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ID PMID Title PublicationDate abstract
22925458 Cross-cultural adaptation and validation of a Bengali version of the modified fibromyalgia 2012 Aug 27 BACKGROUND: Currently, no validated instruments are available to measure the health status of Bangladeshi patients with fibromyalgia (FM). The aims of this study were to cross-culturally adapt the modified Fibromyalgia Impact Questionnaire (FIQ) into Bengali (B-FIQ) and to test its validity and reliability in Bangladeshi patients with FM. METHODS: The FIQ was translated following cross-cultural adaptation guidelines and pretested in 30 female patients with FM. Next, the adapted B-FIQ was physician-administered to 102 consecutive female FM patients together with the Health Assessment Questionnaire (HAQ), selected subscales of the SF-36, and visual analog scales for current clinical symptoms. A tender point count (TPC) was performed by an experienced rheumatologist. Forty randomly selected patients completed the B-FIQ again after 7 days. Two control groups of 50 healthy people and 50 rheumatoid arthritis (RA) patients also completed the B-FIQ. RESULTS: For the final B-FIQ, five physical function sub-items were replaced with culturally appropriate equivalents. Internal consistency was adequate for both the 11-item physical function subscale (α = 0.73) and the total scale (α = 0.83). With exception of the physical function subscale, expected correlations were generally observed between the B-FIQ items and selected subscales of the SF-36, HAQ, clinical symptoms, and TPC. The B-FIQ was able to discriminate between FM patients and healthy controls and between FM patients and RA patients. Test-retest reliability was adequate for the physical function subscale (r = 0.86) and individual items (r = 0.73-0.86), except anxiety (r = 0.27) and morning tiredness (r = 0.64). CONCLUSION: This study supports the reliability and validity of the B-FIQ as a measure of functional disability and health status in Bangladeshi women with FM.
22791116 Allergic rhinitis and vascular endothelial growth factor. 2012 Vascular endothelial growth factor (VEGF) was identified in 1980s as a protein that increases vascular permeability and induces endothelial cell-specific mitosis. VEGF plays an important role in angiogenesis during the embryonic stage and in angiogenesis and in increasing vascular permeability during postnatal life, both physiologically and pathologically. Great progress has been made in studies of VEGF, mainly in the field of oncology, and VEGF-targeted therapy has been successfully used to treat patients with cancer. In research related to chronic inflammation, several reports concerning rheumatoid arthritis or retinopathy and VEGF have been published. In the lower respiratory tract, increased levels of VEGF have been detected in biological samples from patients with asthma. However, VEGF has not been studied in detail in upper-airway diseases, such as rhinosinusitis. This review article focuses on VEGF and allergic rhinitis to advance studies of VEGF in chronic inflammation of the upper respiratory tract. VEGF levels in nasal secretions and nasal lavage fluid were higher in perennial allergic rhinitis than in nonallergic rhinosinusitis, after, rather than before, the antigen provocation test. The major VEGF isoforms were confirmed to be VEGF₁₂₁ and VEGF₁₆₅ in allergic rhinitis. Expression of VEGF mRNA was higher in serous versus mucous acini. In allergic rhinitis, serous acini produced significant quantities of VEGF, which was hypersecreted after antigen provocation. VEGF seems to play an important role in the pathophysiology of allergic rhinitis. Modulation of VEGF function seems to contribute to the successful treatment of conditions with airway inflammation such as allergic rhinitis.
