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Sample records for human arthritic synovium

  1. PGNAA of human arthritic synovium for boron neutron capture synovectomy

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    Binello, E.; Yanch, J.C. [Massashucetts Institute of Technology, Cambridge, MA (United States); Shortkroff, S. [Brigham and Women`s Hospital, Boston, MA (United States)

    1997-12-01

    Boron neutron capture synovectomy (BNCS), is a proposed new therapy modality for the treatment of rheumatoid arthritis, an autoimmune disease afflicting the joints. The synovium, which is the membrane lining the joint, becomes inflamed and represents the target tissue for therapy. When a joint is unresponsive to drug treatment, physical removal of the synovium, termed synovectomy, becomes necessary. Existing options include surgery and radiation synovectomy. BNCS has advantages over these options in that it is noninvasive and does not require the administration of radioactive substances. Previous studies have shown that the uptake of {sup 10}B by human arthritic synovium ex vivo is high, ranging from 194 to 545 ppm with an unenriched boron compound. While tissue samples remain viable up to 1 week, ex vivo conditions do not accurately reflect those in vivo. This paper presents results from experiments assessing the washout of boron from the tissue and examines the implications for in vivo studies.

  2. Stereological quantification of mast cells in human synovium

    DEFF Research Database (Denmark)

    Damsgaard, T E; Sørensen, Flemming Brandt; Herlin, T;

    1999-01-01

    Mast cells participate in both the acute allergic reaction as well as in chronic inflammatory diseases. Earlier studies have revealed divergent results regarding the quantification of mast cells in the human synovium. The aim of the present study was therefore to quantify these cells in the human...... synovium, using stereological techniques. Different methods of staining and quantification have previously been used for mast cell quantification in human synovium. Stereological techniques provide precise and unbiased information on the number of cell profiles in two-dimensional tissue sections of......, in this case, human synovium. In 10 patients suffering from osteoarthritis a median of 3.6 mast cells/mm2 synovial membrane was found. The total number of cells (synoviocytes, fibroblasts, lymphocytes, leukocytes) present was 395.9 cells/mm2 (median). The mast cells constituted 0.8% of all the cell profiles...

  3. Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants

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    Uitterlinden EJ

    2008-09-01

    Full Text Available Abstract Background Glucosamine (GlcN used by patients with osteoarthritis was demonstrated to reduce pain, but the working mechanism is still not clear. Viscosupplementation with hyaluronic acid (HA is also described to reduce pain in osteoarthritis. The synthesis of HA requires GlcN as one of its main building blocks. We therefore hypothesized that addition of GlcN might increase HA production by synovium tissue. Methods Human osteoarthritic synovium explants were obtained at total knee surgery and pre-cultured for 1 day. The experimental conditions consisted of a 2 days continuation of the culture with addition of N-Acetyl-glucosamine (GlcN-Ac; 5 mM, glucosamine-hydrochloride (GlcN-HCl; 0.5 and 5 mM, glucose (Gluc; 0.5 and 5 mM. Hereafter HA production was measured in culture medium supernatant using an enzyme-linked binding protein assay. Real time RT-PCR was performed for hyaluronic acid synthase (HAS 1, 2 and 3 on RNA isolated from the explants. Results 0.5 mM and 5 mM GlcN-HCl significantly increased HA production compared to control (approximately 2 – 4-fold, whereas GlcN-Ac had no significant effect. Addition of 5 mM Gluc also increased HA production (approximately 2-fold, but 0.5 mM Gluc did not. Gene expression of the HA forming enzymes HAS 1, 2 and 3 was not altered by the addition of GlcN or Gluc. Conclusion Our data suggest that exogenous GlcN can increase HA production by synovium tissue and is more effective at lower concentrations than Gluc. This might indicate that GlcN exerts its potential analgesic properties through stimulation of synovial HA production.

  4. Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium

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    de Vries, Marieke; Bennink, Miranda B.; van Lent, Peter L. E. M.; van der Kraan, Peter M.; Koenders, Marije I.; Thurlings, Rogier M.; van de Loo, Fons A. J.

    2016-01-01

    Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use. We set out to determine the consequences of slow-freezing of human OA synovial tissue. Therefore, we validated a method that can be applied in every routine laboratory and performed a comparative study of five cryoprotective agent (CPA) solutions. To determine possible deleterious cryopreservation-thaw effects on viability, the synovial tissue architecture, metabolic activity, RNA quality, expression of cryopreservation associated stress genes, and expression of OA characteristic disease genes was studied. Furthermore, the biological activity of the cryopreserved tissue was determined by measuring cytokine secretion induced by the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium, no difference in cell and tissue morphology could be identified in the conditions using the CS10, standard and CryoSFM CPA solution for cryopreservation. However, we observed significantly lower preservation of tissue morphology with the Biofreeze and CS2 media. The other viability assays showed trends in the same direction but were not sensitive enough to detect significant differences between conditions. In all assays tested a clearly lower viability was detected in the condition in which synovium was frozen without CPA solution. This detailed analysis showed that OA synovial tissue explants can be cryopreserved while maintaining the morphology, viability and

  5. Expression of mu-opioid receptors in human chronic inflamed knee joint synovium tissue

    Institute of Scientific and Technical Information of China (English)

    YUAN Hong-bin; HE Xing-ying; XU Hai-tao; ZHU Qiu-feng; WANG Ya-hua; SHI Xue-yin

    2006-01-01

    Objective:To examine the changes of mu-opioid receptors (MORs) expression in human chronic inflamed knee joint synovium tissue. Methods:Knee joint synovium tissues were taken from 21 patients with chronic arthritis(inflamed group) and 6 fresh bodies with normal knee joints(control group). And the expression of MORs was detected by using immunohistochemistry, flow cytometry (FCM) and reverse-transcription polymerase chain reaction(RT-PCR). Results: The expression of MORs in the inflamed group was significantly higher than that in the normal group by using the 3 techniques(P<0.05).Conclusion: Chronic inflammation enhances the up-regulation of MORs in human knee joint synovium tissue.

  6. Alarmin S100A9 Induces Proinflammatory and Catabolic Effects Predominantly in the M1 Macrophages of Human Osteoarthritic Synovium.

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    van den Bosch, Martijn H; Blom, Arjen B; Schelbergen, Rik F; Koenders, Marije I; van de Loo, Fons A; van den Berg, Wim B; Vogl, Thomas; Roth, Johannes; van der Kraan, Peter M; van Lent, Peter L

    2016-10-01

    The alarmins S100A8 and S100A9 have been shown to regulate synovial activation, cartilage damage, and osteophyte formation in osteoarthritis (OA). Here we investigated the effect of S100A9 on the production of proinflammatory cytokines and matrix metalloprotease (MMP) in OA synovium, granulocyte macrophage colony-stimulating factor (GM-CSF)-differentiated/macrophage colony-stimulating factor (M-CSF)-differentiated macrophages, and OA fibroblasts. We determined which cell types in the synovium produced S100A8 and S100A9. Further, the production of proinflammatory cytokines and MMP, and the activation of canonical Wnt signaling, was determined in human OA synovium, OA fibroblasts, and monocyte-derived macrophages following stimulation with S100A9. We observed that S100A8 and S100A9 were mainly produced by GM-CSF-differentiated macrophages present in the synovium, and to a lesser extent by M-CSF-differentiated macrophages, but not by fibroblasts. S100A9 stimulation of OA synovial tissue increased the production of the proinflammatory cytokines interleukin (IL) 1β, IL-6, IL-8, and tumor necrosis factor-α. Additionally, various MMP were upregulated after S100A9 stimulation. Experiments to determine which cell type was responsible for these effects revealed that mainly stimulation of GM-CSF-differentiated macrophages and to a lesser extent M-CSF-differentiated macrophages with S100A9 increased the expression of these proinflammatory cytokines and MMP. In contrast, stimulation of fibroblasts with S100A9 did not affect their expression. Finally, stimulation of GM-CSF-differentiated, but not M-CSF-differentiated macrophages with S100A9 activated canonical Wnt signaling, whereas incubation of OA synovium with the S100A9 inhibitor paquinimod reduced the activation of canonical Wnt signaling. Predominantly mediated by M1-like macrophages, the alarmin S100A9 stimulates the production of proinflammatory and catabolic mediators and activates canonical Wnt signaling in OA

  7. Bone morphogenetic protein 2 promotes transforming growth factor β3-induced chondrogenesis of human osteoarthritic synovium-derived stem cells

    Institute of Scientific and Technical Information of China (English)

    RUI Yun-feng; DU Lin; WANG You; WANG Yang; LUI Pauline po-yee; TANG Ting-ting; CHAN Kai-ming; DAI Ke-rong

    2010-01-01

    Background Synovium-derived stem cells (SDSCs) with higher chondrogenic potential are attracting considerable attention as a cell source for cartilage regeneration. We investigated the effect of bone morphogenetic protein 2 (BMP-2) on transforming growth factor beta3 (TGF-β3)-induced chondrogenesis of SDSCs isolated from human osteoarthritic synovium in a pellet culture system. Methods The clonogenicity, stem cell marker expression and multi-differentiation potential of isolated SDSCs were determined by colony forming unit assay, flow cytometry and specific staining including alizarin red S, Oil red O and alcian blue staining, respectively. SDSCs pellet was cultured in chondrogenic medium with or without TGF-β3 or/and BMP-2. At day 21, the diameter and the weight of the pellets were measured. Chondrogenic differentiation of SDSCs was evaluated by Safranin O staining, immunohistochemical staining of collagen type Ⅱ, sulfated glycosaminoglycan (sGAG) synthesis and mRNA expression of collagen type Ⅱ, aggrecan, SOX9, link-protein, collagen type X and BMP receptor Ⅱ. Results Cells isolated under the optimized culturing density (104/60 cm2) showed clonogenicity and multi-differentiation potential. These cells were positive (>99%) for CD44, CD90, CD105 and negative (<10%) for CD34 and CD71. SDSCs differentiated to a chondrocytic phenotype in chondrogenic medium containing TGF-β3 with or without BMP-2. Safranin O staining of the extracellular matrix was positive and the expression of collagen type Ⅱ was detected. Cell pellets treated with TGF-β3 and BMP-2 were larger in diameter and weight, produced more sGAGs, and expressed higher levels of collagen type Ⅱ and other chondrogenic markers, except COL10A1, than medium with TGF-β3 alone. Conclusions SDSCs could be isolated from human osteoarthritic synovium. Supplementation with BMP-2 significantly promoted the in vitro TGF-β3-induced chondrogenic differentiation of SDSCs.

  8. Alarmin S100A9 Induces Proinflammatory and Catabolic Effects Predominantly in the M1 Macrophages of Human Osteoarthritic Synovium

    NARCIS (Netherlands)

    Bosch, M.H.J. van den; Blom, A.B.; Schelbergen, R.F.; Koenders, M.I.; Loo, F.A.J. van de; Berg, W.B. van den; Vogl, T.; Roth, J.; Kraan, P.M. van der; Lent, P.L.E.M. van

    2016-01-01

    OBJECTIVE: The alarmins S100A8 and S100A9 have been shown to regulate synovial activation, cartilage damage, and osteophyte formation in osteoarthritis (OA). Here we investigated the effect of S100A9 on the production of proinflammatory cytokines and matrix metalloprotease (MMP) in OA synovium, gran

  9. Overexpression of TGF-β1 enhances chondrogenic differentiation and proliferation of human synovium-derived stem cells

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    Kim, Yong Il; Ryu, Jae-Sung; Yeo, Jee Eun; Choi, Yun Jin; Kim, Yong Sang [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of); Ko, Kinarm [Center for Stem Cell Research, Institute of Advanced Biomedical Science, Konkuk University, Seoul 143-701 (Korea, Republic of); Koh, Yong-Gon, E-mail: yonseranglab@daum.net [Center for Stem Cell and Arthritis Research, Department of Orthopedic Surgery, Yonsei Sarang Hospital, Seoul (Korea, Republic of)

    2014-08-08

    Highlights: • Continuous TGF-β1 overexpression in hSD-MSCs did not influence their phenotypes. • Retroviral-mediated transduction of TGFB1 in hSD-MSCs enhances cell proliferation. • TGF-β1 overexpression did not effect to adipo- or osteogenic potential of hSD-MSCs. • TGF-β1 overexpression in hSD-MSCs could stimulate and accelerate chondrogenesis. - Abstract: Transforming growth factor-beta (TGF-β) superfamily proteins play a critical role in proliferation, differentiation, and other functions of mesenchymal stem cells (MSCs). During chondrogenic differentiation of MSCs, TGF-β up-regulates chondrogenic gene expression by enhancing the expression of the transcription factor SRY (sex-determining region Y)-box9 (Sox9). In this study, we investigated the effect of continuous TGF-β1 overexpression in human synovium-derived MSCs (hSD-MSCs) on immunophenotype, differentiation potential, and proliferation rate. hSD-MSCs were transduced with recombinant retroviruses (rRV) encoding TGF-β1. The results revealed that continuous overexpression of TGF-β1 did not affect their phenotype as evidenced by flow cytometry and reverse transcriptase PCR (RT-PCR). In addition, continuous TGF-β1 overexpression strongly enhanced cell proliferation of hSD-MSCs compared to the control groups. Also, induction of chondrogenesis was more effective in rRV-TGFB-transduced hSD-MSCs as shown by RT-PCR for chondrogenic markers, toluidine blue staining and glycosaminoglycan (GAG)/DNA ratio. Our data suggest that overexpression of TGF-β1 positively enhances the proliferation and chondrogenic potential of hSD-MSCs.

  10. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

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    Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young; Yeo, Jee Eun; Choi, Yun-Jin; Kim, Yong Il; Koh, Yong-Gon, E-mail: yonseranglab@daum.net

    2014-05-16

    Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.

  11. Rational Design of Benzylidenehydrazinyl-Substituted Thiazole Derivatives as Potent Inhibitors of Human Dihydroorotate Dehydrogenase with in Vivo Anti-arthritic Activity

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    Li, Shiliang; Luan, Guoqin; Ren, Xiaoli; Song, Wenlin; Xu, Liuxin; Xu, Minghao; Zhu, Junsheng; Dong, Dong; Diao, Yanyan; Liu, Xiaofeng; Zhu, Lili; Wang, Rui; Zhao, Zhenjiang; Xu, Yufang; Li, Honglin

    2015-01-01

    Human dihydroorotate dehydrogenase (hDHODH) is an attractive therapeutic target for the treatment of rheumatoid arthritis, transplant rejection and other autoimmune diseases. Based on the X-ray structure of hDHODH in complex with lead compound 7, a series of benzylidenehydrazinyl-substituted thiazole derivatives as potent inhibitors of hDHODH were designed and synthesized, of which 19 and 30 were the most potent with IC50 values in the double-digit nanomolar range. Moreover, compound 19 displayed significant anti-arthritic effects and favorable pharmacokinetic profiles in vivo. Further X-ray structure and SAR analyses revealed that the potencies of the designed inhibitors were partly attributable to additional water-mediated hydrogen bond networks formed by an unexpected buried water between hDHODH and the 2-(2-methylenehydrazinyl)thiazole scaffold. This work not only elucidates promising scaffolds targeting hDHODH for the treatment of rheumatoid arthritis, but also demonstrates that the water-mediated hydrogen bond interaction is an important factor in molecular design and optimization. PMID:26443076

  12. Anti-arthritic effects of magnolol in human interleukin 1β-stimulated fibroblast-like synoviocytes and in a rat arthritis model.

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    Jyh-Horng Wang

    Full Text Available Fibroblast-like synoviocytes (FLS play an important role in the pathologic processes of destructive arthritis by producing a number of catabolic cytokines and metalloproteinases (MMPs. The expression of these mediators is controlled at the transcriptional level. The purposes of this study were to evaluate the anti-arthritic effects of magnolol (5,5'-Diallyl-biphenyl-2,2'-diol, the major bioactive component of the bark of Magnolia officinalis, by examining its inhibitory effects on inflammatory mediator secretion and the NF-κB and AP-1 activation pathways and to investigate its therapeutic effects on the development of arthritis in a rat model. The in vitro anti-arthritic activity of magnolol was tested on interleukin (IL-1β-stimulated FLS by measuring levels of IL-6, cyclooxygenase-2, prostaglandin E(2, and matrix metalloproteinases (MMPs by ELISA and RT-PCR. Further studies on how magnolol inhibits IL-1β-stimulated cytokine expression were performed using Western blots, reporter gene assay, electrophoretic mobility shift assay, and confocal microscope analysis. The in vivo anti-arthritic effects of magnolol were evaluated in a Mycobacterium butyricum-induced arthritis model in rats. Magnolol markedly inhibited IL-1β (10 ng/mL-induced cytokine expression in a concentration-dependent manner (2.5-25 µg/mL. In clarifying the mechanisms involved, magnolol was found to inhibit the IL-1β-induced activation of the IKK/IκB/NF-κB and MAPKs pathways by suppressing the nuclear translocation and DNA binding activity of both transcription factors. In the animal model, magnolol (100 mg/kg significantly inhibited paw swelling and reduced serum cytokine levels. Our results demonstrate that magnolol inhibits the development of arthritis, suggesting that it might provide a new therapeutic approach to inflammatory arthritis diseases.

  13. Osteogenic differentiation of human synovium-derived mesenchymal stem cells from osteoarthritic knee joints%晚期骨关节炎患者膝关节滑膜间充质干细胞的体外成骨分化

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    芮云峰; 林禹丞; 陈辉; 王宸

    2013-01-01

    BACKGROUND:Mesenchymal stem cells are commonly used in tissue engineering, while whether synovium-derived mesenchymal stem cells from human knee joints can make a role in repair and regeneration of bone tissue as the appropriate seed cells need to be further verified. OBJECTIVE:To study the osteogenic differentiation potential of synovium-derived mesenchymal stem cells which were harvested from human knee joint with end-stage osteoarthritis in vitro. Meanwhile, to identify the osteogenic characteristics of these induced synovium-derived mesenchymal stem cells. METHODS:cellpopulations were enzymatical y released from the synovial membrane obtained from total knee arthroplasty. Nucleated cells were plated at an appropriate density (200 cells/cm2) for expansion at the maximum rate without colony-to-colony contact. Monoclone was obtained by selecting as primary synovium-derived mesenchymal stem cells. After primary cultured in control medium and expanded to three passages, synovium-derived mesenchymal stem cells were subjected to in vitro assays to investigate their osteogenesis potential in osteogenic medium containing dexamethasone,β-glycerophosphate and ascorbic acid. RESULTS AND CONCLUSION:Nucleated cells from the synovial membrane formed single cel-derived colonies, which were of polygon shape and star shape, uniform in size. After three passages, homogeneous populations of fibroblast-like cells were observed. Under appropriate culture conditions, synovium-derived mesenchymal stem cells were induced to differentiate to the osteocyte lineages which had typical“slabstone”appearance of osteoblasts. Osteogenesis was stained positively for alkaline phosphatase staining at day 7 and formed mineralized nodular structures at day 21, which was confirmed by Alizarin red staining. Alkaline phosphatase activity assay showed a rise after the osteogenesis induction and reached the peak at day 7. Expressions of osteocyte specific genes, such as col agen type Ⅰ, Runx2

  14. Surgery For The Arthritic Knee

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    Gross, Allan E.

    1985-01-01

    The optimal surgical procedure for the arthritic knee depends upon the type of arthritis and the patient. If the patient is ‘high demand’ (i.e., relatively active and young), and has incongruous arthritis (in either the medial or lateral compartments but not both), then realignment by osteotomy transfers the weight to the healthy compartment. If the osteotomy is successful, the patient may continue a physically demanding lifestyle. Knee replacement is indicated if the patient is ‘low demand’ (i.e., elderly or suffering from multiple joint disease) and has congruous arthritis, with destruction of both weight-bearing compartments. Knee replacement does not allow the same activity level as realignment but, fortunately, the low demand patient tends to have congruous disease (e.g., rheumatoid arthritis) and the high demand patient incongruous disease (e.g., osteoarthritis). ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Figs. 6A-BFigs. 6C-DFig. 7Fig. 8Fig. 9 PMID:21274227

  15. Psidium guajava leaves decrease arthritic symptoms in adjuvant-induced arthritic rats

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    Hanif Nasiatul Baroroh

    2016-04-01

    Psidium guajava leaf extract is effective in decreasing the inflammatory response and arthritic symptoms in rats with adjuvant-induced arthritis. Psidium guajava leaves can be developed into an alternative anti-arthritis treatment.

  16. Isolation and characterization of multipotential mesenchymal cells from the mouse synovium.

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    Ippei Futami

    Full Text Available The human synovium contains mesenchymal stem cells (MSCs, which are multipotential non-hematopoietic progenitor cells that can differentiate into a variety of mesenchymal lineages and they may therefore be a candidate cell source for tissue repair. However, the molecular mechanisms by which this can occur are still largely unknown. Mouse primary cell culture enables us to investigate the molecular mechanisms underlying various phenomena because it allows for relatively easy gene manipulation, which is indispensable for the molecular analysis. However, mouse synovial mesenchymal cells (SMCs have not been established, although rabbit, cow, and rat SMCs are available, in addition to human MSCs. The aim of this study was to establish methods to harvest the synovium and to isolate and culture primary SMCs from mice. As the mouse SMCs were not able to be harvested and isolated using the same protocol for human, rat and rabbit SMCs, the protocol for humans was modified for SMCs from the Balb/c mouse knee joint. The mouse SMCs obtained showed superior proliferative potential, growth kinetics and colony formation compared to cells derived from muscle and bone marrow. They expressed PDGFRá and Sca-1 detected by flow cytometry, and showed an osteogenic, adipogenic and chondrogenic potential similar or superior to the cells derived from muscle and bone marrow by demonstrating in vitro osteogenesis, adipogenesis and chondrogenesis. In conclusion, we established a primary mouse synovial cell culture method. The cells derived from the mouse synovium demonstrated both the ability to proliferate and multipotentiality similar or superior to the cells derived from muscle and bone marrow.

  17. Anti-arthritic effects of Musa paradisiaca sapientum L. and Aloe vera L. in adjuvant-induced arthritic rats

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    ENDANG DARMAWAN

    2006-07-01

    Full Text Available Anti-arthritic effects of Musa paradisiaca sapientum L. and Aloe vera L. on the index responses of arthritic were investigated using adjuvant-induced arthritic rats. M. paradisiaca sapientum and A. vera pulp were blended into juice then the juices were administered orally on 17-30th day. To evaluate anti-arthritic effect of the juice, an arthritic rat model was developed using Complete Freund Adjuvant on 1-16th day. In addition, the research was divided into groups (n=5 including normal control groups, positive control groups, negative control groups, 3 groups were treated by M. paradisiaca juice at 50, 100, 200 mg/kgBW doses and the other groups were treated by A. vera juices at 1, 2 and 4 mg/kgBW doses. The indexes of arthritic were determined on 17th and 31st days then analyzed using ANOVA test and t test (p<0.05. The result showed that the indexes of arthritic rats were evidently decreased by either M. sapientum or A. vera juice. Moreover, indexes of arthritic to be closely restored to the normal levels through M. paradisiaca treatment at 50 mg/kg BW dose. In conclusion, both of juice is found to be effective in decreasing the inflammatory response and arthritic symptoms in adjuvant-induced arthritic rats.

  18. Bcl-x(L) expression in vivo in rheumatoid synovium.

    LENUS (Irish Health Repository)

    Busteed, S

    2012-02-03

    To examine the expression of the apoptosis regulatory protein, Bcl-x(L), in the synovium of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Immunohistochemistry for Bcl-x(L) was carried out on synovial samples from patients with RA and OA. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis were performed to qualitatively examine the expression of Bcl-x(L). Bcl-x(L) expression was detected in the lining, endothelium and inflammatory cells of both RA (n=20) and OA (n=10) samples. However, there was significantly more expression in the lining of RA synovium compared to OA (77 vs 61%, p<0.05). Many of the positive cells in the RA subsynovium were noted to be plasma cells. There was a significant correlation between Bcl-x(L) expression and the number of inflammatory cells in the subsynovium of RA and OA patients (r (s)=0.376, p<0.05, n=30). Age and disease duration did not correlate with Bcl-x(L) expression in rheumatoid patients. Bcl-x(L) may play a role in the extended survival of synoviocytes and inflammatory cells in rheumatoid synovium.

  19. Ectopic lymphoid structures support ongoing production of class-switched autoantibodies in rheumatoid synovium.

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    Frances Humby

    2009-01-01

    Full Text Available BACKGROUND: Follicular structures resembling germinal centres (GCs that are characterized by follicular dendritic cell (FDC networks have long been recognized in chronically inflamed tissues in autoimmune diseases, including the synovium of rheumatoid arthritis (RA. However, it is debated whether these ectopic structures promote autoimmunity and chronic inflammation driving the production of pathogenic autoantibodies. Anti-citrullinated protein/peptide antibodies (ACPA are highly specific markers of RA, predict a poor prognosis, and have been suggested to be pathogenic. Therefore, the main study objectives were to determine whether ectopic lymphoid structures in RA synovium: (i express activation-induced cytidine deaminase (AID, the enzyme required for somatic hypermutation and class-switch recombination (CSR of Ig genes; (ii support ongoing CSR and ACPA production; and (iii remain functional in a RA/severe combined immunodeficiency (SCID chimera model devoid of new immune cell influx into the synovium. METHODS AND FINDINGS: Using immunohistochemistry (IHC and quantitative Taqman real-time PCR (QT-PCR in synovial tissue from 55 patients with RA, we demonstrated that FDC+ structures invariably expressed AID with a distribution resembling secondary lymphoid organs. Further, AID+/CD21+ follicular structures were surrounded by ACPA+/CD138+ plasma cells, as demonstrated by immune reactivity to citrullinated fibrinogen. Moreover, we identified a novel subset of synovial AID+/CD20+ B cells outside GCs resembling interfollicular large B cells. In order to gain direct functional evidence that AID+ structures support CSR and in situ manufacturing of class-switched ACPA, 34 SCID mice were transplanted with RA synovium and humanely killed at 4 wk for harvesting of transplants and sera. Persistent expression of AID and Igamma-Cmu circular transcripts (identifying ongoing IgM-IgG class-switching was observed in synovial grafts expressing FDCs/CD21L

  20. Hinged distraction of the adolescent arthritic hip.

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    Thacker, Mihir M; Feldman, David S; Madan, Sanjeev S; Straight, Joseph J; Scher, David M

    2005-01-01

    From 1996 to 2000, 11 adolescents with hip joint arthritis secondary to osteonecrosis or idiopathic chondrolysis were treated with articulated hinged distraction arthroplasty. Indications for surgery were severe pain and limited ambulation. Charts and radiographs were reviewed. Clinical status was assessed preoperatively and at latest follow-up (mean 4.8 years after surgery) using criteria of pain, range of motion, and ambulation level. Ten patients showed improved clinical status, with seven having an excellent outcome and three a good outcome. One patient failed distraction. Mean joint space was 2.6 mm before surgery and 4.8 mm at latest follow-up. Average duration of fixator use was 4.4 months. Four patients (36.4%) had complications. Articulated hip distraction was effective in eliminating pain, improving function, and preventing progressive degenerative changes in young patients' hips. It should be considered a salvage procedure for arthritic hips and an alternative to arthrodesis in this difficult-to-treat group of patients.

  1. Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants

    NARCIS (Netherlands)

    E.J. Uitterlinden (Elian); C.F. Verkoelen; S.M. Bierma-Zeinstra (Sita); H. Jahr (Holger); H.H. Weinans (Harrie); J.A.N. Verhaar (Jan); G.J.V.M. van Osch (Gerjo); J.L.M. Koevoet (Wendy)

    2008-01-01

    textabstractBackground. Glucosamine (GlcN) used by patients with osteoarthritis was demonstrated to reduce pain, but the working mechanism is still not clear. Viscosupplementation with hyaluronic acid (HA) is also described to reduce pain in osteoarthritis. The synthesis of HA requires GlcN as one o

  2. In vitro and in vivo evaluation of anti-arthritic, antioxidant efficacy of fucoidan from Undaria pinnatifida (Harvey) Suringar.

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    Phull, Abdul-Rehman; Majid, Muhammad; Haq, Ihsan-Ul; Khan, Muhammad Rashid; Kim, Song Ja

    2017-04-01

    Seaweed and their constituents have been traditionally employed for the management of various human pathologic conditions such as edema, urinary disorders and inflammatory anomalies. The current study was performed to investigate the antioxidant and anti-arthritic effects of fucoidan from Undaria pinnatifida. A noteworthy in vitro antioxidant potential at 500μg/ml in 2, 2-diphenyl-1-picrylhydrazyl scavenging assay (80% inhibition), nitrogen oxide inhibition assay (71.83%), hydroxyl scavenging assay (71.92%), iron chelating assay (73.55%) and a substantial ascorbic acid equivalent reducing power (399.35μg/mg ascorbic acid equivalent) and total antioxidant capacity (402.29μg/mg AAE) suggested fucoidan a good antioxidant agent. Down regulation of COX-2 expression in rabbit articular chondrocytes in a dose (0-100μg) and time (0-48h) dependent manner, unveiled its in vitro anti-inflammatory significance. In vivo carrageenan induced inflammatory rat model demonstrated a 68.19% inhibition of inflammation whereas an inflammation inhibition potential of 79.38% was recorded in anti-arthritic complete Freund's adjuvant-induced arthritic rat model. A substantial ameliorating effect on altered hematological and biochemical parameters in arthritic rats was also observed. Therefore, findings of the present study prospects fucoidan as a potential antioxidant that can effectively abrogate oxidative stress, edema and arthritis-mediated inflammation and mechanistic studies are recommended for observed activities.

  3. Melanocortin Peptide Therapy for the Treatment of Arthritic Pathologies

    Directory of Open Access Journals (Sweden)

    S. J. Getting

    2009-01-01

    Full Text Available Arthritic pathologies are a major cause of morbidity within the western world, with rheumatoid arthritis affecting approximately 1% of adults. This review highlights the therapeutic potential of naturally occurring hormones and their peptides, in both arthritic models of disease and patients. The arthritides represent a group of closely related pathologies in which cytokines, joint destruction, and leukocytes play a causal role. Here we discuss the role of naturally occurring pro-opiomelanocortin (POMC-derived melanocortin peptides (e.g., alpha melanocyte stimulating hormone [a-MSH] and synthetic derivatives in these diseases. Melanocortins exhibit their biological efficacy by modulating proinflammatory cytokines and subsequent leukocyte extravasation. Their biological effects are mediated via seven transmembrane G-protein-coupled receptors, of which five have been cloned, identified, and termed MC1 to MC5. Adrenocorticotrophic hormone represents the parent molecule of the melanocortins; the first 13 amino acids of which (termed a-MSH have been shown to be the most pharmacologically active region of the parent hormone. The melanocortin peptides have been shown to display potent anti-inflammatory effects in both animal models of disease and patients. The potential anti-inflammatory role for endogenous peptides in arthritic pathologies is in its infancy. The ability to inhibit leukocyte migration, release of cytokines, and induction of anti-inflammatory proteins appears to play an important role in affording protection in arthritic injury, and thus may lead to potential therapeutic targets.

  4. Arthroscopic Debridement and Synovium Resection for Inflammatory Hip Arthritis

    Institute of Scientific and Technical Information of China (English)

    Mi Zhou; Zhong-li Li; Yan Wang; Yu-jie Liu; Shu-ming Zhang; Jie Fu; Zhi-gang Wang; Xu Cai; Min Wei

    2013-01-01

    Objective To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis. Methods A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflam-matory arthritis. There were 17 cases of ankylosing spondylitis,11 cases of rheumatoid arthritis,and 8 cases of psoriatic arthritis. The joints were irrigated and the inflamed tissues were debrided with anthroscopy. The patients were followed up with Harris hip score,Oxford hip score,Visual Analog Scale (VAS),and magnetic resonance imaging (MRI). Statistical analysis was performed using Student t test. Results All of the 36 cases were followed up for 46-103 months,averaging 67.2±8.4 months. Har-ris and Oxford scores increased from 66.9±12.1 and 69.4±16.4 before operation to 78.4±19.3 and 80.2±18.8 after operation,respectively (P<0.05). VAS score decreased from pre-operative 8.5±2.5 to post-operative 7.2±2.5 (P<0.05). All the patients showed improved joint range of motion. MRI revealed al-leviation of hip synovitis. The results were classified as excellent in 8 patients,good in 17 patients,fair in 8 patient,and poor in 3 according to Harris hip score. Twenty-seven patients were satisfied with the operative outcomes as they regained normal daily activities. Conclusions Arthroscopy-assisted joint debridement and synovium resection is an effective proce-dure for hip lesion in inflammatory arthritis. The inflammatory lesion might be thereby controlled and the symptoms be relieved.

  5. Anti-arthritic potential of the plant Justicia gendarussa Burm F

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    Jaijesh Paval

    2009-04-01

    Full Text Available OBJECTIVE: To evaluate the anti-arthritic potential of the plant Justicia gendarussa using two different rat models. MATERIALS AND METHOD: The anti-arthritic potential of the alcoholic extract of the plant Justicia gendarussa was evaluated using the Freund's adjuvant-induced and collagen-induced arthritic rat models. The rats were treated with the ethanolic extract of Justicia gendarussa and with standard aspirin. RESULTS: The ethanolic extract of Justicia gendarussa showed significant anti-arthritic activity that was statistically similar to that of aspirin. Our results suggest that the alcoholic extract of Justicia gendarussa exhibits significant anti-arthritic potential.

  6. Anti-arthritic potential of the plant Justicia gendarussa Burm F.

    Science.gov (United States)

    Paval, Jaijesh; Kaitheri, Srinivasan Keloth; Potu, Bhagath Kumar; Govindan, Sreejith; Kumar, Raju Suresh; Narayanan, Sareesh Naduvil; Moorkoth, Sudheer

    2009-01-01

    To evaluate the anti-arthritic potential of the plant Justicia gendarussa using two different rat models. The anti-arthritic potential of the alcoholic extract of the plant Justicia gendarussa was evaluated using the Freund's adjuvant-induced and collagen-induced arthritic rat models. The rats were treated with the ethanolic extract of Justicia gendarussa and with standard aspirin. The ethanolic extract of Justicia gendarussa showed significant anti-arthritic activity that was statistically similar to that of aspirin. Our results suggest that the alcoholic extract of Justicia gendarussa exhibits significant anti-arthritic potential.

  7. A novel tumor-suppressor candidate gene-ndr2 is differentially expressed between osteoarthritis synovium cells and rheumatoid arthritis synovium fibroblasts

    Institute of Scientific and Technical Information of China (English)

    DENG Yan-chun; WANG Ji-cun; LIU Xin-ping; YAO Li-bo

    2004-01-01

    To test whether the novel tumor-suppressor candidate gene-ndr2 is also differentially expressed between osteoarthritis synovium cells (OASC) and rheumatoid arthritis synovium fibroblasts (RASF), and whether ndr2 can suppress the growth of RASF in vitro. Methods: Dot blotting, cell culture and gene transfection, cell cycle nalysis techniques were applied to investigate the effect of ndr2 on the cell phenotype and cell cycles. Results: ndr2 is expressed in OASC but absent in RASF. Transient transfection of ndr2 into RASF can suppress the growth of RASF from phenotype observation. Cell cycle analysis showed that apoptotic peaks can be detected in RASF cells transfected with ndr2 gene. Conclusion: Novel tumor suppressor candidate ndr2 is not only differentially expressed between OASC and RASF but also can induce the apoptosis of RASF in vitro.

  8. Effect of methotrexate on the mandibular development of arthritic rabbits

    Science.gov (United States)

    Meyer, Philipp; Rafayelyan, Smbat; Minden, Kirsten; Jost-Brinkmann, Paul-Georg

    2015-01-01

    Summary Introduction: Juvenile idiopathic arthritis affecting the temporomandibular joint (TMJ) can cause severe disturbances of the mandibular development. Methotrexate (MTX) is often administered as a common used remission-inducing agent to treat this disease. The aim of this study was to investigate the effect of low dose MTX on the mandibular growth in arthritic rabbits. Subjects and methods: Eighteen 10-week-old female New Zealand white rabbits were randomly assigned to three groups with six animals in each group. After being sensitized to ovalbumin (OA), the first and the second group received intra-articular injections with OA. The first group remained untreated, the second was treated by weekly injections of MTX. Cephalograms were taken from each animal at 10, 13, 16, 19, and 22 weeks of age and six mandibular distances measured. Results: All distances showed an increase between 10 and 20 per cent, whereas growth was more accentuated in the sagittal dimension. Significant differences in the overall growth could be observed between the arthritic and the control animals and less accentuated between the arthritic and the MTX animals. In contrast, existing differences between the groups were not significant during the intervals, but time had the greatest influence on mandibular growth. Conclusions: MTX seems to have a positive impact on growth in rabbits suffering from experimental arthritis of the TMJ. PMID:25518996

  9. Inhibition of JNK in synovium by treatment with golimumab in rheumatoid arthritis.

    Science.gov (United States)

    Kanbe, Katsuaki; Chiba, Junji; Nakamura, Atsushi

    2014-01-01

    The aim of this study was to investigate immunohistological changes in mitogen-activated protein kinases (MAPKs) in the synovium following treatment with golimumab, compared with methotrexate (MTX). We assessed synovial tissues for 13 different molecules to detect cytokine levels histologically from 10 methotrexate (MTX)-treated rheumatoid arthritis (RA) patients as controls and 10 golimumab plus MTX-treated RA patients. Synovium samples from both groups were assessed by hematoxylin and eosin (HE) staining and analyzed for expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cells), CD8 (T cells), CD20 (B cells), CD68 (macrophages), receptor activator of nuclear (kappa) B ligand (RANKL), bromodeoxyuridine (BrdU), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (ERK1/ERK2), and phospho-c-Jun N-terminal kinase (JNK), by an immunohistological examination. HE staining showed that there was a significant decrease in cell proliferation in the synovium in RA patients who received golimumab compared with the controls. TNF-α, IL-6, MMP3, BrdU, p38, and ERK were not seen at significant levels in either group. On the other hand, CD4, CD8, CD20, CD29, CD68, RANKL, and JNK were significantly decreased in the golimumab group compared with the control. Based on a histological analysis of the synovium, it appears that the efficacy of the treatment with golimumab may involve the inhibition of cell proliferation, with decreases in T cells, B cells, macrophages, β-1 integrin, RANKL, and JNK in the synovium, compared with MTX treatment, in RA.

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

    Science.gov (United States)

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

    2012-01-01

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

  11. RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation.

    Directory of Open Access Journals (Sweden)

    Jane A C Wilson

    2017-02-01

    Full Text Available Chikungunya virus (CHIKV is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection, acute arthritis (day 7 and chronic disease (day 30 in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent. Although day 2, 7 and 30 represent distinct stages of infection and disease, there was a pronounced overlap in up-regulated host genes and pathways. Type I interferon response genes (IRGs represented up to ≈50% of up-regulated genes, even after loss of type I interferon induction on days 7 and 30. Bioinformatic analyses suggested a number of interferon response factors were primarily responsible for maintaining type I IRG induction. A group of genes prominent in the RNA-Seq analysis and hitherto unexplored in viral arthropathies were granzymes A, B and K. Granzyme A-/- and to a lesser extent granzyme K-/-, but not granzyme B-/-, mice showed a pronounced reduction in foot swelling and arthritis, with analysis of granzyme A-/- mice showing no reductions in viral loads but reduced NK and T cell infiltrates post CHIKV infection. Treatment with Serpinb6b, a granzyme A inhibitor, also reduced arthritic inflammation in wild-type mice. In non-human primates circulating granzyme A levels were elevated after CHIKV infection, with the increase correlating with viral load. Elevated granzyme A levels were also seen in a small cohort of human CHIKV patients. Taken together these results suggest granzyme A is an important driver of arthritic inflammation and a potential target for therapy.ClinicalTrials.gov NCT00281294.

  12. RNA-Seq analysis of chikungunya virus infection and identification of granzyme A as a major promoter of arthritic inflammation

    Science.gov (United States)

    Schroder, Wayne A.; Ellis, Jonathan J.; Cumming, Helen E.; Poo, Yee Suan; Hertzog, Paul J.; Di Giallonardo, Francesca; Hueston, Linda; Le Grand, Roger; Tang, Bing; Gardner, Joy; Mahalingam, Suresh; Bird, Phillip I.

    2017-01-01

    Chikungunya virus (CHIKV) is an arthritogenic alphavirus causing epidemics of acute and chronic arthritic disease. Herein we describe a comprehensive RNA-Seq analysis of feet and lymph nodes at peak viraemia (day 2 post infection), acute arthritis (day 7) and chronic disease (day 30) in the CHIKV adult wild-type mouse model. Genes previously shown to be up-regulated in CHIKV patients were also up-regulated in the mouse model. CHIKV sequence information was also obtained with up to ≈8% of the reads mapping to the viral genome; however, no adaptive viral genome changes were apparent. Although day 2, 7 and 30 represent distinct stages of infection and disease, there was a pronounced overlap in up-regulated host genes and pathways. Type I interferon response genes (IRGs) represented up to ≈50% of up-regulated genes, even after loss of type I interferon induction on days 7 and 30. Bioinformatic analyses suggested a number of interferon response factors were primarily responsible for maintaining type I IRG induction. A group of genes prominent in the RNA-Seq analysis and hitherto unexplored in viral arthropathies were granzymes A, B and K. Granzyme A-/- and to a lesser extent granzyme K-/-, but not granzyme B-/-, mice showed a pronounced reduction in foot swelling and arthritis, with analysis of granzyme A-/- mice showing no reductions in viral loads but reduced NK and T cell infiltrates post CHIKV infection. Treatment with Serpinb6b, a granzyme A inhibitor, also reduced arthritic inflammation in wild-type mice. In non-human primates circulating granzyme A levels were elevated after CHIKV infection, with the increase correlating with viral load. Elevated granzyme A levels were also seen in a small cohort of human CHIKV patients. Taken together these results suggest granzyme A is an important driver of arthritic inflammation and a potential target for therapy. Trial Registration: ClinicalTrials.gov NCT00281294 PMID:28207896

  13. Topical ethosomal capsaicin attenuates edema and nociception in arthritic rats.

    Science.gov (United States)

    Kumar Sarwa, Khomendra; Rudrapal, Mithun; Mazumder, Bhaskar

    2015-12-01

    In this study, topical ethosomal formulation of capsaicin was prepared and evaluated for bio-efficacy in arthritic rats. Physical and biological characterizations of prepared capsaicin-loaded nano vesicular systems were also carried out. Ethosomal capsaicin showed significant reduction of rat paw edema along with promising antinociceptive action. The topical antiarthritic efficacy of prepared formulation of capsaicin was found more than that of Thermagel, a marketed gel of capsaicin. From toxicological study, no predictable signs of toxicity such as skin irritation (of experimental rats) were observed. Based on this finding, ethosomal capsaicin could be proposed as an effective as well as a safe topical delivery system for the long-term treatment of arthritis and associated inflammo-musculoskeletal disorders. Such exciting result would eventually enlighten the analgesic and anti-inflammatory potential of capsaicin for topical remedy.

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

    Science.gov (United States)

    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.

  15. Effects of intra articular tramadol on articular cartilage and synovium of rats

    OpenAIRE

    Musa Kola; Sennur Uzun; Naciye Dilara Zeybek; Fatma Sarıcaoğlu; Seda Banu Akıncı; Ülkü Aypar; Esin Asan

    2015-01-01

    Objective: To investigate the effects of intra articular tramadol injection on articular cartilage and synovium in rat knee joint.Methods: After Animal Ethical Committee approval, a total of 20 Sprague-Dawley rats were used and divided into 4 groups. Each group was composed of 5 rats. 0.2 ml of tramadol HCl was injected into the right knee joints and left knee joints of all the rats were considered as control. Control side joints received saline injection. Rats were sacrificed with ketamin on...

  16. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    OpenAIRE

    Zhang, Jing; Li, Pei; Guo, Hai-fang; Liu, Li; Liu, Xiao-dong

    2012-01-01

    Aim: To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker. Methods: The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE2 level in the rats was measured using an enzyme immunoassay. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibitio...

  17. Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review

    OpenAIRE

    Piacente S; Cheeke PR; Oleszek W

    2006-01-01

    Abstract Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa...

  18. Local Gene Delivery System by Bubble Liposomes and Ultrasound Exposure into Joint Synovium

    Directory of Open Access Journals (Sweden)

    Yoichi Negishi

    2011-01-01

    Full Text Available Recently, we have developed novel polyethylene glycol modified liposomes (bubble liposomes; BL entrapping an ultrasound (US imaging gas, which can work as a gene delivery tool with US exposure. In this study, we investigated the usefulness of US-mediated gene transfer systems with BL into synoviocytes in vitro and joint synovium in vivo. Highly efficient gene transfer could be achieved in the cultured primary synoviocytes transfected with the combination of BL and US exposure, compared to treatment with plasmid DNA (pDNA alone, pDNA plus BL, or pDNA plus US. When BL was injected into the knee joints of mice, and US exposure was applied transcutaneously to the injection site, highly efficient gene expression could be observed in the knee joint transfected with the combination of BL and US exposure, compared to treatment with pDNA alone, pDNA plus BL, or pDNA plus US. The localized and prolonged gene expression was also shown by an in vivo luciferase imaging system. Thus, this local gene delivery system into joint synovium using the combination of BL and US exposure may be an effective means for gene therapy in joint disorders.

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

    Science.gov (United States)

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

    2007-01-01

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

  20. Enhancing Methotrexate Tolerance with Folate Tagged Liposomes in Arthritic Mice.

    Science.gov (United States)

    Nogueira, Eugénia; Lager, Franck; Le Roux, Delphine; Nogueira, Patrícia; Freitas, Jaime; Charvet, Celine; Renault, Gilles; Loureiro, Ana; Almeida, Catarina R; Ohradanova-Repic, Anna; Machacek, Christian; Bernardes, Gonçalo J L; Moreira, Alexandra; Stockinger, Hannes; Burnet, Michael; Carmo, Alexandre M; Gomes, Andreia C; Preto, Ana; Bismuth, Georges; Cavaco-Paulo, Artur

    2015-12-01

    Methotrexate is the first line of treatment of rheumatoid arthritis. Since many patients become unresponsive to methotrexate treatment, only very expensive biological therapies are effective and increased methotrexate tolerance strategies need to be identified. Here we propose the encapsulation of methotrexate in a new liposomal formulation using a hydrophobic fragment of surfactant protein conjugated to a linker and folate to enhance their tolerance and efficacy. In this study we aim to evaluate the efficiency of this system to treat rheumatoid arthritis, by targeting folate receptor β present at the surface of activated macrophages, key effector cells in this pathology. The specificity of our liposomal formulation to target folate receptor β was investigated both in vitro as in vivo using a mouse model of arthritis (collagen-induced arthritis in DBA/1J mice strain). In both systems, the liposomal constructs were shown to be highly specific and efficient in targeting folate receptor β. These liposomal formulations also significantly increase the clinical benefit of the encapsulated methotrexate in vivo in arthritic mice, together with reduced expression of CD39 and CD73 ectonucleotidases by joint-infiltrating macrophages. Thus, our formulation might be a promising cost effective way to treat rheumatoid arthritis and delay or reduce methotrexate intolerance.

  1. Potential of capsaicin-loaded transfersomes in arthritic rats.

    Science.gov (United States)

    Sarwa, Khomendra Kumar; Mazumder, Bhaskar; Rudrapal, Mithun; Verma, Vinod Kumar

    2015-01-01

    In the present study, the biopotential of capsaicin (an active principle of capsicum) as a topical antiarthritic agent was studied in arthritic rats. Transfersomal vesicular system was employed for the topical administration of capsaicin in experimental rats. The characterization of prepared capsaicin-loaded transfersomes reveals their nano size (94 nm) with negative surface charge (-14.5 mV) and sufficient structural flexibility, which resulted in 60.34% entrapment efficacy, penetration across the biomembrane (220 µm) and 76.76% of drug release from vesicular system in 24 h in their intact form as evident from confocal laser scanning micrographic study. Results of transfersomal nanoformulation (capsaicin loaded, test) were compared with that of conventional gel formulation available in the market (Thermagel, standard), with an aim to assess the antiarthritic efficacy of our prepared capsaicin-loaded transfersomal formulation. In vivo antiarthritic activity study shows that our formulation possesses superior inhibitory activity than the marketed Thermagel formulation at the same dosage level, which could probably be due to the lesser permeability of Thermagel across the dermal barriers compared to our specially designed transfersomal delivery system. Moreover, the better tolerance of prepared vesicular formulation in biological system further enlightens the suitability of the transfersomal vesicle to be used as a novel carrier system for the topical administration of such highly irritant substance.

  2. Amelioratory effect of flavonoids rich Pergularia daemia extract against CFA induced arthritic rats.

    Science.gov (United States)

    Ananth, Devanesan Arul; Rameshkumar, Angappan; Jeyadevi, Ramachandran; Aseervatham, G Smilin Bell; Sripriya, Jaganathan; Bose, Prabaharan Chandra; Sivasudha, Thilagar

    2016-05-01

    Pergularia daemia Forsk. (Asclepiadaceae) is a traditionally reported medicinal herb used to treat joint pain and arthritis. However, there are no scientific reports about anti-arthritic activity of P. daemia methanolic extract on rats as animal model. This study identifies bioactive compounds present in the P. daemia methanolic extract and evaluates its anti-arthritic potential in CFA induced arthritic rats. Phytoconstituents of P. daemia extract were examined using LC-ESI/MS method. Anti-arthritic activity of P. daemia extract was determined by various biochemical experiments (RF, ESR and CRP), ultrasonography and histological analysis. LC-ESI/MS analysis resulted in the identification of major flavonoids compounds such as formononetin, qurecetin, chrysoeriol, taxifolin and naringenin. Serum biomarker analysis, after the treatment with PDME (500mg/kg b.w.) revealed that the hemoglobin (11.84±0.42g/dL) and RBC (8.38±0.67million/mm(3)) levels were significantly increased whereas WBC (8.91±0.38thousands/mm(3)), RF (17.94±0.45IU/mL), ESR (7.91±0.12mm/h) and CRP (22.56±0.26mg/L) levels were decreased when compared with the CFA induced arthritic control group. Histology results revealed that treatment with PDME has resulted in significant prevention against bony destruction by decreasing soft tissue swelling and narrowing of joint spaces (250 and 500mg/kg b.w.). Anti-arthritic effect of P. daemia might be due to the presence of these bioactive flavonoids. These findings lend pharmacological support to the reported folkloric use of P. daemia in the treatment and management of painful, arthritic inflammatory conditions. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Quantification of arthritic bone degradation by analysis of 3D micro-computed tomography data

    Science.gov (United States)

    Svensson, Carl-Magnus; Hoffmann, Bianca; Irmler, Ingo M.; Straßburger, Maria; Figge, Marc Thilo; Saluz, Hans Peter

    2017-01-01

    The use of animal models of arthritis is a key component in the evaluation of therapeutic strategies against the human disease rheumatoid arthritis (RA). Here we present quantitative measurements of bone degradation characterised by the cortical bone profile using glucose-6-phosphate isomerase (G6PI) induced arthritis. We applied micro-computed tomography (μCT) during three arthritis experiments and one control experiment to image the metatarsals of the hind paws and to investigate the effect of experimental arthritis on their cortical bone profile. For measurements of the cortical profile we automatically identified slices that are orthogonal to individual metatarsals, thereby making the measurements independent of animal placement in the scanner. We measured the average cortical thickness index (CTI) of the metatarsals, as well as the thickness changes along the metatarsal. In this study we introduced the cortical thickness gradient (CTG) as a new measure and we investigated how arthritis affects this measure. We found that in general both CTI and CTG are able to quantify arthritic progression, whilst CTG was found to be the more sensitive measure. PMID:28290525

  4. Single dose of inducible nitric oxide synthase inhibitor induces prolonged inflammatory cell accumulation and fibrosis around injured tendon and synovium

    Directory of Open Access Journals (Sweden)

    Homa Darmani

    2004-01-01

    Full Text Available THE aim of the current study was to investigate the effect of inhibition of nitric oxide (NO production after injury on inflammatory cell accumulation and fibrosis around digital flexor tendon and synovium. A standard crush injury was applied to the flexor tendons of the middle digit of the hindpaw and the overlying muscle and synovium of female Wistar rats. Thirty animals received an intraperitoneal injection of either isotonic saline or N(G-nitro-l-arginine methyl ester (L-NAME; 5 mg/kg immediately following the crush injury, and five animals were then sacrificed at various intervals and the paws processed for histology. Another group of five animals was sacrificed after 3 days for nitrite determinations. The results showed that nitrite production and hence NO synthase activity is doubled at the acute phase of tendon wound healing, and we can prevent this by administering a single dose of L-NAME immediately after injury. The incidence and severity of fibrocellular adhesions between tendon and synovium was much more marked in animals treated with L-NAME. Treatment with L-NAME elicited a chronic inflammatory response characterised by a persistent and extraordinarily severe accumulation of large numbers of inflammatory cells in the subcutaneous tissues, in muscle and in tendon. These findings indicate that in the case of injured tendon and synovium, NO could act to protect the healing tissue from an uncontrolled inflammatory response.

  5. [Establishment of rat models with altered anterior guidance and observation of histological changes in temporomandibular joint synovium].

    Science.gov (United States)

    Yuxuan, Li; Tong, Zhai; Wenhong, Tan; Lekang, Bai; Min, Xiao

    2017-06-01

    This study aims to establish a stable animal model with altered anterior guidance and investigate histological changes on temporomandibular joint (TMJ) synovium in rats. Thirty-two rats were divided into four groups, namely, control group, anterior-guidance-deficient group (T1), and anterior guidance inclined up to 15 degree (T2) and 30 degree (T3) groups. Metal crowns that add 15 and 30 degrees to the palatal side were cemented to the incisors of maxilla to increase the inclination of anterior guidance. The low-speed diamond wheel shorts for both upper and lower incisors of rats were applied to avoid contact between anterior teeth in all direction, thus establishing an anterior guidance deletion model. TMJ joints on one side of two animals in each group were harvested after 3, 7, 14, and 28 days. Pathological changes were investigated in the TMJ synovium using hematoxylin-eosin (HE) staining. The weight of T1 decreased briefly at first, and then increased slightly (P<0.05). The weight of T3 obviously reduced and then slowly increased, but remained below the initial weight (P<0.05). T3 manifested obvious synovial lining proliferation and vascular dilation (P<0.05). The rat model of anterior guidance inclined up to 30 degree could imitate the pathological features of TMJ synovium with excessive increase in anterior guidance. A higher inclination of anterior guidance might cause more damage of TMJ synovium. The effect of anterior guidance deletion on TMJ synovium is yet to be determined.
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  6. Surface Markers for Chondrogenic Determination: A Highlight of Synovium-Derived Stem Cells

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    Douglas D. Campbell

    2012-11-01

    Full Text Available Cartilage tissue engineering is a promising field in regenerative medicine that can provide substantial relief to people suffering from degenerative cartilage disease. Current research shows the greatest chondrogenic potential for healthy articular cartilage growth with minimal hypertrophic differentiation to be from mesenchymal stem cells (MSCs of synovial origin. These stem cells have the capacity for differentiation into multiple cell lineages related to mesenchymal tissue; however, evidence exists for cell surface markers that specify a greater potential for chondrogenesis than other differentiation fates. This review will examine relevant literature to summarize the chondrogenic differentiation capacities of tested synovium-derived stem cell (SDSC surface markers, along with a discussion about various other markers that may hold potential, yet require further investigation. With this information, a potential clinical benefit exists to develop a screening system for SDSCs that will produce the healthiest articular cartilage possible.

  7. Relationship between PI3K pathway and angiogenesis in CIA rat synovium.

    Science.gov (United States)

    Zou, Lin; Zhang, Guichun; Liu, Lifeng; Chen, Chen; Cao, Xuecheng; Cai, Jinfang

    2016-01-01

    To investigate the expression of hypoxia inducible factor (HIF-1α) and vascular endothelial growth factor (VEGF) in the synovium of collagen-induced arthritis (CIA) joint, and whether the PI3K pathway regulates angiogenesis in rheumatoid arthritis or not. A randomized controlled according to the principle of the rats were divided into normal control group (10 rats) and the experimental group (40 rats). The experimental group rats were established as type II collagen plus adjuvant Freund's complete adjuvant-induced arthritis model. HIF-1α and VEGF proteins' expression in serum of CIA rats group and normal control group were detected by ELISA. Microvessel density (MVD) in synovial tissue of CIA rats group and normal control group were detected by immunohistochemistry (IHC) staining. The protein expression of PTEN, PI3K, and AKT in synovial tissue were detected by Western Blot. Compared with normal control group, toes and ankle swelling and arthritis index (AI) of CIA rat increased, and the expression of VEGF and HIF-1α proteins in peripheral serum increased, IHC showed that MVD was significantly higher than that of the control group, and the difference was statistically significant (pCIA synovial tissue of rats increased, while the expression of PTEN protein decreased. Correlation analysis showed that VEGF and HIF-1 levels in the peripheral serum of CIA rats were positively correlated with arthritis index (AI); the contents of HIF-1α and VEGF in the peripheral serum of CIA rats were positively correlated with MVD in synovium tissue. The CIA rat model regulated the expression of HIF-1α and VEGF proteins in peripheral serum by PI3K signaling pathway, and then regulated neovascularization in RA.

