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ID PMID Title PublicationDate abstract
20166130 Testing for genetic association in the presence of linkage and gene-covariate interactions 2010 Feb In order to study family-based association in the presence of linkage, we extend a generalized linear mixed model proposed for genetic linkage analysis (Lebrec and van Houwelingen (2007), Human Heredity 64, 5-15) by adding a genotypic effect to the mean. The corresponding score test is a weighted family-based association tests statistic, where the weight depends on the linkage effect and on other genetic and shared environmental effects. For testing of genetic association in the presence of gene-covariate interaction, we propose a linear regression method where the family-specific score statistic is regressed on family-specific covariates. Both statistics are straightforward to compute. Simulation results show that adjusting the weight for the within-family variance structure may be a powerful approach in the presence of environmental effects. The test statistic for genetic association in the presence of gene-covariate interaction improved the power for detecting association. For illustration, we analyze the rheumatoid arthritis data from GAW15. Adjusting for smoking and anti-cyclic citrullinated peptide increased the significance of the association with the DR locus.
19952070 The numbers of Foxp3 + Treg cells are positively correlated with higher grade of infiltrat 2010 Feb This study was designed to investigate whether Foxp3( +) regulatory T (Treg) cells play a role in the histopathologic changes of primary Sjögren's Syndrome (pSS) and to evaluate other factors possibly associated with Foxp3(+) Treg cells in pSS patients. The number of FoxP3-expressing T cells in peripheral blood (PB) of 39 patients with pSS, 40 patients with rheumatoid arthritis (RA), and 28 healthy controls was measured by flow-cytometer analysis. FoxP3-expressing CD4(+)CD25(+) Treg cells were analyzed in minor salivary gland (SG) tissues of 39 pSS patients. Histopathologic changes were examined by light microscopy according to Chisholm's classification. Immunohistochemistry and immunofluorescence were performed to assess the Foxp3(+) Treg in SG biopsy specim-ens. The numbers of CD4(+) T cells and FoxP3-expressing CD4(+) T cells in PB were similar in all groups. Expression of CD25 on CD4(+) T cells in PB of patients with pSS and RA was significantly higher than in healthy controls, especially for RA patients. Immunohistochemistry and immunofluorescence showed that FoxP3(+) Treg were enriched in the SGs of pSS patients, with a positive correlation between the increase in FoxP3(+) Treg in SG and the Chisholm score in pSS (p < 0.001, r = +0.605). The increase of FoxP3( +) Treg cells in the SGs of pSS patients, which is correlated with gland infiltration, suggests that natural regulatory T cells play an important role in the pathogenesis of pSS. Further studies are required to explore the mechanisms that mediate the relationship between Treg and the pathogenesis of pSS.
19204014 A plant-derived glucocorticoid receptor modulator attenuates inflammation without provokin 2010 Jan BACKGROUND: Acquired resistance to glucocorticoids constitutes a major clinical challenge, often overlooked in the search for improved alternatives to classic steroids. We sought to unravel how two glucocorticoid receptor-activating compounds, dexamethasone and Compound A, influence glucocorticoid receptor levels and how this can be correlated to their gene regulatory potential. METHODS: Compound A and dexamethasone were applied in a short-term and long-term treatment protocol. By quantitative PCR analysis in fibroblast-like synoviocytes (FLS) the gene regulatory potential of both compounds in the two experimental conditions was analysed. A parallel Western blot assay revealed the glucocorticoid receptor protein levels in both conditions (ex vivo). In addition, this study examined the effect of systemic administration of dexamethasone and Compound A, in concentrations effective to inhibit collagen-induced arthritis, in DBA/1 mice on glucocorticoid receptor levels (in vivo). RESULTS: Compound A does not induce a homologous downregulation of glucocorticoid receptor in vivo and ex vivo, thereby retaining its anti-inflammatory effects after prolonged treatment in FLS. This is in sharp contrast to dexamethasone, showing a direct link between prolonged dexamethasone treatment, decreasing glucocorticoid receptor levels, and the abolishment of inflammatory gene repression in FLS. It was also observed that the acquired low receptor levels after prolonged dexamethasone treatment are still sufficient to sustain the transactivation of endogenous glucocorticoid-responsive element-driven genes in FLS, a mechanism partly held accountable for the metabolic side-effects. CONCLUSION: Compound A is less likely to evoke therapy resistance, as it does not lead to homologous glucocorticoid receptor downregulation, which is in contrast to classic glucocorticoids.