22665479 Autolytic proteolysis within the function to find domain (FIIND) is required for NLRP1 inf 2012 Jul 20 Nucleotide-binding domain leucine-rich repeat proteins (NLRs) play a key role in immunity and disease through their ability to modulate inflammation in response to pathogen-derived and endogenous danger signals. Here, we identify the requirements for activation of NLRP1, an NLR protein associated with a number of human pathologies, including vitiligo, rheumatoid arthritis, and Crohn disease. We demonstrate that NLRP1 activity is dependent upon ASC, which associates with the C-terminal CARD domain of NLRP1. In addition, we show that NLRP1 activity is dependent upon autolytic cleavage at Ser(1213) within the FIIND. Importantly, this post translational event is dependent upon the highly conserved distal residue His(1186). A disease-associated single nucleotide polymorphism near His(1186) and a naturally occurring mRNA splice variant lacking exon 14 differentially affect this autolytic processing and subsequent NLRP1 activity. These results describe key molecular pathways that regulate NLRP1 activity and offer insight on how small sequence variations in NLR genes may influence human disease pathogenesis.
22442099 Prevalence of autoimmune diseases in in-patients with schizophrenia: nationwide population 2012 May BACKGROUND: The association between autoimmune diseases and schizophrenia has rarely been systematically investigated. AIMS: To investigate the association between schizophrenia and a variety of autoimmune diseases and to explore possible gender variation in any such association. METHOD: Taiwan's National Health Insurance Research Database was used to identify 10 811 hospital in-patients with schizophrenia and 108 110 age-matched controls. Univariate and multiple logistic regression analyses were performed, separately, to evaluate the association between autoimmune diseases and schizophrenia. We applied the false discovery rate to correct for multiple testing. RESULTS: When compared with the control group, the in-patients with schizophrenia had an increased risk of Graves' disease (odds ratio (OR) = 1.32, 95% CI 1.04-1.67), psoriasis (OR = 1.48, 95% CI 1.07-2.04), pernicious anaemia (OR = 1.71, 95% CI 1.04-2.80), celiac disease (OR = 2.43, 95% CI 1.12-5.27) and hypersensitivity vasculitis (OR = 5.00, 95% CI 1.64-15.26), whereas a reverse association with rheumatoid arthritis (OR = 0.52, 95% CI 0.35-0.76) was also observed. Gender-specific variation was found for Sjögren syndrome, hereditary haemolytic anaemia, myasthenia gravis, polymyalgia rheumatica and dermatomyositis. CONCLUSIONS: Schizophrenia was associated with a greater variety of autoimmune diseases than was anticipated. Further investigation is needed to gain a better understanding of the aetiology of schizophrenia and autoimmune diseases.
22229536 Lipid profiles in untreated patients with dermatomyositis. 2013 Feb BACKGROUND AND OBJECTIVE: Altered lipid levels may occur in autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. However, serum lipid profiles in patients with dermatomyositis (DM) have not been investigated. Our aim was to identify lipid profiles in untreated DM patients, and to assess the relationship of the inflammatory condition of DM with lipid profiles. METHODS: This work was designed and conducted as a case-control study. Forty-one DM patients and 41 age- and gender-matched healthy controls were included. None of the patients had received corticosteroids or disease-modifying antirheumatic drugs prior to the study. Triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were assessed using standard techniques. RESULTS: Twenty-nine patients (70.7%) had an increase level of TG, and 41.5% had a decrease level of HDL-C. The levels of HDL-C in DM were significantly lower than in controls (P < 0.01). The levels of TG, Non- HDL-cholesterol and very LDL-cholesterol (VLDL-C) were significantly higher than in controls (P < 0.001, P < 0.001 and P < 0.05 respectively). The ratios of VLDL-C/LDL-C, TC/HDL-C and LDL-C/HDL-C were significantly higher than in controls (P < 0.001). Spearman's correlation test demonstrated that serum CRP levels correlated negatively with HDL-C in DM(r = -0.420, P = 0.006). CONCLUSION: Dyslipoproteinemia is a common feature in patients with DM that is characterized by an increase in TG and a decrease in HDL-C, suggesting a high risk of atherosclerosis. Inflammation might partly account for the changes of serum lipid profiles in DM.