  8. Antioxidant activity of Desmodium gangeticum and its phenolics in arthritic rats.

    Science.gov (United States)

    Govindarajan, Raghavan; Vijayakumar, Madhavan; Shirwaikar, Annie; Rawat, Ajay Kumar Singh; Mehrotra, Shanta; Pushpangadan, Palpu

    2006-12-01

    Total alcoholic extract of Desmodium gangeticum, which exhibited significant anti-inflammatory activity, was evaluated for the possible mode of action by studying its antioxidant potential in adjuvant-induced arthritic rats. Activity guided fractionation and isolation were carried out. The phenolics fraction showed maximum potency. Solid phase extraction followed by preparative HPLC of the active phenolic fraction yielded for the first time two potent antioxidant compounds, caffeic acid and chlorogenic acid, from this plant. The biological antioxidant defense system, involving superoxide dismutase, glutathione and catalase, showed a significant increase with their levels close to the normal control with a decrease in the lipid peroxide content upon administration of D. gangeticum extract (100 mg kg(-1)) and its phenolics (50 mg kg(-1)) in arthritic rats, thereby indicating the extracts antioxidant property under arthritic conditions.

  9. Anti-arthritic activity of ethanolic extract of Tridax procumbens (Linn. in Sprague Dawley rats

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    R Ramesh Petchi

    2013-01-01

    Full Text Available Objective: To determine the anti-arthritic effect of whole plant ethanolic extract of Tridax procumbens (Asteraceae in female Sprague Dawley (SD rats using the Freund′s Complete Adjuvant (FCA model. Materials and Methods: The plant was collected from different regions of Madurai District, Tamil Nadu, and the phytoconstituents were identified through chemical tests. Ethanol (95% was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for anti-arthritic screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of T. procumbens 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, the liver enzyme levels were determined and a radiological examination was carried out. Result: The preliminary phytochemical analysis of the ethanolic extract of T. procumbens indicated the presence of alkaloids, tannins, flavonoids and saponins. T. procumbens at 250 and 500 mg/kg significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control animals exhibited a significant decrease in body weight compared with control animals without arthritis. T. procumbens animals showed dose dependent reduction in decrees in body weight and arthritis. At the same time, T. procumbens significantly altered the biochemical and haematological changes induced by FCA ( P < 0.05. The anti-arthritic effect of T. procumbens was comparable with that of indomethacin. Conclusion: The whole plant extract of T. procumbens showed significant anti-arthritic activity against FCA-induced arthritis in female SD rats.

  10. Arthritic disease is more severe in older rats in a kaolin/carrageenan-induced arthritis model.

    Science.gov (United States)

    Kim, Kyoung Soo; Kim, Myung-Hwan; Yeom, Mijung; Choi, Hyun Mi; Yang, Hyung-In; Yoo, Myung Chul; Hahm, Dae-Hyun

    2012-12-01

    This study examined in an arthritis animal model whether elderly onset rheumatoid arthritis (EORA) is a more severe disease than younger onset rheumatoid arthritis. Arthritis was induced by injecting 5% kaolin/carrageenan into the left tibiotarsal ankles of 18-month-old and 4-week-old rats. Various parameters were measured to evaluate the arthritic progression of kaolin/carrageenan-induced arthritis in the rats. Immunohistochemical staining of arthritic joints was performed to determine the degree of inflammation in old and young rats. Measurements of ankle volume and thickness, arthritic index, number of squeaks, and the paw pressure test showed the 18-month-old rats had more severe disease than the young rats in a kaolin/carrageenan-induced arthritis model. The degree of inflammation and MMP-1 expression of arthritic joints in old rats was significantly higher than that of young rats based on histological evaluation with hematoxylin and eosin (H&E) staining and immunochemistry. More severe disease symptoms were found in old rats with EORA, but the molecular mechanisms still remain to be elucidated. Understanding the molecular mechanisms will be helpful to develop clinical protocols to efficiently treat patients with EORA, which is difficult to control with current protocols.

  11. Anti-arthritic activity of various extracts of Sida rhombifolia aerial parts.

    Science.gov (United States)

    Gupta, S R; Nirmal, S A; Patil, R Y; Asane, G S

    2009-01-01

    Aerial parts of the plant Sida rhombifolia Linn. (Malvaceae) were extracted successively to produce various extracts. These extracts were screened for various parameters of anti-arthritic activity, such as adjuvant-induced arthritis, motor performance, mean distance travelled, and histopathological study. Results showed that the polar constituents (ethanol and aqueous extracts) of the plant S. rhombifolia were useful in the treatment of arthritis.

  12. Mesenchymal progenitor cells derived from synovium and infrapatellar fat pad as a source for superficial zone cartilage tissue engineering: analysis of superficial zone protein/lubricin expression.

    Science.gov (United States)

    Lee, Sang Yang; Nakagawa, Toshiyuki; Reddi, A Hari

    2010-01-01

    Superficial zone protein (SZP) is a boundary lubricant of articular cartilage in joints. As SZP at the surface of articular cartilage plays an important role in the normal function of synovial joints, the localization of SZP-secreting cells at the surface of tissue-engineered cartilage is prerequisite. The aim of this study was to identify suitable progenitor cell sources for tissue engineering of superficial zone cartilage. We investigated whether mesenchymal progenitor cells (MPCs) from synovium and infrapatellar fat pad (IFP) have the potential for secretion of SZP after chondrogenic differentiation in an aggregate pellet culture system. SZP was immunolocalized in pellets from synovium-MPCs and IFP-MPCs. The enzyme-linked immunosorbent assay analysis of SZP demonstrated that chondrogenically differentiated synovium-MPC and IFP-MPC pellets secreted SZP into media. Real-time polymerase chain reaction analysis showed significant upregulation of SZP mRNA in synovium-MPC and IFP-MPC pellets after chondrogenic differentiation. The synovium-MPCs demonstrated the higher colony-forming, proliferative, and chondrogenic potential, and exhibited greater SZP secretion after chondrogenic induction compared with IFP-MPCs. In conclusion, both synovium and IFP are promising cell sources for tissue engineering of superficial zone cartilage.

  13. Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

    Institute of Scientific and Technical Information of China (English)

    Jing ZHANG; Pei LI; Hai-fang GUO; Li LIU; Xiao-dong LIU

    2012-01-01

    Aim:To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E2 (PGE2) as a biomarker.Methods:The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats.PGE2 level in the rats was measured using an enzyme immunoassay.A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production.The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE2 production in blood cells was investigated in vitro.Results:Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats.Diclofenac significantly decreased the plasma levels of PGE2 in both normal and arthritic rats.The inhibitory effect on PGE2 levels in the plasma was in proportion to the plasma concentration of diclofenac.No delay in the onset of inhibition was observed,suggesting that the effect compartment was located in the central compartment.An inhibitory effect sigmoid/max model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE2 production in vivo.The /max model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE2 production in blood cells in vitro.Conclusion:Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats,but the pharmacodynamics of diclofenac is slightly affected.A PK-PD model characterizing an inhibitory effect sigmoid /max can be used to fit the relationship between the plasma PGE2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.

  14. Effects of intra articular tramadol on articular cartilage and synovium of rats

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    Musa Kola

    2015-12-01

    Full Text Available Objective: To investigate the effects of intra articular tramadol injection on articular cartilage and synovium in rat knee joint. Methods: After Animal Ethical Committee approval, a total of 20 Sprague-Dawley rats were used and divided into 4 groups. Each group was composed of 5 rats. 0.2 ml of tramadol HCl was injected into the right knee joints and left knee joints of all the rats were considered as control. Control side joints received saline injection. Rats were sacrificed with ketamin on 1st, 7th, 14th and 21st days and knee joints were removed. Obtained tissue samples were decalcified and were dyed with Hematoxylin-eosin and Masson’s trichrome stain and examined by light microscopy for the presence of inflammation in periarticular area and synovia. Results: Congestion of synovial veins and perivascular cell infiltration were observed in tramadol group on days 1 and 7 (P < 0.05. The inflammation process was replaced by fibrosis on day 14 and fibrosis was significantly decreased on day 21. Conclusion: Intra articular tramadol should be used cautiously, keeping in mind that it may cause synovial inflammation in early phases and fibrosis in late phases. J Clin Exp Invest 2015; 6 (4: 337-342

  15. Comparing the anti-arthritic activities of the plants Justicia gendarussa Burm F. and Withania somnifera Linn

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    Paval Jaijesh

    2009-01-01

    Full Text Available The aim of this study was to compare the anti-arthritic activities of the plants Justicia gendarussa and Withania somnifera. Arthritis is induced in male albino rats using Freund′s complete adjuvant and bovine type II collagen. Leaves of J. gendarussa and roots of W. somnifera were powdered and extracted with ethanol (95% using the soxhlet method. The effect of these plant extracts on arthritic rats were assessed by various blood parameters and also by taking the change in paw volume. The plants J. gendarussa and W. somnifera suppressed the anti-arthritic changes induced in rats and the results were statistically significant.

  16. EVALUATION OF ANTI ARTHRITIC ACTIVITY OF PET – ETHER EXTRACT OF PORTULACA OLERACEA (Linn.

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    B. Mallikarjuna Rao

    2012-08-01

    Full Text Available To investigate the antiarrthritic activity of petroleum-ether extract of Portulaca oleracea. The petroleum-ether extract of Portulaca oleracea was subjected to preliminary phytochemical screening. Acute toxicity studies were carried out in Male Wistar rats and anti-arthritic activity by Fruends adjuant arthritis model. Phytochemical evaluation revealed the presence of alkaloids, tannins, flavonoids, saponins and triterpenoids. Acute toxicity studies showed that the extract was non-toxic upto a maximum dose of 2000 mg/kg body weight. Petroleum-ether extract exhibited significant anti-arthritic activity. The present study indicates that the petroleumether extract of Portulaca oleracea has a potential anti-arthritic activity can be used as anti-arthritic drug.

  17. Treatment Algorithm for Patients with Non-arthritic Hip Pain, Suspect for an Intraarticular Pathology

    DEFF Research Database (Denmark)

    Jørgensen, Rasmus Wejnold; Dippmann, Christian; Dahl, L

    2016-01-01

    BACKGROUND: The amount of patients referred with longstanding, non-arthritic hip pain is increasing, as are the treatment options. Left untreated hip dysplasia, acetabular retroversion and femoroacetabular impingement (FAI) may lead to osteoarthritis (OA). Finding the right treatment option...... associated with acetabular retroversion described in the literature were the crossover sign, the posterior wall sign and the ischial spine sign, while Wiberg's lateral center-edge angle (CE-angle) together with Leqeusne's acetabular index indicate hip dysplasia. A Tönnis index >2 indicates osteoarthritis...... for the right patient can be challenging in patients with non-arthritic hip pain. PURPOSE: The purpose of this study was to categorize the radiographic findings seen in patients with longstanding hip pain, suspect for an intraarticular pathology, and provide a treatment algorithm allocating a specific treatment...

  18. Anti-arthritic effects and toxicity of the essential oils of turmeric (Curcuma longa L.).

    Science.gov (United States)

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

    2010-01-27

    Turmeric (Curcuma longa L., Zingiberaceae) rhizomes contain two classes of secondary metabolites, curcuminoids and the less well-studied essential oils. Having previously identified potent anti-arthritic effects of the curcuminoids in turmeric extracts in an animal model of rheumatoid arthritis (RA), studies were undertaken to determine whether the turmeric essential oils (TEO) were also joint protective using the same experimental model. Crude or refined TEO extracts dramatically inhibited joint swelling (90-100% inhibition) in female rats with streptococcal cell wall (SCW)-induced arthritis when extracts were administered via intraperitoneal injection to maximize uniform delivery. However, this anti-arthritic effect was accompanied by significant morbidity and mortality. Oral administration of a 20-fold higher dose TEO was nontoxic, but only mildly joint-protective (20% inhibition). These results do not support the isolated use of TEO for arthritis treatment but, instead, identify potential safety concerns in vertebrates exposed to TEO.

  19. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

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    Roberto Furlanetto Jr

    2017-02-01

    Full Text Available Objective: We studied the effect of resistance exercise (RE on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF. Material and methods : Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams were randomly allocated into five groups: control group (CT-Sham; n = 6; group with rheumatoid arthritis (RA; n = 6; group with rheumatoid arthritis subjected to RE (RAEX; n = 6; ovariectomy group with rheumatoid arthritis (RAOV; n = 6; and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6. After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results : The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV, but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions : LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1. However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF.

  20. IN VIVO ANTI INFLAMMATORY AND ANTI ARTHRITIC ACTIVITY OF ETHANOLIC EXTRACT OF ASPARAGUS RACEMOSUS ROOTS

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    Suchita Mittal

    2013-04-01

    Full Text Available The present study is aimed to appraise the anti-inflammatory and anti-arthritic activity of ethanolic extract of Asparagus racemosus roots belonging to family Liliaceae. Carrageenan is used to induce inflammation and Freund’s Complete Adjuvant is used to induce arthritis. The result of this study revealed that Asparagus racemosus show potent effect on both the condition at a dose of 200mg/kg and 400mg/kg respectively.

  1. Acute resistance exercise reduces increased gene expression in muscle atrophy of ovariectomised arthritic rats

    Science.gov (United States)

    Furlanetto, Roberto; de Paula Souza, Aletéia; de Oliveira, Anselmo Alves; Nunes, Paulo Ricardo Prado; Michelin, Márcia Antoniazi; Chica, Javier Emilio Lazo; Murta, Eddie Fernando Candido

    2017-01-01

    Objective We studied the effect of resistance exercise (RE) on mRNA levels of atrogin-1, MuRF-1, and myostatin in the gastrocnemius muscle of arthritic rats after loss of ovarian function (LOF). Material and methods Thirty female Wistar rats (nine weeks old, 195.3 ±17.4 grams) were randomly allocated into five groups: control group (CT-Sham; n = 6); group with rheumatoid arthritis (RA; n = 6); group with rheumatoid arthritis subjected to RE (RAEX; n = 6); ovariectomy group with rheumatoid arthritis (RAOV; n = 6); and an ovariectomy group with rheumatoid arthritis subjected to RE (RAOVEX; n = 6). After 15 days of intra-articular injections with Met-BSA the animals were subjected to RE and six hours after workout were euthanised. Results The rheumatoid arthritis provoked reduction in the cross-sectional area (CSA) of muscle fibres, but the CSA was lower in the RAOV when compared to the RA groups. Skeletal muscle atrogin-1 mRNA level was increased in arthritic rats (RA and RAOV), but the atrogin-1 level was higher in RAOV group when compared to other arthritic groups. The Muscle MuRF-1 mRNA level was also increased in the RAOV group. The increased atrogin-1 and MuRF-1 mRNA levels were lower in the RAOVEX group than in the RAOV group. The myostatin mRNA level was similar in all groups, except for the RAOVEX group, in which it was lower than the other groups. Conclusions LOF results in increased loss of skeletal muscle-related ubiquitin ligases (atrogin-1 and MuRF-1). However, the RE reduces the atrogin-1, MuRF-1, and myostatin mRNA levels in muscle of arthritic rats affected by LOF. PMID:28250722

  2. Synovial Fluid Antioxidant Vitamins and Trace Elements in Clinically Healthy and Arthritic Joints of Dromedary Camels

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    Aliasghar CHALMEH

    2016-01-01

    Full Text Available Forty six male dromedary camels (Camelus dromedarius, 5 to 10 years of age were entered in this study. Before slaughtering, the animals were visually examined for abnormalities in musculoskeletal system. 33 out of 46 camels did not have any clinical articular abnormalities, whereas 13 ones had gross problems such as lameness and swollen tarsal joints. Based on clinical signs and disease history, these animals were suspected to arthritis. After slaughtering, synovial fluid specimens were taken from tarsal joints of all animals, aseptically and concentrations of zinc, copper, selenium, iron and vitamin A, E and C were assayed. Concentrations of selenium and vitamin C in arthritic joints were significantly lower than clinically healthy camels (P<0.05. Zinc concentration of arthritic synovial fluid was significantly higher than normal joints. These data showed that the arthritis could change the synovial fluid vitamins and trace elements in dromedary camels. In conclusion, the results of the current research showed that arthritic joints are in an oxidative stress situation and information regarding the changing patterns of vitamins and trace elements in synovial fluids can be considered as prognostic and diagnostic criteria for articular inflammatory processes.

  3. Analgesic, anti-inflammatory and anti-arthritic activity of Cassia uniflora Mill

    Institute of Scientific and Technical Information of China (English)

    She S Chaudhari; Sanjay R Chaudhari; Machindra J Chavan

    2012-01-01

    Objective: To evaluate the analgesic, anti-inflammatory and anti-arthritic activity of leaves of Cassia uniflora (C. uniflora) Mill. Methods: Petroleum ether, ethyl acetate and methanolic extract of C. uniflora (100 and 200 mg/kg, body weight) was screened for analgesic (Eddy's hot plate and acetic acid induced writhing), anti-inflammatory (Carrageenan induced paw edema) and anti-arthritic (Complete Freund's Adjuvant induced arthritis). In Complete Freund's Adjuvant arthritis model degree of inflammation was evaluated by hind paw swelling, body weight, and biochemical parameters and supported by radiological analysis. Results: Treatment with extracts of C. uniflora showed significant (P<0.05) and dose dependant increase in paw licking time in Eddy's hot plate method. In writhing test, extracts were significantly reduced the number of writhes. A dose dependant and significant inhibition of edema was observed in carrageenan induced paw edema. Petroleum ether extract at a dose of 100 mg/kg body weight showed most potent and significant activity which is supported by the results of body weight, biochemical parameters and radiological analysis in complete Freund's Adjuvant arthritis model. Conclusion:The extract possesses analgesic, anti-inflammatory and anti-arthritic activity which may be mediated through the phytochemical constituents of the plant.

  4. Anti-inflammatory and anti-arthritic effects of yucca schidigera: A review

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    Piacente S

    2006-03-01

    Full Text Available Abstract Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E. These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS, which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

  5. Anti-inflammatory and anti-arthritic effects of Yucca schidigera: a review.

    Science.gov (United States)

    Cheeke, P R; Piacente, S; Oleszek, W

    2006-03-29

    Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

  6. The Features of the Synovium in Early Rheumatoid Arthritis According to the 2010 ACR/EULAR Classification Criteria

    Science.gov (United States)

    van de Sande, Marleen G. H.; de Hair, Maria J. H.; Schuller, Yvonne; van de Sande, Gijs P. M.; Wijbrandts, Carla A.; Dinant, Huib J.; Gerlag, Danielle M.; Tak, Paul P.

    2012-01-01

    Objectives It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA) enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. Methods At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD)-naïve early RA patients (clinical signs and symptoms EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. Conclusion The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria. PMID:22574210

  7. The features of the synovium in early rheumatoid arthritis according to the 2010 ACR/EULAR classification criteria.

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    Marleen G H van de Sande

    Full Text Available OBJECTIVES: It has been shown in early arthritis cohorts that the 2010 ACR/EULAR criteria for rheumatoid arthritis (RA enable an earlier diagnosis, perhaps at the cost of a somewhat more heterogeneous patient population. We describe the features of synovial inflammation in RA patients classified according to these new criteria. METHODS: At baseline, synovial tissue biopsy samples were obtained from disease-modifying antirheumatic drug (DMARD-naïve early RA patients (clinical signs and symptoms <1 year. Synovial tissue was analyzed for cell infiltration, vascularity, and expression of adhesion molecules. Stained sections were evaluated by digital image analysis. Patients were classified according to the two different sets of classification criteria, autoantibody status, and outcome. FINDINGS: Synovial tissue of 69 RA patients according to 2010 ACR/EULAR criteria was analyzed: 56 patients who fulfilled the criteria for RA at baseline and 13 who were initially diagnosed as undifferentiated arthritis but fulfilled criteria for RA upon follow up. The synovium at baseline was infiltrated by plasma cells, macrophages, and T cells as well as other cells, and findings were comparable to those when patients were selected based on the 1987 ACR criteria for RA. There was no clear cut difference in the characteristics of the synovium between RA patients initially diagnosed as undifferentiated arthritis and those who already fulfilled classification criteria at baseline. CONCLUSION: The features of synovial inflammation are similar when the 2010 ACR/EULAR classification criteria are used compared to the 1987 ACR criteria.

  8. Use of synovium-derived stromal cells and chitosan/collagen type I scaffolds for cartilage tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Gong Zhongcheng; Lin Zhaoquan [Department of Oral and Maxillofacial Surgery, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054 (China); Xiong Hui; Long Xing; Wei Lili; Li Jian; Wu Yang, E-mail: xinglong1957@yahoo.com.c [State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079 (China)

    2010-10-01

    The objective was to investigate synovium-derived stromal cells (SDSCs) coupled with chitosan/collagen type I (CS/COL-I) scaffolds for cartilage engineering. CS/COL-I scaffolds were fabricated through freeze-drying and cross-linked by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. SDSCs were isolated from synovium and cultured onto CS/COL-I scaffolds, constructs of which were incubated in serum-free chondrogenic medium with sequential application of TGF-{beta}1 and bFGF for up to 21 days and then implanted into nude mice. The physical characteristics of the scaffolds were examined. The quality of the in vitro constructs was assessed in terms of DNA content by PicoGreen assay and cartilaginous matrix by histological examination. The implants of the constructs were evaluated by histological and immunohistochemical examinations and reverse transcription PCR. Results indicated that the CS/COL-I scaffold showed porous structures, and the DNA content of SDSCs in CS/COL-I scaffolds increased at 1 week culture time. Both of the constructs in vitro and the implants were examined with positive stained GAGs histologically and the implants with positive collagen type II immunohistochemically. RT-PCR of the implants indicated that aggrecan and collagen type II expressed. It suggested that SDSCs coupled with CS/COL-I scaffolds treated sequentially with TGF-{beta}1 and bFGF in vitro were highly competent for engineered cartilage formation in vitro and in vivo.

  9. Anti-Arthritic Activity of Bartogenic Acid Isolated from Fruits of Barringtonia racemosa Roxb. (Lecythidaceae

    Directory of Open Access Journals (Sweden)

    Kalpesh Ramdas Patil

    2011-01-01

    Full Text Available The fruits of Barringtonia racemosa are prescribed in the ayurvedic literature for the treatment of pain, inflammation and rheumatic conditions. In present investigation, activity guided isolation of bartogenic acid (BA and its evaluation in the Complete Freund's Adjuvant (CFA-induced arthritis in rats is reported. Among the various extracts and fractions investigated preliminarily for carrageenan-induced acute inflammation in rats, the ethyl acetate fraction displayed potent anti-inflammatory activity. Large-scale isolation and characterization using chromatography and spectral study confirmed that the constituent responsible for the observed pharmacological effects was BA. Subsequently the BA was evaluated for effectiveness against CFA-induced arthritis in rats. The results indicate that at doses of 2, 5, and 10 mg kg−1 day−1, p.o., BA protects rats against the primary and secondary arthritic lesions, body weight changes and haematological perturbations induced by CFA. The serum markers of inflammation and arthritis, such as C-reactive protein and rheumatoid factor, were also reduced in the BA-treated arthritic rats. The overall severity of arthritis as determined by radiological analysis and pain scores indicated that BA exerts a potent protective effect against adjuvant-induced arthritis in rats. In conclusion, the present study validates the ethnomedicinal use of fruits of B. racemosa in the treatment of pain and inflammatory conditions. It further establishes the potent anti-arthritic effects of BA. However, additional clinical investigations are needed to prove the efficacy of BA in the treatment of various immuno-inflammatory disorders.

  10. Cyclosporin inhibits hyperalgesia and edema in arthritic rats: role of the central nervous system

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    J.N. Francischi

    1997-01-01

    Full Text Available Since arthritis induced by Mycobacterium products (adjuvant in rats is considered to be immunologically driven, the objective of the present study was to determine if the immunosuppressor drug cyclosporin could affect hindpaw edema and joint hyperalgesia simultaneously. Female Holtzman rats (140-170 g presented hyperalgesia and edema on the 8th and 12th day following adjuvant injection. Daily systemic (oral or intramuscular administration of cyclosporin (0.5-5.0 mg kg-1 day-1 or dexamethasone (0.01-0.1 mg kg-1 day-1 for 15 days starting on day zero dose-dependently inhibited the hindpaw edema and hyperalgesia in arthritic rats. However, hyperalgesia but not edema could be detected two days after cyclosporin withdrawal. We concluded that a the continuous presence of cyclosporin is essential to reduce the development of joint hyperalgesia and that b different mechanisms underlie the appearance of hyperalgesia and edema in this model. The intracerebroventricular (icv administration of 5-50-fold smaller doses of cyclosporin (1.5-150 µg/day or dexamethasone (15 µg/day also reduced the arthritic hindpaw edema and hyperalgesia. Peripheral blood from animals injected with effective systemic cyclosporin doses showed detectable levels of the drug, whereas peripheral blood from those injected with icv cyclosporin did not, as measured by specific RIA. Our results indicate that cyclosporin administered by the central route is as effective as by the systemic route to reduce joint hyperalgesia and hindpaw edema in arthritic rats. The antiarthritic effect induced by low doses of cyclosporin in the central nervous system (CNS could be explored to avoid its often associated systemic side effects during chronic therapy. However, the mechanism(s involved in the antiarthritic response to cyclosporin in the CNS remain to be elucidated

  11. Detailed analysis of the cell infiltrate and the expression of mediators of synovial inflammation and joint destruction in the synovium of patients with psoriatic arthritis: implications for treatment

    NARCIS (Netherlands)

    A.W.R. van Kuijk; P. Reinders-Blankert; T.J.M. Smeets; B.A.C. Dijkmans; P.P. Tak

    2006-01-01

    Background: The synovial tissue is a primary target of many inflammatory arthropathies, including psoriatic arthritis ( PsA). Identification of proinflammatory molecules in the synovium may help to identify potentially therapeutic targets. Objective: To investigate extensively the features of cell i

  12. TWEAK and its receptor Fn14 in the synovium of patients with rheumatoid arthritis compared to psoriatic arthritis and its response to tumour necrosis factor blockade

    NARCIS (Netherlands)

    A.W.R. van Kuijk; C.A. Wijbrandts; M. Vinkenoog; T.S. Zheng; K.A. Reedquist; P.P. Tak

    2010-01-01

    Objective: To investigate the expression of tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) in the inflamed synovium of patients with arthritis, as TWEAK blockade has been observed to have a beneficial effect in an ani

  13. Chromatographic finger print analysis and lysosomal membrane stabilisation activity of active fraction of Alstonia scholaris leaf extract in arthritic rats

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    Swapnil Goyal

    2014-01-01

    Full Text Available Object: The present study was aimed to assess the anti-arthritic activity of chloroform fraction of Alstonia scholaris leaf extract against Freund′s complete adjuvant (FCA-induced arthritis in rats. Materials and Methods: The anti-inflammatory activity of various fractions of ethanolic extract of Alstonia scholaris at concentration of 100 mg/kg was studied using the carrageenan-induced inflammatory models. The chloroform fraction shows significant anti-inflammatory activity. The chloroform fraction was further studied for anti-arthritic activity and HPTLC fingerprint analysis. For anti-arthritic activity, the active chloroform fraction was administered at the concentrations of 50 and 100 mg/kg body weight. The effect of chloroform fraction on liver ALP, ACP and LDH levels of lysosomal enzymes of FCA arthritic animals were studied. Indomethacin and prednisolone (10 mg/kg was used as standard. HPTLC studies were carried out using CAMAG HPTLC system equipped with linomat IV applicator, TLC scanner; Reprostar 3 and WIN CATS-4 software were used. Results: The chloroform fraction at 100 mg/kg, showed maximum inhibition (34.16% of inflammation induced by carrageenan. In FCA-induced arthritis, the chloroform fraction showed a highly significant reduction in paw volume (50 mg/kg-72.71%; 100 mg/kg-74.35%. The levels of lysosomal enzymes were significantly decreased in the chloroform fraction-treated groups. Conclusion: The possible mechanism of action of the chloroform fraction of Alstonia scholaris leaf extract may be through its stabilising action on lysosomal membranes. Future studies will provide new insights into the anti-arthritic activity of Alstonia scholaris and isolation of compound from it may eventually lead to development of a new class of anti-arthritic agent.

  14. Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology

    DEFF Research Database (Denmark)

    Volck, B; Johansen, J S; Stoltenberg, M

    2001-01-01

    OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other......, which increased again at clinical relapse. CONCLUSIONS: YKL-40 in SF is derived from cells in the inflamed synovium, chondrocytes and SF neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved in the pathophysiology of the arthritic processes and reflect local disease activity....

  15. Novel organ-slice culturing system to simulate meniscal repair: Proof of concept using a synovium-based pool of meniscoprogenitor cells.

    Science.gov (United States)

    Hunziker, Ernst B; Lippuner, Kurt; Keel, Marius J B; Shintani, Nahoko

    2016-09-01

    Meniscal injuries can occur secondary to trauma or be instigated by the changes in knee-joint function that are associated with aging, osteo- and rheumatoid arthritis, disturbances in gait, and obesity. Sixty percent of persons over 50 years of age manifest signs of meniscal pathology. The surgical and arthroscopic measures that are currently implemented to treat meniscal deficiencies bring only transient relief from pain and effect but a temporary improvement in joint function. Although tissue-engineering-based approaches to meniscal repair are now being pursued, an appropriate in-vitro model has not been conceived. The aim of this study was to develop an organ-slice culturing system to simulate the repair of human meniscal lesions in vitro. The model consists of a ring of bovine meniscus enclosing a chamber that represents the defect and reproduces its sequestered physiological microenvironment. The defect, which is closed with a porous membrane, is filled with fragments of synovial tissue, as a source of meniscoprogenitor cells, and a fibrin-embedded, calcium-phosphate-entrapped depot of the meniscogenic agents BMP-2 and TGF-β1. After culturing for 2 to 6 weeks, the constructs were evaluated histochemically and histomorphometrically, as well as immunohistochemically, for the apoptotic marker caspase 3 and collagen types I and II. Under the defined conditions, the fragments of synovium underwent differentiation into meniscal tissue, which bonded with the parent meniscal wall. Both the parent and the neoformed meniscal tissue survived the duration of the culturing period without significant cell losses. The concept on which the in-vitro system is based was thus validated. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1588-1596, 2016.

  16. Chondrogenic capacity of CD105-positive synovium-derived mesenchymal stem cells%CD105+滑膜间充质干细胞成软骨能力

    Institute of Scientific and Technical Information of China (English)

    范文帅; 刘嘉; 潘建锋; 陈晨; 阎作勤; 郭常安

    2015-01-01

    Objective To evaluate the proliferation and chondrogenic differentiation of CD105 + enriched synovium-derived mesenchymal stem cells (SMSCs).Methods The synovium-derived mesenchymal stem cells (SMSCs) were obtained from human synovium by enzyme digestion and CD105-positive (CD105 +) ceils were enriched using fluorescence activated cell sorting (FACS).The proliferation ability of CD105 + SMSCs was measured through WST-1 at day 3 and day 7.The chondrogenic differentiation of CD105 + SMSCs was detected by toluidine blue staining for aggrecan and immunohistochemistry staining for type Ⅱ collagen after 21 days introduction.Results The synovium-derived mesenchymal stem cells (SMSCs) showed star or spindle shape.No obvious differences in morphology were noted after sorting.Immunofluorescence staining showed that there were more CD105 + cells in the sorted group than the unsorted.There was statistical difference between sorted and unsorted cells at day 3 (0.376 ± 0.012,0.329±0.012) andday7 (0.581 ±0.009,0.524 ±0.007) on theA value by WST-1 (P<0.05).The toluidine blue staining for aggrecan and immunohistochemistry staining for type Ⅱ collagen were more and stronger in sorted cells than unsorted after 21 days chondrogenic differentiation,which indicated that CD105 + SMSCs synthesized more cartilage extracellular matrix.Conclusion The CD105 + SMSCs have stronger proliferation ability and chondrogenic capacity,which may be promising cell sources for cartilage tissue engineering.%目的 分选CD105+滑膜间充质干细胞(SMSCs),观察其增殖和向软骨细胞分化的能力.方法 酶消化滑膜组织分离SMSCs,流式细胞仪分选CD105+ SMSCs;第3、7天采用WST-1测定SMSCs的增殖能力;软骨诱导21 d进行免疫组织化学染色,检测蛋白聚糖和Ⅱ型胶原.结果 酶消化获取的SMSCs为星形或梭形,分选后SMSCs形态无明显变化.免疫荧光显示分选组CD105+细胞较未分选组明显增多.WST-1增殖检测

  17. Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis.

    Science.gov (United States)

    Sun, Antonia RuJia; Panchal, Sunil K; Friis, Thor; Sekar, Sunderajhan; Crawford, Ross; Brown, Lindsay; Xiao, Yin; Prasadam, Indira

    2017-01-01

    Epidemiological and experimental studies have established obesity to be an important risk factor for osteoarthritis (OA), however, the mechanisms underlying this link remains largely unknown. Here, we studied local inflammatory responses in metabolic-OA. Wistar rats were fed with control diet (CD) and high-carbohydrate, high-fat diet (HCHF) for period of 8 and 16 weeks. After euthanasia, the knees were examined to assess the articular cartilage changes and inflammation in synovial membrane. Further IHC was conducted to determine the macrophage-polarization status of the synovium. In addition, CD and HCHF synovial fluid was co-cultured with bone marrow-derived macrophages to assess the effect of synovial fluid inflammation on macrophage polarisation. Our study showed that, obesity induced by a high-carbohydrate, high-fat (HCHF) diet is associated with spontaneous and local inflammation of the synovial membranes in rats even before the cartilage degradation. This was followed by increased synovitis and increased macrophage infiltration into the synovium and a predominant elevation of pro-inflammatory M1 macrophages. In addition, bone marrow derived macrophages, cultured with synovial fluid collected from the knees of obese rats exhibited a pro-inflammatory M1 macrophage phenotype. Our study demonstrate a strong association between obesity and a dynamic immune response locally within synovial tissues. Furthermore, we have also identified synovial resident macrophages to play a vital role in the inflammation caused by the HCHF diet. Therefore, future therapeutic strategies targeted at the synovial macrophage phenotype may be the key to break the link between obesity and OA.

  18. Anti-arthritic activity of a classical Ayurvedic formulation Vatari Guggulu in rats

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    Madhavi G. Patel

    2016-10-01

    Full Text Available In India, Vatari Guggulu has been traditionally used in the Ayurvedic system of medicine to treat rheumatoid arthritis (RA. The current study was undertaken to evaluate anti-arthritic activity of alcoholic extract of Vatari Guggulu in rats. Arthritis was induced by administration of formaldehyde (2%v/v or Complete Freund's Adjuvant (CFA into the sub-plantar surface of left hind paw of the animals. The extract was administered to the rats by oral gavages in different doses. Joint swelling was measured in formaldehyde induced arthritis. Various physical, biochemical and histopathological parameters were determined in CFA induced arthritis. Vatari Guggulu extract (VGE produced significant (P < 0.05 inhibition of joint swelling in both formaldehyde and CFA induced arthritis. The treatment also brought to normalcy the increased white blood cell (WBC count, rheumatoid factor (RF, erythrocyte sedimentation rate (ESR, cholesterol, triglycerides and LDL with an enhancement of haemoglobin (Hb levels and red blood cell (RBC count. These effects were found to be dose dependent. These effects were comparable with standard drug indomethacin. Histo-pathological studies of the ankles of VGE treated animals exhibited significant improvements. VGE did not show any toxic symptoms even at a dose of 2000 mg/kg in acute toxicity studies on rats. Thus, Vatari Guggulu, a classical Ayurvedic formulation of the Indian System of Medicine, exhibited significant anti-arthritic activity in formaldehyde and CFA induced arthritis in rats. This study corroborates the claims of Ayurveda on Vatari Guggulu.

  19. The effects of pressure on arthritic knees in a rat model of CFA-induced arthritis.

    Science.gov (United States)

    Koo, Sung Tae; Lee, Chang-Hyung; Choi, Hyeunseok; Shin, Yong Il; Ha, Ki Tae; Ye, Hanna; Shim, Hyun Bo

    2013-01-01

    Pain is influenced by weather changes under certain circumstances, and inflammatory pain in animal models is ameliorated by pressure, but the underlying mechanism of atmospheric pressure has not been clearly elucidated. To examine the effect of pressure on pain in an arthritic animal model. Controlled animal study. Laboratory animal study. Following an injection of complete Freund's adjuvant (CFA) into one side of a knee joint, 32 rats were assigned randomly to 2 groups and either placed under 1 or 2.5 atmospheres absolute (ATA) in a hyperbaric chamber for 5 hours. The pain levels were assessed daily for up to 2 weeks post-injection to determine the changes in weight bearing (WB) of the affected limbs. In addition, the levels of gelatinase, MMP-2, and MMP-9 expression in the synovial fluids of the knees were analyzed. After arthritis induction, the rats in the 1 ATA group showed reduced WB of the affected limbs (CFA injection in the 1 ATA group. However, repetitive exposure to 2.5 ATA significantly reduced this ratio in the 2.5 ATA group. Although a sufficient number of samples were used to support the hypothesis that high atmospheric pressure improves a painful condition in this study, an additional larger-scale study will be needed to confirm these findings. Exposure to elevated pressures appears to relieve arthritic pain for extended periods by reducing the inflammatory process and should be considered as a possible alternative pain-reducing therapy.

  20. The pattern of health care utilization of elderly people with arthritic pain in the hip or knee

    NARCIS (Netherlands)

    Hopman-Rock, M.; Bock, G.H. de; Bijlsma, J.W.J.; Springer, M.P.; Hofman, A.; Kraaimaat, F.W.

    1997-01-01

    Objective: The aim of the study was to determine the pattern of health care utilization of people aged 55-74 years with arthritic pain in the knee or hip. Design: People with current pain were identified in a population- based study. A filter model was used to describe the pattern of health care uti

  1. Anti-arthritic activity of ethanol extract of Claoxylon indicum on Freund's complete adjuvant-induced arthritis in mice.

    Science.gov (United States)

    Chen, Yong; Wang, Qi-Wen; Zuo, Jian; Chen, Jian-Wei; Li, Xiang

    2017-01-05

    Claoxylon indicum Hassk. (Euphorbiaceae), named Diu Le Bang, have functions of dehumidification and relieving swelling pain, and is used as a folk medicine to treat Rheumatoid arthritis (RA), lumbocrural pain and foot edema in the south of China. The aim of the present study was to investigate the anti-arthritic activity of the ethanol extract of Claoxylon indicum (CIE) on mice with adjuvant induced joint arthritis. Adjuvant arthritis was induced in mice by subcutaneous injection of complete Freund's adjuvant into the plantar surface of right hind paw. Arthritis severity was evaluated by arthritic score, hind paws oedema and spleen index, and histological examinations. Serum samples were collected for determination of malondialdehyde (MDA) and alkaline phosphatase (ALP) levels. The expression of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in the specimens of knee joints was determined by standard immunohistochemical techniques. CIE administration (0.4 and 0.8 g/kg) suppressed the inflammatory responses in the joints of adjuvant-induced arthritis (AIA) mice, suggested by the modulatory effects on paw swelling, hyperplasia of lymphatic tissues and synovial membrane. It also decreased the levels of MDA and ALP in serum and downregulated the expression of IL-1β and TNF-α in the arthritic joints of AIA mice. These results suggested that CIE possessed substantial anti-arthritic activity due to immumodepression and regulation of cytokines. CIE may be a potential candidate for the treatment of RA.

  2. Quantitative Assessment of Synovial Vascularity Using Contrast-Enhanced Power Doppler Ultrasonography: Correlation with Histologic Findings and MR Imaging Findings in Arthritic Rabbit Knee Model

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Hoon; Shin, Myung Jin; Kim, Seong Moon; Kim, Namkug; Suh, Sang Hyun [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2008-02-15

    To validate contrast-enhanced power Doppler ultrasonography (PD US) for the evaluation of synovial vascularity in an arthritic rabbit knee model in correlation with MR and histological findings. Power Doppler ultrasonography was performed for carrageenin-induced arthritic left knee and control right knee of 13 rabbits, first without and then with sonic contrast agent enhancement (Levovist, Schering, Berlin Germany), followed by gadolinium-enhanced MR imaging. Synovial vascularity was quantitatively assessed by calculating the color pixel area in power Doppler sonography using a computer-aided image analysis program and by grading the enhancement on MR images: grade 1, enhancement of knee joint is less than one-third of the area; grade 2, one-third to two-thirds enhancement; and grade 3, more than two-thirds enhancement. Microvessel density (MVD) was measured on slides stained immunohistochemically for CD31 antigen for histological assessment. The mean area of color pixels in PD US changed from 4.37 to 16.42 mm{sup 2} in the arthritic knee after enhancement (p < 0.05), whereas it changed from 0.77 to 2.31 mm{sup 2} in the control knee (p < 0.05). Arthritic knees had greater power Doppler signal than control knees both before and after contrast administration (p < 0.05). The average MVD was 88 in arthritic knees and 46 in control knees. MVDs correlated with color pixel areas of contrast-enhanced power Doppler imaging in arthritic knees. In MR grading of arthritic knees, five were grade 2 and eight were grade 3. MVD and PD US revealed no significant difference between grade 2 and 3 arthritic knees (p > 0.05). Sonic contrast-enhanced PD US improves the visualization of synovial vascularity and allows quantitative measurement in experimentally induced rabbit arthritic knees.

  3. ANTI-INFLAMMATORY AND ANTI-ARTHRITIC ACTIVITIES OF DELONIX ELATA BARK EXTRACTS

    Directory of Open Access Journals (Sweden)

    G. Murugananthan

    2011-06-01

    Full Text Available Delonix elata (D. elata, has long been used in traditional herbal medicine for the treatment of arthritis pain. In the present study an attempt was made to study the effect of D. elata barks for its anti-inflammatory and anti-arthritic effect in animal models. Barks were subjected for extraction with pet. ether, chloroform and 40% hydroalcohol successively and evaporated under rotary evaporator to get the concentrated extract. All the extracts were subjected for acute oral toxicity studies in rats and found to be safe up to the dose of 5g/kg body weight. Anti-inflammatory screening by carrageenan-induced paw oedema and cotton pellet induced granuloma method, the hydro alcohol extract of D. elata barks showed significant protection against the inflammation. In Complete Freund’s Adjuvant induced arthritis model also the hydro alcohol exhibited significant protection on day 7 onwards.

  4. Comparative Study of Early Maladaptive Schemas in Rheumatoid Arthrits Patients and Normal Adults

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    Fatemeh Rezaei

    2014-01-01

    Full Text Available Early maladaptive schemas (EMSs designed to ases early distres. EMSs are at he core of personality pathology and psychological distres. The main objective of this study was to find out he diferences betwen rheumatoid arthrits (RA patients and normal adults on EMSs. 10 RA patients and 10 normal adults completed Young’s Schema Questionaire developed by Jefery Young (198. The results showed that data was subjected to statistical analysis; T- test showed that the RA patients reported a signifcantly greater severity of early maladaptive schemata than the normal subjects. This study sugested that a remarkable amount of RA patients may sufer from EMSs which have an efect on their pain situation. These findings confirm those pieces of evidence indicating the psychological treatments included in multidisciplinary programs for this disorder.

  5. Analysis of myosin-V immunoreactive myenteric neurons from arthritic rats

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    Ivan Domicio da Silva Souza

    2011-09-01

    Full Text Available CONTEXT: The inflammatory response itself and the consequent oxidative stress are able to promote neurodegeneration. So, it is possible that enteric nervous system is affected by inflammatory diseases threatening quality of life of patients. However, gastrointestinal symptoms of arthritis are usually attributed to anti-inflammatory drugs rather than neural damage. OBJECTIVE: To confirm if the general population of myenteric neurons from the ileum and jejunum of rats is affected by arthritis. METHODS: Twenty Holtzmann rats, 58-day-old male, were used and divided in four groups: control group (C30, arthritic group (Art30, older control group (C60 and older arthritic group (Art60. At 58 days old, the animals in groups Art30 and Art60 received an injection of the complete Freund's adjuvant in order to induce arthritis. The whole-mount preparations of ileum and jejunum were processed for myosin-V immunohistochemistry. Quantitative and morphometric analyses were performed. RESULTS: Groups Art30 and Art60 presented, respectively, a reduction of 2% and 6% in intestinal area when compared to their control groups. No significant differences were observed in general neuronal density among the four groups (P>0.05. Group C60 presented a reduction of 14.4% and 10.9% in mean neuronal cell body area when compared to group C30 (P0.05. CONCLUSION: Arthritis does not promote quantitative or morphological damages in general myenteric population. However, studies in progress have revealed some significant alterations in myenteric neurons subpopulations (nitrergic and VIP-ergic neurons.

  6. Tamarind seed extract mitigates the liver oxidative stress in arthritic rats.

    Science.gov (United States)

    Sundaram, Mahalingam Shanmuga; Hemshekhar, Mahadevappa; Thushara, Ram M; Santhosh, Martin Sebastin; Kumar, Somanathapura K Naveen; Paul, Manoj; Devaraja, Sannaningaiah; Kemparaju, Kempaiah; Rangappa, Kanchugarakoppal S; Girish, Kesturu S

    2014-03-01

    Although arthritis is primarily a joint disorder that mainly targets the articular cartilage and subchondral bone, several recent investigations have reported oxidative burst and vital organ damage that are being considered as secondary complications of arthritis. The continuous generation of free radicals like reactive oxygen and nitrogen species is considered as a key culprit in the initiation and propagation of oxidative damage. In addition, activation of T and B cells, macrophages, inflammatory mediators such as TNF-α, IL-1β and IL-6 aggravates the oxidative damage of the vital organs, particularly the liver. The current piece of work demonstrates oxidative stress in the liver of arthritic rats and its amelioration by the procyanidin-rich tamarind seed extract (TSE). The arthritic liver homogenate, mitochondrial and cytosolic fractions were found with increased levels of oxidative stress markers including free radicals. As a consequence, depletion in the levels of glutathione, total thiols, glutathione peroxidase and reductase was evident. Furthermore, the activities of endogenous antioxidant enzymes like superoxide dismutase, catalase and glutathione-S-transferase were found to be significantly altered. The increased and decreased activity of transaminases respectively in serum and liver, along with histological observations, further confirms the liver damage. Unfortunately, the commonly used drugs like NSAIDs and DMARDs have failed to prevent oxidative damage, rather they were found to be the inducers themselves. Interestingly, TSE supplementation was found to significantly inhibit oxidative burst in the liver and maintain homeostasis. Thus, the study clearly demonstrates the protective efficacy of TSE against arthritis-associated oxidative liver damage, including mitochondrial oxidative burst and its associated secondary complications.

  7. Quality and Usability of Arthritic Pain Self-Management Apps for Older Adults: A Systematic Review.

    Science.gov (United States)

    Bhattarai, Priyanka; Newton-John, Tro; Phillips, Jane L

    2017-05-25

     To appraise the quality and usability of currently available pain applications that could be used by community-dwelling older adults to self-manage their arthritic pain. A systematic review. Searches were conducted in App Store and Google Play to identify pain self-management apps relevant to arthritic pain management. English language pain management apps providing pain assessment and documentation function and pain management education were considered for inclusion. A quality evaluation audit tool based on the Stanford Arthritis Self-Management Program was developed a priori to evaluate app content quality. The usability of included apps was assessed using an established usability evaluation tool. Out of the 373 apps that were identified, four met the inclusion criteria. The included apps all included a pain assessment and documentation function and instructions on medication use, communication with health professionals, cognitive behavioral therapy-based pain management, and physical exercise. Management of mood, depression, anxiety, and sleep were featured in most apps (N = 3). Three-quarters (N = 3) of the apps fell below the acceptable moderate usability score (≥3), while one app obtained a moderate score (3.2).  Few of the currently available pain apps offer a comprehensive pain self-management approach incorporating evidence-based strategies in accordance with the Stanford Arthritis Self-Management Program. The moderate-level usability across the included apps indicates a need to consider the usability needs of the older population in future pain self-management app development endeavors.

  8. Comparative Expression Analyses of Pro- versus Anti-Inflammatory Mediators within Synovium of Patients with Joint Trauma, Osteoarthritis, and Rheumatoid Arthritis

    Science.gov (United States)

    Shaqura, Mohammed; John, Thilo; Likar, Rudolf; Ebied, Reham Said; Schäfer, Michael

    2017-01-01

    Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium.

  9. Growth factor priming differentially modulates components of the extracellular matrix proteome in chondrocytes and synovium-derived stem cells.

    Directory of Open Access Journals (Sweden)

    Elena Alegre-Aguarón

    Full Text Available To make progress in cartilage repair it is essential to optimize protocols for two-dimensional cell expansion. Chondrocytes and SDSCs are promising cell sources for cartilage repair. We previously observed that priming with a specific growth factor cocktail (1 ng/mL transforming growth factor-β1, 5 ng/mL basic fibroblast growth factor, and 10 ng/mL platelet-derived growth factor-BB in two-dimensional culture, led to significant improvement in mechanical and biochemical properties of synovium-derived stem cell (SDSC-seeded constructs. The current study assessed the effect of growth factor priming on the proteome of canine chondrocytes and SDSCs. In particular, growth factor priming modulated the proteins associated with the extracellular matrix in two-dimensional cultures of chondrocytes and SDSCs, inducing a partial dedifferentiation of chondrocytes (most proteins associated with cartilage were down-regulated in primed chondrocytes and a partial differentiation of SDSCs (some collagen-related proteins were up-regulated in primed SDSCs. However, when chondrocytes and SDSCs were grown in pellet culture, growth factor-primed cells maintained their chondrogenic potential with respect to glycosaminoglycan and collagen production. In conclusion, the strength of the label-free proteomics technique is that it allows for the determination of changes in components of the extracellular matrix proteome in chondrocytes and SDSCs in response to growth factor priming, which could help in future tissue engineering strategies.

  10. Whole-Genome Expression Analysis and Signal Pathway Screening of Synovium-Derived Mesenchymal Stromal Cells in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Jingyi Hou

    2016-01-01

    Full Text Available Synovium-derived mesenchymal stromal cells (SMSCs may play an important role in the pathogenesis of rheumatoid arthritis (RA and show promise for therapeutic applications in RA. In this study, a whole-genome microarray analysis was used to detect differential gene expression in SMSCs from RA patients and healthy donors (HDs. Our results showed that there were 4828 differentially expressed genes in the RA group compared to the HD group; 3117 genes were upregulated, and 1711 genes were downregulated. A Gene Ontology analysis showed significantly enriched terms of differentially expressed genes in the biological process, cellular component, and molecular function domains. A Kyoto Encyclopedia of Genes and Genomes analysis showed that the MAPK signaling and rheumatoid arthritis pathways were upregulated and that the p53 signaling pathway was downregulated in RA SMSCs. Quantitative real-time polymerase chain reaction was applied to verify the expression variations of the partial genes mentioned above, and a western blot analysis was used to determine the expression levels of p53, p-JNK, p-ERK, and p-p38. Our study found that differentially expressed genes in the MAPK signaling, rheumatoid arthritis, and p53 signaling pathways may help to explain the pathogenic mechanism of RA and lead to therapeutic RA SMSC applications.

  11. Assessment of anti-inflammatory and anti-arthritic properties of Acmella uliginosa (Sw.) Cass. based on experiments in arthritic rat models and qualitative gas chromatography-mass spectrometry analyses

    Science.gov (United States)

    Paul, Subhashis; Sarkar, Sudeb; Dutta, Tanmoy; Bhattacharjee, Soumen

    2016-01-01

    Aim: The principle objective of the study was to explore the anti-arthritic properties of Acmella uliginosa (AU) (Sw.) Cass. flower in a rat model and to identify potential anti-inflammatory compounds derived from flower extracts. The synergistic role played by a combination of AU flower and Aloe vera (AV) gel crude extracts was also investigated. Materials and Methods: Male Wistar rats induced with Freund’s complete adjuvant (FCA) were used as a disease model of arthritic paw swelling. There were three experimental and two control groups, each consisting of five rats. Paw circumference and serum biochemical parameters were evaluated to investigate the role of the flower extracts in disease amelioration through a feeding schedule spanning 21 days. Gas chromatography/mass spectrometry (GC/MS) analyses were performed to search for the presence of anti-inflammatory compounds in the ethanolic and n-hexane solvent extracts of the flower. Results: As a visual cue to the experimental outcomes, FCA-induced paw swelling decreased to the normal level; and hemoglobin, serum protein, and albumin levels were significantly increased in the treated animals. The creatinine level was estimated to be normal in the experimental rats after the treatment. The combination of AU and AV showed the best recovery potential in all the studied parameters, confirming the synergistic efficacy of the herbal formulation. GC/MS analyses revealed the presence of at least 5 anti-inflammatory compounds including 9-octadecenoic acid (Z)-, phenylmethyl ester, astaxanthin, à-N-Normethadol, fenretinide that have reported anti-inflammatory/anti-arthritic properties. Conclusion: Our findings indicated that the crude flower homogenate of AU contains potential anti-inflammatory compounds which could be used as an anti-inflammatory/anti-arthritic medication. PMID:27366352

  12. Screening of Stepping Forces in an Arthritic Rat Model Using a Novel Analgesic Meter and Data Acquisition System

    Directory of Open Access Journals (Sweden)

    Rusliza Basir

    2012-07-01

    Full Text Available The stepping forces of normal and Freund Complete Adjuvant (FCA-induced arthritic rats were studied in vivo using a proposed novel analgesic meter. An infrared charge-coupled device (CCD camera and a data acquisition system were incorporated into the analgesic meter to determine and measure the weight of loads on the right hind paw before and after induction of arthritis by FCA injection into the paw cavity. FCA injection resulted in a significant reduction in the stepping force of the affected hind paw. The stepping force decreased to the minimum level on day 4 after the injection and then gradually increased up to day 25. Oral administration of prednisolone significantly increased the stepping forces of FCA-induced arthritic rats on days 14 and 21. These results suggest that the novel device is an effective tool for measuring the arthritic pain in in vivo studies even though walking is a dynamic condition.

  13. Three-dimensional microarchitecture of human osteoporotic, osteoarthrotic and rheumatoid arthritic cancellous bones

    DEFF Research Database (Denmark)

    Ding, Ming; Overgaard, Søren

    Introduction: Osteoporosis (OP), osteoarthrosis (OA), and rheumatoid arthritis (RA) are the most common age-related degenerative bone diseases, and major public health problems in terms of enormous amount of economic cost. RA is considered as a major cause of secondary osteoporosis. At late stage......, OP often leads to skeletal fractures, and OA and RA result in severe joint disability. Over the last a few decades, much significant research on the properties has been carried out on these diseases, however, a detailed comparison of the microarchitecture of cancellous bones of these diseases...... is not available. In this study, we investigated three-dimensional (3-D) microarchitectural properties of OP, OA and RA cancellous bone. We hypothesized that there were significant differences in microarchitecture among OP, OA and RA bone tissues that might lead to different bone quality. Materials and Method...

  14. Three-dimensional microarchitecture of human osteoporotic, osteoarthrotic and rheumatoid arthritic cancellous bones

    DEFF Research Database (Denmark)

    Ding, Ming; Overgaard, Søren

    Introduction: Osteoporosis (OP), osteoarthrosis (OA), and rheumatoid arthritis (RA) are the most common age-related degenerative bone diseases, and major public health problems in terms of enormous amount of economic cost. RA is considered as a major cause of secondary osteoporosis. At late stage...... did not support the traditional notion that RA and OP had similar low bone density. Thus, whether femur head bone tissues from these diseases have similar bone collagen, mineral and mechanical properties, more importantly bone quality, should be clarified in the future....

  15. Disease-regulated gene therapy for arthritic diseases. From experimental arthritis to human in vitro models

    NARCIS (Netherlands)

    Broeren, M.G.A.

    2017-01-01

    A modern treatment for rheumatoid arthritis often consists of the administration of so-called ‚biologics‘. These are protein-based drugs, which are often administered by weekly injections to suppress the immune system. Although they work well for many patients, the continuous immune suppression can

  16. Tibial torsion in non-arthritic Indian adults: A computer tomography study of 100 limbs

    Directory of Open Access Journals (Sweden)

    Mullaji Arun

    2008-01-01

    Full Text Available Background: Knowledge of normal tibial torsion is mandatory during total knee replacement (TKR, deformity correction and fracture management of tibia. Different values of tibial torsion have been found in different races due to biological and mechanical factors. Value of normal tibial torsion in Indian limbs is not known, hence this study to determine the norm of tibial torsional value in normal Indian population. Materials and Methods: Computer tomography (CT scans were performed in 100 non-arthritic limbs of 50 Indian adults (42 males, eight females; age 26-40 years. Value of tibial torsion was measured using dorsal tangent to tibial condyles proximally and bimalleolar axis distally. Results: Normal tibial torsion was found to be 21.6 ± 7.6 (range 4.8 to 39.5 with none of the values in internal rotation. Right tibia was externally rotated by 2 degrees as compared to the left side ( P 0.029. No significant difference was found in male and female subjects. Value of tibial torsion was less than in Caucasian limbs, but was comparable to Japanese limbs when studies using similar measurement technique were compared. Conclusions: Indian limbs have less tibial torsion than Caucasian limbs but the value of tibial torsion is comparable to Japanese limbs.

  17. Experimental investigation of anti-rheumatoid activity of Pleurotus sajorcaju in adjuvant-induced arthritic rats

    Institute of Scientific and Technical Information of China (English)

    Patel Pinal; Patel Dharmik; Patel Natvarlal

    2012-01-01

    Pleurotus sajorcaju (P.sajorcaju),an edible and non-toxic mushroom,was evaluated as antioxidant,antitumor,anti-inflammatory and antihypertensive activities.P.sajorcaju is a good source of carbohydrates,dietary fiber,essential amino acids,minerals,vitamin B,folic acid and steroids.Anti-inflammatory,immunomodulatory and analgesic activities of aqueous and methanolic extracts of mycelium of P.sajorcaju were investigated (data is not shown).This finding suggests that extracts of P.sajorcaju can be used against inflammatory and autoimmune disease.So,P.sajorcaju examined for its antiarthritic activity.Plant was collected and separately extracted with water and methanol.For antiarthritic activity 500 and 1 000 mg·kg-1 of both extracts were prepared and administered by oral route.Body weight,paw edema (inflammation),hematological parameter,spleen weight,radiological and histological analysis of bone damage were assessed in rats with Freund's adjuvant induced paw inflammation.Both extracts showed significant and dose-dependent anti-inflammatory and anti-arthritic effects compared to control group.

