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ID PMID Title PublicationDate abstract
27862681 Differences in analgesic use in community-dwelling persons with and without Alzheimer's di 2017 Apr BACKGROUND: There are conflicting findings about analgesic use among persons with cognitive impairment compared to cognitively intact older persons. The objective of our study was to investigate the prevalence of analgesic use in community-dwelling persons with and without Alzheimer's disease (AD), within six months after AD diagnosis and to find out factors associated with the use of analgesics and specific analgesic groups. METHOD: We utilized data from register based MEDALZ (Medication use and Alzheimer's disease) cohort consisting of all community-dwelling persons diagnosed with AD during 2005-2011 in Finland and their matched comparison persons without AD. Altogether, 67,215 persons with AD and one comparison person for each case were included. Drug use data were collected from the Prescription Register and comorbidities from Special Reimbursement and Hospital Discharge Registers. RESULTS: Statistically significant (p < 0.001) yet mostly small differences were found for analgesics use: analgesics were used by 34.9% and 33.5% of persons with and without AD, respectively. Paracetamol was the most frequently used analgesic both among persons with (25.0%) and without AD (19.1%). Persons with AD used less frequently NSAIDs (Nonsteroidal Anti-inflammatory Drugs) (13.2% vs. 17.3%) and mild opioids (5.0% vs. 7.1%), while the use of strong opioids was more common in comparison to persons without AD (1.3% vs. 1.1%, respectively). Analgesic users were more likely women, aged ≥80 years, had asthma/COPD, cardiovascular disease, diabetes, cancer, hip fracture, osteoporosis, rheumatoid arthritis, and lower socioeconomic position. CONCLUSION: Further studies are needed to evaluate the adequateness of pain relief in older persons with and without AD. SIGNIFICANCE: Persons with Alzheimer's disease (AD) used more frequently paracetamol and less frequently NSAIDs and mild opioids. A decreasing trend of NSAID use was observed among persons with AD during the study period.
27861372 Soluble vascular cell adhesion molecular-1 is a potential biological indicator of hemophil 2016 Nov Hemophilic arthropathy is the most common chronic complication in patients with hemophilia. The pathogenesis of hemophilic arthropathy involves the inflammatory processes associated with rheumatoid arthritis (RA). Determining the severity and/or progression of joint damage is crucial when evaluating the effect of treatment modalities. Identifying reliable biomarkers in the peripheral blood of patients with hemophilic arthropathy may be beneficial in clinical practice. Circulating soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin, and P-selectin levels are elevated in patients with RA. Our study investigated whether these soluble adhesion molecules can be used as biological indicators in the course of joint damage in patients with hemophilia A.Patients with hemophilia A (mild, moderate, and severe) were enrolled. The plasma levels of sVCAM-1, E-selectin, and P-selectin in patients with hemophilia A and control were measured using specific enzyme-linked immunosorbent assay kits. Joint damages were evaluated using Pettersson scores.No statistically significant differences were observed in E-selectin and P-selectin levels between patients and controls. The sVCAM-1 level was significantly higher in patients with hemophilia A than in controls. The differences remained significant in patients with severe hemophilia A but not in patients with mild or moderate hemophilia A. The degree of hemophilic arthropathy was evaluated using Pettersson scores, and a score higher than 5 indicated marked arthropathy. Patients with more than 1 joint with marked arthropathy showed significantly higher sVCAM-1 levels.sVCAM-1 levels in patients with hemophilia A are associated with the severity of hemophilic arthropathy.
