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ID PMID Title PublicationDate abstract
26167547 Effects of Multi-glycosides of Tripterygium wilfordiion in the Treatment of Sjögren's Syn 2015 OBJECTIVE: To investigate the effects of the multi-glycosides of Tripterygium wilfordii (GTW) on Sjögren's syndrome (SS) in the non-obese diabetic (NOD) mouse model. METHODS: Twenty-seven 8-week-old, female NOD mice were divided into the GTW group, the hydroxychloroquine (HCQ) group, and control (normal saline) group, and received corresponding treatment for 16 weeks. The treatment-induced changes in stimulated total saliva flow rate (STFR), level of serum anti-SSA/SSB, ratio of regulatory T (Treg) cells, histology of the submandibular gland (SMG) and the gene expression profile that is related to inflammation and autoimmunization were evaluated. RESULTS: Compared to the untreated (control) mice, STRF, SMG index and Treg/CD4+ cell ratio were significantly higher, whereas anti-SSA, anti-SSB and lymphoid foci were remarkably lower in GTW-treated mice. HCQ-treated mice showed similar results except SMG index was not different from the untreated mice. NOD mice showed 19.03% altered gene expression with maturation from the age of 8 weeks to 24 weeks. Treatment with HCQ and GTW reduced the change in gene expression to 13.09% and 7.14%, respectively. CONCLUSION: GTW is as effective as HCQ in the treatment of Sjögren's syndrome in the NOD mouse model.
25656459 Efficacy and safety of biological agents in adult-onset Still's disease. 2015 OBJECTIVES: To describe the efficacy and safety of different biological agents in a large cohort of 20 patients with adult-onset Still's disease (AOSD). METHOD: We retrospectively evaluated 20 patients with severe or refractory AOSD treated with at least one biological agent (anakinra, etanercept, tocilizumab, and adalimumab), followed up for at least 12 months at our Institution. We collected and analysed data on the disease course, treatment outcome, and adverse effects, and compared our data with other published series. RESULTS: The median duration of follow-up was 5 years. In 12 patients a single biological drug induced a clinical response. In eight patients the biological agent that was first administered proved ineffective, and a switch to a different biologic was necessary. In three patients a third biologic was necessary to achieve disease control. The biologics eventually determined a clinical response in all patients. Patients with systemic disease showed better responses than patients with chronic articular disease (p < 0.05). Biological agents allowed either the withdrawal or the tapering of corticosteroid therapy (p < 0.0001) and of disease-modifying anti-rheumatic agents (DMARDs; p < 0.05). Three patients experienced herpes zoster reactivation. CONCLUSIONS: This is the longest follow-up of a cohort of AOSD patients treated with biological agents. Our data show that biologics are safe and generally effective in the long-term management of AOSD, particularly in cases with systemic disease, and suggest that a clinical response can be obtained in almost all AOSD patients, although a switch to drugs with a different mechanism of action may be necessary.
26004258 [Angiographically documented hemorrhagic transformation of embolic stroke: A case report]. 2015 A 81-year-old man with rheumatoid vasculitis presented with total aphasia followed by right hemiplegia. The NIHSS score was 24. Diffusion weighted magnetic resonance imaging (DWI) demonstrated an acute infarct in the left middle cerebral artery (MCA) territory, and magnetic resonance angiogram (MRA) revealed left MCA M1 occlusion. We administrated recombinant tissue plasminogen activator (rt-PA) at 132 min after symptom onset, but symptom was not improved. Emergency neuroendovascular recanalization was conducted with Penumbra(®) system. After MCA was recanalized partially, extravasations appeared on left lenticulostriate arteries territory at 376 min from symptom onset. Multiple extravasations spread over perforating branches, and ventricular rupture recognized angiographically. After the procedure, head CT demonstrated hematoma on left basal ganglia territory with intraventricular bleeding. Rheumatoid vasculitis might affect hemorrhagic infarction in emergency neuroendovascular recanalization procedure, and careful choice of treatment would be required.