  18. The effects of sodium hyaluronate on mRNA expressions of matrix metalloproteinase-1,-3 and tissue inhibitor of metalloproteinase-1 in cartilage and synovium of traumatic osteoarthritis model

    Institute of Scientific and Technical Information of China (English)

    邱波; 刘世清; 彭昊; 王海斌

    2005-01-01

    Objective: To observe the influence of intra-articular injection of sodium hyaluronate (HA) on the mRNA expressions of matrix metalloproteinase-1,-3 (MMP-1,-3) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in cartilage and synovium of traumatic osteoarthritis (OA).Methods: Sixteen white rabbits underwent unilateral anterior cruciate ligament transection (ACLT) were divided into 2 groups randomly 5 weeks after transection. The experimental group rabbits received 0.3 ml of 1% HA by intra-articular injection once a week. Animals in the control group were treated under the same conditions using physiological saline. Ten weeks following surgery, cartilage and synovium were harvested. The mRNA expressions of MMP-1, MMP-3 and TIMP-1 were analyzed using reverse transcription-polymerase chain reaction (RT-PCR).Results: In synovium, the mRNA expression of MMP-3 was suppressed in the HA injection group. HA treatment had no effect on the MMP-3 expression in cartilage. No significant difference of MMP-1 and TIMP-1 expressions in cartilage and synovium was found between the HA injection group and the control group.Conclusions: One of the mechanisms of the therapeutic effect of HA may be the inhibition of expression of MMP-3 in synovium during early stage of traumatic OA.

  19. Influence of sodium hyaluronate on iNOS expression in synovium and NO content in synovial fluid of rabbits with traumatic osteoarthritis

    Institute of Scientific and Technical Information of China (English)

    QIU Bo; LIU Shi-qing; PENG Hao

    2008-01-01

    Objective: To observe the influence of intra-articular injection of sodium hyaluronate (SH) on the expression of inducible nitric oxide synthase (iNOS) in the synovium and nitric oxide (NO) content in synovial fluid of rabbits with traumatic osteoarthritis (OA).Methods: Sixteen white rabbits underwent unilateral anterior cruciate ligament transection and were randomly divided into 2 groups 5 weeks after the operation.Rabbits in the experimental group received intra-articular injection of 0.3 ml of 1% SH,once a week for 5 weeks.Animals in the control group were treated under the same conditions using physiological saline.All the animals were sacrificed at the 10th week after surgery.The mRNA expression of iNOS in the synovium was analyzed using reverse transcriptionpolymerase chain reaction.The content of NO in the synovial fluid was assayed.Results: The level of iNOS expression of thesynovium in the experimental group was lower than that in control group (0.47 ±0.09 vs.0.65±0.12,t =3.45,P<0.01).Compared with control group,the content of NO decreased significantly in synovial fluid of SH injection group (134.11 μmol/L ± 12.47 μmol/L vs.152.17 μmol/L±15.69 μmol/L,t =2.55,Psynovium.It may be one of the mechanisms of the therapeutic effect of SH on early traumatic OA.

  20. Age-Independent Cartilage Generation for Synovium-Based Autologous Chondrocyte Implantation.

    Science.gov (United States)

    Hunziker, Ernst B; Lippuner, Kurt; Keel, Marius J B; Shintani, Nahoko

    2015-07-01

    neoformed cartilage that is deposited after only 1 week within the outer juxtasynovial space would yield sufficient cells for ACI. Since the BMP-2-bearing patches would be implanted transcutaneously in humans, only one surgical or arthroscopic intervention would be called for. Moreover, most importantly, sufficient numbers of cells could be generated in patients of all ages.

  1. A diclofenac suppository-nabumetone combination therapy for arthritic pain relief and a monitoring method for the diclofenac binding capacity of HSA site II in rheumatoid arthritis.

    Science.gov (United States)

    Setoguchi, Nao; Takamura, Norito; Fujita, Ken-ichi; Ogata, Kenji; Tokunaga, Jin; Nishio, Toyotaka; Chosa, Etsuo; Arimori, Kazuhiko; Kawai, Keiichi; Yamamoto, Ryuichi

    2013-03-01

    Diclofenac suppository, a non-steroidal anti-inflammatory drug (NSAID), is used widely in rheumatoid arthritis (RA) patients with severe arthritic pain. As the binding percentage of diclofenac to serum proteins is high, its free (unbound) concentration after rectal administration is low. To increase temporarily the free concentration of diclofenac and to enhance its analgesic effect by inhibiting the protein binding of diclofenac, the analgesic effect of diclofenac was examined before and after the start of an inhibitor administration to RA patients with insufficient control of arthritic pain, and the protein binding capacity of diclofenac was evaluated. Binding experiments were performed by ultrafiltration, and arthritic pain was recorded by the face scale. Free fractions of diazepam and diclofenac were augmented by increasing 6-methoxy-2-naphthylacetic acid (6-MNA; the active metabolite of the NSAID nabumetone) concentrations. The free fraction of diazepam increased after the start of nabumetone administration to RA patients, and arthritic pain relief was observed. These results suggest that 6-MNA has an inhibitory effect on the protein binding of diclofenac and the free fraction of diazepam can be used to evaluate the binding capacity of diclofenac. It is considered that diclofenac suppository-nabumetone combination therapy and the method for protein binding monitoring by diazepam can positively benefit RA patients with insufficient control of arthritic pain.

  2. Anti-inflammatory and anti-arthritic effects of Guge Fengtong Formula: in vitro and in vivo studies.

    Science.gov (United States)

    Cheng, Xiao-Lan; Liu, Xin-Guang; Wang, Qi; Zhou, Ling; Qi, Lian-Wen; Li, Ping; Liu, E-Hu

    2015-11-01

    Rheumatoid arthritis (RA) is the most common inflammatory arthritis and a major cause of disability. Presently, the clinical therapeutic medicines for inflammatory and arthritic diseases are unsatisfactory due to severe adverse effects or ineffectiveness. The Guge Fengtong formula (GGFT), containing the standardized extracts of Dioscoreae Nipponicae Rhizoma, Spatholobi Caulis, and Zingiberis Rhizoma, has long been used for RA treatment by Chinese doctorsin China. However, the detailed anti-inflammatory and anti-arthritic activity of GGFT has not been reported so far. In the present work, we aimed to evaluate the anti-inflammatory and anti-arthritic effects of GGFT using three in vivo animal models, and tried to uncover its preliminarythe underlying mechanism of action mechanism in RAW 264.7 macrophages. The obtained results indicated that GGFT significantly attenuated ear edema, decreased carrageenan-induced paw edema, reduced the arthritis score, and reversed the weight loss of the complete Freund's adjuvant (CFA)CFA-injected rats. Additionally, marked decrease of in synovial inflammatory infiltration and synovial lining hyperplasia in the joints and decline of inflammatory factors (TNF-α and IL-1β) in the serum were observed in the GGFT-treated rats. In lipopolysaccharide-activated RAW264.7 macrophages, GGFT reduced the production of NO, PGE2, and IL-6, and inhibited the expression of iNOS, COX-2, and NF-κB expression. Our results demonstrated that GGFT possessed considerable anti-inflammatory activity and have had potential therapeutic effects on adjuvant induced arthritis in rats, which provided providing experimental evidences for its traditional application in the treatment of RA and other inflammatory diseases. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  3. Anti-inflammatory and Anti-arthritic Effects of a Novel Leflunomide Analogue, UTL-5b (GBL-5b).

    Science.gov (United States)

    Shaw, Jiajiu; Chen, Ben; Wooley, Paul; Huang, Wen-Hsin; Lee, An-Rong; Zeng, Dustin

    2011-01-01

    Rheumatoid arthritis (RA) is a common disease characterized by chronic inflammation and irreversible destruction of articular cartilage and bone. In this report, we examined the anti-inflammatory and anti-arthritic effects of a novel leflunomide analogue, UTL-5b (also known as GBL-5b), for potential RA treatment. Using a carrageenan-induced edema study in rats, UTL-5b exhibited a better anti-inflammatory effect as compared with leflunomide and its metabolite. The chronic efficacy of UTL-5b was examined using type II collagen-induced arthritis (CIA) mouse model. UTL-5b exerted an anti-arthritic effect in a dose-dependant manner with mice given 30 mg/kg exhibiting amelioration of disease early in the trial, but losing statistical significance over time. In contrast, mice treated with 60 mg/kg showed reduced clinical disease parameters early in the trial and these effects were sustained over the ten week trial period. Mechanistic studies indicate that UTL-5b is an inhibitor of TNF-α production in vivo. Oral administration of UTL-5b prior to i.p. injection with lethal dose of lipopolysaccharide (LPS)/D-galactosamine markedly reduced the levels of serum TNF-α and increased survival rates of animals from septic shock-induced death. Acute toxicity study using mice receiving increasing doses of UTL-5b showed that no animals were killed by UTL-5b at 2,000 mg/kg (LD(50) >2,000 mg/kg). Our studies show that UTL-5b represents a novel anti-inflammatory and anti-arthritic agent with potential therapeutic application for RA treatment.

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

    Science.gov (United States)

    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 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 of synovial inflammatory infiltration and synovial lining hyperplasia in the joints of JSTF-treated animalsSix flavonoids were isolated and from JSTF including: Catechin, quercitrin, isoquercitrin, isoscutellarein 7-O-β-D-xylopyranoside, isoscutellarein 7-O-β-D-xylopyranose-(1 → 3)-α-L- rhamnoside, and rutin. Abbreviations used: JSTF: Total flavonoids from Juniperus sabina; CFA: Complete Freund's Adjuvant; TG: Tripterygium glycoside; TNF-α: Tumor necrosis factor alpha; IL-1β: Interleukin 1beta; IL-6: Interleukin 6; H and E: Hematoxylin and eosin. PMID:27601846

  5. Effect ofVitex negundo leaf extract on the free radicals scavengers in complete Freund's adjuvant induced arthritic rats

    OpenAIRE

    Devi, P. Renuka; Kumari, S Krishna; Kokilavani, C

    2007-01-01

    The effect of the oral administration ofVitex negundo leaf extract on the levels of enzymic and non-enzymic antioxidants were studied in the adjuvant induced arthritic (AIA) rats The levels of antioxidant enzymes such as SOD, CAT, GPx, G6PD, GSH and Vit-C were estimated in various groups of the experimental rats. It was observed that the antioxidant enzyme levels in the AIA were significantly low when compared to normal rats. A significant decrease in enzymic antioxidant—SOD, CAT, GPx, G6PD a...

  6. The utility of chelating agents as antidotes for nephrotoxicity of gold sodium thiomalate in adjuvant-arthritic rats.

    Science.gov (United States)

    Takahashi, Y; Funakoshi, T; Shimada, H; Kojima, S

    1995-03-31

    The effects of 2,3-dimercaptopropane sulphonate (DMPS) and N-(2-mercapto-2-methylpropanoyl)-L-cysteine (bucillamine) against the renal damage induced by gold sodium thiomalate (AuTM) in adjuvant-arthritic rats were studied. Arthritic rats induced by adjuvant using Mycobacterium butyricum were injected intraperitoneally with a chelating agent (0.6 mmol/kg) immediately after intramuscular injection of AuTM (0.066 mmol/kg) every other day for 21 days. Treatment with DMPS and bucillamine prevented increases in the urinary excretion of protein, aspartate aminotransferase, and glucose and blood urea nitrogen level after AuTM injection. AuTM prevented the increase in both adjuvant-injected and uninjected hind-feet volumes. The prevention of these inflamed lesions by AuTM was not affected by DMPS and bucillamine. These chelating agents decreased the gold concentration in the kidney and liver after AuTM administration, but did not affect the hepatic and renal concentrations of copper, zinc, iron, and calcium except the renal copper level after AuTM. These findings suggest that DMPS and bucillamine are very useful antidotes for gold toxicity.

  7. Proniosomal formulation of curcumin having anti-inflammatory and anti-arthritic activity in different experimental animal models.

    Science.gov (United States)

    Kumar, K; Rai, A K

    2012-10-01

    Curcumin, the active ingredient of the spice turmeric, has a long history as an herbal remedy for a variety of diseases. Transdermal drug delivery has been recognized as an alternative route to oral delivery. Proniosomes offer a versatile vesicle delivery concept with the potential for drug delivery via the transdermal route. In this study, different proniosomal gel bases were prepared by the ether injection method, using Span 60 and Span 80, Tween 20, cholesterol, and formulation PA2. They were characterized by scanning electron microscopy, revealing vesicular structures, and assessed for stability and effect on in vitro skin permeation using rat skin. Anti-inflammatory and anti-arthritic effects of formulation PA2 and PB1 were compared with a standard market product containing indomethacin. The effect of formulation PA2 and PB1 was evaluated for acute inflammation in carrageenan induced rat paw edema and for chronic inflammation in complete Freud's adjuvant (CFA) induced arthritis in rats. Further histopathological and radiographic evaluation was performed. The investigated curcumin loaded proniosomal formula proved to be non-irritant, non-toxic, but had lower anti-inflammatory and anti-arthritic effects than the marketed indomethacin products.

  8. Expression of Prostaglandin E2 Enzymes in the Synovium of Arthralgia Patients at Risk of Developing Rheumatoid Arthritis and in Early Arthritis Patients.

    Directory of Open Access Journals (Sweden)

    Maria J H de Hair

    Full Text Available Arthralgia may precede the development of synovial inflammation in autoantibody-positive individuals at risk of developing rheumatoid arthritis (RA. A major pathway involved in pain is the prostaglandin (PG E2 pathway. We investigated this pathway in the synovium of individuals with RA-specific autoantibodies and in early arthritis patients.Nineteen autoantibody-positive individuals (IgM-rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies with arthralgia (n=15 and/or a positive family history of RA (n=8, who had been prospectively followed for at least 2 years, were included. In addition, we included early arthritis patients (disease-modifying antirheumatic drug naïve who after 2 years follow up fulfilled classification criteria for RA (n=63, spondyloarthritis (SpA; n=14, or had unclassified arthritis (UA; n=27. In all subjects we assessed pain and performed synovial biopsy sampling by mini-arthroscopy at baseline. Tissue sections were examined by immunohistochemistry to detect and quantify PGE2 pathway enzymes expression levels (mPGES-1; COX-1 and -2; 15-PGDH.In both study groups synovial expression of PGE2 enzymes was not clearly related to pain sensation. Expression levels at baseline were not associated with the development of arthritis after follow up (6 out of 19 autoantibody-positive individuals. However, in early SpA patients the expression levels of mPGES-1 and COX-1 were significantly increased compared to RA and UA patients.Pain in autoantibody-positive individuals without synovial inflammation who are at risk of developing RA and in early arthritis patients may be regulated by pathways other than the PGE2 pathway or originate at sites other than the synovium. In contrast, in SpA, the PGE2 pathway may be inherently linked to the pathophysiology/etiology of the disease.

  9. In vivo quantification of lymph viscosity and pressure in lymphatic vessels and draining lymph nodes of arthritic joints in mice.

    Science.gov (United States)

    Bouta, Echoe M; Wood, Ronald W; Brown, Edward B; Rahimi, Homaira; Ritchlin, Christopher T; Schwarz, Edward M

    2014-03-15

    Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with episodic flares. In TNF-Tg mice, a model of inflammatory-erosive arthritis, the popliteal lymph node (PLN) enlarges during the pre-arthritic 'expanding' phase, and then 'collapses' with adjacent knee flare associated with the loss of the intrinsic lymphatic pulse. As the mechanisms responsible are unknown, we developed in vivo methods to quantify lymph viscosity and pressure in mice with wild-type (WT), expanding and collapsed PLN. While no differences in viscosity were detected via multiphoton fluorescence recovery after photobleaching (MP-FRAP) of injected FITC-BSA, a 32.6% decrease in lymph speed was observed in vessels afferent to collapsed PLN (P pressure (LNP) demonstrated a decrease in expanding PLN versus WT pressure (3.41 ± 0.43 vs. 6.86 ± 0.56 cmH2O; P pressure (LPP), measured indirectly by slowly releasing a pressurized cuff occluding indocyanine green (ICG), demonstrated an increase in vessels afferent to expanding PLN versus WT (18.76 ± 2.34 vs. 11.04 ± 1.47 cmH2O; P pressure, and provide evidence to support the hypothesis that lymphangiogenesis and lymphatic transport are compensatory mechanisms to prevent synovitis via increased drainage of inflamed joints. Furthermore, the decrease in lymphatic flow and loss of LPP during PLN collapse are consistent with decreased drainage from the joint during arthritic flare, and validate these biomarkers of RA progression and possibly other chronic inflammatory conditions.

  10. Periodontitis increases rheumatic factor serum levels and citrullinated proteins in gingival tissues and alter cytokine balance in arthritic rats

    Science.gov (United States)

    Corrêa, Mônica G.; Sacchetti, Silvana B.; Ribeiro, Fernanda Vieira; Pimentel, Suzana Peres; Casarin, Renato Corrêa Viana; Cirano, Fabiano Ribeiro; Casati, Marcio Z.

    2017-01-01

    This study investigated some immunological features by experimental periodontitis (EP) and rheumatoid arthritis (RA) disease interact in destructive processes in arthritic rats. Rats were assigned to the following groups: EP +RA; RA; EP; and Negative Control. RA was induced by immunizations with type-II collagen and a local immunization with Complete Freund’s adjuvant in the paw. Periodontitis was induced by ligating the right first molars. The serum level of rheumatoid factor (RF) and anti-citrullinated protein antibody (ACCPA) were measured before the induction of EP (T1) and at 28 days after (T2) by ELISA assay. ACCPA levels were also measured in the gingival tissue at T2. The specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for the quantification of interleukin IL-1β, IL-4, IL-6, IL-17 and TNF-α using a Luminex/MAGpix assay. Paw edema was analyzed using a plethysmometer. Periodontitis increased the RF and ACCPA levels in the serum and in the gingival tissue, respectively. Besides, the level of paw swelling was increased by EP and remained in progress until the end of the experiment, when EP was associated with RA. Greater values of IL-17 were observed only when RA was present, in spite of PE. It can be concluded that periodontitis increases rheumatic factor serum levels and citrullinated proteins level in gingival tissues and alter cytokine balance in arthritic rats; at the same time, arthritis increases periodontal destruction, confirming the bidirectional interaction between diseases. PMID:28358812

  11. Fabrication and efficacy evaluation of chloroquine nanoparticles in CFA-induced arthritic rats using TNF-α ELISA.

    Science.gov (United States)

    Bhalekar, Mangesh R; Upadhaya, Prashant G; Madgulkar, Ashwini R

    2016-03-10

    Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, stimulates various immune cells especially macrophages, causing release of various proinflammatory cytokines such as TNF-α leading to persistent synovitis. Chloroquine, an anti-malarial drug inhibits the production of TNF-α, thus, halting the disease progression. The aim of the present study was fabrication, characterization and demonstration of kinetic and dynamic efficacy of chloroquine loaded solid lipid nanoparticles (CQ-SLNs) in arthritic rats and in lowering TNF-α levels. CQ-SLNs were prepared using melt homogenization method and subjected to lyophilization. The particle size, zeta potential, PDI and entrapment efficiency were found to be 113.6±0.15nm, -27.8±1.21mV, 0.125±0.03 and 93.45±0.43% respectively. Ex vivo endocytic uptake studies revealed engrossment of endocytic pathways in the uptake of SLN from intestine. Plasma drug profile upon pharmacokinetic evaluation demonstrated increased AUC, half-life and decreased elimination rate of the drug. Pharmacodynamic studies revealed reduction in the paw volume, bone erosion and cartilage destruction, the same was also reflected in histopathological studies. The TNF-α ELISA concluded that the TNF-α level was significantly reduced in the synovial fluid upon treatment with CQ-SLN, thus, leading to the conclusion that CQ-SLN could be used as a potential in reducing inflammatory TNF-α at the arthritic site and halting the disease progression. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

    Science.gov (United States)

    Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

    2015-01-01

    Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways.

  13. Electro-Acupuncture at Acupoint ST36 Reduces Inflammation and Regulates Immune Activity in Collagen-Induced Arthritic Mice

    Directory of Open Access Journals (Sweden)

    Yun-Kyoung Yim

    2007-01-01

    Full Text Available This study aimed to investigate the anti-inflammatory, anti-arthritic and immuno-regulatory effects of electro-acupuncture (EA at ST36 on Collagen-induced arthritis (CIA in mice. Male DBA/1J mice were divided into five groups: Normal, Control, NR (needle retention, EAI and EAII. All mice except those in the normal group were immunized with Collagen II for arthritis induction. Acupuncture needles were inserted into mice ST36 and electrical currents at a frequency of 2 Hz in a continuous rectangular wave form were conducted through the needles for 15 min, 3 times a week. EA treatments were administered for 5 weeks in the EAI group and for 9 weeks in the EAII group. The mice in the NR group were acupunctured in the same manner as the EA groups and the needles were retained for 15 min without electrical stimulation. CIA incidence analysis, ELISA, histological analysis and FACS analysis were performed to evaluate the effect of EA on CIA. EA at ST36 significantly reduced CIA incidence, IL-6, TNF-a, INF-γ, collagen II antibody, IgG and IgM levels in CIA mice serum and prevented knee joint destruction. EA at ST36 also reduced CD69+/CD3e+ cells and CD11a+/CD19+ cells in CIA mice lymph nodes, and CD11b+/Gr1+ cells in CIA mice knee joints. The ratios of CD3e+ cells to CD19+ cells, and CD8+ cells to CD4+ cells were maintained closer to the normal range in the EA groups as compared with the control group or the NR group. EAII was more effective than EAI throughout all the measurements. The NR was effective as well, though less effective than EA. EA at ST36 may have an anti-inflammatory, anti-arthritic and immuno-regulatory effects on CIA in mice. The effectiveness is stronger when EA starts earlier and is applied longer. Needle retention without electrical stimulation may be effective on CIA as well, however less effective than EA. Electrical stimulation and acupoint ST36 may have synergistic effects on CIA.

  14. MHC class II compartment, endocytosis and phagocytic activity of macrophages and putative dendritic cells isolated from normal tissues rich in synovium.

    Science.gov (United States)

    Moghaddami, Mahin; Mayrhofer, Graham; Cleland, Leslie G

    2005-08-01

    The endocytic and phagocytic activities of a population of MHC IIhi CD11c+ dendritic cell (DC)-like cells in synovium-rich tissues (SRTs) of normal rat paws were compared with CD163+ cells (putative macrophages) from the same tissues and pseudo-afferent lymph DCs, peritoneal macrophages and blood monocytes. Fifty percent of CD11c+ cells and 75% of CD163+ cells isolated from SRT internalized fluorescein-conjugated dextran (FITC-DX). Of these endocytic cells, half of those expressing CD11c, but only 30% of those expressing CD163, were surface MHC class II+ (sMHC II+). CD11c+ cells were more endocytic than monocytes or pseudo-afferent lymph DC, but some CD163+ cells (type A synoviocytes) were found to be highly endocytic. CD163+ cells from SRT were more phagocytic (25%) than the general MHC class II+ population (16%). Of phagocytic cells, 40% of CD163+ cells were sMHC II(variable) and they constituted 60% of all MHC class II+ phagocytic cells. Only 18% of phagocytic MHC II+ cells expressed CD11c and the most of these were MHC IIhi. In comparison, 60% of CD163+ peritoneal macrophages were phagocytic, while blood monocytes were poorly phagocytic. Intracellular MHC class II-rich compartments (MIIC) were prominent in sMHC IIhi cells in SRT but rare in CD163+ cells. Most MHC IIhi CD11c+ cells did not have a detectable MIIC.

  15. Meniscus reconstruction through coculturing meniscus cells with synovium-derived stem cells on small intestine submucosa--a pilot study to engineer meniscus tissue constructs.

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    Tan, Yunbing; Zhang, Yuanyuan; Pei, Ming

    2010-01-01

    The purpose of this study was to investigate the feasibility of coculturing meniscus cells (MCs) and synovium-derived stem cells (SDSCs) on small intestine submucosa (SIS) to establish an innovative method to engineer in vitro meniscus constructs. About 0.9 million cells (MCs, prelabeled SDSCs [with Vybrant DiI], and a coculture of MCs and prelabeled SDSCs [50:50]) were mixed with fibrin gel and seeded onto freeze-dried SIS discs (5 mm diameter x 1-2 mm thickness) individually. The tissue constructs were incubated in a serum-free defined medium supplemented with 10 ng/mL transforming growth factor beta-1 and 500 ng/mL insulin-like growth factor I for 1 month. One day after cell seeding, samples for scanning electron microscopy were prepared to evaluate cell attachment on the SIS surface. During incubation, fluorescent microscopy was used to trace cell migration (with 4',6-diamidino-2-phenylindole as a counterstain) on SIS scaffold. The tissue constructs were assessed using histology, immunostaining, biochemical analysis, real-time polymerase chain reaction, and compressive modulus. All three groups of cells attached well on SIS. The coculture with SDSCs yielded MC-based tissue constructs with greater cell survival and differentiation into chondrogenic phenotypes, which exhibited higher glycosaminoglycan, collagen II, and Sox 9 but relatively low collagen I, resulting in the concomitant increase in equilibrium modulus. This pilot study demonstrates the advantages of coculturing MCs with SDSCs on SIS for meniscus tissue engineering and regeneration.

  16. Protoporphyrin IX distribution after intra-articular and systemic application of 5-aminolevulinic acid in healthy and arthritic joints

    Science.gov (United States)

    Huettmann, Gereon; Hendrich, Christian; Birngruber, Reginald; Lehnert, Christiane; Seara, Jose; Siebert, Werner E.; Diddens, Heyke C.

    1996-04-01

    Arthroscopic synovectomy, which is limited today to the large joints, is an important early treatment of rheumatoid arthritis (RA). Photodynamic therapy (PDT) is potentially to be a less invasive method of removing the synovial membrane. Therefore, in a rabbit model of RA, the accumulation of the photosensitizer Protoporphyrin IX (PPIX) after intra-articular and systemic application of ALA into arthritic rabbit knee joints was studied in skin, patella, synovial tissue, and meniscus by fluorescence microscopy. PPIX fluorescence was measured in biopsies taken at different times after application of neutral and acid ALA solutions. Significant PPIX fluorescence was observed in the synovial membrane and skin 2 and 4 hours after application. Using intra-articular application, ALA solutions prepared with pH 5.5 were at least as efficient as neutral solutions in sensitizing the synovial membrane. Skin also showed PPIX within 4 hours after application. After 24 hours, a marginal PPIX fluorescence was detected in these tissues. On the other hand, in cartilage and meniscus significant PPIX accumulation was still observed 24 hours after ALA injection. Systemic application of ALA also showed a good accumulation of PPIX. Further experiments are needed to show whether accumulation of the photosensitizer and tissue selectivity are sufficient for a successful treatment of rheumatoid synovitis.

  17. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis.

    Science.gov (United States)

    Malfait, A M; Gallily, R; Sumariwalla, P F; Malik, A S; Andreakos, E; Mechoulam, R; Feldmann, M

    2000-08-15

    The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked progression of arthritis. CBD was equally effective when administered i.p. or orally. The dose dependency showed a bell-shaped curve, with an optimal effect at 5 mg/kg per day i.p. or 25 mg/kg per day orally. Clinical improvement was associated with protection of the joints against severe damage. Ex vivo, draining lymph node cells from CBD-treated mice showed a diminished CII-specific proliferation and IFN-gamma production, as well as a decreased release of tumor necrosis factor by knee synovial cells. In vitro effects of CBD included a dose-dependent suppression of lymphocyte proliferation, both mitogen-stimulated and antigen-specific, and the blockade of the Zymosan-triggered reactive oxygen burst by peritoneal granulocytes. It also was found that CBD administration was capable of blocking the lipopolysaccharide-induced rise in serum tumor necrosis factor in C57/BL mice. Taken together, these data show that CBD, through its combined immunosuppressive and anti-inflammatory actions, has a potent anti-arthritic effect in CIA.

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

    Science.gov (United States)

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

    2005-01-15

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

  19. The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor α expression in the synovium

    Science.gov (United States)

    Wijbrandts, C A; Dijkgraaf, M G W; Kraan, M C; Vinkenoog, M; Smeets, T J; Dinant, H; Vos, K; Lems, W F; Wolbink, G J; Sijpkens, D; Dijkmans, B A C; Tak, P P

    2008-01-01

    Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)α blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFα expression in the synovium before initiation of treatment. Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 ⩾1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response. Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNFα expression is a significant predictor of response to TNFα blocking therapy. TNFα expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNFα) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1β, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNFα treatment. Conclusion: The effects of TNFα blockade are in part dependent on synovial TNFα expression and infiltration by TNFα producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms. PMID:18055470

  20. Transplantatation of scaffold-free spheroids composed of synovium-derived cells and chondrocytes for the treatment of cartilage defects of the knee

    Directory of Open Access Journals (Sweden)

    J-I Lee

    2011-11-01

    Full Text Available Autologous chondrocyte implantation (ACI is the treatment of choice for osteoarthritis. However, to regenerate articular cartilage using this method, the procedure paradoxically demands that the cell source of the articular chondrocytes (ACs for ex vivo expansion be from the patient’s own healthy cartilage, which can result in donor site morbidity. Accordingly, it is essential to develop a substitute for AC. In the present study, we investigated whether synovium-derived cells (SYs could be used as a partial replacement for ACs in ACI. ACs and SYs from the knees of rabbits were isolated and cultured, and the growth rates of the cells were compared. To manufacture the cellular transplants, we developed a high-density suspension-shaking culture method (HDSS, which circulates the cells in culture media, promoting self-assembly of scaffold-free cellular aggregates. ACs and SYs were mixed in various ratios using HDSS. Injectable cellular transplants were harvested and transplanted into full-thickness osteochondral defects. Simultaneously, histological evaluations were conducted with toluidine blue and safranin O, and immunohistochemistry of collagen type I and II was conducted. Gene expression to evaluate chondrocyte-specific differentiation was also performed. We successfully prepared a large quantity of spheroids (spheroidal cell aggregates in a short time using mixed ACs and SYs, for all cellular composition ratios. Our data showed that the minimal therapeutic unit for the transplants contributed to in situ regeneration of cartilage. In summary, SYs can be used as a replacement for ACs in clinical cases of ACI in patients with broad areas of osteoarthritic lesions.

  1. Intra-articular injection of synovium-derived mesenchymal stem cells and hyaluronic acid promote regeneration of massive cartilage defects in rabbits

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    Vyacheslav Ogay

    2014-01-01

    Full Text Available Introduction: The purpose of this study was to investigate whether intra-articular injection of synovium-derived mesenchymal stem cells (SD MSCs with low molecular weight hyaluronic acid (HA could promote regeneration of massive cartilage in rabbits. Material and methods: The SD MSCs were harvested from the knees of 10 Flemish giant rabbits, expanded in culture, and characterized. A reproducible 4-mm cylindrical defect was created in the intercondylar groove area using a kit for the mosaic chondroplasty of femoral condyle COR (De Puy, Mitek. The defect was made within the cartilage layer without destruction of subchondral bone. Two weeks after the cartilage defect, SD MSCs (2 × 106 cell/0.15 ml were suspended in 0.5% low molecular weight HA (0.15 ml and injected into the left knee, and HA solution (0.30 ml alone was placed into the right knee. Cartilage regeneration in the experimental and control groups were evaluated by macroscopically and histologically at 10, 30, and 60 days. Results: On day 10, after intra-articular injection of SD MSCs, we observed an early process of cartilage regeneration in the defect area. Histological studies revealed that cartilage defect was covered by a thin layer of spindle-shaped undifferentiated cells and proliferated chodroblasts. In contrast, an injection of HA did not induce reparation of cartilage in the defect area. At 30 days, macroscopic observation showed that the size of cartilage defect after SD MSC injection was significantly smaller than after HA injection. Histological score was also better in the MSC- treated intercondylar defect. At 60 days after MSC treatment, cartilage defect was nearly nonexistent and looked similar to an intact cartilage. Conclusion: Thus, intra-articular injection of SD MSCs can adhere to the defect in the intercondylar area, and promote cartilage regeneration in rabbits.

  2. Activation of calcitonin gene-related peptide signaling through the prostaglandin E2-EP1/EP2/EP4 receptor pathway in synovium of knee osteoarthritis patients.

    Science.gov (United States)

    Minatani, Atsushi; Uchida, Kentaro; Inoue, Gen; Takano, Shotaro; Aikawa, Jun; Miyagi, Masayuki; Fujimaki, Hisako; Iwase, Dai; Onuma, Kenji; Matsumoto, Toshihide; Takaso, Masashi

    2016-10-17

    Calcitonin gene-related peptide (CGRP) is a 37-amino-acid vasodilatory neuropeptide that binds to receptor activity-modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CLR). Clinical and preclinical evidence suggests that CGRP is associated with hip and knee joint pain; however, the regulation mechanisms of CGRP/CGRP receptor signaling in synovial tissue are not fully understood. Synovial tissues were harvested from 43 participants with radiographic knee osteoarthritis (OA; unilateral Kellgren/Lawrence (K/L) grades 3-4) during total knee arthroplasty. Correlationships between the mRNA expression levels of CGRP and those of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, and cycloxygenase-2 (COX-2) were evaluated using real-time PCR analysis of total RNA extracted from the collected synovial tissues. To investigate the factors controlling the regulation of CGRP and CGRP receptor expression, cultured synovial cells were stimulated with TNF-α, IL-1β, IL-6, and prostaglandin E2 (PGE2) and were also treated with PGE2 receptor (EP) agonist. CGRP and COX-2 localized in the synovial lining layer. Expression of COX-2 positively correlated with CGRP mRNA expression in the synovial tissue of OA patients. The gene expression of CGRP and RAMP1 increased significantly in synovial cells exogenously treated with PGE2 compared to untreated control cells. In cultured synovial cells, CGRP gene expression increased significantly following EP4 agonist treatment, whereas RAMP1 gene expression increased significantly in the presence of exogenously added EP1 and EP2 agonists. PGE2 appears to regulate CGRP/CGRP receptor signaling through the EP receptor in the synovium of knee OA patients.

  3. Structural reorganization of the knee joint cartilage and synovium during diaphyseal femoral fracture management using intramedullary locked nails ^perime^al and morphological study

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    A. A. Emanov

    2015-01-01

    Full Text Available The purpose - to study structural changes in knee articular cartilage and synovial membrane during locking intramedullary osteosynthesis of femoral fractures. Material and methods. The study tested structural changes in the articular cartilage of the femoral condyles and synovium during femoral fracture repair under the conditions of intramedullary locked nailing. Transverse diaphyseal femoral fractures were modeled in 12 adult mongrel dogs. Synovitis severity was assessed with a V. Krenn scale. Wilcoxon Test was used for testing hypothesis. Results. In the first group (n = 6 fractures were fixed with locked intramedullary nails ILoc (Biomedtrix, USA, while the same type of fixation in group 2 (n = 6 was performed on 4th day postoperatively after reduction by skeletal traction. It was revealed that in the first group a unified medullary cavity was seen by day 70 and the cortical layer at the fracture site approximated to the condition of the uninjured bone in intensity of bone formation and thickness. These featured were observed in the second group only by day 100. The histological study showed that the structure of the femoral condyle articular cartilage was regular in the first group but its changes were reduced thickness and reduced volumetric density of chondrocytes that might result due to disturbed trophical condition. In the second group the articular cartilage fibres tended to disintegrate on the surface that was accompanied by disturbed integrity of the basophil line and penetration of the vessels into the cartilage. Moreover, the cartilage destruction progressed as the experiment continued and chondrocyte proliferation sharply decreased. Synovitis was considerably expressed. The data obtained in the second group proved high risk of developing osteoarthrosis.

  4. Effects of a Sun-style Tai Chi exercise on arthritic symptoms, motivation and the performance of health behaviors in women with osteoarthritis.

    Science.gov (United States)

    Song, Rhayun; Lee, Eun-Ok; Lam, Paul; Bae, Sang-Cheol

    2007-03-01

    Tai Chi exercise, an ancient Chinese martial art, has drawn more and more attention for its health benefits. The purpose of the study was to identify the effects of a Sun-style Tai Chi exercise on arthritic symptoms (joint pain and stiffness), motivation for performing health behaviors, and the performance of health behaviors among older women with osteoarthritis. Total of 72 women with the mean age of 63 years old were recruited from outpatients clinic or public health centers according to the inclusion criteria and assigned randomly to either the Tai Chi exercise group or the control. A Sun-style Tai Chi exercise has been provided three times a week for the first two weeks, and then once a week for another 10 weeks. In 12 weeks of study period, 22 subjects in the Tai Chi exercise group and 21 subjects in the control group completed the posttest measure with the dropout rate of 41%. Outcome variables included arthritic symptoms measured by K-WOMAC, motivation for health behavior, and health behaviors. At the completion of the 12 week Tai Chi exercise, the Tai Chi group perceived significantly less joint pain (t=-2.19, p=0.03) and stiffness (t=-2.24, p=0.03), perceived more health benefits (t=2.67, p=0.01), and performed better health behaviors (t=2.35, p=0.02), specifically for diet behavior (t=2.06, p=0.04) and stress management (t=2.97, p=0.005). A Sun-style Tai Chi exercise was found as beneficial for women with osteoarthritis to reduce their perceived arthritic symptoms, improve their perception of health benefits to perform better health behaviors.

  5. Patients with inflammatory arthritic diseases harbor elevated serum and synovial fluid levels of free and immune-complexed glucose-6-phosphate isomerase (G6PI)

    DEFF Research Database (Denmark)

    Schaller, Monica; Stohl, William; Benoit, Vivian

    2006-01-01

    in the sera of most immune-based inflammatory arthritis patients are elevated and may reflect ongoing inflammation and cell destruction. The high serum levels of enzymatically inactive forms of G6PI in RA relative to those in other arthritic diseases are partially due to G6PI-containing immune complexes...... arthritides, serum and SF obtained concomitantly from 91 clinically well-defined arthritis patients were assessed in a blinded manner for G6PI enzymatic assay and for G6PI protein concentration by ELISA. Sera and SF from patients with immune-based inflammatory arthritis contained significantly higher levels...

  6. Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resonance imaging (19F MRI

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    Balducci Anthony

    2012-06-01

    Full Text Available Abstract Background Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA, and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present. Methods Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28. Results Quantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease. Conclusion These results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory

  7. Intra-articular injection of Botulinum toxin A reduces neurogenic inflammation in CFA-induced arthritic rat model.

    Science.gov (United States)

    Wang, Lin; Wang, Kaile; Chu, Xiao; Li, Tieshan; Shen, Nana; Fan, Chenglei; Niu, Zhenyuan; Zhang, Xiaochen; Hu, Luoman

    2017-02-01

    Currently, administration of Botulinum toxin Type A (BoNT/A) to treat arthritic pain has promising efficacy in clinical research. However, the mechanisms underlying anti-neurogenic inflammation mediated by BoNT/A remains unclear. The aim of this study was to demonstrate the effectiveness in macro and micro levels and to explore the causal mechanism of BoNT/A. Wistar rats (n = 60) were injected with 50ul complete Freund's adjuvant (CFA) in the left ankle joint capsule to establish a model of chronic monoarthritis. Pain behaviour (Evoked pain assessment) and infrared thermal imaging testing were performed at the macroscopic level to assess the effectiveness of analgesia and anti-inflammation. Western blotting and immunofluorescence staining were used at the microscopic level in an attempt to determine the mechanisms of anti-nociceptive or anti-inflammatory effects of BoNT/A. Additionally, hematoxylin-eosin staining was also used to visualise the cartilage and the synovial degenerative conditions of arthritis. By comparing the outcome of the evoked pain test and immunofluorescence staining, there was a significant improvement in BoNT/A compared with the normal saline (NS) injected control group. In addition, thermal variations showed that the temperature of ipsilateral ankle joint increased between 1 and 2 weeks following injection of CFA, but decreased after 3 weeks (still above the contralateral side). However, the temperature showed no difference between the BoNT/A group and NS group after treatment. The expression of IL-1β or TNF-α in the ankle synovial tissue was significantly decreased in the BoNT/A group compared to the NS group (p < 0.05). Based on the HE assessment, cartilage degeneration and infiltration of inflammatory cells in the BoNT/A group was alleviated compared to the NS group after treatment. In conclusion, we proposed the hypothesis that intra-articular BoNT/A administration does play an important role in anti-neurogenic inflammation. The

  8. Therapeutic effects of Semecarpus anacardium Linn. nut milk extract on the changes associated with collagen and glycosaminoglycan metabolism in adjuvant arthritic Wistar rats.

    Science.gov (United States)

    Ramprasath, Vanu Ramkumar; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2006-07-25

    The effect of milk extract of Semecarpus anacardium Linn. nut milk extract (SA) was studied to gain some insight into this intriguing disease with reference to collagen metabolism. Arthritis was induced in rats by injecting Freund's complete adjuvant containing 10mg of heat killed mycobacterium tuberculosis in 1 ml paraffin oil (0.1 ml) into the left hind paw of the rat intradermally. After 14 days of induction, SA (150 mg/kg body weight/day) was administered orally by gastric intubations for 14 days. Decreased levels of collagen and glycosaminoglycans (GAGS) components (chondroitin sulphate, heparan sulphate, hyaluronic acid) and increase in the levels of connective tissue degrading lysosomal glycohydrolases such as acid phosphatase, beta-glucuronidase, beta-N-acetyl glucosaminidase and cathepsin-D observed in arthritic animals were reverted back to near normal levels upon treatment with SA. The drug effectively regulated the uriniray markers of collagen metabolism namely hexosamine, hexuronic acid, hydroxyproline and total GAGS. Electron microscopic studies also revealed the protective effect of SA. Hence, it can be suggested that SA very effectively regulate the collagen metabolism that derange during arthritic condition.

  9. Semecarpus anacardium Linn. nut milk extract, an indigenous drug preparation, modulates reactive oxygen/nitrogen species levels and antioxidative system in adjuvant arthritic rats.

    Science.gov (United States)

    Ramprasath, Vanu Ramkumar; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2005-08-01

    Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive transient chemical species, which play an important role in the etiology of tissue injury in rheumatoid arthritis (RA). The effects of milk extract of Semecarpus anacardium Linn. nut (SA) was studied on adjuvant arthritis in rats. Arthritis was induced by injecting 0.1 ml of heat killed mycobacterium tuberculosis (10 mg/ml of paraffin oil) intradermally into the left hind paw. A significant increase in the levels of lipid peroxides (LPO), ROS (superoxide radical, hydroxyl radical, H(2)O(2) and myeloperoxidase) and RNS (nitrate+nitrite) observed in adjuvant arthritic animals were found to be significantly decreased on administration of the drug at 150 mg/kg body weight/day. The antioxidant defense system studied in arthritic animals were altered significantly as evidenced by the decrease in antioxidants. Treatment with SA recouped the altered antioxidant defense components to near normal levels. These evidences suggest that the free radical mediated damage during arthritis could have been controlled by SA by its free radical quenching and antioxidative potential. (Mol Cell Biochem 276: 97-104, 2005).

  10. Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses

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    Jiang Pu

    2016-08-01

    Full Text Available To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days. Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

  11. Matrine Exerts a Strong Anti-Arthritic Effect on Type II Collagen-Induced Arthritis in Rats by Inhibiting Inflammatory Responses.

    Science.gov (United States)

    Pu, Jiang; Fang, Fan-Fu; Li, Xiu-Qing; Shu, Zhi-Heng; Jiang, Yi-Ping; Han, Ting; Peng, Wei; Zheng, Cheng-Jian

    2016-08-26

    To investigate anti-arthritic effects of matrine isolated from the roots of S. flavescens on type II collagen-induced arthritis (CIA) in rats and to explore its related potential mechanisms, CIA rats were established and administered with matrine (20, 40 or 80 mg/kg/days, for 30 days). Subsequently, blood was collected to determine serum levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, IL-10, MMP-2, MMP-3 and MMP-9, and hind paws and knee joints were collected for histopathological examination. Furthermore, indices of the thymus and spleen were determined, and synovial tissues were collected to determine the protein expressions of p-IκB, IκB, Cox-2 and iNOS. Our results indicated that matrine significantly suppressed inflammatory reactions and synovial tissue destruction. Matrine inhibited paw swelling, arthritis indices and weight loss in CIA rats. Additionally, matrine decreased the levels of TNF-α, IL-1β, IL-6, IL-8, IL-17A, MMP-2, MMP-3 and MMP-9. Matrine also down-regulated expressions of p-IκB, Cox-2, and iNOS but up-regulated IκB in synovial tissues in CIA rats. The results suggested matrine possesses an anti-arthritic effect in CIA rats via inhibiting the release of pro-inflammatory cytokines and proteins that promote the NF-κB pathway.

  12. 臭氧对兔膝关节滑膜中IL-1、TNF-α的影响%Effects of ozone on IL - 1 and TNF - α in rabbit articular synovium

    Institute of Scientific and Technical Information of China (English)

    林庆荣; 余斌; 陈辉强; 卢昌怀; 王博炜

    2011-01-01

    [Objective] To observe the effect of ozone in different concentrations on proinflammatory cytokines IL - 1 and TNF - a in rabbit articular synovium,and therefore to explore the mechanism of ozone-therapy for osteoarthritis. [ Method] Sixty-four New Zealand white rabbits were randomly divided into 8 groups;the ozone groups of 10 μg/ml,20 μg/ml,30 μg/ml,40 μg/ ml and 50 μg/ml, normal group ,oxygen group and model group. All the rabbits were made osteoarthritis models expect in the normal group. The oxygen group was given an injection of 2 ml pure oxygen in the knee joint cavity weekly for 3 weeks. And the o-zone groups received the concentrations of ozone weekly for 3 weeks. Then articular synovium morphology was observed,and IL - 1 and TNF - α in the synovium were detected. [ Result]The decrease of articular synovium was seen in ozone groups,and synovi-al tissue atrophy as well as apoptosis was found under the pathological section with mild infiltration of inflammatory cells. The distribution of IL - 1 and TNF - α agreed with the experiment results, which was: ozone 50 u,g/ml group > oxygen group and model group > ozone 40 μg/ml group > ozone 10 μg/ml group and 30 μg/ml group > ozone 20 μg/ml group > control group. [ Conclusion ] Ozone can affect IL - 1 and TNF - α in articular synovium. Ozone of low concentration could delay the progression of osteoarthritis, but the higher concentration may be harmful.%[目的] 观察不同浓度臭氧对兔膝关节滑膜中致炎因子IL -1、TNF -α的影响,探讨臭氧治疗骨关节炎的机制.[方法]将64只新西兰大白兔随机分为8组,分别为臭氧10 ~ 50 μg/ml组及正常组、纯氧组和模型组,正常组不予任何处理,模型组仅造模,余6组分别在兔膝关节腔中注射相应浓度的臭氧或纯氧2ml,1次/周,共3次.观察各组关节滑膜形态,并检测滑膜中IL -1及TNF -α的含量.[结果]臭氧各组膝关节的滑膜数量明显减少,病理切片显示滑膜组织明

  13. Gene Expression Analysis of Murine and Human Osteoarthritis Synovium Reveals Elevation of Transforming Growth Factor beta-Responsive Genes in Osteoarthritis-Related Fibrosis

    NARCIS (Netherlands)

    Remst, D. F. G.; Blom, A. B.; Vitters, E. L.; Bank, R. A.; van den Berg, W. B.; Davidson, E. N. Blaney; van der Kraan, P. M.

    Objective. Synovial fibrosis is a major contributor to joint stiffness in osteoarthritis (OA). Transforming growth factor beta (TGF beta), which is elevated in OA, plays a key role in the onset and persistence of synovial fibrosis. However, blocking of TGF beta in OA as a therapeutic intervention

  14. Pre-Treatment of Human Mesenchymal Stem Cells With Inflammatory Factors or Hypoxia Does Not Influence Migration to Osteoarthritic Cartilage and Synovium.

    Science.gov (United States)

    Leijs, Maarten J C; van Buul, Gerben M; Verhaar, Jan A N; Hoogduijn, Martin J; Bos, Pieter K; van Osch, Gerjo J V M

    2017-04-01

    Mesenchymal stem cells (MSCs) are promising candidates as a cell-based therapy for osteoarthritis (OA), although current results are modest. Pre-treatment of MSCs before application might improve their therapeutic efficacy. Pre-treatment of MSCs with inflammatory factors or hypoxia will improve their migration and adhesion capacities toward OA-affected tissues. Controlled laboratory study. We used real-time polymerase chain reaction to determine the effects of different fetal calf serum (FCS) batches, platelet lysate (PL), hypoxia, inflammatory factors, factors secreted by OA tissues, and OA synovial fluid (SF) on the expression of 12 genes encoding chemokine or adhesion receptors. Migration of MSCs toward factors secreted by OA tissues was studied in vitro, and attachment of injected MSCs was evaluated in vivo in healthy and OA knees of male Wistar rats. Different FCS batches, PL, or hypoxia did not influence the expression of the migration and adhesion receptor genes. Exposure to inflammatory factors altered the expression of CCR1, CCR4, CD44, PDGFRα, and PDGFRβ. MSCs migrated toward factors secreted by OA tissues in vitro. Neither pre-treatment with inflammatory factors nor the presence of OA influenced MSC migration in vitro or adhesion in vivo. Factors secreted by OA tissues increase MSC migration in vitro. In vivo, no difference in MSC adhesion was found between OA and healthy knees. Pre-treatment with inflammatory factors influenced the expression of migration and adhesion receptors of MSCs but not their migration in vitro or adhesion in vivo. To improve the therapeutic capacity of intra-articular injection of MSCs, they need to remain intra-articular for a longer period of time. Pre-treatment of MSCs with hypoxia or inflammatory factors did not increase the migration or adhesion capacity of MSCs and will therefore not likely prolong their intra-articular longevity. Alternative approaches to prolong the intra-articular presence of MSCs should be developed to increase the therapeutic effect of MSCs in OA.

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

    Directory of Open Access Journals (Sweden)

    Sekiguchi Yuusuke

    2012-04-01

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

  16. Anti-nociceptive, anti-hyperalgesic and anti-arthritic activity of amides and extract obtained from Piper amalago in rodents.

    Science.gov (United States)

    da Silva Arrigo, Jucicléia; Balen, Eloise; Júnior, Ubirajara Lanza; da Silva Mota, Jonas; Iwamoto, Renan Donomae; Barison, Andersson; Sugizaki, Mario Mateus; Leite Kassuya, Cândida Aparecida

    2016-02-17

    Piper amalago (Piperaceae) has been used in folk medicine as an analgesic. This study aimed to evaluate the pharmacological effects of extract and pure amides obtained from P. amalago on pain to provide a pharmacological basis for their use in traditional medicine. This study evaluated the anti-nociceptive, anti-hyperalgesic, anti-arthritic and anti-depressive activities of the ethanolic extract of P. amalago (EEPA) and the amides N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine (1) and N-[7-(3',4'-methylenedioxyphenyl)-2(E),4(E)-heptadienoyl] pyrrolidine (2) obtained from P. amalago in animal models. Mice treated daily with EEPA (100mg/kg, p.o.) were assayed for 20 days for knee edema (micrometer measurement), mechanical hyperalgesia (analgesiometer analysis), heat sensitivity and immobility (forced swim test) in the Complete Freund's Adjuvant (CFA) model. Cold (acetone test) and mechanical hyperalgesia (electronic von Frey analysis) responses were evaluated for 15 days in rats treated with oral EEPA (100mg/kg) in the spared nerve injury (SNI) model. Meanwhile, mice were evaluated for carrageenan-induced edema and mechanical hyperalgesia and for nociception using the formalin model after a single administration of EEPA (100mg/kg) or amides 1 and 2 (1mg/kg). Amides (1) and (2) were detected and isolated from the EEPA. The EEPA inhibited mechanical hyperalgesia, knee edema, and heat hyperalgesia, but not depressive-like behavior, induced by the intraplantar injection of CFA. When evaluated in the SNI model, the EEPA inhibited mechanical and cold hyperalgesia. The EEPA, 1 and 2 prevented the mechanical hyperalgesia induced by carrageenan and the anti-nociceptive effects in both phases of formalin nociception. The EEPA did not induce alterations in the open field test. The EEPA was effective for inhibition of pain and arthritic parameters but was not effective against depressive-like behavior; additionally, it did not alter locomotor activity. The

  17. Histamine H3 and H4 receptor ligands modify vascular histamine levels in normal and arthritic large blood vessels in vivo.

    Science.gov (United States)

    Kyriakidis, Konstantinos; Zampeli, Evangelia; Palaiologou, Marina; Tiniakos, Dina; Tiligada, Ekaterini

    2015-01-01

    Growing evidence associates histamine with arthritis, but its implication in shaping vascular function in chronic inflammation remains largely elusive. This study explored the involvement of vascular histamine in the extra-articular responses in peripheral large blood vessels using a rat model of adjuvant-induced arthritis. Histamine levels were increased in the abdominal aorta and the inferior vena cava of arthritic animals. Contrary to the H1 receptor antagonist dimetindene, histamine induction was observed following administration of the H3 and H4 receptor ligands GSK334429 and JNJ7777120, respectively. In arthritis, prophylactic treatment with GSK334429 partially attenuated the clinical signs and restored basal histamine levels only in the abdominal aorta. This study is the first to implicate the H3 and H4 receptors in a concerted constitutive regulation of basal vascular histamine in the rat large blood vessels and to identify the H3 receptor as a component that may influence arterial histamine during the onset of arthritis.

  18. Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens in Adjuvant Arthritis in Rats: Role of FOXP3+ Treg Cells

    Science.gov (United States)

    Eissa, Maha M.; Ghazy, Amany A.; El azzouni, Mervat Z.; Boulos, Laila M.; Younis, Layla K.

    2016-01-01

    A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund’s adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals’ gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints’ histopathology and immunohistochemistry of Foxp3+ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws’ inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3+ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a

  19. Photoacoustic evaluation of human inflammatory arthritis in human joints

    Science.gov (United States)

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

    2017-03-01

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

  20. Antinociceptive Effect of Rat D-Serine Racemase Inhibitors, L-Serine-O-Sulfate, and L-Erythro-3-Hydroxyaspartate in an Arthritic Pain Model

    Directory of Open Access Journals (Sweden)

    Claudio Laurido

    2012-01-01

    Full Text Available N-methyl-D-aspartic acid receptor (NMDAr activation requires the presence of D-serine, synthesized from L-serine by a pyridoxal 5′-phosphate-dependent serine racemase (SR. D-serine levels can be lowered by inhibiting the racemization of L-serine. L-serine-O-sulfate (LSOS and L-erythro-3-hydroxyaspartate (LEHA, among others, have proven to be effective in reducing the D-serine levels in culture cells. It is tempting then to try these compounds in their effectiveness to decrease nociceptive levels in rat arthritic pain. We measured the C-reflex paradigm and wind-up potentiation in the presence of intrathecally injected LSOS (100 μg/10 μL and LEHA (100 μg/10 μL in normal and monoarthritic rats. Both compounds decreased the wind-up activity in normal and monoarthritic rats. Accordingly, all the antinociceptive effects were abolished when 300 μg/10 μL of D-serine were injected intrathecally. Since no in vivo results have been presented so far, this constitutes the first evidence that SR inhibitions lower the D-serine levels, thus decreasing the NMDAr activity and the consequent development and maintenance of chronic pain.

  1. A kinematic and kinetic analysis of the sit-to-stand transfer using an ejector chair: implications for elderly rheumatoid arthritic patients.

    Science.gov (United States)

    Munro, B J; Steele, J R; Bashford, G M; Ryan, M; Britten, N

    1998-03-01

    Twelve elderly female rheumatoid arthritis patients (mean age = 65.5 +/- 8.6 yr) were assessed rising from an instrumented Eser Ejector chair under four conditions: high seat (540 mm), low seat (450 mm), with and without the ejector mechanism operating. Sagittal plane motion, ground reaction forces, and vertical chair arm rest forces were recorded during each trial with the signals synchronised at initial subject head movement. When rising from a high seat, subjects displayed significantly (p ejector mechanism, time to seat off and trunk and knee angle at seat off significantly increased, whereas trunk and knee angular displacement, and total net and normalised arm rest forces significantly decreased compared to rising unassisted. Regardless of seat height or ejector mechanism use, there were no significant differences in the peak, or time to peak horizontal velocity of the subjects' total body centre of mass, or net knee and ankle moments. It was concluded that increased seat height and use of the ejector mechanism facilitated sit-to-stand transfers performed by elderly female rheumatoid arthritic patients. However, using the ejector chair may be preferred by these patients compared to merely raising seat height because it does not necessitate the use of a footstool, a possible obstacle contributing to falls.

