Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 24478766 | Blood dendritic cells: "canary in the coal mine" to predict chronic inflammatory disease? | 2014 | The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g., cancer). Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDCs) in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of dendritic cell homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome) and activation state of these mDCs. These may provide important clues ("the canary in the coal mine") of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia. | |
| 24398382 | Linear propargylic alcohol functionality attached to the indazole-7-carboxamide as a JAK1- | 2014 Feb 1 | Selective inhibition of JAK1 has recently been proposed as an appropriate therapeutic rationale for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). In this study, through pairwise comparison and 3D alignment of the JAK isozyme structures bound to the same inhibitor molecule, we reasoned that an alkynol functionality would serve as an isozyme-specific probe group, which would enable the resulting inhibitor to differentiate the ATP-binding site of JAK1 from those of other isozymes. The 3-alkynolyl-5-(4'-indazolyl)indazole-7-carboxamide derivatives were thus prepared, and in vitro evaluation of their inhibitory activity against the JAK isozymes revealed that the propargyl alcohol functionality endowed the 5-(4'-indazolyl)indazole-7-carboxamide scaffold with JAK1 selectivity over other JAK isozymes, particularly JAK2. | |
| 26050653 | Pharmacology and Clinical Effect of Platonin, a Cyanine Photosensitizing Dye: Potential Mo | 2014 | Platonin, a photosensitizing dye, is known to possess antioxidant and anti-inflammatory activity. Platonin has been used to treat trauma, ulcers and some acute inflammations and it also reported to improve blood circulation and reduce mortality in endotoxin-induced rat models. Our previous studies established that platonin suppresses the lipopolysaccharides (LPS)-induced inflammatory cytokines, including interleukin-1β (IL-1β-+), IL-6, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS). Nuclear factor-kB (NF-kB) and activator protein-1 (AP-1) transcription factors are reported to be essential in mediating the endotoxin-induced production of inflammatory molecules. In vivo studies from our groups revealed that platonin has potential effects on inhibiting pyrogen release, tissue damage and ischemia during heatstroke, ischemia reperfusion injury in lungs and also improve the survival of skin allografts in rats. Clinically, this compound has been proven to cure juvenile rheumatoid arthritis (JRA) and polyarteritis nodosa (PN). In this review, we summarize the pharmacological and clinical effects of platonin via describing the potential molecular mechanism of regulation of inflammatory molecules of mitogen-activated protein kinases (MAPKs), including extracellular regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 MAPK and also NF-kB activation. Moreover, this paper discusses the signaling pathways expedited by NF-kB, AP-1, MAPKs and NO/NOS, these all have been reflected in inflammatory processes, and could be the encouraging molecular targets for the design of pharmaceutical drugs targeting antiinflammatory therapy. | |
| 24366787 | Total knee replacement system with a ceramic femoral component versus two traditional meta | 2013 Dec | PURPOSE: To compare the short-term outcome of the Multigen Plus system using a symmetric ceramic femoral component with that of 2 metallic total knee replacement (TKR) systems. METHODS: 60 patients (62 knees) with osteoarthritis or rheumatoid arthritis underwent primary TKR using the Genia system (n=20), the Multigen Plus system (n=17), and the Multigen Plus system with a ceramic femoral component (n=25). Outcome was evaluated pre- and post-operatively (at 3, 12, and 24 months) using the Hospital for Special Surgery (HSS) score, the Western Ontario and McMaster Universities (WOMAC) score, and the Short-Form 36 (SF-36) score. RESULTS: The 3 groups did not differ significantly at all 4 time points in terms of the HSS score, WOMAC score, and SF-36 score. The range of motion was significantly less in patients treated with the Genia system. Postoperatively, the HSS and WOMAC scores improved significantly in all 3 groups, whereas the SF-36 score improved significantly (at 12 and 24 months) only in patients treated with the Multigen Plus system with a ceramic femoral component. The implant position in most patients was optimal. All radiolucent lines were within 1 mm and did not progress. CONCLUSION: The short-term outcome of the 3 TKR systems was comparable. Ceramic femoral components performed comparably to traditional metallic designs. | |
