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ID PMID Title PublicationDate abstract
26583877 Feasibility study of using intravoxel incoherent motion mri to detect parotid gland abnorm 2016 Jun PURPOSE: To determine whether intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) could detect parotid gland abnormalities in Sjögren's syndrome (SS) patients who were not identified by conventional MRI. MATERIALS AND METHODS: Ten consecutive patients with clinically proven SS who were not identified by conventional MRI were assessed by IVIM MRI with a 3.0T MRI scanner. Quantitative parameters (tissue diffusivity, D; pseudodiffusion coefficient, D*; perfusion fraction, f) derived from IVIM MRI were compared between the SS group and healthy control group (n = 15). A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of each significant parameter. RESULTS: Excellent inter- and intrareader agreements were obtained during the measurement of D, f, and D* values (interreader, 0.980, 0.942, and 0.883; intrareader, 0.991, 0.952, and 0.896, respectively). All three parameters of the SS group were significantly higher than those of the healthy group (D, 1.049 ± 0.056 × 10(-3) mm(2) /s vs. 0.976 ± 0.116 × 10(-3) mm(2) /s, P = 0.012; D*, 20.410 ± 1.786 × 10(-3) mm(2) /s vs. 18.764 ± 2.433 × 10(-3) mm(2) /s, P = 0.013; f, 0.207 ± 0.003 vs. 0.182 ± 0.002, P = 0.004). ROC analysis showed that the f value had the best diagnostic performance (AUC, 0.712; Sensitivity, 0.80; Specificity, 0.57; Cutoff value, 0.185) in detecting the parotid gland abnormalities in early SS patients. CONCLUSION: IVIM MRI detected parotid gland abnormalities in early-stage SS patients. J. Magn. Reson. Imaging 2016;43:1455-1461.
25743017 Corticoid therapy for overlapping syndromes in an HIV-positive patient. 2015 Human immunodeficiency virus (HIV) infection disturbs the host's immune function and often coexists with various autoimmune and/or systemic rheumatic diseases with manifestations that sometimes overlap with each other. We herein present the case of a 43-year-old Japanese man infected with HIV who exhibited elevated serum creatine kinase and transaminases levels without any symptoms. He was diagnosed with autoimmune hepatitis, polymyositis and Sjögren's syndrome and received combined antiretroviral therapy (cART); however, the laboratory abnormalities persisted. We successfully administered cART with the addition of oral prednisolone, and the patient's condition recovered without side effects related to the metabolic or immunosuppressive effects of these drugs.
25512474 The Interleukin 33/ST2 axis in patients with primary Sjögren syndrome: expression in seru 2015 Feb OBJECTIVE: To evaluate the expression of interleukin 33 (IL-33) and its receptor in sera and salivary tissues of patients with primary Sjögren syndrome (pSS), and to investigate the association with clinical profiles. METHODS: Serum IL-33 and soluble ST2 (sST2) of 55 patients with pSS and 48 controls were determined by ELISA and assessed for clinical correlation. The expression of IL-33/ST2 in salivary tissues was investigated by immunohistochemical staining and was further characterized by confocal microscopy. We also measured IL-33 production in salivary glandular epithelial cells by proinflammatory stimuli. RESULTS: Serum levels of IL-33 and sST2 were higher in patients with pSS compared to those in controls (p = 0.018 and p < 0.0001, respectively). Among patients with pSS, sST2 concentration was associated with thrombocytopenia (p = 0.029) and correlated with disease duration (p = 0.013) and the European League Against Rheumatism Sjögren Syndrome Disease Activity Index (p = 0.042). The expression of IL-33 and ST2 was elevated in salivary glands of patients with pSS with grade 2 inflammation, and diminished in advanced inflammation. In patients with pSS, IL-33 was mainly observed in epithelial and endothelial cells of glandular tissue. The production of IL-33 mRNA by salivary gland epithelial cell line increased under stimulation with interferon-γ. CONCLUSION: The expression of IL-33 and its receptor was elevated in sera and salivary tissues of patients with pSS. These results suggest that the IL-33/ST2 axis might have a role in the pathogenesis of pSS.