  2. Novel Method of Monitoring Trace Cytokines and Activated STAT Molecules in the Paws of Arthritic Mice using Multiplex Bead Technology

    Directory of Open Access Journals (Sweden)

    Stump Kristine L

    2010-11-01

    Full Text Available Abstract Background The use of mouse models to study human disease provides useful data that can provide support for research projects or an existing drug discovery program. How well a model recapitulates the human condition and the ease and reproducibility of data collected will determine how much confidence a scientist can place on results obtained. Designing new treatments for rheumatic diseases, such as rheumatoid arthritis (RA, requires complex immunocompetent models that depend on intricate cytokine networks. Using local cytokines, signal transduction and transcription factor molecules as potential biomarkers to monitor disease and treatment efficacy is the best method to follow the progression of tissue damage and repair when testing an unknown compound or biologic. Described here in this report, a novel method for the non-enzymatic extraction and measurement of cytokines and signal transducers and activators of transcription (STAT molecules using Luminex® bead array technology in two different mouse models for human RA - collagen antibody-dependent arthritis (CAIA and collagen-induced arthritis (CIA. Results Dynamic expression of several pro-inflammatory cytokines responsible for promoting disease augmentation overtime were monitored, such as IL-1β, TNFα, IL-6 and IL-12, locally in the paws of affected animals directly ex vivo. Local cytokine responses could be matched with serum cytokine levels and joint pathology results. In addition, STAT1, 3, and 5a/b activation status could be monitored with confidence using specifically formulated extraction buffer that protected the phosphorylation site. STAT3 activation followed paw swelling and cytokine levels in both models and correlates of disease could be ablated upon treatment with dexamethasone. Here reported a novel method of extracting joint fluid from the paws of inflamed mice coupled with powerful multiplex bead technology allowing us to measure cytokine responses, pharmacodynamic

  3. In vivo evaluation of early disease progression by X-ray phase-contrast imaging in the adjuvant-induced arthritic rat

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Yongqiang; Xiong, Zhuang; Lv, Yizhong; Qian, Yinfeng [First Affiliated Hospital of Anhui Medical University, Department of Radiology, Hefei (China); Jiang, Shiping [University of Science and Technology of China, Synchrotron Radiation Laboratory, Hefei (China); Tian, Yulian [Institute of High Energy Physics, Chinese Academy of Science, Synchrotron Radiation Laboratory, Beijing (China)

    2006-03-15

    To study the early change of bone matrix and soft tissue around articulation in adjuvant-induced arthritic (AIA) rats non-invasively by X-ray phase-contrast imaging (XPCI), a new imaging method. Adjuvant-induced arthritis was established in male Sprague-Dawley (SD) rats (n=6, age 40 days) by subcutaneous injection of Freund's complete adjuvant (FCA) into the left hindpaw. In vivo XPCI evaluation of the early soft tissue and bone changes in AIA rats was consecutively performed and correlated with changes in volumes of right hindpaws and body weights. In comparison, the changes in the AIA rats were also evaluated with absorption-contrast imaging using the same X-ray source as XPCI and conventional radiography at the same time. After the imaging evaluation, AIA rats were subjected to histological examination. There was significant difference between the score of XPCI and the other two methods in demonstrating soft tissue (P<0.01), bone details (P<0.01) and lesions (P<0.001). By day 10 after subcutaneous injection of FCA, bone changes in the right hindpaw were not obvious, but swelling of soft tissue appeared. By day 12, bone erosion in the articular facet and the area around the articular facet, was detected, along with osteoporosis, and swelling of soft tissue was aggravated. By day 14 bone erosions became fused and expanded, especially in the margin area around the articular facet. At day 16 bone erosion still existed. Joint interspaces seemed wider than normal, and swelling of soft tissue was significant. By day 18 periosteal new bone formation was seen definitely, destruction of bone decreased, bone density around the articular was enhanced, and swelling of soft tissue was relieved. XPCI could clearly distinguish all these alterations, which could not be demonstrated by absorption-contrast imaging and conventional radiography. During the test period, the volume of the right hindpaw and the body weight of the AIA rats also changed significantly compared with

  4. Environmental cold exposure increases blood flow and affects pain sensitivity in the knee joints of CFA-induced arthritic mice in a TRPA1-dependent manner.

    Science.gov (United States)

    Fernandes, Elizabeth S; Russell, Fiona A; Alawi, Khadija M; Sand, Claire; Liang, Lihuan; Salamon, Robin; Bodkin, Jennifer V; Aubdool, Aisah A; Arno, Matthew; Gentry, Clive; Smillie, Sarah-Jane; Bevan, Stuart; Keeble, Julie E; Malcangio, Marzia; Brain, Susan D

    2016-01-11

    The effect of cold temperature on arthritis symptoms is unclear. The aim of this study was to investigate how environmental cold affects pain and blood flow in mono-arthritic mice, and examine a role for transient receptor potential ankyrin 1 (TRPA1), a ligand-gated cation channel that can act as a cold sensor. Mono-arthritis was induced by unilateral intra-articular injection of complete Freund's adjuvant (CFA) in CD1 mice, and in mice either lacking TRPA1 (TRPA1 KO) or respective wildtypes (WT). Two weeks later, nociception and joint blood flow were measured following exposure to 10 °C (1 h) or room temperature (RT). Primary mechanical hyperalgesia in the knee was measured by pressure application apparatus; secondary mechanical hyperalgesia by automated von Frey system; thermal hyperalgesia by Hargreaves technique, and weight bearing by the incapacitance test. Joint blood flow was recorded by full-field laser perfusion imager (FLPI) and using clearance of (99m)Technetium. Blood flow was assessed after pretreatment with antagonists of either TRPA1 (HC-030031), substance P neurokinin 1 (NK1) receptors (SR140333) or calcitonin gene-related peptide (CGRP) (CGRP8-37). TRPA1, TAC-1 and CGRP mRNA levels were examined in dorsal root ganglia, synovial membrane and patellar cartilage samples. Cold exposure caused bilateral primary mechanical hyperalgesia 2 weeks after CFA injection, in a TRPA1-dependent manner. In animals maintained at RT, clearance techniques and FLPI showed that CFA-treated joints exhibited lower blood flow than saline-treated joints. In cold-exposed animals, this reduction in blood flow disappears, and increased blood flow in the CFA-treated joint is observed using FLPI. Cold-induced increased blood flow in CFA-treated joints was blocked by HC-030031 and not observed in TRPA1 KOs. Cold exposure increased TRPA1 mRNA levels in patellar cartilage, whilst reducing it in synovial membranes from CFA-treated joints. We provide evidence that environmental

  5. A HEV-restricted sulfotransferase is expressed in rheumatoid arthritis synovium and is induced by lymphotoxin-α/β and TNF-α in cultured endothelial cells

    Directory of Open Access Journals (Sweden)

    Palao Guillermo

    2005-03-01

    Full Text Available Abstract Background The recruitment of lymphocytes to secondary lymphoid organs relies on interactions of circulating cells with high endothelial venules (HEV. HEV are exclusive to these organs under physiological conditions, but they can develop in chronically-inflamed tissues. The interaction of L-selectin on lymphocytes with sulfated glycoprotein ligands on HEV results in lymphocyte rolling, which represents the initial step in lymphocyte homing. HEV expression of GlcNAc6ST-2 (also known as HEC-GlcNAc6ST, GST-3, LSST or CHST4, an HEV-restricted sulfotransferase, is essential for the elaboration of L-selectin functional ligands as well as a critical epitope recognized by MECA-79 mAb. Results We examined the expression of GlcNAc6ST-2 in relationship to the MECA-79 epitope in rheumatoid arthritis (RA synovial vessels. Expression of GlcNAc6ST-2 was specific to RA synovial tissues as compared to osteoarthritis synovial tissues and localized to endothelial cells of HEV-like vessels and small flat-walled vessels. Double MECA-79 and GlcNAc6ST-2 staining showed colocalization of the MECA-79 epitope and GlcNAc6ST-2. We further found that both TNF-α and lymphotoxin-αβ induced GlcNAc6ST-2 mRNA and protein in cultured human umbilical vein endothelial cells. Conclusion These observations demonstrate that GlcNAc6ST-2 is induced in RA vessels and provide potential cytokine pathways for its induction. GlcNAc6ST-2 is a novel marker of activated vessels within RA ectopic lymphoid aggregates. This enzyme represents a potential therapeutic target for RA.

  6. EFFECT OF ELECTROACUPUNCTURE ON THE IMMUNOREACTIVITY OF FOCAL CUTANEOUS μ-OPIOID RECEPTOR IMMUNOREACTION-POSITIVE FIBERS IN ADJUVANT ARTHRITIC RATS

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the effect of μ-opioid receptor (MOR) expression in the inflammatory skin tissue and the effect of electroacupuncture (EA) onthe topical immunoreaction (IR) of MOR positive fibers in adjuvant arthritic (AA) rats. Methods: A total of 48 SD rats were randomized into control (n =8), model (n= 10), focus-side-EA (n = 10), non-acupoint-EA (n = 10), and healthy-side-EA (n = 10) groups. AA model was established by subcutaneous injection of complete Freund's adjuvant (CFA, 50 μL) into the left hind paw.EA (4-16 Hz, 0.5-1.5 V) was applied to "Huantiao" (环跳 GB 30) and "Yanglingquan" (阳陵泉 GB 34)on the focus or healthy side and non-acupoints for 30 min. Non-acupoints used were the two sites 5 mm to GB 30 and GB 34 on the healthy side. The topical MOR IR-positive fibers in the dermal and subcutaneous tissues of the focus was stained with immunohistochemical method. The severity of pain was detected by foot (anklejoint)-bending test. Results: Compared with model group, the "foot-bending test" score decreased significantly in focus-side-EA group on the 9th and 11th day (P<0.05) and in non-acupoint-EA group on the 8th, 9th and 11thd after injection of CFA (P <0.05), indicating that EA of bilateral GB 30 and GB 34 and non-acupoints all can relieve pain. From the 13th day on, no significant differences were found in "foot-bending test"scores among the 3 EA groups and model group (P>0.05). In comparison with control group, the area values of MOR IR-positive nerve fibers in the focus tissue were significantly higher in 3 EA groups (P<0.05).The area values of MOR IR-positive nerve fibers in the focus in model group and 3 EA groups were significant higher than that in control group (P<0.05). Compared with model group, the area values of MOR IR-positive fibers in focus-side-EA group and healthy-side-EA group increased significantly ( P <0.05); while those of MOR IR-positive fibers in non-acupoint-EA group and healthy-side-EA group were

  7. Therapeutic effect of the anti-Fas antibody on arthritis in HTLV-1 tax transgenic mice.

    Science.gov (United States)

    Fujisawa, K; Asahara, H; Okamoto, K; Aono, H; Hasunuma, T; Kobata, T; Iwakura, Y; Yonehara, S; Sumida, T; Nishioka, K

    1996-07-15

    We have recently demonstrated Fas-mediated apoptosis in the synovium, of patients with rheumatoid arthritis (RA) and suggested that it may be one factor responsible for the regression of RA. To examine whether the induction of apoptosis caused by anti-Fas mAb may play a potential role as a new therapeutic strategy for RA, we investigated the effect of anti-Fas mAb (RK-8) on synovitis in an animal model of RA, the human T cell leukemia virus type I (HTLV-1) tax transgenic mice. We report here that administration of anti-Fas mAb into mice intra-articularly improved the paw swelling and arthritis within 48 h. Immunohistochemical study and in vitro culture studies showed that 35% of synovial fibroblasts, 75% of mononuclear cells, and some of polymorphonuclear leukocytes infiltrating in synovium underwent apoptosis by anti-Fas mAb. In situ nick end labeling analysis and electron microscope analysis clearly showed that many cells in synovium were induced apoptosis by anti-Fas mAb administration. However, local administration of anti-Fas mAb did not produce systemic side effects. Results demonstrated that administration of anti-Fas mAb in arthritic joints of the HTLV-1 tax transgenic mice produced improvement of arthritis. These findings suggest that local administration of anti-Fas mAb may represent a useful therapeutic strategy for proliferative synovitis such as RA.

  8. ARG098, a novel anti-human Fas antibody, suppresses synovial hyperplasia and prevents cartilage destruction in a severe combined immunodeficient-HuRAg mouse model

    Directory of Open Access Journals (Sweden)

    Matsubara Tsukasa

    2010-09-01

    Full Text Available Abstract Background The anti-human Fas/APO-1/CD95 (Fas mouse/human chimeric monoclonal IgM antibody ARG098 (ARG098 targets the human Fas molecule. The cytotoxic effects of ARG098 on cells isolated from RA patients, on normal cells in vitro, and on RA synovial tissue and cartilage in vivo using implanted rheumatoid tissues in an SCID mouse model (SCID-HuRAg were investigated to examine the potential of ARG098 as a therapy for RA. Methods ARG098 binding to each cell was analyzed by cytometry. The effects of ARG098 on several cells were assessed by a cell viability assay in vitro. Effects on the RA synovium, lymphocytes, and cartilage were assessed in vivo using the SCID-HuRAg mouse model. Results ARG098 bound to cell surface Fas molecules, and induced apoptosis in Fas-expressing RA synoviocytes and infiltrating lymphocytes in the RA synovium in a dose-dependent manner. However, ARG098 did not affect the cell viability of peripheral blood mononuclear cells of RA patients or normal chondrocytes. ARG098 also induced apoptosis in RA synoviocytes and infiltrating lymphocytes in the RA synovium in vivo. The destruction of cartilage due to synovial invasion was inhibited by ARG098 injection in the modified SCID-HuRAg mouse model. Conclusions ARG098 treatment suppressed RA synovial hyperplasia through the induction of apoptosis and prevented cartilage destruction in vivo. These results suggest that ARG098 might become a new therapy for RA.

  9. 挑筋法诱导佐剂型关节炎大鼠滑膜细胞凋亡的实验研究%Experimental study on the effect of fibrous-tissue-broken pricking on apoptosis of rat synovium in Freund's adjuvant arthritis

    Institute of Scientific and Technical Information of China (English)

    童娟; 明顺培; 罗健

    2004-01-01

    目的:实验研究挑筋法对佐剂型关节炎大鼠滑膜细胞凋亡影响. 方法:将 40只 SD大鼠随机分为正常组、模型组、药物组、挑筋组,每组 10只,实验中建立佐剂型关节炎模型,运用 TUNEL法检测挑筋法对大鼠滑膜细胞凋亡的影响. 结果:致炎后模型组大鼠后踝关节红、肿,大鼠跛行,体质量下降,跖围与体质量分别为( 25.48± 2.16) mm,(123.4± 12.8) g,经挑筋疗法治疗后大鼠后踝关节红、肿消失,跖围、体质量分别为 (22.15± 1.17) mm,(132.5± 14.2) g,与模型组比较差异有显著性意义( P< 0.001).运用 TUNEL检测各组滑胞细胞凋亡发现挑筋组和药物组出现明显的细胞凋亡,两者凋亡率分别为( 43.81± 3.84)%,( 51.58± 9.73)%,两者差异有显著性意义( P< 0.05),药物组细胞凋亡率高于挑筋组. 结论:挑筋法诱导佐剂型关节炎大鼠滑膜细胞凋亡,故可能通过抑制和减少滑膜细胞的过度增生治疗炎性疾病.%AIM:To study the effect of fibrous-tissue-broken pricking on apoptosis of rat synovium in Freund's adjuvant arthritis. METHODS:A total of 40 SD rats were divided into normal group,model group,medication group,and pricking group,with 10 rats in each group. Freund's adjuvant arthritis model was established and the effect of fibrous-tissue-broken pricking on apoptosis in rat synovium was detected using TUNEL method. RESULTS:The inflammatory rats in model group limped with swollen posterior ankle joint and their body mass decreased,the width of plantar circumference and body mass of (25.48± 2.16) mm and (123.4± 12.8) g,respectively.After the treatment by fibrous-tissue-broken pricking, the swelling relieved,with plantar circumference and body mass of (22.15± 1.17) mm and (132.5± 14.2) g,respectively.There was a significant difference compared with the model group(P< 0.001).TUNEL detection revealed that the apoptosis index of the medication group ( 51.58± 9.73)% was higher than that of the pricking

  10. Effects of Kunxian Capsule on γIP-10 of Blood Serum and Synovium in CIA Rats%昆仙胶囊对大鼠诱导性关节炎滑膜及血清γIP-10的影响

    Institute of Scientific and Technical Information of China (English)

    王笑丹; 徐强; 林昌松; 郭钟慧; 林云斌; 李卓璐

    2012-01-01

    Objective : To observe regulating effect of Kunxian oapsule on oytokine γ IP-10 in Collagen Induced Arthritis ( CIA ) rat synovium and blood serum, to discuss the function mechanism of Kunxian capsule in the treatment of RA by tonifying kidney and dispelling wind and dampness. Methods: CIA rats model was established through subcutaneous injection with collagen protein Ⅱ in root of tail multipoint. SPF Wistar rats were divided randomly into six groups: normal control group, oollogen induced arthritis ( CIA ) model group, MTX-treated group, low dose Kunxian-treated group, middle dose Kunxian-treated group and high dose Kunxian-treated group. Measure swollen degree of crural rats limbs of all groups, test X-ray changes of hind limbs and pathological changes in synovial hind joint of all rats. The expression of γ IP-10 in the peripheral blood was detected by ELISA. The expression of γlP-10 mRNA in rats synovium was detected by RT-PCR. Result: For MTX and all dose Kunxian-treated groups, inflammation degree of rats arthritis were alleviated, impairment of synovium cells hyperplasia, soakage of inflammatory cells and formation of pannus were more significantly improved than those in model group (P<0.05 ). Expression of γ IP-10 in peripheral bloods serum and γ IP-10 mRNA in rats synovium of model group were obviously higher than that of normal control group (P<0.05 ). Compared with model group, expression of γ IP-10 in blood serum of MTX-treated group, middle and high dose Kunxian-treated groups declined (P<0.05 ), expression of γ IP-10 mRNA in rats synovium of MTX-treated group and high dose Kunxian-treated group declined ( P<0.05 ), especially more significantly for high dose of Kunxian-treated group ( P<0.01 ). Conclusion: Kunxian capsule can significantly relieve arthritis symptoms and impairment of synovial cell of CIA rats, cause inhibition of high expression level of γ IP-10 in blood and synovium, and alleviate joints synovitis and vasculitis of CIA rats

  11. 胶原性关节炎大鼠血浆肿瘤坏死因子α和滑膜血管内皮生长因子表达的相关性%Correlation between plasma contents of tumor necrosis factor-alpha and expressions of vascular endothelium growth factor of synovium in collagen-induced arthritis rats

    Institute of Scientific and Technical Information of China (English)

    熊新贵; 梁清华; 陈疆; 李春燕; 何金华; 李霞玲; 张花先; 刘小春

    2006-01-01

    积分的关系,与血浆肿瘤坏死因子α含量及滑膜血管内皮生长因子表达的关系,胶原性关节炎大鼠血浆肿瘤坏死因子α与滑膜血管内皮生长因子表达相关分析.结果:纳入动物40只,均进入结果分析.随着胶原性关节炎发病时间的延长,滑膜新生血管逐渐增多、滑膜增厚、关节炎指数积分逐渐增加、肿瘤坏死因子α含量和血管内皮生长因子水平也随之升高;其关节炎指数积分与血管内皮生长因子表达水平呈正相关(r=0.535,P<0.05),与肿瘤坏死因子α含量虽有相关增高趋势,但差异无显著性(r=0.371,P>0.05).血浆肿瘤坏死因子α含量与血管内皮生长因子表达水平呈显著正相关(r=0.893,P<0.01).结论:肿瘤坏死因子α与血管内皮生长因子在类风湿关节炎炎症反应,滑膜新生血管形成的细胞因子网络中起重要作用,二者相互可能具有影响,相互促进,充当恶性网络循环的调控作用;是介导类风湿关节炎发生和发展以及骨质侵蚀、致残的众多因子中的关键因子.%BACKGROUND: Pathological change of synovium in rheumatoid arthritis (RA) has the characteristic of tumor-like growth, it appears thickening of the synovium tissue and the formatiom of pannus, which generate periarticular erosion and destruction. Multiplicate cell factors and growth factors participate in the development course of tumor-like lesion of synovium, and the tumor necrosis factor-α(TNF-α) and vascular endothelial growth factor(VEGF)play important roles in the development of RA and the formation of pannus.OBJECTIVE: To observe the contents of plasma TNF-α of collagen-induced arthritis and the expression change of VEGF of synovium at different time point, and investigate the effect and correlation of TNF-α and VEGF in the pathogenesis of RA.DESIGN: Randomized grouping experiment taking animals as subjects.SETTING: Institute integrated traditional and western medicine of Xiangya

  12. Anti-adjuvant arthritis of recombinant human endostatin in rats via inhibition of angiogenesis and proinflammatory factors

    Institute of Scientific and Technical Information of China (English)

    Li YUE; Hua WANG; Li-hua LIU; Yu-xian SHEN; Wei WEI

    2004-01-01

    AIM: To investigate the profile of endostatin on adjuvant arthritis (AA) and angiogenesis blockade in synovitis.METHODS: The model of rat AA was induced by injection of intradermal complete Freund's adjuvant (CFA). Hind paw volume of rat was measured by volume meter and the activities of interleukin- 1 (IL- 1) and IL-2 Were measured by the assay of thymocytes proliferation. IL-1 β and tumor necrosis factor-α (TNF-α) produced by synoviocytes was estimated with radioimmunoassay. The number of new blood vessels in knee joint synovium was counted under microscope by hematoxylin and eosin (HE) staining. RESULTS: The secondary inflammation of AA rats appeared on the 10th day after injection of CFA. The therapeutic administration of endostatin (0.1, 0.5, and 2.5secondary paw swelling and the number of new blood vessels in the synovium of AA rats. Endostatin significantly decreased the production of IL-1 derived from both peritoneal macrophages and synoviocytes and IL-2 from splenocytes, especially at the dose of 2.5 mg/kg. This effect of endostatin also was seen on TNF-α produced by synoviocytes. CONCLUSION: The recombinant human endostatin had an inhibitory effect on rat AA, which was related to its anti-angiogenesis and inhibition of proinflammatory cytokines.

  13. Slit2在类风湿性关节炎大鼠滑膜的表达与益赛普对其干预的影响%The expression of Slit2 in the synovium of the RA rat and the effects of etanercept intervention on this expression

    Institute of Scientific and Technical Information of China (English)

    刘志群

    2012-01-01

    To study the pathogenesis of rheumatoid arthritis, we investigated the linkage between Slit2 protein and clinicopathological features of rheumatoid arthritis, the role of Slit2 protein in synovium in rheumatoid arthritis, and the therapeutic effects of Etanercept on the expression of Slit2 in rheumatoid arthritis synovial tissue. The model of adjuvant arthritis were established by intradermal injecting of complete Freund's adjuvant, and 14 days later, 8 rats from the model were treated with Etanercept. Then we observed the synovial tissue pathology of normal, model, and treatment groups by HE staining, and determined the expression of Slit2 protein by immunohistochemistry. The pathological score and the Slit2 protein expression were significantly higher in the synovium of adjuvant arthritis rats than those of normal group, while the treatment group demonstrated moderate level of pathological score and the Slit2 protein. All results indicated that Slit2 protein may play an important role in the pathogenesis of RA, and Etanercept can down-regulate the expression of Slit2 protein.%目的 探讨Slit2表达在类风湿性关节炎大鼠滑膜中的作用及益赛普对类风湿性关节炎大鼠滑膜Slit2表达的影响.方法 用弗氏完全佐剂皮下注射建立佐剂性关节炎模型,其中8只造模14 d后予益赛普治疗,取正常、模型及治疗组膝关节组织进行HE染色及免疫组化观察Slit2的表达.结果 模型组病理学积分明显高于正常组,Slit2在佐剂性关节炎大鼠滑膜表达水平显著增加,且与时间相关,通过益赛普治疗后病理学积分减少,Slit2表达下调.结论 Slit2蛋白可能在大鼠佐剂性关节炎的发生发展中发挥着重要作用,益赛普可以下调Slit2蛋白的表达.

  14. Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ(12,14)-Prostaglandin J2 (15d-PGJ2) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4(+)CD25(-)FOXP3(+) Cells.

    Science.gov (United States)

    Carregaro, Vanessa; Napimoga, Marcelo H; Peres, Raphael S; Benevides, Luciana; Sacramento, Laís Amorim; Pinto, Larissa G; Grespan, Renata; Cunha, Thiago M; da Silva, João Santana; Cunha, Fernando Q

    2016-01-01

    The prostaglandin, 15-deoxy Δ(12,14)-prostaglandin J2 (15d-PGJ2), is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4(+) Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4(+)CD25(-) population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4(+)CD25(-) cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.

  15. 资木瓜总苷对佐剂性关节炎大鼠滑膜肥大细胞脱颗粒和类胰蛋白酶表达的影响%Effects of Total Saponins of Chaenomeles speciosa on the Number and Degranulation Ratio of Mast Cells and Expression of Tryptase in Synovium of Rats with Adjuvant Arthritis

    Institute of Scientific and Technical Information of China (English)

    李世刚; 刘朝霞; 张永琦; 陈燕

    2012-01-01

    . Synovial tissues of the right hind ankles were sampled and stained with HE for observing synovial pathology to evaluate the effects of TSCS on AA, then stained with TB for observing the number and degranulalion ratio of synovial mast cells and finally detected by immunohistochemical staining method to investigate the expression of tryptase in synovium. Result; TSCS increased significantly the body weight of AA rats, while decreased obviously the paw volume. TSCSsignificantly inhibited inflammatory cell infiltration, synovial cell hyperplasia, and synovial fibroplasia in synovium of AA rats. TSCS could significantly diminish the numbers of total and degranulated mast cells in AA rats, TSCS decreased the expression of tryptase in synovium. Analyzed by Spearman's bivariate correlation, (he number of mast cells and degranulation ratio of mast cells were positively correlated with the pathological scores. Conclusion; TSCS can improve pathological condition of inflammatory synovium in AA rats by inhibiting the function of synovial mast cells, which may play an important underlying role in the immunoregulation of TSCS on AA.

  16. Transient Receptor Potential Ankyrin 1 Channel Expression on Peripheral Blood Leukocytes from Rheumatoid Arthritic Patients and Correlation with Pain and Disability

    Science.gov (United States)

    Pereira, Ione; Mendes, Saulo J. F.; Pereira, Domingos M. S.; Muniz, Thayanne F.; Colares, Valderlane L. P.; Monteiro, Cinara R. A. V.; Martins, Mahiba M. R. de S.; Grisotto, Marcos A. G.; Monteiro-Neto, Valério; Monteiro, Sílvio G.; Calixto, João B.; Brain, Susan D.; Fernandes, Elizabeth S.

    2017-01-01

    Patients with rheumatoid arthritis (RA) suffer from pain and joint disability. The transient receptor potential ankyrin 1 (TRPA1) channel expressed on sensory neurones and non-neuronal cells mediates pain transduction and inflammation and it has been implicated in RA. However, there is little information on the contribution of TRPA1 for human disease. Here, we investigated the expression of TRPA1 on peripheral blood leukocytes and the circulating levels of its endogenous activators 4-hydroxynonenal (4-HNE) and hydrogen peroxide (H2O2) in RA patients treated or not with the anti-rheumatic leflunomide (LFN) or the anti-TNFα adalimumab (ADA). We also assessed whether TRPA1 expression correlates with joint pain and disability, in addition to the immune changes in RA. TRPA1 expression on peripheral blood leukocytes correlated with pain severity and disability. TRPA1 levels on these cells were associated with the numbers of polymorphonuclear and the activation of CD14+ cells. No correlations were found between the lymphocyte population and TRPA1 expression, pain or disability. Patients recently diagnosed with RA expressed increased levels of TRPA1 on their leukocytes whilst treatment with either LFN or ADA down-regulated this receptor probably by reducing the numbers of polymorphonuclears and the activation of CD14+ cells. We suggest that the activation levels of CD14+ cells, the numbers of PMNs in the peripheral blood and the expression of TRPA1 on peripheral blood leukocytes correlate with RA progression, affecting joint pain sensitivity and loss of function. PMID:28239353

  17. 2-photon laser scanning microscopy on native human cartilage

    Science.gov (United States)

    Martini, Joerg; Toensing, Katja; Dickob, Michael; Anselmetti, Dario

    2005-08-01

    Native hyaline cartilage from a human knee joint was directly investigated with laser scanning microscopy via 2-photon autofluorescence excitation with no additional staining or labelling protocols in a nondestructive and sterile manner. Using a femtosecond, near-infrared (NIR) Ti:Sa laser for 2-photon excitation and a dedicated NIR long distance objective, autofluorescence imaging and measurements of the extracellular matrix (ECM) tissue with incorporated chondrocytes were possible with a penetration depth of up to 460 μm inside the sample. Via spectral autofluorescence separation these experiments allowed the discrimination of chondrocytes from the ECM and therefore an estimate of chondrocytic cell density within the cartilage tissue to approximately 0.2-2•107cm3. Furthermore, a comparison of the relative autofluorescence signals between nonarthritic and arthritic cartilage tissue exhibited distinct differences in tissue morphology. As these morphological findings are in keeping with the macroscopic diagnosis, our measurement has the potential of being used in future diagnostic applications.

  18. Relationship between synovium pathological change and injection timing in rabbits with papain-induced knee osteoarthritis%木瓜蛋白酶诱导膝关节骨关节炎模型兔滑膜病理变化与药物注射时间的关系

    Institute of Scientific and Technical Information of China (English)

    孙鲁宁; 赵燕华; 黄桂成; 夏建龙

    2011-01-01

    背景:木瓜蛋白酶诱导兔膝关节骨性关节炎的造模方法可获得稳定的退行性关节炎模型.目的:观察兔膝关节腔内注射木瓜蛋白酶诱导骨关节炎后,滑膜炎性病理改变与药物注射时间的关系.方法:将木瓜蛋白酶水溶液分别在实验开始的第1,4,7天分别注射入15只西兰大白兔右膝关节腔内,建立膝关节骨性关节炎兔模型,于首次注射后第2,4,6周分别观察膝关节滑膜大体及组织病理学变化,每个时间点5只.结果与结论:木瓜蛋白酶首次注射后第2周,兔膝关节滑膜炎性反应最严重,表现为滑膜细胞增生最明显,下层疏松纤维及血管组织明显增生,可见较多淋巴浆细胞浸润,第4,6周时炎性反应逐渐减轻.说明兔膝关节首次注射木瓜蛋白酶后2周时滑膜炎性反应最严重.%BACKGROUND: A stable degenerative knee osteroarthritis model in rabbits can be established by the induction of papain. OBJECT IVE: To explore the relationship between the pathological change of synovium and injection timing in rabbits with kneeMETHODS: Papain solution was injected into the right knee joint cavity of 15 Hew Zealand white rabbits on the 1sl.4hand7h2rd , 4h and Bh weeks after first injection. Five rabbits were examined at each time point.RESULT SAND CONCLUSION: The synovium inflammatory reaction of rabbit knee joint was the most serious at the 2rd weekafter the first injection of papain, characterized by the most obvious proliferation of synovia I cell, obvious proliferation of vas:cuarreaction relieved gradualy in the 4h and 6h weeks. These results il lustrate th at th e syn oviu m inf lammato ry reaction of knee joint in rabbits reach its maximum effect in the 2rd week after the fifst injection of papain.

  19. 关节腔内注射洛伐他汀预防骨关节炎软骨退变%The effects of lovastatin on matrix metalloproteinase-1 ,-3 mRNA expression in cartilage and synovium of osteoarthritis rabbits

    Institute of Scientific and Technical Information of China (English)

    范李; 杨述华

    2009-01-01

    Objective To observe the influence of intra-articular injection of lovastatin on cartilage degeneration and mRNA expres-sion of matrix metalloproteiase-1,-3 (MMP-1,-3) in cartilage and synovium of osteoarthritis (OA) model. Methods Thirty New Zeal-and rabbits underwent unilateral anterior cruciate ligament transection (ACLT) were random divided into two groups. The rabbits in experi-mental group received 0.1 mg/ml intra-articular lovastatin injection at 0.2 ml/kg of body weight immediately after surgery , once a week. Those in control group were treated with intra-articular injection of normal saline. At the 6th week after surgery, all rabbits were sacrificed. The articular cartilage degeneration of medial femoral condyle was evaluated under microscopy. Gene expression of MMP-1,-3 was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results Cartilage degeneration in untreated group was significantly more severe than that in experimental group. In cartilage, no significant difference on the expression of MMP-1 and MMP-3 mRNA was found be-tween the experimental group and control group. In synovium, the expression of MMP-1 and MMP-3 mRNA was significantly suppressed in experimental group compared with control group. Conclusion During the development of experimental OA, intra-articular administration of lovastatin reduces the expression of matrix degrading enzyme, thus alleviate cartilage degradation.%目的 研究洛伐他汀关节腔内注射对骨关节炎(OA)模型关节软骨退变及对基质金属蛋白酶(matrix metalloprotein-ase-1,3)mRNA表达的影响.方法 30只6个月龄新西兰大白兔行右膝关节前交叉韧带切断术.手术后将动物随机分为实验组和对照组,实验组术后立即给予关节腔内注射0.5 mg/ml洛伐他汀0.2 ml/kg,每周1次,连续6周;对照组则关节腔内注射等容量的生理盐水.术后6周处死动物.在解剖镜下观察股骨内髁关节软骨的大体形态学改变并评分.用

  20. Effects of Wenhua Juanbi Recipe on the Gene Expression Profile of the Synovium in Collagen-Induced Arthritis Rats%温化蠲痹方对胶原诱导性关节炎大鼠滑膜基因表达谱的影响

    Institute of Scientific and Technical Information of China (English)

    刘喜德; 洪旭涛; 王云卿; 王芳; 蔡龙; 冯莹莹

    2012-01-01

    目的 研究中药温化蠲痹方对胶原诱导性关节炎( collagen-induced arthritis,CIA)大鼠滑膜基因表达谱的影响,探讨其治疗CIA的作用机制.方法 选用健康雄性Wistar大鼠40只,采用大鼠尾根部注射牛Ⅱ型胶原乳剂的方法建立CIA模型.选取造模成功的16只大鼠随机分为模型组和中药组,每组8只.中药组给予温化蠲痹方22.9 g/(kg·d)灌胃,模型组以生理盐水灌胃,均每天1次,连续30天.给药结束后,提取两组大鼠滑膜总RNA,运用Illumina基因表达谱芯片分析每个样本基因变化.结果 与模型组比较,温化蠲痹方干预后大鼠滑膜差异表达基因有222条,其中上调基因76条,如防御素3b( RatNP-3b)等;下调基因146条,如血管生成素样蛋白2( Angptl 2)、黏蛋白1(Muc1)、B细胞淋巴瘤/白血病-2(bcl-2)等.差异表达基因主要涉及细胞凋亡、血管生成素、防御素基因、细胞因子、信号转导、癌基因等.结论 中药温化蠲痹方可能通过对多基因表达进行调控,从而发挥多靶点治疗CIA的作用.%Objective To study the effects of Wenhua Juanbi Recipe (WJR) on the gene expression pro-file of the synovium in collagen-induced arthritis (CIA) rats, and to explore its mechanisms for treating CIA. Methods The CIA model was induced by intradermal injection of bovine collagen type Ⅱ emulsion from the tail of 40 healthy male Wistar rats. Selected 16 successfully modeled rats were randomly divided into the model group and the WJR-treated group, 8 in each group. WJR at the daily dose of 22. 9 g/kg was given to rats in the WJR-treated group by gastrogavage, while normal saline was given to those in the model group. Both were performed once daily, for 30 successive days. By the end of medication, the total RNA was extracted from the synovium of rats in the two groups. The gene expression profile of each sample was analyzed using Illumina oligonucleotide microarray. Results Compared with the model group, after

  1. Inefficacy of Topical Diclofenac in Arthritic Horses

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    Nicolís F.  Villarino

    2006-01-01

    Full Text Available The objective of the present study was test the anti-inflammatory efficacy of diclofenac dietilamine, applied epicutaneously at a dose rate of 0.44 mg kg-1, in a model of acute arthritis in horses. Four clinical end-points, as well as two biochemical markers, were used as surrogate markers of the required clinical response (analgesia, anti-inflammatory. Low diclofenac concentrations were measured in blood (Cmax 0.04±0.03 ug mL-1 and synovial fluid (Cmax 0.08 ±0.08 ug mL-1 from the first to the last sampling time. The statistical comparison of the clinical end-points and biochemical markers between placebo and dicilofenac treated group indicated a lack of pharmacological effect of this compound after epicutaneous administration.

  2. Effect of kanggutong injection on arthritic change of ankle and severity of swelling in rats%抗骨痛注射液对大鼠踝关节炎性变化及肿胀程度的影响

    Institute of Scientific and Technical Information of China (English)

    赵艳; 赵英; 张孟玲; 段永梅; 路秀珍; 孙美

    2004-01-01

    BACKGROUND: By several screenings and more than ten-year clinical observation, it is discovered that the outstanding results have been achieved by the treatment of joint swelling and pain with Kanggutong injection (KGT)in the aspects of releasing joint swelling and pain, cervical spondylosis, the symptoms and physical signs of osteoarthropathy. In order to study on the mechanism of KGT on joint swelling and pain, cervical spandylosis and osteoarthropathy, the writers carried on the animal experiment.OBJECTIVE: To probe into the mechanism of KGT injection on the treatment of local soft tissue hyperplasia, edema, pricking pain or neural compression.DESIGN: A randomized controlled study.SETTING: Department of Physiotherapy, the 202 Hospital of Chinese PLA,Department of Experimental Animal, Shanghai University of Traditional Chinese Medicine.PARTICIPANTS: The experiment was accomplished in the Department of Experimental Animal of Shanghai University of Traditional Chinese Medicine from May 2002 to January 2003. The department provided 21 normal female SD rats, aged 4 months, clean grade, which were divided into 3 groups at random, named as control group, dexamethasone(DXM) group and KGT group, 7 rats in each group.INTERVENTIONS: Abdominal injection with physiological saline 6ml was done in control, with DXM 0.08 g/L, 6 mL in DXM group and with KGT 6 mL in KGT group. 0.5 hour later, uric acid sodium 0. 3 mL (25 g/L) was injected peripherally on the right ankle joint of each rat in 3 groups to induce arthritis. The perimeter of the right ankle joint was tested before and 10 and 20 hours after experiment.MAIN OUTCOME MEASURES: The perimeter of the right ankle joint before and 10 and 20 hours after experimentRESULTS: The right ankle joints of rats in the 3 groups were induced aseptic arthritic and local swelling by uric acid sodium. But the severity of swelling was various due to intra-abdominal injection of different medicines. Comparison of joint swelling severity 10

  3. Update on human health effects of boron.

    Science.gov (United States)

    Nielsen, Forrest H

    2014-10-01

    In vitro, animal, and human experiments have shown that boron is a bioactive element in nutritional amounts that beneficially affects bone growth and central nervous system function, alleviates arthritic symptoms, facilitates hormone action and is associated with a reduced risk for some types of cancer. The diverse effects of boron suggest that it influences the formation and/or activity of substances that are involved in numerous biochemical processes. Several findings suggest that this influence is through the formation of boroesters in biomolecules containing cis-hydroxyl groups. These biomolecules include those that contain ribose (e.g., S-adenosylmethionine, diadenosine phosphates, and nicotinamide adenine dinucleotide). In addition, boron may form boroester complexes with phosphoinositides, glycoproteins, and glycolipids that affect cell membrane integrity and function. Both animal and human data indicate that an intake of less than 1.0mg/day inhibits the health benefits of boron. Dietary surveys indicate such an intake is not rare. Thus, increasing boron intake by consuming a diet rich in fruits, vegetables, nuts and pulses should be recognized as a reasonable dietary recommendation to enhance health and well-being.

  4. 脊髓IL-12在大鼠关节炎性痛维持中的作用%Role of interleukin-12 in spinal cord in maintenance of arthritic pain in rats

    Institute of Scientific and Technical Information of China (English)

    周亚兰; 李号令; 李卉; 熊源长; 张玉秋; 许华

    2015-01-01

    Objective To evaluate the role of interleukin-12 (IL-12) in the spinal cord in the maintenance of arthritic pain (AP) in rats.Methods Adult male Sprague-Dawley rats, aged 6-8 weeks,weighing 200-300 g, were randomly divided into 4 groups using a random number table: control group (group C, n=6);AP group (n=9);phosphate buffer solution (PBS) group (n=6);IL-12 antibody group (n =6).AP was induced by injecting 50 μl of complete Freund' s adjuvant into the ankle joint cavity of the left hindpaw of rats anesthetized with isoflurane.Goat anti-rat IL-12 antibody 1.50 μg (20 μl) was intrathecally injected on 9 days after establishment of the model in group IL-12 antibody, while 0.01 mol/L PBS (20 μl) was administered in group PBS.The mechanical paw withdrawal threshold to yon Frey filament stimulation (MWT) was measured before establishment of the model (baseline) and on 9 and 10 days after establishment of the model.The rats were sacrificed after the last measurement of pain threshold, and the L4 6 segments of the spinal cord were obtained for detection of IL-12 expression in the spinal dorsal horn (by immunofluorescence) , and the co-expression of IL-12 and glial fibrillary acidic protein (an astrocyte marker) was examined simultaneously in group AP.Results Compared with group C, the MWT was significantly decreased, and the expression of IL-12 was up-regulated on 9 and 10 days after establishment of the model in AP, PBS and IL-12 antibody groups.Compared with group AP, the MWT was significantly increased at 10 days after establishment of the model, and the expression of IL-12 was down-regulated in group IL-12 antibody, and no significant change was found in the MWT at 10 days after establishment of the model and expression of IL-12 in group PBS.IL-12 was co-expressed with glial fibrillary acidic protein in group AP.Conclusion IL-12 in the spinal cord is involved in the maintenance of AP in rats.%目的 评价脊髓IL-12在大鼠关节炎

  5. EXPERIENCE OF INTRAVENOUS INJECTION OF NORMAL HUMAN IMMUNOGLOBULIN IN A PATIENT WITH KAWASAKI SYNDROME

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    T. V. Sleptsova

    2014-01-01

    Full Text Available The article presents a case of late diagnosis of cutaneomucosal lymphonodular syndrome (Kawasaki syndrome. The child featured fever, mucosal lesion (conjunctivitis, stomatitis, rash, thick edemas on arms and feet, arthritis and coronaritis. Initial therapy proved ineffective. Pathogenetic therapy, which proved to be rather effective, was prescribed after diagnosis was confirmed. The authors present a case of successful use of normal human immunoglobulin for intravenous injections in the dose of 2 g/kg of body weight per course in combination with acetylsalicylic acid in the dose of 80 mg/kg per day. Body temperature decreased down to subfebrile figures and foot pain attenuated as early as after 1 day of treatment. Fever, rash, stomatitis and conjunctivitis terminated, edemas of limbs and arthritic manifestations attenuated considerably and laboratory parameters of disease activity normalized after 1 week (ESR and CRP. Inflammation of coronary arteries terminated after 3 weeks. No adverse events in the setting of immunoglobulin therapy were observed.  

  6. Mesenchymal Stem Cell Levels of Human Spinal Tissues.

    Science.gov (United States)

    Harris, Liam; Vangsness, C Thomas

    2017-09-06

    .: Systematic Review. .: The aim of this study was to investigate, quantify, compare and compile the various mesenchymal stem cell tissue sources within human spinal tissues to act as a compendium for clinical and research application. .: Recent years have seen a dramatic increase in academic and clinical understanding of human mesenchymal stem cells (MSCs). Previously limited to cells isolated from bone marrow, the past decade has illicited the characterization and isolation of human MSCs from adipose, bone marrow, synovium, muscle, periosteum, peripheral blood, umbilical cord, placenta and numerous other tissues. As researchers explore practical applications of cells in these tissues, the absolute levels of MSCs in specific spinal tissue will be critical to guide future research. .: The PubMED, MEDLINE, EMBASE and Cochrane databases were searched for articles relating to the harvest, characterization, isolation and quantification of human mesenchymal stem cells from spinal tissues. Selected articles were examined for relevant data, categorized according to type of spinal tissue, and when possible, standardized to facilitate comparisons between sites. .: Human mesenchymal stem cell levels varied widely between spinal tissues. Yields for Intervertebral disc demonstrated roughly 5% of viable cells to be positive for MSC surface markers. Cartilage endplate cells yielded 18,500- 61,875 cells/ 0.8 mm thick sample of cartilage end plate. Ligamentum flavum yielded 250,000- 500,000 cells per gram of tissue. Annulus fibrosus FACS treatment found 29% of cells positive for MSC marker Stro-1. Nucleus pulposus yielded mean tissue samples of 40,584-234,137 MSCs/gram of tissue. .: Numerous tissues within and surrounding the spine represent a consistent and reliable source for the harvest and isolation of human mesenchymal stem cells. Among the tissues of the spine, the annulus fibrosus and ligamentum flavum each offer considerable levels of mesenchymal stem cells, and may

  7. Effect of Heat Reinforcing Acupuncture Manipulation on Articular Synovium LDH, SDH and CCO in Rheumatoid Arthritis ;Rabbits%热补针法对类风湿关节炎家兔关节滑膜LDH、SDH和CCO活性的影响

    Institute of Scientific and Technical Information of China (English)

    杜小正; 王金海; 秦晓光; 方晓丽; 张小江

    2016-01-01

    平补平泻组和捻转补法组(P<0.05)。结论热补针法治疗RA疗效确切,可增强RA模型家兔SDH、CCO活性,从而增强有氧代谢,使机体局部产生更多的能量,这可能是热补针法“取热”的可能机制之一。%Objective To investigate the regulating effect of heat reinforcing acupuncture manipulation on body energy metabolism enzymes in rheumatoid arthritis (RA) and preliminarily explain the mechanism of heat-producing action of heat reinforcing acupuncture manipulation. Method Forty chinchilla rabbits were randomized into normal, model, equal reinforcement and reduction, twirling reinforcement, and heat reinforcing acupuncture manipulation groups. A model of cold syndrome-type RA was made by ovalbumin induction and exposure to low temperature in the other four groups not including the normal group. From two days after successful model making, the normal and model groups were grabbed and fastened (bound) by the same way as for the acupuncture groups, 30 min once daily. The equal reinforcement and reduction group received even reinforcing-reducing method;the twirling reinforcement group, twirling reinforcement method;the heat reinforcing group, heat reinforcing acupuncture manipulation. The needle was manipulated for 1 min and retained for 30 min once daily, for a total of seven days. The RA rabbit knee joint circumference was measured and the inflammation score was recorded according to synovial histopathological sections before and after treatment. After the completion of intervention, the rabbits were sacrificed and the articular synovium was rapidly separated for frozen sections. Articular synovium lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and cytochrome oxidase (CCO) activities were measured by histochemical staining. Result After acupuncture intervention, the RA rabbit knee joint circumference was shortened in all the equal reinforcement and reduction, twirling reinforcement, and heat reinforcing acupuncture

  8. Limited efficacy of COX-2 inhibitors on nerve growth factor and metalloproteinases expressions in human synovial fibroblasts.

    Science.gov (United States)

    Yorifuji, Makiko; Sawaji, Yasunobu; Endo, Kenji; Kosaka, Taiichi; Yamamoto, Kengo

    2016-05-01

    Nerve growth factor (NGF) is associated with arthritic pain and metalloproteinases are implicated in collagen and aggrecan degradation. Although selective COX-2 inhibitors are recommended for the treatment of arthritic diseases, their effects on NGF and metalloproteinases remain unclear. This study investigated the regulations of NGF and metalloproteinases by selective COX-2 inhibitors in isolated human synovial cells. The isolated human synovial cells were stimulated with IL-1β in the presence of selective COX-2 inhibitors (NS-398 or celecoxib) with or without exogenous PGE2 or its receptor (EP1-4) agonists. The expressions of NGF, MMP-1, -3, -13, ADAMTS-4, and -5 were quantified by real-time PCR and their proteins were determined by Western blotting. The amount of PGE2 released was measured by enzyme-linked immunosorbent assay (ELISA). The IL-1β inductions of NGF and MMP-1 and MMP-13 were augmented by the COX-2 inhibitors, whereas the inductions of ADAMTS-4 and ADAMTS-5 were inhibited. These actions were reversed by supplementing PGE2 or the EP4 agonist exogenously. Our comprehensive analysis revealed that COX-2 inhibitors may be beneficial for suppressing aggrecan degradation and for reducing inflammatory pain by inhibiting PGE2 release, although they may have limited efficacy in suppressing collagen degradation and nerve growth. This study suggests the feedback roles of PGE2 in the negative regulation of NGF and MMP-1 and MMP-13 and the positive regulation of ADAMTS-4 and ADAMTS-5. Copyright © 2016 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

  9. Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ12,14-Prostaglandin J2 (15d-PGJ2 Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4+CD25−FOXP3+ Cells

    Directory of Open Access Journals (Sweden)

    Vanessa Carregaro

    2016-01-01

    Full Text Available The prostaglandin, 15-deoxy Δ12,14-prostaglandin J2 (15d-PGJ2, is a lipid mediator that plays an important role in the control of chronic inflammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA is not well determined. We demonstrated the therapeutic effect of 15d-PGJ2 in an experimental model of arthritis. Daily administration of 15d-PGJ2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ2 treatment was associated with a marked reduction in joint levels of proinflammatory cytokines. Although the mRNA expression of ROR-γt was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ2-treated arthritic mice. The specific and polyclonal CD4+ Th17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4+CD25− population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4+CD25− cells selectively suppressed Th17 differentiation and promoted the enhancement of FOXP3 under polarization conditions. Thus, 15d-PGJ2 ameliorated symptoms of collagen-induced arthritis by regulating Th17 differentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ2 may represent a potential therapeutic strategy in RA.

  10. Human parvovirus PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V

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    Rotellini Matteo

    2010-10-01

    Full Text Available Abstract Background PARV4 is a new member of the Parvoviridae family not closely related to any of the known human parvoviruses. Viremia seems to be a hallmark of PARV4 infection and viral DNA persistence has been demonstrated in a few tissues. Till now, PARV4 has not been associated with any disease and its prevalence in human population has not been clearly established. This study was aimed to assess the tissue distribution and the ability to persist of PARV4 in comparison to parvovirus B19 (B19V. Results PARV4 and B19V DNA detection was carried out in various tissues of individuals without suspect of acute viral infection, by a real time PCR and a nested PCR, targeting the ORF2 and the ORF1 respectively. Low amount of PARV4 DNA was found frequently (>40% in heart and liver of adults individuals, less frequently in lungs and kidneys (23,5 and 18% respectively and was rare in bone marrow, skin and synovium samples (5,5%, 4% and 5%, respectively. By comparison, B19V DNA sequences were present in the same tissues with a higher frequency (significantly higher in myocardium, skin and bone marrow except than in liver where the frequency was the same of PARV4 DNA and in plasma samples where B19V frequency was significantly lower than that of PARV4 Conclusions The particular tropism of PARV4 for liver and heart, here emerged, suggests to focus further studies on these tissues as possible target for viral replication and on the possible role of PARV4 infection in liver and heart diseases. Neither bone marrow nor kidney seem to be a common target of viral replication.

  11. Acquired resistance to auranofin in cultured human cells.

    Science.gov (United States)

    Glennås, A; Rugstad, H E

    1985-01-01

    A substrain (HEAF) of cultured human epithelial cells, grown as monolayers, was selected for resistance to auranofin (AF), a gold-containing anti-arthritic drug, by growing the parental HE cells with stepwise increased concentrations of AF in the medium. HEAF cells acquired resistance to 2 mumol AF/l, twice the concentration tolerated by the sensitive HE cells. Resistance to AF was also demonstrated in another substrain (HE100) originally selected for by its cadmium resistance, and characterized by a high cytosolic metallothionein (MT) content. Following continuous exposure to 2 mumol AF/l for 4 days, 58% of the HEAF cells, 67% of the HE100 cells, and 16% of the HE cells remained adherent to the flasks, compared with non-treated controls. Following 24 h AF exposure to living cells, HEAF cells had one-half and HE100 cells twice the cellular and cytosolic gold concentration per mg protein, as compared with HE cells. Gel filtration of cell cytosols revealed gold-binding proteins with a mol. wt. of about 10 000 apparently occurring on AF exposure in HEAF and HE cells. They bound 10-15% of cytosolic gold. MT in HE100 cells bound AF-gold to about the same extent. We suggest that the ability of cells to maintain the gold concentration at a low level (HEAF) and trapping of gold by MT (HE100) or low molecular weight proteins occurring on AF treatment (HEAF) may be mechanisms contributing to the observed cellular resistance to AF.

  12. Induction of PNAd and N-acetylglucosamine 6-O-sulfotransferases 1 and 2 in mouse collagen-induced arthritis

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    Rosen Steven D

    2006-06-01

    Full Text Available Abstract Background Leukocyte recruitment across blood vessels is fundamental to immune surveillance and inflammation. Lymphocyte homing to peripheral lymph nodes is mediated by the adhesion molecule, L-selectin, which binds to sulfated carbohydrate ligands on high endothelial venules (HEV. These glycoprotein ligands are collectively known as peripheral node addressin (PNAd, as defined by the function-blocking monoclonal antibody known as MECA-79. The sulfation of these ligands depends on the action of two HEV-expressed N-acetylglucosamine 6-O-sulfotransferases: GlcNAc6ST-2 and to a lesser degree GlcNAc6ST-1. Induction of PNAd has also been shown to occur in a number of human inflammatory diseases including rheumatoid arthritis (RA. Results In order to identify an animal model suitable for investigating the role of PNAd in chronic inflammation, we examined the expression of PNAd as well as GlcNAc6ST-1 and -2 in collagen-induced arthritis in mice. Here we show that PNAd is expressed in the vasculature of arthritic synovium in mice immunized with collagen but not in the normal synovium of control animals. This de novo expression of PNAd correlates strongly with induction of transcripts for both GlcNAc6ST-1 and GlcNAc6ST-2, as well as the expression of GlcNAc6ST-2 protein. Conclusion Our results demonstrate that PNAd and the sulfotransferases GlcNAc6ST-1 and 2 are induced in mouse collagen-induced arthritis and suggest that PNAd antagonists or inhibitors of the enzymes may have therapeutic benefit in this widely-used mouse model of RA.

  13. Pathogenesis and clinical manifestations of juvenile rheumatoid arthritis.

    Science.gov (United States)

    Hahn, Youn-Soo; Kim, Joong-Gon

    2010-11-01

    Juvenile rheumatoid arthritis (JRA) is the most common rheumatic childhood disease; its onset is before 16 years of age and it persists for at least 6 weeks. JRA encompasses a heterogeneous group of diseases that is classified according to 3 major presentations: oligoarthritis, polyarthritis, and systemic onset diseases. These presentations may originate from the same or different causes that involve interaction with specific immunogenetic predispositions, and result in heterogeneous clinical manifestations. An arthritic joint exhibits cardinal signs of joint inflammation, such as swelling, pain, heat, and loss of function; any joint can be arthritic, but large joints are more frequently affected. Extra-articular manifestations include high fever, skin rash, serositis, and uveitis. The first 2 types of JRA are regarded as T helper 1 (Th1) cell-mediated inflammatory disorders, mainly based on the abundance of activated Th1 cells in the inflamed synovium and the pathogenetic role of proinflammatory cytokines that are mainly produced by Th1 cell-stimulated monocytes. In contrast, the pathogenesis of systemic onset disease differs from that of other types of JRA in several respects, including the lack of association with human leukocyte antigen type and the absence of autoantibodies or autoreactive T cells. Although the precise mechanism that leads to JRA remains unclear, proinflammatory cytokines are thought to be responsible for at least part of the clinical symptoms in all JRA types. The effectiveness of biologic therapy in blocking the action of these cytokines in JRA patients provides strong evidence that they play a fundamental role in JRA inflammation.

  14. Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology

    DEFF Research Database (Denmark)

    Volck, B; Johansen, J S; Stoltenberg, M;

    2001-01-01

    OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other bioch...

  15. Medicinal plants with potential anti-arthritic activity:

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    Manjusha Choudhary

    2015-06-01

    Conclusion: This review clearly indicates that list of medicinal plants presented in this review might be useful to researchers as well as practioners. This review can be useful for preliminary screening of potential anti- arthritis plants. Further toxicity profile given in the review can be useful for the researchers for finding the safe dose. [J Intercult Ethnopharmacol 2015; 4(2.000: 147-179

  16. RANK, RANKL and osteoprotegerin in arthritic bone loss

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    M.C. Bezerra

    2005-02-01

    Full Text Available Rheumatoid arthritis is characterized by the presence of inflammatory synovitis and destruction of joint cartilage and bone. Tissue proteinases released by synovia, chondrocytes and pannus can cause cartilage destruction and cytokine-activated osteoclasts have been implicated in bone erosions. Rheumatoid arthritis synovial tissues produce a variety of cytokines and growth factors that induce monocyte differentiation to osteoclasts and their proliferation, activation and longer survival in tissues. More recently, a major role in bone erosion has been attributed to the receptor activator of nuclear factor kappa B ligand (RANKL released by activated lymphocytes and osteoblasts. In fact, osteoclasts are markedly activated after RANKL binding to the cognate RANK expressed on the surface of these cells. RANKL expression can be upregulated by bone-resorbing factors such as glucocorticoids, vitamin D3, interleukin 1 (IL-1, IL-6, IL-11, IL-17, tumor necrosis factor-alpha, prostaglandin E2, or parathyroid hormone-related peptide. Supporting this idea, inhibition of RANKL by osteoprotegerin, a natural soluble RANKL receptor, prevents bone loss in experimental models. Tumor growth factor-ß released from bone during active bone resorption has been suggested as one feedback mechanism for upregulating osteoprotegerin and estrogen can increase its production on osteoblasts. Modulation of these systems provides the opportunity to inhibit bone loss and deformity in chronic arthritis.

  17. Antinociceptive and anti-arthritic properties of hydroethanolic leaf ...

    African Journals Online (AJOL)

    olayemitoyin

    Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of ... Hook. f. ex Benth (Rutaceae) is used in Traditional African medicine for ...... inhibition of prostaglandin inhibited significantly the.

  18. Increased levels of IgG antibodies against human HSP60 in patients with spondyloarthritis.

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    Astrid Hjelholt

    expression of human HSP60 in the synovium of patients with SpA.