| 24327058 | MicroRNA-499 rs3746444 polymorphism and autoimmune diseases risk: a meta-analysis. | 2014 Apr | BACKGROUND AND OBJECTIVE: MicroRNA (miR)-499 rs3746444 polymorphisms may participate in the pathogenesis of autoimmune diseases, but the results remain conflicting. We further investigated this association using a meta-analysis. METHODS: We conducted a retrieval of studies and obtained the eligible studies if they met inclusion criteria. Two researchers independently extracted the data from original articles. The genotype frequencies were analysed using Stata software. RESULTS: We finally archived six eligible studies that included 1,118 cases and 1,673 controls. After pooling the data, the results indicated that homozygote TT had an overall association with autoimmune diseases (TC + CC vs. TT: odds ratio [OR] 1.31, 95% CI 1.11-1.55, p = 0.001). The allele C, genotype TC and CC, may be associated with rheumatoid arthritis (RA) risks in Mediterranean populations (C vs. T: OR 2. 00, 95% CI 1.37-2.91, p < 0.001; TC vs. CC + TT: OR 1.76, 95% CI 1.27-2.44; p = 0.001; CC vs. TC + TT: OR 2.31, 95% CI 1.24-4.27, p = 0.008; CC vs. TT: OR 2.92, 95% CI 1.59-5.37, p = 0.001; TC vs. TT: OR 1.98, 95% CI 1.42-2.77). The genotype TT may decrease the risk of RA in Mediterranean populations (TC + CC vs. TT: OR 2.15, 95% CI 1.57-2.94, p < 0.001) rather than in East Asians. CONCLUSIONS: This study suggested that miR-499 polymorphisms were associated with a significantly increased risk of RA in Mediterranean populations. | |
| 24176752 | Quantitative determination of triterpenoid glycosides in Fatsia japonica Decne. & Planch. | 2014 Jan | Fatsia japonica Decne. & Planch. is a triterpenoid glycoside-rich herb with anti-inflammatory activity for the treatment of rheumatoid arthritis. A method for quantitative analysis of the complex triterpenoid glycosides in this medicinal plant has not been established so far. In this study, a high performance liquid chromatography (HPLC) method was developed for simultaneous qualification of 11 glycosides in F. japonica. The analysis was performed on an ODS-2 Hypersil column (250mm×4.6mm, 5μm) with a binary gradient mobile phase of water and acetonitrile. The established HPLC method was validated in terms of linearity, sensitivity, stability, precision, accuracy, and recovery. Results showed that this method had good linearity with R(2) at 0.99992-0.99999 in the test range of 0.04-9.00μg/μL. The limit of detection (LOD) and limit of quantification (LOQ) for the standard compounds were 0.013-0.020μg/μL and 0.040-0.060μg/μL. The relative standard deviations (RSDs%) of run variations were 0.83-1.40% for intra-day and 0.84-3.59% for inter-day. The analyzed compounds in the samples were stable for at least 36h, and the spike recoveries of the detected glycosides were 99.67-103.11%. The developed HPLC method was successfully applied for the measurements of the contents of 11 triterpenoid glycoside in different parts of F. japonica. Taken together, the HPLC method newly developed in this study could be used for qualitative and quantitative analysis of the bioactive triterpenoid glycosides in F. japonica and its products. | |
| 25627226 | [Influence of genetic polymorphisms (IL-10/CXCL8/CXCR2/NFκB) on the susceptibility of aut | 2014 Jul | The autoimmune rheumatologic disorders mostly have a common genetic path to the autoimmunity. Several genes have been associated with rheumatologic disorders; therefore, we are analyzing just the ones in those containing several evidences of the existence of association with the risk or protection from autoimmune disorder. The nuclear factor kappa beta (NF-kappa B), which regulates the autoimmune and anti-inflammatory responses, is associated with systemic sclerosis (SS), rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), just as the CXCR2 e CXCL8 genes. On the other hand, the interleukin-10 (IL-10), which is an