characterization, as well as discussing the effects of these interactions on vaccine potency. PMID:24757512

  6. Adjuvant chemotherapy for rectal cancer: Is it needed?

    PubMed Central

    Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

    2015-01-01

    Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

  7. Imaging techniques in childhood arthritis.

    PubMed

    Harcke, H T; Mandell, G A; Cassell, I L

    1997-08-01

    Technological advances in imaging have given physicians caring for children with arthritis a greater opportunity to detect abnormalities early in the course of a disease and better methods for monitoring chronic changes. Indications for using radiography, bone densitometry, nuclear medicine, ultrasound, CT scanning, and MR imaging are discussed in this article. In this era of managed care, the practicing clinician is urged more than ever to consult with the radiologist in selecting the study or sequence of studies to be used in particular case. In this way, evaluation can be limited to the most effective strategy from both the clinical and cost perspectives. PMID:9287376

  8. Arthritis in the Durer family.

    PubMed

    Weisz, George M

    2007-01-01

    Deciphering the secret language of painters became a discipline into which Art historians have branched ever since the Renaissance. Various aspects of paintings and sculptures were decoded in this process. This decoding system remains however incomplete without interpreting also the medical conditions that appear in the painted subjects. History of Medicine and of Arts could be both enriched by diagnosing retrospectively diseases existent in that historical period; by identifying portraits or describing genetic family diseases. One such case is the arthritis identifiable in three out of four artists in the Durer family, visible in paintings or engravings of the early 16-th century. PMID:17943408

  9. Rational design of small molecules as vaccine adjuvants.

    PubMed

    Wu, Tom Y-H; Singh, Manmohan; Miller, Andrew T; De Gregorio, Ennio; Doro, Francesco; D'Oro, Ugo; Skibinski, David A G; Mbow, M Lamine; Bufali, Simone; Herman, Ann E; Cortez, Alex; Li, Yongkai; Nayak, Bishnu P; Tritto, Elaine; Filippi, Christophe M; Otten, Gillis R; Brito, Luis A; Monaci, Elisabetta; Li, Chun; Aprea, Susanna; Valentini, Sara; Calabrό, Samuele; Laera, Donatello; Brunelli, Brunella; Caproni, Elena; Malyala, Padma; Panchal, Rekha G; Warren, Travis K; Bavari, Sina; O'Hagan, Derek T; Cooke, Michael P; Valiante, Nicholas M

    2014-11-19

    Adjuvants increase vaccine potency largely by activating innate immunity and promoting inflammation. Limiting the side effects of this inflammation is a major hurdle for adjuvant use in vaccines for humans. It has been difficult to improve on adjuvant safety because of a poor understanding of adjuvant mechanism and the empirical nature of adjuvant discovery and development historically. We describe new principles for the rational optimization of small-molecule immune potentiators (SMIPs) targeting Toll-like receptor 7 as adjuvants with a predicted increase in their therapeutic indices. Unlike traditional drugs, SMIP-based adjuvants need to have limited bioavailability and remain localized for optimal efficacy. These features also lead to temporally and spatially restricted inflammation that should decrease side effects. Through medicinal and formulation chemistry and extensive immunopharmacology, we show that in vivo potency can be increased with little to no systemic exposure, localized innate immune activation and short in vivo residence times of SMIP-based adjuvants. This work provides a systematic and generalizable approach to engineering small molecules for use as vaccine adjuvants. PMID:25411473

  10. [Recent advance in adjuvant therapy for breast cancer].

    PubMed

    Shimizu, Chikako; Watanabe, Toru

    2002-12-01

    Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467

  11. Modern Vaccines/Adjuvants Formulation—Session 2 (Plenary II)

    PubMed Central

    Collin, Nicolas

    2013-01-01

    On the 15–17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies. PMID:23966098

  12. Sulfasalazine and its metabolites inhibit platelet function in patients with inflammatory arthritis.

    PubMed

    MacMullan, Paul A; Madigan, Anne M; Paul, Nevin; Peace, Aaron J; Alagha, Ahmed; Nolan, Kevin B; McCarthy, Geraldine M; Kenny, Dermot

    2016-02-01

    The purpose of this study is to assess the effect of sulfasalazine and its metabolites on platelet function in patients with inflammatory arthritis (IA). One hundred thirty-five consecutive patients with an established diagnosis of IA were screened. Those with a history of cardiovascular disease (CVD), taking anti-platelet agents or non-steroidal anti-inflammatory drugs (NSAIDs) were excluded. A total of 32 patients were investigated, 15 taking sulfasalazine and 17 taking other disease-modifying anti-rheumatic drugs (DMARDs) and no sulfasalazine. These two cohorts were compared to 15 patients with stable CVD on long-term aspirin. The effect of sulfasalazine and its metabolites on arachidonic acid (AA)-induced platelet aggregation was also tested in vitro in samples from healthy donors (n = 18). Demographics, CVD risk factors and disease activity indices were similar in the sulfasalazine and other DMARD groups. AA-induced platelet aggregation was significantly inhibited in the sulfasalazine group (9 ± 7 %) and comparable to that in the aspirin group (10 ± 6 %). In contrast, there was no effect on AA-induced platelet aggregation in the other DMARDs group (77 ± 12 %) (p < 0.001). Furthermore, sulfasalazine therapy had no effect on platelet aggregation in response to multiple other agonists. Sulfasalazine and its metabolites (5-aminosalicylic acid and sulfapyridine) exerted an additive and dose-dependent inhibitory effect on AA-induced platelet aggregation in vitro (p < 0.001). The inhibition of AA-induced platelet aggregation by sulfasalazine is comparable to that achieved by aspirin and is dependent on both sulfasalazine and its metabolites. This represents a potential mechanism that may contribute to the known cardioprotective effect of sulfasalazine in patients with IA. PMID:25253538

  13. Lipid peroxidation in Rheumatoid arthritis; consequences and monitoring.

    PubMed

    Luczaj, Wojciech; Jarocka-Karpinska, Iwona; Sierakowski, Stanislaw; Andrisic, Luka; Zarkovic, Neven; Skrzydlewska, Elzbieta

    2014-10-01

    The epidemiological studies have shown that rheumatoid arthritis (RA) leads to oxidative stress formation. Therefore the aim of this study has been to estimate the lipid peroxidation in RA patients. Moreover the reasons and consequences of changes in lipid peroxidation were estimated. 73 patients with RA and 62 healthy subjects were included into the study. Lipid peroxidation was estimated by the measurement of phospholipid arachidonic acid (AA) and linoleic acid (LA) as well as aldehydes: 4-hydroxynonenal (4-HNE), 4-hydroxyhexenal (4-HHE), malondialdehyde (MDA), acrolein, crotonaldehyde, and 4-oxononenal (4-ONE) that were determined by GC and GCMS, while 8-isoprostanes (8-isoPGF2a) - was determined by LCMS. Phospholipase A2 (PLA2), platelet-activating factor acetylhydrolase (PAF-AH) and glutathione peroxidase (GSH-Px) activity were determined spectrophotometrically, while vitamin E was determined by HPLC. Plasma of RA patients was characterized by higher vitamin E level and decreased GSH-Px activity as well as the level of phospholipid AA and LA compared to healthy subjects. The level of all examined aldehydes was significantly increased in plasma patients but higher increase was observed in urine of RA patients in comparison with control group. The 8-isoprostanes level was approximately 9-fold higher in the plasma and 3-fold higher in the urine of RA patients compared to healthy subjects, but in the urine the changes in 8-isoprostanes level was correlated with RA progression. A significant increase in 4-HNE-modified protein adducts level as well as a decrease in the activity of PAF-AH and PLA2 were observed in the plasma of RA patients. The level of lipid peroxidation products in the plasma and the urine may be the indicator of RA, but additionally urine 8-isoprostanes may be the useful and reliable biomarker of RA progression. PMID:26461394

  14. Indirect costs of rheumatoid arthritis

    PubMed Central

    Raciborski, Filip; Kwiatkowska, Brygida

    2015-01-01

    It is estimated that in Poland about 400,000 persons in general suffer from inflammatory joint diseases, including rheumatoid arthritis (RA). Epidemiological surveys documenting the frequency and disturbance of musculoskeletal disorders in the Polish population are few in number. Most of the estimations are based on epidemiological data from other countries (prevalence of 0.5–1%). According to the data of the National Health Fund in Poland 135,000–157,000 persons in total are treated because of rheumatoid arthritis per year [ICD10 (International Statistical Classification of Diseases and Related Health Problems): M05, M06]. In the case of this group of diseases indirect costs significantly outweigh the direct costs. Indirect costs increase together with activity level of the disease. The cost analysis of productivity loss of RA patients indicates that sickness absenteeism and informal care are the most burdensome. At the national level it amounts in total from 1.2 billion to 2.8 billion PLN per year, depending on the method of analysis. These costs could be significantly reduced through early diagnosis and introduction of effective treatment. PMID:27407258

  15. [Imaging modalities in psoriatic arthritis].

    PubMed

    Hermann, K-G A; Ohrndorf, S; Werner, S G; Finzel, S; Backhaus, M

    2013-10-01

    This review presents an overview of the range of imaging modalities used in the diagnostic evaluation of patients with psoriatic arthritis (PsA). Conventional radiography is used to detect structural changes of the joints and tendon attachments. These changes occur late in the course of PsA hence conventional radiography contributes little to the early detection of PsA; however, the detection of periosteal proliferations on radiographs allows a relatively specific diagnosis of PsA. Skeletal scintigraphy and computed tomography are rarely used in PsA. Arthrosonography (ultrasound of the joints) is gaining increasing importance in the early identification of inflammatory soft tissue signs of PsA in the peripheral joints. Sonography enables early detection of synovitis and tenosynovitis as well as superficial erosions and also inflammatory processes of the tendon attachments. Magnetic resonance imaging (MRI) is indispensable for identifying possible involvement of the axial skeleton. Moreover, it allows good visualization of periostitis and arthritis. High resolution microcomputed tomography is an interesting novel diagnostic tool which allows highly sensitive evaluation of the bone structure and can detect very tiny bone lesions where typical signs of PsA are omega-shaped erosions and small corona-like spikes. Another interesting new diagnostic technique is fluorescence optical imaging (FOI) with the Xiralite system which is highly sensitive for detecting inflammatory processes of the hands. PMID:24085530

  16. [Reiter disease or reactive arthritis?].

