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ID PMID Title PublicationDate abstract
20856230 IL17: potential therapeutic target in Sjögren's syndrome using adenovirus-mediated gene t 2011 Jan Sjögren's syndrome (SS) involves a chronic, progressive inflammation primarily of the salivary and lacrimal glands leading to decreased levels of saliva and tears that eventually result in dry mouth and dry eye diseases. T(H)17 cell populations secreting IL17A have been shown to have an important function in an increasing number of autoimmune diseases, including SS. In this study, we investigated the function of IL17A on SS development and onset. Adenovirus-5 vectors expressing either IL17R:fragment of crystallization (Fc) fusion protein or LacZ were injected through retrograde cannulation into the salivary glands of SS-susceptible (SS(S)) C57BL/6.NOD-Aec1Aec2 mice between 6 and 8 weeks of age (a pre-disease stage) or 15 and 17 weeks of age (a diseased stage). The mice were subsequently characterized for their SS phenotypes. Mice cannulated with the Ad5-IL17R:Fc viral vector at either 7 or 16 weeks of age exhibited a rapid temporal, yet persistent, decrease in the levels of serum IL17 as well as the overall numbers of CD4+IL17+T cells present in their spleens. Disease profiling indicated that these mice showed decreased lymphocytic infiltrations of their salivary glands, normalization of their antinuclear antibodies repertoire, and increased saliva secretion. In contrast, mice cannulated with the control Ad5-LacZ viral vector did not exhibit similar changes and progressed to the overt disease stage. The capacity of the Ad5-IL17R:Fc-blocking factor to reduce SS pathology in SS(S) mice strongly suggests that IL17 is an important inflammatory cytokine in salivary gland dysfunction. Thus, therapeutic approach targeting IL17 may be effective in preventing glandular dysfunction.
20854935 Clinical and laboratory aspects of Ro/SSA-52 autoantibodies. 2011 Jan Anti-Ro/SSA antibodies, which were described for the first time in systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS), are the most prevalent extractable nuclear antigen (ENA) specificity identified in laboratories. Two types of anti-Ro/SSA antibodies have been described, anti-SSA-52 kDa (aSSA52) and anti-SSA-60 kDa (aSSA60), each specific to different antigens. Anti-Ro/SSA52 autoantibodies are more frequent than other autoantibodies possibly because of the antigen's accessible and ubiquitous nature. The sites involved and the symptoms associated with these autoantibodies depend on the antigen's structural variability. Isolated congenital complete atrioventricular block (CAVB) shows a close association with maternal anti-Ro/SSA and anti-La/SSB antibodies; the highest relative risks of CAVB are seen in offspring of mothers with antibodies against 52-kDa Ro and 48-kDa La proteins. Anti-Ro/SSA52 antibodies have little impact on adult rheumatic autoimmune diseases or adult cardiac arrhythmias, but the course of autoimmune liver diseases is greatly worsened by their presence, and solid tumours tend to relapse. Their diagnostic role in rheumatic diseases is controversial, although a significant association between isolated anti-Ro/SSA52-kDa positivity and myositis and to a lesser extent with systemic sclerosis (SSc) has been described. However, the majority of the specific diagnosis is mostly based on the simultaneous presence of other autoantibodies that seems diagnostically more relevant.
