Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
23251581 Meta-analysis of 125 rheumatoid arthritis-related single nucleotide polymorphisms studied 2012 OBJECTIVE: Candidate gene association studies and genome-wide association studies (GWAs) have identified a large number of single nucleotide polymorphisms (SNPs) loci affecting susceptibility to rheumatoid arthritis (RA). However, for the same locus, some studies have yielded inconsistent results. To assess all the available evidence for association, we performed a meta-analysis on previously published case-control studies investigating the association between SNPs and RA. METHODS: Two hundred and sixteen studies, involving 125 SNPs, were reviewed. For each SNP, three genetic models were considered: the allele, dominant and recessive effects models. For each model, the effect summary odds ratio (OR) and 95% CIs were calculated. Cochran's Q-statistics were used to assess heterogeneity. If the heterogeneity was high, a random effects model was used for meta-analysis, otherwise a fixed effects model was used. RESULTS: The meta-analysis results showed that: (1) 30, 28 and 26 SNPs were significantly associated with RA (P<0.01) for the allele, dominant, and recessive models, respectively. (2) rs2476601 (PTPN22) showed the strongest association for all the three models: OR = 1.605, 95% CI: 1.540-1.672, P<1.00E-15 for the T-allele; OR = 1.638, 95% CI: 1.565-1.714, P<1.00E-15 for the T/T+T/C genotype and OR = 2.544, 95% CI: 2.173-2.978, P<1.00E-15 for the T/T genotype. (3) Only 23 (18.4%), 13 (10.4%) and 15 (12.0%) SNPs had high heterogeneity (P<0.01) for the three models, respectively. (4) For some of the SNPs, there was no publication bias according to Funnel plots and Egger's regression tests (P<0.01). For the other SNPs, the associations were tested in only a few studies, and may have been subject to publication bias. More studies on these loci are required. CONCLUSION: Our meta-analysis provides a comprehensive evaluation of the RA association studies from the past two decades. The detailed meta-analysis results are available at: http://210.46.85.180/DRAP/index.php/Metaanalysis/index.
22810269 Notes from the field: severe varicella in an immunocompromised child exposed to an unvacci 2012 Jul 20 Varicella usually is a self-limited disease but can result in serious complications (e.g., encephalitis, pneumonia, sepsis, hemorrhagic varicella, and death), especially among immunocompromised persons. Implementation of the varicella vaccination program in the United States, beginning in 1995, has led to declines of >95% in varicella-related hospitalizations and deaths among populations routinely vaccinated (1).
23207287 p38 mitogen-activated protein kinase (p38 MAPK)-mediated autoimmunity: lessons to learn fr 2013 Mar Evidence is beginning to accumulate that p38 mitogen activated protein kinase (p38 MAPK) signaling pathway plays an important role in the regulation of cellular and humoral autoimmune responses. The exact mechanisms and the degree by which the p38 MAPK pathway participates in the immune-mediated induction of diseases have started to emerge. This review discusses the recent advances in the molecular dissection of the p38 MAPK pathway and the findings generated by reports investigating its role in the pathogenesis of autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and autoimmune hepatitis. Application of newly-developed protocols based on sensitive flow cytometric detection has proven to be a useful tool in the investigation of the phosphorylation of p38 MAPK within different peripheral blood mononuclear cell populations and may help us to better understand the enigmatic role of this signaling cascade in the induction of autoimmunity as well as its role in immunosuppressive-induced remission. Special attention is paid to reported data proposing a specific role for autoantibody-induced activation of p38 MAPK-mediated immunopathology in the pathogenesis of autoimmune blistering diseases and anti-neutrophilic antibody-mediated vasculitides.