anti-inflammatory cytokine, is associated with almost all rheumatologic disorders. In this article, we are reviewing the potential roles of these genes in the immune system and in several rheumatologic disorders. In relation to IL-10, several studies have been carried out, but most of them are controversial - some detected the absence of association, and others found association in different genetic polymorphisms. Conversely, in relation to NF-kappa B, it was studied just in RA and SLE, and no relevant significant analyses were observed. The genetic polymorphisms of the CXCR2 gene were associated with SS, but not with RA e SLE. On the other side, the genetic polymorphisms of the CXCL8 gene are not associated with SS, but with RA. | |
| 25620685 | Plantar pressure relief under the metatarsal heads: therapeutic insole design using three- | 2015 Feb 26 | Therapeutic footwear with specially-made insoles is often used in people with diabetes and rheumatoid arthritis to relieve ulcer risks and pain due to high pressures from areas beneath bony prominences of the foot, in particular to the metatarsal heads (MTHs). In a three-dimensional finite element study of the foot and footwear with sensitivity analysis, effects of geometrical variations of a therapeutic insole, in terms of insole thicknesses and metatarsal pad (MP) placements, on local peak plantar pressure under MTHs and stress/strain states within various forefoot tissues, were determined. A validated musculoskeletal finite element model of the human foot was employed. Analyses were performed in a simulated muscle-demanding instant in gait. For many design combinations, increasing insole thicknesses consistently reduce peak pressures and internal tissue strain under MTHs, but the effects reach a plateau when insole becomes very thick (e.g., a value of 12.7mm or greater). Altering MP placements, however, showed a proximally- and a distally-placed MP could result in reverse effects on MTH pressure-relief. The unsuccessful outcome due to a distally-placed MP may attribute to the way it interacts with plantar tissue (e.g., plantar fascia) adjacent to the MTH. A uniform pattern of tissue compression under metatarsal shaft is necessary for a most favorable pressure-relief under MTHs. The designated functions of an insole design can best be achieved when the insole is very thick, and when the MP can achieve a uniform tissue compression pattern adjacent to the MTH. | |
| 25481420 | Burden of disability due to musculoskeletal (MSK) disorders. | 2014 Jun | This chapter summarises the global and regional prevalence, disability (Years Lived with Disability (YLDs)) and overall burden (Disability Adjusted Life Years (DALYs)) and costs for the common musculoskeletal disorders including low back and neck pain, hip and knee osteoarthritis, rheumatoid arthritis, gout, and a remaining combined group of other MSK conditions. The contribution of the role of pain in disability burden is introduced. Trends over time and predictions of increasing MSK disability with demographic changes are addressed and the particular challenges facing the developing world are highlighted. | |
| 25228524 | [Vitamin D in allergic disorders]. | 2014 Sep 12 | Vitamin D is a factor that plays a significant role in calcium-phosphate balance. It has an effect on bone metabolism and also has modulator and anti-inflammatory activity. It is claimed that vitamin D inhibits immunological reactions with Th1 and Th17 lymphocytes. The influence of vitamin D on Th2 lymphocytes is not clear. The main effect of vitamin D is probably the activation of Treg lymphocytes. It was observed that vitamin D had a beneficial influence on diseases connected with excessive activation of Th1 lymphocytes, such as multiple sclerosis, rheumatoid arthritis, non-specific enteritis, diabetes type 1 or psoriasis. The role of vitamin D in allergic diseases, in which increased activation of Th2-dependent reactions are of great importance, is controversial. However, due to a wide range of vitamin D activity, this view seems to be simplified. A beneficial effect on the course of allergic diseases was observed in up-to-date studies although the role of vitamin D in their pathogenesis has not been explained yet. On the basis of recent studies and well-known mechanisms of vitamin D activity on particular elements of the immunological system, the influence of vitamin D on the course of chosen allergic diseases, such as allergic asthma, atopic dermatitis and allergic rhinitis was presented considering the possibility of contribution of allergen-specific immunotherapy. | |