22216302 Multiple polymorphisms affect expression and function of the neuropeptide S receptor (NPSR 2011 BACKGROUND: neuropeptide S (NPS) and its receptor NPSR1 act along the hypothalamic-pituitary-adrenal axis to modulate anxiety, fear responses, nociception and inflammation. The importance of the NPS-NPSR1 signaling pathway is highlighted by the observation that, in humans, NPSR1 polymorphism associates with asthma, inflammatory bowel disease, rheumatoid arthritis, panic disorders, and intermediate phenotypes of functional gastrointestinal disorders. Because of the genetic complexity at the NPSR1 locus, however, true causative variations remain to be identified, together with their specific effects on receptor expression or function. To gain insight into the mechanisms leading to NPSR1 disease-predisposing effects, we performed a thorough functional characterization of all NPSR1 promoter and coding SNPs commonly occurring in Caucasians (minor allele frequency >0.02). PRINCIPAL FINDINGS: we identified one promoter SNP (rs2530547 [-103]) that significantly affects luciferase expression in gene reporter assays and NPSR1 mRNA levels in human leukocytes. We also detected quantitative differences in NPS-induced genome-wide transcriptional profiles and CRE-dependent luciferase activities associated with three NPSR1 non-synonymous SNPs (rs324981 [Ile107Asn], rs34705969 [Cys197Phe], rs727162 [Arg241Ser]), with a coding variant exhibiting a loss-of-function phenotype (197Phe). Potential mechanistic explanations were sought with molecular modelling and bioinformatics, and a pilot study of 2230 IBD cases and controls provided initial support to the hypothesis that different cis-combinations of these functional SNPs variably affect disease risk. SIGNIFICANCE: these findings represent a first step to decipher NPSR1 locus complexity and its impact on several human conditions NPS antagonists have been recently described, and our results are of potential pharmacogenetic relevance.
22138587 A new long-acting liposomal topical antifungal formula: human clinical study. 2012 Feb PURPOSE: To study the clinical effect of a topical controlled-release ophthalmic fluconazole liposomal formulation on patients with Candida keratitis. METHODS: Eleven eyes of 11 patients with Candida albicans corneal fungal infection (proved by cultures) were included in this study. All were treated with topical liposomal fluconazole (2 mg/mL) 3 times daily. The response to the treatment was divided into 3 categories: complete improvement, complete healing with scar formation at the end of 1 month; partial improvement, decrease in the ulcer size at the end of 1 month; and no improvement, includes extension of ulcer size and/or perforation that necessitates other approaches of management. The patients were examined daily over a 30-day period, and the results were recorded. RESULTS: Eleven eyes with C. albicans as proved with laboratory cultures were included in this study (7 men and 4 women). Three of the patients included in this study had diabetes mellitus, and 2 patients had rheumatoid arthritis. Mean corneal ulcer diameter (mean of both horizontal and vertical diameters) was 5.5 mm (range, 3.5-6.5 mm). Mean duration of the ulcers at presentation was 7.6 days (range, 3-14 days). Eight patients improved after 1 month, whereas 1 patient had partial improvement and 2 patients did not improve and underwent amniotic membrane transplantation. One of the nonimproved patients progressed to perforation, and keratoplasty was performed. Mean decimal notation best-corrected visual acuity on presentation was 0.06, which was not improved at the end of the study. CONCLUSIONS: Therapy with topical liposomal fluconazole (2 mg/mL) carries a high success rate and fast effect in treating patients with C. albicans keratitis.