22514802 2012 Mar OBJECTIVES: To assess the test performance of antinuclear antibody (ANA), rheumatoid factor (RF), and cyclic-citrullinated peptide (CCP) tests in children and adolescents with undiagnosed musculoskeletal (MSK) pain or joint swelling, compared with clinical diagnoses of pediatric systemic lupus erythematosus (pSLE) and juvenile idiopathic arthritis (JIA). To explore differences in test performance for accuracy modifiers including age, sex, race or ethnicity, comorbidities, and recent infections. To evaluate the impact of test results on clinical decisionmaking and clinically important outcomes such as referrals, ordering of additional tests, clinical management, and anxiety experienced by children and parents. DATA SOURCES: We conducted comprehensive searches in nine electronic databases. We also hand searched reference lists and conference proceedings. There were no restrictions on language, year of publication, and study design. REVIEW METHODS: Study selection, quality assessment, data extraction, and grading the evidence were conducted independently by two reviewers. A combination of qualitative and quantitative approaches was used to synthesize the data. We calculated sensitivity (Sn) and specificity (Sp). RESULTS: The search identified 11,695 citations; 28 were included in the review. Only one cohort study examined the test performance of RF to diagnose JIA among children with undiagnosed MSK pain. It demonstrated an Sn of 5 percent and an Sp of 98 percent. Fifteen case-control studies did not specifically address the test performance of RF among children with MSK pain. The strength of evidence is low for both Sn and Sp. The 12 case-control studies that examined other test-disease combinations did not specifically address the prevalence of positive tests for ANA or CCP among children presenting with undiagnosed MSK pain. The strength of evidence is insufficient to determine the test performance of ANA or CCP to diagnose JIA or pSLE in children with undiagnosed MSK pain. No studies addressed children with joint swelling. There was no evidence addressing the prespecified accuracy modifiers or clinically important outcomes. CONCLUSIONS: Most of the evidence from the 28 studies included in the review was not applicable to the population of interest as most studies examined children with known disease rather than with undiagnosed MSK pain. No studies provided a complete investigation on accuracy modifiers. No studies examined clinically important outcomes such as the impact of the test results on referrals, ordering of additional tests, patient management, and patient and parent anxiety levels. Because the Sn and Sp of these tests have yet to be verified, current evidence does not support their use as diagnostic tests for children with undiagnosed MSK pain. They have a potential application as an adjunct to a clinical assessment that suggests the presence of an inflammatory arthritis or connective tissue disease.
24820632 Tartrate-resistant acid phosphatase 5a in sarcoidosis: further evidence for a novel macrop 2014 Jun BACKGROUND/PURPOSE: Tartrate-resistant acid phosphatase (TRACP) 5a is expressed strongly in inflammatory macrophages (MΦ). Serum TRACP5a is elevated in rheumatoid arthritis patients with extra-articular manifestations of rheumatoid nodules, in a percentage of patients with end-stage chronic kidney disease, and may be a risk marker for acute myocardial infarction. This proof-of-concept study was undertaken in patients with sarcoidosis to further substantiate our hypothesis that TRACP5a protein is a biomarker for macrophages in other chronic inflammatory diseases. METHODS: Immunohistochemical staining for TRACP5a and CD68 was performed in tissues of 19 patients with sarcoidosis. We also measured circulating TRACP5a protein and other inflammation biomarkers including interkeukin-6, angiotensin-converting enzyme, and C-reactive protein in 13 patients. Twenty healthy age-matched nonsmoking individuals were used as the reference group. RESULTS: All sarcoidosis tissues showed strong staining for TRACP5a and CD68 in the non-caseating granulomatous lesions and localized specifically to MΦ, multinucleate giant cells, and epithelioid MΦ. Serum TRACP5a protein was elevated significantly in active sarcoidosis patients compared with the control group, and levels fluctuated with disease activity in one patient studied longitudinally. CONCLUSION: TRACP5a protein is expressed abundantly in the granulomatous tissues and may be elevated in a significant proportion of sarcoidosis patients. These findings further support our hypothesis that serum TRACP5a is derived from systemic inflammatory MΦ and thereby may be a biomarker of inflammation for sarcoidosis and also reflect its disease activity.