  19. Kallikrein-kinin in stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Julie; Chao; Grant; Bledsoe; Lee; Chao

    2014-01-01

    The tissue kallikrein-kinin system exerts a wide spectrum of biological activities in the cardiovascular, renal and central nervous systems. Tissue kallikrein-kinin modulates the proliferation, viability, mobility and functional activity of certain stem cell populations, namely mesenchymal stem cells(MSCs), endothelial progenitor cells(EPCs), mononuclear cell subsets and neural stem cells. Stimulation of these stem cells by tissue kallikrein-kinin may lead to protection against renal, cardiovascular and neural damage by inhibiting apoptosis, inflammation, fibrosis and oxidative stress and promoting neovascularization. Moreover, MSCs and EPCs genetically modified with tissue kallikrein are resistant to hypoxia- and oxidative stress-induced apoptosis, and offer enhanced protective actions in animal models of heart and kidney injury and hindlimb ischemia. In addition, activation of the plasma kallikrein-kinin system promotes EPC recruitment to the inflamed synovium of arthritic rats. Conversely, cleaved high molecular weight kininogen, a product of plasma kallikrein, reduces the viability and vasculogenic activity of EPCs. Therefore, kallikrein-kinin provides a new approach in enhancing the efficacy of stem cell therapy for human diseases.

  20. PGE2受体EP2和EP4调节CIA小鼠脾B细胞表面分子和细胞因子表达%Prostaglandin E2 receptors,EP2 and EP4,regulate expression of surface molecules and cytokines in B-cells of collagen-induced arthritic mice

    Institute of Scientific and Technical Information of China (English)

    张敬各; 陈海英; 秦瑾; 丛斌; 李巧霞; 贾娴娴; 马春玲; 于峰

    2011-01-01

    目的:探讨前列腺素E2(PGE2)受体EP2和EP4在胶原诱导性关节炎(CIA)小鼠脾B细胞免疫调节中的作用.方法:建立CIA小鼠模型,用CD19+ 免疫磁珠分选脾B细胞,流式细胞术检测MHCⅡ、CD80和CD86的表达,实时荧光定量PCR技术检测EPs 和细胞因子IFN-γ、TNF-α、IL-6、IL-4、IL-10和TGF-β的表达.结果:小鼠脾B细胞表达EP的4个亚型,CIA模型小鼠EP2和EP4表达增加;EP2阻断剂可以降低MHCⅡ、CD80和CD86的表达,而EP4阻断剂对CD80没有明显影响;EP2和EP4阻断剂均可以降低IFN-γ、TNF-α 和IL-6的表达(P<0.05或P<0.01),促进IL-10的表达(P<0.01或P<0.05),并可以分别促进IL-4和TGF-β的表达(P<0.01).结论:PGE2可通过EP2/EP4调节B细胞表面分子和细胞因子参与CIA发病,EP2/EP4有可能成为类风湿关节炎治疗的新靶点.%AIM : To observe the immunoregulatory effects of prostaglandin E2 receptor ( EP ) subtypes EP2/EP4 on the B - cells of collagen - induced arthritic( CIA )mice.METHODS : DBA/1 mice were immunized with chicken type Ⅱ collagen emulsified in Freund's complete adjuvant to induce arthritis.B - cells were isolated from the splenocyte suspension by positive selection using anti - CD19 monoclonal antihody immunomagnetic heads.The expression of MHC Ⅱ,CD 80 and CD86 was examined by flow cytometry.The mRNA levels of EPs, interferon γ ( IFN -γ ), tumor necrosis factor α ( TNF - α ), IL -6, IL -4, IL - 10 and transforming growth factor - β ( TGF - β ) were detected by real - time RT PCR.RESULTS : The rank of the mRNA levels of EPs was EP2 > EP1 > EP3 > EP4 in B - cells and EP2/EP4 mRNA expression was obviously increased in CIA mice.EP2 antagonists inhihited the expression of MHC Ⅱ.CD80 and CD86.EP4 antagonist had little effect on CD80.EP2/EP4 antagonists inhibited the mRNA expression of IFN - γ , TNF - α , and IL 6 ( P < 0.05 or P <0.01 ) and increased the expression of IL - 10 ( P <0.01 or P <0.05 ).Furthermore, the

  1. The role of human umbilical cord tissue-derived mesenchymal stromal cells (UCX® in the treatment of inflammatory arthritis

    Directory of Open Access Journals (Sweden)

    Santos Jorge M

    2013-01-01

    Full Text Available Abstract Background ECBio has developed proprietary technology to consistently isolate, expand and cryopreserve a well-characterized population of stromal cells from human umbilical cord tissue (UCX® cells. The technology has recently been optimized in order to become compliant with Advanced Medicine Therapeutic Products. In this work we report the immunosuppressive capacity of UCX® cells for treating induced autoimmune inflammatory arthritis. Methods UCX® cells were isolated using a proprietary method (PCT/IB2008/054067 that yields a well-defined number of cells using a precise proportion between tissue digestion enzyme activity units, tissue mass, digestion solution volume and void volume. The procedure includes three recovery steps to avoid non-conformities related to cell recovery. UCX® surface markers were characterized by flow cytometry and UCX® capacity to expand in vitro and to differentiate into adipocyte, chondrocyte and osteoblast-like cells was evaluated. Mixed Lymphocyte Reaction (MLR assays were performed to evaluate the effect of UCX® cells on T-cell activation and Treg conversion assays were also performed in vitro. Furthermore, UCX® cells were administered in vivo in both a rat acute carrageenan-induced arthritis model and rat chronic adjuvant induced arthritis model for arthritic inflammation. UCX® anti-inflammatory activity was then monitored over time. Results UCX® cells stained positive for CD44, CD73, CD90 and CD105; and negative for CD14, CD19 CD31, CD34, CD45 and HLA-DR; and were capable to differentiate into adipocyte, chondrocyte and osteoblast-like cells. UCX® cells were shown to repress T-cell activation and promote the expansion of Tregs better than bone marrow mesenchymal stem cells (BM-MSCs. Accordingly, xenogeneic UCX® administration in an acute carrageenan-induced arthritis model showed that human UCX® cells can reduce paw edema in vivo more efficiently than BM-MSCs. Finally, in a chronic adjuvant

  2. Human See, Human Do.

    Science.gov (United States)

    Tomasello, Michael

    1997-01-01

    A human demonstrator showed human children and captive chimpanzees how to drag food or toys closer using a rakelike tool. One side of the rake was less efficient than the other for dragging. Chimps tried to reproduce results rather than methods while children imitated and used the more efficient rake side. Concludes that imitation leads to…

  3. Establishment and evaluation of a transgenic mouse model of arthritis induced by overexpressing human tumor necrosis factor alpha

    Directory of Open Access Journals (Sweden)

    Ge Li

    2016-04-01

    Full Text Available Tumor necrosis factor alpha (TNFα plays a key role in the pathogenesis of rheumatoid arthritis (RA. Blockade of TNFα by monoclonal antibody has been widely used for the therapy of RA since the 1990s; however, its mechanism of efficacy, and potential safety concerns of the treatment are still not fully understood. This study sought to establish a transgenic arthritic mouse model by overexpressing human TNFα (hTNFα and to apply this model as a means to evaluate therapeutic consequences of TNFα inhibitors. The transgenic mouse line (TgTC with FVB background was generated by incorporating 3′-modified hTNFα gene sequences. A progressively erosive polyarthritis developed in the TgTC mice, with many characteristics observed in human rheumatoid arthritis, including polyarticular swelling, impairment of movement, synovial hyperplasia, and cartilage and bone erosion. Gene expression analysis demonstrated that hTNFα is not only expressed in hyperplastic synovial membrane, but also in tissues without lesions, including brain, lung and kidney. Treatment of the TgTC mice with anti-hTNFα monoclonal antibodies (mAb significantly decreased the level of hTNFα in the diseased joint and effectively prevented development of arthritis in a dose-dependent response fashion. Our results indicated that the TgTC mice represent a genetic model which can be used to comprehensively investigate the pathogenesis and therapeutics of TNFα-related diseases.

  4. More Human than Human.

    Science.gov (United States)

    Lawrence, David

    2017-07-01

    Within the literature surrounding nonhuman animals on the one hand and cognitively disabled humans on the other, there is much discussion of where beings that do not satisfy the criteria for personhood fit in our moral deliberations. In the future, we may face a different but related problem: that we might create (or cause the creation of) beings that not only satisfy but exceed these criteria. The question becomes whether these are minimal criteria, or hierarchical, such that those who fulfill them to greater degree should be afforded greater consideration. This article questions the validity and necessity of drawing divisions among beings that satisfy the minimum requirements for personhood; considering how future beings-intelligent androids, synthezoids, even alternate-substrate sentiences-might fit alongside the "baseline" human. I ask whether these alternate beings ought to be considered different to us, and why this may or may not matter in terms of a notion of "human community." The film Blade Runner, concerned in large part with humanity and its key synthezoid antagonist Roy Batty, forms a framing touchstone for my discussion. Batty is stronger, faster, more resilient, and more intelligent than Homo sapiens. His exploits, far beyond the capability of normal humans, are contrasted with his frailty and transient lifespan, his aesthetic appreciation of the sights he has seen, and his burgeoning empathy. Not for nothing does his creator within the mythos term him "more human than human."

  5. Human Development, Human Evolution.

    Science.gov (United States)

    Smillie, David

    One of the truly remarkable events in human evolution is the unprecedented increase in the size of the brain of "Homo" over a brief span of 2 million years. It would appear that some significant selective pressure or opportunity presented itself to this branch of the hominid line and caused a rapid increase in the brain, introducing a…

  6. Importance of timing of post-contrast MRI in rheumatoid arthritis: what happens during the first 60 minutes after IV gadolinium-DTPA?

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Klarlund, Mette

    2001-01-01

    compromises the differentiation of synovium from joint fluid. OBJECTIVE: To determine the time period after IV MRI contrast (gadolinium-DTPA (Gd)) injection in which synovial membrane volume determination is reliable. METHODS: MRI of five RA knees with clinical synovitis was carried out, with axial, T(1...... threshold. Thereafter, the measured volumes remained practically unchanged. CONCLUSION: This study suggests that MR image acquisition in arthritic knee joints should be performed within the initial approximately 10 minutes after gadolinium contrast injection to achieve the most accurate distinction between...

  7. Imaging of normal and pathologic joint synovium using nonlinear optical microscopy as a potential diagnostic tool

    Science.gov (United States)

    Tiwari, Nivedan; Chabra, Sanjay; Mehdi, Sheherbano; Sweet, Paula; Krasieva, Tatiana B.; Pool, Roy; Andrews, Brian; Peavy, George M.

    2010-09-01

    An estimated 1.3 million people in the United States suffer from rheumatoid arthritis (RA). RA causes profound changes in the synovial membrane of joints, and without early diagnosis and intervention, progresses to permanent alterations in joint structure and function. The purpose of this study is to determine if nonlinear optical microscopy (NLOM) can utilize the natural intrinsic fluorescence properties of tissue to generate images that would allow visualization of the structural and cellular composition of fresh, unfixed normal and pathologic synovial tissue. NLOM is performed on rabbit knee joint synovial samples using 730- and 800-nm excitation wavelengths. Less than 30 mW of excitation power delivered with a 40×, 0.8-NA water immersion objective is sufficient for the visualization of synovial structures to a maximum depth of 70 μm without tissue damage. NLOM imaging of normal and pathologic synovial tissue reveals the cellular structure, synoviocytes, adipocytes, collagen, vascular structures, and differential characteristics of inflammatory infiltrates without requiring tissue processing or staining. Further study to evaluate the ability of NLOM to assess the characteristics of pathologic synovial tissue and its potential role for the management of disease is warranted.

  8. Malassezia species infection of the synovium after total knee arthroplasty surgery

    Directory of Open Access Journals (Sweden)

    Leylabadlo, Hamed Ebrahimzadeh

    2016-09-01

    Full Text Available Infection is a serious complication after implantation of total knee-prostheses. However, fungal infection is rarely found in periprosthetic joints, and in most reports, the infecting organism is a species. This is a case report of infection after left knee total arthroplasty caused by species. The patient is still undergoing antifungal therapy with voriconazole and is still being followed-up. To the authors’ knowledge, the present case is the first report of species in a patient after total knee arthroplasty.

  9. SIRT1 overexpression in the rheumatoid arthritis synovium contributes to proinflammatory cytokine production and apoptosis resistance

    NARCIS (Netherlands)

    Niederer, F.; Ospelt, C.; Brentano, F.; Hottiger, M.O.; Gay, R.E.; Gay, S.; Detmar, M.; Kyburz, D.

    2011-01-01

    Objective To analyse the expression of SIRT1 in synovial tissues and cells of patients with rheumatoid arthritis (RA) and to study the function of SIRT1 in inflammation and apoptosis in RA. Methods Levels of SIRT1 expression were analysed in synovial tissues and cells from patients with RA by

  10. Gene delivery of TGF-β1 induces arthrofibrosis and chondrometaplasia of synovium in vivo.

    Science.gov (United States)

    Watson, Rachael S; Gouze, Elvire; Levings, Padraic P; Bush, Marsha L; Kay, Jesse D; Jorgensen, Marda S; Dacanay, E Anthony; Reith, John W; Wright, Thomas W; Ghivizzani, Steven C

    2010-11-01

    To understand the cellular and molecular events contributing to arthrofibrosis, we used an adenovirus to deliver and overexpress transforming growth factor-beta 1 (TGF-β1) cDNA (Ad.TGF-β1) in the knee joints of immunocompromised rats. Following delivery, animals were killed periodically, and joint tissues were examined macroscopically and histologically. PCR-array was used to assay alterations in expression patterns of extracellular matrix (ECM)-associated genes. By days 5 and 10, TGF-β1 induced an increase in knee diameter and complete encasement of joints in dense scar-like tissue, locking joints at 90° of flexion. Histologically, massive proliferation of synovial fibroblasts was seen, followed by their differentiation into myofibroblasts. The fibrotic tissue displaced the normal architecture of the joint capsule and fused with articular cartilage. RNA expression profiles showed high levels of transcription of numerous MMPs, matricellular and ECM proteins. By day 30, the phenotype of the fibrotic tissue had undergone chondrometaplasia, indicated by cellular morphology, matrix composition and >100-fold increases in expression of collagen type II and cartilage link protein. Pre-labeling of articular cells by injection with recombinant lentivirus containing eGFP cDNA showed fibrotic/cartilaginous tissues appeared to arise almost entirely from local proliferation and differentiation of resident fibroblasts. Altogether, these results indicate that TGF-β1 is a potent inducer of arthrofibrosis, and illustrate the proliferative potential and plasticity of articular fibroblasts. They suggest the mechanisms causing arthrofibrosis share many aspects with tumorigenesis.

  11. Malassezia species infection of the synovium after total knee arthroplasty surgery

    Science.gov (United States)

    Leylabadlo, Hamed Ebrahimzadeh; Zeinalzadeh, Elham; Akbari, Najibeh Asl Rahnemaii; Kafil, Hossein Samadi

    2016-01-01

    Infection is a serious complication after implantation of total knee-prostheses. However, fungal infection is rarely found in periprosthetic joints, and in most reports, the infecting organism is a Candida species. This is a case report of infection after left knee total arthroplasty caused by Malassezia species. The patient is still undergoing antifungal therapy with voriconazole and is still being followed-up. To the authors’ knowledge, the present case is the first report of Malassezia species in a patient after total knee arthroplasty. PMID:27730027

  12. Exercise increases interleukin-10 levels both intraarticularly and peri-synovially in patients with knee osteoarthritis

    DEFF Research Database (Denmark)

    Helmark, Ida C; Mikkelsen, Ulla R; Børglum, Jens

    2010-01-01

    The microdialysis method was applied to the human knee joint with osteoarthritis (OA) in order to reveal changes in biochemical markers of cartilage and inflammation, intraarticularly and in the synovium, in response to a single bout of mechanical joint loading....

  13. Human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2006-01-01

    Human rights reflect a determined effort to protect the dignity of each and every human being against abuse of power. This endeavour is as old as human history. What is relatively new is the international venture for the protection of human dignity through internationally accepted legal standards an

  14. Structural analysis and promoter characterization of the human collagenase-3 gene (MMP13)

    Energy Technology Data Exchange (ETDEWEB)

    Pendas, A.M.; Balbin, M.; Llano, E. [Universidad de Oviedo (Spain)] [and others

    1997-03-01

    Human collagenase-3 (MMP13) is a recently identified member of the matrix metalloproteinase (MMP) family that is expressed in breast carcinomas and in articular cartilage from arthritic patients. In this work we have isolated and characterized genomic clones coding for human collagenase-3. This gene is composed of 10 exons and 9 introns and spans over 12.5 kb. The overall organization of the collagenase-3 gene is similar to that of other MMP genes clustered at chromosome 11q22, including fibroblast collagenase (MMP-1), matrilysin (MMP-7), and macrophage metalloelastase (MMP-12), but is more distantly related to genes coding for stromelysin-3 (MMP-11), gelatinase-A (MMP-2), and gelatinase-B (MMP-9), which map outside of this gene cluster. Nucleotide sequence analysis of about 1 kb of the 5{prime}-flanking region of the collagenase-3 gene revealed the presence of a TATA box, an AP-1 motif, a PEA-3 consensus sequence, an osteoblast specific element (OSE-2), and a TGF-{beta} inhibitory element. Transient transfection experiments in HeLa and COS-1 cells with chloramphenicol acetyltransferase (CAT)-containing constructs showed that the AP-1 site is functional and responsible for the observed inducibility of the reporter gene by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). However, and in contrast to other MMP genes, no significative synergistic effect on CAT activity between the AP-1 and PEA-3 elements found in the collagenase-3 gene promoter was found. DNA binding analysis with nuclear extracts from HeLa cells revealed the formation of specific complexes between collagenase-3 promoter sequences containing the AP-1 site and nuclear proteins. The presence of this AP-1 functional site, which is able to confer responsiveness to a variety of tumor promoters and oncogene products, may contribute to explaining the high-level expression of collagenase-3 in breast carcinomas and degenerative joint diseases. 48 refs., 5 figs., 2 tabs.

  15. Human Rights, Human Needs, Human Development, Human Security

    OpenAIRE

    Gasper, Des

    2009-01-01

    Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each has emerged within the United Nations world; each relies implicitly on a conceptualisation of human need; each has specific strengths. Yet mutual communication, understanding and co-operation are deficient, espec...

  16. Development and construction of a neutron beam line for accelerator-based boron neutron capture synovectomy.

    Science.gov (United States)

    Gierga, D P; Yanch, J C; Shefer, R E

    2000-01-01

    A potential application of the 10B(n, alpha)7Li nuclear reaction for the treatment of rheumatoid arthritis, termed Boron Neutron Capture Synovectomy (BNCS), is under investigation. In an arthritic joint, the synovial lining becomes inflamed and is a source of great pain and discomfort for the afflicted patient. The goal of BNCS is to ablate the synovium, thereby eliminating the symptoms of the arthritis. A BNCS treatment would consist of an intra-articular injection of boron followed by neutron irradiation of the joint. Monte Carlo radiation transport calculations have been used to develop an accelerator-based epithermal neutron beam line for BNCS treatments. The model includes a moderator/reflector assembly, neutron producing target, target cooling system, and arthritic joint phantom. Single and parallel opposed beam irradiations have been modeled for the human knee, human finger, and rabbit knee joints. Additional reflectors, placed to the side and back of the joint, have been added to the model and have been shown to improve treatment times and skin doses by about a factor of 2. Several neutron-producing charged particle reactions have been examined for BNCS, including the 9Be(p,n) reaction at proton energies of 4 and 3.7 MeV, the 9Be(d,n) reaction at deuteron energies of 1.5 and 2.6 MeV, and the 7Li(p,n) reaction at a proton energy of 2.5 MeV. For an accelerator beam current of 1 mA and synovial boron uptake of 1000 ppm, the time to deliver a therapy dose of 10,000 RBEcGy ranges from 3 to 48 min, depending on the treated joint and the neutron producing charged particle reaction. The whole-body effective dose that a human would incur during a knee treatment has been estimated to be 3.6 rem or 0.75 rem, for 1000 ppm or 19,000 ppm synovial boron uptake, respectively, although the shielding configuration has not yet been optimized. The Monte Carlo design process culminated in the construction, installation, and testing of a dedicated BNCS beam line on the high

  17. Human Technology and Human Affects

    DEFF Research Database (Denmark)

    Fausing, Bent

    2009-01-01

    Human Technology and Human Affects  This year Samsung introduced a mobile phone with "Soul". It was made with a human touch and included itself a magical touch. Which function does technology and affects get in everyday aesthetics like this, its images and interactions included this presentation ...... often mentioned post-human condition....

  18. Human microbiomics

    OpenAIRE

    Rajendhran, J.; P. Gunasekaran

    2010-01-01

    The sequencing of the human genome has driven the study of human biology in a significant way and enabled the genome-wide study to elucidate the molecular basis of complex human diseases. Recently, the role of microbiota on human physiology and health has received much attention. The influence of gut microbiome (the collective genomes of the gut microbiota) in obesity has been demonstrated, which may pave the way for new prophylactic and therapeutic strategies such as bacteriotherapy. The sig...

  19. Human Smuggling

    NARCIS (Netherlands)

    Siegel - Rozenblit, Dina; Zaitch, Damian

    2014-01-01

    Human smuggling is based on a consensus between smuggler, smuggled, and his/her family (which usually guarantees or effectuates payment). However, unauthorized immigrants are violating immigration laws and human smugglers are profiting from enabling illegal immigration. Both human smuggling and its

  20. Human Rights/Human Needs.

    Science.gov (United States)

    Canning, Cynthia

    1978-01-01

    The faculty of Holy Names High School developed an interdisciplinary human rights program with school-wide activities focusing on three selected themes: the United Nations Universal Declaration of Human Rights, in conjunction with Human Rights Week; Food; and Women. This article outlines major program activities. (SJL)

  1. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    Science.gov (United States)

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  2. Digital Humanities

    DEFF Research Database (Denmark)

    Brügger, Niels

    2016-01-01

    the humanities for decades, starting with research fields such as humanities computing or computational linguistics in the 1950s, and later new media studies and internet studies. The historical development of digital humanities has been characterized by a focus on three successive, but co-existing types......Digital humanities is an umbrella term for theories, methodologies, and practices related to humanities scholarship that use the digital computer as an integrated and essential part of its research and teaching activities. The computer can be used for establishing, finding, collecting......, and preserving material to study, as an object of study in its own right, as an analytical tool, or for collaborating, and for disseminating results. The term "digital humanities" was coined around 2001, and gained currency within academia in the following years. However, computers had been used within...

  3. Human Rights, Human Needs, Human Development, Human Security - Relationships between four international human discourses.

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    markdownabstractAbstract: Human rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and

  4. Human Rights and Human Nature

    Directory of Open Access Journals (Sweden)

    Vittorio Possenti

    2013-11-01

    Full Text Available There seems to be two different versions of human rights in Western tradition: say Rationalistic and Christian; the former adopted in revolutionary France, the latter highly developed in Renaissance Spain. Current relativistic criticisms attempt to deny the universality of human rights alleging that this theory has been created in Western countries or it has no strong justification, and therefore cannot have universal approach; but this objection can be dismissed with an alternative justification of human rights.

  5. Human kapital

    DEFF Research Database (Denmark)

    Grosen, Anders; Nielsen, Peder Harbjerg

    2007-01-01

    finansiel og human kapital. Den traditionelle rådgivnings snævre synsvinkel kan føre til forkerte investeringsråd. Der skal derfor opfordres til, at de finansielle virksomheder i tilrettelæggelsen af deres rådgivning af private kunder systematisk inddrager den humane kapitals størrelse og karakteristika i...

  6. Human trichuriasis

    DEFF Research Database (Denmark)

    Betson, Martha; Søe, Martin Jensen; Nejsum, Peter

    2015-01-01

    Human trichuriasis is a neglected tropical disease which affects hundreds of millions of people worldwide and is particularly prevalent among children living in areas where sanitation is poor. This review examines the current knowledge on the taxonomy, genetics and phylogeography of human Trichuris...

  7. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  8. Human evolution

    DEFF Research Database (Denmark)

    Llamas, Bastien; Willerslev, Eske; Orlando, Ludovic Antoine Alexandre

    2017-01-01

    , and true population genomic studies of Bronze Age populations. Among the emerging areas of aDNA research, the analysis of past epigenomes is set to provide more new insights into human adaptation and disease susceptibility through time. Starting as a mere curiosity, ancient human genetics has become...

  9. Think Human

    DEFF Research Database (Denmark)

    Nielsen, Charlotte Marie Bisgaard

    2013-01-01

    years' campaigns suggests that the theory of communication underlying the campaign has its basis in mechanical action rather than in human communication. The practice of 'Communication design' is investigated in relation to this metaphorical 'machine thinking' model of communication and contrasted...... with the human-centered theory of communication advocated by integrationism....

  10. Teaching humanism.

    Science.gov (United States)

    Stern, David T; Cohen, Jordan J; Bruder, Ann; Packer, Barbara; Sole, Allison

    2008-01-01

    As the "passion that animates authentic professionalism," humanism must be infused into medical education and clinical care as a central feature of medicine's professionalism movement. In this article, we discuss a current definition of humanism in medicine. We will also provide detailed descriptions of educational programs intended to promote humanism at a number of medical schools in the United States (and beyond) and identify the key factors that make these programs effective. Common elements of programs that effectively teach humanism include: (1) opportunities for students to gain perspective in the lives of patients; (2) structured time for reflection on those experiences; and (3) focused mentoring to ensure that these events convert to positive, formative learning experiences. By describing educational experiences that both promote and sustain humanism in doctors, we hope to stimulate the thinking of other medical educators and to disseminate the impact of these innovative educational programs to help the profession meet its obligation to provide the public with humanistic physicians.

  11. Identification of candidate synovial membrane biomarkers after Achyranthes aspera treatment for rheumatoid arthritis.

    Science.gov (United States)

    Zheng, Wen; Lu, Xianghong; Fu, Zhirong; Zhang, Lin; Li, Ximin; Xu, Xiaobao; Ren, Yina; Lu, Yongzhuang; Fu, Hongwei; Tian, Jingkui

    2016-03-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main symptom is a heightened inflammatory response in synovial tissues. To verify the anti-arthritic activities of Achyranthes aspera and its possible therapy-related factors on the pathogenesis of RA, the saponins in A. aspera root were isolated and identified to treat the collagen-induced arthritis (CIA) rats. Phytochemical analysis isolated and identified methyl caffeate, 25-S-inokosterone, 25-S-inokosterone β-D-glucopyranosyl 3-(O-β-D-glucopyranosyloxy)-oleanolate, and β-D-glucopyranosyl 3-(O-β-D-galactopyranosyl (1→2)(O-β-D-glucopyranosyloxy)-oleanolate as main compounds in the root of A. aspera. Proteomics was performed to determine the differentially expressed proteins in either inflamed or drug-treated synovium of CIA rats. Treatment resulted in dramatically decreased paw swelling, proliferation of inflammatory cells, and bone degradation. Fibrinogen, procollagen, protein disulfide-isomerase A3, and apolipoprotein A-I were all increased in inflamed synovial tissues and were found to decrease when administered drug therapy. Furthermore, Alpha-1-antiproteinase and manganese superoxide dismutase were both increased in drug-treated synovial tissues. The inhibition of RA progression shows that A. aspera is a promising candidate for future treatment of human arthritis. Importantly, the total saponins found within A. aspera are the active component. Finally, autoantigens such as fibrinogen and collagen could act as inducers of RA due to their aggravation of inflammation. Given this, it is possible that the vimentin and PDIA3 could be the candidate biomarkers specific to Achyranthes saponin therapy for rheumatoid arthritis in synovial membrane.

  12. Human Computation

    CERN Document Server

    CERN. Geneva

    2008-01-01

    What if people could play computer games and accomplish work without even realizing it? What if billions of people collaborated to solve important problems for humanity or generate training data for computers? My work aims at a general paradigm for doing exactly that: utilizing human processing power to solve computational problems in a distributed manner. In particular, I focus on harnessing human time and energy for addressing problems that computers cannot yet solve. Although computers have advanced dramatically in many respects over the last 50 years, they still do not possess the basic conceptual intelligence or perceptual capabilities...

  13. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    In contemporary societies, the humanities are under constant pressure and have to justify their existence. In the ongoing debates, Humboldt’s ideals of ‘Bildung’ and ‘pure science’ are often used to justify the unique function of the humanities of ensuring free research and contributing to a vital...... philosophy. Contrary to Humboldt’s idea that the non-practical is the most practical in the long run, philosophical pragmatism recommends to the humanities to situate knowledge in practices and apply knowledge to practices....

  14. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  15. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    . The first section of this chapter outlines the complete cause-effect pathway, from emissions of toxic substances to intake by the population up to damages in terms of human health effects. Section 2 outlines the framework for assessing human toxicity in LCIA. Section 3 discusses the contributing substances......This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... – demonstrates the importance to account for both outdoor and indoor exposure, including consumer products. Analysing the variations in intake fraction (the fraction of the emitted or applied chemical that is taken in by the consumer and the general population), effect factor and characterisation factor across...

  16. Human influences

    NARCIS (Netherlands)

    Lanen, van H.A.J.; Kasparek, L.; Novicky, O.; Querner, E.P.; Fendeková, M.; Kupczyk, E.

    2004-01-01

    Human activities can cause drought, which was not previously reported (man-induced hydrological drought). Groundwater abstractions for domestic and industrial use are a well-known example of such an environmental change

  17. Human phantom

    CERN Multimedia

    CERN PhotoLab

    1973-01-01

    This human phantom has been received by CERN on loan from the State Committee of the USSR for the Utilization of Atomic Energy. It is used by the Health Physics Group to study personel radiation doses near the accelerators.

  18. Human expunction

    Science.gov (United States)

    Klee, Robert

    2017-10-01

    Thomas Nagel in `The Absurd' (Nagel 1971) mentions the future expunction of the human species as a `metaphor' for our ability to see our lives from the outside, which he claims is one source of our sense of life's absurdity. I argue that the future expunction (not to be confused with extinction) of everything human - indeed of everything biological in a terran sense - is not a mere metaphor but a physical certainty under the laws of nature. The causal processes by which human expunction will take place are presented in some empirical detail, so that philosophers cannot dismiss it as merely speculative. I also argue that appeals to anthropic principles or to forms of mystical cosmology are of no plausible avail in the face of human expunction under the laws of physics.

  19. Human babesiosis.

    Science.gov (United States)

    Rożej-Bielicka, Wioletta; Stypułkowska-Misiurewicz, Hanna; Gołąb, Elżbieta

    2015-01-01

    Babesiosis is an emerging parasitic, anthropo-zoonotic tick-borne disease, seldom diagnosed in humans. Caused by Protozoa, Babesia (also called Piroplasma) intraerytrocytic piriform microorganism. Infection of vertebrates is transmitted by ticks. Out of more than 100 Babesia species/genotypes described so far, only some were diagnosed in infected humans, mostly B. microti, B. divergens and B. venatorum (Babesia sp. EU1). Infection in humans is often asymptomatic or mild but is of a particular risk for asplenic individuals, those with congenital or acquired immunodeficiencies, and elderly. Infections transmitted with blood and blood products raise concerns in hemotherapy. Epidemiological situation of babesiosis varies around the world. In Europe, no increase in the number of cases was reported, but in the USA its prevalence is increasing and extension of endemic areas is observed. The aim of this publication is to describe the problems connected with the current epidemiological situation, diagnosis and treatment of human babesiosis with regard to clinical status of patients.

  20. Human energy

    OpenAIRE

    2010-01-01

    In the midst of big-oil record profits and growing debate on global warming, the Chevron Corporation launched its “Human Energy” public relations campaign. In television commercials and print advertisements, Chevron portrays itself as a compassionate entity striving to solve the planet’s energy crisis. Yet, the first term in this corporate oxymoron misleadingly reframes the significance of the second, suggesting that the corporation has a renewed focus. In depicting Chevron as a green/human o...

  1. Human Echolocation

    OpenAIRE

    Teng, Santani

    2013-01-01

    The use of active natural echolocation as a mobility aid for blind humans has received increased scientific and popular attention in recent years (Engber, 2006; Kreiser, 2006; NPR, 2011), in part due to a focus on several blind individuals who have developed remarkable expertise. However, perhaps surprisingly, the history of empirical human echolocation research is not much younger than the era of echolocation research (cf. Griffin, 1958). Nevertheless, compared to its bat and cetacean count...

  2. Human ehrlichiosis

    Directory of Open Access Journals (Sweden)

    Đokić Milomir

    2006-01-01

    Full Text Available Background. Human ehrlichiosis is a newly recognized disease. It is a tick-borne disease caused by several bacterial species of the genhus Erlichia. These are small gram-negative pleomorphic cocci, that are obligatory intracellular bacteria. Tick Ixodes is the principle vector in Europe, and Amblyomma americanum in the United States. Bacterial organisms replicate in a tick, and are transmited from infected cells in a vector to the blood cells of animals or humans. Human ehrlichiosis is a name for a group of diseases caused by different species of Ehrlichia. One of them is the disease named human monocytic ehrlichiosis, caused by Ehrlichia chaffeensis, and the other is a human granulocytic ehrlichiosis caused by Anaplasma phagocytophilia. Case report. We reported a 23-year-old patient admitted for the clinical treatment with the symptoms of high febrility (above 40 °C, headache, vomiting, general weakness and exhaustion, but without data on a tick bite. The patient was treated with trimetoprim-sulfamethoxazole for a week when Ehrlichia chaffeensis was confirmed by the immunofluoroscence test, and the therapy contimed with doxacyclin. Conclusion. Human ehrlichiosis is also present in our country, so this disease should be considered everyday, especially in infectology practice.

  3. Effects of cichoric acid extract from Echinacea purpurea on collagen-induced arthritis in rats.

    Science.gov (United States)

    Jiang, Ling; Li, Weizu; Wang, Yuchan; Zhang, Xiaosu; Yu, Deqiang; Yin, Yanyan; Xie, Zhongwen; Yuan, Yi

    2014-01-01

    Cichoric acid extract (CAE) from Echinacea purpurea L. was used to investigate the anti-arthritic effect by using collagen-induced arthritis (CIA) rat model. The hind paw swelling volume and the body weight were measured and recorded. All the drug solutions were administered orally to rats for a total of 28 days. On day 28, the rats were anaesthetized and decapitated. The thymus and spleen were weighed for the determination of the organ index. The concentration of tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β) and prostaglandin E2 (PGE-2) in the serum was measured using commercially available ELISA kits. Total and phosphor-NF-κB and Cox-2 protein expression in synovial tissues were determined by histological slides quantification and western blot analysis. Our data showed that administration of all doses of CAE (8, 16, and 32 mg/kg) significantly decreased the paw swelling, restored body weight gain and decreased the organ index of the thymus and spleen compared with that of the CIA group. CAE (8, 16, and 32 mg/kg) treatment significantly reduced the levels of TNFα, IL-1β and PGE-2 in serum compared with the CIA group. Histopathological analysis demonstrated that CAE has obvious anti-arthritic activity. In addition, CAE (32 mg/kg) significantly decreased the levels of nuclear factor-κB (NF-κB), TNFα and cyclooxygenase 2 (Cox-2) in synovium tissues of the ankle joint compared with the CIA group. Furthermore, CAE administration significantly decreased the protein expression of phosphor-NF-κB and Cox-2 in synovium tissues of the knee joint compared with the CIA group. The results suggest that the anti-inflammatory activity of CAE may account for its anti-arthritic effect, and CAE could be a potential therapeutic drug for the treatment of rheumatoid arthritis (RA).

  4. Human Amniotic Membrane-Derived Products in Sports Medicine: Basic Science, Early Results, and Potential Clinical Applications.

    Science.gov (United States)

    Riboh, Jonathan C; Saltzman, Bryan M; Yanke, Adam B; Cole, Brian J

    2016-09-01

    Amniotic membrane (AM)-derived products have been successfully used in ophthalmology, plastic surgery, and wound care, but little is known about their potential applications in orthopaedic sports medicine. To provide an updated review of the basic science and preclinical and clinical data supporting the use of AM-derived products and to review their current applications in sports medicine. Systematic review. A systematic search of the literature was conducted using the Medline, EMBASE, and Cochrane databases. The search term amniotic membrane was used alone and in conjunction with stem cell, orthopaedic, tissue engineering, scaffold, and sports medicine. The search identified 6870 articles, 80 of which, after screening of the titles and abstracts, were considered relevant to this study. Fifty-five articles described the anatomy, basic science, and nonorthopaedic applications of AM-derived products. Twenty-five articles described preclinical and clinical trials of AM-derived products for orthopaedic sports medicine. Because the level of evidence obtained from this search was not adequate for systematic review or meta-analysis, a current concepts review on the anatomy, physiology, and clinical uses of AM-derived products is presented. Amniotic membranes have many promising applications in sports medicine. They are a source of pluripotent cells, highly organized collagen, antifibrotic and anti-inflammatory cytokines, immunomodulators, and matrix proteins. These properties may make it beneficial when applied as tissue engineering scaffolds, improving tissue organization in healing, and treatment of the arthritic joint. The current body of evidence in sports medicine is heavily biased toward in vitro and animal studies, with little to no human clinical data. Nonetheless, 14 companies or distributors offer commercial AM products. The preparation and formulation of these products alter their biological and mechanical properties, and a thorough understanding of these

  5. Anti-inflammatory activity of an ethanolic Caesalpinia sappan extract in human chondrocytes and macrophages

    Science.gov (United States)

    Wu, Shengqian Q; Otero, Miguel; Unger, Frank M; Goldring, Mary B; Phrutivorapongkul, Ampai; Chiari, Catharina; Kolb, Alexander; Viernstein, Helmut; Toegel, Stefan

    2012-01-01

    Aim of the study Caesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages. Materials and Methods Primary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1ß) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1ß, TNF-α, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-κB) p50 and p65 expression vectors in the presence or absence of CSE. Results CSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1ß and TNF-α in IL-1ß-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter. Conclusions The present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1ß-induced over-expression of

  6. Role of phosphatidylinositol 3-kinase p110β in spinal dorsal horn neurons in the development of arthritic pain in rats: relationship with TRPV1 and ASIC1a%脊髓背角神经元磷脂酰肌醇-3激酶p110β在大鼠关节炎性痛形成中的作用:与辣椒素受体及酸敏感离子通道1a的关系

    Institute of Scientific and Technical Information of China (English)

    张亚军; 杨承祥; 王汉兵; 张斌; 项红兵; 田玉科

    2013-01-01

    目的 评价脊髓背角神经元磷脂酰肌醇-3激酶(PI3K) p110β在大鼠关节炎性痛形成中的作用及与辣椒素受体(TRPV1)及酸敏感离子通道1a(ASIC1a)的关系.方法 鞘内置管成功的成年雌性SD大鼠40只,3月龄,体重250 ~ 300 g,采用随机数字表法,将其分为4组(n=10)∶对照组(C组)、关节炎性痛组(AP组)、AP+ PI3K p110β错义寡核苷酸组(MS组)和AP+ PI3K p110β反义寡核苷酸组(AS组).采用右踝关节腔内注射完全弗氏佐剂建立关节炎性痛模型,模型制备后即刻AP组、MS组、AS组分别经鞘内注射生理盐水、错义寡核苷酸15 μg和反义寡核苷酸15 μg,容量20μl,1次/d,连续6d.于术前1d、术后4、7、10d时测定机械缩足反应阈(MWT)和热缩足反应潜伏期(TWL),术后10 d处死大鼠,取腰段脊髓,采用Western blot法检测脊髓背角神经元PI3K p110β表达,采用免疫组化法检测脊髓背角神经元TRPV1和ASICla的表达.结果 与C组比较,AP组、MS组和AS组术后各时点MWT降低,TWL缩短,脊髓背角神经元PI3K p110β、TRPV1和ASICla表达上调(P<0.01);与AP组和MS组比较,AS组术后各时点MWT升高,TWL延长,脊髓背角神经元PI3K p110β、TRPV1和ASIC1a表达下调(P<0.01).结论 脊髓背角神经元PI3K p110β参与大鼠关节炎性痛的形成,其机制与上调脊髓背角神经元TRPVl和ASICla的表达有关.%Objective To evaluate the role of phosphatidylinositol 3-kinase (PI3K) p110β in spinal dorsal horn neurons in the development of arthritic pain (AP) in rats and the relationship with transient receptor potential vanilloid 1 (TRPV1) and acid-sensing ion channel (ASIC)1 a.Methods Forty adult female Sprague-Dawley rats in which intrathecal catheters were successfully placed,aged 3 months,weighing 250-300 g,were randomly divided into 4 groups (n =10 each):control group (group C),group AP,AP + PI3K p110β missense oligo-deoxynucleotide group (group MS) and AP + PI3K p110β antisense oligo

  7. [Human influenza].

    Science.gov (United States)

    Stock, Ingo

    2006-10-01

    Human influenza is one of the most common human infectious diseases, contributing to approximately one million deaths every year. In Germany, each year between 5.000 and 20.000 individuals die from severe influenza infections. In several countries, the morbidity and mortality of influenza is greatly underestimated. This is reflected by general low immunization rates. The emergence of avian influenza against the background of the scenario of a human influenza pandemic has revived public interest in the disease. According to the World Health Organisation, it is only the question on the beginning of a new influenza pandemic. The virus type of the new pandemic is still uncertain and it is also unclear, if a pandemic spread of the virus may be prevented by consistent controlling of avian influenza.

  8. [Humanized childbirth].

    Science.gov (United States)

    Kuo, Su-Chen

    2005-06-01

    Childbirth is a major event in a family. The expectant parent's perception of the childbirth experience influences his or her development as a parent. Making childbirth a positive and satisfying experience for women is the responsibility of health care providers. Women want to have physical and emotional privacy during labor and delivery, and to experience both in a friendly, comfortable environment. For women expected to undergo normal deliveries, humanized childbirth is one accessible approach. This article explores the definition and evolution of humanized childbirth and the care practice that it involves. It also explores birth plans and birth experiences, and the improvements necessary to routine labor practices to enable women to participate in decision making about their childbirth experiences. The author emphasizes that when health-care providers recognize the value of humanized childbirth and make changes accordingly, the dignity of women's childbirth experiences will be enhanced.

  9. Beyond Humanisms

    Directory of Open Access Journals (Sweden)

    Capurro, Rafael

    2012-01-01

    Full Text Available In the first part of this paper a short history of Western humanisms (Socrates, Pico della Mirandola, Descartes, Kant is presented. As far as these humanisms rest on a fixation of the ‘humanum’ they are metaphysical, although they might radically differ from each other. The second part deals with the present debate on trans- and posthumanism in the context of some breath-taking developments in science and technology.Angeletics, a theory of messengers and messages, intends to give an answer to the leading question of this paper, namely: ‘what does it mean to go beyond humanisms?’ The conclusion exposes briefly an ethics of hospitality and care from an angeletic perspective.

  10. Ability of Interleukin-33- and Immune Complex-Triggered Activation of Human Mast Cells to Down-Regulate Monocyte-Mediated Immune Responses.

    Science.gov (United States)

    Rivellese, Felice; Suurmond, Jolien; Habets, Kim; Dorjée, Annemarie L; Ramamoorthi, Nandhini; Townsend, Michael J; de Paulis, Amato; Marone, Gianni; Huizinga, Tom W J; Pitzalis, Costantino; Toes, René E M

    2015-09-01

    Mast cells have been implicated in the pathogenesis of rheumatoid arthritis (RA). In particular, their activation by interleukin-33 (IL-33) has been linked to the development of arthritis in animal models. The aim of this study was to evaluate the functional responses of human mast cells to IL-33 in the context of RA. Human mast cells were stimulated with IL-33 combined with plate-bound IgG or IgG anti-citrullinated protein antibodies (ACPAs), and their effects on monocyte activation were evaluated. Cellular interactions of mast cells in RA synovium were assessed by immunofluorescence analysis, and the expression of messenger RNA (mRNA) for mast cell-specific genes was evaluated in synovial biopsy tissue from patients with early RA who were naive to treatment with disease-modifying antirheumatic drugs. IL-33 induced the up-regulation of Fcγ receptor type IIa and enhanced the activation of mast cells by IgG, including IgG ACPAs, as indicated by the production of CXCL8/IL-8. Intriguingly, mast cell activation triggered with IL-33 and IgG led to the release of mediators such as histamine and IL-10, which inhibited monocyte activation. Synovial mast cells were found in contact with CD14+ monocyte/macrophages. Finally, mRNA levels of mast cell-specific genes were inversely associated with disease severity, and IL-33 mRNA levels showed an inverse correlation with the levels of proinflammatory markers. When human mast cells are activated by IL-33, an immunomodulatory phenotype develops, with human mast cells gaining the ability to suppress monocyte activation via the release of IL-10 and histamine. These findings, together with the presence of synovial mast cell-monocyte interactions and the inverse association between the expression of mast cell genes at the synovial level and disease activity, suggest that these newly described mast cell-mediated inhibitory pathways might have a functional relevance in the pathogenesis of RA. © 2015, American College of Rheumatology.

  11. Human Rights, Human Needs, Human Development, Human Security : Relationships between four international 'human' discourses

    NARCIS (Netherlands)

    D.R. Gasper (Des)

    2007-01-01

    textabstractHuman rights, human development and human security form increasingly important, partly interconnected, partly competitive and misunderstood ethical and policy discourses. Each tries to humanize a pre-existing and unavoidable major discourse of everyday life, policy and politics; each

  12. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  13. Human Trafficking

    Science.gov (United States)

    Wilson, David McKay

    2011-01-01

    The shadowy, criminal nature of human trafficking makes evaluating its nature and scope difficult. The U.S. State Department and anti-trafficking groups estimate that worldwide some 27 million people are caught in a form of forced servitude today. Public awareness of modern-day slavery is gaining momentum thanks to new abolitionist efforts. Among…

  14. Human waste

    NARCIS (Netherlands)

    Amin, Md Nurul; Kroeze, Carolien; Strokal, Maryna

    2017-01-01

    Many people practice open defecation in south Asia. As a result, lot of human waste containing nutrients such as nitrogen (N) and phosphorus (P) enter rivers. Rivers transport these nutrients to coastal waters, resulting in marine pollution. This source of nutrient pollution is, however, ignored in

  15. Nothing Human

    Science.gov (United States)

    Wharram, C. C.

    2014-01-01

    In this essay C. C. Wharram argues that Terence's concept of translation as a form of "contamination" anticipates recent developments in philosophy, ecology, and translation studies. Placing these divergent fields of inquiry into dialogue enables us read Terence's well-known statement "I am a human being--I deem nothing…

  16. Practicing Humanities

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2016-01-01

    and self-reflective democracy. Contemporary humanities have adopted a new orientation towards practices, and it is not clear how this fits with the ideals of ‘Bildung’ and ‘pure science’. A possible theoretical framework for this orientation towards practices could be found in John Dewey’s pragmatic...

  17. Cytokines profiling by multiplex analysis in experimental arthritis: which pathophysiological relevance for articular versus systemic mediators?

    Science.gov (United States)

    Paquet, Joseph; Goebel, Jean-Christophe; Delaunay, Camille; Pinzano, Astrid; Grossin, Laurent; Cournil-Henrionnet, Christel; Gillet, Pierre; Netter, Patrick; Jouzeau, Jean-Yves; Moulin, David

    2012-03-13

    We have taken advantage of the large screening capacity of a multiplex immunoassay to better define the respective contribution of articular versus systemic cytokines in experimental arthritis. We performed a follow up (from 7 hours to 14 days) multiplex analysis of 24 cytokines in synovial fluid and sera of rats developing Antigen-Induced Arthritis (AIA) and confronted their protein level changes with molecular, biochemical, histological and clinical events occurring in the course of the disease. The time-scheduled findings in arthritic joints correlated with time-dependent changes of cytokine amounts in joint effusions but not with their blood levels. From seven hours after sensitization, high levels of chemokines (MCP-1, MIP1α, GRO/KC, RANTES, eotaxin) were found in synovial fluid of arthritic knees whereas perivascular infiltration occurred in the synovium; local release of inflammatory cytokines (IFNγ, IL-1β, IL-6) preceded the spreading of inflammation and resulted in progressive degradation of cartilage and bone. Finally a local overexpression of several cytokines/adipocytokines poorly described in arthritis (IL-13, IL-18, leptin) was observed. Distinct panels of cytokines were found in arthritic fluid during AIA, and the expected effect of mediators correlated well with changes occurring in joint tissues. Moreover, multiplex analysis could be helpful to identify new pathogenic mediators and to elucidate the mechanisms supporting the efficacy of putative targeted therapies.

  18. ANTIARTHRITIC ACTIVITY OF MILK EXTRACT OF SEMECARPUS ANACARDIUM NUT

    National Research Council Canada - National Science Library

    Dhirendra Prakash; M. C. Bindal; Santosh Kumar Gupta; Anil Kumar Gupta; Vedpal

    2013-01-01

    The present study is aimed to evaluate the anti-arthritic activity of milk extract of Semecarpus anacardium nut using inhibition of protein denaturation model and human red blood cell Membrane stabilization model...

  19. APL1, an altered peptide ligand derived from human heat-shock protein 60, increases the frequency of Tregs and its suppressive capacity against antigen responding effector CD4 + T cells from rheumatoid arthritis patients.

    Science.gov (United States)

    Barberá, Ariana; Lorenzo, Noraylis; van Kooten, Peter; van Roon, Joel; de Jager, Wilco; Prada, Dinorah; Gómez, Jorge; Padrón, Gabriel; van Eden, Willem; Broere, Femke; Del Carmen Domínguez, María

    2016-07-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by a chronic relapsing-remitting joint inflammation. Perturbations in the balance between CD4 + T cells producing IL-17 and CD4 + CD25(high)FoxP3 + Tregs correlate with irreversible bone and cartilage destruction in RA. APL1 is an altered peptide ligand derived from a CD4+ T-cell epitope of human HSP60, an autoantigen expressed in the inflamed synovium, which increases the frequency of CD4 + CD25(high)FoxP3+ Tregs in peripheral blood mononuclear cells from RA patients. The aim of this study was to evaluate the suppressive capacity of Tregs induced by APL1 on proliferation of effector CD4+ T cells using co-culture experiments. Enhanced Treg-mediated suppression was observed in APL1-treated cultures compared with cells cultured only with media. Subsequent analyses using autologous cross-over experiments showed that the enhanced Treg suppression in APL1-treated cultures could reflect increased suppressive function of Tregs against APL1-responsive T cells. On the other hand, APL1-treatment had a significant effect reducing IL-17 levels produced by effector CD4+ T cells. Hence, this peptide has the ability to increase the frequency of Tregs and their suppressive properties whereas effector T cells produce less IL-17. Thus, we propose that APL1 therapy could help to ameliorate the pathogenic Th17/Treg balance in RA patients.

  20. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  1. Human Rights in the Humanities

    Science.gov (United States)

    Harpham, Geoffrey

    2012-01-01

    Human rights are rapidly entering the academic curriculum, with programs appearing all over the country--including at Duke, Harvard, Northeastern, and Stanford Universities; the Massachusetts Institute of Technology; the Universities of Chicago, of Connecticut, of California at Berkeley, and of Minnesota; and Trinity College. Most of these…

  2. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  3. Human paleoneurology

    CERN Document Server

    2015-01-01

    The book presents an integrative review of paleoneurology, the study of endocranial morphology in fossil species. The main focus is on showing how computed methods can be used to support advances in evolutionary neuroanatomy, paleoanthropology and archaeology and how they have contributed to creating a completely new perspective in cognitive neuroscience. Moreover, thanks to its multidisciplinary approach, the book addresses students and researchers approaching human paleoneurology from different angles and for different purposes, such as biologists, physicians, anthropologists, archaeologists

  4. Digital Humanities

    DEFF Research Database (Denmark)

    Nielsen, Hans Jørn

    2015-01-01

    Artiklen præsenterer først nogle generelle problemstillinger omkring Digital Humanities (DH) med det formål at undersøge dem nærmere i relation til konkrete eksempler på forskellige digitaliseringsmåder og ændringer i dokumentproduktion. I en nærmere afgrænsning vælger artiklen den tendens i DH...

  5. Human universe

    CERN Document Server

    Cox, Brian

    2014-01-01

    Human life is a staggeringly strange thing. On the surface of a ball of rock falling around a nuclear fireball in the blackness of a vacuum the laws of nature conspired to create a naked ape that can look up at the stars and wonder where it came from. What is a human being? Objectively, nothing of consequence. Particles of dust in an infinite arena, present for an instant in eternity. Clumps of atoms in a universe with more galaxies than people. And yet a human being is necessary for the question itself to exist, and the presence of a question in the universe - any question - is the most wonderful thing. Questions require minds, and minds bring meaning. What is meaning? I don't know, except that the universe and every pointless speck inside it means something to me. I am astonished by the existence of a single atom, and find my civilisation to be an outrageous imprint on reality. I don't understand it. Nobody does, but it makes me smile. This book asks questions about our origins, our destiny, and our place i...

  6. ANTIARTHRITIC ACTIVITY OF DESMODIUM GANGETICUM ROOT

    Directory of Open Access Journals (Sweden)

    Vedpal

    2013-09-01

    Full Text Available The present study is aimed to evaluate the in-vitro anti-arthritic activity of aqueous extract of Desmodium gangeticum root using inhibition of protein denaturation model and human red blood cell Membrane stabilization model. Diclofenac sodium was used as a standard drug. Results revealed that the aqueous extract of Desmodium gangeticum root at different concentrations possessed significant anti-arthritic activity as compared to standard drug used as Diclofenac sodium. The results obtained in the present investigation Indicate that aqueous extract of Desmodium gangeticum root showed anti-arthritic activity.

  7. ANTIARTHRITIC ACTIVITY OF MILK EXTRACT OF SEMECARPUS ANACARDIUM NUT

    Directory of Open Access Journals (Sweden)

    Dhirendra Prakash

    2013-08-01

    Full Text Available The present study is aimed to evaluate the anti-arthritic activity of milk extract of Semecarpus anacardium nut using inhibition of protein denaturation model and human red blood cell Membrane stabilization model. Diclofenac sodium was used as a standard drug. Results revealed that the milk extract of Semecarpus anacardium nut at different concentrations possessed significant anti-arthritic activity as compared to standard drug used as Diclofenac sodium. The results obtained in the present investigation Indicate that milk extract of Semecarpus anacardium nut showed anti-arthritic activity.

  8. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  9. Human Capital, (Human) Capabilities and Higher Education

    Science.gov (United States)

    Le Grange, L.

    2011-01-01

    In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…

  10. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  11. Human steroidogenesis

    DEFF Research Database (Denmark)

    Andersen, Claus Y; Ezcurra, Diego

    2014-01-01

    steroid concentrations cause alterations in endometrial development, affecting oocyte viability in assisted reproductive technology. Furthermore, it has been proposed that elevated progesterone levels have a negative effect on the reproductive outcome of COS. This may arise from an asynchrony between...... reviews current knowledge of the regulation of progesterone in the human ovary during the follicular phase and highlights areas where knowledge remains limited. In this review, we provide in-depth information outlining the regulation and function of gonadotropins in the complicated area of steroidogenesis...

  12. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  13. Human Toxocariasis

    Directory of Open Access Journals (Sweden)

    Mehmet Burak Selek

    2013-09-01

    Full Text Available Human toxocariasis is an parasitic infection caused by the ingestion of larvae of dog nematode Toxocara canis and less frequently of cat nematode T.cati. Toxocara eggs, shed to environment by infected dogs' and cats' droppings, become infective by embryonation. Humans, particularly children, can be infected by accidentally ingesting embryonated Toxocara eggs. Larvae hatch in the small intestine, penetrate the intestinal wall and migrate to other parts of body via the bloodstream. It is generally a benign, asymptomatic, and self-limiting disease, although migrating larvae can cause damage to tissues and organs, especially brain involvement can cause severe morbidity. The two main clinical presentations of toxocariasis are visceral larva migrans (VLM (a systemic disease caused by larval migration through major organs and ocular larva migrans (OLM (a disease limited to the eyes and optic nerves. There are also two less-severe syndromes which have recently been described, one mainly in children (covert toxocariasis and the other mainly in adults (common toxocariasis. Diagnosis is usually made by clinical signs/symptoms, epidemiological background of the patient and the use of immunological methods (ELISA or western-blot. On the other hand definitive diagnosis is much more challenging, since it requires the demonstration of larvae via biopsy or autopsy. Most cases of toxocariasis clear up without any treatment. VLM is primarily treated with antihelmintic drugs, such as; albendazole or mebendazole. Treatment of OLM is more difficult and usually consists of measures to prevent progressive damage to the eye like steroids. Laser photocoagulation and cryoretinopexy may also be used to treat severe cases. Since eradicating T.canis infection is difficult due to the complexity of its life cycle, prevention of toxocariasis is always preferred. Toxocara eggs have a strong protective layer which makes the eggs able to survive in the environment for months or

  14. Intra-articular injection of tenoxicam in rats: assessment of the local effects on the articular cartilage and synovium.

    Science.gov (United States)

    Ozyuvaci, H; Bilgic, B; Ozyuvaci, E; Altan, A; Altug, T; Karaca, C

    2004-01-01

    This study investigated the possible local adverse effects of intra-articular administration of tenoxicam in the rat knee joint. A total of 50 rats were given 0.25 ml of a standard preparation of tenoxicam by injection into the right knee joint and 0.25 ml of 0.9% saline solution by injection into the left knee joint as a control. Groups of 10 rats were killed 24 h, 48 h, 7 days, 14 days and 21 days after tenoxicam administration. Two rats were sham operated; one was killed on the first day and the other on the second day after this procedure. All the joints were prepared and sectioned for histological examination. Tissue loss and oedema were observed in the specimens obtained 24 h and 48 h after treatment with tenoxicam. No pathological changes were observed in the 7-day, 14-day and 21-day specimens, or in the control joints. Caution should be exercised when using intra-articular tenoxicam for post-operative analgesia.