27687027 Lupus nephritis is associated with more corticosteroid-associated organ damage but less co 2017 May Objective The objective of this study was to investigate the association of lupus nephritis on organ damage and mortality in patients with systemic lupus erythematosus (SLE). Methods A total of 1112 patients with SLE were investigated. Lupus nephritis was defined as a proteinuria based on the 1997 American College of Rheumatology criteria. Damage was assessed using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. The associations of lupus nephritis with overall, non-renal, corticosteroid-associated, and non-associated damage were analyzed using logistic regression. The age-adjusted and sex-adjusted standardized mortality ratio was evaluated in patients with and without lupus nephritis. Results The prevalence of lupus nephritis in patients with SLE was 46.3%. Patients with lupus nephritis had a higher percentage of overall cumulative damage than patients without lupus nephritis (51.5% vs. 35.7%, p < 0.001). The odds ratio was 1.40 after adjusting for age at SLE diagnosis, sex, disease duration, anti-malarial agents, immunosuppressive agents and cumulative corticosteroid dose. Among non-renal damage, the odds of corticosteroid-associated damage were higher (2.06, 95% confidence interval (CI) 1.43-2.96) whereas the odds of non-associated damage were lower (0.50, 95% CI 0.35-0.75) in patients with lupus nephritis. The standardized mortality ratios of patients with and without lupus nephritis were 5.17 (95% CI 3.49-7.38) and 2.32 (95% CI 1.47-3.48), respectively. Conclusion In patients with SLE, the presence of lupus nephritis is associated with increased corticosteroid-associated damage but less corticosteroid non-associated damage. Also, mortality is significantly higher in patients with lupus nephritis than in those without lupus nephritis.
27658548 PTPN2-deficiency exacerbates T follicular helper cell and B cell responses and promotes th 2017 Jan Non-coding single nucleotide polymorphisms that repress PTPN2 expression have been linked with the development of type 1 diabetes, rheumatoid arthritis and Crohn's disease. PTPN2 attenuates CD8(+) T cell responses to self and prevents overt autoreactivity in the context of T cell homeostasis and antigen cross-presentation. The role of PTPN2 in other immune subsets in the development of autoimmunity remains unclear. Here we show that the inducible deletion of PTPN2 in hematopoietic compartment of adult non-autoimmune prone mice results in systemic inflammation and autoimmunity. PTPN2-deficient mice had increased inflammatory monocytes, B cells and effector T cells in lymphoid and non-lymphoid tissues and exhibited symptoms of dermatitis, glomerulonephritis, pancreatitis and overt liver disease. Autoimmunity was characterised by the formation of germinal centers in the spleen and associated with markedly increased germinal center B cells and T follicular helper (T(fh)) cells and circulating anti-nuclear antibodies, inflammatory cytokines and immunoglobulins. CD8(+) T cell proliferative responses were enhanced, and interleukin-21-induced STAT-3 signalling in T(fh) cells and B cells was increased and accompanied by enhanced B cell proliferation ex vivo. These results indicate that deficiencies in PTPN2 across multiple immune lineages, including naive T cells, T(fh) cells and B cells, contribute to the development of autoimmunity.
27418295 Improving Risk Adjustment Above Current Centers for Disease Control and Prevention Methodo 2016 Oct OBJECTIVE To identify comorbid conditions associated with surgical site infection (SSI) among patients undergoing renal transplantation and improve existing risk adjustment methodology used by the Centers for Disease Control and Prevention National Healthcare Safety Network (NHSN). PATIENTS Patients (≥18 years) who underwent renal transplantation at University of Maryland Medical Center January 1, 2010-December 31, 2011. METHODS Trained infection preventionists reviewed medical records to identify surgical site infections that developed within 30 days after transplantation, using NHSN criteria. Patient demographic characteristics and risk factors for surgical site infections were identified through a central data repository. International Statistical Classification of Disease, Ninth Revision, Clinical Modification codes were used to analyze individual component comorbid conditions and calculate the Charlson and Elixhauser comorbidity indices. These indices were compared with the current NHSN risk adjustment methodology. RESULTS A total of 441 patients were included in the final cohort. In bivariate analysis, the Charlson components of cerebrovascular disease, peripheral vascular disease, and rheumatologic disorders and Elixhauser components of obesity, rheumatoid arthritis, and weight loss were significantly associated with the outcome. A model utilizing the variables from the NHSN methodology had a c-statistic of 0.56 (95% CI, 0.48-0.63), whereas a model that also included comorbidities from the Charlson and Elixhauser indices had a c-statistic of 0.65 (95% CI, 0.58-0.73). The model with all 3 risk adjustment scores performed best and was statistically different from the NHSN model alone, demonstrated by improvement in the c statistic (0.65 vs 0.56). CONCLUSION Risk adjustment models should incorporate electronically available comorbid conditions. Infect Control Hosp Epidemiol 2016;1-6.