22053211 High prevalence of systemic autoimmune diseases in patients with Menière's disease. 2011 BACKGROUND: Autoimmunity appears to be associated with the pathophysiology of Meniere's disease (MD), an inner ear disorder characterized by episodes of vertigo associated with hearing loss and tinnitus. However, the prevalence of autoimmune diseases (AD) in patients with MD has not been studied in individuals with uni or bilateral sensorineural hearing loss (SNHL). METHODS AND FINDINGS: We estimated the prevalence of AD in 690 outpatients with MD with uni or bilateral SNHL from otoneurology clinics at six tertiary referral hospitals by using clinica criteria and an immune panel (lymphocyte populations, antinuclear antibodies, C3, C4 and proinflammatory cytokines TNFα, INFγ). The observed prevalence of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and ankylosing spondylitis (AS) was higher than expected for the general population (1.39 for RA, 0.87 for SLE and 0.70 for AS, respectively). Systemic AD were more frequently observed in patients with MD and diagnostic criteria for migraine than cases with MD and tension-type headache (p = 0.007). There were clinical differences between patients with uni or bilateral SNHL, but no differences were found in the immune profile. Multiple linear regression showed that changes in lymphocytes subpopulations were associated with hearing loss and persistence of vertigo, suggesting a role for the immune response in MD. CONCLUSIONS: Despite some limitations, MD displays an elevated prevalence of systemic AD such as RA, SLE and AS. This finding, which suggests an autoimmune background in a subset of patients with MD, has important implications for the treatment of MD.
21984295 [Denosumab for treatment of postmenopausal osteoporosis]. 2011 Oct 4 BACKGROUND: Treatment with bisphosphonates reduces the risk of new fractures and is the treatment of choice for osteoporosis. Denosumab inhibits bone resorption via a different mechanism than bisphosphonates, and is a new option in the treatment of osteoporosis. In this paper we give an overview of the mode of action and clinical effects. MATERIAL AND METHODS: The paper is based on a non-systematic literature search in Pubmed/Medline. RESULTS: Denosumab is a human monoclonal antibody to receptor-activated nuclear factor kappa B (RANKL), a member of the TNF family that is formed in the osteoblast. Binding to RANKL results in reduced recruitment and activity of osteoclasts. Denosumab 60 mg given subcutaneously every six months is shown to inhibit bone resorption to a greater degree than bisphosphonates. In a three-year study of 7,868 women with postmenopausal osteoporosis, a reduction in the relative risk of vertebral, non-vertebral and hip fractures compared to placebo was found (68. 20 and 40 %, correspondingly). In the clinical trials with denosumab, the safety profile was similar to placebo, except for a slightly higher incidence of cellulitis and exanthema. Denosumab has also shown promising skeletal effects in the treatment of cancer and rheumatoid arthritis. INTERPRETATION: Treatment with denosumab has an effect on postmenopausal osteoporosis and may be an alternative to treatment with bisphosphonates. There are few adverse effects and it is simple to administer.
21733721 Risk of stroke in 28,000 patients with celiac disease: a nationwide cohort study in Sweden 2012 Nov BACKGROUND: Earlier studies on stroke in celiac disease (CD) have been underpowered, but a recent study suggested that childhood CD is associated with a 10-fold increased risk of death from stroke, although it was based on small numbers. We examined the risk of stroke in patients with biopsy-verified CD. METHODS: We collected biopsy data from all 28 pathology departments in Sweden and identified 28,676 individuals with CD diagnosed between 1969 and 2007 (Marsh 3: villous atrophy). In the main analyses, we used Cox regression to estimate hazard ratios (HRs) for stroke in patients with CD compared with HRs for stroke in 141,806 sex- and age-matched controls. RESULTS: During follow-up, there were 785 first-stroke diagnoses in patients with CD and 2937 in reference individuals. Patients with CD were at increased risk of stroke (HR 1.10; 95% confidence interval [CI] 1.01-1.19). HRs were similar for ischemic stroke and brain hemorrhage and were not affected by adjustment for type 1 diabetes, rheumatoid arthritis, use of medication against hypertension, or dyslipidemia. The absolute risk of stroke in patients with CD was 267 per 100,000 person-years (excess risk 24/100,000). The highest risk estimates occurred in the first year, with virtually no increased risk after more than 5 years of follow-up after CD diagnosis. The HR for stroke in childhood CD was 1.10 (95% CI 0.37-3.22). CONCLUSIONS: Patients with CD are at only a small increased risk of stroke, which persists only for a brief period after diagnosis. CD does not seem to be a major risk factor for stroke.