  15. The Treatment of Fibrosis of Joint Synovium and Frozen Shoulder by Smad4 Gene Silencing in Rats

    Science.gov (United States)

    Xue, MingFeng; Gong, SuiLiang; Dai, JiaPing; Chen, Gang; Hu, JunYu

    2016-01-01

    Soft tissue fibrosis at the joint induced by inflammation is the pathological basis of frozen shoulder. In the present study, we utilized a lentiviral approach to silence the Smad4 gene in an in vitro fibrosis model of fibroblasts and an in vivo frozen shoulder model. We observed the change in the fibrosis process and the biological indicators of frozen shoulder. The in vitro fibrosis models (Rat myoblasts L6, Rat synovial cell RSC-364 and Rat chondrocytes RCs) were established using TGF-β1 induction, and the effect of Smad4 gene silencing on fibrosis was analyzed. The method of Kanno A was employed to establish a rat model of frozen shoulder, and Smad4 in the relevant part was knocked down with the lentiviral approach. We then examined the abduction and rotation angles and the length of synovial intima and measured the inflammatory factors in effusion and the fibrotic markers of tissues. We found that Smad4 knockdown suppressed the proliferation and expression of fibrotic markers in L6, RSC-364 and RCs cells induced by TGF-β1. MMP activity measurements showed that Smad4 knockdown significantly reversed the decrease in MMP activity in these three cell lines that were induced by TGF-β1. Furthermore, using lentivirus in the rat frozen shoulder model, we found that Smad4 silencing attenuated the inflammatory response and fibrosis. It significantly inhibited the increase of the Vimentin, α-SMA, collagen I and III, Lama1 and Timp1 proteins in synovial tissue as well as the inflammatory factors of TNF-a, IL-1α/β, IL-6 and IL-10 in effusion. MMP acidity assays revealed that Smad4 silencing inhibited MMP activity in the synovial, cartilage and ligament tissues in the model animals. The assessment of the phosphorylated Smad2/3 in the nuclei isolated from the synovial tissues showed that Smad4 silencing significantly inhibited the phosphorylation and subsequent nuclear translocation of Smad2/3 proteins. Moreover, Smad4-shRNA lentivirus inhibited the decrease in both the abduction and rotation angles caused by immobilization as well as the decrease in the length of the synovial intima. Based on shoulder movement data, Smad4 knockdown can increase the rotation limitation caused by immobilization. In summary, Smad4 silencing can suppress chronic inflammation and fibrosis in joint tissues by inhibiting the TGF-β/Smad pathway and can play a positive role in the prevention and treatment of joint stiffness. PMID:27351864

  16. Expression of IL-20 in synovium and lesional skin of patients with psoriatic arthritis: differential response to alefacept treatment

    NARCIS (Netherlands)

    M.C. Lebre (Maria); C.L. Jonckheere (Christina); M.C. Kraan; A.W.R. van Kuijk (Arno); J.D. Bos; M.A. de Rie; D.M. Gerlag; P.P. Tak (Paul)

    2012-01-01

    textabstractIntroduction: Psoriatic arthritis (PsA) is an inflammatory joint disease associated with psoriasis. Alefacept (a lymphocyte function-associated antigen (LFA)-3 Ig fusion protein that binds to CD2 and functions as an antagonist to T-cell activation) has been shown to result in improvement

  17. HISTOMORPHOMETRIC ANALYSIS OF THE KNEE ARTICULAR CARTILAGE AND SYNOVIUM FOR METADIAPHYSEAL LEG LENGTHENING (EXPERIMENTAL-AND-MORPHOLOGICAL STUDY

    Directory of Open Access Journals (Sweden)

    T. A. Stupina

    2013-01-01

    Full Text Available The knee articular cartilage and synovial membrane have been studied for metadiaphyseal leg lengthening using the methods of light miscroscopy, computer morpho- and stereometry. The manner of bone integrity breaking, the rate and rhythm of distraction conformed to the lengthening technique most often used in the clinic. The results of the histomorphometric analysis have demonstrated that when osteotomy at the level of metadiaphysis and manual distraction by 1 mm a day for 4 times is performed, synovitis of mild and moderate degree develops through subsynovial layer hypervascularization, as well as reactive-destructive changes in nerve fibers with the tendency to regeneration. The structural-functional changes of reactive and/or destructive-reparative character have been revealed in the articular cartilage, and the manifestation degree of these changes correlates with synovial membrane changes. The intensity of the destructive-reparative processes in the articular cartilage and synovial membrane depends on fixation stability.

  18. Increase of circulating CD11b(+)Gr1(+) cells and recruitment into the synovium in osteoarthritic mice with hyperlipidemia.

    Science.gov (United States)

    Uchida, Kentaro; Naruse, Kouji; Satoh, Masashi; Onuma, Kenji; Ueno, Masaki; Takano, Shotaro; Urabe, Ken; Takaso, Masashi

    2013-01-01

    Although recent studies suggest that hyperlipidemia is a risk factor for osteoarthritis (OA), the link between OA and hyperlipidemia is not fully understood. As the number of activated, circulating myeloid cells is increased during hyperlipidemia, we speculate that myeloid cells contribute to the pathology of OA. Here, we characterized myeloid cells in STR/Ort mice, a murine osteoarthritis model, under hyperlipidemic conditions. Ratios of myeloid cells in bone marrow, the spleen, and peripheral blood were determined by flow cytometry. To examine the influence of the hematopoietic environment, including abnormal stem cells, on the hematopoietic profile of STR/Ort mice, bone marrow transplantations were performed. The relationship between hyperlipidemia and abnormal hematopoiesis was examined by evaluating biochemical parameters and spleen weight of F2 animals (STR/Ort x C57BL/6J). In STR/Ort mice, the ratio of CD11b(+)Gr1(+) cells in spleens and peripheral blood was increased, and CD11b(+)Gr1(+) cells were also present in synovial tissue. Splenomegaly was observed and correlated with the ratio of CD11b(+)Gr1(+) cells. When bone marrow from GFP-expressing mice was transplanted into STR/Ort mice, no difference in the percentage of CD11b(+)Gr1(+) cells was observed between transplanted and age-matched STR/Ort mice. Analysis of biochemical parameters in F2 mice showed that spleen weight correlated with serum total cholesterol. These results suggest that the increase in circulating and splenic CD11b(+)Gr1(+) cells in STR/Ort mice originates from hypercholesterolemia. Further investigation of the function of CD11b(+)Gr1(+) cells in synovial tissue may reveal the pathology of OA in STR/Ort mice.

  19. Trapped in a vicious loop: Toll-like receptors sustain the spontaneous cytokine production by rheumatoid synovium

    NARCIS (Netherlands)

    Abdollahi-Roodsaz, S.; Loo, F.A. van de; Berg, W.B. van den

    2011-01-01

    Synovial tissue of patients with rheumatoid arthritis (RA) spontaneously produces several cytokines, of which a fundamental role in joint inflammation and destruction has been established. However, the factors sustaining this phenomenon remain poorly understood. In a recent report, blockade of Toll-

  20. NATO Human View Architecture and Human Networks

    Science.gov (United States)

    Handley, Holly A. H.; Houston, Nancy P.

    2010-01-01

    The NATO Human View is a system architectural viewpoint that focuses on the human as part of a system. Its purpose is to capture the human requirements and to inform on how the human impacts the system design. The viewpoint contains seven static models that include different aspects of the human element, such as roles, tasks, constraints, training and metrics. It also includes a Human Dynamics component to perform simulations of the human system under design. One of the static models, termed Human Networks, focuses on the human-to-human communication patterns that occur as a result of ad hoc or deliberate team formation, especially teams distributed across space and time. Parameters of human teams that effect system performance can be captured in this model. Human centered aspects of networks, such as differences in operational tempo (sense of urgency), priorities (common goal), and team history (knowledge of the other team members), can be incorporated. The information captured in the Human Network static model can then be included in the Human Dynamics component so that the impact of distributed teams is represented in the simulation. As the NATO militaries transform to a more networked force, the Human View architecture is an important tool that can be used to make recommendations on the proper mix of technological innovations and human interactions.

  1. Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2012-02-01

    OBJECTIVES: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2\\'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers. METHODS: Oxygen levels in synovial tissue were assessed using an oxygen\\/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry. 8-Oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) levels were also measured by ELISA. RESULTS: The median oxygen tension in synovial tissue was profoundly hypoxic at 19.35 mm Hg (2.5%). Nuclear 8-oxo-dG levels were significantly higher than nuclear 4-HNE levels in the lining and sublining layers (all p<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG levels in both cell layers (all p<0.001). Reduced in vivo oxygen tension correlated with high lipid peroxidation in synovial fluid (p=0.027; r=0.54) and tissue (p=0.004; r=0.58). Serum VEGF levels were positively correlated with cytoplasmic 4-HNE expression (p=0.05; r=0.43) and intensity (p=0.006; r=0.59) in the lining layer. Serum Ang2 levels were positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p < or = 0.05). DAS28-C-reactive protein was correlated with nuclear 4-HNE expression in the sublining layer (p=0.02; r=0.48) and DAS28-erythrocyte sedimentation rate was correlated with nuclear 4-HNE expression in both cell layers (p < or = 0.03). CONCLUSIONS: Lipid peroxidation is associated with low oxygen tension in vivo, disease activity and angiogenic marker expression in inflammatory arthritis.

  2. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats.

    Science.gov (United States)

    Moreno-Rocha, Luis Alfonso; López-Muñoz, Francisco Javier; Medina-López, José Raúl; Domínguez-Ramírez, Adriana Miriam

    2016-11-01

    Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively) is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P metamizol and tramadol was found under acute treatment (P > 0.05). The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites' pharmacokinetics (P < 0.05) were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  3. Effect of metamizol on morphine pharmacokinetics and pharmacodynamics after acute and subchronic administration in arthritic rats.

    Science.gov (United States)

    Domínguez-Ramírez, Adriana Miriam; Cortés-Arroyo, Alma Rosa; Y de la Peña, Marcela Hurtado; López, José Raúl Medina; López-Muñoz, Francisco Javier

    2010-10-25

    The aim of the present study was to investigate whether metamizol alters the pharmacokinetics of morphine and to determine the relationship between morphine plasma levels and antinociceptive effect produced after co-administration of drugs under acute and subchronic treatments using the pain-induced functional impairment model in rat (PIFIR model). Administration of morphine+metamizol under acute treatment produced a significantly higher antinociceptive effect than that obtained with morphine alone (Pmetamizol combination produced an accumulation of the drug in plasma (Pmetamizol may be explained by a possible enzymatic inhibition of the glucuronosyl-transferase system involved in the metabolism of morphine. This study reveals both a pharmacodynamic and a pharmacokinetic interaction between morphine and metamizol, leading to an increased antinociceptive effect and a delay in tolerance development. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. Effect of tramadol on metamizol pharmacokinetics and pharmacodynamics after single and repeated administrations in arthritic rats

    Directory of Open Access Journals (Sweden)

    Luis Alfonso Moreno-Rocha

    2016-11-01

    Full Text Available Combined administration of certain doses of opioid compounds with a non-steroidal anti-inflammatory drug can produce additive or supra-additive effects while reducing unwanted effects. We have recently reported that co-administration of metamizol with tramadol produces antinociceptive effect potentiation, after acute treatment. However, none information about the effect produced by the combination after chronic or repeated dose administration exists. The aims of this study were to investigate whether the antinociceptive synergism produced by the combination of metamizol and tramadol (177.8 + 17.8 mg/kg, s.c. respectively is maintained after repeated treatment and whether the effects observed are primarily due to pharmacodynamic interactions or may be related to pharmacokinetics changes. Administration of metamizol plus tramadol acute treatment significantly enhanced the antinociceptive effect of the drugs given alone (P  0.05. The mechanism involved in the synergism of the antinociceptive effect observed with the combination of metamizol and tramadol in single dose cannot be attributed to a pharmacokinetic interaction, and other pharmacodynamic interactions have to be considered. On the other hand, when metamizol and tramadol were co-administered under repeated administrations, a pharmacokinetic interaction and tolerance development occurred. Differences found in metamizol active metabolites’ pharmacokinetics (P < 0.05 were related to the development of tolerance produced by the combination after repeated doses. This work shows an additional preclinical support for the combination therapy. The clinical utility of this combination in a suitable dose range should be evaluated in future studies.

  5. Evaluation of the anti-inflammatory and anti-arthritic effects of some plant extracts

    OpenAIRE

    2011-01-01

    The objective of the present research was to study the anti-inflammatory activity of sweet basil flowers, leaves of eucalyptus and the aerial parts of celery and sage on acute inflammation along with the effect of a methanol extract of celery, sage and eucalyptus on adjuvant induced arthritis in rats. The effect of the methanol extract of celery, sage and eucalyptus on certain biochemical parameters in adjuvant arthritis and its safety in liver and kidney functions were evaluated. The fatty a...

  6. Salvage of a post-traumatic arthritic wrist using the scaphoid as an osteochondral graft.

    Science.gov (United States)

    Marcuzzi, A; Ozben, H; Russomando, A

    2014-09-01

    The authors describe a case of post-traumatic wrist arthritis with an osteochondral defect in the scaphoid fossa of the radius. The patient was treated with proximal row carpectomy, radial styloidectomy and reconstruction of the defect using the proximal half of the scaphoid as an autologous osteochondral graft. Pain relief was achieved while wrist motion and strength were improved. The carpal bones are a source of osteochondral grafts and can be used to expand the indications of motion-preserving wrist salvage procedures.

  7. Quantitative versus semiquantitative MR imaging of cartilage in blood-induced arthritic ankles: preliminary findings

    Energy Technology Data Exchange (ETDEWEB)

    Doria, Andrea S. [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); Zhang, Ningning [Children' s Hospital, Department of Radiology, Beijing (China); Lundin, Bjorn [Skaane University Hospital and Lund University, University Hospital of Lund, Center for Medical Imaging and Physiology, Lund (Sweden); Hilliard, Pamela [The Hospital for Sick Children, Department of Rehabilitation Services, Toronto, ON (Canada); Man, Carina; Weiss, Ruth; Detzler, Garry [The Hospital for Sick Children, Department of Diagnostic Imaging, Toronto, ON (Canada); Blanchette, Victor [The Hospital for Sick Children, Department of Hematology, Toronto, ON (Canada); Moineddin, Rahim [Family and Community Medicine, Department of Public Health, Toronto, ON (Canada); Eckstein, Felix [Paracelsus Medical University, Institute of Anatomy and Musculoskeletal Research, Salzburg (Austria); Chondrometrics GmbH, Ainring (Germany); Sussman, Marshall S. [University of Toronto, Department of Medical Imaging, Toronto, ON (Canada); University Health Network, Department of Medical Imaging, Toronto, ON (Canada)

    2014-05-15

    Recent advances in hemophilia prophylaxis have raised the need for accurate noninvasive methods for assessment of early cartilage damage in maturing joints to guide initiation of prophylaxis. Such methods can either be semiquantitative or quantitative. Whereas semiquantitative scores are less time-consuming to be performed than quantitative methods, they are prone to subjective interpretation. To test the feasibility of a manual segmentation and a quantitative methodology for cross-sectional evaluation of articular cartilage status in growing ankles of children with blood-induced arthritis, as compared with a semiquantitative scoring system and clinical-radiographic constructs. Twelve boys, 11 with hemophilia (A, n = 9; B, n = 2) and 1 with von Willebrand disease (median age: 13; range: 6-17), underwent physical examination and MRI at 1.5 T. Two radiologists semiquantitatively scored the MRIs for cartilage pathology (surface erosions, cartilage loss) with blinding to clinical information. An experienced operator applied a validated quantitative 3-D MRI method to determine the percentage area of denuded bone (dAB) and the cartilage thickness (ThCtAB) in the joints' MRIs. Quantitative and semiquantitative MRI methods and clinical-radiographic constructs (Hemophilia Joint Health Score [HJHS], Pettersson radiograph scores) were compared. Moderate correlations were noted between erosions and dAB (r = 0.62, P = 0.03) in the talus but not in the distal tibia (P > 0.05). Whereas substantial to high correlations (r range: 0.70-0.94, P < 0.05) were observed between erosions, cartilage loss, HJHS and Pettersson scores both at the distal tibia and talus levels, moderate/borderline substantial (r range: 0.55-0.61, P < 0.05) correlations were noted between dAB/ThCtAB and clinical-radiographic constructs. Whereas the semiquantitative method of assessing cartilage status is closely associated with clinical-radiographic scores in cross-sectional studies of blood-induced arthropathy, quantitative measures provide independent information and are therefore less applicable for that research design. (orig.)

  8. The arthritic wrist. II--the degenerative wrist: indications for different surgical treatments.

    Science.gov (United States)

    Laulan, J; Bacle, G; de Bodman, C; Najihi, N; Richou, J; Simon, E; Saint-Cast, Y; Obert, L; Saraux, A; Bellemère, P; Dréano, T; Le Bourg, M; Le Nen, D

    2011-06-01

    For the patient (and the surgeon) the ideal wrist is one that has good mobility, however very often the optimal surgical treatment is one that provides effective pain relief. The patient must be informed of the potential complications and limitations of each procedure. The patient's psychological profile and functional requirements will determine how well he/she adapts to the changes. Also, each surgeon has beliefs and personal experiences that influence the treatment decision and final result. Proximal row carpectomy (PRC) and the Watson procedure are two reference operations for osteoarthritis secondary to scapholunate instability and scaphoid non-union (SLAC and SNAC). Beyond the early complications and drawbacks specific to each, they provide good results that are maintained over time. PRC, which can be performed up to Stage II, is mainly indicated in patients with moderate functional demands, while the Watson procedure is more often done on a patient who performs manual labour, as long as the radiolunate joint space is maintained. Complete denervation is effective in three out of four cases and preserves the remaining mobility. Because of its low morbidity, the procedure can be suggested in patients with a mobile wrist and low functional demands or in older patients, independent of their wrist mobility. Total wrist fusion is not only a rescue procedure. For a young patient who performs heavy manual labour with extensive osteoarthritis and progressive forms of Kienböck's disease, this procedure provides the greatest chance of returning to work and not being socially outcast. The role of osteochondral autografts, implants and wrist prostheses in the treatment arsenal need to be better defined.

  9. Imaging of hemodynamic effects in arthritic joints with dynamic optical tomography

    Science.gov (United States)

    Hielscher, Andreas H.; Lasker, Joseph M.; Fong, Christopher J.; Dwyer, Edward

    2007-07-01

    Optical probing of hemodynamics is often employed in areas such as brain, muscular, and breast-cancer imaging. In these studies an external stimulus is applied and changes in relevant physiological parameters, e.g. oxy or deoxyhemoglobin concentrations, are determined. In this work we present the first application of this method for characterizing joint diseases, especially effects of rheumatoid arthritis (RA) in the proximal-interphalangeal (PIP) finger joints. Using a dual-wavelength tomographic imaging system together with previously implemented model-based iterative image reconstruction schemes, we have performed dynamic imaging case studies on a limited number of healthy volunteers and patients diagnosed with RA. Inflating a sphygmomanometer cuff placed around the forearm we elicited a controlled vascular response. We observed pronounced differences between the hemodynamic effect occurring in healthy volunteers and patients affected by RA.

  10. Comparative anti-inflammatory effects of anti-arthritic herbal medicines and ibuprofen.

    Science.gov (United States)

    Kang, Joshua J; Samad, Mohammed A; Kim, Kye S; Bae, Soochan

    2014-09-01

    Non-steroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen, are widely used over-the-counter drugs to treat arthritis, but they are often associated with side effects. Herbal medicines have been used to treat various diseases such as arthritis, but the scientific profiles are not well understood. In this study, we examined, in comparison with ibuprofen, the inhibitory effects on various inflammatory markers of the most commonly used herbal medicines to treat arthritis, boswellia (Boswellia sapindales), licorice (Glycyrrhiza glabra), guggul (Commiphora wightii), and neem (Azadirachta indica). To elicit inflammatory response, we exposed mouse myoblast C2C12 cells to lipopolysaccharide (LPS). Tumor necrosis factor-alpha (TNF-α) and monocyte chemotactic protein-1 (MCP-1), which are cytokines activated during an inflammatory response, were determined. The optimal non-toxic concentration was determined by exposing different concentrations of drugs (from 0.01 to 10 mg/mL). Cell death measurement revealed that the drug concentrations lower than 0.05 mg/mL were non-toxic concentrations for each drug, and these doses were used for the main experiments. We found that neem and licorice showed robust anti-inflammatory responses compared with ibuprofen. However, boswellia and guggul did not demonstrate significant anti-inflammatory responses. We concluded that neem and licorice are more effective than ibuprofen in suppressing LPS-induced inflammation in C2C12 cells.

  11. In Vitro Anti-arthritic activity of Tecoma stans (Linn. Leaves

    Directory of Open Access Journals (Sweden)

    Dharmeshkumar Prajapati

    2015-04-01

    Full Text Available The World Health Organization (WHO estimates 80% of the world population presently use herbal medicine for some aspects of primary health care. Rheumatoid arthritis (RA is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. There are many herbs which are described in Ayurveda for arthritis. The medicinal plant contains flavonoids, terpenes, quinones, catechins, alkaloids, anthocyanins and anthoxanthins phytoconstituents, having anti-inflammatory effects. Tecoma stans (Linn. belongs to the family of Bignoniaceae. The root of Tecoma stans as diuretic, vermifuge and tonic. Pharmacological reports revealed that it is having antidiabetic, anticancer, antioxidant, anti-inflammatory activity, antimicrobial, and antifungal properties, and extensively used in the treatment of diabetes. Alcohol, Water, successive extracts of Petroleum ether, Chloroform, Methanol and Water extracts of T. stans leaves were tested for Antiarthritic activity using Diclofenac sodium as standard by In-vitro models like, Inhibition of protein denaturation and effect on membrane stabilization. Alcohol, Water and succesive Methanol extracts of T. stans leaves exhibited significant Antiarthritic activity. The results of the investigations justify us the folklore use of T. stans leaves in the treatment of inflammation during arthritis and the plant is worth for further chemical isolation and pharmacological investigations.

  12. Magnetic resonance imaging of stem cell apoptosis in arthritic joints with a caspase activatable contrast agent.

    Science.gov (United States)

    Nejadnik, Hossein; Ye, Deju; Lenkov, Olga D; Donig, Jessica S; Martin, John E; Castillo, Rostislav; Derugin, Nikita; Sennino, Barbara; Rao, Jianghong; Daldrup-Link, Heike

    2015-02-24

    About 43 million individuals in the U.S. encounter cartilage injuries due to trauma or osteoarthritis, leading to joint pain and functional disability. Matrix-associated stem cell implants (MASI) represent a promising approach for repair of cartilage defects. However, limited survival of MASI creates a significant bottleneck for successful cartilage regeneration outcomes and functional reconstitution. We report an approach for noninvasive detection of stem cell apoptosis with magnetic resonance imaging (MRI), based on a caspase-3-sensitive nanoaggregation MRI probe (C-SNAM). C-SNAM self-assembles into nanoparticles after hydrolysis by caspase-3, leading to 90% amplification of (1)H MR signal and prolonged in vivo retention. Following intra-articular injection, C-SNAM causes significant MR signal enhancement in apoptotic MASI compared to viable MASI. Our results indicate that C-SNAM functions as an imaging probe for stem cell apoptosis in MASI. This concept could be applied to a broad range of cell transplants and target sites.

  13. Decrease of CD68 Synovial Macrophages in Celastrol Treated Arthritic Rats.

    Directory of Open Access Journals (Sweden)

    Rita Cascão

    Full Text Available Rheumatoid arthritis (RA is a chronic immune-mediated inflammatory disease characterized by cellular infiltration into the joints, hyperproliferation of synovial cells and bone damage. Available treatments for RA only induce remission in around 30% of the patients, have important adverse effects and its use is limited by their high cost. Therefore, compounds that can control arthritis, with an acceptable safety profile and low production costs are still an unmet need. We have shown, in vitro, that celastrol inhibits both IL-1β and TNF, which play an important role in RA, and, in vivo, that celastrol has significant anti-inflammatory properties. Our main goal in this work was to test the effect of celastrol in the number of sublining CD68 macrophages (a biomarker of therapeutic response for novel RA treatments and on the overall synovial tissue cellularity and joint structure in the adjuvant-induced rat model of arthritis (AIA.Celastrol was administered to AIA rats both in the early (4 days after disease induction and late (11 days after disease induction phases of arthritis development. The inflammatory score, ankle perimeter and body weight were evaluated during treatment period. Rats were sacrificed after 22 days of disease progression and blood, internal organs and paw samples were collected for toxicological blood parameters and serum proinflammatory cytokine quantification, as well as histopathological and immunohistochemical evaluation, respectively.Here we report that celastrol significantly decreases the number of sublining CD68 macrophages and the overall synovial inflammatory cellularity, and halted joint destruction without side effects.Our results validate celastrol as a promising compound for the treatment of arthritis.

  14. Septic arthritis of a lumbar facet joint; Arthrite septique interapophysaire posterieure lombaire

    Energy Technology Data Exchange (ETDEWEB)

    Ben Hamouda, M.; Rajhi, H.; Golli, M.; Ganouni, A.; Bergaoui, N. [Centre Hospitalier Universitaire de Monastir (Tunisia); Chaouch, A. [Centre Hospitalier Universitaire de Mahdia (Tunisia); Hassine, H. [Centre Hospitalier Universitaire de Sahloul, Sousse (Tunisia)

    1997-05-01

    Septic arthritis of the posterior lumbar joints is extremely rare. The clinical picture of the unusual site of infection can easily lead to confusion with spondylo-discitis which is more common. We report a case of a 50-year-old women with Staphylococcus aureus septic arthritis of the left L5-S1 lumbar facet joint. CT scan was helpful to establish the diagnosis and to guide the percutaneous needle biopsy. (authors). 10 refs.

  15. Effects of local heat and cold treatment on surface and articular temperature of arthritic knees

    NARCIS (Netherlands)

    Oosterveld, Frederikus G.J.; Rasker, Johannes J.

    1994-01-01

    Objective: To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis. Methods. Thirty-nine patients with arthritis of the knee were divided at random into 4 treatment groups (ice chips, nitrogen cold air, ligno-

  16. Measurements of functional ability and health status in the arthritic patient

    NARCIS (Netherlands)

    Jacobs, J.W.G.; van der Heide, A.; Rasker, Hans J.; Bijlsma, J.W.J.

    1993-01-01

    Chronic arthritis may have great impact on the patient but also on his or her family, relatives and friends. The assessment of the consequences of chronic arthritis and the effect of therapy not only in terms of physical, but also psychological and social dimensions deserves more attention.

  17. Treatment of habitual dislocation of patella in an adult arthritic knee

    Directory of Open Access Journals (Sweden)

    Raghuveer K Reddy

    2013-01-01

    Full Text Available Habitual dislocation of the patella (HDP is a common presentation in pediatric age unlike adults. Many surgical procedures using proximal realignment and distal realignment have been reported to treat HDP in children with satisfactory results. However, late presentation of habitual patellar dislocation with osteoarthritis is rare and treatment plan has not yet been established. We present a case of neglected iatrogenic habitual patellar dislocation with osteoarthritis in a 50-year-old woman. Two-staged procedure was planned, first with patellar realignment and later with definitive total knee arthroplasty. Quadricepsplasty, medial patello-femoral ligament reconstruction, lateral release and tibial tuberosity transfer was done as primary procedure and total knee arthroplasty, which was planned as secondary procedure, was deferred as the patient improved functionally.

  18. Endoscopic Facet Debridement for the treatment of facet arthritic pain - a novel new technique

    Directory of Open Access Journals (Sweden)

    Scott M.W. Haufe, Anthony R. Mork

    2010-01-01

    Full Text Available Study design: Retrospective, observational, open label. Objective: We investigated the efficacy of facet debridement for the treatment of facet joint pain. Summary of background data: Facet joint disease, often due to degenerative arthritis, is common cause of chronic back pain. In patients that don't respond to conservative measures, nerve ablation may provide significant improvement. Due to the ability of peripheral nerves to regenerate, ablative techniques of the dorsal nerve roots often provide only temporary relief. In theory, ablation of the nerve end plates in the facet joint capsule should prevent reinnervation. Methods: All patients treated with endoscopic facet debridement at our clinic from 2003-2007 with at least 3 years follow-up were included in the analysis. Primary outcome measure was percent change in facet-related pain as measured by Visual Analog Scale (VAS score at final follow-up visit. Results: A total of 174 people (77 women, 97 men; mean age 64, range 22-89 were included. Location of facet pain was cervical in 45, thoracic in 15, and lumbar in 114 patients. At final follow-up, 77%, 73%, and 68% of patients with cervical, thoracic, or lumbar disease, respectively, showed at least 50% improvement in pain. Mean operating time per joint was 17 minutes (range, 10-42. Mean blood loss was 40 ml (range, 10-100. Complications included suture failure in two patients, requiring reclosure of the incision. No infection or nerve damage beyond what was intended occurred. Conclusions: Our results demonstrate a comparable efficacy of endoscopic facet debridement compared to radiofrequency ablation of the dorsal nerve branch, with durable results. Large scale, randomized trials are warranted to further evaluate the relative efficacy of this surgical treatment in patients with facet joint disease.

  19. Patellofemoral Joint Arthroplasty: Our Experience in Isolated Patellofemoral and Bicompartmental Arthritic Knees

    Science.gov (United States)

    Sabatini, L.; Schirò, M.; Atzori, F.; Ferrero, G.; Massè, A.

    2016-01-01

    INTRODUCTION Isolated patellofemoral (PF) arthritis is rare, and there is no complete agreement about the best surgical treatment. The operative treatments are total knee arthroplasty and patellofemoral replacement (PFR). The incidence of many early complications of PF arthroplasty has decreased with the introduction of newer designs. Nowadays, the main cause of revision surgery is the progression of tibiofemoral osteoarthritis. In the past, PF arthroplasty was contraindicated in patients with evidence of osteoarthritis or pain in medial or lateral tibiofemoral compartments. The improvement in implant designs and surgical techniques has allowed the addition of a monocompartmental arthroplasty for the medial or lateral tibiofemoral compartment. In this work, we evaluate our first experience with PF arthroplasty and its combination with unicompartmental knee arthroplasty. MATERIALS AND METHODS From May 2014 to March 2016, we treated 14 patients. An isolated PF arthroplasty was performed in six knees (five patients), and a combined PF and unicompartmental knee arthroplasty was performed in nine cases. We observed a significant improvement in the clinical and functional Knee Society Scores (KSSs) after surgery in our patients. RESULTS We obtained good results in our cases both for clinical and functional KSSs. Patellar clunk was recorded in one case. DISCUSSION AND CONCLUSION We are going toward a new attitude in which partial osteoarthritic changes could be treated with partial resurfacing prosthetic solutions such as unicompartmental, bi–unicompartmental or PFR alone, or unicompartmental combined, which respects the cruciates and achieves maximal bone preservation, which is vital, particularly, for young patients. PMID:27891054

  20. Arthroscopic decompressive medial release of the varus arthritic knee: Expanding the functional envelope.

    Science.gov (United States)

    Leon, H O; Blanco, C E; Guthrie, T B

    2001-05-01

    We present the rationale and technique for treating medial knee osteoarthritis by dynamically unloading the medial compartment of the knee. Recent advances in kinematic studies indicate a dynamic linkage between differing degrees of freedom in the knee joint. Both the adduction moment and the foot progression angle are important determinants of medial compartment loading. The medially osteoarthritic knee has progressive compromise of free motion in more than 1 plane. Arthroscopic decompressive medial release unloads the medial compartment by release of the medial capsule and medial collateral ligament in the presence of intact cruciate ligaments, which may allow a decreased adduction moment and decrease of the external rotation restraint in extension found in more severely osteoarthritic knees. A case series of 38 patients with medial gonarthrosis was treated by this technique at the Hermanos Ameijeiras Hospital in Havana, Cuba. All patients had good results without postoperative valgus instability or significant complications. We feel that this technique warrants further clinical and biomechanical study for its use in isolation or in combination with high tibial osteotomy or minimally invasive selective osteotomy for the treatment of medial gonarthrosis of the knee. A minimally invasive, selective approach to biomechanical factors in osteoarthritis may be combined with other modulating techniques in efforts to forestall or prevent the need for total joint replacement.

  1. Evaluation of the anti-inflammatory and anti-arthritic effects of some plant extracts

    Directory of Open Access Journals (Sweden)

    Abdel-Moein, N. M.

    2011-12-01

    Full Text Available The objective of the present research was to study the anti-inflammatory activity of sweet basil flowers, leaves of eucalyptus and the aerial parts of celery and sage on acute inflammation along with the effect of a methanol extract of celery, sage and eucalyptus on adjuvant induced arthritis in rats. The effect of the methanol extract of celery, sage and eucalyptus on certain biochemical parameters in adjuvant arthritis and its safety in liver and kidney functions were evaluated. The fatty acids, hydrocarbons and phytosterols of all plants under investigation were studied. The results revealed a marked anti-inflammatory activity of all the studied plant extracts with different degrees ranging from 47 to 62%. The methanol extract of celery, sage and eucalyptus showed improvement in the level of plasma malondialdehyde, tumor necrosis factor-α and uric acid and also showed significant improvements in body weight and total food intake. The methanol extract of celery, sage and eucalyptus showed complete safety for liver and kidney functions. α-Linolenic acid and linoleic acid were present in all the studied plants. Stigmasterol and β-sitosterol were present in all the studied plants.

    El objetivo de la presente investigación ha sido estudiar la actividad anti-inflamatoria de flores de albahaca dulces, hojas de eucalipto, hojas de apio y salvia. Se ha estudiado el efecto sobre la inflamación aguda de extractos metanólicos de apio, salvia y eucalipto y sobre la artritis inducida en ratas. Se han evaluado los efectos de los extractos metanólicos de apio, salvia y eucalipto sobre los parámetros bioquímicos determinados en la artritis inducida y su seguridad en las funciones del hígado y el riñón. Se han estudiado los ácidos grasos, hidrocarburos y fitoesteroles de todas las plantas objeto de la investigación. Los resultados han revelado una actividad antiinflamatoria de los extractos de las plantas estudiadas con diferentes grados entre un 47 y un 62%. Los extractos metanólico de apio, de salvia y de eucalipto han mostrado una mejoría de los niveles de malondialdehído en plasma, factor de necrosis tumoral α y de ácido úrico, también se muestra una mejoría significativa en el peso corporal y en la ingesta total de alimentos. Los extractos metanólicos de apio, de salvia y de eucalipto han mostrado una total seguridad sobre la función hepática y renal. Los ácidos α-linolénico y linoleico estaban presentes en todas las plantas estudiadas así como los esteroles Estigmasterol y β-sitosterol.

  2. Appraisal of anti-arthritic and nephroprotective potential of Cuscuta reflexa.

    Science.gov (United States)

    Niazi, Samia Gul; Uttra, Ambreen Malik; Qaiser, Muhammad Naeem; Ahsan, Haseeb

    2017-12-01

    Cuscuta reflexa Roxb. (Cuscutaceae) has been used traditionally for treating sore knees and kidney problems, but its efficacy has not been scientifically examined in treating arthritis and nephrotoxicity. Present study determines antiarthritic and nephroprotective potential of the aqueous methanolic extract of Cuscuta reflexa (AMECR). Antiarthritic activity of Cuscuta reflexa in formaldehyde and turpentine oil-induced rat arthritis models was appraised at 200, 400 and 600 mg/kg doses for 10 days and 6 h period, respectively, and in vitro protein denaturation (bovine serum albumin, egg albumin) inhibition was studied at 25-800 μg/mL concentration. The nephroprotective effect involved gentamicin-induced nephrotoxicity in rats at 200, 400 and 600 mg/kg doses. Plant extract at 600 mg/kg significantly reduced paw oedema and joint swelling with maximal inhibition of 71.22% at the 6th hour for turpentine oil and 76.74% on 10th day for formaldehyde. Likewise, in vitro results corroborated significant concentration-dependent increase in percentage protection at 800 μg/mL against both bovine serum albumin (89.30%) and egg albumin (93.51%) denaturation. Similarly, 600 mg/kg dose showed maximum nephroprotection by reducing serum urea (41.400 ± 0.510 mg/dL), uric acid (0.740 ± 0.032 mg/dL), blood urea nitrogen (18.370 ± 0.328), creatinine (3.267 ± 0.076) and minimizing kidney weight gain (0.586 ± 0.005) and histopathological alterations on 8th day. Furthermore, phytochemical and HPLC analysis revealed the presence of important phytoconstituents. These results suggest that AMECR provides protection against arthritis and nephrotoxicity that might be due to the existence of phytoconstituents, thus supporting folkloric claim.

  3. Tuberculosis chemoprophylaxis in rheumatoid arthritic patients receiving tumor necrosis factor inhibitors or conventional therapy

    Directory of Open Access Journals (Sweden)

    Saad Rabie Samra

    2015-01-01

    Conclusion: There was no significant increased risk for tuberculosis among RA patients receiving anti-TNF therapy when screening and chemoprophylaxis was applied, so screening of RA patients before anti-TNF therapy for latent tuberculosis and TB chemoprophylaxis should be done.

  4. A decreased subchondral trabecular bone tissue elastic modulus is associated with pre-arthritic cartilage damage

    DEFF Research Database (Denmark)

    Day, J; Ding, Ming; van der Linden, JC

    2001-01-01

    In osteoarthritis, one postulate is that changes in the mechanical properties of the subchondral bone layer result in cartilage damage. The goal of this study was to examine changes in subchondral trabecular bone properties at the calcified tissue level in the early stages of cartilage damage....... Finite element models were constructed from microCT scans of trabectilar bone from the proximal tibia of donors with mild cartilage damage and from normal donors. In the donors with cartilage damage, macroscopic damage was present only in the medial compartment. The effective tissue elastic moduli were...... determined using a combination of finite element models and mechanical testing. The bone tissue modulus was reduced by 60% in the medial condyle of the cases with cartilage damage compared to the control specimens. Neither the presence of cartilage damage nor the anatomic site (medial vs. lateral) affected...

  5. [Baropodometric walking analysis in healthy elderly and in arthritic patients before and after knee prosthesis implantation].

    Science.gov (United States)

    Marsico, V; Moretti, B; Patella, V; De Serio, S; Simone, C

    2002-01-01

    Standing and walking are complex activities which require integral skeletal-muscular and central nervous systems. Body is usually, evenly distributed between both the lower limbs with 40% on the ball of the foot and 60% on the heel, therefore, the body's centre of gravity falls between the feet in correspondence to Chopart's articulation. Some diseases can influence standing and walking including cardiovascular diseases (chronic edema, claudication, cardiopathies etc.) neurosensorial ones (cataract, Menière's disease, Parkinson's disease etc.) and orthopedic ones (kyphosis, scoliosis, hallux valgus, metatarsalgia, osteoarthritis etc.). In this study arthritis was considered the main cause of changes in posture and deambulation. An electric baropodometer with a modular platform 240 cm long and 40 cm wide was used which provided the pressure information for each in three distinct phases: static, dynamic and postural Baropodometric step analysis was performed on ten healthy, elderly subjects and ten elderly subjects with arthritis of the knee. The latter group was evaluated both pre- and post prosthetic knee surgery. The data revealed that the ten healthy subjects with arthritis who, prior to surgery presented unequal weight distribution on the diseased side which was slowly redistributed after surgery.

  6. [Human papillomaviruses].

    Science.gov (United States)

    Gross, G

    2003-10-01

    Human papillomaviruses (HPV) infect exclusively the basal cells of the skin and of mucosal epithelia adjacent to the skin such as the mouth, the upper respiratory tract, the lower genital tract and the anal canal. HPV does not lead to a viremia. Basically there are three different types of HPV infection: Clinically visible lesions, subclinical HPV infections and latent HPV infections. Distinct HPV types induce morphologically and prognostically different clinical pictures. The most common HPV associated benign tumor of the skin is the common wart. Infections of the urogenitoanal tract with specific HPV-types are recognised as the most frequent sexually transmitted viral infections. So-called "high-risk" HPV-types (HPV16, 18 and others) are regarded by the world health organisation as important risk-factors for the development of genital cancer (mainly cervical cancer), anal cancer and upper respiratory tract cancer in both genders. Antiviral substances with a specific anti-HPV effect are so far unknown. Conventional therapies of benign skin warts and of mucosal warts are mainly nonspecific. They comprise tissue-destroying therapies such as electrocautery, cryotherapy and laser. In addition cytotoxic substances such as podophyllotoxin and systemic therapy with retinoids are in use. Systemically and topically administered immunotherapies represent a new approach for treatment. Both interferons and particularly the recently developed imiquimod, an interferon-alpha and cytokine-inductor lead to better results and are better tolerated then conventional therapies. HPV-specific vaccines have been developed in the last 5 years and will be used in future for prevention and treatment of benign and malignant HPV-associated tumors of the genitoanal tract in both sexes.

  7. Human Development Report 1991: Financing Human Development

    OpenAIRE

    United Nations Development Programme, UNDP

    1991-01-01

    Lack of political commitment rather than financial resources is often the real barrier to human development. This is the main conclusion of Human Development Report 1991 - the second in a series of annual reports on the subject.

  8. The golden triangle of human dignity: human security, human development and human rights

    NARCIS (Netherlands)

    Gaay Fortman, B. de

    2004-01-01

    The success or failure of processes of democratization cannot be detached from processes of development related to the aspirations of people at the grassroots. Human rights, in a more theoretical terminology, require human development in order to enhance human security.

  9. Human-machine interactions

    Science.gov (United States)

    Forsythe, J. Chris; Xavier, Patrick G.; Abbott, Robert G.; Brannon, Nathan G.; Bernard, Michael L.; Speed, Ann E.

    2009-04-28

    Digital technology utilizing a cognitive model based on human naturalistic decision-making processes, including pattern recognition and episodic memory, can reduce the dependency of human-machine interactions on the abilities of a human user and can enable a machine to more closely emulate human-like responses. Such a cognitive model can enable digital technology to use cognitive capacities fundamental to human-like communication and cooperation to interact with humans.

  10. Bone-seeking therapeutic radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Srivastava Suresh C.

    2002-01-01

    Full Text Available Bone-seeking therapeutic radiopharmaceuticals are utilized on the basis of the radionuclide?s particulate emissions (primarily low to intermediate beta emission. The requirements therefore are different from those of bone imaging agents that consist mainly of short-lived single photon emitters. Lately, the therapeutic bone seeking radiopharmaceuticals have attained increasing importance due to their potential role in alleviating pain from osseous metastases in cancer patients, for the treatment of joint pain resulting from inflamed synovium (radiosynoviorthesis, or radiosynovectomy, or from various other forms of arthritic disease. There is, however, a paucity of published data on the bio-pharmacokinetics of these agents when used following intravenous administration for bone pain palliation. This paper will briefly review and summarize the presently available chemical and biopharmacokinetic information on the various clinically approved as well as experimental bone-localizing therapeutic radiopharmaceuticals, and make projections on their clinical application for the treatment of primary/metastatic cancer in bone.

  11. Special Section: Human Rights

    Science.gov (United States)

    Frydenlund, Knut; And Others

    1978-01-01

    Eleven articles examine human rights in Europe. Topics include unemployment, human rights legislation, role of the Council of Europe in promoting human rights, labor unions, migrant workers, human dignity in industralized societies, and international violence. Journal available from Council of Europe, Directorate of Press and Information, 67006…

  12. Scalability of human models

    NARCIS (Netherlands)

    Rodarius, C.; Rooij, L. van; Lange, R. de

    2007-01-01

    The objective of this work was to create a scalable human occupant model that allows adaptation of human models with respect to size, weight and several mechanical parameters. Therefore, for the first time two scalable facet human models were developed in MADYMO. First, a scalable human male was

  13. Visualizing Humans by Computer.

    Science.gov (United States)

    Magnenat-Thalmann, Nadia

    1992-01-01

    Presents an overview of the problems and techniques involved in visualizing humans in a three-dimensional scene. Topics discussed include human shape modeling, including shape creation and deformation; human motion control, including facial animation and interaction with synthetic actors; and human rendering and clothing, including textures and…

  14. The Human/Machine Humanities: A Proposal

    Directory of Open Access Journals (Sweden)

    Ollivier Dyens

    2016-03-01

    Full Text Available What does it mean to be human in the 21st century? The pull of engineering on every aspect of our lives, the impact of machines on how we represent ourselves, the influence of computers on our understanding of free-will, individuality and species, and the effect of microorganisms on our behaviour are so great that one cannot discourse on humanity and humanities without considering their entanglement with technology and with the multiple new dimensions of reality that it opens up. The future of humanities should take into account AI, bacteria, software, viruses (both organic and inorganic, hardware, machine language, parasites, big data, monitors, pixels, swarms systems and the Internet. One cannot think of humanity and humanities as distinct from technology anymore.

  15. From Human Past to Human Future

    OpenAIRE

    Robert G. Bednarik

    2013-01-01

    This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic an...

  16. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  17. Has Human Evolution Stopped?

    OpenAIRE

    TEMPLETON, Alan R

    2010-01-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important ...

  18. Preference for human eyes in human infants.

    Science.gov (United States)

    Dupierrix, Eve; de Boisferon, Anne Hillairet; Méary, David; Lee, Kang; Quinn, Paul C; Di Giorgio, Elisa; Simion, Francesca; Tomonaga, Masaki; Pascalis, Olivier

    2014-07-01

    Despite evidence supporting an early attraction to human faces, the nature of the face representation in neonates and its development during the first year after birth remain poorly understood. One suggestion is that an early preference for human faces reflects an attraction toward human eyes because human eyes are distinctive compared with other animals. In accord with this proposal, prior empirical studies have demonstrated the importance of the eye region in face processing in adults and infants. However, an attraction for the human eye has never been shown directly in infants. The current study aimed to investigate whether an attraction for human eyes would be present in newborns and older infants. With the use of a preferential looking time paradigm, newborns and 3-, 6-, 9-, and 12-month-olds were simultaneously presented with a pair of nonhuman primate faces (chimpanzees and Barbary macaques) that differed only by the eyes, thereby pairing a face with original nonhuman primate eyes with the same face in which the eyes were replaced by human eyes. Our results revealed that no preference was observed in newborns, but a preference for nonhuman primate faces with human eyes emerged from 3months of age and remained stable thereafter. The findings are discussed in terms of how a preference for human eyes may emerge during the first few months after birth.

  19. Economics of human trafficking.

    Science.gov (United States)

    Wheaton, Elizabeth M; Schauer, Edward J; Galli, Thomas V

    2010-01-01

    Because freedom of choice and economic gain are at the heart of productivity, human trafficking impedes national and international economic growth. Within the next 10 years, crime experts expect human trafficking to surpass drug and arms trafficking in its incidence, cost to human well-being, and profitability to criminals (Schauer and Wheaton, 2006: 164-165). The loss of agency from human trafficking as well as from modern slavery is the result of human vulnerability (Bales, 2000: 15). As people become vulnerable to exploitation and businesses continually seek the lowest-cost labour sources, trafficking human beings generates profit and a market for human trafficking is created. This paper presents an economic model of human trafficking that encompasses all known economic factors that affect human trafficking both across and within national borders. We envision human trafficking as a monopolistically competitive industry in which traffickers act as intermediaries between vulnerable individuals and employers by supplying differentiated products to employers. In the human trafficking market, the consumers are employers of trafficked labour and the products are human beings. Using a rational-choice framework of human trafficking we explain the social situations that shape relocation and working decisions of vulnerable populations leading to human trafficking, the impetus for being a trafficker, and the decisions by employers of trafficked individuals. The goal of this paper is to provide a common ground upon which policymakers and researchers can collaborate to decrease the incidence of trafficking in humans.

  20. Protective effect of low dose intra-articular cadmium on inflammation and joint destruction in arthritis.

    Science.gov (United States)

    Bonaventura, Paola; Courbon, Guillaume; Lamboux, Aline; Lavocat, Fabien; Marotte, Hubert; Albarède, Francis; Miossec, Pierre

    2017-05-25

    Synovium hyperplasia characterizes joint diseases, such as rheumatoid arthritis (RA). The cytotoxic effect of low-dose Cadmium (Cd) was tested in vitro and ex vivo on synoviocytes, the mesenchymal key effector cells of inflammation and proliferation in arthritis. The anti-inflammatory and anti-proliferative effects of Cd were tested in vivo by intra-articular injection in the adjuvant induced arthritis rat joints, where the clinical scores and the consequences of arthritis were evaluated. Cell death through apoptosis was highly induced by Cd in inflammatory synoviocytes (80% reduction of cell viability, p < 0.01). TNF plus IL-17 cytokine combination induced a two-fold increase of Cd cell content by enhancing the ZIP-8 importer and the MT-1 homeostasis regulator expression. Addition of Cd reduced IL-6 production in TNF plus IL-17-activated synoviocytes (up to 83%, p < 0.05) and in ex-vivo synovium biopsies (up to 94%, p < 0.01). Cd-injection in rat joints improved arthritis, reducing clinical scores (arthritic score reduced from 4 to 2, p < 0.01), inflammatory cell recruitment (up to 50%, p < 0.01) and protecting from bone/cartilage destruction. This proof of concept study is supported by the limited Cd spread in body reservoirs, with low-dose Cd providing a safe risk/benefit ratio, without toxic effects on other cell types and organs.

  1. The role of rose hip (Rosa canina L powder in alleviating arthritis pain and inflammation – part II animal and human studies

    Directory of Open Access Journals (Sweden)

    Marstr

    2016-05-01

    Full Text Available Kristian Marstrand,1 Joan Campbell-Tofte2 1Department of Orthopaedic Surgery, Elverum Hospital, Elverum, Norway; 2Coordinating Research Unit, Frederiksberg University Hospital, Frederiksberg, Copenhagen, Denmark Abstract: Rosa canina fruits (often known as rose hip have been used in herbal remedies since ancient times. On the basis of anecdotal reports about the effects of rose hip preparations on human health and citations to the same in ancient texts, in vitro and in vivo studies have been conducted that have made it possible to learn about some active ingredients in rose hip, as well as how the component compounds might exert their effects. From such studies, it has been documented that there is a great variation in active ingredients when comparing different rose hip products. Factors which affect the quality and quantity of active ingredients in the rose hip products include the subspecies of the particular R. canina from which the fruits are harvested, the environment during plant growth, time of harvesting, and the amount of seeds and shells/husks incorporated into the preparation. Studies in animals and in humans are of great importance for determining the true bio-effects of rose hip. Such in vivo studies that have only been performed during the last 2 decades indicate that the treatment of patients with different types of joint disease with rose hip powder based on a subspecies of R. canina (Lito containing a certain galactolipid (GOPO can alleviate pain, improve daily activity, and even reduce the consumption of regular pain relievers. As several rose hip components have been shown to be anti-inflammatory, it is suggested that anti-inflammatory mechanisms might explain some reductions in symptoms associated with administering rose hip to arthritic conditions. Although the number of publications of randomized and placebo-controlled clinic studies with rose hip is small, the overriding evidence is that the anti-inflammatory effects from

  2. Human assisted robotic exploration

    Science.gov (United States)

    Files, B. T.; Canady, J.; Warnell, G.; Stump, E.; Nothwang, W. D.; Marathe, A. R.

    2016-05-01

    In support of achieving better performance on autonomous mapping and exploration tasks by incorporating human input, we seek here to first characterize humans' ability to recognize locations from limited visual information. Such a characterization is critical to the design of a human-in-the-loop system faced with deciding whether and when human input is useful. In this work, we develop a novel and practical place-recognition task that presents humans with video clips captured by a navigating ground robot. Using this task, we find experimentally that human performance does not seem to depend on factors such as clip length or familiarity with the scene and also that there is significant variability across subjects. Moreover, we find that humans significantly outperform a state-of-the-art computational solution to this problem, suggesting the utility of incorporating human input in autonomous mapping and exploration techniques.

  3. Human Use Index (Future)

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  4. Human Papillomavirus (HPV) Vaccines

    Science.gov (United States)

    ... Directory Cancer Prevention Overview Research Human Papillomavirus (HPV) Vaccines On This Page What are human papillomaviruses? Which ... infections? Can HPV infections be prevented? What HPV vaccines are available? Who should get the HPV vaccines? ...

  5. Human Use Index

    Data.gov (United States)

    U.S. Environmental Protection Agency — Human land uses may have major impacts on ecosystems, affecting biodiversity, habitat, air and water quality. The human use index (also known as U-index) is the...

  6. Telling the Human Story.

    Science.gov (United States)

    Richardson, Miles

    1987-01-01

    Proposes that one of the fundamental human attributes is telling stories. Explores the debate on whether Neanderthals possessed language ability. Discusses the role of the "human story" in teaching anthropology. (DH)

  7. Human Services Offices

    Data.gov (United States)

    Fairfax County, Virginia — This data contains point features representing the human services offices within Fairfax County.“HS_Region” is the office for each human services region, “DFS_Area”...

  8. Human Resource Accounting System

    Science.gov (United States)

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  9. The Growing Human Population.

    Science.gov (United States)

    Keyfitz, Nathan

    1989-01-01

    Discusses the issue of human population. Illustrates the projections of the growing human population in terms of developed and less developed countries. Describes the family planning programs in several countries. Lists three references for further reading. (YP)

  10. Human bites (image)

    Science.gov (United States)

    Human bites present a high risk of infection. Besides the bacteria which can cause infection, there is ... the wound extends below the skin. Anytime a human bite has broken the skin, seek medical attention.

  11. Monogenic human obesity syndromes

    National Research Council Canada - National Science Library

    Farooqi, I S; O'Rahilly, S

    2004-01-01

    .... This chapter will consider the human monogenic obesity syndromes that have been characterized to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  12. Skin and the non-human human

    DEFF Research Database (Denmark)

    Rösing, Lilian Munk

    2013-01-01

    The article puts forward an aesthetic and psychoanalytic analysis of Titian's painting, The Flaying of Marsyas, arguing that the painting is a reflection on the human subject as a being constituted by skin and by a core of non-humanity. The analysis is partly an answer to Melanie Hart's (2007......) article 'Visualizing the mind: Looking at Titian's Flaying of Marsyas', addressing features of the painting not commented on by Hart, and supplementing Hart's (Kleinian) theoretical frame by involving Didier Anzieu's 'skin ego', Slavoj Zizek's concept of the 'non-human', Giorgio Agamben's term...

  13. Human productivity program definition

    Science.gov (United States)

    Cramer, D. B.

    1985-01-01

    The optimization of human productivity on the space station within the existing resources and operational constraints is the aim of the Human Productivity Program. The conceptual objectives of the program are as follows: (1) to identify long lead technology; (2) to identify responsibility for work elements; (3) to coordinate the development of crew facilities and activities; and (4) to lay the foundation for a cost effective approach to improving human productivity. Human productivity work elements are also described and examples are presented.

  14. Human Resource Management System

    OpenAIRE

    Navaz, A. S. Syed; Fiaz, A. S. Syed; Prabhadevi, C.; V.Sangeetha; Gopalakrishnan,S.

    2013-01-01

    The paper titled HUMAN RESOURCE MANAGEMENT SYSTEM is basically concerned with managing the Administrator of HUMAN RESOURCE Department in a company. A Human Resource Management System, refers to the systems and processes at the intersection between human resource management and information technology. It merges HRM as a discipline and in particular its basic HR activities and processes with the information technology field, whereas the programming of data processing systems evolved into standa...

  15. Human nature and enhancement.

    Science.gov (United States)

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  16. Human Document Project

    NARCIS (Netherlands)

    Vries, de J.; Abelmann, L.; Manz, A.; Elwenspoek, M.C.

    2012-01-01

    “The Human Document Project” is a project which tries to answer all of the questions related to preserving information about the human race for tens of generations of humans to come or maybe even for a future intelligence which can emerge in the coming thousands of years. This document mainly focuss

  17. Has Human Evolution Stopped?

    Directory of Open Access Journals (Sweden)

    Alan R. Templeton

    2010-07-01

    Full Text Available It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  18. Has human evolution stopped?

    Science.gov (United States)

    Templeton, Alan R

    2010-07-01

    It has been argued that human evolution has stopped because humans now adapt to their environment via cultural evolution and not biological evolution. However, all organisms adapt to their environment, and humans are no exception. Culture defines much of the human environment, so cultural evolution has actually led to adaptive evolution in humans. Examples are given to illustrate the rapid pace of adaptive evolution in response to cultural innovations. These adaptive responses have important implications for infectious diseases, Mendelian genetic diseases, and systemic diseases in current human populations. Moreover, evolution proceeds by mechanisms other than natural selection. The recent growth in human population size has greatly increased the reservoir of mutational variants in the human gene pool, thereby enhancing the potential for human evolution. The increase in human population size coupled with our increased capacity to move across the globe has induced a rapid and ongoing evolutionary shift in how genetic variation is distributed within and among local human populations. In particular, genetic differences between human populations are rapidly diminishing and individual heterozygosity is increasing, with beneficial health effects. Finally, even when cultural evolution eliminates selection on a trait, the trait can still evolve due to natural selection on other traits. Our traits are not isolated, independent units, but rather are integrated into a functional whole, so selection on one trait can cause evolution to occur on another trait, sometimes with mildly maladaptive consequences.

  19. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...

  20. Human Machine Learning Symbiosis

    Science.gov (United States)

    Walsh, Kenneth R.; Hoque, Md Tamjidul; Williams, Kim H.

    2017-01-01

    Human Machine Learning Symbiosis is a cooperative system where both the human learner and the machine learner learn from each other to create an effective and efficient learning environment adapted to the needs of the human learner. Such a system can be used in online learning modules so that the modules adapt to each learner's learning state both…

  1. Monogenic human obesity.

    Science.gov (United States)

    Farooqi, I Sadaf

    2008-01-01

    We and others have identified several single gene defects that disrupt the molecules in the leptinmelanocortin pathway causing severe obesity in humans. In this review, we consider these human monogenic obesity syndromes and discuss how far the characterisation of these patients has informed our understanding of the physiological role of leptin and the melanocortins in the regulation of human body weight and neuroendocrine function.

  2. The suppressive effects of Saposhnikovia divaricata (Fangfeng) chromone extract on rheumatoid arthritis via inhibition of nuclear factor-κB and mitogen activated proteinkinases activation on collagen-induced arthritis model.

    Science.gov (United States)

    Kong, Xiangying; Liu, Chunfang; Zhang, Cun; Zhao, Juan; Wang, Jianzhu; Wan, Hongye; Zhu, Hongwei; Zhang, Ping; Chen, Weiheng; Xiao, Yongqing; Lin, Na

    2013-07-30

    Saposhnikovia divaricata (SD), called "Fangfeng" in China, is commonly used in clinical compound prescription for treatment of rheumatoid arthritis (RA), but its actions on RA have not been clarified. The present study aims to determine the anti-inflammatory activity of SD chromone extract (SCE), the major bioactive component of SD, on collagen-induced arthritis (CIA) rats, and elucidate its underlying mechanisms with regards to its molecular basis of action on human fibroblast-like synoviocytes derived from RA patients (HFLS-RA). CIA model on rats was constructed by injection of bovine type II collagen. Rats were pre-treated with different dosages of SCE from 3 days before till 35 days after model building. The progression of CIA was evaluated by macroscopic scoring, X-ray observation and hematoxylin and eosin (HE) staining of paws. HFLS-RA were pre-treated with different concentrations of SCE prior to stimulation with 10 ng/ml of tumor necrosis factor (TNF) α. By radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA), levels of interleukin (IL)-1β, IL-6, TNFα and prostaglandin E2 (PGE2) were quantified respectively. Nuclear factor (NF-κB) p65 expression and DNA-binding activity were tested by immunohistochemisty and electrophoretic mobility shift assay (EMSA) respectively. Phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 MAPKs were examined by immunohistochemisty staining and western blot analysis. Histological examination and radiological observation demonstrated that SCE significantly reduced the inflammatory responses in the joints of CIA rats. SCE inhibited the production of TNFα, IL-1β, and IL-6 in the joint tissues and sera. The level of PGE2 in sera was also decreased by SCE. Moreover, SCE treatment in vivo was able to reduce protein level of NF-κB, the transcriptional factor closely related to the inflammatory process, in articular synovium and cartilage of CIA rats. In addition, SCE

  3. From Human Past to Human Future

    Directory of Open Access Journals (Sweden)

    Robert G. Bednarik

    2013-01-01

    Full Text Available This paper begins with a refutation of the orthodox model of final Pleistocene human evolution, presenting an alternative, better supported account of this crucial phase. According to this version, the transition from robust to gracile humans during that period is attributable to selective breeding rather than natural selection, rendered possible by the exponential rise of culturally guided volitional choices. The rapid human neotenization coincides with the development of numerous somatic and neural detriments and pathologies. Uniformitarian reasoning based on ontogenic homology suggests that the cognitive abilities of hominins are consistently underrated in the unstable orthodoxies of Pleistocene archaeology. A scientifically guided review establishes developmental trajectories defining recent changes in the human genome and its expressions, which then form the basis of attempts to extrapolate from them into the future. It is suggested that continuing and perhaps accelerating unfavorable genetic changes to the human species, rather than existential threats such as massive disasters, pandemics, or astrophysical events, may become the ultimate peril of humanity.

  4. 对比关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白对脊柱关节炎和类风湿关节炎膝关节炎的疗效%The effect of intra-articular injection of recombinant human tumor necrosis factor-Fc in knee in patients with spondyloarthritis and rheumatoid arthritis

    Institute of Scientific and Technical Information of China (English)

    梁东风; 黄烽; 张江林; 朱剑; 张红

    2013-01-01

    目的 比较单次膝关节腔内注射重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)对脊柱关节炎(SpA)和类风湿关节炎(RA)膝关节炎的疗效差异.方法 入选确诊SpA或RA并伴有至少一侧膝关节肿胀及积液的受试者,X线显示该膝关节无变形、中重度骨破坏及关节间隙明显狭窄,入组前经过常规剂量改善病情抗风湿药(DMARDs)治疗至少6周,于目标膝关节腔穿刺,吸净滑液后注射1次25 mg rhTNFR:Fc.在注射4周后评价疗效和不良事件,主要疗效指标为改良(纽约)特种外科医院(HSS)膝关节评分.采用配对t检验,两样本t检验和秩和检验进行统计学分析.结果 27例SpA和15例RA受试者入选并完成研究.SpA组改良HSS膝关节评分基线值为(66±14)分,注射4周后为(86±11)分,治疗前后比较差异有统计学意义(P<0.05);RA组基线值为(64±13)分,注射4周后为(80±9)分,治疗前后比较差异有统计学意义(P<0.05).SpA组的改良HSS膝关节评分改善率为24.2%(16.5%~41.9%),RA组为22.2%(15.3%~37.7%),2组比较差异无统计学意义(P>0.05).SpA组膝关节滑膜厚度改善率为31.8%(9.3%~57.3%),RA组为1.5%(-19.3%~25.5%),2组比较差异有统计学意义(P<0.05).SpA组6例、RA组2例发生了不良事件,无严重不良事件发生.结论 单次膝关节腔内注射rhTN FR:Fc对SpA和RA膝关节炎安全有效,且SpA膝关节滑膜厚度的减轻程度要大于RA膝关节.%Objective To compare the effect of intra-articular injection of recombinant human tumor necrosis factor-Fc (rhTNFR:Fc) in the treatment of knee arthritis in spondyloarthritis (SPA) with that in rheumatoid arthritis (RA).Methods The subjects included in this study were SpA and RA patients with knee arthritis without deformity,moderate or severe bone erosion and obvious joint space narrowing in radiography,who had taken at least 6-week therapy with routine dosage of disease modifying anti

  5. Humanity at the Edge

    DEFF Research Database (Denmark)

    Svendsen, Mette N.; Gjødsbøl, Iben M.; Dam, Mie S.

    2017-01-01

    At the heart of anthropology and the social sciences lies a notion of human existence according to which humans and animals share the basic need for food, but only humans have the capacity for morality. Based on fieldwork in a pig laboratory, a neonatal intensive care unit (NICU), and a dementia ...... human and animal value and agency with approaches that focus on human experience and virtue ethics, we argue that ‘the human’ at stake in the moral laboratory of feeding precarious lives puts ‘the human’ in anthropology at disposal for moral experimentation....

  6. Jordan Adjusted Human Development

    OpenAIRE

    Ababsa, Myriam

    2014-01-01

    Jordan Human Development Index (HDI) and Adjusted Human Development Index (IHDI) In 1990, the United Nations Development Programme designed a Human Development Index composed of life expectancy at birth, level of education and gross domestic product (GDP) per capita. In 2011, the UNDP ranked Jordan 95th out of 187 countries with a human development index of 0.698, up from 0.591 in 1990, making it the leading medium-range country for human development (fig. VIII.1). In 2010, the inequality adj...

  7. Human Beings And Water

    OpenAIRE

    2016-01-01

    The writer of this paper on this writing is talking about the human beings and water. Water is one of the very fundamentally things that human beings need to keep their lives. Human beings sometimes do not realise that the water is very important for them because they actually cannot live their lives without the present of water. Human beings can keep their lives without rice, but cannot without water. For instances the use of water for human beings are domestic use, cooking, washing, bathing...

  8. Human rights and bioethics.

    Science.gov (United States)

    Barilan, Y M; Brusa, M

    2008-05-01

    In the first part of this article we survey the concept of human rights from a philosophical perspective and especially in relation to the "right to healthcare". It is argued that regardless of meta-ethical debates on the nature of rights, the ethos and language of moral deliberation associated with human rights is indispensable to any ethics that places the victim and the sufferer in its centre. In the second part we discuss the rise of the "right to privacy", particularly in the USA, as an attempt to make the element of personal free will dominate over the element of basic human interest within the structure of rights and when different rights seem to conflict. We conclude by discussing the relationship of human rights with moral values beyond the realm of rights, mainly human dignity, free will, human rationality and response to basic human needs.

  9. Human Milk Banking.

    Science.gov (United States)

    Haiden, Nadja; Ziegler, Ekhard E

    2016-01-01

    Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

  10. Anti-inflammatory and antioxidant effect of Kerabala: a value-added ayurvedic formulation from virgin coconut oil inhibits pathogenesis in adjuvant-induced arthritis.

    Science.gov (United States)

    Ratheesh, M; Sandya, S; Pramod, C; Asha, S; Svenia, Jose P; Premlal, S; GrishKumar, B

    2017-02-01

    Kerabala (CB) is a novel ayurvedic formulation used for treating various inflammatory diseases. This formulation was made from virgin coconut oil and it comprises extracts of Sida cordifolia, coconut milk and sesame oil. The current study was performed to evaluate the anti-inflammatory action of CB on carrageenan-induced acute and adjuvant-induced chronic experimental models. 5 mg/kg bwt was found to be potent dose from carrageenan model and evaluated its effect in adjuvant-induced chronic arthritic model. The antioxidant assays like SOD, catalase, glutathione peroxidase, lipid peroxidation product, nitrate level and GSH were measured in paw tissue. Hematological parameters like hemoglobin (HB) count, ESR, WBC count, plasma CRP levels were analyzed. By RT-PCR, the inflammatory markers like cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) expressions were evaluated. The extracellular matrix proteins like MMP-2 and MMP-9 were determined by zymography and its expression by western blotting. Histopathology and cytology of paw tissue and synovium were analyzed. The result indicated that there was a significant increment in the levels of antioxidant enzymes on CB administration. The hematological markers such as ESR, WBC and plasma CRP levels were reduced by CB treatment and it also increases the HB level. The upregulated gene level expressions of inflammatory markers like COX-2, iNOS, TNF-α and IL-6 were down regulated by administration of CB. MMP-2 and MMP-9 expression significantly reduced by CB administration. Massive influx of inflammatory cell infiltration, proliferative collagen in histological analysis of paw tissue of arthritic rat was decreased by CB administration. Synovial cytology of CB administrated group shows reduced number of reactive mesothelial cells and synovial inflammatory cells. This current study shows that ayurvedic drug CB has an antioxidant, anti-inflammatory and

  11. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint

    Directory of Open Access Journals (Sweden)

    K. Okamoto

    2015-02-01

    Full Text Available Several epidemiological studies have reported that temporomandibular disorders (TMDs are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ is made up of connective tissue with an extracellular matrix (ECM composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs, was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta. In the in vivo study, both normal and osteoarthritic (OA human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL in the presence or absence of DHEA (10 μM. The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican

  12. Effect of interleukin-1beta and dehydroepiandrosterone on the expression of lumican and fibromodulin in fibroblast-like synovial cells of the human temporomandibular joint.

    Science.gov (United States)

    Okamoto, K; Kiga, N; Shinohara, Y; Tojyo, I; Fujita, S

    2015-02-23

    Several epidemiological studies have reported that temporomandibular disorders (TMDs) are more prevalent in women than in men. It has recently been proposed that sex hormones such as estrogen, testosterone and dehydroepiandrosterone (DHEA) are involved with the pathogenesis of TMDs. Although studies have investigated the relationship between estrogen and testosterone and the restoration of TMDs, the relationship between DHEA and TMDs is unknown. The synovial tissue of the temporomandibular joint (TMJ) is made up of connective tissue with an extracellular matrix (ECM) composed of collagen and proteoglycan. One proteoglycan family, comprised of small leucine-rich repeat proteoglycans (SLRPs), was found to be involved in collagen fibril formation and interaction. In recent years, the participation of SLRPs such as lumican and fibromodulin in the internal derangement of TMJ has been suggested. Although these SLRPs may contribute to the restoration of the synovium, their effect is still unclear. The purpose of this study was to investigate the effect of DHEA, a sex hormone, on the expression of lumican and fibromodulin in human temporomandibular specimens and in cultured human TMJ fibroblast-like synovial cells in the presence or absence of the pro-inflammatory cytokine interleukin-1beta (IL-1beta). In the in vivo study, both normal and osteoarthritic (OA) human temporomandibular synovial tissues were immunohistochemically examined. In the in vitro study, five fibroblast-like synoviocyte (FLS) cell lines were established from human TMJ synovial tissue of patients with osteoarthritis. The subcultured cells were then incubated for 3, 6, 12 or 24 h with/without IL-1beta (1 ng/mL) in the presence or absence of DHEA (10 μM). The gene expression of lumican and fibromodulin was examined using the real-time polymerase chain reaction (PCR) and their protein expression was examined using immunofluorescent staining. We demonstrated that the expression of lumican significantly

  13. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients

    Directory of Open Access Journals (Sweden)

    Niimoto Takuya

    2010-09-01

    Full Text Available Abstract Background Interleukin (IL-17 is an important factor in rheumatoid arthritis (RA pathogenesis. MicroRNA (miRNAs are a family of non coding RNAs and associated with human diseases including RA. The purpose of this study is to identify the miRNAs in the differentiation of IL-17 producing cells, and analyze their expression pattern in the peripheral blood mononuclear cells (PBMC and synovium from RA patients. Methods IL-17 producing cells were expanded from CD4+T cell. MiRNA microarray was performed to identify the miRNAs in the differentiation of IL-17 producing cells. Quantitative polymerase chain reaction was performed to examine the expression patterns of the identified miRNAs in the PBMC and synovium from RA and osteoarthritis (OA patients. Double staining combining in situ hybridization and immunohistochemistry of IL-17 was performed to analyze the expression pattern of identified miRNA in the synovium. Results Six miRNAs, let-7a, miR-26, miR-146a/b, miR-150, and miR-155 were significantly up regulated in the IL-17 producing T cells. The expression of miR-146a and IL-17 was higher than in PBMC in the patients with low score of Larsen grade and short disease duration. MiR-146a intensely expressed in RA synovium in comparison to OA. MiR-146a expressed intensely in the synovium with hyperplasia and high expression of IL-17 from the patients with high disease activity. Double staining revealed that miR-146a expressed in IL-17 expressing cells. Conclusion These results indicated that miR-146a was associated with IL-17 expression in the PBMC and synovium in RA patients. There is the possibility that miR-146a participates in the IL-17 expression.

  14. Human Capital and Sustainability

    Directory of Open Access Journals (Sweden)

    Garry Jacobs

    2011-01-01

    Full Text Available A study of sustainability needs to consider the role of all forms of capital—natural, biological, social, technological, financial, cultural—and the complex ways in which they interact. All forms of capital derive their value, utility and application from human mental awareness, creativity and social innovation. This makes human capital, including social capital, the central determinant of resource productivity and sustainability. Humanity has entered the Anthropocene Epoch in which human changes have become the predominant factor in evolution. Humanity is itself evolving from animal physicality to social vitality to mental individuality. This transition has profound bearing on human productive capabilities, adaptability, creativity and values, the organization of economy, public policy, social awareness and life styles that determine sustainability. This article examines the linkages between population, economic development, employment, education, health, social equity, cultural values, energy intensity and sustainability in the context of evolving human consciousness. It concludes that development of human capital is the critical determinant of long-term sustainability and that efforts to accelerate the evolution of human consciousness and emergence of mentally self-conscious individuals will be the most effective approach for ensuring a sustainable future. Education is the primary lever. Human choice matters.

  15. Integrated Environmental Modelling: human decisions, human challenges

    Science.gov (United States)

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  16. Exposure to Candida albicans polarizes a T-cell driven arthritis model towards Th17 responses, resulting in a more destructive arthritis.

    Directory of Open Access Journals (Sweden)

    Renoud J Marijnissen

    Full Text Available BACKGROUND: Fungal components have been shown very effective in generating Th17 responses. We investigated whether exposure to a minute amount of C. albicans in the arthritic joint altered the local cytokine environment, leading to enhanced Th17 expansion and resulting in a more destructive arthritis. METHODOLOGY: Chronic SCW arthritis was induced by repeated injection with Streptococcus pyogenes (SCW cell wall fragments into the knee joint of C57Bl/6 mice, alone or in combination with the yeast of C. albicans or Zymosan A. During the chronic phase of the arthritis, the cytokine levels, mRNA expression and histopathological analysis of the joints were performed. To investigate the phenotype of the IL-17 producing T-cells, synovial cells were isolated and analyzed by flowcytometry. PRINCIPAL FINDINGS: Intra-articular injection of either Zymosan A or C. albicans on top of the SCW injection both resulted in enhanced joint swelling and inflammation compared to the normal SCW group. However, only the addition of C. albicans during SCW arthritis resulted in severe chondrocyte death and enhanced destruction of cartilage and bone. Additionally, exposure to C. albicans led to increased IL-17 in the arthritic joint, which was accompanied by an increased synovial mRNA expression of T-bet and RORγT. Moreover, the C. albicans-injected mice had significantly more Th17 cells in the synovium, of which a large population also produced IFN-γ. CONCLUSION: This study clearly shows that minute amounts of fungal components, like C. albicans, are very potent in interfering with the local cytokine environment in an arthritic joint, thereby polarizing arthritis towards a more destructive phenotype.

  17. Human organ markets and inherent human dignity.

    Science.gov (United States)

    MacKellar, Calum

    2014-01-01

    It has been suggested that human organs should be bought and sold on a regulated market as any other material property belongingto an individual. This would have the advantage of both addressing the grave shortage of organs available for transplantation and respecting the freedom of individuals to choose to do whatever they want with their body parts. The old arguments against such a market in human organs are, therefore, being brought back into question. The article examines the different arguments both in favour and against the sale of human organs. It concludes that the body and any of its elements is a full expression of the whole person. As such, they cannot have a price if the individual is to retain his or her full inherent dignity and if society is to retain and protect this very important concept.

  18. Chimeras and human dignity.

    Science.gov (United States)

    de Melo-Martín, Inmaculada

    2008-12-01

    Discussions about whether new biomedical technologies threaten or violate human dignity are now common. Indeed, appeals to human dignity have played a central role in national and international debates about whether to allow particular kinds of biomedical investigations. The focus of this paper is on chimera research. I argue here that both those who claim that particular types of human-nonhuman chimera research threaten human dignity and those who argue that such threat does not exist fail to make their case. I first introduce some of the arguments that have been offered supporting the claim that the creation of certain sorts of chimeras threatens or violates human dignity. I next present opponents' assessments of such arguments. Finally I critically analyze both the critics' and the supporters' claims about whether chimera research threatens human dignity.

  19. Human Performance in Space

    Science.gov (United States)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    Human factors is a critical discipline for human spaceflight. Nearly every human factors research area is relevant to space exploration -- from the ergonomics of hand tools used by astronauts, to the displays and controls of a spacecraft cockpit or mission control workstation, to levels of automation designed into rovers on Mars, to organizational issues of communication between crew and ground. This chapter focuses more on the ways in which the space environment (especially altered gravity and the isolated and confined nature of long-duration spaceflight) affects crew performance, and thus has specific novel implications for human factors research and practice. We focus on four aspects of human performance: neurovestibular integration, motor control and musculo-skeletal effects, cognitive effects, and behavioral health. We also provide a sampler of recent human factors studies from NASA.

  20. Developing human technology curriculum

    Directory of Open Access Journals (Sweden)

    Teija Vainio

    2012-10-01

    Full Text Available During the past ten years expertise in human-computer interaction has shifted from humans interacting with desktop computers to individual human beings or groups of human beings interacting with embedded or mobile technology. Thus, humans are not only interacting with computers but with technology. Obviously, this shift should be reflected in how we educate human-technology interaction (HTI experts today and in the future. We tackle this educational challenge first by analysing current Master’s-level education in collaboration with two universities and second, discussing postgraduate education in the international context. As a result, we identified core studies that should be included in the HTI curriculum. Furthermore, we discuss some practical challenges and new directions for international HTI education.

  1. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research......Todays expanding digital landscape constitutes an important research object as well as the research environment for the Humanities at the beginning of the 21st century. Taking this state of affairs as a starting point this inaugural lecture presents a vision for how the digital affects...

  2. Advancing Human Rights

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The National Human Rights Action Plan of China (2012-2015) was initiated after the successful conclusion of the National Human Rights Action Plan of China (2009-2010).The Chinese government in late July published an assessment report on the implementation of the plan,elaborating on the full implementation of China's first-ever national program on human rights development,which was drafted in April 2009.

  3. Human hemoglobin genetics

    Energy Technology Data Exchange (ETDEWEB)

    Honig, G.R.; Adams, J.G.

    1986-01-01

    This book contains the following 10 chapters: Introduction; The Human Hemoglobins; The Human Globin Genes; Hemoglobin Synthesis and Globin Gene Expression; The Globin Gene Mutations - A. Mechanisms and Classification; The Globin Gene Mutations - B. Their Phenotypes and Clinical Expression; The Genetics of the Human Globin Gene Loci: Formal Genetics and Gene Linkage; The Geographic Distribution of Globin Gene Variation; Labortory Identification, Screening, Education, and Counseling for Abnormal Hemoglobins and Thalassemias; and Approaches to the Treatment of the Hemoglobin Disorders.

  4. Modern Human Capital Management

    OpenAIRE

    Feldberger, Madita

    2008-01-01

    Title: Modern Human Capital Management Seminar date: 30th of May 2008 Course: Master thesis in Business Administration, 15 ECTS Authors: Madita Feldberger Supervisor: Lars Svensson Keywords: Human capital, SWOT Analysis, Strategic Map, Balanced Scorecard Research Problem: Despite of the success of Human Capital Management (HCM) in research it did not arrive yet in the HR departments of many companies. Numerous firms even have problems to set their strategic goals with focus on HR. The HR Bala...

  5. Robotics for Human Exploration

    Science.gov (United States)

    Fong, Terrence; Deans, Mathew; Bualat, Maria

    2013-01-01

    Robots can do a variety of work to increase the productivity of human explorers. Robots can perform tasks that are tedious, highly repetitive or long-duration. Robots can perform precursor tasks, such as reconnaissance, which help prepare for future human activity. Robots can work in support of astronauts, assisting or performing tasks in parallel. Robots can also perform "follow-up" work, completing tasks designated or started by humans. In this paper, we summarize the development and testing of robots designed to improve future human exploration of space.

  6. [Human physiology: kidney].

    Science.gov (United States)

    Natochin, Iu V

    2010-01-01

    The content of human physiology as an independent part of current physiology is discussed. Substantiated is the point that subjects of human physiology are not only special sections of physiology where functions are inherent only in human (physiology of intellectual activity, speech, labor, sport), but also in peculiarities of functions, specificity of regulation of each of physiological systems. By the example of physiology of kidney and water-salt balance there are shown borders of norm, peculiarities of regulation in human, new chapters of renal physiology which have appeared in connection with achievements of molecular physiology.

  7. Human Performance Research Center

    Data.gov (United States)

    Federal Laboratory Consortium — Biochemistry:Improvements in energy metabolism, muscular strength and endurance capacity have a basis in biochemical and molecular adaptations within the human body....

  8. Extraterritorial Human Rights Obligations

    DEFF Research Database (Denmark)

    Amsinck Boie, Hans Nikolaj; Torp, Kristian

    adequately be addressed without including the approach to the problem taken in practice; Corporate Social Responsibility, CSR. The book therefore draws upon the concept of CSR and the approaches developed here and discusses whether states may utilize the CSR-based concept of human rights due diligence...... to fulfil their possible obligations to protect against human rights violations by corporations.......The book addresses the issue of corporate respect for human rights by examining if and how states are obligated to ensure that corporations originating from their jurisdiction respect human rights when they operate abroad. The existence of such a duty is much debated by academics at national...

  9. The psychology of humanness.

    Science.gov (United States)

    Haslam, Nick; Loughnan, Steve; Holland, Elise

    2013-01-01

    This chapter explores the ways in which the concept of "humanness" illuminates a wide and fascinating variety of psychological phenomena. After introducing the concept--everyday understandings of what it is to be human--we present a model of the diverse ways in which humanness can be denied to people. According to this model people may be perceived as lacking uniquely human characteristics, and thus likened to animals, or as lacking human nature, and thus likened to inanimate objects. Both of these forms of dehumanization occur with varying degrees of subtlety, from the explicit uses of derogatory animal metaphors, to stereotypes that ascribe lesser humanness or simpler minds to particular groups, to nonconscious associations between certain humans and nonhumans. After reviewing research on dehumanization through the lens of our model we examine additional topics that the psychology of humanness clarifies, notably the perception of nonhuman animals and the objectification of women. Humanness emerges as a concept that runs an integrating thread through a variety of research literatures.

  10. The Human Toolmaker

    OpenAIRE

    Kassuba, Tanja; Kastner, Sabine

    2014-01-01

    Do you enjoy building airplanes, cars, houses, or robots with Lego blocks? Humans are the only animal species that can create complicated constructions from simple Lego blocks – our Lego building ability is “human-specific,” since it is only found in human beings. What would our closest relatives, apes or monkeys, do with a box of Lego blocks? They would probably chew on them, and lose interest when they find out that they are not edible! Why are humans the only Lego builders in the animal ki...

  11. Photography after the Human

    OpenAIRE

    Zylinska, Joanna

    2016-01-01

    How can we visualise and subsequently reimagine the abstraction that is the extinction of human species while there is still time? The article addresses this question by considering the existence of images – and, in particular, light-induced mechanical images known as photographs – after the human. The “after the human” designation does not just refer to the material disappearance of the human in some kind of distant future, but also to the present imagining of the disappearance of the human ...

  12. Refractoriness in human atria

    DEFF Research Database (Denmark)

    Skibsbye, Lasse; Jespersen, Thomas; Christ, Torsten

    2016-01-01

    drugs. Cardiomyocyte excitability depends on availability of sodium channels, which involves both time- and voltage-dependent recovery from inactivation. This study therefore aims to characterise how sodium channel inactivation affects refractoriness in human atria. METHODS AND RESULTS: Steady......-state activation and inactivation parameters of sodium channels measured in vitro in isolated human atrial cardiomyocytes were used to parameterise a mathematical human atrial cell model. Action potential data were acquired from human atrial trabeculae of patients in either sinus rhythm or chronic atrial...... in pharmacological management of chronic atrial fibrillation....

  13. Humanities, Digital Humanities, Media studies, Internet studies

    DEFF Research Database (Denmark)

    Brügger, Niels

    the interplay between four areas which until now to a certain extent have been separated: Traditional Hu- manities, Digital Humanities, Media studies, and Internet studies. The vision is followed by an outline of how it can be unfolded in concrete activities, in the form of research projects, research...

  14. Developing Human Resources through Actualizing Human Potential

    Science.gov (United States)

    Clarken, Rodney H.

    2012-01-01

    The key to human resource development is in actualizing individual and collective thinking, feeling and choosing potentials related to our minds, hearts and wills respectively. These capacities and faculties must be balanced and regulated according to the standards of truth, love and justice for individual, community and institutional development,…

  15. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century

  16. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  17. Human Capital and Retirement

    NARCIS (Netherlands)

    P. Alders

    1999-01-01

    textabstractThis paper investigates the relation between human capital and retirement when the age of retirement is endogenous. This relation is examined in a life-cycle earnings model. An employee works full time until retirement. The worker accumulates human capital by training- on-the-job and by

  18. Cohabitation: Humans & Agriculture

    NARCIS (Netherlands)

    Woodington, W.

    2012-01-01

    This "designers' manual" is made during the TIDO-course AR0531 Smart & Bioclimatic Design. Cohabitation of humans and agriculture can be used to improve building climate, human health and the state of the world. It affects building design and requires new building components. This manual explains w

  19. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  20. Human Resource Accounting

    Science.gov (United States)

    Woodruff, Robert L., Jr.

    1973-01-01

    An interview is reported which discussed the implications for the hiring, recruiting, screening and development of employees in the light of human resource accounting, here defined as the identification, accumulation and dissemination of information about human resources in dollar terms. (SA)

  1. Hooking Kids with Humanities.

    Science.gov (United States)

    Anstead, Neil L.

    1993-01-01

    Humanitas is part of Collaboratives for Humanities and Arts Teaching (CHART), a nationwide network funded primarily by the Rockefeller Foundation. In 11 large school districts and numerous rural districts, high school teachers, academics, artists, and business and community leaders are cooperating to promote teaching of the arts and humanities.…

  2. The Human Technology

    DEFF Research Database (Denmark)

    Fausing, Bent

    with fundamental human values like intuition, vision and sensing; all the qualities the technology, the industrialisation and rationalisation, or in short modernity, has been criticized for having taken away from human existence. What technology has taken away now comes back through new technology as an aid...

  3. Manage "Human Capital" Strategically

    Science.gov (United States)

    Odden, Allan

    2011-01-01

    To strategically manage human capital in education means restructuring the entire human resource system so that schools not only recruit and retain smart and capable individuals, but also manage them in ways that support the strategic directions of the organization. These management practices must be aligned with a district's education improvement…

  4. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  5. Human Rights Guaranteed

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Report says China’s human rights plan successfully implemented According to a detailed assessment report published by China’s State Council Information Office (SCIO),all the measures outlined in the National Human Rights Action Plan of China (2009-10) had been successfully put into place by the end of 2010.

  6. Defects in Human Nature

    Institute of Scientific and Technical Information of China (English)

    黄靓

    2008-01-01

    By tracing the defects of society back to the defects of human nature, humanity's essence is proved to be inherent evil. Man's natural tendency to do evil remain harnessed through the controls and conventions imposed by civilization, however, when rules or civilization are weakened, man' s dark side is unleashed.

  7. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  8. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues its first white paper on human resources The Chinese Government issued a white paper on its human resources on September 10, highlighting the country’s policies to cope with employment pressures and a lack of "high-level innovative talents.

  9. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    2008-01-01

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a Colo

  10. Humanism within Globalization

    Science.gov (United States)

    Weber, Jennifer E.

    2014-01-01

    The complexity of adult learning connects it to almost all other facets of human endeavor. Consequently, the future of adult education depends, to a large extent on who participates and the quality of such participation. Quality participation, when teamed with environments committed to a concern for humanity, launches opportunities for varied…

  11. Damping Effect of Humans

    DEFF Research Database (Denmark)

    Pedersen, Lars

    Passive humans (sitting or standing) might well be present on flooring-systems, footbridges or other structures that carry humans. An active croud of people might generate structural vibrations, and these might be problematic. The passive crowd of people, however, will interact with the structural...

  12. Human Mind Maps

    Science.gov (United States)

    Glass, Tom

    2016-01-01

    When students generate mind maps, or concept maps, the maps are usually on paper, computer screens, or a blackboard. Human Mind Maps require few resources and little preparation. The main requirements are space where students can move around and a little creativity and imagination. Mind maps can be used for a variety of purposes, and Human Mind…

  13. Translating the human microbiome

    NARCIS (Netherlands)

    Brown, J.; Vos, de W.M.; Distefano, P.S.; Doré, J.; Huttenhower, C.; Knight, R.; Lawley, T.D.; Raes, J.; Turnbaugh, P.

    2013-01-01

    Over the past decade, an explosion of descriptive analyses from initiatives, such as the Human Microbiome Project (HMP) and the MetaHIT project, have begun to delineate the human microbiome. Inhabitants of the intestinal tract, nasal passages, oral cavities, skin, gastrointestinal tract and urogenit

  14. Human Resource Construction

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Centering on strategic objective of reform and development,CIAE formulated its objectives in human resource construction for the 13th Five-year Plan period,and achieved new apparent progress in human resource construction in 2015.1 Implementation of"LONGMA Project"

  15. Modeling human color categorization

    NARCIS (Netherlands)

    van den Broek, Egon; Schouten, Th.E.; Kisters, P.M.F.

    A unique color space segmentation method is introduced. It is founded on features of human cognition, where 11 color categories are used in processing color. In two experiments, human subjects were asked to categorize color stimuli into these 11 color categories, which resulted in markers for a

  16. Human Rights Improving

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    China issues a white paper on its human rights,highlighting freedom of speech on the Interne The Chinese Government released a white paper on its human rights in 2009 on September 26,highlighting the role of Internet freedom and the country’s efforts in safeguarding citizens’legitimate civil and political rights.

  17. Human Rights, History of

    NARCIS (Netherlands)

    de Baets, Antoon; Wright, James

    2015-01-01

    In this article, six basic debates about human rights are clarified from a historical perspective: the origin of human rights as moral rights connected to the natural law doctrine and opposed to positive rights; the wave of criticism of their abstract and absolute character by nineteenth-century lib

  18. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... a shared interdisciplinary research and educational collaboration. As a creative research initiative it focuses on change and innovative thinking. The innovativeness is a result of the strongly interdisciplinary perspective which is at the heart of Designing Human Technologies. Designing Human Technologies...

  19. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...... der mellem Human Relations (Hawthorne-eksperimenter ne) og Neo-Human Relations (behovsteorierne), men i denne fremstilling bruges Human Relations som en samlebetegnelse for begge disse – noget forskellige – forskningstraditioner. De har i dag opnået stor udbredelse og er praktisk talt obligatorisk...

  20. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthritis.

    Science.gov (United States)

    van den Bosch, Martijn H; Blom, Arjen B; van de Loo, Fons A; Koenders, Marije I; Lafeber, Floris P; van den Berg, Wim B; van der Kraan, Peter M; van Lent, Peter L

    2017-07-05

    Increased Wnt signaling in chondrocytes is associated with development of osteoarthritis (OA). However, OA is considered a disease of the entire joint, where the synovium has been attributed an important role in disease pathogenesis and progression. This study was undertaken to determine whether Wnt signaling in synovial tissue could contribute to pathologic development of OA through the production of matrix metalloproteinases (MMPs), and to assess the relationship of synovial expression of Frizzled (FZD) receptors and the Wnt inhibitor FRZB to MMP expression and disease progression in patients with early OA in the Dutch Cohort Hip and Cohort Knee (CHECK) study cohort. In mouse knee joints, human WNT8A and mouse Wnt16 were overexpressed using adenoviral vectors, and expression of messenger RNA (mRNA) for MMPs in the synovium was determined by reverse transcription-polymerase chain reaction or Luminex assay. In human synovial tissue from a subgroup of patients with early OA with knee pain enrolled in the CHECK cohort, levels of Wnt family members were assessed for linkage to MMP expression and disease progression. In addition, MMP production in human synovium from patients with end-stage OA was determined after stimulation of Wnt signaling with WNT3A or inhibition with FRZB or DKK1 in the synovium. Overexpression of WNT8A and Wnt16 in mouse knee joints induced MMP expression in vivo. Expression of MMPs relevant to human OA in the synovium from CHECK study participants significantly correlated with expression of FZD1, FZD10, and FRZB mRNA. Moreover, increased FZD1 mRNA expression and decreased FRZB mRNA expression were observed in CHECK study patients who experienced disease progression compared to those who were nonprogressors. Stimulation of human OA synovium with WNT3A induced the production of various MMPs, whereas inhibition of Wnt signaling with FRZB or DKK1 reduced the production of MMPs. Wnt signaling in the synovium may potently induce progression of OA via

  1. Human to Human Transmission of Brucella Melitensis

    Directory of Open Access Journals (Sweden)

    Patrice Vigeant

    1995-01-01

    Full Text Available Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely mode of transmission in this case.

  2. Human to Human Transmission of Brucella Melitensis

    OpenAIRE

    Patrice Vigeant; Jack Mendelson; Miller, Mark A.

    1995-01-01

    Human brucellosis is acquired mainly through contact with infected animal tissues, ingestion of unpasteurized dairy products or infected aerosols. Person to person transmission is still considered uncertain. The case of a woman diagnosed with proven brucellosis after her husband suffered a relapse of bacteremia with Brucella melitensis biotype 3, which was originally acquired abroad by eating goat cheese, is described. It was postulated that person to person spread of brucellosis is a likely ...

  3. Archaea on human skin.

    Directory of Open Access Journals (Sweden)

    Alexander J Probst

    Full Text Available The recent era of exploring the human microbiome has provided valuable information on microbial inhabitants, beneficials and pathogens. Screening efforts based on DNA sequencing identified thousands of bacterial lineages associated with human skin but provided only incomplete and crude information on Archaea. Here, we report for the first time the quantification and visualization of Archaea from human skin. Based on 16 S rRNA gene copies Archaea comprised up to 4.2% of the prokaryotic skin microbiome. Most of the gene signatures analyzed belonged to the Thaumarchaeota, a group of Archaea we also found in hospitals and clean room facilities. The metabolic potential for ammonia oxidation of the skin-associated Archaea was supported by the successful detection of thaumarchaeal amoA genes in human skin samples. However, the activity and possible interaction with human epithelial cells of these associated Archaea remains an open question. Nevertheless, in this study we provide evidence that Archaea are part of the human skin microbiome and discuss their potential for ammonia turnover on human skin.

  4. Human Power Empirically Explored

    Energy Technology Data Exchange (ETDEWEB)

    Jansen, A.J.

    2011-01-18

    Harvesting energy from the users' muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are convenient and can be environmentally and economically beneficial. This work provides insight into the knowledge required to design human-powered energy systems in consumer products from a scientific perspective. It shows the developments of human-powered products from the first introduction of the BayGen Freeplay radio in 1995 till current products and provides an overview and analysis of 211 human-powered products currently on the market. Although human power is generally perceived as beneficial for the environment, this thesis shows that achieving environmental benefit is only feasible when the environmental impact of additional materials in the energy conversion system is well balanced with the energy demands of the products functionality. User testing with existing products showed a preference for speeds in the range of 70 to 190 rpm for crank lengths from 32 to 95 mm. The muscular input power varied from 5 to 21 W. The analysis of twenty graduation projects from the Faculty of Industrial Design Engineering in the field of human-powered products, offers an interesting set of additional practice based design recommendations. The knowledge based approach of human power is very powerful to support the design of human-powered products. There is substantial potential for improvements in the domains energy conversion, ergonomics and environment. This makes that human power, when applied properly, is environmentally and economically competitive over a wider range of applications than thought previously.

  5. Human pancreas development.

    Science.gov (United States)

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  6. Enhancing human capacities

    CERN Document Server

    Savulescu, Julian; Kahane, Guy

    2011-01-01

    Enhancing Human Capacities is the first to review the very latest scientific developments in human enhancement. It is unique in its examination of the ethical and policy implications of these technologies from a broad range of perspectives. Presents a rich range of perspectives on enhancement from world leading ethicists and scientists from Europe and North America The most comprehensive volume yet on the science and ethics of human enhancement Unique in providing a detailed overview of current and expected scientific advances in this area Discusses both general conceptual and ethical issues

  7. Aluminium in human sweat.

    Science.gov (United States)

    Minshall, Clare; Nadal, Jodie; Exley, Christopher

    2014-01-01

    It is of burgeoning importance that the human body burden of aluminium is understood and is measured. There are surprisingly few data to describe human excretion of systemic aluminium and almost no reliable data which relate to aluminium in sweat. We have measured the aluminium content of sweat in 20 healthy volunteers following mild exercise. The concentration of aluminium ranged from 329 to 5329μg/L. These data equate to a daily excretion of between 234 and 7192μg aluminium and they strongly suggest that perspiration is the major route of excretion of systemic aluminium in humans. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Human exposure to aluminium.

    Science.gov (United States)

    Exley, Christopher

    2013-10-01

    Human activities have circumvented the efficient geochemical cycling of aluminium within the lithosphere and therewith opened a door, which was previously only ajar, onto the biotic cycle to instigate and promote the accumulation of aluminium in biota and especially humans. Neither these relatively recent activities nor the entry of aluminium into the living cycle are showing any signs of abating and it is thus now imperative that we understand as fully as possible how humans are exposed to aluminium and the future consequences of a burgeoning exposure and body burden. The aluminium age is upon us and there is now an urgent need to understand how to live safely and effectively with aluminium.

  9. Human dignity and bioethics

    Directory of Open Access Journals (Sweden)

    Marjanović Miloš

    2013-01-01

    Full Text Available By opening the field of bioethics followed a new wave of intense debate on the theological, philosophical and legal significance of the concept of human dignity . Exactly ten years ago (December 2003 American bioethicist Ruth Maclin has proposed to divest ourselves of the concept of human dignity because it is vague, useless and redundant and that, without any loss, we can replace it by the ethical principle of personal autonomy. Her article was followed by harsh reactions and opposite views. What is this term in so broad, almost inflationary and opposite use is not a reason to deprive him, but, on the contrary, it shows how important it is and that it should be determined at least outline. As universal values and general concept, the human dignity has no pre-defined and narrow, precise meaning. It is more an evaluation horizon, the guiding principle and regulatory ideas that must constantly define and codify by many guaranted human rights and fundamental freedoms. As generic notion of each reasonable law, it is their foundation and a common denominator, legitimising basis of natural but also of positive law. As intrinsic and static value which means the humaneness, the humanity it is absolute, inherent to every human being without distinction and conditioning, as a unique and unrepeatable creation. In this meaning, the dignity is the obligation and limitation of the state, society and each of us. As an ethical and dynamic category, it is not given to us, but it is assign to us, and it is not in us, but always before us, as a guide of our actions in accordance with virtues, to treat ourselves, each other and the nature in a human way. The century in which we live is named the century of molecular biology and genetic engineering because of the enormous potential but also risks to human dignity. Because of that human dignity has become a central principle in all international documents relating to the human genome, genetics and bioethics, adopted

  10. Human Genome Project

    Energy Technology Data Exchange (ETDEWEB)

    Block, S. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Cornwall, J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dally, W. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Dyson, F. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Fortson, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Joyce, G. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Kimble, H. J. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Lewis, N. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Max, C. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Prince, T. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Schwitters, R. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Weinberger, P. [The MITRE Corporation, McLean, VA (US). JASON Program Office; Woodin, W. H. [The MITRE Corporation, McLean, VA (US). JASON Program Office

    1998-01-04

    The study reviews Department of Energy supported aspects of the United States Human Genome Project, the joint National Institutes of Health/Department of Energy program to characterize all human genetic material, to discover the set of human genes, and to render them accessible for further biological study. The study concentrates on issues of technology, quality assurance/control, and informatics relevant to current effort on the genome project and needs beyond it. Recommendations are presented on areas of the genome program that are of particular interest to and supported by the Department of Energy.

  11. Human Capital Tracking Tool -

    Data.gov (United States)

    Department of Transportation — AVS is now required to collect, track, and report on data from the following Flight, Business and Workforce Plan. The Human Resource Management’s Performance Target...

  12. Human Research Program

    Data.gov (United States)

    National Aeronautics and Space Administration — Strategically, the HRP conducts research and technology development that: 1) enables the development or modification of Agency-level human health and performance...

  13. Human Papillomavirus (HPV)

    Science.gov (United States)

    ... Español Text Size Email Print Share Human Papillomavirus (HPV) Page Content Article Body According to the Centers ... and how to prevent it. How to Prevent HPV: There are 3 types of HPV vaccine: Cervarix , ...

  14. Human Reliability Program Overview

    Energy Technology Data Exchange (ETDEWEB)

    Bodin, Michael

    2012-09-25

    This presentation covers the high points of the Human Reliability Program, including certification/decertification, critical positions, due process, organizational structure, program components, personnel security, an overview of the US DOE reliability program, retirees and academia, and security program integration.

  15. Human Emotion Recognition System

    Directory of Open Access Journals (Sweden)

    Dilbag Singh

    2012-08-01

    Full Text Available This paper discusses the application of feature extraction of facial expressions with combination of neural network for the recognition of different facial emotions (happy, sad, angry, fear, surprised, neutral etc... Humans are capable of producing thousands of facial actions during communication that vary in complexity, intensity, and meaning. This paper analyses the limitations with existing system Emotion recognition using brain activity. In this paper by using an existing simulator I have achieved 97 percent accurate results and it is easy and simplest way than Emotion recognition using brain activity system. Purposed system depends upon human face as we know face also reflects the human brain activities or emotions. In this paper neural network has been used for better results. In the end of paper comparisons of existing Human Emotion Recognition System has been made with new one.

  16. Humanism vs. Behaviorism

    Science.gov (United States)

    Hunter, Madeline

    1977-01-01

    Author argues that humanism and behaviorism are not necessarily exclusive of one another, and that principles of behaviorism, when thoughtfully applied, can lead to the achievement of humanistic goals. (RW)

  17. Bridging Humanism and Behaviorism.

    Science.gov (United States)

    Chu, Lily

    1980-01-01

    Humanistic behaviorism may provide the necessary bridge between behaviorism and humanism. Perhaps the most humanistic approach to teaching is to learn how certain changes will help students and how these changes can be accomplished. (Author/MLF)

  18. BIOETHICS AND HUMAN CLONING

    Directory of Open Access Journals (Sweden)

    Željko Kaluđerović

    2011-12-01

    Full Text Available In this paper the authors analyze the process of negotiating and beginning of the United Nations Declaration on Human Cloning as well as the paragraphs of the very Declaration. The negotiation was originally conceived as a clear bioethical debate that should have led to a general agreement to ban human cloning. However, more often it had been discussed about human rights, cultural, civil and religious differences between people and about priorities in case of eventual conflicts between different value systems. In the end, a non-binding Declaration on Human Cloning had been adopted, full of numerous compromises and ambiguous formulations, that relativized the original intention of proposer states. According to authors, it would have been better if bioethical discussion and eventual regulations on cloning mentioned in the following text had been left over to certain professional bodies, and only after the public had been fully informed about it should relevant supranational organizations have taken that into consideration.

  19. Human Resource Planning

    Science.gov (United States)

    Hoffman, W. H.; Wyatt, L. L.

    1977-01-01

    By using the total resource approach, we have focused attention on the need to integrate human resource planning with other business plans and highlighted the importance of a productivity strategy. (Author)

  20. Viruses and human cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gallo, R.C.; Haseltine, W.; Klein, G.; Zur Hausen, H.

    1987-01-01

    This book contains papers on the following topics: Immunology and Epidemiology, Biology and Pathogenesis, Models of Pathogenesis and Treatment, Simian and Bovine Retroviruses, Human Papilloma Viruses, EBV and Herpesvirus, and Hepatitis B Virus.

  1. CHINESE OF HUMANITY

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Humanism Education in Language Class,Innovative model university English teaching,Analysis on Information Literacy of College English Teachers Based On Net Environment,Cultural Differences between E-C Idioms and Teaching of English Idioms

  2. Human Factors Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  3. Will Technology Humanize Us?

    Science.gov (United States)

    Snider, Robert C.

    1972-01-01

    The author considers the question of whether technology will cause humanization or dehumanization in the schools. He concludes that we can not stop tecchnology; we can only give it direction and purpose. (Author/MS)

  4. Report Details Human Resources

    Institute of Scientific and Technical Information of China (English)

    YIN PUMIN

    2010-01-01

    @@ The Chinese Government issued a white paper on its human resources on September I0, highlighting the coun-try's policies to cope with employ-ment pressures and a lack of "high-level innovative talents."

  5. Statement on Human Cloning

    Science.gov (United States)

    ... ban on efforts to implant a human cloned embryo for the purpose of reproduction. The scientific evidence ... stem cell research, including the use of nuclear transplantation techniques (also known as research or therapeutic cloning), ...

  6. Science and Humanism

    Science.gov (United States)

    Auger, Pierre

    1971-01-01

    Science and humanism are separated so completely as to bring about the creation of two cultures quite distinct from each other within contemporary civilization. Pragmatic, rational attitudes are needed on both sides to bring them together. (DF)

  7. Human Assisted Assembly Processes

    Energy Technology Data Exchange (ETDEWEB)

    CALTON,TERRI L.; PETERS,RALPH R.

    2000-01-01

    Automatic assembly sequencing and visualization tools are valuable in determining the best assembly sequences, but without Human Factors and Figure Models (HFFMs) it is difficult to evaluate or visualize human interaction. In industry, accelerating technological advances and shorter market windows have forced companies to turn to an agile manufacturing paradigm. This trend has promoted computerized automation of product design and manufacturing processes, such as automated assembly planning. However, all automated assembly planning software tools assume that the individual components fly into their assembled configuration and generate what appear to be a perfectly valid operations, but in reality the operations cannot physically be carried out by a human. Similarly, human figure modeling algorithms may indicate that assembly operations are not feasible and consequently force design modifications; however, if they had the capability to quickly generate alternative assembly sequences, they might have identified a feasible solution. To solve this problem HFFMs must be integrated with automated assembly planning to allow engineers to verify that assembly operations are possible and to see ways to make the designs even better. Factories will very likely put humans and robots together in cooperative environments to meet the demands for customized products, for purposes including robotic and automated assembly. For robots to work harmoniously within an integrated environment with humans the robots must have cooperative operational skills. For example, in a human only environment, humans may tolerate collisions with one another if they did not cause much pain. This level of tolerance may or may not apply to robot-human environments. Humans expect that robots will be able to operate and navigate in their environments without collisions or interference. The ability to accomplish this is linked to the sensing capabilities available. Current work in the field of cooperative

  8. [Demography and human ecology].

    Science.gov (United States)

    Nazareth, J M

    1993-01-01

    At the end of the 19th century the German biologist Ernest Haekel was the first scientist to use the term ecology, which was defined as the study of relationships of organisms or groups of organisms with the environment and indicated the interdependence of the living world, including plants, animals, and humans. This concept also indicates a continuous process of adaptation of organisms to their external environment. The basic concepts of scientific ecology, which developed at the end of the 19th century, can be attributed to Darwin: the relationships between living beings and the notion of the process of adaptation to their environment. The term human ecology appeared in the early 1920s. Human ecology embodies fundamental ideas: biotype, habitat, community, biocenosis, ecosystem, biomass, interchange and equilibrium, and circulation of energy. The accumulated knowledge about human ecology is broken down using the criteria of topography (ecology of humid forests, deserts, lakes, etc.); followed by the appearance of species; and the variants of classical division: auto ecology (influence of external factors on living beings) and sinecology (the study of groups of associated organisms, i.e., natural, animal, and vegetation communities). The species are considered on the basis of equality or sinecology (all of them have the same interests), while in human ecology a species is determined by its relation to a reference group--autoecology or anthropocentric ecology. In 1911, J. Thompson bridged the gap between biological knowledge and social sciences; in 1921, H. Barrows identified human ecology as a component of geography; in 1925, L. Bernard presented the classification of ecosystems; and in 1936, Ezra Park published his work, Human Ecology, followed in 1945 by the emergence of the Chicago school. Demography and human ecology are intimately connected because population is the result of natural and migratory movements, therefore the two sciences require a methodology

  9. Human Resources Accounting

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    The 21 st century will be the epoch of knowled ge economy. Knowledge economy is to develop economy on the basis of knowledge will surely become the major resources of economy development. Therefore, human resources accounting which provides such information as the ebb and follow of hu man resources investment, the size of the human resources employment, will bec ome the main stream of accounting the time of knowledge economy. To face China 's reality, to develop economy, and to flourish enterprise...

  10. Human motricity and health

    Directory of Open Access Journals (Sweden)

    Manuel Sérgio Vieira e Cunha

    2008-06-01

    Full Text Available If human motricity science intends to study motor conduct (or actions in which the human being pursues transcendence (or surmounting, it inevitably relates to the large realm of health. What are the aspects it evinces? Transdisciplinarity, solidarity among the various knowledge types (including poetical, complexity, (where the physical is integrated but surmounted and the firm belief that to be healthy is to have in ourselves, alive and working, the capacity for surmounting anything.

  11. Human Happiness Is Sensuous

    Institute of Scientific and Technical Information of China (English)

    吕静

    2003-01-01

    All human happiness is biological happiness. That is strictly scientific. At the risk of being misunderstood. I must make it clearer: all human happiness is sensuous happiness. The spiritualists will misunderstand me. I am sure; the spiritualists and materialists must forever misunderstand each other, because they don’t talk the same language, or mean by the same word different things. Are we, too, in this problem

  12. Evolution and human sexuality.

    Science.gov (United States)

    Gray, Peter B

    2013-12-01

    The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory.

  13. Meeting human needs

    Science.gov (United States)

    Nicogossian, Arnauld E.

    1992-01-01

    The degree of autonomy of future long duration manned missions will emphasize interactions between human operators and automated systems aimed at the most effective allocations of tasks between humans and machines. Knowledge of crewmembers' physical status, encompassing both capabilities and limitations, will also be critical during EVA and planetary roving missions; psychological evaluation and support, with a view to both individual health and group cohesion and productivity, may become a critical consideration. Attention is here given to crewmembers' medical and psychological vulnerabilities.

  14. Human bites - self-care

    Science.gov (United States)

    Bites - human - self-care ... Human bites can occur in 2 ways: If someone bites you If your hand comes into contact ... bite to express anger or other negative feelings. Human bites may be more dangerous than animal bites. ...

  15. Testing for Human Immunodeficiency Virus

    Science.gov (United States)

    ... education Fact Sheet PFS005: Testing for Human Immunodeficiency Virus AUGUST 2015 • Reasons for Getting Tested • Who Should ... For More Information • Glossary Testing for Human Immunodeficiency Virus Human immunodeficiency virus (HIV) is the virus that ...

  16. A WORLD BEYOND HUMAN

    Directory of Open Access Journals (Sweden)

    David Abram

    2013-12-01

    Full Text Available From an initial project to investigate the relationship between magic and traditional medicine as practiced by shamans in Southern rural Asia, the focus of attention gradually shifted to an awareness of the negotiation traditional medicine people or shamans exert between the human community and the larger community of beings. This attentiveness to a more-than-human world does not occur at a supernatural domain above nature or inside her personal self but is the result of the shaman’s special ability to project her consciousness horizontally to other forms of sensibility with which human existence is interwoven. The ecological function of the shaman is to maintain a constant balance between what is taken and what is given from the human community to the larger community. The spirits of indigenous cultures are not defined in opposition to materiality but are essentially those modes of intelligence or awareness that do not possess a human form. By exploring different landscapes, and the sensibility living in them, a new sensitivity is awoken that allows for communication with those intelligences. However, the drowning of these other voices in Western culture, which reduces otherness to an object, creates an uneasiness that is hardly perceived except as an inability to interact with anything more-than-human and its dire consequences in the form of “civilization’s” destructive behavior.

  17. Genomics of human longevity.

    Science.gov (United States)

    Slagboom, P E; Beekman, M; Passtoors, W M; Deelen, J; Vaarhorst, A A M; Boer, J M; van den Akker, E B; van Heemst, D; de Craen, A J M; Maier, A B; Rozing, M; Mooijaart, S P; Heijmans, B T; Westendorp, R G J

    2011-01-12

    In animal models, single-gene mutations in genes involved in insulin/IGF and target of rapamycin signalling pathways extend lifespan to a considerable extent. The genetic, genomic and epigenetic influences on human longevity are expected to be much more complex. Strikingly however, beneficial metabolic and cellular features of long-lived families resemble those in animals for whom the lifespan is extended by applying genetic manipulation and, especially, dietary restriction. Candidate gene studies in humans support the notion that human orthologues from longevity genes identified in lower species do contribute to longevity but that the influence of the genetic variants involved is small. Here we discuss how an integration of novel study designs, labour-intensive biobanking, deep phenotyping and genomic research may provide insights into the mechanisms that drive human longevity and healthy ageing, beyond the associations usually provided by molecular and genetic epidemiology. Although prospective studies of humans from the cradle to the grave have never been performed, it is feasible to extract life histories from different cohorts jointly covering the molecular changes that occur with age from early development all the way up to the age at death. By the integration of research in different study cohorts, and with research in animal models, biological research into human longevity is thus making considerable progress.

  18. Human Milk Fortification.

    Science.gov (United States)

    Simmer, Karen

    2015-01-01

    Human milk is the feed of choice for preterm infants. However, human milk does not provide enough nutrition, especially protein, for preterm infants to achieve target growth rates similar to those in utero (15-20 g/kg per day). Fortifiers for human milk, manufactured from bovine milk, are commercially available and routinely used for patients born milk fortifier that is manufactured from donor human milk is available in some developed countries and may confer some clinical benefits, including a reduction in necrotizing enterocolitis. Fortification can be added in a standardized protocol as per manufacturers' instructions. Human milk composition can be analyzed and fortification individualized to take into account the large variation from mother to mother. Alternatively, fortification can be increased in a stepwise manner based on assumed composition while monitoring blood urea levels for safety. The current aim is to prevent preterm infants dropping percentiles and falling below the 10th percentile at 36 weeks' corrected gestational age or discharge home. More data are required on how best to fortify human milk for preterm infants to achieve optimal growth, development and health outcomes in the long term. There is an urgent need for well-designed and informed randomized clinical trials in this vulnerable preterm population.

  19. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  20. Time Trend Investigation of PCBs, PBDEs, and Organochlorine Pesticides in Selected n-3 Polyunsaturated Fatty Acid Rich Dietary Fish Oil and Vegetable Oil Supplements; Nutritional Relevance for Human Essential n-3 Fatty Acid Requirements

    OpenAIRE

    Jacobs, M.N.; Covaci, A; Gheorghe, A; Schepens, P

    2004-01-01

    In addition to being used in the food and animal feed industry, fish oils have also been used traditionallyas dietary supplements. Due to the presence of long-chain n-3 fatty acids, fish oils have therapeuticbenefits in the prevention and treatment of cardiovascular, immunological, and arthritic diseases, aswell as childhood deficiency diseases such as rickets, because of a high content of vitamin D. However,fish oils are also susceptible to contamination with lipophilic organic chemicals tha...

  1. [Antinociceptive effects of the combination metamizol + morphine in rats with intense pain (arthritic gout-type pain produced with AU)].

    Science.gov (United States)

    Godínez-Chaparro, Beatriz; Guevara-López, Uriah; de la O-Arciniega, Minarda; Cortés-Arroyo, Alma Rosa; López-Muñoz, Francisco Javier

    2007-01-01

    The antinociceptive effects of metamizol and morphine administered either separately or in combination were determined in the "Pain-Induced Functional Impairment Model in the Rat" (PIFIR antinociceptive model). Intense nociception (or intense pain) was induced by the intra-articular injection of uric acid (50%) in the right hind limb inducing its dysfunction. Animals then received analgesic agents, and the recovery of functionality over time was assessed as an expression of antinociception. Metamizol (177.8 mg/kg s.c.) or morphine (3.2 mg/kg s.c.) separately resulted in a lower antinociceptive effect (22.1+/-5.4 area units [au] and 31.8+/-9.4 au, respectively). Moreover, the combination of metamizol (177.8 mg/kg) with morphine (3.2 mg/kg) resulted in a potentiation (293.7+/-16.6 au). The antinociceptive effect observed using the combination was significantly greater than expected on the basis of addition of the individual effects. The percent change in antinociceptive effects, using the combination, was 444.9%. This represents the first study to show that metamizol + morphine can produce potentiation of their antinociceptive effects in intense pain.

  2. Pharmacokinetics and pharmacodynamics of metamizol in co-administration with morphine under acute and chronic treatments in arthritic rats.

    Science.gov (United States)

    Carrillo-Calzadilla, Patricia Esmeralda; López-Muñoz, Francisco Javier; Moreno-Rocha, Luis Alfonso; Medina-López, José Raúl; Cortés-Arroyo, Alma Rosa; Domínguez-Ramírez, Adriana Miriam

    2017-06-01

    To investigate the relationship between metamizol pharmacokinetics and the antinociceptive effect produced after subcutaneous administration of metamizol (177.8 mg/kg) alone or in combination with morphine (3.2 mg/kg), under acute and chronic treatments. Antinociception was assessed using the pain-induced functional impairment model in rat (PIFIR). Serial blood samples were collected from the same animals to study the pharmacokinetics of metamizol. The co-administration of the drugs in single dose, confirmed the potentiation of their individual antinociceptive effects. When the drugs were administered alone following the chronic schedule, a pronounced tolerance development to their antinociceptive effects was found, whereas it was significantly attenuated when they were administered together. Metamizol pharmacokinetics was unaltered by the presence of morphine. Plasma concentrations of 4-methylaminoantipyrine, an active metabolite markedly decreased under chronic administration. The mechanism involved in the potentiation of the antinociceptive effect produced by the combination, cannot be explained by the interaction of morphine on metamizol pharmacokinetics. Other pharmacokinetic interactions along with known pharmacodynamic interactions in which metamizol active metabolites contribute, should be considered. The frequency of administration enhances tolerance development and induces metamizol elimination process. © 2017 Royal Pharmaceutical Society.

  3. Resistive Exercise for Arthritic Cartilage Health (REACH: A randomized double-blind, sham-exercise controlled trial

    Directory of Open Access Journals (Sweden)

    Smith Richard M

    2009-01-01

    Full Text Available Abstract Background This article provides the rationale and methodology, of the first randomised controlled trial to our knowledge designed to assess the efficacy of progressive resistance training on cartilage morphology in women with knee osteoarthritis. Development and progression of osteoarthritis is multifactorial, with obesity, quadriceps weakness, joint malalignment, and abnormal mechanical joint forces particularly relevant to this study. Progressive resistance training has been reported to improve pain and disability in osteoarthritic cohorts. However, the disease-modifying potential of progressive resistance training for the articular cartilage degeneration characteristic of osteoarthritis is unknown. Our aim was to investigate the effect of high intensity progressive resistance training on articular cartilage degeneration in women with knee osteoarthritis. Methods Our cohort consisted of women over 40 years of age with primary knee osteoarthritis, according to the American College of Rheumatology clinical criteria. Primary outcome was blinded measurement of cartilage morphology via magnetic resonance imaging scan of the tibiofemoral joint. Secondary outcomes included walking endurance, balance, muscle strength, endurance, power, and velocity, body composition, pain, disability, depressive symptoms, and quality of life. Participants were randomized into a supervised progressive resistance training or sham-exercise group. The progressive resistance training group trained muscles around the hip and knee at 80% of their peak strength and progressed 3% per session, 3 days per week for 6 months. The sham-exercise group completed all exercises except hip adduction, but without added resistance or progression. Outcomes were repeated at 3 and 6 months, except for the magnetic resonance imaging scan, which was only repeated at 6 months. Discussion Our results will provide an evaluation of the disease-modifying potential of progressive resistance training for osteoarthritis. Trial Registration ANZCTR Reference No. 12605000116628

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

    Energy Technology Data Exchange (ETDEWEB)

    Darwish, Hebatallah A. [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg [Department of Biochemistry, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt); Abdelsalam, Rania M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562 (Egypt)

    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. • They upregulated StAR expression and testosterone with restoration of LH and FSH. • They abrogated myeloperoxidase, TNF-α and COX-2 and iNOS expression. • They suppressed oxidative stress and FasL-associated apoptosis.

  5. Role of pain catastrophizing during pain processing in a cohort of patients with chronic and severe arthritic knee pain.

    Science.gov (United States)

    Wade, James B; Riddle, Daniel L; Price, Donald D; Dumenci, Levent

    2011-02-01

    We examined the relationship between catastrophizing and a 3-stage model of pain processing, consisting of pain sensation intensity (stage 1), pain unpleasantness (stage 2), and suffering (stage 3). We studied 310 patients with chronic and severe osteoarthritic knee pain (68.7% female) using 4 competing structural equation models. A strong relationship was found between the suffering construct and its indicators. Of the 4 theoretically plausible models, we found a model with 3 specific pathways of pain sensation leading to the final stage of pain-related suffering. A unique contribution of this study is the integration of catastrophizing into the 3 pain stages. In this model, catastrophizing mediates the relationship between pain-related unpleasantness and suffering, as well as the relationship between sensation and suffering through unpleasantness. Psychological intervention targeting catastrophizing could provide reduction of pain-related suffering that adds to the benefits of therapies directed toward the primary sensory and immediate unpleasant dimensions of pain. These results emphasize the benefit of integrating knowledge of the psychological and neural mechanisms of pain. Catastrophizing makes a unique contribution to suffering apart from the contribution of immediate unpleasantness. The study results emphasize the benefit of integrating knowledge of the psychological and neural mechanisms of pain, and the importance of psychological intervention targeting catastrophizing to reduce pain-related suffering.

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

    Science.gov (United States)

    Narendhirakannan, R T; Limmy, T P

    2012-04-01

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

  7. Therapeutic effect of Linum usitatissimum (flaxseed/linseed) fixed oil on acute and chronic arthritic models in albino rats.

    Science.gov (United States)

    Kaithwas, Gaurav; Majumdar, Dipak K

    2010-06-01

    The present study was undertaken to assess the activity/anti-inflammatory potential of Linum usitatissimum fixed oil against castor oil-induced diarrhoea, turpentine oil-induced joint oedema, formaldehyde and Complete Freund's Adjuvant (CFA)-induced arthritis in Wistar albino rats. The oil intraperitoneally, significantly inhibited the castor oil-induced diarrhoea and turpentine oil-induced exudative joint oedema in a dose-dependent manner. Significant inhibitory effect of L. usitatissimum fixed oil was observed in formaldehyde-induced proliferative global oedematous arthritis when given intraperitoneally, with significant checking of the serum glutamic oxaloacetic acid transaminase and serum glutamic pyruvic acid transaminase. Further, L. usitatissimum fixed oil showed a significant dose-dependent protective effect against CFA-induced arthritis as well. Secondary lesions produced by CFA due to a delayed hypersensitivity reaction were also reduced in a significant manner. Anti-inflammatory activity of L. usitatissimum fixed oil can be attributed to the presence of alpha linolenic acid (57.38%, an omega-3 fatty acid, 18:3, n-3) having dual inhibitory effect on arachidonate metabolism resulting in suppressed production of proinflammatory n-6 eicosanoids (PGE(2), LTB(4)) and diminished vascular permeability. These observations suggest possible therapeutic potential of L. usitatissimum fixed oil in inflammatory disorders like rheumatoid arthritis.

  8. In Vivo Molecular Imaging of Cathepsin and Matrix Metalloproteinase Activity Discriminates between Arthritic and Osteoarthritic Processes in Mice

    Directory of Open Access Journals (Sweden)

    Eline A. Vermeij

    2014-01-01

    Full Text Available Rheumatoid arthritis (RA and osteoarthritis (OA are serologically and clinically distinctive, but at the local level, both diseases have many molecular pathways in common. In vivo molecular imaging can unravel the local pathologic processes involved in both diseases. In this study, we investigated matrix metalloproteinase (MMP and cathepsin activity during cartilage destruction, in an RA and an OA mouse model, using biophotonic imaging of substrate-based probes. Mice with collagen-induced arthritis (CIA or destabilization of the medial meniscus (DMM were imaged using near-infrared fluorescent probes, activated by several cathepsins or MMPs. Fluorescence signal intensity was compared to synovial gene expression, histology, and cartilage staining of a neoepitope of aggrecan cleaved by MMPs with the amino acids DIPEN. Increased cathepsin and MMP activity was seen during CIA, whereas the DMM model only showed increased MMP activity. DIPEN expression was seen only during CIA. A possible explanation can be differences in gene expressions; MMP3 and -13, known to produce DIPEN neoepitopes, were upregulated in the CIA model, whereas MMP12, known to be involved in elastin degradation and chemokine inhibition, was upregulated in the DMM model. Thus, molecular imaging showed no cathepsin activity at the time of cartilage damage in the DMM model, whereas both cathepsins and MMPs are active in the CIA model during disease progression.

  9. Force transmission through the juvenile idiopathic arthritic wrist : a novel approach using a sliding rigid body spring model

    NARCIS (Netherlands)

    Manal, K; Lua, XP; Nieuwenhuis, MK; Helders, PJM; Buchanan, TS

    2002-01-01

    Force transmission across the wrist during a grasping maneuver of the hand was simulated for three children with juvenile idiopathic arthritis (JIA) and for one healthy age-matched child. Joint reaction forces were estimated using a series of springs between articulating bones. This method (i.e., ri

  10. Discovering Green, Aqueous Suzuki Coupling Reactions: Synthesis of Ethyl (4-Phenylphenyl)Acetate, a Biaryl with Anti-Arthritic Potential

    Science.gov (United States)

    Costa, Nancy E.; Pelotte, Andrea L.; Simard, Joseph M.; Syvinski, Christopher A.; Deveau, Amy M.

    2012-01-01

    Suzuki couplings are powerful chemical reactions commonly employed in academic and industrial research settings to generate functionalized biaryls. We have developed and implemented a discovery-based, microscale experiment for the undergraduate organic chemistry laboratory that explores green Suzuki coupling using water as the primary solvent.…

  11. Nonsteriodal Antiinflamatory Drugs As A Risk Factor Of Gastro-Oesophageal Reflux Oesophagitis, And Posterior Laryngitis In Arthritic Patients

    Directory of Open Access Journals (Sweden)

    Mahmoud A.Saleh M.D*, Khaled H.Abdel Mageed**, Kadry

    2001-06-01

    Full Text Available Non steroidal anti inflammatory drugs (NSAIDs are known to cause ulcers of the stomach and to a lesser degree, the duodenum. Consumption of NSAIDs has been associated with the infrequent occurrence of ulcers at other locations, such as the jejunum, ileum and colon. Several studies have suggested that consumption of NSAIDS also constitutes a risk factor for the development of erosive oesophagitis, including oesophageal strictures. It is now documented that NSAIDS are associated with gastro-oesophageal reflux disease (GERD. It was found recently that GERD is associated with a variety of laryngeal conditions and symptoms, of which "reflux laryngitis" is the most common. AIM OF THE WORK: is to study the effect of NSAIDs on the development of laryngitis in patients with GERD. PATIENTS AND METHODS: study included 60 patients, 42 males and 18 females aged between 26 ­ 52 years old (mean 37.9, a detailed history was taken from all patients. All the sixty patients were suspected to have GERD based on symptoms including acid reflux, Group I: - 40 patients were receiving daily-recommended doses of NSAIDs for at least one month for a diagnosed rheumatological disease, Group II: - 20 patients who were diagnosed as GERD, and were not receiving any NSAIDs for at least one month prior to the present study. The sixty patients were subjected to upper gastrointestinal endoscopy. Patients who were diagnosed as GERD with or without oesophagitis were subjected to ENT fibro-optic laryngoscopy. RESULTS: 42% of all patients with GERD have hoarseness of voice, 30% have recurrent chocking, 53% have excessive throat cleaning. Postglottic oedema, arytenoid oedema, vocal fold oedema, were all significantly higher in group I than in group II. CONCLUSION: The chronic use of NSAIDs can be considered as a risk factor for developing GERD, erosive oesophagitis with or without subsequent posterior laryngitis. Laryngoscopy may have a predictive value for the occurrence of GERD in those patients. Patients who were on regular use of NSAIDS, and are symptomatic for GERD are recommended to start medical treatment for GERD to guard against erosive oesophagitis and/or posterior laryngitis.

  12. Efficacy of boswellic acid on lysosomal acid hydrolases, lipid peroxidation and anti-oxidant status in gouty arthritic mice

    Institute of Scientific and Technical Information of China (English)

    Evan Prince Sabina; Haridas Indu; Mahaboobkhan Rasool

    2012-01-01

    Objective:To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice. Methods:The mice were divided into four experimental groups. Group I served as control;mice in group II were injected with monosodium urate crystal;group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.);group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-αwere determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro. Results:The activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-αlevels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells. Conclusions: The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.

  13. Anti-inflammatory and anti-arthritic activity of a methanol extract from Vitellaria paradoxa stem bark

    Directory of Open Access Journals (Sweden)

    Harquin Simplice Foyet

    2015-01-01

    Full Text Available Background: Vitellaria paradoxa is a traditional medicinal plant of Cameroon. Several studies on this plant have focused on the cosmetic profile of its fruits. The present study focuses on the anti-inflammatory potency of stem barks extract of this plant. Objective: The objective was to evaluate the effect of methanolic extract of V. paradoxa (VPME stem barks on inflammatory response in rats. Materials and Methods: Anti-inflammatory effects of VPME were evaluated in acute and chronic (28 days inflammation induced in Wistar albino rats. The effects on hyperalgesia and locomotors activity were also quantified. The relative weight of lymphoid organs was obtained as well as some hematological parameters. Results: In the carrageenan-induced inflammation, VPME (75 mg/kg exhibited a significant (66.67% inhibition after 1 h. On the complete Freund′s adjuvant-induced rheumatoid arthritis, VPME showed a significant protective effect with 8.12% inflammation against 25.00% for the control group after 2 days of the treatment. The extract (75 and 150 mg/kg significantly reduced the score of arthritis with a maximum obtained on day 19 th of the experimentation. There was a significant increase in the reaction time of rats on the hot plate as well as the exploratory activities of the animals in the open field. This extract significantly prevented weight, hemoglobin and red blood cells losses, and spleen hypertrophy. A protective action against skin destruction and cartilage erosion was evident. Liquid chromatography-mass spectrometry analysis of the extract revealed the presence of catechins. Conclusions: These findings suggested that V. paradoxa may contribute to the reduction of the inflammatory response.

  14. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis

    OpenAIRE

    Malfait, A. M.; Gallily, R; Sumariwalla, P. F.; Malik, A. S.; Andreakos, E; Mechoulam, R.; Feldmann, M

    2000-01-01

    The therapeutic potential of cannabidiol (CBD), the major nonpsychoactive component of cannabis, was explored in murine collagen-induced arthritis (CIA). CIA was elicited by immunizing DBA/1 mice with type II collagen (CII) in complete Freund's adjuvant. The CII used was either bovine or murine, resulting in classical acute CIA or in chronic relapsing CIA, respectively. CBD was administered after onset of clinical symptoms, and in both models of arthritis the treatment effectively blocked pro...

  15. Anti-inflammatory and anti-arthritic activity of a methanol extract from Vitellaria paradoxa stem bark

    Science.gov (United States)

    Foyet, Harquin Simplice; Tsala, David Emery; Zogo Essono Bodo, J.C; Carine, Azanfack Name; Heroyne, Lissia Toussoumna; Oben, Eyong Kenneth

    2015-01-01

    Background: Vitellaria paradoxa is a traditional medicinal plant of Cameroon. Several studies on this plant have focused on the cosmetic profile of its fruits. The present study focuses on the anti-inflammatory potency of stem barks extract of this plant. Objective: The objective was to evaluate the effect of methanolic extract of V. paradoxa (VPME) stem barks on inflammatory response in rats. Materials and Methods: Anti-inflammatory effects of VPME were evaluated in acute and chronic (28 days) inflammation induced in Wistar albino rats. The effects on hyperalgesia and locomotors activity were also quantified. The relative weight of lymphoid organs was obtained as well as some hematological parameters. Results: In the carrageenan-induced inflammation, VPME (75 mg/kg) exhibited a significant (66.67%) inhibition after 1 h. On the complete Freund's adjuvant-induced rheumatoid arthritis, VPME showed a significant protective effect with 8.12% inflammation against 25.00% for the control group after 2 days of the treatment. The extract (75 and 150 mg/kg) significantly reduced the score of arthritis with a maximum obtained on day 19th of the experimentation. There was a significant increase in the reaction time of rats on the hot plate as well as the exploratory activities of the animals in the open field. This extract significantly prevented weight, hemoglobin and red blood cells losses, and spleen hypertrophy. A protective action against skin destruction and cartilage erosion was evident. Liquid chromatography-mass spectrometry analysis of the extract revealed the presence of catechins. Conclusions: These findings suggested that V. paradoxa may contribute to the reduction of the inflammatory response. PMID:26692752

  16. Lactobacillus casei and Lactobacillus acidophilus regulate inflammatory pathway and improve antioxidant status in collagen-induced arthritic rats.

    Science.gov (United States)

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

    2013-01-01

    In view of well-established immunomodulatory properties of Lactobacillus, present investigation was carried out to evaluate antioxidant and anti-inflammatory potential of Lactobacillus casei and Lactobacillus acidophilus, against inflammatory pathway and oxidative stress developed in an experimental model of arthritis. Collagen-induced arthritis (CIA) model was used. Oral administration of L. casei, L. acidophilus, standard antiarthritic drug indomethacin, and vehicle were started after induced arthritis and continued up to day 28. Interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-1β, IL-17, IL-4, and IL-10 levels were estimated in serum. In parallel, oxidative stress parameters were also measured from synovial effsuate. All rats were graded for arthritis score at the end of each week. L. casei, L. acidophilus, and indomethacin treatment significantly downregulated proinflammatory and upregulated anti-inflammatory cytokines at Pacidophilus was more pronounced than that of indomethacin. These lines of evidence suggest that L. casei and L. acidophilus exert potent protective effect against CIA. It further establishes effective anti-inflammatory and antioxidant properties of Lactobacillus. However, additional clinical investigations are needed to prove the efficacy of Lactobacillus in treatment/management of rheumatoid arthritis.

  17. Effects of triptolide from Radix Tripterygium wilfordii (Leigongteng on cartilage cytokines and transcription factor NF-κB: a study on induced arthritis in rats

    Directory of Open Access Journals (Sweden)

    Zhao Linhua

    2009-07-01

    Full Text Available Abstract Background Triptolide, an active compound of Radix Tripterygium wilfordii, is immunosuppressive, cartilage protective and anti-inflammatory both in human and animal studies of various inflammatory and autoimmune diseases, including rheumatoid arthritis, but its therapeutic mechanism remains unclear. The aim of this study is to investigate the effects of triptolide on cartilage cytokines in the CIA model. Methods Sprague Dawley rats were immunized with type II collagen and orally administered with triptolide. The arthritic scores and incidence changes of the rats were observed. The expression of TNF-α, IL-6, COX-2 and NF-κB in paw cartilage was studied with immunohistochemical staining. Results Triptolide, at both high and low doses, significantly lowered the arthritic scores, delayed the onset of arthritis and lowered the arthritis incidence. Triptolide treatment at both high and low doses lowered the expression of TNF-α, IL-6, COX-2 and NF-κB in paw cartilage in arthritic rats. Conclusion Triptolide lowers the arthritic scores, delays the onset of collagen induced arthritis and reduces the expressions of TNF-α, IL-6, NF-κB and COX-2 in paw cartilage in arthritic rats.

  18. Philosophical foundations of human rights

    CERN Document Server

    Liao, Matthew S

    2015-01-01

    What makes something a human right? What is the relationship between the moral foundations of human rights and human rights law? What are the difficulties of appealing to human rights? This book offers the first comprehensive survey of current thinking on the philosophical foundations of human rights. Divided into four parts, this book focusses firstly on the moral grounds of human rights, for example in our dignity, agency, interests or needs. 'Secondly, it looks at the implications that different moral perspectives on human rights bear for human rights law and politics. Thirdly, it discusses specific and topical human rights including freedom of expression and religion, security, health and more controversial rights such as a human right to subsistence. The final part discusses nuanced critical and reformative views on human rights from feminist, Kantian and relativist perspectives among others. The essays represent new and canonical research by leading scholars in the field. Each part is comprised of a set...

  19. Why Geo-Humanities

    Science.gov (United States)

    Graells, Robert Casals i.; Sibilla, Anna; Bohle, Martin

    2016-04-01

    Anthropogenic global change is a composite process. It consists of societal processes (in the 'noosphere') and natural processes (in the 'bio-geosphere'). The 'noosphere' is the ensemble of social, cultural or political insights ('shared subjective mental concepts') of people. Understanding the composite of societal and natural processes ('human geo-biosphere intersections'), which shapes the features of anthropogenic global change, would benefit from a description that draws equally on natural sciences, social sciences and humanities. To that end it is suggested to develop a concept of 'geo-humanities': This essay presents some aspects of its scope, discussing "knowledge that is to manage", "intentions that are to shape", "choices that are to justify" and "complexity that is to handle". Managing knowledge: That people understand anthropogenic global change requires their insights into how 'human geosphere intersections' function. Insights are formed ('processed') in the noosphere by means of interactions between people. Understanding how 'human geosphere intersections' functions combines scientific, engineering and economic studies with studies of the dynamics of the noosphere. Shaping intentions: During the last century anthropogenic global change developed as the collateral outcome of humankind's accumulated actions. It is caused by the number of people, the patterns of their consumption of resources, and the alterations of their environments. Nowadays, anthropogenic global chance is either an intentional negligence or a conscious act. Justifying choices: Humanity has alternatives how to alter Earth at planetary scale consciously. For example, there is a choice to alter the geo-biosphere or to adjust the noosphere. Whatever the choice, it will depend on people's world-views, cultures and preferences. Thus beyond issues whether science and technology are 'sound' overarching societal issues are to tackle, such as: (i) how to appropriate and distribute natural

  20. [Human ehrlichiosis. Review].

    Science.gov (United States)

    Arraga-Alvarado, C

    1994-12-01

    Human ehrlichiosis is a newly recognized tick-borne disease. Since 1935 Ehrlichia canis has been known as a cause of illness in dogs and other canine species, and for a few years it was related with human disease. In 1990, Ehrlichia chaffeensis was isolated from a man suspected of having ehrlichiosis. Partial sequencing of the rRNAS from the human isolate and E. canis, indicated that they are 98.7% related. More recently (May 1994) an "human granulocytic ehrlichiosis" have been reported in USA. PCR amplification and sequence of 16S rDNA, showed that the human isolate was virtually identical to those reported for E. phagocytophila y E. equi, organisms that cause ehrlichiosis in rumiant and in horses. Most patients shows fever, headache, malaise, nausea or vomiting, anorexia and in a minority of cases rash is present. Some of them have complications such as pulmonary infiltrates, gastrointestinal problems, renal dysfunction or failure, hepatoesplenomegaly, neurologic abnormalities, DIC and some times death. Leucopenia, thrombocytopenia and elevated liver enzyme values have been common findings. Tetracycline and cloramphenicol have been using in adults and children as especific theraphy.

  1. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  2. Humanity and Sustainability

    Directory of Open Access Journals (Sweden)

    Shu-Kun Lin

    2011-09-01

    Full Text Available So far our open access publishing company MDPI (Multidisciplinary Digital Publishing Institute has published mainly science, medicine and technology journals. To become a multidisciplinary publisher, we launched the journal Sustainability [1]. More recently, we started to run several social science journals, including Societies [2], Religions [3], Administrative Sciences [4] and Behavioral Sciences [5]. Today we published the first paper [6] of the inaugural issue of Humanities (ISSN 2076-0787. This will be an international open access journal, publishing scholarly papers of high quality across all humanities disciplines. As a publisher, I would like to publish journals surrounding the topics of sustainability and I believe the humanities as a discipline of academic studies are very important. As a scientist, I believed science and technology will only benefit human beings. I was raised in a small village, living a very primitive life in a peasant family: no electricity, no machines, of course no TV and no refrigerator. Now, the life of my children is completely different. Even my own life has completely changed. I have witnessed very rapid changes: more and more machines are used to consume mineral resources and energy and to pollute the environment, in order to produce more and more powerful machines (we are also launching a journal titled Machines, in which the relationship between Man and machine should be an interesting topic.. Machines are more and more like human individuals consuming resources themselves (we are launching a journal titled Resources. [...

  3. NOOSPHERE HUMAN COMMUNITY

    Directory of Open Access Journals (Sweden)

    Novozhilova Elena Olegovna

    2013-01-01

    Full Text Available The author dwells upon typical features of noosphere human communities, assessing prospects and hazards of genetic engineering, namely of recombinant DNA technology. Background: Socio-historical ecology ushers in a new approach to studying society in its relation to nature. This interrelation is regarded as a series of socio-ecological transformations ending up in certain types of socio-ecological systems being formed. One of such historical types is represented by a noosphere human community [1]. Results: A number of characteristic features of this kind of community have been outlined, namely: its existence and functioning on global scale, major role of information in making up social wealth, creation of living matter. Conclusion: The noosphere human community is currently the latest stage in the sequence of historical types of socio-ecological systems. Widespread use of information and genetic technology may enable noosphere people to create in future a totally man-made world superseding evolutionary biosphere.

  4. Human Relations-skolen

    DEFF Research Database (Denmark)

    Scheuer, Steen

    2014-01-01

    , men også arbejdssociologien, arbejdspsykologien og human resource development. Den første retning udsprang af de såkaldte Hawthorne-eksperimenter og psykologen Elton Mayos bearbejdelse af resultaterne derfra. Den anden er en løsere gruppering bestående af navne som Abraham Maslow og Frederick Herzberg......Human Relations-skolen er en samlebetegnelse for to forskningsretninger, som tilsammen bidrog som nogle af de første til at indkredse og belyse de mellemmenneskelige relationers betydning for motivation og trivsel i arbejdslivet, og som skulle få stor ind"ydelse ikke bare på organisationsteorien......, som formulerede en række teorier og modeller om menneskets motivation, trivsel og behov i arbejdslivet. Selvom de ikke nødvendigvis relaterede sig til hinandens arbejde, er de forskellige bidragsydere i dag kendt som repræsentanter for den paradigmatiske betegnelse Human Relations. Undertiden skelnes...

  5. [Human pulmonary trichomonoses].

    Science.gov (United States)

    Duboucher, Christophe; Caby, Stéphanie; Chabé, Magali; Gantois, Nausicaa; Delgado-Viscogliosi, Pilar; Pierce, Raymond; Capron, Monique; Dei-Cas, Eduardo; Viscogliosi, Eric

    2007-05-01

    Colonization of human lungs by various Trichomonas species is a frequent occurrence, but is unknown to most physicians. At this site of infection, the parasite develops into an amoeboid form that renders it unrecognizable. For this reason it has been overlooked until recently. Morphological identification is not feasible under these conditions and molecular tools provide the only means of identification. The species involved are not restricted to Trichomonas tenax, a saprophyte of the mouth that is usually cited in the rare cases of pleuropulmonary trichomoniasis reported in the literature. The recent discovery of species previously unknown in humans raises further questions, including the zoonotic potential of these microorganisms and the existence of species of animal origin that have adapted to humans. Anaerobiosis in poorly ventilated alveolar lumen, rather than immunodepression, seems to be the factor that promotes proliferation of this parasite. The diagnosis of trichomoniasis and its treatment by specific drugs will make it possible to evaluate the pathogenicity of these parasites.

  6. Scientists and Human Rights

    Science.gov (United States)

    Makdisi, Yousef

    2012-02-01

    The American Physical Society has a long history of involvement in defense of human rights. The Committee on International Freedom of Scientists was formed in the mid seventies as a subcommittee within the Panel On Public Affairs ``to deal with matters of an international nature that endangers the abilities of scientists to function as scientists'' and by 1980 it was established as an independent committee. In this presentation I will describe some aspects of the early history and the impetus that led to such an advocacy, the methods employed then and how they evolved to the present CIFS responsibility ``for monitoring concerns regarding human rights for scientists throughout the world''. I will also describe the current approach and some sample cases the committee has pursued recently, the interaction with other human rights organizations, and touch upon some venues through which the community can engage to help in this noble cause.

  7. Helicopter human factors

    Science.gov (United States)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  8. Human Systems Design Criteria

    DEFF Research Database (Denmark)

    Rasmussen, Jens

    1982-01-01

    the necessary functional qualities but also the needed human qualities. The author's main argument is, that the design process should be a dialectical synthesis of the two points of view: Man as a System Component, and System as Man's Environment. Based on a man's presentation of the state of the art a set...... of design criteria is suggested and their relevance discussed. The point is to focus on the operator rather than on the computer. The crucial question is not to program the computer to work on its own conditions, but to “program” the operator to function on human conditions.......This paper deals with the problem of designing more humanised computer systems. This problem can be formally described as the need for defining human design criteria, which — if used in the design process - will secure that the systems designed get the relevant qualities. That is not only...

  9. Reflections on humanizing biomedicine.

    Science.gov (United States)

    Marcum, James A

    2008-01-01

    Although biomedicine is responsible for the "miracles" of modern medicine, paradoxically it has also led to a quality-of-care crisis in which many patients feel disenfranchised from the health-care industry. To address this crisis, several medical commentators make an appeal for humanizing biomedicine, which has led to shifts in the philosophical boundaries of medical knowledge and practice. In this paper, the metaphysical, epistemological, and ethical boundaries of biomedicine and its humanized versions are investigated and compared to one another. Biomedicine is founded on a metaphysical position of mechanistic monism, an epistemology of objective knowing, and an ethic of emotionally detached concern. In humanizing modern medicine, these boundaries are often shifted to a metaphysical position of dualism/holism, an epistemology of subject knowing, and an ethic of empathic care. In a concluding section, the question is discussed whether these shifts in the philosophical boundaries are adequate to resolve the quality-of-care crisis.

  10. HUMAN MISSION OF EDUCATION

    Directory of Open Access Journals (Sweden)

    Suzana Miovska Spaseva

    2013-06-01

    Full Text Available The article examines the complex role and great responsibility of the education today in development of the moral strength and human values of the children and youth. At the beginning of the article the author reconsiders the pedagogical ideas of Maria Montessori and her concept of education for peace as an instrument for reconstruction of the society and for improvement of the human living. Than the analysis of the moral values in the contemporary society is made and several issues and dilemmas are discussed referring the value disorientation of the youth and the importance of the models of adult’s moral behavior in their search for personal identity. On the basis of this analysis, the human dimension of the education is elaborated enhancing the need for its understanding as support of development, which is based on several crucial elements: love, freedom and spirit of community.

  11. (Human) Resourcing For CI

    DEFF Research Database (Denmark)

    Jørgensen, Frances; S., Jacob; Kofoed, Lise Busk

    2005-01-01

    More and more, the ability to compete in today’s market is viewed as being dependent on human capital. One of the most challenging aspects of human resource management involves supplying the organization with the human capital necessary to fulfill its objectives. This task becomes especially...... challenging in organizations involved in change processes such as Continuous Improvement (CI), as the technical skills traditionally valued are no longer adequate. These companies are faced with the question: “What competencies should our employees possess in order to contribute to our success, given...... the change processes in which we are engaged?” Without a clear picture of the types of competencies required to implement CI, it is impossible for companies to make informed decisions regarding recruitment, hiring, and training of their workforce. The objective of this paper is therefore to define...

  12. Designing Human Technologies

    DEFF Research Database (Denmark)

    Simonsen, Jesper

    and the design process, in ethical and society-related concerns, and in evaluating how designs fulfill needs and solve problems. Designing Human Technologies subscribes to a broad technology concept including information and communication, mobile, environmental/sustainable and energy technologies......, the Humanities, and Social Science. The initiative broadens the perspective of IS and recognize reflections on aesthetics, ethics, values, connections to politics, and strategies for enabling a better future as legitimate parts of the research agenda. Designing Human Technologies is a design-oriented Strategic...... and technologies relating to performances and experiences, urban design, climate adaptation, etc. The research takes a process-oriented and participatory approach and involves interaction between different user interests and designs. It is based on empirical, typical case- and action research-oriented studies...

  13. Abortion and human rights.

    Science.gov (United States)

    Shaw, Dorothy

    2010-10-01

    Abortion has been a reality in women's lives since the beginning of recorded history, typically with a high risk of fatal consequences, until the last century when evolutions in the field of medicine, including techniques of safe abortion and effective methods of family planning, could have ended the need to seek unsafe abortion. The context of women's lives globally is an important but often ignored variable, increasingly recognised in evolving human rights especially related to gender and reproduction. International and regional human rights instruments are being invoked where national laws result in violations of human rights such as health and life. The individual right to conscientious objection must be respected and better understood, and is not absolute. Health professional organisations have a role to play in clarifying responsibilities consistent with national laws and respecting reproductive rights. Seeking common ground using evidence rather than polarised opinion can assist the future focus.

  14. Human-Robot Interaction

    Science.gov (United States)

    Rochlis-Zumbado, Jennifer; Sandor, Aniko; Ezer, Neta

    2012-01-01

    Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI) is a new Human Research Program (HRP) risk. HRI is a research area that seeks to understand the complex relationship among variables that affect the way humans and robots work together to accomplish goals. The DRP addresses three major HRI study areas that will provide appropriate information for navigation guidance to a teleoperator of a robot system, and contribute to the closure of currently identified HRP gaps: (1) Overlays -- Use of overlays for teleoperation to augment the information available on the video feed (2) Camera views -- Type and arrangement of camera views for better task performance and awareness of surroundings (3) Command modalities -- Development of gesture and voice command vocabularies

  15. Human immune system variation.

    Science.gov (United States)

    Brodin, Petter; Davis, Mark M

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

  16. [Human rights and procreation].

    Science.gov (United States)

    Leroy, F

    1990-04-01

    The impact of procreation on freedom, health and welfare of human beings, is considerable. This relationship, however, is not mirrored in texts devoted to Human Rights. This omission obviously implies a neglect of women's and children's rights. The history of anticonceptive methods exemplifies the struggle for these rights. This conquest, which has lasted two hundred years, is far from completed. Because of the demographic outbreak in Third World countries, an ideological conflict has appeared between first generation Human Rights concerned with individual freedom ("rights of") and those of second generation aiming at social fairness ("rights to"). Adequate political and economic adjustment between North and South is a prerequisite to any balanced compromise that would resolve this conflict through democratic, albeit intensive, birth control.

  17. Monogenic obesity in humans.

    Science.gov (United States)

    Farooqi, I Sadaf; O'Rahilly, Stephen

    2005-01-01

    Until relatively recently, the small number of identifiable inherited human diseases associated with marked obesity were complex, pleiotropic developmental disorders, the molecular basis for which were entirely obscure. The molecular basis for many of these complex syndromes, such as Bardet Beidl syndrome, has been revealed, providing novel insights into processes essential for human hypothalamic function and energy balance. In addition to these discoveries, which were the fruits of positional cloning, the molecular constituents of the signaling pathways responsible for the control of mammalian energy homeostasis have been identified, largely through the study of natural or artificial mutations in mice. We discuss the increasing number of human disorders that result from genetic disruption of the leptin-melanocortin pathways that have been identified. Practical implications of these findings for genetic counseling, prognostication, and even therapy have already emerged.

  18. Monogenic human obesity syndromes.

    Science.gov (United States)

    Farooqi, I S

    2006-01-01

    Over the past decade we have witnessed a major increase in the scale of scientific activity devoted to the study of energy balance and obesity. This explosion of interest has, to a large extent, been driven by the identification of genes responsible for murine obesity syndromes, and the novel physiological pathways revealed by those genetic discoveries. Others and we have also recently identified several single gene defects causing severe human obesity. Many of these defects have been in molecules identical or similar to those identified as a cause of obesity in rodents. I will review the human monogenic obesity syndromes that have been characterised to date and discuss how far such observations support the physiological role of these molecules in the regulation of human body weight and neuroendocrine function.

  19. Social cognition in humans

    DEFF Research Database (Denmark)

    Frith, Christopher; Frith, Uta

    2007-01-01

    We review a diversity of studies of human social interaction and highlight the importance of social signals. We also discuss recent findings from social cognitive neuroscience that explore the brain basis of the capacity for processing social signals. These signals enable us to learn about...... the world from others, to learn about other people, and to create a shared social world. Social signals can be processed automatically by the receiver and may be unconsciously emitted by the sender. These signals are non-verbal and are responsible for social learning in the first year of life. Social...... signals can also be processed consciously and this allows automatic processing to be modulated and overruled. Evidence for this higher-level social processing is abundant from about 18 months of age in humans, while evidence is sparse for non-human animals. We suggest that deliberate social signalling...

  20. Human Security Agendas

    Institute of Scientific and Technical Information of China (English)

    Alan Hunter

    2012-01-01

    Ⅰ.IntroductionThe need for governments and international organisations to gain a better understanding of "security" is ever more urgent.For example in the conflict in Libya in early 2011,many security dilemmas were visible:the protection of Libyan civilians,the security of the regime,whether and how the UN or NATO should intervene,whether Europe would be threatened with a massive refugee flow,how to protect or evacuate foreign citizens (including Chinese),how to secure food and medical supplies in the midst of armed conflict.Such events may be termed "complex emergencies" which often raise legal, military and humanitarian issues simultaneously.International law and practice do not provide clear guidelines on such situations,and responses can be random,contingent on a variety of factors.Traditional concepts of security,for example protection of national borders,are certainly still relevant and legally enforceable,but more sophisticated concepts are needed to respond to security dilemmas in today's globalised world.Human security as a concept was first developed within the UN system in the 1990s,and set out,for example,in Human Security Now [1] The first section of this paper tracks the development of Human Security discourse,and also examines the broadening of the "security"concept in recent years.The second section reports on institutions with a specific interest in Human Security,for example within the UN system and in universities.The third section acknowledges some critiques of the Human Security paradigm.The last section reports on new directions that may enrich the Human Security agenda.

  1. Human migraine models

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg

    2001-01-01

    The need for experimental models is obvious. In animal models it is possible to study vascular responses, neurogenic inflammation, c-fos expression etc. However, the pathophysiology of migraine remains unsolved, why results from animal studies not directly can be related to the migraine attack......, which is a human experience. A set-up for investigations of experimental headache and migraine in humans, has been evaluated and headache mechanisms explored by using nitroglycerin and other headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated cascade seems to be responsible...

  2. Human Environmental Disease Network

    DEFF Research Database (Denmark)

    Taboureau, Olivier; Audouze, Karine

    2017-01-01

    During the past decades, many epidemiological, toxicological and biological studies have been performed to assess the role of environmental chemicals as potential toxicants for diverse human disorders. However, the relationships between diseases based on chemical exposure have been rarely studied...... by computational biology. We developed a human environmental disease network (EDN) to explore and suggest novel disease-disease and chemical-disease relationships. The presented scored EDN model is built upon the integration on systems biology and chemical toxicology using chemical contaminants information...

  3. On human health.

    Science.gov (United States)

    van Spijk, Piet

    2015-05-01

    If it is true that health is a priority objective of medicine, then medical practice can only be successful if the meaning of the term "health" is known. Various attempts have been made over the years to define health. This paper proposes a new definition. In addition to current health concepts, it also takes into account the distinction between specifically human (great) health and health as the absence of disease and illness-i.e. small health. The feeling of leading a life that makes sense plays a key role in determining specifically human great health.

  4. Handbook of human computation

    CERN Document Server

    Michelucci, Pietro

    2013-01-01

    This volume addresses the emerging area of human computation, The chapters, written by leading international researchers, explore existing and future opportunities to combine the respective strengths of both humans and machines in order to create powerful problem-solving capabilities. The book bridges scientific communities, capturing and integrating the unique perspective and achievements of each. It coalesces contributions from industry and across related disciplines in order to motivate, define, and anticipate the future of this exciting new frontier in science and cultural evolution. Reade

  5. When computers were human

    CERN Document Server

    Grier, David Alan

    2013-01-01

    Before Palm Pilots and iPods, PCs and laptops, the term ""computer"" referred to the people who did scientific calculations by hand. These workers were neither calculating geniuses nor idiot savants but knowledgeable people who, in other circumstances, might have become scientists in their own right. When Computers Were Human represents the first in-depth account of this little-known, 200-year epoch in the history of science and technology. Beginning with the story of his own grandmother, who was trained as a human computer, David Alan Grier provides a poignant introduction to the wider wo

  6. We Are Human Beings

    Science.gov (United States)

    McGee, Andrew

    2016-01-01

    In this paper, I examine Jeff McMahan’s arguments for his claim that we are not human organisms, and the arguments of Derek Parfit to the same effect in a recent paper. McMahan uses these arguments to derive conclusions concerning the moral status of embryos and permanent vegetative state (PVS) patients. My claim will be that neither thinker has successfully shown that we are not human beings, and therefore these arguments do not establish the ethical conclusions that McMahan has sought to draw from the arguments in respect of the moral status of embryos and PVS patients. PMID:26810918

  7. Biodemography of human ageing

    DEFF Research Database (Denmark)

    Vaupel, James W

    2010-01-01

    Human senescence has been delayed by a decade. This finding, documented in 1994 and bolstered since, is a fundamental discovery about the biology of human ageing, and one with profound implications for individuals, society and the economy. Remarkably, the rate of deterioration with age seems...... to be constant across individuals and over time: it seems that death is being delayed because people are reaching old age in better health. Research by demographers, epidemiologists and other biomedical researchers suggests that further progress is likely to be made in advancing the frontier of survival...... - and healthy survival - to even greater ages....

  8. Understanding digital humanities

    CERN Document Server

    Berry, D

    2012-01-01

    The application of new computational techniques and visualisation technologies in the Arts and Humanities are resulting in fresh approaches and methodologies for the study of new and traditional corpora. This 'computational turn' takes the methods and techniques from computer science to create innovative means of close and distant reading. This book discusses the implications and applications of 'Digital Humanities' and the questions raised when using algorithmic techniques. Key researchers in the field provide a comprehensive introduction to important debates surrounding issues such as th

  9. Artificial human vision.

    Science.gov (United States)

    Dowling, Jason

    2005-01-01

    Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the visual cortex of an individual led to the perception of spots of light, known as phosphenes [1] . The aim of artificial human vision systems is to attempt to utilize the perception of phosphenes to provide a useful substitute for normal vision. Currently, four locations for electrical stimulation are being investigated; behind the retina (subretinal), in front of the retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface electrodes). This review discusses artificial human vision technology and requirements, and reviews the current development projects.

  10. Post-human Viewing

    DEFF Research Database (Denmark)

    Blaagaard, Bolette

    2013-01-01

    to become part of a global cultural flow, thus calling into question the physical connection between viewer and image. This article analyses what happens to that connection when not only the image but also the physical body is mediated and challenged in post-human relations, and examines the ensuing ethical...... implications. The author takes photojournalism and, in particular, mobile phone footage as a starting point for an exploration of the (post-human) body as evidence and sign of authenticity in the modern age of digital communications and journalism....

  11. Ayahuasca and human destiny.

    Science.gov (United States)

    McKenna, Dennis J

    2005-06-01

    In this essay, the author shares his personal reflections gleaned from a lifetime of research with ayahuasca, and speculates on the societal, political, planetary, and evolutionary implications of humanity's aeons-old symbiosis with this shamanic plant. The thesis is developed that at this critical historical juncture, ayahuasca has developed a strategy to broadcast its message to a wider world--a reflection of the urgent need to avert global ecological catastrophe. While ayahuasca has much to teach us, the critical question is, will humanity hear it, and heed it, in time?

  12. Human Factors Model

    Science.gov (United States)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  13. Defining Therapeutic Targets by Using Adenovirus: Blocking NF-kappa B Inhibits Both Inflammatory and Destructive Mechanisms in Rheumatoid Synovium but Spares Anti-Inflammatory Mediators

    Science.gov (United States)

    Bondeson, Jan; Foxwell, Brian; Brennan, Fionula; Feldmann, Marc

    1999-05-01

    The role of the transcription factor NF-kappa B in the pathogenesis of rheumatoid arthritis has long been a subject of controversy. We used an adenoviral technique of blocking NF-kappa B through overexpression of the inhibitory subunit Ikappa Bα , which has the advantage that it can be used in the diseased tissue itself, with >90% of the synovial macrophages, fibroblasts, and T cells infected. We found that the spontaneous production of tumor necrosis factor α and other pro-inflammatory cytokines is NF-kappa B-dependent in rheumatoid synovial tissue, in contrast to the main anti-inflammatory mediators, like IL-10 and -11, and the IL-1 receptor antagonist. Of even more interest, Ikappa Bα overexpression inhibited the production of matrix metalloproteinases 1 and 3 while not affecting their tissue inhibitor. Blocking NF-kappa B in the rheumatoid joint thus has a very beneficial profile, reducing both the inflammatory response and the tissue destruction. The adenoviral technique described here has widespread applicability, allowing rapid testing of the effects of blocking a potential therapeutic target in either cultures of normal cells or in the diseased tissue itself.

  14. Pragmatic Challenges to Human Rights

    DEFF Research Database (Denmark)

    Schaumburg-Müller, Sten

    2007-01-01

    Pragmatism offers a platform for posing relevant questions. This article uses a pragmatic point of departure to question a natural law conception of human rights and to take a closer look at three pressing human rights problems: The human rights situation in states with little or no state capacity......; the revision and adaptation of human rights law; and the not straightforward relationship betweemn human rights and democracy....

  15. Human automation integration

    NARCIS (Netherlands)

    Barnes, M.; Cosenzo, K.; Galster, s.; Hollnagel, E.; Miller, C.; Parasuraman, R.; Reising, J.; Taylor, R.; Breda, L. van

    2007-01-01

    Many versions of future concept of operations (CONOPS) rely heavily on UMVs. The pressure to take the human out of immediate control of these vehicles is being driven by several factors. These factors include a reduction in cost for the production and maintenance of the vehicle, operational viabilit

  16. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID frame-work, and a sample of 54 papers from workshops, conferences and journals from the period 2009-2014. We group the papers into six topical groups, and then ...

  17. Human Work Interaction Design

    DEFF Research Database (Denmark)

    2015-01-01

    In this paper, we review research in the emerging practice and research field of Human Work Interaction Design (HWID). We present a HWID framework, and a sample of 54 HWID related papers from workshops, conferences and journals from the period 2009–2014. We group the papers into six topical group...

  18. Biotechnologies and Human Dignity

    Science.gov (United States)

    Sweet, William; Masciulli, Joseph

    2011-01-01

    In this article, the authors review some contemporary cases where biotechnologies have been employed, where they have had global implications, and where there has been considerable debate. The authors argue that the concept of dignity, which lies at the center of such documents as the 2005 Universal Declaration on Bioethics and Human Rights, the…

  19. Predictors of human rotation.

    Science.gov (United States)

    Stochl, Jan; Croudace, Tim

    2013-01-01

    Why some humans prefer to rotate clockwise rather than anticlockwise is not well understood. This study aims to identify the predictors of the preferred rotation direction in humans. The variables hypothesised to influence rotation preference include handedness, footedness, sex, brain hemisphere lateralisation, and the Coriolis effect (which results from geospatial location on the Earth). An online questionnaire allowed us to analyse data from 1526 respondents in 97 countries. Factor analysis showed that the direction of rotation should be studied separately for local and global movements. Handedness, footedness, and the item hypothesised to measure brain hemisphere lateralisation are predictors of rotation direction for both global and local movements. Sex is a predictor of the direction of global rotation movements but not local ones, and both sexes tend to rotate clockwise. Geospatial location does not predict the preferred direction of rotation. Our study confirms previous findings concerning the influence of handedness, footedness, and sex on human rotation; our study also provides new insight into the underlying structure of human rotation movements and excludes the Coriolis effect as a predictor of rotation.

  20. Humanizing science education

    Science.gov (United States)

    Donnelly, James F.

    2004-09-01

    This paper argues that the diverse curriculum reform agendas associated with science education are strongly and critically associated with the educational characteristics of the humanities. The article begins with a survey of interpretations of the distinctive contribution which the humanities make to educational purposes. From this survey four general characteristics of the humanities are identified: an appeal to an autonomous self with the right and capacity to make independent judgements and interpretations; indeterminacy in the subject matter of these judgements and interpretations; a focus on meaning, in the context of human responses, actions, and relationships, and especially on the ethical, aesthetic, and purposive; and finally, the possibility of commonality in standards of judgement and interpretation, under conditions of indeterminacy. Inquiry and science technology and society (STS) orientated curriculum development agendas within science education are explored in the light of this analysis. It is argued that the four characteristics identified are central to the educational purposes of these and other less prominent modes of curriculum development in science, though not unproblematically so. In the light of this discussion the prognosis and challenges for science curriculum development are explored.

  1. Learning to Be Human

    Science.gov (United States)

    Macmurray, John

    2012-01-01

    This article presents "Learning to be Human", which John Macmurray delivered on 5 May 1958 as the annual public lecture at Moray House College of Education, now part of Edinburgh University. The key themes of the paper are ones to which Macmurray returned again and again in both his educational and his philosophical writing for over 40 years and…

  2. Human memory search

    NARCIS (Netherlands)

    Davelaar, E.J.; Raaijmakers, J.G.W.; Hills, T.T.; Robbins, T.W.; Todd, P.M.

    2012-01-01

    The importance of understanding human memory search is hard to exaggerate: we build and live our lives based on what whe remember. This chapter explores the characteristics of memory search, with special emphasis on the use of retrieval cues. We introduce the dependent measures that are obtained

  3. Human Memory: The Basics

    Science.gov (United States)

    Martinez, Michael E.

    2010-01-01

    The human mind has two types of memory: short-term and long-term. In all types of learning, it is best to use that structure rather than to fight against it. One way to do that is to ensure that learners can fit new information into patterns that can be stored in and more easily retrieved from long-term memory.

  4. Parasites and human evolution.

    Science.gov (United States)

    Perry, George H

    2014-01-01

    Our understanding of human evolutionary and population history can be advanced by ecological and evolutionary studies of our parasites. Many parasites flourish only in the presence of very specific human behaviors and in specific habitats, are wholly dependent on us, and have evolved with us for thousands or millions of years. Therefore, by asking when and how we first acquired those parasites, under which environmental and cultural conditions we are the most susceptible, and how the parasites have evolved and adapted to us and we in response to them, we can gain considerable insight into our own evolutionary history. As examples, the tapeworm life cycle is dependent on our consumption of meat, the divergence of body and head lice may have been subsequent to the development of clothing, and malaria hyperendemicity may be associated with agriculture. Thus, the evolutionary and population histories of these parasites are likely intertwined with critical aspects of human biology and culture. Here I review the mechanics of these and multiple other parasite proxies for human evolutionary history and discuss how they currently complement our fossil, archeological, molecular, linguistic, historical, and ethnographic records. I also highlight potential future applications of this promising model for the field of evolutionary anthropology.

  5. Antihumanism in the Humanities.

    Science.gov (United States)

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  6. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  7. Human thimet oligopeptidase.

    Science.gov (United States)

    Dando, P M; Brown, M A; Barrett, A J

    1993-01-01

    We have purified human thimet oligopeptidase to homogeneity from erythrocytes, and compared it with the enzyme from rat testis and chicken liver. An antiserum raised against rat thimet oligopeptidase also recognized the human and chicken enzymes, suggesting that the structure of the enzyme has been strongly conserved in evolution. Consistent with this, the properties of the human enzyme were very similar to those for the other species. Thus human thimet oligopeptidase also is a thiol-dependent metallo-oligopeptidase with M(r) about 75,000. Specificity for cleavage of a number of peptides was indistinguishable from that of the rat enzyme, but Ki values for the four potent reversible inhibitors tested were lower. In discussing the results, we consider the determinants of the complex substrate specificity of thimet oligopeptidase. We question whether substrates containing more than 17 amino acid residues are cleaved, as has been suggested. We also point out that the favourable location of a proline residue and a free C-terminus in the substrate may be as important as the hydrophobic residues in the P2, P1 and P3' positions that have been emphasized in the past. Images Figure 1 PMID:8373360

  8. Visible Human Project

    Science.gov (United States)

    ... Library of Medicine thanks the men and the women who will their body to science, thereby enabling medical research and development. Further Information General Information A description of The Visible Human Project ® image data and how to obtain it (includes license ...

  9. Marketing Human Resource Development.

    Science.gov (United States)

    Frank, Eric, Ed.

    1994-01-01

    Describes three human resource development activities: training, education, and development. Explains marketing from the practitioners's viewpoint in terms of customer orientation; external and internal marketing; and market analysis, research, strategy, and mix. Shows how to design, develop, and implement strategic marketing plans and identify…

  10. Computational human body models

    NARCIS (Netherlands)

    Wismans, J.S.H.M.; Happee, R.; Dommelen, J.A.W. van

    2005-01-01

    Computational human body models are widely used for automotive crashsafety research and design and as such have significantly contributed to a reduction of traffic injuries and fatalities. Currently crash simulations are mainly performed using models based on crash-dummies. However crash dummies dif

  11. Human Power Empirically Explored

    NARCIS (Netherlands)

    Jansen, A.J.

    2011-01-01

    Harvesting energy from the users’ muscular power to convert this into electricity is a relatively unknown way to power consumer products. It nevertheless offers surprising opportunities for product designers; human-powered products function independently from regular power infrastructure, are conven

  12. Narratology beyond the Human

    Directory of Open Access Journals (Sweden)

    David Herman

    2014-12-01

    Full Text Available This essay uses Lauren Groff’s 2011 short story “Above and Below” to explore aspects of a narratology beyond the human, considering how ideas developed by scholars of narrative bear on questions about the nature and scope of human-animal relationships in the larger biosphere. Bringing Groff’s text into dialogue with the concept of “self-narratives” as developed by Kenneth J. Gergen and Mary M. Gergen, anthropological research on the ontologies projected by the members of different cultures, and ideas from literary narratology, I discuss how the structure and narration of Groff’s story reveal a fault line between two competing ontologies in the culture of modernity, one parsimonious and the other prolific when it comes to allocating possibilities for selfhood across species lines. More generally, in addition to illuminating how a given self-narrative locates the human agent in a transspecies constellation of selves, a narratology beyond the human can assist with the construction of new, more sustainable individual and collective self-narratives that situate the self within wider webs of creatural life.

  13. Communicating Humanism Nonverbally.

    Science.gov (United States)

    Hillison, John

    1983-01-01

    Discusses the importance of nonverbal communication by counselors in expressing humanistic feeling. Notes that facial expression (i.e., smiling) provides immediate feedback to the observer; use of space (i.e., close proximity) communicates warmth and humaneness; and tone of voice can complement spoken words and give them more meaning. (WAS)

  14. Cultivating human nature

    NARCIS (Netherlands)

    Derksen, Maarten

    2007-01-01

    Evolutionary psychology claims to offer a unified perspective on human nature and culture, which can serve to further the integration of psychology and the social sciences. I describe four approaches to evolutionary psychology, and note increasing attention to the agency of the individual in constru

  15. "Healthy" Human Development Indices

    Science.gov (United States)

    Engineer, Merwan; Roy, Nilanjana; Fink, Sari

    2010-01-01

    In the Human Development Index (HDI), life expectancy is the only indicator used in modeling the dimension "a long and healthy life". Whereas life expectancy is a direct measure of quantity of life, it is only an indirect measure of healthy years lived. In this paper we attempt to remedy this omission by introducing into the HDI the morbidity…

  16. Human social genomics.

    Directory of Open Access Journals (Sweden)

    Steven W Cole

    2014-08-01

    Full Text Available A growing literature in human social genomics has begun to analyze how everyday life circumstances influence human gene expression. Social-environmental conditions such as urbanity, low socioeconomic status, social isolation, social threat, and low or unstable social status have been found to associate with differential expression of hundreds of gene transcripts in leukocytes and diseased tissues such as metastatic cancers. In leukocytes, diverse types of social adversity evoke a common conserved transcriptional response to adversity (CTRA characterized by increased expression of proinflammatory genes and decreased expression of genes involved in innate antiviral responses and antibody synthesis. Mechanistic analyses have mapped the neural "social signal transduction" pathways that stimulate CTRA gene expression in response to social threat and may contribute to social gradients in health. Research has also begun to analyze the functional genomics of optimal health and thriving. Two emerging opportunities now stand to revolutionize our understanding of the everyday life of the human genome: network genomics analyses examining how systems-level capabilities emerge from groups of individual socially sensitive genomes and near-real-time transcriptional biofeedback to empirically optimize individual well-being in the context of the unique genetic, geographic, historical, developmental, and social contexts that jointly shape the transcriptional realization of our innate human genomic potential for thriving.

  17. Lessons in Human Relations.

    Science.gov (United States)

    Glenn, Joanne Lozar

    2003-01-01

    Explores the importance of relationship literacy--the ability to create good relationships with others--in the next economy and offers perspectives on how business education instructors can help students develop and improve their human relations skills for business success. (Author/JOW)

  18. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  19. Human health and groundwater

    Science.gov (United States)

    The high quality of most groundwaters, consequent upon the self-purification capacity of subsurface strata, has long been a key factor in human health and wellbeing. More than 50% of the world’s population now rely on groundwater for their supply of drinking water – and in most circumstances a prope...

  20. Humanizing the Secondary School.

    Science.gov (United States)

    Hamilton, Norman K., Ed.; Saylor, J. Galen, Ed.

    These papers, presented during ASCD-sponsored conference, confront educators with issues in and alternatives for making secondary schools a more humanizing experience for students. The contributors and their articles are: Norman K. Hamilton, "Alternatives in Secondary Education"; Thornton B. Monez and Norman L. Bussiere, "The High School in Human…