24661359 Immunolocalization of AQP5 in resting and stimulated normal labial glands and in Sjögren' 2015 Jan OBJECTIVE: In our current work, in vivo examination of AQP5 distribution in labial salivary glands following stimulation of secretion has been carried out in normal individuals and in patients with Sjögren's syndrome. SUBJECTS AND METHODS: For this study, we selected five patients with primary Sjögren's syndrome (mean age 62.4 ± 10.6 s.d. years) diagnosed in accordance with the European Cooperative Community classification criteria. There were five patients (mean age 27 ± 2.5 s.d. years) in the control group. The subcellular distribution of AQP5 in human labial gland biopsies was determined with light and immunoelectron microscopy before and 30 min after administration of oral pilocarpine. RESULTS: In unstimulated control and Sjögren's labial glands, AQP5 is about 90% localized in the apical plasma membrane, with only rarely associated gold particles with intracellular membrane structures. We have found no evidence of pilocarpine-induced changes in localization of AQP5 in either healthy individuals or patients with Sjögren's syndrome. CONCLUSIONS: Our studies indicate that neither Sjögren's syndrome itself, nor muscarinic cholinergic stimulation in vivo caused any significant changes in the distribution of AQP5 in the labial salivary gland cells.
26872871 Steroid-resistant protein-losing gastroenteropathy complicated with Sjögren's syndrome su 2018 Jul A 64-year-old woman with leg edema was diagnosed with protein-losing gastroenteropathy and Sjögren's syndrome. Central venous nutrition led to infection of her catheter, ascites, and deep vein thrombosis. Following successful treatment of these conditions with antibiotics and anticoagulants, she was treated unsuccessfully with prednisolone and steroid pulse therapy. Mizoribine add-on markedly reduced edema and normalized serum albumin. This is the first report of a steroid-resistant protein-losing gastroenteropathy patient with Sjögren's syndrome successfully treated with mizoribine.
26866723 Association of Increased Treg Cell Levels With Elevated Indoleamine 2,3-Dioxygenase Activi 2016 Jul OBJECTIVE: Indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme that converts tryptophan to kynurenine, is driven in part by type I and type II interferons (IFNs). Naive T cells are polarized into FoxP3+ Treg cells upon exposure to either IDO+ cells or kynurenine. Recent studies have suggested that the kynurenine pathway reflects a crucial interface between the immune and nervous system. The aims of the present study were to evaluate whether Treg cell levels are elevated, in conjunction with increased IDO activity, in patients with primary Sjögren's syndrome (SS) who are positive for the IFN gene expression signature, and to investigate the downstream kynurenine pathway in these patients. METHODS: Serum from 71 healthy controls, 58 IFN-negative patients with primary SS, and 66 IFN-positive patients with primary SS was analyzed using high-performance liquid chromatography to measure the levels of tryptophan and kynurenine. Expression levels of messenger RNA (mRNA) for IDO and downstream enzymes in the kynurenine pathway were assessed in CD14+ monocytes using real-time quantitative polymerase chain reaction. CD4+CD45RO+ T helper memory cell populations were analyzed by flow cytometry. RESULTS: Significantly increased levels of IDO activity (assessed as the kynurenine:tryptophan ratio) (P = 0.0054) and percentages of CD25(high) FoxP3+ Treg cells (P = 0.039) were observed in the serum from IFN-positive patients with primary SS, and these parameters were significantly correlated with one another (r = 0.511, P = 0.002). In circulating monocytes from IFN-positive patients with primary SS, the expression of IDO1 mRNA was up-regulated (P < 0.0001), and this was correlated with the IFN gene expression score (r = 0.816, P < 0.0001). Interestingly, the proapoptotic and neurotoxic downstream enzyme kynurenine 3-monooxygenase was up-regulated (P = 0.0057), whereas kynurenine aminotransferase I (KATI) (P = 0.0003), KATIII (P = 0.016), and KATIV (P = 0.04) were down-regulated in IFN-positive patients with primary SS compared to healthy controls. CONCLUSION: These findings demonstrate enhanced IDO activity in conjunction with increased percentages of CD25(high) FoxP3+ Treg cells in primary SS patients who carry the IFN signature. In addition, IFN-positive patients with primary SS exhibit an imbalanced kynurenine pathway, with evidence of a shift toward potentially more proapoptotic and neurotoxic metabolites. Intervening in these IFN- and IDO-induced immune system imbalances may offer a new array of possibilities for therapeutic interventions in patients with primary SS.