    PubMed

    Eppinger, S; Schmitt, J; Meurer, M

    2006-04-01

    There is an ongoing international discussion on whether the condition reactive arthritis should be named after a former Nazi functionary. The German dermatological community should participate in this debate. In 1916, Hans Reiter described a disease with the symptoms urethritis, conjunctivitis, and arthritis, which was later named after him. After becoming titular professor in May 1918, Reiter was appointed director of the regional public health department Mecklenburg-Schwerin in 1926. At the same time he taught social hygiene at the University of Rostock, where he was appointed full professor in 1928. In 1931, Hans Reiter became a member of the National Socialist German Workers Party (NSDAP). In July 1932 he was elected representative of the NSDAP to the seventh assembly of Mecklenburg-Schwerin. After becoming its acting director in July 1933, Reiter was appointed president of the Reich public health department in Berlin on October 1, 1933. Both his excellent professional qualifications, as well as his National Socialist attitudes, were considered key criteria for taking over this important position. As the president of the Reich public health department, Reiter was said to have known about the conduct of experiments with typhus-fever at the concentration camp Buchenwald in which 250 humans died. From the end of the Second World War until 1947, Reiter was imprisoned in the Nuremberg Prison for War Criminals, but never convicted of a crime. PMID:17419129

  17. Diet therapy for rheumatoid arthritis.

    PubMed

    Panush, R S; Carter, R L; Katz, P; Kowsari, B; Longley, S; Finnie, S

    1983-04-01

    Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease. PMID:6838671

  18. 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

  19. 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

  20. [Adjuvant drug therapies for breast cancer].

    PubMed

    Huovinen, Riikka; Auvinen, Päivi; Mattson, Johanna; Joensuu, Heikki

    2015-01-01

    Most breast cancers are hormone receptor positive and exhibit a slow growth pattern. Based on biological properties, breast cancers are divided into four different biological subtypes. Furthermore, these subtypes are indicative of the risk of recurrence, which is also influenced by the size of the tumor and extension to lymph nodes. Postoperative adjuvant drug therapy is chosen on the basis of the biological type. Chemotherapy can be used in all subtypes. Hormonal therapies are used exclusively for the treatment of hormone receptor positive breast cancer. Trastuzumab antibody belongs to the treatment of the HER2 positive subtype. PMID:26245052

  1. Septic and aseptic arthritis: a continuum?

    PubMed

    Taylor-Robinson, D; Keat, A

    1999-03-01

    This chapter considers the likelihood that a wide spectrum of infection-provoked arthritis exists, ranging from overt sepsis to apparently aseptic chronic arthritis in which very small numbers of causal bacteria can be detected only by using highly sensitive techniques. It asks whether joints are, as conventionally held, normally devoid of micro-organisms and how to judge the significance of bacteria detected within apparently sterile joints. Through a consideration of known septic, probably infective and apparently aseptic forms of arthritis, a set of criteria for attributing causality to putative arthritogenic micro-organisms is proposed. PMID:10952856

  2. Chemokines and angiogenesis in rheumatoid arthritis

    PubMed Central

    Szekanecz, Zoltan; Pakozdi, Angela; Szentpetery, Agnes; Besenyei, Timea; Koch, Alisa E.

    2010-01-01

    In rheumatoid arthritis, chemokines mediate the migration of inflammatory leukocytes into the synovium. Among the four known chemokine families, CXC, CC chemokines and fractalkine seem to be of outstanding importance in this process. Angiogenesis, the formation of new vessels, is also important during the perpetuation of inflammation underlying rheumatoid arthritis. In this review, authors discuss the role of the most important chemokines and chemokine repetors in arthritis-associated neovascularization. The process and regulation of angiogenesis are described in this context as well. Apart from discussing the pathogenic role of chemokines and chemokine receptors in arthritic vessel formation, authors also review the important relevance of chemokines and angiogenesis for therapeutic intervention. PMID:19482623

  3. Systemic Juvenile Idiopathic Arthritis: Diagnosis and Management.

    PubMed

    Kumar, Sathish

    2016-04-01

    Systemic juvenile idiopathic arthritis (sJIA) is an inflammatory condition characterized by fever, lymphadenopathy, arthritis, rash and serositis. In sJIA, systemic inflammation has been associated with dysregulation of the innate immune system, suggesting that it is an autoinflammatory disorder. IL-1 and IL-6 play a major role in the pathogenesis of sJIA and treatment with IL-1 and IL-6 inhibitors has shown to be highly effective. Recent data suggests that early cytokine blockage might abrogate chronic, destructive, therapy resistant arthritis phase, reflecting a potential "window of opportunity" in the care of children with sJIA. PMID:26916892

  4. Adjuvant Immunotherapy of Melanoma, and Development of New Approaches Using the Neo- Adjuvant Approach in Melanoma

    PubMed Central

    Davar, Diwakar; Tarhini, Ahmad

    2013-01-01

    Melanoma is the third most common skin cancer but the leading cause of death from cutaneous malignancies. While early-stage disease is frequently cured by surgical resection with excellent long-term survival, patients with deeper primary lesions (AJCC stage IIB-C) and those with microscopic (IIIA) or clinically evident regional lymph node or in-transit metastases (IIIB-C) have an increased risk of relapse and death–the latter approaching 70% or more at 5 years. In patients at high-risk of recurrence/metastases, adjuvant therapy with high-dose interferon alpha-2b (HDI) following definitive surgical resection has been shown to improve relapse free and overall survival. Neo-adjuvant chemotherapy and/or radiotherapy have offered the prospect to improve regional recurrence risk and overall survival in several solid tumors. The advent of effective new molecularly targeted therapies for metastatic disease and new immunotherapies that overcome checkpoints of immune response have augmented the range of new options that are in current trial evaluation to determine their role as potential adjuvant therapies, alone and in combination with one another, and the established modality of IFNα. The differential characteristics of the host immune response between early and advanced melanoma provide a strong mechanistic rationale for the use of neo-adjuvant immunotherapeutic approaches in melanoma, and the opportunity to evaluate the mechanism of action suggest neoadjuvant trial evaluation for each of the new candidate agents and combinations of interest. Several neo-adjuvant trials have been conducted in the phase II setting, which have illuminated the mechanism of IFNα, as well as providing insight to the effects of anti-CTLA4 blocking antibodies. These agents (anti-CTLA4 blocking antibody ipilimumab [BMS], and BRAF inhibitor vemurafenib [Genentech]) are likely to be followed by other immunotherapies that may overcome the PD-1 checkpoint (anti-PD1 [BMS, Merck, Curetech] and anti

  5. A Comparative Metabolomic Evaluation of Behcet's Disease with Arthritis and Seronegative Arthritis Using Synovial Fluid.

    PubMed

    Ahn, Joong Kyong; Kim, Sooah; Kim, Jungyeon; Hwang, Jiwon; Kim, Kyoung Heon; Cha, Hoon-Suk

    2015-01-01

    Behcet's disease (BD) with arthritis is often confused with seronegative arthritis (SNA) because of shared clinical symptoms and the lack of definitive biomarkers for BD. To investigate possible metabolic patterns and potential biomarkers of BD with arthritis, metabolomic profiling of synovial fluid (SF) from 6 patients with BD with arthritis and 18 patients with SNA was performed using gas chromatography/time-of-flight mass spectrometry in conjunction with univariate and multivariate statistical analyses. A total of 123 metabolites were identified from samples. Orthogonal partial least square-discriminant analysis showed clear discrimination between BD with arthritis and SNA. A set of 11 metabolites were identified as potential biomarkers for BD using variable importance for projection values and the Wilcoxon-Mann-Whitney test. Compared with SNA, BD with arthritis exhibited relatively high levels of glutamate, valine, citramalate, leucine, methionine sulfoxide, glycerate, phosphate, lysine, isoleucine, urea, and citrulline. There were two markers identified, elevated methionine sulfoxide and citrulline, that were associated with increased oxidative stress, providing a potential link to BD-associated neutrophil hyperactivity. Glutamate, citramalate, and valine were selected and validated as putative biomarkers for BD with arthritis (sensitivity, 100%; specificity, 61.1%). This is the first report to present potential biomarkers from SF for discriminating BD with arthritis from SNA. The metabolomics of SF may be helpful in searching for potential biomarkers and elucidating the clinicopathogenesis of BD with arthritis. PMID:26270538

  6. Ultrasound Detection of Salmonella Septic Arthritis in a Rheumatoid Arthritis Patient on Anti-TNF Treatment

    PubMed Central

    Kelly, Stephen

    2014-01-01

    We report a case of Salmonella septic arthritis detected by ultrasound in a 40-year-old man with rheumatoid arthritis while he was on anti–tumor necrosis factor-α monoclonal antibody certolizumab. An aspirate of his left elbow joint showed Salmonella enteritidis infection that was sensitive to ceftraixone. This was preceded by a brief episode of loose stools following a visit to the Far East. He was treated with antibiotics and made a good recovery. There have only been a few case reports of Salmonella septic arthritis in a rheumatoid arthritis patient on anti–tumor necrosis factor treatment but none previously in association with certolizumab. PMID:26425605

  7. Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes

    PubMed Central

    2015-01-01

    Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use. PMID:25648619

  8. Efficacy of an immunotoxin to folate receptor beta in the intra-articular treatment of antigen-induced arthritis

    PubMed Central

    2012-01-01

    Introduction We previously demonstrated that synovial sublining macrophages express folate receptor beta (FRβ). The aim of this study was to evaluate the efficacy of intra-articular administration of a recombinant immunotoxin to FRβ for treating rat antigen-induced arthritis. Methods A monoclonal antibody (mAb) to rat FRβ was produced by immunizing mice with B300-19 cells (murine pre-B cells) transfected with the rat FRβ gene. Recombinant immunotoxin was prepared by conjugating the Fv portion of the anti-rat FRβ mAb heavy chain with a truncated Pseudomonas exotoxin A and the Fv portion of the anti-rat FRβ mAb light chain. Antigen-induced arthritis was induced through intra-articular injection of methylated bovine serum albumin (mBSA) after two subcutaneous injections of mBSA and complete Freund's adjuvant. Immunotoxin was intra-articularly injected into the arthritis joint every other day for seven days after arthritis onset. Joint swelling was measured and histological scores of inflammation, synovial thickness, cartilage, and bone destruction were determined. Immunohistochemistry was performed to detect osteoclast and osteoclast precursor FRβ-expressing macrophages and cathepsin K-positive cells on day 21. Results Intra-articular administration of the immunotoxin attenuated joint swelling (61% suppression; P < 0.01 compared to the control on day 21) and improved histological findings, particularly cartilage and bone destruction (scores of rats treated with control versus the immunotoxin: 2.2 versus 0.5; P < 0.01), by reducing the number of FRβ-expressing macrophages and cathepsin K-positive cells. Conclusions Intra-articular administration of an immunotoxin to FRβ is effective for improving rat antigen-induced arthritis. PMID:22551402