21700926 The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherog 2011 Sep OBJECTIVE: Spleen tyrosine kinase (SYK) has come into focus as a potential therapeutic target in chronic inflammatory diseases, such as rheumatoid arthritis and asthma, as well as in B-cell lymphomas. SYK has also been involved in the signaling of immunoreceptors, cytokine receptors, and integrins. We therefore hypothesized that inhibition of SYK attenuates the inflammatory process underlying atherosclerosis and reduces plaque development. METHODS AND RESULTS: Low-density lipoprotein receptor-deficient mice consuming a high-cholesterol diet supplemented with 2 doses of the orally available SYK inhibitor fostamatinib for 16 weeks showed a dose-dependent reduction in atherosclerotic lesion size by up to 59±6% compared with the respective controls. Lesions of fostamatinib-treated animals contained fewer macrophages but more smooth muscle cells and collagen-characteristics associated with more stable plaques in humans. Mechanistically, fostamatinib attenuated adhesion and migration of inflammatory cells and limited macrophage survival. Furthermore, fostamatinib normalized high-cholesterol diet -induced monocytosis and inflammatory gene expression. CONCLUSIONS: We present the novel finding that the SYK inhibitor fostamatinib attenuates atherogenesis in mice. Our data identify SYK inhibition as a potentially fruitful antiinflammatory therapeutic strategy in atherosclerosis.
21615434 A one-hour infusion of infliximab during maintenance therapy is safe and well tolerated: a 2011 Jul BACKGROUND: Infliximab is a chimeric monoclonal antibody to tumour necrosis factor alpha (TNFα) with efficacy in inducing and maintaining remission of inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis and psoriasis. Infliximab is generally administered over 2h with a further 1-h postinfusion observation. This time interval has substantial impact on healthcare resources and is costly in terms of patient's time away from work. AIM: To examine the safety and tolerability of a 1-h, relative to a 2-h maintenance of infusion of infliximab, and to determine the effect of corticosteroid premedication and concurrent immunosuppressor use on infusion reaction rates. METHOD: A prospective cohort study with variable follow-up duration of 2165 consecutive infliximab infusions in 415 patients during 2009 was conducted. Diagnosis, infusion episode number, infusion rate, premedication, concurrent immunosuppressor therapy, the nature and the outcome of infusion reactions were examined. RESULTS: The majority of infusions (74%) were for management of inflammatory bowel disease. Infusion reactions clustered within the first eight infusions with subsequent sporadic reactions. The infusion reaction incidence rate per 1000 person days in 274 1-h infusions from 54 patients and 1356 2-h infusions from 256 patients were 0.08 and 0.28 respectively (P=0.07). Poisson regression model confirmed that the concurrent use of immunosuppressor therapy was associated with a lower infusion reaction rate, whereas corticosteroid premedication was not. CONCLUSIONS: During maintenance therapy, infliximab infusion can be safely administered over 1h in patients with no past history of significant infliximab infusion reaction. Corticosteroid premedication had no impact on the infusion reaction rates.
21451509 Pharmacokinetic and pharmacodynamic evaluation of the novel CCR1 antagonist CCX354 in heal 2011 May The safety and pharmacokinetic (PK)/pharmacodynamic (PD) profile of the novel CCR1 antagonist CCX354 was evaluated in double-blind, placebo-controlled, single- and multiple-dose phase I studies (1-300 mg/day oral doses). CCX354 was well tolerated and displayed a linear dose-exposure profile, with half-life approaching 7 h at the 300-mg dose. The extent of CCR1 receptor blockade on blood monocytes, which correlated well with plasma concentrations of the drug, was assessed using fluorescently labeled CCL3 binding in whole blood from phase I subjects. High levels of receptor coverage at the 12-h time point were achieved after a single dose of 100 mg CCX354. Preclinical studies indicate that effective blockade of inflammatory cell infiltration into tissues requires ≥90% CCR1 inhibition on blood leukocytes at all times. The comparison of the properties of CCX354 with those published for other CCR1 antagonists has informed the dose selection for ongoing clinical development of CCX354 in rheumatoid arthritis (RA).