23246354 Clinical characteristics of the patients with systemic amyloidosis in 2000-2010. 2013 May BACKGROUND: The epidemiology of systemic amyloidosis has been changing in the last decades. We aim to describe the clinical characteristics of the patients seen at our institution with systemic amyloidosis in 2000-2010 and compare them with previous Spanish series. PATIENTS AND METHODS: An observational, retrospective study was performed on all patients admitted to a tertiary hospital in Madrid, Spain who had been diagnosed of amyloidosis from January 2000 to December 2010. Patients without a proven diagnosis of amyloidosis, with dialysis-associated, senile, or localized forms of amyloidosis were excluded from the study. A systematic review was made of the clinical records, collecting the demographic, clinical and biochemical variables at diagnosis and patients' outcome. RESULTS: A total of 55 patients were studied, 24 (44%) of whom had AL amyloidosis, 30 (56%) AA amyloidosis, and 1 a familiar form. The most frequent underlying disorders were rheumatoid arthritis (9 patients, 30%) and ankylosing spondylitis (4 cases, 13%). The kidneys were the most frequently involved organ (36 patients, 67%) with nephrotic-range proteinuria at diagnosis (3.4 ± 3.7 g/24 h). Median time to diagnosis was 3 months (interquartile range [IQR]: 1-17). Median follow-up time was 24 months (IQR: 10-91). During follow-up 31 patients died; 18 of those deaths were related to amyloidosis. CONCLUSIONS: Renal dysfunction dominates the course of systemic amyloidosis, which does not seem to have changed in the last decades. We have observed an important delay in the diagnosis of these processes. Therefore, it is necessary to maintain a high degree of clinical suspicion regarding these conditions.
23231541 Novel methods and strategies in the discovery of TACE inhibitors. 2013 Feb INTRODUCTION: Tumor necrosis factor-α (TNF-α) is a key player in inflammation and joint damage in rheumatoid arthritis (RA). One treatment approach to exclude TNF-α from the biological system is by inhibiting tumor necrosis factor-alpha converting enzyme (TACE), the enzyme responsible for the production of its active form. To date, a number of TACE inhibitors have been reported in the literature from various strategies and methods. AREAS COVERED: The following article presents the design and development strategies for the discovery of novel TACE inhibitors which could be of therapeutic utility for the alleviation of inflammatory conditions. The review is based on literature of the subject from 2005 onward. EXPERT OPINION: Discovery of a selective TACE inhibitor has remained a major goal for many academic and pharmaceutical industrial research laboratories for quite some time. Identification of selective TACE inhibitors has proved elusive until recently due to structural similarities between TACE and MMPs. The differences in the shape and size of the S1' pocket of TACE and MMPs could be exploited to design selective TACE inhibitors devoid of any MMP inhibitory activity in the near future. It would be a Herculean task to develop a specific TACE inhibitor for clinical treatment of RA because binding subsites of TACE and MMPs are quite similar. However, developments taking place currently in the field as well as in the application of molecular modeling techniques at a wider scale could yet provide clinically useful selective TACE inhibitors in the not too distant future.
22905067 Emotional disclosure interventions for chronic pain: from the laboratory to the clinic. 2012 Mar Life stress and the avoidance of negative emotions may contribute to chronic pain. The technique of written or spoken emotional disclosure can reverse emotional avoidance and improve health, and 18 randomized studies have tested it among people with chronic pain. We review these studies to provide guidance for the clinical use of this technique. The benefits of emotional disclosure for chronic pain are quite modest overall. Studies in rheumatoid arthritis show very limited effects, but two studies in fibromyalgia suggest that disclosure may be beneficial. Effects in other populations (headaches, cancer pain, pelvic pain, abdominal pain) are mixed. Moderator findings suggest that some patients are more likely to benefit than others. Emotional disclosure has been tested in well-controlled efficacy trials, leaving many unanswered questions related to translating this technique to practice. Issues needing further study include determining disclosure's effects outside of randomized controlled trials, identifying the optimal pain populations and specific individuals to target for disclosure, presenting a valid rationale for disclosure, selecting the location and method of disclosure, and choosing between cognitive-behavioral or emotional disclosure techniques.