  9. IL-10-producing regulatory B10 cells ameliorate collagen-induced arthritis via suppressing Th17 cell generation.

    PubMed

    Yang, Min; Deng, Jun; Liu, Yang; Ko, King-Hung; Wang, Xiaohui; Jiao, Zhijun; Wang, Shengjun; Hua, Zichun; Sun, Lingyun; Srivastava, Gopesh; Lau, Chak-Sing; Cao, Xuetao; Lu, Liwei

    2012-06-01

    IL-10-producing CD1d(hi)CD5(+) B cells, also known as B10 cells, have been shown to possess a regulatory function in the inhibition of immune responses, but whether and how B10 cells suppress the development of autoimmune arthritis remain largely unclear. In this study, we detected significantly decreased numbers of IL-10-producing B cells, but increased IL-17-producing CD4(+) T (Th17) cells in both spleen and draining lymph nodes of mice during the acute stage of collagen-induced arthritis (CIA) when compared with adjuvant-treated control mice. On adoptive transfer of in vitro expanded B10 cells, collagen-immunized mice showed a marked delay of arthritis onset with reduced severity of both clinical symptoms and joint damage, accompanied by a substantial reduction in the number of Th17 cells. To determine whether B10 cells directly inhibit the generation of Th17 cells in culture, naive CD4(+) T cells labeled with carboxyfluorescein succinimidyl ester (CFSE) were co-cultured with B10 cells. These B10 cells suppressed Th17 cell differentiation via the reduction of STAT3 phosphorylation and retinoid-related orphan receptor γt (RORγt) expression. Moreover, Th17 cells showed significantly decreased proliferation when co-cultured with B10 cells. Although adoptive transfer of Th17 cells triggered the development of collagen-induced arthritis in IL-17(-/-)DBA/1J mice, co-transfer of B10 cells with Th17 cells profoundly delayed the onset of arthritis. Thus, our findings suggest a novel regulatory role of B10 cells in arthritic progression via the suppression of Th17 cell generation. PMID:22538089

  10. Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4

    PubMed Central

    2009-01-01

    Introduction Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-γ and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-γ and IL-4. Methods DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-γ and/or IL-4. Systemic IL-17, IFN-γ, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis. Results Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-γ. Neutralization of IFN-γ accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-γ/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-γ and was associated with increased bone and cartilage damage without an increase in the levels of IL-17. Conclusions IL-4 and IFN-γ both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation. PMID:19852819

  11. Mucosal adjuvants to improve wildlife rabies vaccination.

    PubMed

    Fry, Tricia; Van Dalen, Kaci; Hurley, Jerome; Nash, Paul

    2012-10-01

    RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs. PMID:23060506

  12. Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.

    PubMed

    Mallmann, Peter; Mallmann, Christoph

    2016-01-01

    Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740

  13. Adjuvant chemotherapy for soft tissue sarcoma.

    PubMed

    Casali, Paolo G

    2015-01-01

    Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233

  14. Safety assessment of adjuvanted vaccines: Methodological considerations

    PubMed Central

    Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

    2015-01-01

    Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

  15. Safety assessment of adjuvanted vaccines: Methodological considerations.

    PubMed

    Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

    2015-01-01

    Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

  16. Arthritis mutilans: a report from the GRAPPA 2012 annual meeting.

    PubMed

    Chandran, Vinod; Gladman, Dafna D; Helliwell, Philip S; Gudbjörnsson, Björn

    2013-08-01

    Arthritis mutilans is often described as the most severe form of psoriatic arthritis. However, a widely agreed on definition of the disease has not been developed. At the 2012 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members hoped to agree on a definition of arthritis mutilans and thus facilitate clinical and molecular epidemiological research into the disease. Members discussed the clinical features of arthritis mutilans and definitions used by researchers to date; reviewed data from the ClASsification for Psoriatic ARthritis study, the Nordic psoriatic arthritis mutilans study, and the results of a premeeting survey; and participated in breakout group discussions. Through this exercise, GRAPPA members developed a broad consensus on the features of arthritis mutilans, which will help us develop a GRAPPA-endorsed definition of arthritis mutilans. PMID:23908536

  17. 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. PMID:27026299

  18. Therapeutic effect of umbelliferon-α-D-glucopyranosyl-(2(I)→1(II))-α-D-glucopyranoside on adjuvant-induced arthritic rats.

    PubMed

    Kumar, Vikas; Anwar, Firoz; Verma, Amita; Mujeeb, Mohd

    2015-06-01

    The aim and objective of the present investigation was to evaluate the antiarthritic and antioxidant effect of umbelliferon-α-D-glucopyranosyl-(2I→1II)-α-D-glucopyranoside (UFD) in chemically induced arthritic rats. The different doses of the UFD were tested against the turpentine oil (TO), formaldehyde induced acute arthritis and complete fruend's adjuvant (CFA) induced chronic arthritis in Wistar rats. Arthritic assessment and body weight was measured at regular interval till 28 days. On day 28, all the groups animals were anaesthetized, blood were collected from the puncturing the ratro orbital and estimated the hematological parameters. The animals were sacrificed; synovial tissue was extracted and estimated the malonaldehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD). The different doses of the UFD showed the protective effect against turpentine oil, formaldehyde induced acute arthritis and CFA induced chronic arthritis at dose dependent manner. Acute model of arthritis such as TOand formaldehyde induced inflammation due to releasing of the inflammatory mediators; significantly inhibited by the UFD at dose dependent manner. CFA induced arthritic rats treated with the different doses of the UFD showed the inhibitory effect on the delayed increase in joint diameter as seen in arthritic control group rats. UFD significantly improved the arthritic index, body weight and confirmed the antiarthritic effect. UFD showed the effect on the hematological parameter such as improved the level of the RBC, Hb and decline the level of the EBC, ESR and confirmed the immune suppressive effect. UFD significantly improved the level of the endogenous antioxidant and confirmed the antioxidant effect. This present investigation suggests that the UFD has prominent antiarthritic impact which can be endorsed to its antiarthritic and antioxidant effects. PMID:26028721

  19. Adjuvant chemotherapy for endometrial cancer after hysterectomy

    PubMed Central

    Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

    2014-01-01

    Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

  20. Spray characteristics affected by physical properties of adjuvants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four drift adjuvants, Array, In-Place, Vector and Control, were tested and physical properties and spray spectrum parameters measured. Array had the highest conductivity, indicating a good potential for the electrostatic charging, and the highest shear viscosity. All adjuvants had very similar neut...

  1. Dispersion and evaporation of droplets amended with adjuvants on soybeans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increased use of adjuvants to improve pesticide spray application efficiency is hindered by a lack of knowledge to enhance droplet adhesion. Dispersion and evaporation of single 300 µm droplets amended with four different spray adjuvants deposited at four different soybean plant locations were inves...

  2. Evaluating spray adjuvants to extend residual activity of microbiol pesticides`

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Based on requests to improve the residual efficacy of baculovirus applications, a commercial adjuvant (Nu-Film 17(R) and an experimental lignin adjuvant were evaluated for resistance to environmental degradation. Nu-Film is a commercial product derived from pine resin; and lignin is a by-product of...

  3. Current status of synthetic hemozoin adjuvant: A preliminary safety evaluation.

    PubMed

    Lee, Michelle Sue Jann; Igari, Yoshikatsu; Tsukui, Toshihiro; Ishii, Ken J; Coban, Cevayir

    2016-04-19

    Although adjuvants are a "must-have" component of successful vaccines, there are very few adjuvants licensed for use in humans, there is therefore an urgent need to develop new and safer adjuvants. Synthetic hemozoin (sHZ), a chemical analog of hemozoin which is produced by the malaria parasite, exhibits a potent adjuvant effect which enhances antigen-specific immune responses to vaccines. The potency of sHZ adjuvanticity is not limited to malaria specific vaccines, it has also been demonstrated to be effective in influenza and dog allergy models. While the synthesis of uniformly sized sHZ with consistent characteristics has proven difficult, we have recently successfully optimized the manufacture of sHZ product with an optimal adjuvant effect. Here, we summarize recent developments on the adjuvant properties of optimized sHZ adjuvant, including its good laboratory practice (GLP) non-clinical safety profile in animals. These studies ensure the safety of optimized sHZ product to be readily used as vaccine adjuvant beforehand in veterinary medicine. PMID:26976665

  4. Vaccine Adjuvants: from 1920 to 2015 and Beyond

    PubMed Central

    Di Pasquale, Alberta; Preiss, Scott; Tavares Da Silva, Fernanda; Garçon, Nathalie

    2015-01-01

    The concept of stimulating the body’s immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190

  5. Adjuvant Effects on Evaporation Time and Wetted Area of Droplets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Appropriate adjuvant selection for pesticide applications is central to improve spray performances on waxy leaves and to reduce off-target losses. Evaporation and deposition patterns of 500 µm sessile droplets with five classes of adjuvants on five different waxy plants were investigated. Droplets g...

  6. Vaccine adjuvant technology: from theoretical mechanisms to practical approaches.

    PubMed

    Schijns, V E J C; Tangerås, A

    2005-01-01

    Poorly immunogenic antigens depend on vaccine adjuvants to evoke an immune response. In addition, adjuvants largely determine the magnitude, quality, time of onset and the duration of immune responses to co-administered antigens. As late as 1989, Janeway aptly called adjuvants: "the immunologist's dirty little secret". This statement reflected the ignorance on the mechanisms of action of most known adjuvants. Yet, rational vaccine design involves a logical choice of adjuvant based on a knowledge of their mode of action and their effects on product efficacy and safety. However, even today the key processes critical for immune induction in general and those evoked by vaccine adjuvants in particular are being disputed among immunologists. This paper presents the four most important concepts likely to explain some of the mechanisms of vaccine adjuvants. They include: (i) the geographical concept of immune reactivity; (ii) the depot concept; (iii) the hypothesis of pathogen-structure recognition, and (iv) the damage/endogenous danger theory. These paradigms are based on observations gathered in mammalian species, largely in murine models. In aquatic animals the processes underlying immune induction will at least partly overlap those in mammals. However, due to inherent species differences, certain pathways may be different. Rational vaccine design, a difficult goal in mammals, is further hampered in aquatic animals by the lack of immunological tools in these species. Extensive trial and error-based approaches have yielded adjuvant candidates for various fish species, with acceptable safety and proven efficacy, some of which are presented. PMID:15962475

  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. Juvenile rheumatoid arthritis with cardiac tamponade.