21473028 (111)In-Labeled recombinant gelonin toxin-B lymphocyte stimulator protein fusion protein. 2004 The B lymphocyte stimulator (BLyS; for other synonyms see Summary Table above) is a glycoprotein belonging to the tumor necrosis factor cytokine family and promotes the survival, proliferation, and differentiation of the B cells (2). Three different receptors on the B cells (for details, see Wen et al. (2)) are known to bind BLyS; among these, the B cell–activating factor receptor shows the strongest affinity for this cytokine. Although BLyS is overexpressed on B cells of individuals suffering from autoimmune diseases such as lupus, rheumatoid arthritis, etc., the BLyS receptors are known to be expressed on the membrane surface of several types of cancerous tumor cells [PubMed]. Because of its specificity of binding to B cells, BLyS-derived fusion toxins such as the gelonin (Gel)-BLyS fusion protein has been studied by investigators to selectively target and treat B cell malignancies (3-6). Gel is an N-glycosidase type I ribosome-inactivating plant toxin that lacks a cell binding or a cell internalization domain and is almost non-toxic to intact cells (2, 7). However, mammalian cells can internalize the toxin in association with a carrier, at which point Gel is lethal to the cells because it inhibits protein synthesis completely within 3–4 days of internalization and release within the cell. Recently a recombinant Gel (rGel)-BLyS fusion protein (rGel/BLyS) was constructed by linking rGel to the N-terminus of BLyS, and rGel/BLys was labeled with (111)In using diethylenetriamine pentaacetic acid (DTPA) to produce the radionuclide chelator [(111)In]-DTPA-rGel/BLyS (2). The biodistribution and tumor-imaging characteristics of [(111)In]-DTPA-rGel/BLyS were then studied in severe combined immunodeficient (SCID) mice bearing B cell lymphoma tumors (2).
21359668 Pattern of use of DXA scans in men: a cross-sectional, population-based study. 2012 Jan Osteoporosis in men is underdiagnosed. The use of dual-emission X-ray absorptiometry (DXA) was evaluated in almost 5,000 men aged 60-74 years. DXA was infrequent, despite the presence of multiple risk factors for osteoporosis and a high FRAX score. There is a need for improved targeting of DXA scans for men at high risk. INTRODUCTION: Clinical and socioeconomic factors associated with bone mass assessment (DXA) in men have seldom been evaluated. This study aimed to evaluate factors associated with the use of DXA in men. METHODS: Self-report information on prior DXA and osteoporosis risk factors were obtained from the baseline data of a study investigating the health perspectives of men aged 60-75 years. Socioeconomic and comorbidity data were retrieved from national registers. The FRAX algorithm was used to calculate the absolute fracture risk. Regression analysis was used to identify factors significantly associated with previous DXA scan. RESULTS: Of the 4,696 men returning questionnaires (50% response rate), 2.7% had prior DXA but 48% had at least one osteoporosis risk factor. Previous DXA was associated with oral glucocorticoid treatment, secondary osteoporosis, rheumatoid arthritis, fracture after age 50, falls within the previous year, smoking, and higher age. Twenty-one percent of men with prior DXA and 10% of men without prior DXA had greater than 20% risk of a major osteoporotic fracture within the next 10 years. One third of those with previous DXA had none of the FRAX osteoporosis risk factors. When family history of osteoporosis and falls were included as risk factors, 18% with previous DXA had no clinical risk factors for osteoporosis. CONCLUSIONS: DXA was infrequent in this group of elderly men, despite the presence of risk factors for osteoporosis. DXA was also used despite a low fracture risk. There is a need for improved targeting of DXA scans for men at high risk.