22862420 Matrix metalloproteinase-3 in the central nervous system: a look on the bright side. 2012 Oct Matrix metalloproteinases (MMPs) are a large family of proteases involved in many cell-matrix and cell-cell signalling processes through activation, inactivation or release of extracellular matrix (ECM) and non-ECM molecules, such as growth factors and receptors. Uncontrolled MMP activities underlie the pathophysiology of many disorders. Also matrix metalloproteinase-3 (MMP-3) or stromelysin-1 contributes to several pathologies, such as cancer, asthma and rheumatoid arthritis, and has also been associated with neurodegenerative diseases like Alzheimer's disease, Parkinson's disease and multiple sclerosis. However, based on defined MMP spatiotemporal expression patterns, the identification of novel candidate molecular targets and in vitro and in vivo studies, a beneficial role for MMPs in CNS physiology and recovery is emerging. The main purpose of this review is to shed light on the recently identified roles of MMP-3 in normal brain development and in plasticity and regeneration after CNS injury and disease. As such, MMP-3 is correlated with neuronal migration and neurite outgrowth and guidance in the developing CNS and contributes to synaptic plasticity and learning in the adult CNS. Moreover, a strict spatiotemporal MMP-3 up-regulation in the injured or diseased CNS might support remyelination and neuroprotection, as well as genesis and migration of stem cells in the damaged brain.
22711544 Inhibition of proinflammatory biomarkers in THP1 macrophages by polyphenols derived from c 2013 Apr Antiinflammatory compounds in the diet can alleviate excessive inflammation, a factor in the pathogenesis of common diseases such as rheumatoid arthritis, atherosclerosis and diabetes. This study examined three European herbs, chamomile (Matricaria chamomilla), meadowsweet (Filipendula ulmaria L.) and willow bark (Salix alba L.), which have been traditionally used to treat inflammation and their potential for use as antiinflammatory agents. Aqueous herbal extracts and isolated polyphenolic compounds (apigenin, quercetin and salicylic acid, 0-100 μM) were incubated with THP1 macrophages, and interleukin (IL)-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were measured. At concentrations of 10 μM, both apigenin and quercetin reduced IL-6 significantly ( p < 0.05). Apigenin at 10 μM and quercetin at 25 μM reduced TNF-α significantly ( p < 0.05). Amongst the herbal extracts, willow bark had the greatest antiinflammatory activity at reducing IL-6 and TNF-α production. This was followed by meadowsweet and then chamomile. The lowest effective antiinflammatory concentrations were noncytotoxic (MTT mitochondrial activity assay). The Comet assay, which was used to study the protective effect of the isolated phenols against oxidative damage, showed positive results for all three polyphenols. These are the first findings that demonstrate the antiinflammatory capacity of these herbal extracts.
22671594 The role for protein tyrosine phosphatase nonreceptor type 2 in regulating autophagosome f 2012 Jun Genome-wide association studies have identified single nucleotide polymorphisms within the gene locus encoding protein tyrosine phosphatase nonreceptor type 2 (PTPN2) as a risk factor for the development of chronic inflammatory diseases, such as inflammatory bowel disease (IBD), type 1 diabetes, and rheumatoid arthritis. IBD is characterized by a breakdown of the intestinal epithelial barrier function leading to an overwhelming and uncontrolled immune response to bacterial antigens. Recent studies demonstrated that PTPN2 regulates cytokine-induced signaling pathways, epithelial barrier function, and cytokine secretion in human intestinal cells. Dysfunction of PTPN2 is also associated with impaired autophagosome formation and defective bacterial handling in intestinal cells. All of these cellular functions have been demonstrated to play a crucial role in the pathogenesis of IBD. The genetic variations within the PTPN2 gene may result in altered protein function, thereby essentially contributing to the onset and perpetuation of chronic inflammatory conditions in the intestine.
22654458 Exceptionally rare cause of a total stomach resection. 2012 May 28 The first-ever case of a 54-year-old woman who overdosed on non-steroidal anti-inflammatory drugs in an attempt at suicide. Before that incident, she had not been treated for coexisting diseases such as rheumatoid arthritis or depression. At the time of admission to the General Surgery Department, the patient reported pains in the epigastric region with accompanying nausea and vomiting with mucous content as well as the inability to ingest food orally. Despite parenteral and enteral feeding, the patient exhibited a drop in body mass. The histopathologic examination of a sample taken from the stomach during gastroscopy showed some non-specific necrotic and inflammatory masses with granulation. Intraoperatively, a very small, infiltrated stomach with an initial section of duodenum was identified. A total stomach resection together with the reconstruction of digestive tract continuity was performed using the Roux-Y method. Histopathologic examination of the stomach revealed a deep, chronic and exacerbated inflammatory condition with an extensive ulceration over the entire length of the stomach, reaching up to the pylorus. Additionally, numerous lymphatic glands with inflammatory reaction changes were observed.
22579542 The relationship of carotid three-dimensional ultrasound vessel wall volume with age and s 2012 Jul The relationship of three-dimensional ultrasound (3DUS)-derived carotid vessel wall volume (VWV) was evaluated with respect to age and sex. B-mode and 3DUS images were acquired for 316 subjects from diverse groups including obese primary prevention, diabetic nephropathy, renal transplant and rheumatoid arthritis populations. The relationship for intima-media thickness (IMT) and VWV with age and sex were determined using Pearson-product-moment correlations. Mean IMT (r = 0.18, p = 0.001) and VWV (r = 0.24, p < 0.01) correlated modestly with age. There were modest correlations in males (IMT, r = 0.19, p = 0.003; VWV, r = 0.34, p < 0.001) and in females for IMT and age (r = 0.30, p = 0.007) but not between 3DUS VWV and age in females (r = 0.10, p = 0.4). Significant associations between plaque and VWV (r = 0.36, p = 0.001) but not IMT suggest different correlations in females that may be attributed to plaque.
22577522 Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis. 2012 The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1(∗)03:01 (OR: 4.04; 95%CI: 1.41-11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1(∗)04:05 (OR: 4.64; 95%CI: 2.14-10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1(∗)04:01 (OR: 3.86; 95%CI: 2.32-6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1(∗)06:02 and DRB1(∗)15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1(∗)06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.
22575561 Protective effect of celastrol in rat cerebral ischemia model: down-regulating p-JNK, p-c- 2012 Jun 29 Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. Celastrol has been proved to elicit a vanity of biological effects through its anti-oxidant, anti-inflammatory properties in the treatment of Alzheimer's disease, systemic lupus erythematosus, and rheumatoid arthritis. However, little is known regarding the effect of celastrol in the acute phase of ischemic stroke. This study investigated the potential protective effects of celastrol and underlying mechanisms in cerebral ischemia. We used a permanent middle cerebral artery occlusion (pMCAO) model and administered celastrol intraperitoneally immediately after stroke. At 24h after stroke, we found that celastrol dramatically reduced neurological deficit, brain water content and infarct sizes, and downregulated the expression of p-JNK, p-c-Jun and NF-κB. The results indicated that celastrol may have the possibility of protective effect against ischemic injury, and this effect may be through downregulation of the expression of p-JNK, p-c-Jun and NF-κB.
22435930 Potential T cell epitopes of Mycobacterium tuberculosis that can instigate molecular mimic 2012 Mar 21 BACKGROUND: Molecular mimicry between microbial antigens and host-proteins is one of the etiological enigmas for the occurrence of autoimmune diseases. T cells that recognize cross-reactive epitopes may trigger autoimmune reactions. Intriguingly, autoimmune diseases have been reported to be prevalent in tuberculosis endemic populations. Further, association of Mycobacterium tuberculosis (M. tuberculosis) has been implicated in different autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Although, in silico analyses have identified a number of M. tuberculosis specific vaccine candidates, the analysis on prospective cross-reactive epitopes, that may elicit autoimmune response, has not been yet attempted. Here, we have employed bioinformatics tools to determine T cell epitopes of homologous antigenic regions between M. tuberculosis and human proteomes. RESULTS: Employing bioinformatics tools, we have identified potentially cross-reactive T cell epitopes restricted to predominant class I and II alleles of human leukocyte antigens (HLA). These are similar to peptides of mycobacterial proteins and considerable numbers of them are promiscuous. Some of the identified antigens corroborated with established autoimmune diseases linked with mycobacterial infection. CONCLUSIONS: The present study reveals many target proteins and their putative T cell epitopes that might have significant application in understanding the molecular basis of possible T cell autoimmune reactions during M. tuberculosis infections.
22365815 [Profitability of a day hospital: analysis of activity, cost and effectiveness]. 2012 Jul OBJECTIVE: Day hospitals are an alternative to conventional hospital care. We analyzed the functioning and profitability of the day hospital of Hospital Clínico de Valladolid, Spain, in 2009. Profitability is expressed as the provision of identical health coverage at a lower cost than that generated by conventional hospital care and with adequate quality indicators. METHODS: We performed a retrospective, observational and descriptive study of the information obtained on each patient attended in the day hospital from January 1 to December 31, 2009. We studied four quality indicators: cancellation of meetings, the rate of transfusion reactions, the out-patient rate and the satisfaction index. The estimated savings for each process was calculated as the difference in the average cost of hospitalization minus the average cost of the process in the day hospital. RESULTS: The most frequent diseases were systemic and connective tissue diseases, accounting for 25.4% of the processes treated; of these, 17.1% corresponded to rheumatoid arthritis. Patient satisfaction was 93%. Meetings cancellations and the rate of transfusion reactions were 0%. The out-patient rate was 26%. Day hospital costs were 8.6% of conventional hospital costs, with savings of 78,390.69 euros. CONCLUSION: The day hospital is cost effective due to savings compared with conventional hospitalization and has a satisfactory quality index.
22207249 Chilblain lupus induced by TNF-α antagonists: a case report and literature review. 2012 Mar We report the case of a 72-year-old man with history of ankylosing spondylitis, who, during the treatment with infliximab, developed painful, erythematous-violaceous plaques with later development of ulcers on his feet associated with cold exposure. Concomitantly with the appearance of these lesions, he presented increased antinuclear antibodies (ANA) titers, positivity for anti-DNA and IgM anticardiolipin antibodies, low complement levels, polyclonal hypergammaglobulinemia, and lymphopenia. He was diagnosed of chilblain lupus induced by infliximab, this agent was withdrawn and initiated treatment for chilblains with improvement of lesions. On reviewing of the literature, we found seven reported cases of tumor necrosis factor α (TNF-α) antagonists-induced chilblain lupus, all in rheumatoid arthritis patients and four of them with clinical and immunological characteristics available are presented and compared with our case. Although it is infrequent, chilblain lupus forms part of the spectrum of TNF-α antagonists-induced lupus erythematosus; usually is limited to skin without progression to systemic lupus erythematosus; presents ANA, anti-DNA, and antinucleosome antibodies positivity as more frequent immunological alterations; and responds appropriately to the specific treatment, TNF-α antagonists withdrawal being not necessary in almost all cases.
22198661 Retrospective study on the effects of immunosuppressive therapy in uveitis associated with 2012 Dec This retrospective study of 432 patients was conducted between 2000 and 2009 to compare immunosuppressive therapy responses in uveitis accompanied or unaccompanied by rheumatic diseases. We divided patients into two groups: uveitis related or unrelated to rheumatic diseases. The clinical improvement after treatment was measured at the end of the observation period. Of the 432 patients with uveitis, 33 (7.6%) patients suffered from associated rheumatic diseases and 399 (92.4%) patients did not. The groups showed similar clinical features, but the mean age at onset of uveitis was lower in the rheumatic disease group (44.06 ± 2.13 years vs. 48.23 ± 0.81 years). The rheumatic diseases included spondyloarthropathy (31%), Behcet's disease (27%), rheumatoid arthritis (18%), systemic lupus erythematosus (15%), Sjogren's syndrome (6%), and mixed connective tissue disease (3%). Erythrocyte sedimentation rate and C-reactive protein level were increased in uveitis associated with rheumatic diseases, whereas ocular complications were not. The response to immunosuppressive therapy was significantly increased in cases of uveitis associated with rheumatic diseases (P < 0.05). Therefore, during early treatment, uveitis accompanied by rheumatic diseases showed better response to immunosuppressive therapy and less frequent complications.
22186621 Tea polyphenols inhibit rat osteoclast formation and differentiation. 2012 Matrix metalloproteinases (MMPs) play an important role in degeneration of the matrix associated with bone and cartilage. Regulation of osteoclast activity is essential in the treatment of bone disease, including osteoporosis and rheumatoid arthritis. Polyphenols in green tea, particularly epigallocatechin-3-gallate (EGCG), inhibit MMPs expression and activity. However, the effects of the black tea polyphenol, theaflavin-3,3'-digallate (TFDG), on osteoclast and MMP activity are unknown. Therefore, we examined whether TFDG and EGCG affect MMP activity and osteoclast formation and differentiation in vitro. TFDG or EGCG (10 and 100 µM) was added to cultures of rat osteoclast precursors cells and mature osteoclasts. Numbers of multinucleated osteoclasts and actin rings decreased in polyphenol-treated cultures relative to control cultures. MMP-2 and MMP-9 activities were lower in TFDG- and EGCG-treated rat osteoclast precursor cells than in control cultures. MMP-9 mRNA levels declined significantly in TFDG-treated osteoclasts in comparison to control osteoclasts. TFDG and EGCG inhibited the formation and differentiation of osteoclasts via inhibition of MMPs. TFDG may suppress actin ring formation more effectively than EGCG. Thus, TFDG and EGCG may be suitable agents or lead compounds for the treatment of bone resorption diseases.
22093538 Rheumatic-musculoskeletal pain and disorders in a naïve group of individuals 15 months fo 2011 Dec BACKGROUND: Prospective community data on arthropathy following Chikungunya (CHIKV), a self-limiting, arboviral infection, causing debilitating arthropathy are lacking. The clinical profile of chronic rheumatic-musculoskeletal (RMSK) pain and disorders, captured inadvertently about 15 months following a CHIKV epidemic is described. MATERIALS AND METHODS: Patients with RMSK pain following the CHIKV epidemic in 2007 were identified from a randomly selected population of 5277 (Age > 15 years) in a village in south India, using a validated questionnaire-based house-to-house survey. Typical narration, records and serology were relied upon to classify CHIKV. Respondents who recorded active pain sites on a human mannequin were evaluated by Rheumatology physicians. RESULTS: A total of 1396 CHIKV infected individuals with painful MSKD were identified, of whom 437 patients (mean age: 48.37 ± 13.62 years; 71.6% women) who were naïve to RMSK pain prior to the epidemic were studied in detail. Incidence of RMSK pain and disorders in the naïve group was 8.3% (437/5277). Knee was the commonest self-reported pain site (83.3%). Majority of the patients (57%) had postviral non-specific polyarthralgia. Soft tissue rheumatism was very common (27.7%). Rheumatoid arthritis and seronegative spondyloarthritis were observed in 6 and 11 patients, respectively. CONCLUSIONS: Although a causal association could not be established, this study has unravelled a wide spectrum of unrecognised post-CHIKV chronic RMSK disorders. Aetiopathogenesis and risk factors of chronicity need to be studied further.