27262798 Argatroban more effectively inhibits the thrombin activity in synovial fluid than naturall 2016 May 30 The purpose of this study was to clarify the precise effect of argatroban on the inhibition of cytokine secretion induced by thrombin on synovial cells. The efficiency of thrombin inactivation by thrombin inhibitors was evaluated in human synovial fluids (SFs). In SFs from 13 osteoarthritis (OA) and 11 rheumatoid arthritis (RA) patients, thrombin, Factor Xa (FXa), plasmin activity, IL-6, MMP-3, VEGF, and D-dimer concentrations were measured. Tissue factor (TF) activity or IL-6, MMP-3, and VEGF secretion of human synovial cells with or without thrombin and argatroban were measured. The efficiency of thrombin inactivation in SFs was compared for thrombin inhibitors: argatroban, antithrombin III (ATIII), or heparin cofactor II (HCII). In SFs, thrombin, FXa, plasmin, D-dimer, IL-6, and MMP-3 were significantly higher in RA than in OA. In synovial cell experiments, TNF-alpha and thrombin enhanced TF activity on the cell surface, and IL-6, MMP-3, and VEGF secretion were enhanced by thrombin. Increased TF activity, and IL-6, MMP-3, and VEGF secretion induced by thrombin were inhibited by argatroban. In SFs, argatroban inactivated thrombin more effectively than ATIII or HCII. Since thrombin plays an important role in the disease activity of OA and RA, it is a potential therapeutic molecular target. Argatroban was the most effective anticoagulant to inhibit thrombin activity in SF. Intra-articular injection is ideal administration because it can deliver high dose of argatroban without high risk of systematic complication.
26709253 Eosinophilic gastrointestinal disorders associated with autoimmune connective tissue disea 2016 Oct OBJECTIVES: To determine the clinical and pathological characteristics of eosinophilic gastrointestinal disease (EGID) associated with autoimmune connective tissue disease (CTD). METHODS: Systematic literature review. RESULTS: Twenty cases of CTD associated with EGID were identified. Systemic lupus erythematosus was the main EGID-associated CTD (35%), followed by rheumatoid arthritis (20%), systemic sclerosis or inflammatory myopathies (15%, each), and Sjögren's syndrome, scleromyositis or other overlapping connective tissue disease (5%, each). No patient had a history of atopy. In contrast with classical EGID among which eosinophilic esophagitis is the most frequent type, eosinophilic gastritis and/or enteritis represented 95% of cases. Gastrointestinal symptoms were often unspecific. Peripheral eosinophilia was found in 67% of cases. Upper and lower gastrointestinal endoscopy showed abnormal findings in only 40% and 30% of cases, respectively. EGID was confirmed by evidence of digestive eosinophilic infiltration, mainly in mucosal or submucosal layer. In all but one patient, the CTD was diagnosed prior to the occurrence of the EGID. In total, 95% of EGID had a favorable outcome, with corticosteroids being used in almost all cases. CONCLUSION: Clinicians should consider EGID as a possible diagnosis and perform gastrointestinal tract biopsies in patients with CTD presenting with gastrointestinal symptoms and unexplained eosinophilia. Conversely, more rarely extra-digestive features during follow-up in patients with EGID may lead to a diagnosis of an associated CTD. More research is needed to better understand the underlying pathophysiological processes leading to eosinophilic gastrointestinal infiltration in patients with CTD.