26071203 Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that ch 2015 Jul Anti-membrane autoantibodies (MbA) have been reported in sera from patients with lupus nephritis (LN) but the targets of the MbA remain to be explored, which is the aim of the current study. Sera were collected from 40 patients with LN determined by renal biopsy, and from 30 systemic lupus erythematosus (SLE) patients without clinical evidence of LN. Thirty autoimmune disease control patients (rheumatoid arthritis, Sjögren's syndrome and systemic sclerosis), and 30 healthy controls were also included. Using flow cytometry, the presence of anti-MbA was explored revealing that IgG anti-MbA positivity was associated with LN (62.5% vs 13.3%) when compared to non-LN SLE patients, autoimmune disease patients (6.7%) and healthy controls (0%). Next, using purified plasma membrane fractions from human embryonic kidney (HEK) cells, the more prominent targets and their occurrence rates were located at 50 kDa, 60/65 kDa, 90 kDa, 110 kDa, 180 kDa and 220 kDa. Alpha-actinin (110 kDa) autoAb was characterized as a major target in LN patients positive for anti-MbA, and anti-MbA binding activity was reduced (36.9 ± 13.7%) in the presence of α-actinin. Laminin (200 kDa) was also characterized as a minor target, which was not the case for annexin A2 (36 kDa). Finally, anti-MbA IgG subclass analysis indicated a predominance of IgG2. In conclusion, IgG anti-MbA were detected at high levels in LN patients supporting a primary pathogenic role for anti-MbA and anti-MbA/α-actinin+ in LN that needs further research.
27440958 A case of figurate urticaria by etanercept. 2016 Apr Etanercept is a competitive inhibitor of tumor necrosis factor-alpha (TNF-α) a polypeptide hormone, involved in the development of the immune system, in host defense and immune surveillance. Even if the etanercept mechanism of action is not completely understood, it is supposed that it negatively modulates biological responses mediated by molecules (cytokines, adhesion molecules, or proteinases) induced or regulated by TNF. For this reason, it is widely used in the treatment of immunologicals diseases, such as rheumatoid and psoriatic arthritis, polyarticular juvenile idiopathic active, ankylosing spondylitis, and plaque psoriasis. Etanercept has a good tolerability profile. Adverse events related to skin are rare, arising usually in about 5% of patients treated with anti-TNF α. In this scenario, we describe a case of figurate urticaria arose after the re-administration of etanercept in a patient affected by psoriasis and hepatitis B. A 65-year-old man, affected by psoriasis, was hospitalized in September 2014 to the Regional Center for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The laboratory analysis detected positivity for hepatitis B virus (HBV) antigens. For this reason, it was administered to him lamivudine 100 mg/die about 30 days before to start etanercept treatment. The etanercept therapy has resulted in a progressive improving of skin manifestations, and the patient decided individually to stop the therapy. Afterwards, for worsening of the psoriatic lesions, he was again hospitalized and treated with the same therapeutic schedule (lamivudine followed by etanercept). Ten days after the start of therapy, the patient showed the onset of urticarial rash. Due to this, the treatment with lamivudine and etanercept was suspended and the patient's clinical conditions improved. It is probably that immunological disorders due to etanercept therapy and HBV infection could explain the onset of figurate urticaria in our patient. In this contest, the post-marketing surveillance confirms its important role in the monitoring of drugs tolerability and effectiveness.
25714941 Temporary scaphocapitate fixation with or without radial shortening for adolescent Kienbö 2015 May We performed temporary scaphocapitate joint fixation with or without radial shortening osteotomy, depending on the ulnar variance, in adolescent Kienböck's disease. The aim of the current study was to evaluate the radiological and clinical results and compare our results with those of other previously reported methods. Temporary scaphocapitate fixation alone or fixation accompanied by radial shortening osteotomy has been performed in three patients since 2003. All six patients were males, and their mean age at surgery was 15.5 years. The fixation was performed using two Kirschner-wires in closed methods, and the shortening of the radius was performed using the volar approach and secured with a plate. Radial shortenings of 4, 2, and 7 mm were applied. Radiological findings of Kienböck's disease, including ulnar variance and carpal height ratio, were investigated at the final follow-up by simple radiography and MRI. Clinical results of pain, range of wrist motion, and grip strength were also evaluated. The mean age at the final follow-up of six patients was 22 years, and the follow-up period was 6.8 years. Sclerosis or fragmentation of all the lunates in the simple radiographs improved, and the carpal height ratio increased to 0.5 at the final follow-up. The signal intensities on the final MRI were all normalized. The final visual analog scale scores decreased to 1.2, and wrist ranges of motion were all statistically significantly increased. In addition, grip strength increased to 69% of that of the normal side at the final follow-up. We suggest that temporary scaphocapitate joint fixation is a recommendable option with or without radial shortening, depending on the ulnar variance, in adolescent Kienböck's disease.