26423426 Clinical and serologic features of primary Sjögren's syndrome concomitant with autoimmune 2015 Nov Autoimmune hemolytic anemia (AIHA) is an uncommon but clinically significant disorder in primary Sjögren's syndrome (pSS). Among 565 pSS patients hospitalized in Peking University People's Hospital from January 2000 to March 2013, 16 patients were diagnosed with AIHA (2.8% prevalence). AIHA presented at the onset of pSS without overt sicca symptoms in 3 of the 16 patients. Primary biliary cirrhosis (PBC) was more prevalent in the patients with SS-AIHA than in those without (p = 0.007). Edema, fever, and liver involvement occurred significantly more frequently in pSS patients with AIHA than those without AIHA (p = 0.035, p = 0.029, p = 0.024, respectively). The pSS patients with AIHA were more vulnerable to leukopenia and thrombocytopenia than those without AIHA (p = 0.004 and p = 0.001, respectively). Additionally, the levels of complement component 3 (C3) and complement component 4 (C4) were significantly lower in the SS-AIHA group (p = 0.008 and p = 0.037, respectively). Taken together, our results indicate that pSS should be considered in the differential diagnosis of AIHA, even in the absence of sicca symptoms. Among pSS patients, the existence of PBC, cytopenia, or hypocomplementemia suggests a higher risk of suffering from AIHA.
26143430 Granulomatous Drug Eruptions. 2015 Jul Granuloma formation is usually regarded as a means of defending the host from persistent irritants of either exogenous or endogenous origin. Noninfectious granulomatous disorders of the skin encompass a challenging group of diseases owing to their clinical and histologic overlap. Drug reactions characterized by a granulomatous reaction pattern are rare, and defined by a predominance of histiocytes in the inflammatory infiltrate. This review summarizes current knowledge on the various types of granulomatous drug eruptions, focusing on the 4 major types: interstitial granulomatous drug reaction, drug-induced accelerated rheumatoid nodulosis, drug-induced granuloma annulare, and drug-induced sarcoidosis.
26060357 T Regulatory and T Helper 17 Cells in Primary Sjögren's Syndrome: Facts and Perspectives. 2015 Historically, primary Sjögren's syndrome (pSS) was thought to be a T helper (h) 1 driven disease due to the predominance of CD4(+)T lymphocytes and their products in target organs and peripheral blood of patients. In the last decades, the identification of a number of T cell subsets, including Th17, T regulatory (Treg), and follicular helper T cells, challenged this long-standing paradigm and prompted to identify their role in pSS pathogenesis. In addition the impact of abnormal proinflammatory cytokine production, such as IL-6, IL-17, IL-22, and IL-23, has also attracted considerable attention. However, although several studies have been carried out in experimental models and patients with pSS, many aspects concerning the role of Treg cells and IL-17/Th17 cell system in pSS pathogenesis are not fully elucidated. In particular, the role played by different IL-17-producing T cell subsets as well as the effects of pharmacological therapies on Treg/Th17 cell balance represents an intriguing issue. The aim of this review article is to provide an overview of current knowledge on Treg cells and IL-17-producing T cells in pSS pathogenesis. We believe that these insights into pSS pathogenesis may provide the basis for successful therapeutic intervention in this disease.