23106895 Role of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth fac 2012 Nov Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF superfamily of structurally related cytokines and is known to induce proliferation, migration, differentiation, apoptotic cell death, inflammation, and angiogenesis. These physiological processes are induced by the binding of TWEAK to fibroblast growth factor-inducible 14 (Fn14), a highly inducible cell-surface receptor that is linked to several intracellular signaling pathways, including the nuclear factor-κB (NF-κB) pathway. This review discusses the role of the TWEAK-Fn14 axis in several rheumatic diseases and the potential therapeutic benefits of modulation of the TWEAK-Fn14 pathway.
22541528 Management of the rigid arthritic flatfoot in adults: triple arthrodesis. 2012 Jun The traditional surgical treatment for adults with a rigid, arthritic flatfoot is a dual-incision triple arthrodesis. Over time, this procedure has proved to be reliable and reproducible in obtaining successful deformity correction through fusion and good clinical results. However, the traditional dual-incision triple arthrodesis is not without shortcomings. Early complications include lateral wound problems, malunion, and nonunion. Long-term follow-up of patients after a triple arthrodesis has shown that many develop adjacent joint arthritis at the ankle or midfoot. This particular problem should be considered an expected consequence, rather than a failure of the procedure. Although the indications for and surgical techniques used in triple arthrodesis have evolved and improved with time (predictably improving results in the intermediate term), the triple arthrodesis should be regarded as a salvage procedure. Certain measures can be taken by the surgeon to avoid some problems. If patients are at risk for lateral wound complications, the arthrodesis could be performed through a single medial incision. However, this can make some aspects of the CC fusion more difficult. Implants would have to be inserted percutaneously, which prevents the surgeon from using either staples or plates. If a patient were to need a lateral column lengthening through a CC distraction fusion, this would not be possible medially. If either the ST or CC joints have minimal degenerative changes, they could be spared through a double or modified double arthrodesis, respectively. Although these procedures that deviate from the traditional triple arthrodesis offer promise, further study is required to better define their role in treatment of the rigid, arthritic AAFD. Triple arthrodesis is, by no means, a simple surgery. It requires preoperative planning, meticulous preparation of bony surfaces, cognizance of hindfoot positioning, and rigidity of fixation. The procedure also requires enough experience on the part of the operating surgeon to anticipate postoperative problems and provide modifications in traditional technique for certain patients.
21751573 [International Classification of Functioning, Disability and Health (ICF) in the most impo 2011 Musculoskeletal conditions are common throughout the world and their impact on individuals and society is enormous. The integrative and bio-psycho-socialy based model, the International Classification of Functioning, Disability and Health (ICF) is highly useful for structuring determinants of disability in these conditions. ICF encompasses health and health-related domains: body functions and structure, activity and participation and environmental factors. In clinical settings ICF is used for functional status assessment, goal setting and treatment planning and monitoring, as well as outcome measurement. In clinical practice the implementation of ICF is facilitated by the use of the ICF-based applications, such as ICF sheets or ICF Core Sets. In this article it is reported on the most important musculoskeletal conditions in rheumatology practice from the point of view of ICF and is complementary to the article by the same author that appeared in the previous issue of this journal.