27407265 The relationship between the presence of autoantibodies, indicators of local and systemic 2015 OBJECTIVES: The aim of this study was to find markers related to activation of B cells, which show a correlation with the systemic inflammation markers - erythrocyte sedimentation rate and C-reactive protein and with the intensity of in situ inflammation. MATERIAL AND METHODS: Forty-one primary Sjögren's syndrome (pSS) patients (33 female, 8 male) of the mean age 52.9 ±15 years were included. A group of 20 healthy volunteers was applied as a control. Erythrocyte sedimentation rate (ESR), concentration of gamma-globulins, C-reactive protein (CRP) and rheumatoid factor (RF) were measured by routine laboratory tests. Titres of antinuclear antibodies (ANAs) were determined by the indirect immunofluorescence method, while anti-SS-A/SS-B antibodies were detected by both the dot-blot method and an enzyme immunoassay. The concentrations of BAFF in sera were measured by sandwich ELISA. Biopsies of minor salivary glands were taken and the focus score (FS) was calculated. Correlations between quantitative variables were assessed using the Spearman correlation coefficient (r). RESULTS: Serum concentrations of BAFF was significantly higher in the pSS patients than in the control group. The study revealed a statistically significant correlation between ANAs titre and the FS (r = 0.421). Anti-SS-A/Ro and anti-SS-B/La antibodies positively correlated with ESR. There was also a positive correlation between the gamma globulin level and the titres of all tested autoantibodies. CONCLUSIONS: The positive correlation between ANAs and FS confirms the importance of these autoantibodies in the local inflammatory process. The positive correlation between anti-SS-A/SS-B antibodies and ESR suggests involvement of these antibodies in generalization of the inflammatory response. In the pSS group serum concentrations of BAFF were statistically significantly higher than healthy volunteers. All presented results confirm the role of activity of B cells in the course of pSS.
26613595 An HLA-C amino-acid variant in addition to HLA-B*27 confers risk for ankylosing spondyliti 2015 Nov 27 INTRODUCTION: The presence of the HLA-B*27 allele is a major risk factor for the development of ankylosing spondylitis (AS), which causes chronic inflammation of the spine and other sites. We investigated residual effects outside HLA-B within the major histocompatibility complex (MHC) region in the Korean population. METHODS: Using the Korean HLA reference panel, we inferred the classic HLA alleles and amino-acid residues of the six HLA genes (HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1) and MHC single-nucleotide polymorphisms in 3820 Korean subjects, including 654 Korean cases of AS and 3166 controls, who were genotyped by using Immunochip. Logistic regression and log-likelihood ratio tests were used in AS association tests for imputed markers. RESULTS: The most significant associations were identified at amino-acid positions in the epitope-binding site of HLA-B (P = 1.71 × 10(-481) at position 70, P = 7.20 × 10(-479) at position 97, and P = 2.54 × 10(-484) at positions 114), highlighting the risk effect of the HLA-B*27 allele and the protective effects of other classic alleles. A secondary effect was located at the leucine at amino-acid position 116 in the epitope-binding site of HLA-C (P = 1.69 × 10(-14)), completely tagging the HLA-C*15:02 allele. This residue had a large effect in HLA-B*27-negative patients (odds ratio = 6.6, 95 % confidence interval = 3.8 to 11.4). CONCLUSIONS: The four amino-acid positions of HLA-B and -C account for most of the associations between AS and MHC in the Korean population. This finding updates the list of AS susceptibility loci and provides new insight into AS pathogenesis mediated by MHC class I molecules.
27179903 Cardiovascular magnetic resonance in rheumatology: Current status and recommendations for 2016 Aug 15 Targeted therapies in connective tissue diseases (CTDs) have led to improvements of disease-associated outcomes, but life expectancy remains lower compared to general population due to emerging co-morbidities, particularly due to excess cardiovascular risk. Cardiovascular magnetic resonance (CMR) is a noninvasive imaging technique which can provide detailed information about multiple cardiovascular pathologies without using ionizing radiation. CMR is considered the reference standard for quantitative evaluation of left and right ventricular volumes, mass and function, cardiac tissue characterization and assessment of thoracic vessels; it may also be used for the quantitative assessment of myocardial blood flow with high spatial resolution and for the evaluation of the proximal coronary arteries. These applications are of particular interest in CTDs, because of the potential of serious and variable involvement of the cardiovascular system during their course. The International Consensus Group on CMR in Rheumatology was formed in January 2012 aiming to achieve consensus among CMR and rheumatology experts in developing initial recommendations on the current state-of-the-art use of CMR in CTDs. The present report outlines the recommendations of the participating CMR and rheumatology experts with regards to: (a) indications for use of CMR in rheumatoid arthritis, the spondyloarthropathies, systemic lupus erythematosus, vasculitis of small, medium and large vessels, myositis, sarcoidosis (SRC), and scleroderma (SSc); (b) CMR protocols, terminology for reporting CMR and diagnostic CMR criteria for assessment and quantification of cardiovascular involvement in CTDs; and (c) a research agenda for the further development of this evolving field.