26594594 Identification of α1-Antitrypsin as a Potential Candidate for Internal Control for Human 2015 Western blot of synovial fluid has been widely used for osteoarthritis (OA) research and diagnosis, but there is no ideal loading control for this purpose. Although β-actin is extensively used as loading control in western blot, it is not suitable for synovial fluid because it is not required in synovial fluid as a cytoskeletal protein. A good loading control for synovial fluid in OA studies should have unchanged content in synovial fluids from normal and OA groups, because synovial fluid protein content can vary with changes in synovial vascular permeability with OA onset. In this study, we explore the potential of using α1-antitripsin (A1AT) as loading control for OA synovial fluid in western blot. A1AT level is elevated in inflammatory conditions such as rheumatoid arthritis (RA). Unlike RA, OA is a non-inflammation disease, which does not induce A1AT. In this study, we identified A1AT as an abundant component of synovial fluid by Mass Spectrometry and confirmed that the level of A1AT is relative constant between human OA and normal synovial fluid by western blot and ELISA. Hence, we proposed that A1AT may be a good loading control for western blot in human OA synovial fluid studies provided that pathological conditions such as RA or A1AT deficiency associated liver or lung diseases are excluded.
26514518 Association of the -2518 A/G Polymorphism of MCP-1 with Breast Cancer in Punjab, North-Wes 2015 BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) is a major chemokine thought to be responsible for monocyte and T-lymphocyte recruitment in acute inflammatory conditions and recruitment of macrophages in tumors. It is also implicated in cardiovascular disease, rheumatoid arthritis and chronic obstructive pulmonary disease. The aim of the present study was to investigate the correlation between MCP-1 -2518 A/G polymorphism and breast cancer risk in patients from Amritsar city of Punjab state in North-West India. MATERIALS AND METHODS: We screened DNA samples of 200 sporadic breast cancer patients and 200 age and gender matched unrelated healthy individuals for MCP-1 -2518 A/G polymorphism using the PCR-RFLP method. RESULTS: A significantly increased frequency of the GG genotype was observed in patients as compared to controls. Individuals carrying the MCP1 -2518GG genotype had a two fold risk for breast cancer (OR=2.06, 95%CI, 1.06-3.98; p=0.03). Genetic models analysis revealed a significant association between MCP-1 -2518 A/G polymorphism and cancer risk in homozygous co-dominant (OR=2.06, 95%CI, 1.06-3.98; p=0.03) and recessive (OR=1.97, 95%CI, 1.05-3.70; p=0.03) models. CONCLUSIONS: We conclude that the GG genotype of the MCP-1-2518 A/G polymorphism is associated with increased risk to breast cancer in Punjab, North-West India.
26390101 A Report of Three Cases With Acquired Generalized Lipodystrophy With Distinct Autoimmune C 2015 Nov CONTEXT: Acquired generalized lipodystrophy (AGL) is associated with leptin deficiency as a result of adipose tissue loss and hypertriglyceridemia, insulin resistance, and hepatic steatosis. It may coexist with other autoimmune diseases such as Hashimoto's thyroiditis, rheumatoid arthritis, hemolytic anemia, and chronic active hepatitis. Metreleptin therapy has been shown to improve metabolic abnormalities in lipodystrophy, but the effect on AGL patients with active autoimmune disease is unknown. CASE DESCRIPTION: We report 3 cases of pediatric patients with AGL and distinct active autoimmune diseases who were treated with metreleptin over a period of 4-6 years. Case 1 is a 9-year-old girl with active juvenile dermatomyositis, who was successfully treated with leptin with no worsening of her dermatomoysitis. Case 2 is a 16-year-old female with Graves' disease, who could discontinue all her antidiabetic medication completely with improved triglyceride levels. Case 3 is an 11-year-old boy with active autoimmune hepatitis and chronic urticaria, whose hyperphagia has resolved and his liver enzymes and hepatosplenomegaly have improved. CONCLUSION: Metreleptin therapy is of considerable clinical benefit to reduce insulin resistance and hypertriglyceridemia and did not appear to alter the clinical course of autoimmune disease nor clinical efficacy of immunosuppressive treatments. Our observations suggest that risk or presence of autoimmune disease should not lead to withholding of metreleptin treatment from patients with AGL, but should prompt close clinical follow up in light of cautionary preclinical data.