21169343 Outcome in rheumatoid arthritis patients with continued conventional therapy for moderate 2011 May OBJECTIVE: To report from early RA network (ERAN) on Years 2 and 3 28-joint DAS (DAS-28) and HAQ outcomes in newly diagnosed RA patients treated with DMARD therapies stratified to DAS-28 status after 1 year. METHODS: ERAN is a prospective observational cohort of newly diagnosed RA patients, monitored and treated according to local practice. Standardized case report forms are completed at first presentation, 3-6 months, 1 year and annually thereafter. RESULTS: A total of 418 newly diagnosed RA patients with 2 years and 302 with 3 years follow-up were identified in 22 ERAN centres from 2002 to 2008. Within their first year from registration, 67% of patients received monotherapy DMARDs, and 26% combination DMARDs including 2% were on anti-TNF therapies. Between Years 1 and 3, 60% received DMARD monotherapy, 34% combination DMARD therapy including 8% on anti-TNF therapies. Seventy-four per cent of patients with Year 1 DAS-28 < 3.2 and 27% with DAS-28 3.2-5.1 achieved a DAS-28 < 3.2 outcome at Year 2 [odds ratio (OR) 7.64; 95% CI 4.6, 12.6], and 71 and 35%, respectively, at Year 3 (OR 4.49; 95% CI 2.5, 7.9). Seventy-nine per cent of patients with a Year 1 DAS-28 < 3.2 and 52% with DAS-28 3.2-5.1 achieved an HAQ < 1.25 at Year 2 (OR 3.47; 95% CI 2.1, 5.6), and 81 and 47%, respectively, at Year 3 (OR 4.92; 95% CI 2.6, 9.0). CONCLUSIONS: In RA patients with a DAS-28 3.2-5.1 at 1 year, the likelihood of achieving a target low DAS-28 < 3.2, or a low HAQ, at Years 2 or 3 is poor in a routine care setting using conventional DMARDs according to current practice.
22513452 CIITA gene variants are associated with rheumatoid arthritis in Scandinavian populations. 2012 Jul Expression of the major autoimmune risk loci DRB1 and DQB1 is regulated by the class II MHC (major histocompatibility complex) transactivator (CIITA), making the CIITA gene a strong autoimmune risk locus candidate. A CIITA promoter single-nucleotide polymorphism (SNP), rs3087456 (-168 A/G), has indeed been associated with several autoimmune diseases, including rheumatoid arthritis (RA). Recently, an intronic SNP rs8048002 has been suggested as a better susceptibility marker in Addison's disease. Therefore, we tested both SNPs in a panel of autoimmune diseases, consisting of Norwegian patients with RA (n=819), juvenile idiopathic arthritis (JIA; n=524), or type 1 diabetes (T1D; n=1211), and 2149 controls. We also included an independent Swedish RA cohort (n=2503) and controls (n=1416). Both rs3087456 and rs8048002 were significantly associated with RA (combined Norwegian and Swedish patients P(corrected)=0.012 and P(corrected)=0.0016, respectively), but not with JIA or T1D. Meta-analysis of 16 RA cohorts confirmed rs3087456 with only marginal significance (P=0.016). However, results were stronger in the Scandinavian subgroup (4 cohorts, P=3.8 × 10(-4)), indicating a population-dependent effect. A similar pattern was observed in a meta-analysis of rs8048002. Our results support involvement of CIITA in RA, but imply that this is population dependent and that the aetiological variant is yet to be discovered.
22015639 High concentrations of hydrogen sulphide elevate the expression of a series of pro-inflamm 2012 Jan 30 OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder, primarily affecting the articular structures and synovial membranes of multiple joints. Beside pharmacologically based treatments, sulphur bath therapy has long been used as a therapy for patients suffering from different rheumatic disorders. But scientific reports about the beneficial effects of H(2)S as well as about the underlying molecular mechanisms are controversial and rare. METHODS: Fibroblast-like synoviocytes (FLS) derived from RA and OA-patients were treated with the H(2)S-donor sodium hydrogen sulphide (NaHS). IL-6 release was quantified by enzyme-linked immunosorbent assay (ELISA). Gene expression of IL-6, IL-8 and COX-2 as well as of the matrix metalloproteinases (MMPs) MMP-2, MMP-3 and MMP-14 was monitored by quantitative real-time PCR (qRT-PCR). Modulation of the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2 was analysed by Western blotting. RESULTS: High concentrations of H(2)S (above 0.5mM) elevated the expression of pro-inflammatory genes in RA- and OA-FLS. This was accompanied by activation of p38 and ERK1/2 MAPK. H(2)S-induced expression of IL-6, IL-8 and COX-2 was completely blocked by specific inhibitors of p38 and ERK1/2 MAPK and NF-κB. CONCLUSION: H(2)S is a potent gaseous molecule that can upregulate the expression of a series of pro-inflammatory genes in RA and OA-FLS. Therefore, caution is advised in patients with active RA when taking sulphur bath therapy.