26963290 A Preoperative Scale for Determining Surgical Readmission Risk After Total Hip Replacement 2016 Aug 1 IMPORTANCE: Total hip replacement is a commonly performed orthopedic procedure for the treatment of painful arthritis, osteonecrosis, or fracture. OBJECTIVE: To develop and verify a scale for predicting readmission rates for total hip replacement patients and allow for the development and implementation of readmission risk-reduction strategies. DESIGN, SETTING, AND PARTICIPANTS: Discharge data on 268 518 patients from New York and California (derivation cohort) and 153 560 patients from Florida and Washington (validation cohort) were collected from the State Inpatient Database, a part of the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality (2006-2011). Analysis of the derivation cohort was performed in July 2013 and analysis of the validation cohort was performed in August 2014. Demographic and clinical characteristics of patients undergoing total hip replacement were abstracted. The Readmission After Total Hip Replacement Risk Scale was developed to predict readmission risk. MAIN OUTCOME AND MEASURE: Readmission rate. RESULTS: Of the 268 518 patients from New York and California (derivation cohort), 151 009 (56.2%) were women and 216 477 (80.6%) were white. Of the 153 560 patients from Florida and Washington (validation cohort), 86 534 (56.3%) were women and 120 591 (78.5%) were white. Overall 30-day readmission rate was 5.89% for the derivation cohort and 5.82% for the validation cohort. Readmission rates for men and women were 5.79% and 6.08% for the derivation cohort (odds ratio [OR], 1.05; 95% CI, 1.02-1.09) and 5.80% and 5.84% for the validation cohort (OR, 0.99; 95% CI, 0.95-1.04), respectively. The following were all determined to be associated with increased risk of readmission after total hip replacement: being older than 71 years (OR, 1.83; 95% CI, 1.77-1.89), African American (OR, 1.23; 95% CI, 1.15-1.31), and in the lowest income quartile (OR, 1.18; 95% CI, 1.12-1.24); revision replacement (OR, 1.82, 95% CI, 1.75-1.90); liver disease (OR, 1.57; 95% CI, 1.39-1.77); congestive heart failure (OR, 1.49; 95% CI, 1.38-1.61); chronic pulmonary disease (OR, 1.33; 95% CI, 1.27-1.39); renal failure (OR, 1.26; 95% CI, 1.18-1.36); diabetes (OR, 1.21; 95% CI, 1.16-1.27); fluid and electrolyte disorder (OR, 1.21; 95% CI, 1.14-1.27); anemia (OR, 1.19; 95% CI, 1.15-1.25); rheumatoid arthritis (OR, 1.19; 95% CI, 1.10-1.29); coagulopathy (OR, 1.19; 95% CI, 1.08-1.32); hypertension (OR, 1.17; 95% CI, 1.12-1.21); and obesity (OR, 1.15; 95% CI 1.09-1.21). They were used to create the Readmission After Total Hip Replacement Risk Scale, which was applied to the validation cohort and explained 89.1% of readmission variability in that cohort. CONCLUSIONS AND RELEVANCE: Data derived from patients in the New York and California State Inpatient Database were reliably able to explain readmission variability for patients in the Florida and Washington State Inpatient Database at a rate of 89.1% based on known preoperative risk factors. Risk-stratification models, such as the Readmission After Total Hip Replacement Risk Scale, can identify high-risk patients for readmission and permit implementation of patient-specific readmission-reduction strategies to reduce readmissions and health care expenditures.