20228199 IL-17-mediated monocyte migration occurs partially through CC chemokine ligand 2/monocyte 2010 Apr 15 Rheumatoid arthritis (RA) is a chronic inflammatory disease that is mediated, in part, by proinflammatory factors produced by RA synovial tissue (ST) fibroblasts and macrophages, resulting in monocyte migration from the blood to the ST. To characterize the potential role of IL-17 in monocyte migration, RA synovial fibroblasts and macrophages were activated with IL-17 and examined for the expression of monocyte chemokines. The two potentially important monocyte chemoattractants identified were CCL20/MIP-3alpha and CCL2/MCP-1, which were significantly induced in RA synovial fibroblasts and macrophages. However, in vivo, only CCL2/MCP-1 was detectable following adenovirus IL-17 injection. We found that IL-17 induction of CCL2/MCP-1 was mediated by the PI3K, ERK, and JNK pathways in RA ST fibroblasts and by the PI3K and ERK pathways in macrophages. Further, we show that neutralization of CCL2/MCP-1 significantly reduced IL-17-mediated monocyte recruitment into the peritoneal cavity. We demonstrate that local expression of IL-17 in ankle joints was associated with significantly increased monocyte migration and CCL2/MCP-1 levels. Interestingly, we show that RA synovial fluids immunoneutralized for IL-17 and CCL2/MCP-1 have similar monocyte chemotaxis activity as those immunoneutralized for each factor alone. In short, CCL2/MCP-1 produced from cell types present in the RA joint, as well as in experimental arthritis, may be responsible, in part, for IL-17-induced monocyte migration; hence, these results suggest that CCL2/MCP-1 is a downstream target of IL-17 that may be important in RA.
20871128 How well do patient reports reflect adverse drug reactions reported by rheumatologists? Ag 2011 Jan OBJECTIVE: To analyse the validity of patient reports on adverse drug reactions (ADRs) compared with the reports given by the treating physician. METHODS: Patients with RA enrolled in the German biologics register rheumatoid arthritis observation of biologic therapy (RABBIT) between May 2001 and September 2006 were included in the study. We investigated concordance of reporting and level of agreement between physician- and patient-reported ADRs, taking the physician as gold standard. RESULTS: Data from 4246 patients were analysed. Patients reported on average 1.2 ADRs per patient-year (PY) compared with 0.8 ADRs reported by the physicians (P<0.001). Gastrointestinal disorders were the most frequently reported ADRs by patients (277.8/1000 PYs) and physicians (137.8/1000 PYs), infections were reported with considerably higher frequency by physicians (124/1000 PYs) than by patients (72/1000 PYs). Agreement between patients and physicians (same or similar event reported at the same time) differed according to the nature of the reported ADR. High agreement was found for easily observable, known ADRs (such as alopecia, agreement 76.7%) In contrast, even for some serious ADRs, many patients did not see a connection between the event and the drug taken (e.g. pneumonia, agreement 37.7%). CONCLUSIONS: Patient reports on ADRs are a useful source of information on the safety of new therapies. However, drug surveillance cannot rely on patient reports only, since even life-threatening events were not reported as ADRs by the patients who failed to associate them with the therapy. When coding patient reports on ADRs to a standard coding system, the differences in language and terminology between patients and physicians should be taken into account.
20595277 Soluble LILRA3, a potential natural antiinflammatory protein, is increased in patients wit 2010 Aug 1 OBJECTIVE: Leukocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of cell-surface receptors with inhibitory or activating functions. LILRA3 lacks transmembrane and cytoplasmic domains, suggesting that it may be secreted. LILRA3 has high homology to activating LILRA1 and A2, hence may act as a soluble agonist/antagonist to these receptors. Individuals lacking the LILRA3 gene have higher incidence of multiple sclerosis and Sjögren's syndrome, suggesting LILRA3 may be antiinflammatory. LILRA3 mRNA was detected in monocytes and mast cells but no protein expression has ever been described. Our aim was to examine LILRA3 protein expression in serum and synovial fluid of patients with rheumatoid arthritis (RA) and determine its in vitro regulation. METHODS: We developed a new ELISA to examine levels of LILRA3 in serum, synovial fluid, and/or culture supernatants from controls and patients with RA, degenerative arthritis, or gout. We used qRT-PCR and flow cytometry to determine the expression and cytokine-mediated regulation of LILRA3. RESULTS: LILRA3 protein is constitutively present in normal serum, with significantly higher concentrations in patients with RA. Serum LILRA3 concentrations from RA patients correlated with disease activity and levels in synovial fluid. Treatment of monocytes with interleukin 10 or interferon-gamma significantly upregulated while tumor necrosis factor-alpha significantly downregulated LILRA3 mRNA and protein expression. CONCLUSION: We show for the first time that LILRA3 is significantly increased in serum of patients with RA and is tightly regulated by key cytokines involved in pathogenesis of RA. These results suggest that LILRA3 may play a role in chronic inflammatory conditions such as RA.