22588312 Elevation of KL-6 serum levels in clinical trials of tumor necrosis factor inhibitors in p 2013 Mar OBJECTIVE: The associations between elevated levels of serum Krebs von den Lungen-6 (KL-6) and treatment of rheumatoid arthritis (RA) with tumor necrosis factor (TNF) inhibitors were investigated in five Japanese clinical trials. METHODS: Percentages and incidence rates were calculated for elevated serum KL-6 levels. Adverse events associated with elevated levels of serum KL-6 were investigated. RESULTS: In RISING, a clinical trial for infliximab, 15.6 % of the enrolled patients met criterion B (KL-6 ≥500 U/ml and >1.5-fold increase over the baseline value) by week 54. In HIKARI, 7.8 % of the certolizumab pegol (CZP) group and 0 % of the placebo group met criterion B during the double-blind (DB) period (p = 0.003). In J-RAPID, 8.4 % of the methotrexate (MTX) + CZP and 3.9 % of the MTX + placebo groups met criterion B during the DB period. In GO-MONO, 1.8 % of the golimumab (GLM) and 1.3 % of the placebo groups met criterion B during the DB period. In GO-FORTH, 7.1 % of the MTX + GLM and 0 % of the MTX + placebo groups met criteron B during the DB period (p = 0.017). No adverse events accompanied the elevation of serum KL-6 levels in 95.7 % of these patients. CONCLUSION: Serum KL-6 levels may increase during anti-TNF therapy without significant clinical events. In these patients, continuing treatment with TNF inhibitors under careful observation is a reasonable option.
21219680 Interferon-inducible protein-10 as a marker to detect latent and active tuberculosis in rh 2011 Feb SETTING: effective tuberculosis (TB) screening should be performed before anti-tumour necrosis factor alpha (TNF-α) treatment in rheumatoid arthritis (RA). The usefulness of the tuberculin skin test (TST) and QuantiFERON®-TB Gold (QFT-G) for detecting latent tuberculosis infection (LTBI) is limited. OBJECTIVE: we tested the diagnostic performance of interferon-gamma (IFN-γ) inducible protein 10 (IP-10) and IFN-γ for detecting LTBI in RA patients receiving anti-TNF-α treatment. DESIGN: IP-10 levels were determined by enzyme-linked immunosorbent assay in 56 RA patients and 18 active TB patients. TST was performed using the Mantoux method and QFT-G was performed by measuring IFN-γ levels in whole blood treated with TB-specific antigens. RESULTS: twenty-four (42.9%) TST-positive patients were defined as having LTBI. Significantly higher levels of baseline, early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) stimulated IP-10 were observed in active TB patients (median 209.9 pg/ml, 899.0 pg/ml and 880.2 pg/ml, respectively) and RA patients with LTBI (165.3 pg/ml, 904.4 pg/ml and 747.5 pg/ml, respectively), compared to those without LTBI (89.3 pg/ml, 579.4 pg/ml and 515.0 pg/ml, respectively). Baseline IP-10 has high sensitivity (83.3% and 100%) and medium specificity (67.9% and 59.6%), while ESAT-6-stimulated IP-10 has high sensitivity (87.5% and 100%) and specificity (85.7% and 71.2%) for detecting LTBI and TB. The performance of IP-10 is superior to IFN-γ for detecting LTBI (TST+) and active TB. CONCLUSION: IP-10 may be used for detecting LTBI and as a potential biomarker to identify active TB in RA patients receiving anti-TNF-α treatment.