    PubMed Central

    Majeed, H A; Kvasnicka, J

    1978-01-01

    A 4-year-old girl with seronegative systemic juvenile rheumatoid arthritis developed acute cardiac tamponade. Pericardiocentesis and systemic corticosteroids resulted in complete recovery of the pericardial involvement. This was followed by complete remission of rheumatoid disease. Images PMID:686861

  9. Juvenile Arthritis: Discoveries Lead to Newer Treatments

    MedlinePlus

    ... Consumers Home For Consumers Consumer Updates Juvenile Arthritis: Discoveries Lead to Newer Treatments Share Tweet Linkedin Pin ... better for different subgroups of the disease. In recent years, FDA has approved several of these treatments. ...

  10. [Arthritis and osteitis at the hand].

    PubMed

    Meier, R; Pillukat, T

    2011-06-01

    Septic arthritis and osteitis at the hand are associated with a high morbidity. Trauma is the major cause for these infections. In the majority of cases the fingers are involved. Causative microorganisms are predominantly Staphylococcus aureus and Streptococcus pyogenes. In addition, an increasing number of Gram-negative bacteria have been found in hand infections. As differential diagnosis, tumours and non-septic arthritis must be considered. Treatment includes surgical debridement, immobilisation and functional rehabilitation. Crucial for the surgical strategy are the virulence of the pathogens, the resistance of the patient and the location of the infection. If functional recovery cannot be expected, salvage procedures like arthrodeses and resection arthroplasties are sometimes required. Surgical treatment is sufficient in septic arthritis and osteomyelitis of the hand. However, to avoid permanent disability, rapid diagnosis and therapy are essential. This review describes our treatment concepts in septic arthritis and osteomyelitis at the hand. PMID:21494997

  11. Acute pseudoseptic arthritis and palmoplantar pustulosis.

    PubMed

    Chamot, A M; Vion, B; Gerster, J C

    1986-01-01

    The case of a 60-year-old woman who developed acute peripheral arthritis of a pseudoseptic character (high synovial leucocytosis and fever) associated to a palmoplantar pustulosis is reported. PMID:3514079

  12. AA amyloidosis in vaccinated growing chickens.

    PubMed

    Murakami, T; Inoshima, Y; Sakamoto, E; Fukushi, H; Sakai, H; Yanai, T; Ishiguro, N

    2013-01-01

    Systemic amyloid-A (AA) amyloidosis in birds occurs most frequently in waterfowl such as Pekin ducks. In chickens, AA amyloidosis is observed as amyloid arthropathy. Outbreaks of systemic amyloidosis in flocks of layers are known to be induced by repeated inflammatory stimulation, such as those resulting from multiple vaccinations with oil-emulsified bacterins. Outbreaks of fatal AA amyloidosis were observed in growing chickens in a large scale poultry farm within 3 weeks of vaccination with multiple co-administered vaccines. This study documents the histopathological changes in tissues from these birds. Amyloid deposits were also observed at a high rate in the tissues of apparently healthy chickens. Vaccination should therefore be considered as a potential risk factor for the development of AA amyloidosis in poultry. PMID:23570943

  13. AAS 228: Day 3 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session 2015 Newton Lacy Pierce Prize Lecture: The Elephant in the Room: Effects of Distant, Massive Companions on Planetary System Architectures (by Leonardo dos Santos)The first session on Wednesday at 228th AAS Meeting was the Newton Lacy Pierce Prize Lecture by Heather Knutson (California Institute of Technology). This talk featured a broad range of research efforts on exoplanets, with the main focus on how we study the composition of their atmospheres, and how multi-body interactions carve the structure of the planetary systems we observe.One of her first points is the well-known idea that the Solar System is an oddball, compared to the exoplanet systems we have found so far: most of these systems contain hot Jupiters and mini-Neptunes at very close-in orbits around their host stars. Moreover, even when studying their transmission spectra, it is difficult to know the exact composition of their atmospheres.Knutson: it is difficult to constrain atmospheric composition of exoplanets (H-poor or H-rich+clouds?) #aas228pic.twitter.com/LdyN4o9RC7 astrobites (@astrobites) June 15, 2016The main proposal on how these systems formed is the migration scenario. In order to validate this idea, Dr. Knutson and her group The Friends of Hot Jupiters study systems with close-in gas giants and their frequency of binary companions, which are supposed to be the main culprits causing gas-giant migration. They found that approximately half of the observed systems have long-distance companions, providing strong validation of the migration scenario. Moreover, Dr. Knutson speculates that wide binaries have more

  14. Pharmacotherapy Options in Rheumatoid Arthritis

    PubMed Central

    Kumar, Pradeep; Banik, Snehashish

    2013-01-01

    Drugs form the mainstay of therapy in rheumatoid arthritis (RA). Five main classes of drugs are currently used: analgesics, non-steroidal anti-inflammatories (NSAIDs), glucocorticoids, nonbiologic and biologic disease-modifying antirheumatic drugs. Current clinical practice guidelines recommend that clinicians start biologic agents if patients have suboptimal response or intolerant to one or two traditional disease modifying agents (DMARDs). Methotrexate, sulfasalazine, leflunomide and hydroxychloroquine are the commonly used DMARDs. Currently, anti-TNF is the commonly used first line biologic worldwide followed by abatacept and it is usually combined with MTX. There is some evidence that tocilizumab is the most effective biologic as a monotherapy agent. Rituximab is generally not used as a first line biologic therapy due to safety issues but still as effective as anti-TNF. The long term data for the newer oral small molecule biologics such as tofacitinib is not available and hence used only as a last resort. PMID:23997576

  15. Arthritis at the shoulder joint.

    PubMed

    Sankaye, Prashant; Ostlere, Simon

    2015-07-01

    The shoulder is a complex joint with numerous structures contributing to mobility and stability. Shoulder pain is a common clinical complaint that may be due to a wide spectrum of disorders including rotator cuff disease, instability, and arthropathy. Primary osteoarthritis of the shoulder joint is uncommon because it is a non-weight-bearing joint. Significant osteoarthritis of the glenohumeral joint is unusual in the absence of trauma, and the detection of advanced degenerative changes in patients without a known history of trauma should alert the clinician to search for other disorders. This article reviews the pathogenesis, clinical manifestations, and key imaging findings of the common categories of the arthritis affecting the glenohumeral joint. PMID:26021591

  16. Psoriasis and psoriatic arthritis treatment.

    PubMed

    Menter, Alan

    2016-06-01

    Over the past several years, an increased understanding of the pathophysiology of psoriasis and psoriatic arthritis (PsA) has led to the development of several new biologic therapies. Appropriate treatment selection and timing may slow, and even halt, the progression of psoriasis and PsA; as a result, it can decrease the economic burden. As treatment options vary based on individual disease characteristics and patient preferences, reviewing the patient's complete clinical picture is imperative. An updated treatment algorithm, based on patients' most severe disease domain, is now available to guide the selection of optimal therapy. Special care should be given to patients with both psoriasis and PsA who experience multiple disease domains, a heavy symptom burden, and an increased risk of comorbidities. PMID:27356194

  17. Psoriasis and psoriatic arthritis overview.

    PubMed

    Menter, Alan

    2016-06-01

    Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases that primarily affect the skin and joints, respectively; these diseases are also associated with high rates of cardiovascular and other comorbidities. Despite over 40 genes proven to be related to the disease, the exact causes of psoriasis and PsA are still to be determined. Recent insights into the underlying pathophysiology of these diseases have revealed novel therapeutic targets. Effective management requires timely diagnosis and initiation of treatment. Yet, both psoriasis and PsA remain underrecognized and undertreated in current clinical practice. Recognizing the true physical, social, and emotional burden of psoriasis and PsA, as well as their associated comorbidities, is the first step to improving the prognosis for affected patients. PMID:27356193

  18. Rheumatoid arthritis affecting temporomandibular joint

    PubMed Central

    Sodhi, Amandeep; Naik, Shobha; Pai, Anuradha; Anuradha, Ardra

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic, systemic, autoimmune inflammatory disorder that is characterized by joint inflammation, erosive properties and symmetric multiple joint involvement. Temporomandibular joint (TMJ) is very rare to be affected in the early phase of the disease, thus posing diagnostic challenges for the dentist. Conventional radiographs fail to show the early lesions due to its limitations. More recently cone-beam computed tomography (CBCT) has been found to diagnose the early degenerative changes of TMJ and hence aid in the diagnosis of the lesions more accurately. Our case highlights the involvement of TMJ in RA and the role of advanced imaging (CBCT) in diagnosing the bony changes in the early phase of the disease. PMID:25684928

  19. AAS 228: Day 3 morning

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session 2015 Newton Lacy Pierce Prize Lecture: The Elephant in the Room: Effects of Distant, Massive Companions on Planetary System Architectures (by Leonardo dos Santos)The first session on Wednesday at 228th AAS Meeting was the Newton Lacy Pierce Prize Lecture by Heather Knutson (California Institute of Technology). This talk featured a broad range of research efforts on exoplanets, with the main focus on how we study the composition of their atmospheres, and how multi-body interactions carve the structure of the planetary systems we observe.One of her first points is the well-known idea that the Solar System is an oddball, compared to the exoplanet systems we have found so far: most of these systems contain hot Jupiters and mini-Neptunes at very close-in orbits around their host stars. Moreover, even when studying their transmission spectra, it is difficult to know the exact composition of their atmospheres.Knutson: it is difficult to constrain atmospheric composition of exoplanets (H-poor or H-rich+clouds?) #aas228pic.twitter.com/LdyN4o9RC7 astrobites (@astrobites) June 15, 2016The main proposal on how these systems formed is the migration scenario. In order to validate this idea, Dr. Knutson and her group The Friends of Hot Jupiters study systems with close-in gas giants and their frequency of binary companions, which are supposed to be the main culprits causing gas-giant migration. They found that approximately half of the observed systems have long-distance companions, providing strong validation of the migration scenario. Moreover, Dr. Knutson speculates that wide binaries have more

  20. Reactive Arthritis Caused by Urinary Tract Infection.

    PubMed

    Nishizaki, Yuji; Yamagami, Shinichiro; Inoue, Hisashi; Uehara, Yuki; Kobayashi, Shigeto; Daida, Hiroyuki

    2016-01-01

    We report the case of a 58-year-old man presenting with chest pain who underwent percutaneous coronary intervention (PCI). The patient subsequently developed a fever over 38°C, pain on micturition, and cloudy urine 3 days following PCI. Urine cultures were positive for Escherichia coli and Enterococcus faecalis, whereas blood cultures were negative. Arthritis occurred two weeks following urinary tract infection (UTI). We herein present a rare case of reactive arthritis caused by UTI following PCI. PMID:27150879

  1. Septic arthritis due to Aerococcus viridans.

    PubMed

    Taylor, P W; Trueblood, M C

    1985-10-01

    A 20-year-old woman was found to have septic arthritis of the hip due to Aerococcus viridans. This organism closely resembles Streptococcus viridans, but forms gram positive tetrads rather than chains in broth media. The organism has been reported rarely to cause endocarditis and one case of osteomyelitis has been observed. To our knowledge septic arthritis due to Aerococcus viridans has not been previously reported. PMID:4087248

  2. Primary and Posttraumatic Arthritis of the Elbow

    PubMed Central

    Biswas, Debdut; Wysocki, Robert W.; Cohen, Mark S.