21339310 Structure, process or outcome: which contributes most to patients' overall assessment of h 2011 Apr RESEARCH QUESTIONS: The paper explores which type of quality aspects (structure, process, outcome) most strongly determines patients' overall assessment of healthcare, and whether there is a variation between different types of patient groups in this respect. METHODS: Secondary analyses were undertaken on survey data from patients who underwent hip or knee surgery, cataract surgery, patients suffering from varicose veins, spinal disc herniation or rheumatoid arthritis. In these analyses, the patient-given global rating served as the dependent variable, and experiences regarding structure (waiting times, continuity of care), process (doctor-patient communication and information) and outcome aspects (improvement or worsening of symptoms) served as independent variables. RESULTS: Experiences regarding process aspects explained most of the variance in the global rating (16.4-23.3%), followed by structure aspects (8.1-21.0%). Experiences regarding outcome did not explain much variance in the global rating in any of the patient groups (5.3-13.5%). The patient groups did not differ with respect to the type of quality aspects that most predicted the overall assessment. DISCUSSION: Improving process and structure aspects of healthcare is most likely to increase patients' overall evaluation of the quality of care as expressed in a global rating. A more sophisticated method of patient reported outcome measurement, with pre- and post-treatment questionnaires and the inclusion of quality-of-life criteria, might lead to higher associations between outcome and the overall evaluation of the received care.
21196592 Epidemiology of the rheumatic diseases in Mexico. A study of 5 regions based on the COPCOR 2011 Jan OBJECTIVE: To estimate the prevalence of musculoskeletal (MSK) disorders and to describe predicting variables associated with rheumatic diseases in 5 regions of México. METHODS: This was a cross-sectional, community-based study performed in 5 regions in México. The methodology followed the guidelines proposed by the Community Oriented Program for the Control of the Rheumatic Diseases (COPCORD). A standardized methodology was used at all sites, with trained personnel following a common protocol of interviewing adult subjects in their household. A "positive case" was defined as an individual with nontraumatic MSK pain of > 1 on a visual analog pain scale (0 to 10) during the last 7 days. All positive cases were referred to internists or rheumatologists for further clinical evaluation, diagnosis, and proper treatment. RESULTS: The study included 19,213 individuals; 11,602 (68.8%) were female, and their mean age was 42.8 (SD 17.9) years. The prevalence of MSK pain was 25.5%, but significant variations (7.1% to 43.5%) across geographical regions occurred. The prevalence of osteoarthritis was 10.5%, back pain 5.8%, rheumatic regional pain syndromes 3.8%, rheumatoid arthritis 1.6%, fibromyalgia 0.7%, and gout 0.3%. The prevalence of MSK manifestations was associated with older age and female gender. CONCLUSION: The prevalence of MSK pain in our study was 25.5%. Geographic variations in the prevalence of MSK pain and specific diagnoses suggested a role for geographic factors in the prevalence of rheumatic diseases.
20814813 Beneficial effect of Eucommia polysaccharides on systemic lupus erythematosus-like syndrom 2011 Oct The stem bark of Eucommia ulmoides Oliv. is commonly used for the treatment of hypertension, rheumatoid arthritis, lumbago, and ischialgia in traditional Chinese medicine. This study was to determine whether the crude polysaccharides (EUPs) isolated from the stem bark of E. ulmoides had beneficial effects on lupus-like syndrome in mice. BALB/c mice were immunized with CJ-S(131) in Freund's complete adjuvant on day 0, and then boosted on day 14. EUPs 15 or 30 mg kg(-1)·day(-1), or prednisone 5 mg kg(-1)·day(-1) was given to BALB/c mice intragastrically from day 0 to 34. Treatment with EUPs 15 or 30 mg kg(-1)·day(-1) for 35 days protected kidney from glomerular injury with reduced immunoglobulin deposition and lowered proteinuria. The increased production of serum autoantibodies and total immunoglobulin G (IgG) was also inhibited. These findings suggested that Eucommia polysaccharides had a beneficial effect on systemic lupus erythematosus-like syndrome induced by CJ-S(131) in BALB/c mice.