22529074 Indications for reverse shoulder replacement: a systematic review. 2012 May The outcome of an anatomical shoulder replacement depends on an intact rotator cuff. In 1981 Grammont designed a novel large-head reverse shoulder replacement for patients with cuff deficiency. Such has been the success of this replacement that it has led to a rapid expansion of the indications. We performed a systematic review of the literature to evaluate the functional outcome of each indication for the reverse shoulder replacement. Secondary outcome measures of range of movement, pain scores and complication rates are also presented.
23041275 Orally active desulfated low molecular weight heparin and deoxycholic acid conjugate, 6ODS 2012 Nov 10 The regulation of angiogenesis is an interesting area to consider for novel therapeutic approaches to rheumatoid arthritis (RA). Chemically modified heparins have been developed as possible candidates for angiogenesis inhibitor; however, they have a major clinical drawback in exhibiting poor oral bioavailability. Here, orally absorbable O-desulfated low molecular weight heparin (ODS-LMWH) derivatives were newly synthesized by conjugating 2-O- or 6-O-desulfated LMWH with deoxycholic acid (DOCA) or bisDOCA (a dimer of DOCA), and their physicochemical properties, antiangiogenic potency and pharmacokinetic profiles were assessed. After selecting the best candidate among those derivatives, its therapeutic efficacy on arthritis was investigated in a murine collagen antibody-induced arthritis (CAIA) model. ODS-LMWH derivatives significantly inhibited the capillary-like tube formation of human umbilical vein endothelial cells (HUVECs) and basic fibroblast growth factor (bFGF)-induced angiogenesis in the Matrigel plug assay. Among all the compounds, 6ODS-LHbD showed the highest oral bioavailability in rats (19.3%). In the CAIA mouse model, 6ODS-LHbD (10 mg/kg, p.o., S.I.D.) significantly inhibited neovascularization in the joint, the increase of hind-paw thickness, and the structural damage in the bone. Therefore, 6ODS-LHbD would be a promising candidate for an orally active drug for the treatment of RA.
22828551 Primary total hip arthroplasty by cemented prosthesis in secondary osteoarthritis of the h 2012 Jul Cemented total hip arthroplasty has been being practiced successfully all over the world for the last 5 decades. Osteoarthritis is the most common indication of total hip arthroplasty. This study was done to observe the outcome of primary total hip arthroplasty by cemented prosthesis in secondary osteoarthritis of the hip joint. This prospective study was conducted at the department of Orthopaedics, Bangabandhu Sheikh Mujib Medical University and some private hospitals in Dhaka, Bangladesh from May 2008 to December 2009. Total 21 patients were evaluated. Among them 38.1% had rheumatoid arthritis, 19.1% had ankylosing spondylitis and 42.8% had avascular necrosis. Average duration of postoperative hospital stay was 14.09 days. Regarding the functional outcome, 76.2% patients had excellent, 19.1% had good and 4.8% had fair outcome. So out of 21 cases, 95.2% had satisfactory and 4.8% had unsatisfactory outcome. Cemented total hip arthroplasty is an effective procedure for the management of secondary osteoarthritis of the hip joint.
21068090 The presence or absence of antibodies to infliximab or adalimumab determines the outcome o 2011 Feb OBJECTIVE: The aim of this study was to test the hypothesis that the reason for non-response (caused by immunogenicity or not) to a first tumour necrosis factor (TNF) inhibitor defines whether a second TNF inhibitor will be effective. METHODS: This cohort study consisted of 292 consecutive patients with rheumatoid arthritis (RA), all treated with etanercept. A total of 89 patients (30%) were treated previously with infliximab or adalimumab ('switchers'), and the remaining 203 (70%) were anti-TNF naive. All switchers were divided into two groups: with and without antibodies against the previous biological. Differences in clinical response to etanercept between switchers with and without antibodies and patients who were anti-TNF naive were assessed after 28 weeks of treatment using changes in Disease Activity Score in 28 joints (DAS28). RESULTS: After 28 weeks of treatment, response to etanercept did not differ between patients who were anti-TNF naive and switchers with anti-drug antibodies (ΔDAS28=2.1 ± 1.3 vs ΔDAS28=2.0 ± 1.3; p = 0.743). In contrast, switchers without anti-drug antibodies had a diminished response to etanercept treatment compared to patients who were TNF naive (ΔDAS28 =1.2±1.3 vs ΔDAS28 = 2.1 ± 1.3; p = 0.001) and switchers with antibodies (ΔDAS28 =1.2±1.3 vs ΔDAS28 = 2.0 ± 1.3; p = 0.017). CONCLUSION: Patients with RA with an immunogenic response against a first TNF-blocking agent had a better clinical response to a subsequent TNF blocker compared to patients with RA without anti-drug antibodies. Hence, determining immunogenicity can be helpful in deciding in which patient switching could be beneficial and can be part of a personalised treatment regimen.