    2013-01-01

    Whether degenerative joint disease of the elbow may be the result of primary or posttraumatic etiologies, arthritis of the elbow commonly leads to pain, loss of motion, and functional disability. A detailed history and focused physical examination, in combination with imaging modalities, can help localize the origin of symptoms and help direct treatment. Although nonoperative treatment is the initial therapy for arthritis of the elbow, surgical interventions may provide substantial relief to the appropriately selected patient. PMID:23781338

  3. Does food cause or cure arthritis?

    PubMed

    Panush, R S

    1991-05-01

    Rheumatoid arthritis and most other forms of inflammatory joint disease--systemic rheumatic diseases--remain illnesses of unknown cause for which current therapy often is inadequate. The possibility that food antigens induce or perpetuate symptoms in at least some patients is novel, rational, and exciting. Studies that relate diet with arthritis might offer the potential of identifying new therapeutic approaches for selected patients and of developing new insights into disease pathogenesis. PMID:1862237

  4. 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

  5. Can Rheumatoid Arthritis Be Prevented?

    PubMed Central

    Deane, Kevin

    2013-01-01

    The discovery of elevations of rheumatoid arthritis (RA)-related biomarkers prior to the onset of clinically apparent RA raises hopes that individuals who are at risk for future RA can be identified in a preclinical phase of disease that is defined as abnormalities of RA-related immune activity prior to the clinically apparent onset of joint disease. Additionally, there is a growing understanding of the immunologic processes that are occurring in preclinical RA, as well as a growing understanding of risk factors that may be mechanistically related to RA development. Furthermore, there are data supporting that treatment of early RA can lead to drug free remission. Taken as a whole, these findings suggest that it may be possible to use biomarkers and other factors to accurately identify the likelihood and timing of onset of future RA, and intervene with immunomodulatory therapies and/or risk factor modification to prevent the future onset of RA in at-risk individuals. Importantly, several clinical prevention trials for RA have already been tried, and one is underway. However, while our understanding of the growing understanding of the mechanisms and natural history of RA development may be leading us to the implementation of prevention strategies for RA, there are still several challenges to be met. These include developing sufficiently accurate methods of predicting those at high risk for future RA so that clinical trials can be developed based on accurate rates of development of arthritis and subjects can be adequately informed of their risk for disease, identifying the appropriate interventions and biologic targets for optimal prevention, and addressing the psychosocial and economic aspects that are crucial to developing broadly applicable prevention measures for RA. These issues notwithstanding, prevention of RA may be within reach in the near future. PMID:24315049

  6. In vitro interactions between macrophages and aluminum-containing adjuvants.

    PubMed

    Rimaniol, Anne-Cécile; Gras, Gabriel; Clayette, Pascal

    2007-09-17

    Intramuscular administration of aluminum-adjuvanted vaccines induces an infiltration of aluminum-containing macrophages between muscle fibers. In vitro stimulation of human monocyte-derived macrophages with aluminum hydroxide (AlOOH) induces similar intracellular crystalline inclusions as well as phenotypical and functional modifications. We compared in this study the ability of other adjuvants to exert similar changes in macrophages in vitro. All mineral salts, i.e. aluminic (AlOOH, AlPO(4)) and non-aluminic mineral adjuvants (CaPO(4), FePO(4)) but not emulsion were able to increase macrophages capacity to potentiate autologous memory T lymphocyte proliferation, while only aluminic adjuvants induced CD83 expression and increased CD86 on macrophages. All together, this suggests that aluminic and non-aluminic adjuvants exerted their immunoactivities by distinct mechanisms on macrophages. PMID:17689842

  7. Adjuvants in micro- to nanoscale: current state and future direction.

    PubMed

    Gupta, Ankur; Das, Soumen; Schanen, Brian; Seal, Sudipta

    2016-01-01

    Adjuvants have been used in vaccines for over 70 years to promote long-lived and sterilizing immunity. Since then, various adjuvant systems were developed by combining nanotechnology with natural and/or synthetic immunomodulatory molecules. These systems are biocompatible, immunogenic, and possess higher antigen carrying capacity. This article showcases advancements made in the adjuvant systems formulations, their synthesis routes, and the improvement of these adjuvants have brought in response to combat against ongoing global health threats such as malaria, hepatitis C, universal influenza, and human immunodeficiency virus. This review also highlights the interaction of adjuvants with the delivery of antigens to cells and unfolds mechanism of actions. In addition, this review discusses the physicochemical factors responsible for the efficient interaction of nanoadjuvants with antigen receptors to develop more effective, less reactogenic, and multifunctional systems for the next generation vaccines. PMID:26053286

  8. Update on Adjuvant Chemotherapy for Early Breast Cancer

    PubMed Central

    Rampurwala, Murtuza M; Rocque, Gabrielle B; Burkard, Mark E

    2014-01-01

    Breast cancer is the second most common cancer in women worldwide. Although most women are diagnosed with early breast cancer, a substantial number recur due to persistent micro-metastatic disease. Systemic adjuvant chemotherapy improves outcomes and has advanced from first-generation regimens to modern dose-dense combinations. Although chemotherapy is the cornerstone of adjuvant therapy, new biomarkers are identifying patients who can forego such treatment. Neo-adjuvant therapy is a promising platform for drug development, but investigators should recognize the limitations of surrogate endpoints and clinical trials. Previous decades have focused on discovering, developing, and intensifying adjuvant chemotherapy. Future efforts should focus on customizing therapy and reducing chemotherapy for patients unlikely to benefit. In some cases, it may be possible to replace chemotherapy with treatments directed at specific genetic or molecular breast cancer subtypes. Yet, we anticipate that chemotherapy will remain a critical component of adjuvant therapy for years to come. PMID:25336961

  9. Near-Infrared Laser Adjuvant for Influenza Vaccine

    PubMed Central

    Kashiwagi, Satoshi; Yuan, Jianping; Forbes, Benjamin; Hibert, Mathew L.; Lee, Eugene L. Q.; Whicher, Laura; Goudie, Calum; Yang, Yuan; Chen, Tao; Edelblute, Beth; Collette, Brian; Edington, Laurel; Trussler, James; Nezivar, Jean; Leblanc, Pierre; Bronson, Roderick; Tsukada, Kosuke; Suematsu, Makoto; Dover, Jeffrey; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C.

    2013-01-01

    Safe and effective immunologic adjuvants are often essential for vaccines. However, the choice of adjuvant for licensed vaccines is limited, especially for those that are administered intradermally. We show that non-tissue damaging, near-infrared (NIR) laser light given in short exposures to small areas of skin, without the use of additional chemical or biological agents, significantly increases immune responses to intradermal influenza vaccination without augmenting IgE. The NIR laser-adjuvanted vaccine confers increased protection in a murine influenza lethal challenge model as compared to unadjuvanted vaccine. We show that NIR laser treatment induces the expression of specific chemokines in the skin resulting in recruitment and activation of dendritic cells and is safe to use in both mice and humans. The NIR laser adjuvant technology provides a novel, safe, low-cost, simple-to-use, potentially broadly applicable and clinically feasible approach to enhancing vaccine efficacy as an alternative to chemical and biological adjuvants. PMID:24349390

  10. The Changing Shape of the AAS

    NASA Astrophysics Data System (ADS)

    Boyce, P. B.

    1995-12-01

    What is the astronomical workforce like? Where do astronomers work? How old are they? How permanent are their jobs? As we move into a period of increased uncertainty in federal funding for science it is important to know the answers to these questions. There are four sources of information for answers: 1. Information from the AAS membership database. 2. A survey of the AAS membership. 3. Surveys of samples of the AAS membership by AIP. 4. Information from the NRC and NSF. We have gender and age data from 1. A survey of the AAS membershWe will have age and gender data from 1. We will complete and analyze a new membersip survey shortly. The latest AIP data is from 1994. They will do a new sample in 1996. Much of the NRC data is aggregated with physics, and that does not give information about astronomers. Nevertheless, we do have some interesting information. The ages and genders of AAS members are available for 1972, 1990 and 1995. The time sequence provides an interesting look at the AAS. For instance, from 1990 to 1995 the number of women in each 5-year age group below the the age of 65 increased. Contrary to popular perception, women are not leaving the Society as they get older. However, the number of men actually decreased in each age group above the age of 35. This and other interesting trends will be discussed.

  11. Abnormal bone remodelling in inflammatory arthritis

    PubMed Central

    Bogoch, Earl R.; Moran, Erica

    1998-01-01

    Osteopenia is responsible for substantial comorbidity in patients suffering from rheumatoid arthritis and is an important factor in the surgical management of joint disease. In animal models of bone loss stimulated by inflammatory arthritis, increased bone remodelling and altered microstructure of bone have been documented. The subchondral bone plate near the joint surface is narrow and perforated by vascular inflammatory invasion, and in the shaft the thin cortices are weakened by giant resorption defects. Biomechanical tests and a mathematical model of bone strength suggest that cortical defects, much larger than those found in normal osteonal remodelling, are principally responsible for the experimentally observed loss of strength. Similarly, these defects may explain the increased femoral fracture risk in rheumatoid arthritis. The osteoclast, the cell resorbing bone, is demonstrated in increased number and activity in rheumatoid arthritis and in animal models. Bisphosphonates, drugs that inhibit osteoclast function, have been shown experimentally to reduce both focal and generalized osteopenia and to prevent loss of bone strength. Bisphosphonates also protect articular cartilage from damage characteristic of inflammatory arthritis. The mechanism of chondroprotection may be prevention of subchondral bone resorption by the osteoclast and also an altered distribution of bone marrow cells. Thus, bisphosphonates, currently in clinical use for other bone metabolic diseases, appear to have potential as prophylaxis and treatment for osteopenia and joint damage in inflammatory arthritis. PMID:9711159