27576331 How is the ultrasound in rheumatology used, implemented, and applied in Latin American cen 2016 Dec This study aimed to perform an overview of how ultrasound (US) is being used, implemented, and applied in rheumatologic centers in Latin America (LA). A retrospective, multicenter 1-year experience study was undertaken. Eighteen centers from eight countries were involved. The following information were collected: demographic data, indication to perform an US examination, physician that required the examination, and the anatomical region required for the examination. A total of 7167 patients underwent an US examination. The request for US examinations came most frequently from their own institution (5981 (83.45 %)) than from external referral (1186 (16.55 %)). The services that more frequently requested an US examination were rheumatology 5154 (71.91 %), followed by orthopedic 1016 (14.18 %), and rehabilitation 375 (5.23 %). The most frequently scanned area was the shoulder in 1908 cases (26.62 %), followed by hand 1754 (24.47 %), knee 1518 (21.18 %), ankle 574 (8.01 %), and wrist 394 (5.50 %). Osteoarthritis was the most common disease assessed (2279 patients (31.8 %)), followed by rheumatoid arthritis (2125 patients (29.65 %)), psoriatic arthritis (869 patients (12.1 %)), painful shoulder syndrome (545 (7.6 %)), connective tissue disorders (systemic sclerosis 339 (4.7 %), polymyositis/dermatomyositis 107 (1.4 %), Sjögren's syndrome 60 (0.8 %), and systemic lupus erythematosus 57 (0.8 %)). US evaluation was more frequently requested for diagnostic purposes (3981 (55.5 %)) compared to follow-up studies (2649 (36.9 %)), research protocols (339 (4.73 %)), and invasive guided procedures (198 (2.76 %)). US registered increasing applications in rheumatology and highlighted its positive impact in daily clinical practice. US increases the accuracy of the musculoskeletal clinical examination, influence the diagnosis, and the disease management.
25872649 Pain reduction with oral methotrexate in knee osteoarthritis, a pragmatic phase iii trial 2015 Mar 4 BACKGROUND: Osteoarthritis (OA) is the fastest growing cause of disability worldwide. Current treatments for OA are severely limited and a large proportion of people with OA live in constant, debilitating pain. There is therefore an urgent need for novel treatments to reduce pain. Synovitis is highly prevalent in OA and is associated with pain. In inflammatory arthritides such as rheumatoid arthritis, methotrexate (MTX) is the gold standard treatment for synovitis and has a well-known, acceptable toxicity profile. We propose that using MTX to treat patients with symptomatic knee OA will be a practical and safe treatment to reduce synovitis and, consequently, pain. METHODS/DESIGN: Pain Reduction with Oral Methotrexate in knee Osteoarthritis, a pragmatic phase III trial of Treatment Effectiveness (PROMOTE) is an investigator-initiated, multi-centre, randomized, double-blind, pragmatic placebo-controlled trial. A total of 160 participants with symptomatic knee OA will be recruited across primary and secondary care sites in the United Kingdom and randomized on a 1:1 basis to active treatment or placebo, in addition to usual care, for 12 months. As is usual practice for MTX, dosing will be escalated over six weeks to 25 mg (or maximum tolerated dose) weekly for the remainder of the study. The primary endpoint is change in average knee pain during the past week (measured on an 11-point numerical rating scale) between baseline and six months. Secondary endpoints include other self-reported pain, function and quality-of-life measures. A health economics analysis will also be performed. A magnetic resonance imaging substudy will be conducted to provide an explanatory mechanism for associated symptom change by examining whether MTX reduces synovitis and whether this is related to symptom change. Linear and logistic regression will be used to compare changes between groups using univariable and multivariable modelling analyses. All analyses will be conducted on an intention-to-treat basis. DISCUSSION: The PROMOTE trial is designed to examine whether MTX is an effective analgesic treatment for OA. The MRI substudy will address the relationship between synovitis and symptom change. This will potentially provide a much needed new treatment for knee OA. TRIAL REGISTRATION: Current Controlled Trials identifier: ISRCTN77854383 (registered: 25 October 2013).
28070525 Tolerogenic Dendritic Cells Generated with Tofacitinib Ameliorate Experimental Autoimmune 2016 It is well known that dendritic cells (DCs) play a pivotal role in triggering self-specific responses. Conversely, tolerogenic DCs (tolDCs), a specialized subset, induce tolerance and negatively regulate autoreactive responses. Tofacitinib, a Janus kinase inhibitor developed by Pfizer for treatment of rheumatoid arthritis, is probable to be a promising candidate for inducing tolDCs. The aims of this study were to evaluate the effectiveness of tolDCs induced by tofacitinib in a myelin oligodendrocyte glycoprotein- (MOG-) specific experimental autoimmune encephalomyelitis (EAE) model and to investigate their effects on Th17/Treg balance in the animal model of multiple sclerosis (MS). Our results revealed that tofacitinib-treated DCs maintained a steady semimature phenotype with a low level of proinflammatory cytokines and costimulatory molecules. DCs treated by tofacitinib also induced antigen-specific T cells hyporesponsiveness in a concentration-dependent manner. Upon intravenous injection into EAE mice, MOG pulsed tolDCs significantly dampened disease activity, and adoptive cell therapy (ACT) disturbed Th17/Treg balance with a remarkable decrease of Th1/Th17 cells and an increase in regulatory T cells (Tregs). Overall, DCs modified by tofacitinib exhibited a typical tolerogenic phenotype, and the antigen-specific tolDCs may represent a new avenue of research for the development of future clinical treatments for MS.