25926385 Analysis of the downstream mediators of toll-like receptor 3-induced apoptosis in labial s 2016 OBJECTIVES: The aim of this study was to clarify the molecular mechanisms elicited by toll-like receptor (TLR)3 in salivary gland cell death in patients with SS. METHODS: Expression of TLR3 and its downstream molecules was examined by immunohistochemical analysis, immunofluorescence, Western blot (WB), and antibody dot-blot array in labial salivary glands (LSGs), and cultured primary salivary gland epithelial cells (SGECs) obtained from patients with SS. We also investigated the difference of expression between ducts/alveoli of LSGs and cultured SGECs. RESULTS: Phosphorylated Fas-associated protein with death domain (p-FADD) or caspase-8 was not found in ducts or alveoli of LSGs from SS patients and controls. Weak expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) was found in SS patients, whereas no staining was observed in LSGs of controls. In contrast to LSGs, stimulation of SGECs with polyinosinic:cytidylic acid (poly I:C) significantly induced the expression of RIPK3, p-FADD, and cleaved caspase-8 by immunofluorescence and RIPK3, p-FADD, and cleaved caspase-3 by WB. However, it was counteracted by epidermal growth factor (EGF). Co-localization of anti-apoptotic molecules hemeoxygenase-2, heat shock protein 27, and p-protein kinase B or p-Akt was induced in EGF-stimulated SGECs. CONCLUSIONS: We observed that poly I:C induced apoptosis of SGECs in vitro compared with a relatively low prevalence of apoptosis found in the ducts and alveoli of LSGs in vivo. Thus, we speculate that other counter-regulatory mechanisms, including those induced by EGF, might exist to protect against TLR3-mediated apoptosis of ductal and acinar epithelial cells in vivo.
25723713 Predicting the outcome of Sjogren's syndrome-associated non-hodgkin's lymphoma patients. 2015 BACKGROUND: Non-Hodgkin's lymphoma (NHL) development in Sjögren's syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions. METHODS: In order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated. RESULTS: MALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14-95.80%) and the EFS was 77.92% (95% CI: 67.37-85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034-26.568) or for event (OR = 4.317, 95% CI: 1.146-9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772-11.637) and OS (HR = 5.946, 95% CI: 1.259-28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656-72.387 and OR = 12.589, 95% CI: 3.911-40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477-21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414-53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes. CONCLUSIONS: At the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.
25708147 Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Prima 2015 Jun OBJECTIVE: To evaluate changes in salivary gland echostructure and vascularization after rituximab treatment in patients with primary Sjögren's syndrome (SS). METHODS: Twenty-eight patients with primary SS included in the multicenter, randomized, double-blind, placebo-controlled Tolerance and Efficacy of Rituximab in Primary Sjögren's Syndrome (TEARS) trial underwent salivary gland ultrasonography before the first placebo or rituximab infusion and then 6 months later. Trial inclusion criteria were scores of ≥50 mm on at least 2 of 4 visual analog scales (VAS) evaluating dryness, pain, fatigue, and global disease; and recent-onset (<10 years) biologically active primary SS and/or systemic primary SS. Patients were randomly assigned (1:1) to rituximab (1 gm at weeks 0 and 2) or placebo. Ultrasonography of both parotid and submandibular glands was performed to assess echostructure (using a semiquantitative score of 0-4, with improvement defined as a ≥1-point decrease), size of each gland, and vascularization based on the resistive index of the transverse facial artery of the parotid gland before and after lemon juice stimulation. RESULTS: Of the 28 patients, 5 (18%; 3 in the placebo group and 2 in the rituximab group) had clinically detectable bilateral parotid gland enlargement at baseline. Parotid parenchyma echostructure improved in 50% of the rituximab-treated patients versus 7% of the placebo-treated patients (P = 0.03). In the submandibular glands, echostructure also improved in a larger proportion of rituximab-treated patients, although the difference was not significant (36% versus 7% of placebo-treated patients; P = 0.16). Gland sizes and resistive index remained unchanged. CONCLUSION: Ultrasonography showed improved salivary gland echostructure in patients with primary SS receiving rituximab, with no changes in salivary gland size or vascularization, 6 months after the first infusion.