20720563 Generation of antibodies of distinct subclasses and specificity is linked to H2s in an act 2011 Jan Epidermolysis bullosa acquisita (EBA) is an autoimmune blistering disease, characterized by antibodies to type VII collagen (COL7). EBA can be induced in mice by immunization with a fragment of the non-collagenous 1 domain of murine COL7. Contrary to other autoimmune diseases, e.g., rheumatoid arthritis, little is known about the genetic susceptibility for EBA. We therefore used the EBA mouse model to address the hypothesis that disease induction depends on the major histocompatibility complex (MHC) haplotype. Mice from different inbred strains were immunized with recombinant murine COL7. Five distinct responses were observed: induction of (i) severe disease in SJL/J (H2s) and female MRL/MpJ (H2k), (ii) mild and transient disease in C57Bl/10.s (H2s), (iii) microscopic blistering in DBA/1J (H2q), (iv) only presence of non-pathogenic autoantibodies in C57Bl/6J (H2b), NZM2410/J (H2z), BXD2 (H2b), and male MRL/MpJ, and (v) complete resistance to EBA in NOD/ShiLtJ (H2g7) and C57Bl/10.q (H2q) mice. Overall, susceptibility to EBA was strongly associated with H2s. In addition, the diseased phenotype was associated with autoantibodies to specific regions of COL7. Our findings show that induction of antibodies with a distinct specificity is linked to the MHC haplotype in experimental EBA. Furthermore, our data are the basis for future studies with the goal of identifying non-MHC EBA susceptibility genes.
21908733 Ginger phenylpropanoids inhibit IL-1beta and prostanoid secretion and disrupt arachidonate 2011 Oct 15 The rhizome of ginger (Zingiber officinale) is employed in Asian traditional medicine to treat mild forms of rheumatoid arthritis and fever. We have profiled ginger constituents for robust effects on proinflammatory signaling and cytokine expression in a validated assay using human whole blood. Independent of the stimulus used (LPS, PMA, anti-CD28 Ab, anti-CD3 Ab, and thapsigargin), ginger constituents potently and specifically inhibited IL-1β expression in monocytes/macrophages. Both the calcium-independent phospholipase A(2) (iPLA(2))-triggered maturation and the cytosolic phospholipase A(2) (cPLA(2))-dependent secretion of IL-1β from isolated human monocytes were inhibited. In a fluorescence-coupled PLA(2) assay, most major ginger phenylpropanoids directly inhibited i/cPLA(2) from U937 macrophages, but not hog pancreas secretory phospholipase A(2). The effects of the ginger constituents were additive and the potency comparable to the mechanism-based inhibitor bromoenol lactone for iPLA(2) and methyl arachidonyl fluorophosphonate for cPLA(2), with 10-gingerol/-shogaol being most effective. Furthermore, a ginger extract (2 μg/ml) and 10-shogaol (2 μM) potently inhibited the release of PGE(2) and thromboxane B2 (>50%) and partially also leukotriene B(4) in LPS-stimulated macrophages. Intriguingly, the total cellular arachidonic acid was increased 2- to 3-fold in U937 cells under all experimental conditions. Our data show that the concurrent inhibition of iPLA(2) and prostanoid production causes an accumulation of free intracellular arachidonic acid by disrupting the phospholipid deacylation-reacylation cycle. The inhibition of i/cPLA(2), the resulting attenuation of IL-1β secretion, and the simultaneous inhibition of prostanoid production by common ginger phenylpropanoids uncover a new anti-inflammatory molecular mechanism of dietary ginger that may be exploited therapeutically.