  12. Mechanism of Immunopotentiation and Safety of Aluminum Adjuvants

    PubMed Central

    HogenEsch, Harm

    2013-01-01

    Aluminum-containing adjuvants are widely used in preventive vaccines against infectious diseases and in preparations for allergy immunotherapy. The mechanism by which they enhance the immune response remains poorly understood. Aluminum adjuvants selectively stimulate a Th2 immune response upon injection of mice and a mixed response in human beings. They support activation of CD8 T cells, but these cells do not undergo terminal differentiation to cytotoxic T cells. Adsorption of antigens to aluminum adjuvants enhances the immune response by facilitating phagocytosis and slowing the diffusion of antigens from the injection site which allows time for inflammatory cells to accumulate. The adsorptive strength is important as high affinity interactions interfere with the immune response. Adsorption can also affect the physical and chemical stability of antigens. Aluminum adjuvants activate dendritic cells via direct and indirect mechanisms. Phagocytosis of aluminum adjuvants followed by disruption of the phagolysosome activates NLRP3-inflammasomes resulting in the release of active IL-1β and IL-18. Aluminum adjuvants also activate dendritic cells by binding to membrane lipid rafts. Injection of aluminum-adjuvanted vaccines causes the release of uric acid, DNA, and ATP from damaged cells which in turn activate dendritic cells. The use of aluminum adjuvant is limited by weak stimulation of cell-mediated immunity. This can be enhanced by addition of other immunomodulatory molecules. Adsorption of these molecules is determined by the same mechanisms that control adsorption of antigens and can affect the efficacy of such combination adjuvants. The widespread use of aluminum adjuvants can be attributed in part to the excellent safety record based on a 70-year history of use. They cause local inflammation at the injection site, but also reduce the severity of systemic and local reactions by binding biologically active molecules in vaccines. PMID:23335921

  13. AAS 228: Day 1 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session: From Space Archeology to Serving the World Today: A 20-year Journey from the Jungles of Guatemala to a Network of Satellite Remote Sensing Facilities Around the World(by Michael Zevin)In the conferences second plenary session, NASAs Daniel Irwin turned the eyes of the conference back to Earth by highlighting the huge impact that NASA missions play in protecting and developing our own planet.Daniel Irwin: using satellite imagery to detect differences in vegetation and find ancient Mayan cities. #aas228 pic.twitter.com/9LFPQdCHTM astrobites (@astrobites) June 13, 2016Irwin came to be involved in NASA through his work mapping Guatemalan jungles, where he would spend 22 days at a time exploring the treacherous jungles on foot armed with a 1st generation GPS, a compass, and a machete. A colleague introduced Irwin to the satellite imagery thathe was exploring, demonstratinghow these images are a strong complement to field work. The sharing of this satellite data with nearby villages helped to show the encroachment of agriculture and the necessity of connecting space to the village. Satellite imagery also played a role in archeological endeavors, uncovering dozens of Mayan cities that have been buried for over a millennia by vegetation, and it provided evidence that the fall of the Mayan civilization may have been due to massive deforestation that ledto drought.Glacial retreat in Chile imaged by ISERV.Irwin displayed the constellation of NASAs Earth-monitoring satellites that have played an integral role in conserving our planet and alerting the world of natural disasters. He also showed

  14. Bilateral Cricoarytenoid Arthritis: A Cause of Recurrent Upper Airway Obstruction in Rheumatoid Arthritis

    PubMed Central

    Pradhan, Pradeep; Bhardwaj, Abhishek; Venkatachalam, VP

    2016-01-01

    We report a case of bilateral cricoarytenoid joint arthritis with history of rheumatoid arthritis, presented with stridor to the outpatient department. Endolaryngoscopy revealed adducted vocal cords and a nodule over left arytenoid which later confirmed to be rheumatoid nodule on histopathologic examination. Initially, although patient responded well to medical treatment, recurrence was noticed after 6 months follow-up.

  15. A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

    PubMed

    Pamuk, Ömer Nuri; Kalyoncu, Umut; Aksu, Kenan; Omma, Ahmet; Pehlivan, Yavuz; Çağatay, Yonca; Küçükşahin, Orhan; Dönmez, Salim; Çetin, Gözde Yıldırım; Mercan, Rıdvan; Bayındır, Özün; Çefle, Ayşe; Yıldız, Fatih; Balkarlı, Ayşe; Kılıç, Levent; Çakır, Necati; Kısacık, Bünyamin; Öksüz, Mustafa Ferhat; Çobankara, Veli; Onat, Ahmet Mesut; Sayarlıoğlu, Mehmet; Öztürk, Mehmet Akif; Pamuk, Gülsüm Emel; Akkoç, Nurullah

    2016-07-01

    In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern. PMID:27221456

  16. AAS 228: Day 1 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.Plenary Session: From Space Archeology to Serving the World Today: A 20-year Journey from the Jungles of Guatemala to a Network of Satellite Remote Sensing Facilities Around the World(by Michael Zevin)In the conferences second plenary session, NASAs Daniel Irwin turned the eyes of the conference back to Earth by highlighting the huge impact that NASA missions play in protecting and developing our own planet.Daniel Irwin: using satellite imagery to detect differences in vegetation and find ancient Mayan cities. #aas228 pic.twitter.com/9LFPQdCHTM astrobites (@astrobites) June 13, 2016Irwin came to be involved in NASA through his work mapping Guatemalan jungles, where he would spend 22 days at a time exploring the treacherous jungles on foot armed with a 1st generation GPS, a compass, and a machete. A colleague introduced Irwin to the satellite imagery thathe was exploring, demonstratinghow these images are a strong complement to field work. The sharing of this satellite data with nearby villages helped to show the encroachment of agriculture and the necessity of connecting space to the village. Satellite imagery also played a role in archeological endeavors, uncovering dozens of Mayan cities that have been buried for over a millennia by vegetation, and it provided evidence that the fall of the Mayan civilization may have been due to massive deforestation that ledto drought.Glacial retreat in Chile imaged by ISERV.Irwin displayed the constellation of NASAs Earth-monitoring satellites that have played an integral role in conserving our planet and alerting the world of natural disasters. He also showed

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

    PubMed Central

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

    2013-01-01

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

  18. Targeted delivery of low-dose dexamethasone using PCL-PEG micelles for effective treatment of rheumatoid arthritis.

    PubMed

    Wang, Qin; Jiang, Jiayu; Chen, Wenfei; Jiang, Hao; Zhang, Zhirong; Sun, Xun

    2016-05-28

    Glucocorticoid (GC) is the cornerstone therapy of rheumatoid arthritis, but high doses are associated with serious adverse effects. In an effort to improve the efficacy of low-dose GC therapy, we developed a micelle system for targeted delivery to inflamed joints and validated the approach in a rat model of arthritis. Micelles loaded with dexamethasone (Dex) self-assembled from the amphipathic poly (ethylene glycol)-block-poly (ε-caprolactone) (PCL-PEG) polymer via film dispersion, and they were injected intravenously at a dose of only 0.8mg/kg into rats with adjuvant-induced arthritis. The micelles persisted for a relatively long time in the circulation, and they accumulated preferentially in inflamed joints. Micelle-delivered Dex potently reduced joint swelling, bone erosion, and inflammatory cytokine expression in both joint tissue and serum. PCL-PEG micelles caused only moderate adverse effects on body weight, lymphocyte count and blood glucose concentration, and they weakly activated the host complement system. These results suggest that encapsulating Dex in PCL-PEG micelles may allow for safe and effective low-dose GC therapy targeting inflammatory disorders. PMID:27057749

  19. Integration of efficacy, pharmacokinetic and safety assessment of interleukin-1 receptor antagonist in a preclinical model of arthritis.

    PubMed

    Zuurmond, Anne-Marie; Koudijs, Angela; van El, Benno; Doornbos, Robert P; van Manen-Vernooij, Babs C T; Bastiaans, Jacqueline H M W; Penninks, André H; van Bilsen, Jolanda H M; Cnubben, Nicole H P; Degroot, Jeroen

    2011-04-01

    Pharmacokinetic properties and safety profile of a drug are likely influenced by the disease state of a patient. In this study, we investigated the influence of arthritic processes on pharmacokinetics and immunotoxicity of interleukin-1 receptor antagonist (Anakinra) in the rat adjuvant arthritis model. Anakinra dose-dependently suppressed joint inflammation and degradation as demonstrated by reduced clinical arthritis score, paw thickness, synovial infiltration and bone degradation. In addition, plasma levels of chemokines MCP-1 and GRO/KC were reduced. Pharmacokinetic behaviour of Anakinra was influenced by disease state of the rats as judged from a decrease in C(max) and an increase of the MRT as the disease progressed at a dose of 24 and 72 mg Anakinra/kg body weight. The pharmacokinetic parameters increased dose-dependently, but non-proportionally with increasing dose. Low level anti-Anakinra antibody formation was observed at prolonged exposure to the biologic. Safety parameters, including haematology, splenic lymphocyte subset analysis, ex vivo stimulation of spleen cells and histopathology of immune system organs were affected by the disease itself to such extent that no additional effects of Anakinra could be observed. In conclusion, we demonstrated that pharmacokinetic behaviour of Anakinra was influenced by the arthritis background of the rats resulting in decreased internal exposure. PMID:21300126

  20. Intermolecular interaction between Cry2Aa and Cyt1Aa and its effect on larvicidal activity against Culex quinquefasciatus.

    PubMed

    Bideshi, Dennis K; Waldrop, Greer; Fernandez-Luna, Maria Teresa; Diaz-Mendoza, Mercedes; Wirth, Margaret C; Johnson, Jeffrey J; Park, Hyun-Woo; Federici, Brian A

    2013-08-01

    The Cyt1Aa protein of Bacillus thuringiensis susbp. israelensis elaborates demonstrable toxicity to mosquito larvae, but more importantly, it enhances the larvicidal activity of this species Cry proteins (Cry11Aa, Cry4Aa, and Cry4Ba) and delays the phenotypic expression of resistance to these that has evolved in Culex quinquefasciatus. It is also known that Cyt1Aa, which is highly lipophilic, synergizes Cry11Aa by functioning as a surrogate membrane-bound receptor for the latter protein. Little is known, however, about whether Cyt1Aa can interact similarly with other Cry proteins not primarily mosquitocidal; for example, Cry2Aa, which is active against lepidopteran larvae, but essentially inactive or has very low toxicity to mosquito larvae. Here we demonstrate by ligand binding and enzyme-linked immunosorbent assays that Cyt1Aa and Cry2Aa form intermolecular complexes in vitro, and in addition show that Cyt1Aa facilitates binding of Cry2Aa throughout the midgut of C. quinquefasciatus larvae. As Cry2Aa and Cry11Aa share structural similarity in domain II, the interaction between Cyt1Aa and Cry2Aa could be a result of a similar mechanism previously proposed for Cry11Aa and Cyt1Aa. Finally, despite the observed interaction between Cry2Aa and Cyt1Aa, only a 2-fold enhancement in toxicity resulted against C. quinquefasciatus. Regardless, our results suggest that Cry2Aa could be a useful component of mosquitocidal endotoxin complements being developed for recombinant strains of B. thuringiensis subsp. israelensis and B. sphaericus aimed at improving the efficacy of commercial products and avoiding resistance. PMID:23727800

  1. 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

  2. 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

  3. Low-level laser therapy stimulates tissue repair and reduces the extracellular matrix degradation in rats with induced arthritis in the temporomandibular joint.

