1,721,003 research outputs found

    Catecholamine-producing cells in the synovial tissue during arthritis: modulation of sympathetic neurotransmitters as new therapeutic target.

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    BACKGROUND: The proinflammatory and anti-inflammatory role of the sympathetic nervous system in early and late inflammation is an unresolved paradox. A drastic loss of sympathetic nerve fibres in the synovial tissue of patients with rheumatoid arthritis (RA) has previously been demonstrated. The presence of tyrosine hydroxylase (TH)-positive cells in RA and osteoarthritis (OA) has been determined, but the role of these cells in inflammation is still unclear. OBJECTIVE: To characterise TH-positive cells in inflamed RA and OA synovial tissue and to study their role in inflammation. METHODS: Synovial samples were obtained from 32 patients with OA and 19 patients with RA and from 10 control patients. Synovial tissue samples were used for immunofluorescence staining. Synovial cells were isolated by tissue digestion and immediately used for cell culture. For in vivo experiments, collagen type-II arthritis in DBA/1J mice was induced. RESULTS: TH+ cells were present only in inflamed tissue and not in controls. Catecholamine-storing vesicles and vesicular monoamine transporter 2 (VMAT2) were identified in the synovial tissue. Experimental increase of cytoplasmic catecholamines by VMAT2 blockade strongly reduced tumour necrosis factor (TNF) independently of canonical extracellular β-adrenergic signalling. In addition, VMAT2 blockade increased cyclic AMP (cAMP) and cAMP responsive element binding protein, responsible for TNF inhibition. In vivo, appearance of VMAT2 positive cells was confirmed. VMAT2 blockade ameliorated inflammation also in vivo. CONCLUSIONS: This study demonstrates that local catecholamine-producing cells start to replace sympathetic nerve fibres around the onset of disease, and modulation of locally produced catecholamines has strong anti-inflammatory effects in vivo and in vitro

    Quantitative determination of steroid hormone receptor positive cells in the synovium of patients with rheumatoid arthritis and osteoarthritis: is there a link to inflammation?

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    Background: Steroid hormone receptors such as glucocorticoid receptors, androgen receptors, and oestrogen receptors alpha (ER alpha) and beta (ER beta) have been identified in synovial cells of patients with rheumatoid arthritis and osteoarthritis. Objectives: To find a quantitative relationship between the number of receptor positive cells and markers of inflammation, and to compare the two groups of patients with rheumatoid arthritis and osteoarthritis. Methods: A total of 36 patients with rheumatoid arthritis (n = 17) and osteoarthritis (n = 19) were included, and receptor positive cells and cellular markers of synovial inflammation were quantified by immunohistochemistry and ELISA (interleukin 6 (IL6) and IL8). Results: Patients with rheumatoid arthritis showed a higher degree of histologically determined inflammation compared with those with osteoarthritis. However, synovial density of gluco-corticoid receptor positive (GR+), androgen receptor positive (AR+), ER alpha+ and ER beta+ cells were not different among patients with rheumatoid arthritis and osteoarthritis. In patients with osteoarthritis, the density of GR+ cells positively correlated with the density of AR+, ERa+ and ERb+ cells (p = 0.007), which was not observed in patients with rheumatoid arthritis. This indicates positively coupled steroid hormone receptor expression in patients with osteoarthritis but not in those with rheumatoid arthritis. In patients with rheumatoid arthritis, secretion of synovial IL6 and IL8 positively correlated with the density of ERa+ and ERb+ cells ( not with gluco-corticoid receptor and androgen receptor), which was not found in the synovium of patients with osteoarthritis. This indicates that inflammatory factors might up regulate the expression of oestrogen receptors in patients with rheumatoid arthritis, or vice versa. Conclusions: In patients with osteoarthritis, expression of different steroid receptors is positively coupled, which was not observed in the synovium of patients with rheumatoid arthritis. This uncoupling phenomenon in rheumatoid arthritis might lead to an imbalance of the normal synovial homeostasis

    Peritoneal fluid macrophages in endometriosis: correlation between the expression of estrogen receptors and inflammation

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    OBJECTIVE: To investigate the expression of estrogen receptors (ERs) and inflammatory cytokines in macrophages obtained from peritoneal fluid (PF) of women with endometriosis. DESIGN: Comparative immunocytochemical study. SETTING: University hospital. PATIENT(S): Thirty women with endometriosis and 22 controls. INTERVENTION(S): The PF samples were collected at laparoscopy. MAIN OUTCOME MEASURE(S): The expression of ERalpha, ERbeta, differentiation markers (CD68, NCL-MACRO, HAM56), and inflammatory cytokines (interleukin [IL]-1beta, tumor necrosis factor-alpha [TNF-alpha], IL-6) in PF macrophages was determined. RESULT(S): The expression of CD68, NCL-MACRO, HAM56, TNFalpha, IL-6, and IL-1beta was significantly higher in PF macrophages obtained from women with endometriosis than in controls. The ERalpha and ERbeta had significantly higher expression in macrophages of women with endometriosis than in controls. A positive correlation was observed between the expression of ERalpha and ERbeta both in women with and without endometriosis. The ERalpha expression was positively correlated with the expression of inflammatory cytokines in women with endometriosis but not in controls; ERbeta expression was correlated to the expression of inflammatory cytokines in the both groups. CONCLUSION(S): There is a correlation between the expression of ERbeta and proinflammatory cytokines both in women with and without endometriosis. The expression of ERalpha correlates with cytokine production selectively in women with endometriosis but not in controls

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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