27913299 The inhibitory effect of beta-lapachone on RANKL-induced osteoclastogenesis. 2017 Jan 22 β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. β-L inhibited osteoclast formation in a dose-dependent manner and also reduced the expression of osteoclast differentiation marker genes, such as tartrate-resistant acid phosphatase (Acp5 or TRAP), cathepsin K (CtsK), the d2 isoform of vacuolar ATPase V0 domain (Atp6v0d2), osteoclast-associated receptor (Oscar), and dendritic cell-specific transmembrane protein (Dc-stamp). β-L treatment of RANKL-induced osteoclastogenesis significantly increased the cellular NAD+/NADH ratio and resulted in the activation of 5' AMP-activated protein kinase (AMPK), a negative regulator of osteoclast differentiation. In addition, β-L treatment led to significant suppression of the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and peroxisome proliferator-activated receptor gamma coactivator 1β (PGC1β), which can stimulate osteoclastogenesis. β-L treatment downregulated c-Fos and nuclear factor of activated T-cells 1 (NFATc1), which are master transcription factors for osteoclastogenesis. Taken together, the results demonstrated that β-L inhibits RANKL-induced osteoclastogenesis and could be considered a potent inhibitor of RANKL-mediated bone diseases, such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis.
27836739 Docosahexaenoic acid signaling attenuates the proliferation and differentiation of bone ma 2017 Jan Docosahexaenoic acid (DHA), a component of omega-3 fatty acids, has been reported to protect against inflammatory bone diseases such as osteoporosis and rheumatoid arthritis. However, its exact mechanism in bone resorbing cells has not been elucidated. In this study, we investigated the effects and the molecular mechanism of DHA on the proliferation, differentiation, and survival of osteoclast lineage cells using mouse bone marrow-derived macrophages (BMMs). DHA suppressed the macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursors, BMMs, in a dose-dependent manner. The attenuated proliferation of DHA-treated BMMs was related to M-CSF inhibition that selectively decreased Akt activation and downregulated cyclin D1 and cyclin D2 expression. DHA also blocked receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation from BMMs. At the molecular level, DHA inhibited JNK, ERK, and p38 MAPKs. In addition, it inhibited NF-κB signaling cascades, as demonstrated by the suppression of RANKL-mediated IκBα phosphorylation, NF-κB subunit p65 nuclear translocation, and NF-κB transcriptional activation. Accordingly, DHA attenuated the induction of c-Fos and nuclear factor of activated T cells c1 (NFATc1). Furthermore, DHA accelerated the apoptosis of mature osteoclasts by inducing Bim expression, a critical modulator of osteoclast apoptosis. Collectively, our data demonstrate that DHA exerts an anti-osteoclastogenic effect by suppressing the proliferation and differentiation of BMMs and enhancing the apoptosis of mature osteoclasts, thereby resulting in a diminished number of bone-resorptive cells.
27822287 Traditional Chinese Medicine Use among Patients with Psoriasis in Taiwan: A Nationwide Pop 2016 Traditional Chinese medicine (TCM) has long been used for patients with psoriasis. This study aimed to investigate TCM usage in patients with psoriasis. We analyzed a cohort of one million individuals representing the 23 million enrollees randomly selected from the National Health Insurance Research Database in Taiwan. We identified 28,510 patients newly diagnosed with psoriasis between 2000 and 2010. Among them, 20,084 (70.4%) patients were TCM users. Patients who were female, younger, white-collar workers and lived in urbanized area tended to be TCM users. The median interval between the initial diagnosis of psoriasis to the first TCM consultation was 12 months. More than half (N = 11,609; 57.8%) of the TCM users received only Chinese herbal medicine. Win-qing-yin and Bai-xian-pi were the most commonly prescribed Chinese herbal formula and single herb, respectively. The core prescription pattern comprised Mu-dan-pi, Wen-qing-yin, Zi-cao, Bai-xian-pi, and Di-fu-zi. Patients preferred TCM than Western medicine consultations when they had metabolic syndrome, hepatitis, rheumatoid arthritis, alopecia areata, Crohn's disease, cancer, depression, fatty liver, chronic airway obstruction, sleep disorder, and allergic rhinitis. In conclusion, TCM use is popular among patients with psoriasis in Taiwan. Future clinical trials to investigate its efficacy are warranted.