27148875 Dry Eye Disease Patients with Xerostomia Report Higher Symptom Load and Have Poorer Meibum 2016 The purpose of the study was to investigate if xerostomia (dry mouth) is associated with symptoms and signs of dry eye disease (DED). At the Norwegian Dry Eye Clinic, patients with symptomatic DED with different etiologies were consecutively included in the study. The patients underwent a comprehensive ophthalmological work-up and completed self-questionnaires on symptoms of ocular dryness (Ocular Surface Disease Index [OSDI] and McMonnies Dry Eye Questionnaire) and the Sjögren's syndrome (SS) questionnaire (SSQ). Three hundred and eighteen patients (52% women and 48% men) with DED were included. Patient demographics were: 0 to 19 years (1%), 20 to 39 (25%), 40 to 59 (34%), 60 to 79 (35%) and 80 to 99 (5%). Xerostomia, defined as "daily symptoms of dry mouth the last three months" (as presented in SSQ) was reported by 23% of the patients. Female sex was more common among patients with xerostomia (81%) than among non-xerostomia patients (44%; P<0.001). Patients with xerostomia (60 ± 15 years) were older than those without xerostomia (51 ± 17; P<0.001). The use of prescription drugs was more prevalent among xerostomia patients (65%) than among non-xerostomia patients (35%; P<0.021; adjusted for age and sex). Patients with xerostomia had a higher OSDI score (19.0 ± 10.0) than those without xerostomia (12.9 ± 8.0; P<0.001). Moreover, xerostomia patients had more pathological meibum expressibility (0.9 ± 0.7) than those without xerostomia (0.7 ± 0.8; P = 0.046). Comparisons of OSDI and ocular signs were performed after controlling for the effects of sex, age and the number of systemic prescription drugs used. In conclusion, xerostomia patients demonstrated a higher DED symptom load and had poorer meibum expressibility than non-xerostomia patients.
27045247 [Transcatheter delivery of recombinant adenovirus vector containing exogenous aquaporin ge 2016 Jan Sjögren's syndrome is a kind of autoimmune disease, whose main clinical symptoms are dry mouth, dry eye and chronic parotid glandular inflammation. The conservative treatments include artificial tears or saliva,oral administration of corticosteroids,and immunosuppressantsl with limited effectiveness. Along with the development of molecular biology, vast attentions are being paid to researches on gene therapy for Sjögren's syndrome, hopefully to bring gospel to patients with Sjögren's syndrome. This article reviews the recent research progresses on transcatheter delivery of recombinant adenovirus vector with aquaporin gene in experimental treatment of Sjögren's syndrome.
26680995 Salivaomics for oral diseases biomarkers detection. 2016 The variation of saliva composition in different physiological and pathological states is well demonstrated. Several saliva constituents (enzymes, hormones, antibodies, cytokines etc.) are up- or down-regulated in respect to benign, premalignant and malignant conditions in the oral cavity, and several patterns of deregulation are associated with specific disorders. Omics technologies have contributed significantly in the identification of alterations in gene expression, transcription, protein coding and small molecules concentration, in biologic systems. In this aspect, salivaomics integrate these technologies in saliva analysis and represent a novel and holistic approach in oral disease management including diagnosis, prognosis and monitoring. This review summarizes the current research in the discovery of biomarkers and molecular signatures with diagnostic or prognostic utility for oral diseases in saliva. The review also focuses on the emerging issues of the salivaomics technology and saliva diagnostics and the translational potential.
25451161 A chimeric human-mouse model of Sjögren's syndrome. 2015 Jan Despite recent advances in the understanding of Sjögren's Syndrome (SjS), the pathogenic mechanisms remain elusive and an ideal model for early drug discovery is not yet available. To establish a humanized mouse model of SjS, peripheral blood mononuclear cells (PBMCs) from healthy volunteers or patients with SjS were transferred into immunodeficient NOD-scid IL-2rγ(null) mouse recipients to produce chimeric mice. While no difference was observed in the distribution of cells, chimeric mice transferred with PBMCs from SjS patients produced enhanced cytokine levels, most significantly IFN-γ and IL-10. Histological examination revealed enhanced inflammatory responses in the lacrimal and salivary glands of SjS chimeras, as measured by digital image analysis and blinded histopathological scoring. Infiltrates were primarily CD4+, with minimal detection of CD8+ T-cells and B-cells. These results demonstrate a novel chimeric mouse model of human SjS that provides a unique in vivo environment to test experimental therapeutics and investigate T-cell disease pathology.