18953542 Impact of sex, age, body mass index and handedness on finger joint space width in patients 2009 Mar To evaluate the associations between sex, age, body mass index (BMI) and handedness regarding the radiogeometric detectable joint space distances of the finger articulations in patients suffering from a prolonged course of rheumatoid arthritis (RA). The joint space widths were measured by a new available Computer-aided joint space analysis (CAJSA); 128 patients with RA underwent computerized semi-automated joint space analysis of joint space distances at the metacarpal-phalangeal articulation (JSD-MCP II-V), proximal-interphalangeal joint (JSD-PIP II-V) and distal-interphalangeal joint (JSD-DIP II-V) based on digitally performed radiographs of the hand (Radiogrammetry Kit, Version 1.3.6; Sectra; Sweden). The joint space distance (JSD) of each articulation was expressed as JSD total in millimeter. The patient cohort was differentiated for gender, age, handedness and BMI (BMI < 20; BMI 20-25, BMI > 25). JSD revealed a significant age-related narrowing of 24.8% (JSD-MCP), 22.6% (JSD-PIP) and 28.7% (JSD-DIP) between the ages of 20 and 79. Additionally, males showed a significantly wider JSD compared to the female cohort for all age groups. All JSD-distances were varied between the right and left hand. The JSD-MCP demonstrated significant differences regarding the BMI groups. In contrast to JSD-MCP an effect of the BMI on measurements of JSD-PIP and JSD-DIP could not be observed. These influences must be differentiated from disease-related alterations caused by RA.
18434448 Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rh 2009 Apr OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.
20105325 A patient with Pfeifer-Weber-Christian disease--successful therapy with cyclosporin A: cas 2010 Jan 27 BACKGROUND: Pfeifer-Weber-Christian disease (PWCD) is a rare inflammatory disorder of the subcutaneous fatty tissue. The diagnosis and therapy of this rare type of panniculitis is still controversial and will be discussed in this article. CASE PRESENTATION: We here report the rare case of a 64-year old male patient, with PWCD. The patient suffered from rheumatoid arthritis for several years, but then developed relapsing fever and recently occurring painful subcutaneous nodules predominantly at the inner part of his left upper limb with no signs of synovitis. Finally, a biopsy from one of the nodules revealed lobular panniculitis with mixed cell infiltrate, which was conformable only with PWCD, after excluding several differential diagnoses. In our patient PWCD developed despite immunosuppressive therapy with steroids and different disease modifying drugs, which the patient received to treat his underlying rheumatoid arthritis. However, when DMARD therapy was switched to Ciclosporin A the patient's symptoms resolved. CONCLUSION: Our observation supports the hypothesis that T cells are involved in the pathogenesis of PWCD. Thus, T cell modifying drugs should be primarily used to treat patients with this rare disorder.
20862788 Pain, executive functioning, and affect in patients with rheumatoid arthritis. 2010 Oct OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease resulting in substantial pain. The physical and emotional effects of RA are well known, but little attention has been given to the potential cognitive effects of RA pain, although intact executive functioning in patients with chronic illness is crucial for the successful completion of many daily activities. We examined the relationship between pain and executive functioning in patients with RA, and also considered the influence of positive and negative affect in the relationship between pain and executive functioning. METHODS: A sample of 157 adults with RA completed measures of pain and positive and negative affect and were tested for working memory and selective attention using the Letter Number Sequencing subtest from the Wechsler Adult Intelligence Scale-Third Edition and the Stroop Color Word Test tests, respectively. RESULTS: Consistent with prior research, pain was inversely related to executive functioning, with higher pain levels associated with poorer performance on executive functioning tasks. This relationship was not moderated or mediated by negative affect; however, positive affect moderated the relationship between pain and executive functioning. For patients high in positive affect there was a significant inverse relationship between pain and executive functioning, whereas there was no such relationship for patients low in positive affect. DISCUSSION: These findings are discussed in the context of cognitive research on the effects of positive affect on executive functioning and functional neuroanatomical research suggesting neurocognitive mechanisms for such moderation.