26363489 Simultaneous determination of triptolide, tripterifordin, celastrol and nine sesquiterpene 2016 Jan 5 Tripterygium wilfordii tablet (TWT) and Tripterygium hypoglaucum tablet (THT), the preparations of the two Tripterygium herbs, are well known for the treatment of rheumatoid arthritis and other related inflammatory diseases clinically. In the present study, a high performance liquid chromatography (HPLC) coupled with electrospray ionization (ESI) tandem triple quadrupole mass spectrometry (QQQ/MS) method was developed for simultaneous quantification of 12 chemical components in Tripterygium preparations. The fragmentation patterns of analytes using ESI and collision-induced dissociation (CID) techniques were reported. This assay method was validated with respect to linearity (r(2)>0.9991), precision, repeatability, and accuracy (recovery rate between 97.2 and 104.2%). The proposed method was successfully applied for simultaneous quantification of the 12 compounds in Tripterygium preparations from the different manufactures. In addition, to evaluate the quality of Tripterygium preparations, partial least square discrimination analysis (PLS-DA) was performed to differentiate the contents of 12 compounds. In conclusion, the established HPLC/QQQ/MS method was proven to be useful and efficient for quality control of Tripterygium preparations.
26337175 Construct validity of clinical spinal mobility tests in ankylosing spondylitis: a systemat 2016 Jul The study aimed to determine, using systematic review and meta-analysis, the level of evidence supporting the construct validity of spinal mobility tests for assessing patients with ankylosing spondylitis. Following the guidelines proposed in the Preferred Reporting Items for Systematic reviews and Meta-Analyses, three sets of keywords were used for data searching: (i) ankylosing spondylitis, spondyloarthritis, spondyloarthropathy, spondylarthritis; (ii) accuracy, association, construct, correlation, Outcome Measures in Rheumatoid Arthritis Clinical Trials, OMERACT, truth, validity; (iii) mobility, Bath Ankylosing Spondylitis Metrology Index-BASMI, radiography, spinal measures, cervical rotation, Schober (a further 19 keywords were used). Initially, 2558 records were identified, and from these, 21 studies were retained. Fourteen of these studies were considered high level of evidence. Compound indexes of spinal mobility showed mostly substantial to excellent levels of agreement with global structural damage. Individual mobility tests for the cervico-thoracic spine showed only moderate agreements with cervical structural damage, and considering structural damage at the lumbar spine, the original Schober was the only test that presented consistently substantial levels of agreement. Three studies assessed the construct validity of mobility measures for inflammation and low to fair levels of agreement were observed. Two meta-analyses were conducted, with assessment of agreement between BASMI and two radiological indexes of global structural damage. The spinal mobility indexes and the original Schober test show acceptable construct validity for inferring the extent of structural damage when assessing patients with ankylosing spondylitis. Spinal mobility measures do not reflect levels of inflammation at either the sacroiliac joints and/or the spine.
26310503 Severe Jaccoud's arthropathy in systemic lupus erythematosus. 2015 Oct Jaccoud's arthropathy (JA) is a clinical situation nowadays present mostly in systemic lupus erythematosus (SLE). It is characterized by the presence of joint deformities such as "swan neck," ulnar deviation and "Z-thumb" resembling rheumatoid arthritis (RA) but that are passively correctable and without bone erosion on plain radiographs. From our cohort of SLE patients with JA, we selected a subgroup with a more severe form of this arthropathy and looked at their clinical and laboratory profile as well as studied the magnetic resonance imaging (MRI) findings or ultrasound (US) obtained from the hand with most evident deformities. Seven SLE patients with a severe form of JA were identified. All seven patients have "swan neck," ulnar deviation and "Z-thumb" deformities. Two out of seven had "mutilans-type JA" and four had fixed deformities in the metacarpophalangeal (MCP) joints. The MRI of the hand with more evident deformity clinically performed in six cases and US performed in one case showed mild synovitis in five and moderate synovitis in two patients, mild flexor tenosynovitis in six and severe tenosynovitis in one. Only two small bone erosions were observed in the second and third MCP joints of one patient with moderate synovitis. Severe JA compromises the functional capacity of the joints and imposes the risk of misdiagnosis of RA. With the improvement of the survival rate of SLE and the lack of specific prophylactic or therapeutical measures for JA, it is reasonable to assume that more and more cases of severe JA are going to be identified.