27207020 Sonoelastographic Modalities in the Evaluation of Salivary Gland Characteristics in Sjögr 2016 Sep The purpose of this study was to investigate salivary tissue assessment with various sonoelastographic modalities (real-time tissue elastography, Virtual Touch imaging and quantification) in patients with Sjögren's syndrome as compared with an appropriate control group. The sonoelastographic modalities were evaluated in 50 patients with primary Sjögren's syndrome (pSS). Patients underwent high-resolution ultrasonography of the submandibular and parotid glands. Results of B-mode, real-time tissue elastography, Virtual Touch imaging-each graded with the appropriate scoring system-and Virtual Touch quantification were compared with those for 50 patients with sicca symptoms who did not fulfill the American-European consensus group criteria. In B-mode, 34 of 50 parotid glands in patients with pSS and 8 of 50 in the control group had abnormal findings (p < 0.001). Compared with 9 of 50 control patients, 38 of 50 patients with pSS had abnormal findings in submandibular gland B-mode (p < 0.001). With real-time tissue elastography, there was a trend toward higher scores for parotid glands in the pSS group (p = 0.238), whereas scores for submandibular glands in the control group were higher (p = 0.107). Virtual Touch imaging did not indicate any difference (p = 0.647 and p = 0.658). In Virtual Touch quantification, values for parotid (mean: 2.99 m/s) and submandibular glands (mean: 2.54 m/s) in the pSS group were higher than those for parotid (mean: 2.16 m/s) and submandibular (mean: 2.04 m/s) glands in the control group (p < 0.001 and p = 0.008). Glandular stiffness, measured by Virtual Touch quantification, was significantly higher in patients with Sjögreńs syndrome than in patients with sicca symptoms.
25584898 A pathogenetic role for IL-21 in primary Sjögren syndrome. 2015 Jun Advances in our understanding of the pathogenesis of primary Sjögren syndrome (pSS) characterize it as a highly complex process encompassing both the initiation of innate immunity and subsequent adaptive immune responses. IL-21 is receiving attention as a potential key player in the pathogenesis of pSS owing to its pleiotropic effects on the type I interferon signalling pathway, and newly identified roles in generation of follicular and IL-17-producing subtypes of helper T cells, as well as plasma-cell differentiation and B-cell activation. Taking into consideration the diverse biological functions of IL-21 and its clinical relevance to pSS, we propose that this cytokine has a central role in orchestrating the complex immune response in pSS. This hypothesis might provide new insight into the pathogenesis of pSS and facilitate the development of effective therapeutic strategies.
27489782 Exercise reduces depressive symptoms in adults with arthritis: Evidential value. 2016 Jul 12 AIM: To determine whether evidential value exists that exercise reduces depression in adults with arthritis and other rheumatic conditions. METHODS: Utilizing data derived from a prior meta-analysis of 29 randomized controlled trials comprising 2449 participants (1470 exercise, 979 control) with fibromyalgia, osteoarthritis, rheumatoid arthritis or systemic lupus erythematosus, a new method, P-curve, was utilized to assess for evidentiary worth as well as dismiss the possibility of discriminating reporting of statistically significant results regarding exercise and depression in adults with arthritis and other rheumatic conditions. Using the method of Stouffer, Z-scores were calculated to examine selective-reporting bias. An alpha (P) value < 0.05 was deemed statistically significant. In addition, average power of the tests included in P-curve, adjusted for publication bias, was calculated. RESULTS: Fifteen of 29 studies (51.7%) with exercise and depression results were statistically significant (P < 0.05) while none of the results were statistically significant with respect to exercise increasing depression in adults with arthritis and other rheumatic conditions. Right-skew to dismiss selective reporting was identified (Z = -5.28, P < 0.0001). In addition, the included studies did not lack evidential value (Z = 2.39, P = 0.99), nor did they lack evidential value and were P-hacked (Z = 5.28, P > 0.99). The relative frequencies of P-values were 66.7% at 0.01, 6.7% each at 0.02 and 0.03, 13.3% at 0.04 and 6.7% at 0.05. The average power of the tests included in P-curve, corrected for publication bias, was 69%. Diagnostic plot results revealed that the observed power estimate was a better fit than the alternatives. CONCLUSION: Evidential value results provide additional support that exercise reduces depression in adults with arthritis and other rheumatic conditions.
26071217 Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mec 2015 Sep Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug.