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ID PMID Title PublicationDate abstract
21912419 Preventing and curing citrulline-induced autoimmune arthritis in a humanized mouse model u 2012 Jul Invariant natural killer T (iNKT) cells are innate lymphocytes with unique reactivity to glycolipid antigens bound to non-polymorphic CD1d molecules. They are capable of rapidly releasing pro- and/or anti-inflammatory cytokines and constitute attractive targets for immunotherapy of a wide range of diseases including autoimmune disorders. In this study, we have explored the beneficial effects of OCH, a Th2-polarizing glycolipid agonist of iNKT cells, in a humanized mouse model of rheumatoid arthritis (RA) in which citrullinated human proteins are targeted by autoaggressive immune responses in mice expressing an RA susceptibility human leukocyte antigen (HLA) DR4 molecule. We found for the first time that treatment with OCH both prevents and cures citrulline-induced autoimmune arthritis as evidenced by resolved ankle swelling and reversed histopathological changes associated with arthritis. Also importantly, OCH treatment blocked the arthritogenic capacity of citrullinated antigen-experienced splenocytes without compromising their global responsiveness or altering the proportion of splenic naturally occurring CD4(+)CD25(+)FoxP3(+) regulatory T cells. Interestingly, administering the Th1-promoting iNKT cell glycolipid ligand α-C-galactosylceramide into HLA-DR4 transgenic mice increased the incidence of arthritis in these animals and exacerbated their clinical symptoms, strongly suggesting a role for Th1 responses in the pathogenesis of citrulline-induced arthritis. Therefore, our findings indicate a role for Th1-mediated immunopathology in citrulline-induced arthritis and provide the first evidence that iNKT cell manipulation by Th2-skewing glycolipids may be of therapeutic value in this clinically relevant model, a finding that is potentially translatable to human RA.
22085511 [From splint to smart syringe: the changing perspective of rheumatology]. 2011 Over the course of the past 30 years the outlook for patients with rheumatic arthritis (RA) has changed substantially. The careful "wait-and-see" attitude of rheumatologists of the past has been replaced by early and intensive intervention in patients with early RA. These days it is possible to bring about remission in half of all patients with, among others, the new medicines-- the "biologicals". Auto-antibodies are now detectable in the pre-clinical phase of RA; this means that in the future it will be possible to trace people with a raised risk of developing RA.
21898865 Endogenous prostaglandin E2 inhibits aberrant overgrowth of rheumatoid synovial tissue and 2011 Sep OBJECTIVE: We recently developed an ex vivo cellular model of pannus, the aberrant overgrowth of human synovial tissue. This study was undertaken to use that model to investigate the role of prostaglandin E2 (PGE2) and its receptor subtypes in the development of pannus growth and osteoclast activity in rheumatoid arthritis (RA). METHODS: Inflammatory cells that infiltrated pannus from patients with RA were collected without enzyme digestion and designated synovial tissue-derived inflammatory cells. Their single-cell suspensions were cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue in vitro. Levels of cytokines produced in culture supernatants were measured using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by the development of resorption pits in calcium phosphate-coated slides. RESULTS: Primary culture of the synovial tissue-derived inflammatory cells resulted in spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during which tumor necrosis factor α, PGE2, macrophage colony-stimulating factor, and matrix metalloproteinase 9 were produced in the supernatant. This aberrant overgrowth was inhibited by antirheumatic drugs including methotrexate and infliximab. On calcium phosphate-coated slides, synovial tissue-derived inflammatory cells showed numerous resorption pits. In the presence of inhibitors of endogenous prostanoid production such as indomethacin and NS398, exogenous PGE1 and EP4-specific agonists significantly inhibited all these activities of synovial tissue-derived inflammatory cells in a dose-dependent manner. Addition of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of these cells' activities. EP2-specific agonist had a partial effect, while EP1- and EP3-specific agonists had no significant effects. CONCLUSION: These results suggest that endogenous PGE2 produced in rheumatoid synovium negatively regulates aberrant synovial overgrowth and the development of osteoclast activity via EP4.
21691040 Dosing time-dependency of the arthritis-inhibiting effect of tacrolimus in mice. 2011 Stiffness and cytokine in blood levels show 24-h rhythms in rheumatoid arthritis (RA) patients. We previously revealed that higher therapeutic effects were obtained in RA patients and RA model animals when the dosing time of methotrexate was chosen according to the 24-h rhythms to cytokine. In this study, we examined whether a dosing time-dependency of the therapeutic effect of tacrolimus (TAC) could be detected in collagen-induced arthritis (CIA) and MRL/lpr mice. To measure the levels of cytokines and serum amyloid A (SAA), blood was collected from CIA mice at different times. TAC was administered at two different dosing times based on these findings and its effects on arthritis and toxicity were examined. Plasma tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), and SAA concentrations showed obvious 24-h rhythms with higher levels during the light phase and lower levels during the dark phase after RA crisis. The arthritis score and leukocyte counts were significantly lower in the group treated at 2 h after the light was turned on (HALO) than in the control and 14 HALO-treated groups. Our findings suggest that choosing an optimal dosing time could lead to the effective treatment of RA by TAC.
21767791 [The "outcome benchmarking in rheumatologic acute care" project of the Association of Rheu 2011 By initiating and taking part in the pilot project obra (outcome benchmarking in rheumatologic acute care), which was supported by the German Ministry of Health, the rheumatologic hospitals committed themselves to the continuous improvement of quality through a collective benchmarking and learning process. In addition to verifiable and concrete improvements in quality, the major achievements of the obra pilot project include a cultural change in the participating hospitals as well as the continuation of outcome benchmarking and its expansion to an increasing number of hospitals.
22942329 Combination therapy for pain management in inflammatory arthritis: a Cochrane systematic r 2012 Sep OBJECTIVE: To assess the efficacy and safety of combination pain therapy for people with inflammatory arthritis (IA). METHODS: Systematic review of randomized controlled trials using Cochrane Collaboration methodology. Combination therapy was defined as at least 2 drugs from the following classes: analgesics, nonsteroidal antiinflammatory drugs (NSAID), opioids, opioid-like drugs, and neuromodulators (antidepressants, anticonvulsants, and muscle relaxants). The main efficacy and safety outcomes were pain and withdrawals due to adverse events, respectively. RESULTS: Twenty-three trials (total of 912 patients) met inclusion criteria [22 in rheumatoid arthritis (RA) and 1 in a mixed population of RA and osteoarthritis]. All except 1 were published before 1990. All trials were at high risk of bias, and heterogeneity precluded metaanalysis. Statistically significant differences between treatment groups were reported in only 5/23 (22%) trials: in 3 trials combination therapy was better (2 trials with NSAID + analgesic versus NSAID only and 1 trial with 2 NSAID versus 1 NSAID), in 1 trial combination therapy was worse (opioid + neuromodulator versus opioid only), and in the fifth trial (NSAID + analgesic versus NSAID alone) reported results were mixed depending on the dosage used in the monotherapy arm. In general, there were no differences in safety and withdrawals due to inadequate analgesia between combination and monotherapy. CONCLUSION: Based on 23 trials, all at high risk of bias, there is insufficient evidence to establish the value of combination therapy over monotherapy for pain management in IA. Well-designed trials are needed to address this question.
23259655 A fresh look at glucocorticoids how to use an old ally more effectively. 2012 Glucocorticoids form a mainstay of therapy for rheumatoid arthritis (RA) and other conditions since they exert strong anti-inflammatory, immunosuppressive, and disease-modifying therapeutic effects. However, there is increasing awareness of the potential for these drugs to produce adverse effects. Therefore, improvement of the glucocorticoid benefit-risk ratio represents both a current need and an ongoing challenge. The development of recommendations to implement a more effective and safer use of these important drugs is one useful path to pursue. An additional avenue is the development of innovative glucocorticoids or glucocorticoid receptor ligands. Also, treatment with conventional glucocorticoid preparations currently available to clinicians may be improved. The most advanced development in the latter regard is a novel chronotherapeutic prednisone formulation called delayed- release (DR) or modified-release prednisone. The CAPRA (Circadian Administration of Prednisone in Rheumatoid Arthritis) studies confirmed that optimizing the timing of GC administration improves the benefit-risk ratio of long- term low dose glucocorticoid treatment in patients with rheumatoid arthritis. DR prednisone has been approved in 16 European countries as well as Australia and Israel. Very recently, DR prednisone was also approved in the United States to treat rheumatologic conditions such as RA, polymyalgia rheumatica and psoriatic arthritis, as well as respiratory conditions such as COPD and asthma.