26183422 In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for 2016 Jul Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosoma cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T. cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans.
26101035 siRNA Delivery Impedes the Temporal Expression of Cytokine-Activated VCAM1 on Endothelial 2016 Apr Leukocyte recruitment plays a key role in chronic inflammatory diseases such as cardiovascular disease, rheumatoid arthritis, and cancer. Leukocyte rolling and arrest are mediated in part by the temporally-regulated surface expression of vascular cell adhesion molecule-1 (VCAM1) on endothelial cells (ECs). In this paper, we engineered a pH-responsive vehicle comprised of 30 mol% dimethylaminoethyl methacrylate (30D) and 70 mol% hydroxyethyl methacrylate (70H) to encapsulate, protect, and deliver VCAM1 small interfering RNA (siRNA). The ability of siRNA to reduce VCAM1 gene expression is in direct opposition to its activation by cytokines. At 12 h post-activation, VCAM1 gene knockdown was 90.1 ± 7.5% when delivered via 30D/70H nanoparticles, which was on par with a leading commercial transfection agent. This translated into a 68.8 ± 6.7% reduction in the surface density of VCAM1 on cytokine-activated ECs. The pH-responsive delivery of VCAM1 siRNA efficiently reduced temporal surface protein expression, which may be used to avert leukocyte recruitment.
26051917 Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular 2015 Sep Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegener's), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçet's disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections.
26009534 Does mindfulness improve outcomes in patients with chronic pain? Systematic review and met 2015 Jun BACKGROUND: Chronic pain and its associated distress and disability are common reasons for seeking medical help. Patients with chronic pain use primary healthcare services five times more than the rest of the population. Mindfulness has become an increasingly popular self-management technique. AIM: To assess the effectiveness of mindfulness-based interventions for patients with chronic pain. DESIGN AND SETTING: Systematic review and meta-analysis including randomised controlled trials of mindfulness-based interventions for chronic pain. There was no restriction to study site or setting. METHOD: The databases MEDLINE(®), Embase, AMED, CINAHL, PsycINFO, and Index to Theses were searched. Titles, abstracts, and full texts were screened iteratively against inclusion criteria of: randomised controlled trials of mindfulness-based intervention; patients with non-malignant chronic pain; and economic, clinical, or humanistic outcome reported. Included studies were assessed with the Yates Quality Rating Scale. Meta-analysis was conducted. RESULTS: Eleven studies were included. Chronic pain conditions included: fibromyalgia, rheumatoid arthritis, chronic musculoskeletal pain, failed back surgery syndrome, and mixed aetiology. Papers were of mixed methodological quality. Main outcomes reported were pain intensity, depression, physical functioning, quality of life, pain acceptance, and mindfulness. Economic outcomes were rarely reported. Meta-analysis effect sizes for clinical outcomes ranged from 0.12 (95% confidence interval [CI] = -0.05 to 0.30) (depression) to 1.32 (95% CI = -1.19 to 3.82) (sleep quality), and for humanistic outcomes 0.03 (95% CI = -0.66 to 0.72) (mindfulness) to 1.58 (95% CI = -0.57 to 3.74) (pain acceptance). Studies with active, compared with inactive, control groups showed smaller effects. CONCLUSION: There is limited evidence for effectiveness of mindfulness-based interventions for patients with chronic pain. Better-quality studies are required.