20472923 Systemic lupus erythematosus, rheumatoid arthritis, and postarthroplasty mortality: a cros 2010 Jul OBJECTIVE: Systemic lupus erythematosus (SLE) is a disease of considerable morbidity, and this may place patients at greater risk for poor in-hospital postoperative outcomes for procedures such as arthroplasty. Our aim was to test this hypothesis. METHODS: We compared the in-hospital postoperative mortality risk for patients with SLE undergoing hip and knee arthroplasty to those with rheumatoid arthritis (RA) and the general population without either condition, using data from the Nationwide Inpatient Sample (1993-2006). We performed parallel, weighted, multivariable logistic regressions to calculate mortality risk stratified by joint site, type of admission, hospital type, income category, race, length of stay, surgical indication, and medical comorbidities. RESULTS: The unadjusted mortality rates (per 1000 procedures) for patients with SLE, patients with RA, and controls were 7.4, 3.0, and 6.5, respectively, for nonelective procedures and 2.4, 1.3, and 1.8 for elective procedures. After adjustment for potential confounders, patients with SLE had an OR of 4.0 (95% CI 1.9-8.0) for postoperative mortality with hip replacements and an OR of 1.2 (95% CI 0.2-7.5) for mortality with knee replacements. Mortality risk of patients with RA was not different from that of controls. The adjusted risk estimates for those who underwent arthroplasty before and after 2002 and those who underwent surgery for nonfracture indications were similar. CONCLUSION: Arthroplasty, especially of hips, in patients with SLE is associated with relatively higher postoperative mortality risk.
20204668 Retrospective clinical study of the efficacy of lower-dose methotrexate and infliximab the 2010 Jun The objective of this study is to compare the long-term outcomes of infliximab therapy with lower-dose methotrexate (MTX; < or = 4 mg per week) and with standard-dose MTX (> or = 6 mg per week) in Japanese rheumatoid arthritis (RA) patients. One hundred thirty-eight patients with refractory RA were treated with intravenous infliximab; 106 patients underwent lower-dose MTX therapy, and 32 patients underwent standard-dose MTX therapy. Treatment responses at 54 weeks or last observation carried forward (LOCF) assessed using the European League Against Rheumatism (EULAR) response criteria were compared between the two groups. Eighty-eight patients (81.1%) in the lower-dose MTX group and 27 patients (84.3%) in the standard-dose MTX therapy completed 54 weeks of infliximab treatment. A EULAR response criteria good and moderate response was seen in 70.9% in the lower-dose group and 74.1% in the standard-dose group. Good and moderate treatment responses at 54 weeks or LOCF were seen in 66.0% in the lower-dose group and 68.7% in the standard-dose group. The outcome in the lower-dose MTX group was not significantly different from that in the standard-dose group. Therapy with MTX and infliximab was effective in Japanese RA patients, regardless of MTX dosage.
19772793 Association of rheumatoid arthritis with Mdm2 SNP309 and genetic evidence for an allele-sp 2009 Jul OBJECTIVE: This study examines two common, functional, single nucleotide polymorphisms (SNP) in the genes coding the human homolog of murine-double-minute-2 (MDM2) and p53 in patients with rheumatoid arthritis (RA) based on the hypothesis that p53 may be an important negative regulator of the pro-inflammatory transcription factor nuclear factor kappa b (NFKappaB). METHODS: Genomic DNA was obtained from 221 patients with RA who fulfilled at least 4 ACR criteria and from 521 healthy controls. Mdm2 SNP309 and p53 P72R were genotyped by polymerase chain reaction and restriction enzyme analysis. RESULTS: In RA patients the frequencies of the mdm2 SNP309 G allele and both G-containing genotypes were significantly reduced (G allele: OR: 0.75, 95% CI: 0.59-0.95, p=0.016; genotype TG: OR: 0.71, 95% CI: 0.50-1.00; genotype GG: OR. 0.58, 95% CI: 0.34-0.99; both: p=0.049). Concerning p53 P72R, no differences in allele or genotype frequencies were detected. A combined analysis of both polymorphisms revealed a significant interaction between them (p=0.046). In individuals carrying >1 p53 72R allele, MDM2 had a protective effect, whereas in individuals homozygous for p53 72P, MDM2 had the opposite effect. CONCLUSION: The function of MDM2 depends on the p53 P72R genotype, resulting in either an increased or reduced risk for RA. We suggest that in most cases MDM2 stabilizes the conformation of p53, whereas in p53 PP-positive subjects MDM2 supports the degradation of p53.