27633406 Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyfla 2016 Dec 24 ETHNOPHARMACOLOGICAL RELEVANCE: Ageratum conyzoides L. is a plant widely used in traditional medicine in tropical and subtropical regions of the world due to its anti-inflammatory, antinociceptive and antibacterial properties. AIM OF THE STUDY: To characterize the standardized extract of polymethoxyflavones (SEPAc) from the plant and evaluate its antinociceptive and anti-inflammatory effects. MATERIALS AND METHODS: The SEPAc purified from the ethanol extract of the plant leaves was characterized by high resolution mass spectrometry and the methoxyflavones were quantified by a validated UPLC-PDA method. The antinociceptive and anti-inflammatory activities of the SEPAc were evaluated after oral administration on the acute nocifensive behavior of mice induced by formalin, prostaglandin E2 (PGE2) and proinflammatory cytokines (interleukin-1beta (IL-1β)) and tumor necrosis factor-alpha (TNF-α) in mice. RESULTS: Qualitative analyses revealed the presence of seven methoxyflavones in the SEPAc, also a simple UPLC-PDA method was developed and validated for the quantification of 5,6,7,3',4',5'-hexametoxyflavone; nobiletin; 5'-methoxynobiletin and eupalestin, major compounds in the extract. The SEPAc exhibited antinociceptive and anti-inflammatory activities in both formalin phases, with significant inhibition of the paw edema formation and significant reduction of the nocifensive response induced by an intraplantar injection of PGE2 and intrathecal injection of interleukin-1β. CONCLUSIONS: The SEPAc exhibited significant antinociceptive and anti-inflammatory effects. These results provided scientific suggestion of its potential as a source of new medicines to treat inflammatory diseases, such rheumatoid arthritis.
27140866 Risk factor analysis and decision-making of surgical strategy for V3 segment anomaly: sign 2016 Sep BACKGROUND CONTEXT: Awareness of vascular anomalies is crucial to avoid iatrogenic injuries during surgical procedure. Although V3 segment anomaly has been well described, the incidence of V3 segment anomaly has been rather variable in the literature, and there are few reports regarding the adequate surgical strategy for each type of V3 segment anomaly. PURPOSE: This study aimed to analyze the incidence of V3 segment anomaly and demonstrate the importance of recognizing vertebral artery (VA) anomaly in deciding the surgical strategy for C1 screw placement. STUDY DESIGN: A retrospective cohort study was carried out. PATIENT SAMPLE: The sample included 147 patients who underwent C1 posterior instrumentation and preoperative three-dimensional computed tomography angiography (3D CTA). OUTCOME MEASURES: The primary outcome of this study was the incidence of V3 segment anomaly using preoperative CTA, and the secondary outcome was the risk factor analysis of the V3 segment anomaly. METHODS: There were 147 patients who underwent C1 posterior instrumentation to treat various kinds of upper cervical disease. The 3D CTA of the patients were assessed preoperatively to identify the anomaly of the VA. Each surgical technique of C1 posterior instrumentation was decided upon the shape and the course of the VA around the atlas. RESULTS: During the study period, 11 cases of V3 segment anomaly (7.5%) were found on 3D CTA. Persistent intersegmental artery was found in nine cases and was the most common variant of VA anomaly. Early branch of posterior inferior cerebellar artery was found in three cases. Most of V3 segment anomaly was found unilaterally, but there were two cases with bilateral V3 anomaly. Seven cases (63.6%) were associated with congenital bony abnormality around craniovertebral junction (CVJ), such as occipital assimilation, Klippel-Feil syndrome, and os odontoideum. V3 segment anomaly was significantly common in the cases with bony abnormality (29.2% (7/24) vs. 3.6% (4/123), p<.05). Compared with patient without bony abnormality, the odds ratio was 10.78 (95% CI: 2.88-40.37) for those with congenital bony abnormalities. Rheumatoid arthritis was not a risk factor of V3 segment anomaly (p=.391). CONCLUSIONS: The course of the VA is heterogenous, and the V3 segment anomaly of the VA is more common in the cases with congenital bony abnormalities around CVJ. Therefore, preoperative radiological studies should be performed to identify V3 segment variations and reduce the risk of VA injury. To avoid significant morbidities associated with VA, surgical technique of C1 posterior instrumentation should be decided depending upon the V3 segment anomaly. A more optimal entry point and trajectory for C1 fixation can be selected.