25995034 Deep-inspiration breath-hold 18F-FDG-PET/CT is useful for assessment of connective tissue 2016 OBJECTIVE: To examine clinical utility of (18)F-flurodeoxyglucose (FDG)-positron emission tomography (PET)/CT for assessment of interstitial lung disease (ILD) in patients with connective tissue diseases (CTDs). METHODS: A total of 69 (18)F-FDG PET/CT scans were conducted under deep inspiratory breath hold (DIBH) conditions in 45 CTD patients with ILD, including 16 dermatomyositis/polymyositis, nine systemic scleroderma and seven rheumatoid arthritis. Intensity and distribution of (18)F-FDG signals in PET/CT were determined by standardized uptake value (SUVmax) and visual score in 18 regions, respectively. ILD was defined as active when immunosuppressive therapy was initiated or intensified. RESULTS: Both SUVmax and visual score were higher in active phase (n = 32) than inactive phase (n = 37) (both p < 0.05), regardless of the underlying CTD and plain CT findings. The both parameters reduced after initiating or intensifying treatment in the follow-up study of 17 active patients except two died patients who showed increased visual score. Another two died patients showed high visual score (15 and 6/18, respectively). Changing ratio of visual score, but not SUVmax was correlated with KL-6 (r(2) = 0.38, p < 0.05) and CRP (r(2) = 0.52, p < 0.05). CONCLUSION: The DIBH (18)F-FDG PET/CT procedure sensitively illustrates active ILD lesions in CTD and the extended signal distribution is associated with unfavorable clinical outcome.
25708053 Leonurine hydrochloride inhibits osteoclastogenesis and prevents osteoporosis associated w 2015 Jun Osteoclasts, the primary bone resorbing cells, are responsible for destructive bone diseases such as postmenopausal osteoporosis, rheumatoid arthritis, and periodontitis. Many plant-derived traditional medicines that might suppress the formation and/or function of osteoclasts are promising treatments for osteoclast-related diseases. In this study, we investigated the effects of leonurine hydrochloride (LH) on receptor activator NF-κB ligand (RANKL)-induced osteoclastogenesis and ovariectomy-induced bone loss. LH is a synthetic chemical compound based on the structure of leonurine, which is found in motherwort and has been reported to exhibit phytoestrogenic activity. In RAW 264.7 cells and mouse bone marrow monocytes (BMMs), LH suppressed RANKL-induced osteoclastogenesis and actin ring formation in a dose-dependent manner. LH targeted RANKL-induced osteoclastogenesis and bone resorption at an early stage. Molecular analysis demonstrated that LH attenuated RANKL-induced NF-κB signaling by inhibiting the phosphorylation and degradation of IκBα and NF-κB p65 nuclear translocation. LH inhibited the RANK-TRAF6 association triggered by RANKL binding and the phosphatidylinositol 3-kinase (PI3K)/Akt axis, without significantly affecting the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) and AP-1 signaling pathways. LH attenuated the RANKL-stimulated expression of osteoclast-related genes including NFATc1, tartrate resistant acid phosphatase (TRAP), cathepsin K, and osteoclast-associated receptor (OSCAR). Consistent with the in vitro results, LH administration attenuated osteoclast activity, thus preventing bone loss caused by estrogen deficiency in mice. In this study, LH suppressed RANKL-induced osteoclastogenesis via RANK-TRAF6, NF-κB, and PI3K/Akt signaling. These data provide the first evidence that LH might be a promising therapeutic compound to treat osteoclast-related diseases, such as osteoporosis.
25505274 Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monoc 2015 Jan 15 The alarmins myeloid-related protein (MRP)8 and MRP14 are the most prevalent cytoplasmic proteins in phagocytes. When released from activated or necrotic phagocytes, extracellular MRP8/MRP14 promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis, and inflammatory bowel disease. The involvement of TLR4 and the multiligand receptor for advanced glycation end products as receptors during MRP8-mediated effects on inflammation remains controversial. By comparative bioinformatic analysis of genome-wide response patterns of human monocytes to MRP8, endotoxins, and various cytokines, we have developed a model in which TLR4 is the dominant receptor for MRP8-mediated phagocyte activation. The relevance of the TLR4 signaling pathway was experimentally validated using human and murine models of TLR4- and receptor for advanced glycation end products-dependent signaling. Furthermore, our systems biology approach has uncovered an antiapoptotic role for MRP8 in monocytes, which was corroborated by independent functional experiments. Our data confirm the primary importance of the TLR4/MRP8 axis in the activation of human monocytes, representing a novel and attractive target for modulation of the overwhelming innate immune response.