21613311 A dominant suppressive MHC class II haplotype interacting with autosomal genes controls au 2011 Sep OBJECTIVE: To investigate the genetic control of chronic arthritis and collagen epitope specific antibody responses in an experimental model for rheumatoid arthritis. METHODS: The chronic collagen induced arthritis (CCIA) model was used, induced with collagen type II (CII) in mineral oil lacking mycobacterium in BALB/c (n=24), B10.Q (n=44), (BALB/c × B10.Q) F1 (n=85) and B10.Q × (BALB/c × B10.Q) N2 (n=684) mice. Genome-wide genotyping for 190 N2 mice was performed with extreme phenotypes: chronic arthritis that persisted for 4 months or non-affected. Statistical and linkage analysis were performed with R/qtl software using arthritis and serum subphenotypes. RESULTS: (BALB/c × B10.Q) F1 mice were highly prone to develop a chronic relapsing arthritis (66%), whereas both parental strains were relatively resistant: BALB/c (H-2(d); 0%) and B10.Q (H-2(q); 4.5%). CCIA experiments were performed on 684 mice backcrossed to B10.Q; 38% of the mice developed arthritis and more than half of them developed chronic arthritis phenotype. Genome-wide genotyping revealed mainly the major histocompatibility complex (MHC) locus that had an independent and dominant influence on the chronicity. Interestingly, the H2(d) allele had a dominant suppressive effect. This effect overrode the role of other loci as interaction analysis, after conditioning MHC, revealed additional loci, controlling arthritis and autoantibody phenotypes. CONCLUSIONS: A dominant negative influence of specific MHC haplotype (H2(d)) on CCIA was identified. Further, loci controlling the autoantibody response to different CII epitopes were also identified, and it has been shown that these are dependent on MHC and non-MHC genes.
22848374 Helminth antigens enable CpG-activated dendritic cells to inhibit the symptoms of collagen 2012 Dendritic cells (DC) have the potential to control the outcome of autoimmunity by modulating the immune response. In this study, we tested the ability of Fasciola hepatica total extract (TE) to induce tolerogenic properties in CpG-ODN (CpG) maturated DC, to then evaluate the therapeutic potential of these cells to diminish the inflammatory response in collagen induced arthritis (CIA). DBA/1J mice were injected with TE plus CpG treated DC (T/C-DC) pulsed with bovine collagen II (CII) between two immunizations with CII and clinical scores CIA were determined. The levels of CII-specific IgG2 and IgG1 in sera, the histological analyses in the joints, the cytokine profile in the draining lymph node (DLN) cells and in the joints, and the number, and functionality of CD4+CD25+Foxp3+ T cells (Treg) were evaluated. Vaccination of mice with CII pulsed T/C-DC diminished the severity and incidence of CIA symptoms and the production of the inflammatory cytokine, while induced the production of anti-inflammatory cytokines. The therapeutic effect was mediated by Treg cells, since the adoptive transfer of CD4+CD25+ T cells, inhibited the inflammatory symptoms in CIA. The in vitro blockage of TGF-β in cultures of DLN cells plus CII pulsed T/C-DC inhibited the expansion of Treg cells. Vaccination with CII pulsed T/C-DC seems to be a very efficient approach to diminish exacerbated immune response in CIA, by inducing the development of Treg cells, and it is therefore an interesting candidate for a cell-based therapy for rheumatoid arthritis (RA).