26658004 At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therap 2016 Feb Neutrophil extracellular traps are associated with a unique form of cell death distinct from apoptosis or necrosis, whereby invading microbes are trapped and killed. Neutrophil extracellular traps can contribute to autoimmunity by exposing autoantigens, inducing IFN-α production, and activating the complement system. The association of neutrophil extracellular traps with autoimmune diseases, particularly systemic lupus erythematosus, will be reviewed. Increased neutrophil extracellular trap formation is seen in psoriasis, antineutrophil cytoplasmic antibody-associated vasculitis, antiphospholipid antibody syndrome rheumatoid arthritis, and systemic lupus erythematosus. Neutrophil extracellular traps may promote thrombus formation in antineutrophil cytoplasmic antibody-associated vasculitis and antiphospholipid antibody syndrome. In systemic lupus erythematosus, increased neutrophil extracellular trap formation is associated with increased disease activity and renal disease, suggesting that neutrophil extracellular traps could be a disease activity marker. Neutrophil extracellular traps can damage and kill endothelial cells and promote inflammation in atherosclerotic plaques, which may contribute to accelerated atherosclerosis in systemic lupus erythematosus. As neutrophil extracellular traps induce IFN-α production, measuring neutrophil extracellular traps may estimate IFN-α levels and identify which systemic lupus erythematosus patients have elevated levels and may be more likely to respond to emerging anti-IFN-α therapies. In addition to anti-IFN-α therapies, other novel agents, such as N-acetyl-cysteine, DNase I, and peptidylarginine deiminase inhibitor 4, target neutrophil extracellular traps. Neutrophil extracellular traps offer insight into the pathogenesis of autoimmune diseases and provide promise in developing disease markers and novel therapeutic agents in systemic lupus erythematosus. Priority areas for basic research based on clinical research insights will be identified, specifically the potential role of neutrophil extracellular traps as a biomarker and therapeutic target in systemic lupus erythematosus.
26654341 The rise and fall of the craniocervical junction relative to the hard palate: a lifetime s 2016 Apr OBJECT: Endoscopic approaches to the anterior craniocervical junction are increasing in frequency. Choice of oral versus endoscopic endonasal approach to the odontoid often depends on the relationship of the C1-2 complex to the hard palate. However, it is not known how this relevant anatomy changes with age. We hypothesize that there is a dynamic relationship of C-2 and the hard palate, which changes with age, and potentially affects the choice of surgical approach. The aim of this study was to characterize the relationship of C-2 relative to the hard palate with respect to age and sex. METHODS: Emergency department billing and trauma records from 2008 to 2014 were reviewed for patients of all ages who underwent cervical or maxillofacial CT as part of a trauma evaluation for closed head injury. Patients who had a CT scan that allowed adequate visualization of the hard palate, opisthion, and upper cervical spine (C-1 and C-2) were included. Patients who had cervical or displaced facial/skull base fractures, a history of rheumatoid arthritis, or craniofacial anomalies were excluded. The distance from McGregor's palatooccipital line to the midpoint of the inferior endplate of C-2 (McL-C2) was measured on midsagittal CT scans. Patients were grouped by decile of age and by sex. A 1-way ANOVA was performed with each respective grouping. RESULTS: Ultimately, 483 patients (29% female) were included. The mean age was 46 ± 24 years. The majority of patients studied were in the 2nd through 8th decades of life (85%). Significant variation was found between McL-C2 and decile of age (p < 0.001) and sex (p < 0.001). The mean McL-C2 was 27 mm in the 1st decade of life compared with the population mean of 37 mm. The mean McL-C2 was also noted to be smaller in females (mean difference 4.8 mm, p < 0.0001). Both decile of age (p = 0.0009) and sex (p < 0.0001) were independently correlated with McL-C2 on multivariate analysis. CONCLUSIONS: The relationship of C-2 and the hard palate significantly varies with respect to age and sex, descending relative to the hard palate a full centimeter on average in adulthood. These findings may have relevance in determining optimal surgical approaches for addressing pathology involving the anterior craniocervical junction.