    PubMed

    Lemos, George Azevedo; Rissi, Renato; de Souza Pires, Ivan Luiz; de Oliveira, Letícia Prado; de Aro, Andrea Aparecida; Pimentel, Edson Rosa; Palomari, Evanisi Teresa

    2016-08-01

    The objective of this study was to characterize morphological and biochemistry action of low-level laser therapy (LLLT) on induced arthritis in the temporomandibular joint (TMJ) of rats. Twenty-four male Wistar rats were randomly divided into groups with 12 animals each: (AG) group with arthritis induced in the left TMJ and (LG) group with arthritis induced in the left TMJ and treated with LLLT (830 nm, 30 mW, 3 J/cm(2)). Right TMJs in the AG group were used as noninjected control group (CG). Arthritis was induced by intra-articular injection of 50 μl Complete Freund's Adjuvant (CFA) and LLLT began 1 week after arthritis induction. Histopathological analysis was performed using sections stained with hematoxylin-eosin, Toluidine Blue, and picrosirius. Biochemical analysis was determined by the total concentration of sulfated glycosaminoglycans (GAGs) and evaluation of matrix metalloproteinases (MMP-2 and MMP-9). Statistical analysis was performed using paired and unpaired t tests, with p < 0.05. Compared to AG, LG had minor histopathological changes in the TMJ, smaller thickness of the articular disc in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001), high birefringence of collagen fibers in the anterior (p < 0.0001), middle (p < 0.0001) and posterior regions (p < 0.0001) on the articular disc, and statistically lower activity of MMP-2 latent (p < 0.0001), MMP-2 active (P = 0.02), MMP-9 latent (p < 0.0001), and MMP-9 active (p < 0.0001). These results suggest that LLLT can increase the remodeling and enhancing tissue repair in TMJ with induced arthritis. PMID:27147076

  4. Glutamine synthetase predicts adjuvant TACE response in hepatocellular carcinoma

    PubMed Central

    Zhang, Bo; Liu, Kai; Zhang, Jian; Dong, Liwei; Jin, Zhichao; Zhang, Xinji; Xue, Feng; He, Jia

    2015-01-01

    Background: Adjuvant transcatheter arterial chemoembolization (TACE) is associated with better outcome and reduced tumor recurrence in hepatocellular carcinoma (HCC) patients. This study aimed to investigate the relationship between glutamine synthetase (GS) expression and survival of HCC patients after postoperative adjuvant TACE. Methods: We retrospectively analyzed 554 HCC patients in two independent cohorts who underwent curative resection. Immunohistochemistry assay was used to investigate the expression of GS protein and evaluate the association with survival and the response to adjuvant TACE. Results: In training cohort, patients with low GS expression who received postoperative adjuvant TACE showed a better overall survival (OS) (P<0.001) and less early phase recurrence (P=0.016). Adjuvant TACE was an independent prognostic factor for 5-year OS (HR=0.408, 95% CI 0.261-0.639, P<0.001) and early phase recurrence (HR=0.592, 95% CI 0.376-0.931, P=0.023). The same result was confirmed in validation cohort. Patients with high GS expression in both cohorts did not have a significant response to adjuvant TACE in OS and early phase recurrence. Conclusions: GS status in tumor might be a useful tool in the selection of HCC patients who would be likely to benefit from postoperative adjuvant TACE. PMID:26884995

  5. Direct-Chill Co-Casting of AA3003/AA4045 Aluminum Ingots via Fusion™ Technology

    NASA Astrophysics Data System (ADS)

    Caron, Etienne J. F. R.; Pelayo, Rosa E. Ortega; Baserinia, Amir R.; Wells, Mary A.; Weckman, David C.; Barker, Simon; Gallerneault, Mark

    2014-06-01

    Laboratory-scale experiments were conducted to cast AA3003/AA4045 clad ingots via Fusion™ Technology, a novel process developed by Novelis Inc. for the production of aluminum clad materials such as brazing sheet. Experimental results were used to validate a steady-state thermofluids model of the Fusion™ Technology co-casting process. The numerical model was able to accurately predict the temperature field within the AA3003/AA4045 clad ingot as well as the shape of the AA3003 liquid sump. The model was also used to quantify the temperature, fraction solid, and velocity fields in a clad ingot cast with an asymmetrical molten metal-feeding system. Feeding of core and clad molten metals at opposite corners of the mold was found to reduce the risks of hot spots and liquid metal breakthrough from the core sump to the clad side of the Fusion™ Technology mold. The use of a diffuser for the AA3003 core molten metal and of a vertical feeding tube for the AA4045 clad produced different flow patterns and liquid sump shapes on either side of the mold. The quality of the metallurgical bond at the core/clad interface appeared good near the clad inlet and at the ingot centerline, but poor near the edges of the ingot. SEM-EDS analysis of the chemical composition across the interface showed that a 1 to 20- μm-deep penetration of silicon from the AA4045 clad into the AA3003 core had occurred at visually acceptable interfaces, whereas silicon diffusion across poor interfaces was very limited. A study of the model-predicted fraction solid history at different points along the interface indicated that reheating of the AA3003 core is not required to form a visually acceptable metallurgical bond. However, a sufficient amount of interaction time between the solid AA3003 core shell and the silicon-rich AA4045 clad liquid is required to chemically dissolve the surface of the core and form a good metallurgical bond. An approximate dissolution depth of 750 to 1000 μm was observed along

  6. Nerve Zap Eased Rheumatoid Arthritis in Small Study

    MedlinePlus

    ... gov/news/fullstory_159838.html Nerve Zap Eased Rheumatoid Arthritis in Small Study Treatment worked some for patients ... the gut may help ease stubborn symptoms of rheumatoid arthritis, preliminary research suggests. The study, of 17 adults ...

  7. 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)

  8. Common Therapy for Rheumatoid Arthritis Reduces Risk of Death

    MedlinePlus

    ... Research 2013 April 2013 (historical) Common Therapy for Rheumatoid Arthritis Reduces Risk of Death Taking methotrexate—a commonly ... reduce the risk of death among patients with rheumatoid arthritis (RA), according to recently-published research in the ...

  9. Antibody and T-cell responses to a virosomal adjuvanted H9N2 avian influenza vaccine: impact of distinct additional adjuvants.

    PubMed

    Radosević, Katarina; Rodriguez, Ariane; Mintardjo, Ratna; Tax, Dennis; Bengtsson, Karin Lövgren; Thompson, Catherine; Zambon, Maria; Weverling, Gerrit Jan; Uytdehaag, Fons; Goudsmit, Jaap

    2008-07-01

    A highly efficacious vaccine is required to counteract a threat of an avian influenza pandemic. Increasing the potency of vaccines by adjuvation is essential not only to overcome generally low immunogenicity of pandemic strains, but also to allow dose sparing and as such to make it feasible to satisfy huge global production demands. In this study we evaluated the ability of four distinct adjuvants to further increase immune responses to a virosomal adjuvanted avian H9N2 influenza vaccine in mice. Currently registered adjuvants aluminium phosphate, aluminium hydroxide and MF59, as well as a novel promising adjuvant MATRIX-M were included in the study. Our results demonstrate that all adjuvants significantly increased the H9N2 haemagglutinin (HA) inhibition and ELISA antibody titers induced with the virosomal adjuvanted vaccine. The adjuvants exhibited different effect on the isotype of virus specific antibodies, with MATRIX-M inducing the most pronounced skewing to IgG2a, i.e. towards Th1 type of response. While the virosomal adjuvanted pandemic influenza vaccine efficiently induced CD4(+) T-cell response, with no further increase upon adjuvation, the CD8(+) T-cell responses induced with virosomal adjuvanted vaccine could be significantly improved upon additional adjuvation with MATRIX-M or MF59. All adjuvants demonstrated a dose sparing effect, i.e. in combination with the virosomal adjuvanted pandemic influenza vaccine they increased immune responses to comparable level independent of the tested vaccine dose. In conclusion, our results demonstrate that immune responses to a virosomal adjuvanted pandemic influenza vaccine can be further enhanced by add-on adjuvants, with MATRIX-M being overall the most potent adjuvant in combination with virosomes, followed by MF59 and finally aluminium-based adjuvants. PMID:18514980

  10. 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

  11. 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

  12. Characterization of the in situ immunological responses to vaccine adjuvants.

    PubMed

    Horohov, D W; Dunham, J; Liu, C; Betancourt, A; Stewart, J C; Page, A E; Chambers, T M

    2015-03-15

    Adjuvants are included with many inactivated and some modified live vaccines to enhance immune responses to specific antigens. While early vaccines relied exclusively upon aluminum salts, still the major adjuvant used in human vaccines, other adjuvant products are used in veterinary medicine. In addition to enhancing antigen presentation, adjuvants can also enhance the development of specific immune responses. Thus, alum adjuvants often preferentially stimulate humoral immune responses. By contrast, lipid-based adjuvants are often more effective at stimulating cell-mediated immune responses. Metastim(®) is a lipid-based adjuvant reported to elicit both humoral and cellular immune responses, though the mechanism responsible for this activity remains unclear. In this study, we compared the ability of equine influenza virus vaccines containing either saline or Metastim(®) or an aluminum phosphate adjuvant to stimulate antigen presenting cell function in vivo. Six ponies were intradermally inoculated with inactivated equine influenza (KY97) mixed with either adjuvant or saline. Multiple sites were injected so that biopsies could be collected at different times post injection. The 4mm punch biopsies were formalin-fixed, paraffin-embedded, and stained with hematoxylin and eosin (H&E). Total RNA was isolated from 2mm punch biopsies for the determination of gene expression by real-time PCR. H&E staining revealed a variety of cells recruited to the injection sites, including lymphocytes, neutrophils, eosinophils and macrophages. Real-time PCR analysis of the injection site confirmed this cellular infiltration and identified increased expression of activation markers. Both vaccines also stimulated gene expressions of pro-inflammatory cytokines. The vaccine containing Metastim(®) elicited significantly higher gene expression of interferon-γ, IL-12, CD4 and CD83 compared to alum (p<0.05). While the greater induction of IFNγ-related gene expression indicates that Metastim

  13. Adjuvants for vaccines to drugs of abuse and addiction.

    PubMed

    Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

    2014-09-22

    Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. PMID:25111169

  14. Detection of AA76, a Common Form of Amyloid A Protein, as a Way of Diagnosing AA Amyloidosis.

    PubMed

    Sato, Junji; Okuda, Yasuaki; Kuroda, Takeshi; Yamada, Toshiyuki

    2016-03-01

    Reactive amyloid deposits consist of amyloid A (AA) proteins, the degradation products of serum amyloid A (SAA). Since the most common species of AA is the amino terminal portion produced by cleavage between residues 76 and 77 of SAA (AA76), the presence of AA76 in tissues could be a consequence of AA amyloid deposition. This study assessed the diagnostic significance of the detection of AA76 for AA amyloidosis using two different approaches. Biopsy specimens (n=130 from 54 subjects) from gastroduodenal mucosa or abdominal fat (n=9 from 9 subjects) of patients who had already been diagnosed with or were suspected of having AA amyloidosis were used. Fixed mucosal sections were subjected to immunohistochemistry using a newly developed antibody recognizing the carboxyl terminal end of AA76 (anti-AA76). The non-fixed materials from gastroduodenal mucosa or abdominal fat were subjected to immunoblotting for detection of the size of AA76. Among the gastroduodenal specimens (n=115) from already diagnosed patients, the positive rates of Congo red staining, immunohistochemistry using anti-AA76, and immunoblotting were 68.4%, 73.0%, and 92.2%, respectively. The anti-AA76 did not stain the supposed SAA in the blood or leakage, which was stained by anti-SAA antibody. AA76 was not detected either by immunohistochemistry or by immunoblot in the materials from patients in whom AA amyloidosis had been ruled out. In the abdominal fat, the immunoblot detected AA76 in 8 materials from 8 already diagnosed patients and did not in 1 patient whose gastroduodenal mucosa was negative. In conclusion, the detection of AA76 may alter the ability to diagnose AA amyloidosis. In immunohistochemistry for fixed specimens, the new anti-AA76 antibody can improve the specificity. Immunoblot for non-fixed materials, which can considerably improve the sensitivity, should be beneficial for small materials like abdominal fat. PMID:27098620

  15. Chitosan as an adjuvant for a Helicobacter pylori therapeutic vaccine.

    PubMed

    Gong, Yanfeng; Tao, Liming; Wang, Fucai; Liu, Wei; Jing, Lei; Liu, Dongsheng; Hu, Sijun; Xie, Yong; Zhou, Nanjin

    2015-09-01

    The aim of the present study was to delineate the therapeutic effect of a Helicobacter pylori vaccine with chitosan as an adjuvant, as well as to identify the potential mechanism against H. pylori infection when compared with an H. pylori vaccine, with cholera toxin (CT) as an adjuvant. Mice were first infected with H. pylori and, following the establishment of an effective infection model, were vaccinated using an H. pylori protein vaccine with chitosan as an adjuvant. Levels of H. pylori colonization, H. pylori‑specific antibodies and cytokines were determined by enzyme‑linked immunosorbent assay. The TLR4 and Foxp3 mRNA and protein levels were determined by reverse transcription polymerase chain reaction and immunohistochemistry, respectively. It was identified that the H. pylori elimination rate of the therapeutic vaccine with chitosan as an adjuvant (58.33%) was greater than the therapeutic vaccine with CT as an adjuvant (45.45%). The therapeutic H. pylori vaccine with chitosan as an adjuvant induced significantly greater antibody and cytokine levels when compared with the control groups. Notably, the IL‑10 and IL‑4 levels in the groups with chitosan as an adjuvant to the H. pylori vaccine were significantly greater than those in the groups with CT as an adjuvant. The mRNA expression levels of TLR4 and Foxp3 were significantly elevated in the mice that were vaccinated with chitosan as an adjuvant to the H. pylori vaccine, particularly in mice where the H. pylori infection had been eradicated. The H. pylori vaccine with chitosan as an adjuvant effectively increased the H. pylori elimination rate, the humoral immune response and the Th1/Th2 cell immune reaction; in addition, the therapeutic H. pylori vaccine regulated the Th1 and Th2 response. The significantly increased TLR4 expression and decreased CD4+CD25+Foxp3+Treg cell number contributed to the immune clearance of the H. pylori infection. Thus, the present findings demonstrate that in mice the H

  16. MDCT evaluation of acute aortic syndrome (AAS).

    PubMed

    Valente, Tullio; Rossi, Giovanni; Lassandro, Francesco; Rea, Gaetano; Marino, Maurizio; Muto, Maurizio; Molino, Antonio; Scaglione, Mariano

    2016-05-01

    Non-traumatic acute thoracic aortic syndromes (AAS) describe a spectrum of life-threatening aortic pathologies with significant implications on diagnosis, therapy and management. There is a common pathway for the various manifestations of AAS that eventually leads to a breakdown of the aortic intima and media. Improvements in biology and health policy and diffusion of technology into the community resulted in an associated decrease in mortality and morbidity related to aortic therapeutic interventions. Hybrid procedures, branched and fenestrated endografts, and percutaneous aortic valves have emerged as potent and viable alternatives to traditional surgeries. In this context, current state-of-the art multidetector CT (MDCT) is actually the gold standard in the emergency setting because of its intrinsic diagnostic value. Management of acute aortic disease has changed with the increasing realization that endovascular therapies may offer distinct advantages in these situations. This article provides a summary of AAS, focusing especially on the MDCT technique, typical and atypical findings and common pitfalls of AAS, as well as recent concepts regarding the subtypes of AAS, consisting of aortic dissection, intramural haematoma, penetrating atherosclerotic ulcer and unstable aortic aneurysm or contained aortic rupture. MDCT findings will be related to pathophysiology, timing and management options to achieve a definite and timely diagnostic and therapeutic definition. In the present article, we review the aetiology, pathophysiology, clinical presentation, outcomes and therapeutic approaches to acute aortic syndromes. PMID:27033344

  17. 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

  18. Immunopathology of chronic lentivirus-induced arthritis.

    PubMed Central

    Wilkerson, M. J.; Davis, W. C.; Baszler, T. V.; Cheevers, W. P.

    1995-01-01

    This study evaluated histopathology and mononuclear cell phenotypes in synovial lesions of chronic arthritis induced by experimental infection of Saanen goats with caprine arthritis-encephalitis lentivirus. Histological examination of carpal joint synovium of three infected goats with clinical arthritis revealed progressive lesions consisting of membrane villus hypertrophy with extensive angiogenesis and mononuclear cell infiltration and degenerative changes of membrane villus necrosis associated with loss of vasculature and infiltrates. Changes in synovial tissue of five age-matched infected goats without clinical arthritis were limited to moderate synovial membrane hyperplasia also noted in an age-matched uninfected goat. Immunohistochemistry identified CD45R+ CD5- B lymphocytes as the principal component of most perivascular infiltrates in arthritic synovium. Other mononuclear cells included perivascular CD4+ and CD8+ T lymphocytes and macrophages with a prominent accumulation of CD8+ T lymphocytes at the lining surface of inflamed villi. T lymphocytes and macrophages as well as synovial lining cells were activated with respect to MHC class II but not for interleukin-2 receptors. Inflamed villi also contained lymphoid aggregates comprised of B cell germinal centers and activated T-cell mantles. B cells expressing immunoglobulin occurred around follicles and throughout inflamed villi. These findings indicate that memory immune responses that favor expansion and maturation of B cells and immunoglobulin production contribute to the immunopathology of chronic arthritis. Images Figure 1 Figure 2 Figure 3 Figure 5 Figure 6 PMID:7778682

  19. Management of Children with Juvenile Idiopathic Arthritis.

    PubMed

    Viswanathan, Vijay; Murray, Kevin J

    2016-01-01

    Juvenile idiopathic arthritis (JIA) comprises a group of heterogeneous disorders of chronic arthritis in childhood and remains the commonest pediatric rheumatic disease associated with significant long-term morbidity. Advances in understanding of the pathogenesis, better definition of disease control/remission measures, and the arrival of biological agents have improved the outcomes remarkably. Methotrexate (Mtx) remains the first-line disease modifying (DMARD) therapy for most children with JIA due to its proven efficacy and safety. Sulphosalazine (SSz) (especially for enthesitis) and leflunomide may also have a secondary role. Tumor necrosis factor inhibitors (TNF-I), alone or in combination with Mtx have shown tremendous benefit in children with polyarticular JIA, enthesitis related arthritis (ERA) and psoriatic arthritis. Tocilizumab appears very efficacious in systemic arthritis and abatacept and tocilizumab also appear to benefit polyarticular JIA; the role of rituximab remains unclear, though clearly beneficial in adult RA. TNF-I with Mtx is also effective in uveitis associated with JIA. Biologicals have demonstrated an impressive safety record in children with JIA, although close monitoring for rare but potentially dangerous adverse events, such as tuberculosis and other infections; paradoxical development of additional autoimmune diseases; and possibly an increased risk of cancers is warranted. PMID:26639461

  20. AAS 228: Day 2 afternoon

    NASA Astrophysics Data System (ADS)

    Kohler, Susanna

    2016-06-01

    Editors Note:This week were at the 228th AAS Meeting in San Diego, CA. Along with a team ofauthors from astrobites.com, I will bewritingupdates on selectedevents at themeeting and posting twiceeach day. Follow along here or atastrobites.com, or catch ourlive-tweeted updates from the@astrobites Twitter account. The usual posting schedule for AAS Nova will resumenext week.The Limits of Scientific Cosmology: Setting the Stage: Accepted Facts, and Testing Limitations in Theory and Data (by Gourav Khullar)With a stellar lineup of speakers to talk about current and future prospects of cosmology and its limits (or lack thereof), the first session kicked off with talks by Risa Wechsler, Joseph Silk, and Sean Carroll (his talk on Multiverses is described below, by Nathan Sanders). Risa set the stage with an elaborate description of the current accepted facts in the era of precision cosmology including the standard model of concordance cosmology, described by seven parameters and an accepted Lambda-CDM paradigm (with a cosmological constant and cold dark matter). The talk stressed on the fact that all these parameters are understood to a percent order precision, which is a remarkable deviation from the time in 1990s when according to Risa, Alan Guth never thought that any of these numbers could be measured precisely!Risa Wechsler describing our current constraints on what Dark Matter could constitute.Joseph Silk discussing limits on cosmological parameters.The CMB measurements, Big Bang Nucleosynthesis estimates and galaxy clustering statistics all contribute to locking down the description of our universe. She emphasized on the tensions between different probes to measure expansion rate H0 of the universe, and small scale predictions of cold dark matter simulations, but she is hopeful that these shall be resolved eventually. Joe Silk followed this up with his interpretation of trying to understand our place in the universe and placing limits on different parameters and