21794769 [Tocilizumab in rheumatoid arthritis]. 2011 Mar Tocilizumab (TCZ) is a humanized monoclonal antibody directed against the receptor for IL-6, approved for the treatment of rheumatoid arthritis (RA) in Japan, Europe and the US. Wide clinical development has shown the efficacy of TCZ in most of the possible situations of RA: RA without prior failure to MTX (AMBITION), RA unresponsive to MTX (SATORI, OPTION, LITHE) or any DMARD (TOWARD, ROSE) as well as RA refractory to anti-TNFa agents (RADIATE). In addition to its early onset, efficacy was constant and even increased as time passed (GROWTH95, GROWTH96). TCZ has shown great efficacy in correcting laboratory alterations in RA, both in acute phase reactants as well as anemia of inflammatory disease. Although in RA TCZ us initially indicated in combination with MTX, it has also shown its efficacy as monotherapy (AMBITION). TCZ is equally effective in the prevention of structural damage (SAMURAI, LITHE). In addition, it has shown to be a safe and well-tolerated drug, similar to other biologic therapies. All of these aspects make TCZ an adequate therapeutic alternative to be considered in any RA scenario.
21187297 Tumour necrosis factor alpha-driven IL-32 expression in rheumatoid arthritis synovial tiss 2011 Apr OBJECTIVE: To investigate the interplay between IL-32 and tumour necrosis factor alpha (TNFα) during the chronic inflammation of rheumatoid arthritis (RA) and to assess whether anti-TNFα treatment of RA patients modulates synovial IL-32 expression. METHODS: Induction of IL-32γ by Pam3Cys, lipopolysaccharide, IL-1β or TNFα was investigated in human fibroblast-like synoviocytes (FLS). Stimulation of TNFα production by IL-32γ was studied by adenoviral overexpression of IL-32γ (AdIL-32γ) and lipopolysaccharide stimulation of THP1 cells. Silencing of endogenous IL-32 was employed to study cytokine regulation in FLS. AdIL-32γ followed by TNFα stimulation was performed in FLS to investigate cytokine induction. Immunohistochemistry was applied to study IL-32 expression in synovial biopsies from RA patients. RESULTS: TNFα potently induced IL-32γ expression in FLS. Increased TNFα, IL-1β, IL-6 and CXCL8 production was observed after IL-32γ overexpression and lipopolysaccharide stimulation of THP1 cells. TNFα stimulation of FLS after silencing IL-32γ resulted in diminished IL-6 and CXCL8 production, whereas IL-32γ overexpression resulted in enhanced IL-6 and CXCL8 levels. Remarkably, the mechanism through which IL-32γ overexpression induced TNFα, IL-1β and CXCL8 was by counteracting messenger RNA decay. Importantly, treatment of RA patients with anti-TNFα resulted in significant reduction of IL-32 protein in synovial tissue. CONCLUSIONS: TNFα is a potent inducer of endogenous IL-32 expression and IL-32 itself contributes to prolonged TNFα production, thus inducing an important auto-inflammatory loop. Treatment of RA patients with anti-TNFα antibodies diminished IL-32 expression in synovial tissue. The potent anti-inflammatory effect of TNFα blockade in RA patients may be partly due to the reduction of synovial IL-32 expression.
23211089 Disease activity and cognition in rheumatoid arthritis: an open label pilot study. 2012 Dec 4 INTRODUCTION: We hypothesised that fatigue in rheumatoid arthritis (RA) is related to TNF-alpha induced dysregulation of cerebral blood flow. Our objectives were to assess fatigue, cognitive function and cerebral blood flow before and after initiation of anti-TNF treatment. METHODS: In a pilot study, 15 patients initiating treatment with adalimumab were assessed for fatigue using a visual analogue scale (FACIT-F), cognitive function using a panel of psychometric tests and regional cerebral blood flow using MR perfusion imaging. RESULTS: Patients improved clinically after anti-TNF therapy in terms of DAS28 and FACIT-F. Furthermore significant improvements were documented in full scale, verbal and performance IQ following therapy. There was a non-significant trend towards reduced cerebral perfusion in both grey and white matter, and fatigue at 3 months correlated with cerebral blood flow in white (p = 0.014) and grey (p = 0.005) matter. CONCLUSIONS: We demonstrate for the first time a significant improvement in cognitive function following effective treatment of RA. Although we observed minor reductions in cerebral blood flow, and a correlation between cerebral blood flow and fatigue, a larger, controlled study would be required to affirm a causal relationship.