22031680 [Pharmacological management of inflammatory rheumatic conditions]. 2011 Sep Inflammatory rheumatic disorders are related to different pathophysiological mechanisms and, hence, their therapeutic management varies according to the underlying disease. Crystal-induced arthritis is characterized by its almost specific responsiveness to colchicine. Regarding ankylosing spondylitis, non steroidal anti-inflammatory drugs (NSAIDs) and TNF blockers are the cornerstones of pharmacological intervention whereas oral corticosteroids at conventional doses are of little value, if any. Conversely, corticosteroids are the drug of choice to treat polymyalgia rheumatica. Furthermore, low-dose corticosteroids were shown to be more effective than NSAIDs in patients with rheumatoid arthritis (RA). However, the main goal being to achieve remission, disease-modifying antirheumatic drugs, either synthetic, especially methotrexate, and/or biologic, such as TNF inhibitors, have a major role in the management of RA. Finally, enhanced understanding of molecular pathogenesis of inflammatory disorders may help to find out how to best target available drugs to right individuals in the future.
21987572 Ubiquitin ligase substrate identification through quantitative proteomics at both the prot 2011 Dec 2 Protein ubiquitination is a key regulatory process essential to life at a cellular level; significant efforts have been made to identify ubiquitinated proteins through proteomics studies, but the level of success has not reached that of heavily studied post-translational modifications, such as phosphorylation. HRD1, an E3 ubiquitin ligase, has been implicated in rheumatoid arthritis, but no disease-relevant substrates have been identified. To identify these substrates, we have taken both peptide and protein level approaches to enrich for ubiquitinated proteins in the presence and absence of HRD1. At the protein level, a two-step strategy was taken using cells expressing His(6)-tagged ubiquitin, enriching proteins first based on their ubiquitination and second based on the His tag with protein identification by LC-MS/MS. Application of this method resulted in identification and quantification of more than 400 ubiquitinated proteins, a fraction of which were found to be sensitive to HRD1 and were therefore deemed candidate substrates. In a second approach, ubiquitinated peptides were enriched after tryptic digestion by peptide immunoprecipitation using an antibody specific for the diglycine-labeled internal lysine residue indicative of protein ubiquitination, with peptides and ubiquitination sites identified by LC-MS/MS. Peptide immunoprecipitation resulted in identification of over 1800 ubiquitinated peptides on over 900 proteins in each study, with several proteins emerging as sensitive to HRD1 levels. Notably, significant overlap exists between the HRD1 substrates identified by the protein-based and the peptide-based strategies, with clear cross-validation apparent both qualitatively and quantitatively, demonstrating the effectiveness of both strategies and furthering our understanding of HRD1 biology.
21598808 Increased vitamin D serum levels correlate with clinical improvement of rheumatic diseases 2011 Apr BACKGROUND: Ultraviolet B (UVB) rays are required by the skin for the production of vitamin D. The intensity of UVB at the Dead Sea area is the lowest in the world. Low vitamin D levels are often associated with musculoskeletal symptoms. OBJECTIVES: To assess the effectiveness of climatotherapy at the Dead Sea on the production of vitamin D in Norwegian patients suffering from various rheumatic diseases and to investigate possible associations between increased vitamin D serum levels, musculoskeletal symptoms and disease severity. METHODS: Sixty Norwegian patients who came to the Dead Sea area for 21 days of medical rehabilitation were divided into three groups according to their diagnosis: chronic pain syndromes, i.e., low back pain or fibromyalgia (Group 1, n=33); rheumatoid arthritis (Group 2, n=16); and osteoarthritis (Group 3, n=11). Serum 25-hydroxyvitamin D (25-OH-D) levels were determined at arrival and prior to departure. The treatment protocol included daily sun exposure (climatotherapy), bathing in the Dead Sea and mineral spring water (balneotherapy), mud applications and fitness classes. RESULTS: 25-OH-D serum levels increased significantly from 71.3 +/- 26.6 nM at arrival to 89.3 +/- 23.2 nM prior to departure (P < 0.001). Adjusted for the initial levels of pain (assessed by a visual analog scale) and disease severity, a direct correlation was observed between increased 25-OH-D serum levels and pain reduction (P = 0.012) and reduction of disease severity (P = 0.02). CONCLUSIONS: Climatotherapy at the Dead Sea induces significant changes in vitamin D. Increased 25-OH-D serum levels are associated with reduced musculoskeletal pain and disease severity.
21506932 Effects of antioxidant polyphenols on TNF-alpha-related diseases. 2011 Oxidative stress and inflammatory responses sustained for a long period of time cause many diseases. A proinflammatory cytokine, tumor necrosis factor α (TNF-α), plays a pivotal role in the pathogenesis of chronic and auto-immune diseases. The present review, supplemented by hitherto unpublished data of the authors and their coworkers, shows that the intake of polyphenols contained in natural sources, such as hydroxytyrosol, tyrosol, oleuropein (olives), naringin and hesperidin (Citrus fruits), resveratrol, procyanidins or oligomeric procyanidin (grapes or grape seed extracts), (-)-epigallocatechin gallate (green tea) and quercetin (grapes, green tea) etc., are able to modulate chronic inflammatory diseases, such as type 2 diabetes, rheumatoid arthritis, inflammatory bowel disease, and affect the formation and interaction of advanced glycation end products with their respective receptors. Furthermore, potent activities of fermented grape marc, prepared as a fine lyophilized powder from fresh skin and seeds of a Japanese grape strain (Koshu) and then fermented with Lactobacillus plantarum, are described. Finally, the bioavailability of representative polyphenols will be discussed.
21210628 Deep vein thrombosis after total knee arthroplasty in asian patients without prophylactic 2011 Jan 3 Deep vein thrombosis (DVT) is an important complication following total knee arthroplasty (TKA). However, the incidence of DVT is generally underestimated due to subclinical or minor symptoms and signs. In Western countries, prophylactic agents against DVT are administered routinely after TKA. However, in Asia, no regular prophylaxis is generally given to patients undergoing TKA. This article presents a prospective study evaluating the incidence of DVT in 724 consecutive Taiwanese patients who underwent TKA without prophylactic anticoagulation therapy. Of these, 328 patients (45.3%) showed positive Homan's sign with calf swelling >3 cm. Ultrasonographic examination revealed the overall incidence of DVT to be 8.6% (62/724). The incidence of DVT was significantly higher in women (P=.035), in patients who underwent bilateral TKA (P=.002), and in patients with a body mass index ≥30 kg/m(2) (P=.026). The incidence of DVT appeared to be increased in patients with higher tourniquet time; however, the difference was not statistically significant. In all of the suspected cases of DVT, the symptoms subsided after the administration of enoxaparin with uneventful follow-up. No patient developed pulmonary embolism. Our results showed a relatively high incidence of DVT in an Asian population following TKA. We therefore consider that following TKA, prophylactic anticoagulation therapy should be administered to high-risk patients.