20126902 Relationship between periodontitis and rheumatoid arthritis and the effect of non-surgical 2009 This study analyzed the association of periodontal disease (PD) and rheumatoid arthritis (RA). Seventy-five 35-60-year-old patients were assigned to 5 groups according to the presence (+) or not (-) of PD and RA and the treatment received (TR+) or not (TR-) for PD. Group 3 uses total prosthesis (TP). Clinical and laboratory evaluations were performed at baseline, 3 and 6 months of follow-up by probing pocket depth, bleeding on probing and plaque index for PD, HAQ, DAS28, SF-36 and laboratory: AAG, ESR, CRP for RA. Statistically significant differences for PD after 3 (p=0.0055) and after 6 months (p=0.0066) were obtained in Group 1 (RA+PD+TR+) and 2(RA+PD+TR-); significant reduction in the % of BOP after 6 months (p=0.0128) and significant reduction in the % of Pl after 3 (p=0.0128) and 6 months (p=0.0002) in Group 1. Statistically significant differences between Groups 1 and 3 (RA+TP) for DAS28 at baseline and after 3 months were observed, but not after 6 months. No other parameters for RA were significantly affected. The relationship between RA and PD disease activities is not clear, but the importance of periodontal treatment in the control of inflammation to avoid tooth extraction is evident.
19649562 The intra-articular efficacy of hyaluronate injections in the treatment of rheumatoid arth 2009 To determine whether the intra-articular injection of hyaluronate (HA) is a potential clinical option for the treatment of rheumatoid arthritis (RA), we have evaluated the clinical efficacy of intra-articular corticosteroid and HA by analyzing the patient-based database from a cross-sectional observational cohort. A total of 668 (14.1%) of 4725 patients in the database received injections. The logistic regression analysis showed that the Japanese version of the Stanford Health Assessment Questionnaire functional index [J-HAQ; odds ratio (OR) 1.53, 95% confidence interval (CI) 1.35-1.73] and disease activity score 28 (DAS28; OR 1.28, 95% CI 1.19-1.39) were predictive in the case of receiving a joint injection compared to non-injection. The patient-perceived satisfactory rate of injection was 64.0 (95% CI 51.9-76.2) for corticosteroid injections and 59.3 (95% CI 50.6-67.9) for HA injections; however, there were no significant differences between the corticosteroid and HA injection groups (P < 0.074). Our results demonstrate that HA and corticosteroid injections generally have similar efficacy rates when the patient-perceived satisfactory rate was employed as an index. These results are encouraging, as the use of HA stimulates interest in clinical studies aimed at assessing the potential role of viscosupplementation in treating RA, and HA may represent another treatment option for RA.
19208557 An examination of work instability, functional impairment, and disease activity in employe 2009 Feb OBJECTIVE: To evaluate the relationship between the Disease Activity Score 28-joint count (DAS28), Health Assessment Questionnaire (HAQ), and Rheumatoid Arthritis-Work Instability Scale (RAWIS); and to define thresholds for clinical assessments associated with moderate to high RA-WIS. METHODS: Employed patients with RA were evaluated using DAS28, HAQ, and RA-WIS during routine clinics. Relationships between these assessments were evaluated by simple correlation. Multiple linear regression modeling was performed using RA-WIS as an outcome variable and HAQ, DAS28, age, sex, occupation, and disease duration as input variables. Receiver-operating characteristic curves were then formulated to determine optimal DAS28, and HAQ cutoff points for RA-WIS >or= 10, along with the odds ratio (OR). RESULTS: Ninety patients with RA completed the RA-WIS, which was moderately correlated with DAS28 (r =0.53) and HAQ (r = 0.66). Fifty-four percent of RA-WIS was explained by DAS28 (p = 0.002), HAQ (p = 0.001), and sex (p = 0.04). A DAS28 of 3.81 and HAQ of 0.55 were clinically important thresholds. High DAS28 and HAQ were associated with high RA-WIS (OR(DAS) 14.17, OR(HAQ) 25.13, OR(DAS+HAQ) 29.9). CONCLUSION: Functional impairment and disease activity significantly and independently contributed to patient-perceived work instability risk.
20082236 Comparison of combination therapies in the treatment of rheumatoid arthritis: leflunomide- 2010 May To compare the efficacy and safety of leflunomide (LEF)-anti-TNF-alpha combination therapy to methotrexate (MTX)-anti-TNF-alpha combination therapy in a group of patients with active rheumatoid arthritis (RA). We have recruited 120 patients with RA with a high disease activity despite being treated with MTX (15 mg/week) or LEF (20 mg/die) for 3 months, without side effects. In each of these patients, therapy with either MTX or LEF was continued and randomly combined with an anti-TNF-alpha drug: etanercept, infliximab, or adalimumab. Patients were assessed at study entry and at 4, 12, and at 24 weeks. The efficacy endpoints included variations in the DAS28-ESR and the ACR20, ACR50, and ACR70 responses. At each visit, any side-effect was recorded. There were no statistically significant differences in the DAS28 variations and in the ACR responses between the two groups or among the six subgroups. The number of discontinuation due to the appearance of serious side effects was higher, but not statistically significant, in the LEF-anti-TNF-alpha group than in the MTX-anti-TNF-alpha group. Other adverse events that did not necessitate the discontinuation of therapy occurred much more frequently in patients treated with MTX than in those treated with LEF. Anti-TNF-alpha drugs can be used in combination not only with MTX, but also with LEF, with the same probability of achieving significant clinical improvement in RA patients and without a significantly greater risk of serious adverse events. In contrast, it seems that combination therapy with LEF-anti-TNF-alpha is more readily tolerated than combination therapy with MTX-anti-TNF-alpha.
18813930 Intracellular calcium responses to cholinergic stimulation of lymphocytes from healthy don 2009 Mar This study was performed to identify the role of cholinergic stimulation on changes of intracellular calcium concentrations as intracellular messenger of neuroimmune interaction. Incubation of PBMC with acetylcholine (ACh) leads to Ca(2+) oscillations in healthy controls. PBMC from rheumatoid arthritis (RA) patients exhibited increased basal Ca(2+) concentrations with a significantly reduced capacity to respond upon ACh stimulation compared to healthy controls. It can be assumed that cholinergic signals in PBMC are mediated via the nicotinergic type of ACh receptors, causing changes in intracellular Ca(2+) concentrations with various types of oscillations. The significantly decreased modulation of intracellular Ca(2+) levels by ACh in PBMC of RA patients points further to a disturbed neuroimmune interaction in this chronic disease.
19940000 Targeted drug-delivery approaches by nanoparticulate carriers in the therapy of inflammato 2010 Feb 6 Limitations in therapy induced by adverse effects due to unselective drug availability and therefore the use of potentially too high doses are a common problem. One prominent example for this dilemma are inflammatory diseases. Colloidal carriers allow one to improve delivery of drugs to the site of action and appear promising to overcome this general therapeutic drawback. Specific uptake of nanoparticles by immune-related cells in inflamed barriers offers selective drug targeting to the inflamed tissue. Here we focus on nanocarrier-based drug delivery strategies for the treatment of common inflammatory disorders like rheumatoid arthritis, multiple sclerosis, uveitis or inflammatory bowel disease.
20398000 Rheumatic diseases and Klinefelter's syndrome. 2010 Apr The article summarizes reports on the concurrence of Klinefelter's syndrome (KS) with inflammatory rheumatic diseases, rheumatoid arthritis (RA), juvenile idiopathic arthritis, psoriatic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, systemic sclerosis, mixed connective tissue disease, the antiphospholipid syndrome, and ankylosing spondylitis. These include two case reports of patients with KS concurrently associated with RA or antisynthetase syndrome, respectively, previously reported by the author and his coworkers. Attention is paid to the pathogenesis and the course of the disease in patients with KS. The importance of early diagnosis of the syndrome, when occurring simultaneously with other diseases of connective tissue, is emphasized.