21872430 The antigen specificity of the rheumatoid arthritis-associated ACPA directed to citrullina 2011 Dec The major targets of the disease-specific autoantibodies to citrullinated proteins (ACPA) in synovium of rheumatoid arthritis (RA) patients are borne by the citrullinated α- and β-chains of fibrin. We demonstrated that ACPA target a limited set of citrullinated fibrin peptides and particularly four multicitrullinated peptides which present the major epitopes. In this study, we established the clear immunodominance of the peptides α36-50Cit(38,42) and β60-74Cit(60,72,74) which were recognised by 51/81 (63%) and 61/81 (75%) of ACPA-positive patients, respectively, more than 90% recognising one, the other or both peptides. We also identified the citrullyl residues αCit(42), βCit(72) and βCit(74) as essential for antigenicity, and at a lesser degree αCit(38). Then, we assayed on overlapping 7-mer peptides encompassing the sequences of the two peptides, 3 series of sera recognising either α36-50Cit(38,42) or β60-74Cit(60,72,74) or both peptides. In each series, the reactivity profiles of the sera, largely superimposable, allowed identification of the two 4/5-mer overlapping epitopes (α: VECit(42)HQ and α': Cit(38)VVE), and the single 5-mer epitope (β: GYCit(72)ACit(74)), all located to a flexible globular domain of fibrin on a topological 3D model. In conclusion, we demonstrated that only 3 immunodominant epitopes are targeted by ACPA on citrullinated fibrin stressing their actual oligoclonality. However, the reactivity to the 3 epitopes distinguishes three subgroups of patients. The closely restricted antigen specificity suggests that the autoimmune reaction to citrullinated fibrin is antigen-driven. The accessibility of the epitopes reinforces the hypothesis of a pathogenic role for ACPA via immune complexe formation in the synovial tissue.
20924627 Serum cysteine proteases and their inhibitors in rheumatoid arthritis: relation to disease 2011 May This study aims to investigate the serum levels of cysteine proteases cathepsins B and H and their inhibitors stefin A, stefin B, and cystatin C, as well as traditional inflammatory markers such as C-reactive protein in patients with rheumatoid arthritis and to correlate these markers with scores of disease activity and radiographic progression. Seventy-two patients with rheumatoid arthritis were included from two previously described cohorts of patients with chronic polyarthritis. At inclusion, disease activity was assessed by a 28-joint count, patient global assessment, and serum C-reactive protein. Erosive status of hands and wrists was expressed by the Larsen score and recorded at inclusion and after 1 year. Serum levels of cathepsin B, cathepsin H, stefin A, stefin B, and cystatin C were determined by enzyme-linked immunosorbent assay. Neither cathepsin B nor cathepsin H serum levels were associated with disease activity, presence or progression of erosive disease. Number of swollen joints correlated with serum levels of stefin A and B and correlated negatively with cystatin C serum levels. Erosive disease was associated with high serum levels of C-reactive protein and stefin A and low serum levels of cystatin C. Progression of radiographic destruction was associated with high serum levels of C-reactive protein, stefin A and B, whereas serum levels of cystatin C were not associated with radiographic progression. The findings in this study support further investigation in the regulation of the activity of cathepsins and their inhibitors in erosive rheumatoid arthritis.
21953304 Development of a novel recombinant biotherapeutic with applications in targeted therapy of 2011 Dec OBJECTIVE: To isolate recombinant antibodies with specificity for human arthritic synovium and to develop targeting reagents with joint-specific delivery capacity for therapeutic and/or diagnostic applications. METHODS: In vivo single-chain Fv (scFv) antibody phage display screening using a human synovial xenograft model was used to isolate antibodies specific to the microvasculature of human arthritic synovium. Single-chain Fv antibody tissue-specific reactivity was assessed by immunostaining of synovial tissues from normal controls and from patients with rheumatoid arthritis and osteoarthritis, normal human tissue arrays, and tissues from other patients with inflammatory diseases displaying neovasculogenesis. In vivo scFv antibody tissue-specific targeting capacity was examined in the human synovial xenograft model using both (125)I-labeled and biotinylated antibody. RESULTS: We isolated a novel recombinant human antibody, scFv A7, with specificity for the microvasculature of human arthritic synovium. We showed that in vivo, this antibody could efficiently target human synovial microvasculature in SCID mice transplanted with human arthritic synovial xenografts. Our results demonstrated that scFv A7 antibody had no reactivity with the microvasculature or with other cellular components found in a comprehensive range of normal human tissues including normal human synovium. Further, we showed that the reactivity of the scFv A7 antibody was not a common feature of neovasculogenesis associated with chronic inflammatory conditions. CONCLUSION: Here we report for the first time the identification of an scFv antibody, A7, that specifically recognizes an epitope expressed in the microvasculature of human arthritic synovium and that has the potential to be developed as a joint-specific pharmaceutical.
21435227 The role of synovial fluid markers of catabolism and anabolism in osteoarthritis, rheumato 2011 Mar 24 INTRODUCTION: The purpose of this study was to correlate the level of anabolic and catabolic biomarkers in synovial fluid (SF) from patients with rheumatoid arthritis (RA), patients with osteoarthritis (OA) and asymptomatic organ donors. METHODS: SF was collected from the knees of 45 OA, 22 RA patients and 20 asymptomatic organ donors. Eight biomarkers were selected and analyzed by using an enzyme-linked immunosorbent assay: interleukin (IL)-1, IL-6, IL-8 and IL-11; leukemia-inhibitory factor (LIF); cartilage oligomeric protein (COMP); osteocalcin; and osteogenic protein 1 (OP-1). Data are expressed as medians (interquartile ranges). The effects of sex and disease activity were assessed on the basis of the Western Ontario and McMaster Universities index score for patients with OA and on the basis of white blood cell count, erythrocyte sedimentation rate and C-reactive protein level for patients with RA. RESULTS: The mean ages (± SD) of the patients were as follows: 53 ± 9 years for patients with OA, 54 ± 11 years for patients with RA and 52 ± 7 years for asymptomatic organ donors. No effect of participants' sex was identified. In the SF of patients with RA, four of five cytokines were higher than those in the SF of patients with OA and those of asymptomatic organ donors. The most significant differences were found for IL-6 and IL-8, where IL-6 concentration in SF of patients with RA was almost threefold higher than that in patients with OA and fourfold higher than that in asymptomatic donor controls: 354.7 pg/ml (1,851.6) vs. 119.4 pg/ml (193.2) vs. 86.97 pg/ml (82.0) (P < 0.05 and P < 0.05, respectively). IL-8 concentrations were higher in SF of patients with RA than that in patients with OA as well as that in asymptomatic donor controls: 583.6 pg/ml (1,086.4) vs. 429 pg/ml (87.3) vs. 451 pg/ml (170.1) (P < 0.05 and P < 0.05, respectively). No differences were found for IL-11 in the SF of patients with RA and that of patients with OA, while a 1.4-fold difference was detected in the SF of patients with OA and that of asymptomatic donor controls: 296.2 pg/ml (257.2) vs. 211.6 pg/ml (40.8) (P < 0.05). IL-1 concentrations were the highest in the SF of RA patients (9.26 pg/ml (11.1)); in the SF of asymptomatic donors, it was significantly higher than that in patients with OA (9.083 pg/ml (1.6) vs. 7.76 pg/ml (2.6); P < 0.05). Conversely, asymptomatic donor control samples had the highest LIF concentrations: 228.5 pg/ml (131.6) vs. 128.4 pg/ml (222.7) in the SF of patients with RA vs. 107.5 pg/ml (136.9) in the SF of patients with OA (P < 0.05). OP-1 concentrations were twofold higher in the SF of patients with RA than those in patients with OA and threefold higher than those in asymptomatic donor control samples (167.1 ng/ml (194.8) vs. 81.79 ng/ml (116.0) vs. 54.49 ng/ml (29.3), respectively; P < 0.05). The differences in COMP and osteocalcin were indistinguishable between the groups, as were the differences between active and inactive OA and RA. CONCLUSIONS: Activation of selected biomarkers corresponds to the mechanisms that drive each disease. IL-11, LIF and OP-1 may be viewed as a cluster of biomarkers significant for OA; while profiling of IL-1, IL-6, IL-8, LIF and OP-1 may be more significant in RA. Larger, better-defined patient cohorts are necessary to develop a biomarker algorithm for prognostic use.
22103390 Does ultrasound guidance improve the outcomes of arthrocentesis and corticosteroid injecti 2012 Feb OBJECTIVE: The present randomized controlled trial compared arthrocentesis of the effusive knee followed by corticosteroid injection performed by the conventional anatomic landmark palpation-guided technique to the same procedure performed with ultrasound (US) needle guidance. METHODS: Sixty-four palpably effusive knees were randomized to (i) palpation-guided arthrocentesis with a conventional 20-mL syringe (22 knees), (ii) US-guided arthrocentesis with a 25-mL reciprocating procedure device (RPD) mechanical aspirating syringe (22 knees), or (iii) US-guided arthrocentesis with a 60-mL automatic aspirating syringe (20 knees). The one-needle two-syringe technique was used. Outcome measures included patient pain by the Visual Analogue Scale (VAS) for pain (0-10 cm), the proportion of diagnostic samples, synovial fluid volume yield, complications, and therapeutic outcome at 2 weeks. RESULTS: Sonographic guidance resulted in 48% less procedural pan (VAS; palpation-guided: 5.8 ± 3.0 cm, US-guided: 3.0 ± 2.8 cm, p < 0.001), 183% increased aspirated synovial fluid volumes (palpation-guided: 12 ± 10 mL, US-guided: 34 ± 25 mL, p < 0.0001), and improved outcomes at 2 weeks (VAS; palpation-guided: 2.8 ± 2.4 cm, US-guided: 1.5 ± 1.9 cm, p = 0.034). Outcomes of sonographic guidance with the mechanical syringe and automatic syringe were comparable in all outcome measures. CONCLUSIONS: US-guided arthrocentesis and injection of the knee are superior to anatomic landmark palpation-guided arthrocentesis, resulting in significantly less procedural pain, improved arthrocentesis success, greater synovial fluid yield, more complete joint decompression, and improved clinical outcomes.
22610585 Effects of aurothiomalate and gold(III) complexes on spontaneous motility of isolated huma 2012 Oct Organic gold complexes have different biological activity, depending on their potential for interactions with key functional molecules.The aim of this study was to investigate potential of several newly synthesized organic gold complexes to influence spontaneous motility of the Fallopian tubes.The effects of [Au(bipy)Cl(2)](+) (dichloride(2,2'-bipyridyl)aurate(III)-ion), aurothiomalate, [Au(DMSO)(2)Cl(2)]Cl and DMSO on spontaneous motility of Fallopian tubes were tested on the isolated tube segments in vitro. Aurothiomalate (from 2.9 × 10(-9) to 4.9 × 10(-4) M/l), [Au(bipy)Cl(2)]Cl (from 3.3 × 10(-9) to 4.2 × 10(-5) M/l) and DMSO (from 1.9 × 10(-8) to 1.0 × 10(-5) M/l) did not affect spontaneous contractions of the isolated Fallopian tube ampulla, while [Au(DMSO)(2)Cl(2)]Cl (from 2.9 × 10(-9) to 4.2 × 10(-5) M/l) showed concentration-dependent increase (stimulation) of spontaneous contractions of the isolated Fallopian tube isthmus, and remained without effect on the isolated ampulla.The drugs designed as organic gold complexes with weaker bonds between the gold itself and organic part of a molecule could adversely affect motility of the Fallopian tubes, and theoretically fertility of women taking such drugs in their reproductive age.
21864722 Vitamin D endocrine system involvement in autoimmune rheumatic diseases. 2011 Dec Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels.
22794097 Advances in the treatment of inflammatory arthritis. 2012 Apr The inflammatory arthritides are a diverse group of conditions characterised by joint inflammation which can lead to pain, deformity and disability. Of these diseases, rheumatoid arthritis (RA) and spondyloarthritis are two of the most common. While the clinical and demographic features of these diseases differ, the central role of inflammation in their pathogenesis has allowed the development of highly effective treatment strategies with wide applicability. These strategies include the use of biological agents which target the cytokine tumour necrosis factor (TNF), a key mediator of inflammation. With the advent of effective agents, therapy has become more aggressive, reducing disease activity and allowing, at least in RA, remission in many patients. While the array of available effective treatments is extensive, the use of objective measures of disease activity can guide treatment decisions (treat to target) and lead to improved outcomes.