| 25175064 | Gold drug auranofin could reduce neuroinflammation by inhibiting microglia cytotoxic secre | 2014 Nov 15 | Neuroinflammation contributes to the pathogenesis of neurological disorders. Anti-inflammatory treatments could potentially be used to slow down the progression of these diseases. We studied the anti-neuroinflammatory activity of gold compounds which have been used to treat rheumatoid arthritis. Non-toxic concentrations of auranofin (0.1-1 μM) significantly reduced the cytotoxic secretions by primary human microglia and microglia-like THP-1 promonocytic cells. Auranofin inhibited primed NADPH-oxidase dependent respiratory burst and secretion of tumor necrosis factor (TNF)-α and nitric oxide by monocytic cells. It had a direct neuroprotective effect on SH-SY5Y neuronal cells. Auranofin could have a novel application in the treatment of neurodegenerative diseases. | |
| 25089121 | Making use of equity sensitive QALYs: a case study on identifying the worse off across dis | 2014 | BACKGROUND: Resource allocation decisions currently lack standard quantitative methods for incorporating concerns about the worse off when analysing the cost-effectiveness of medical interventions. OBJECTIVE: To explore and demonstrate how to identify who are the worse off without a new intervention by measuring lifetime Quality-Adjusted Life Years (QALYs) for patients across different conditions, and compare the results to using proportional shortfall of QALYs. METHODS: Case study of eight condition-intervention pairs that are relevant to priority setting in Norway; childhood deafness (unilateral cochlear implant), unruptured cerebral aneurysm (coiling), morbid obesity (RY gastric bypass), adult deafness (unilateral cochlear implant), atrial fibrillation (catheter ablation), hip osteoarthritis (hip replacement), rheumatoid arthritis (TNF inhibitor) and acute stroke (stroke unit). We extracted prospective QALYs without and with new interventions from published health technology assessments and economic evaluations. RESULTS: Among the eight cases, the lifetime QALY method and the proportional shortfall method yielded conflicting worse-off rank orders. Particularly two conditions had a substantial shift in ranking across the applications of the two methods: childhood deafness and acute stroke. Deaf children had the lowest expected lifetime QALYs (38.5 without a cochlear implant) and were worst off according to the lifetime approach, while patients with acute stroke had the second-highest lifetime QALYs (76.4 without stroke units). According to proportional shortfall of QALYs, patients with acute stroke were ranked as worse off than deaf children, which seems counterintuitive. CONCLUSION: This study shows that it is feasible to identify who are the worse off empirically by the application of lifetime QALYs and proportional shortfalls. These methods ease further examination of whether there is a true conflict between maximization and equity or whether these two concerns actually coincide in real world cases. It is yet to be solved whether proportional prospective health losses are more important than absolute shortfalls in expected lifetime health in judgements about who are worse off. | |
| 24734189 | Comparison of Laboratory Data of Acute Cholangitis Patients Treated with or without Immuno | 2014 | Objective. Symptoms and laboratory data between acute cholangitis (AC) patients treated with and AC patients treated without immunosuppressive drugs (corticosteroids or methotrexate) were compared to identify factors that can be meaningful to the diagnosis of AC. Methods. The Wilcoxon signed-rank test was used for comparison of baseline variables between the patients with AC treated with immunosuppressive drugs and those without it. The chi-squared test was used in the analysis of the symptoms. Results. In total, 69 patients with AC were enrolled. Fifteen patients were treated with immunosuppressants due to rheumatoid arthritis or other collagen diseases. Jaundice was less frequent in the patients treated with immunosuppressive drugs (P = 0.0351). T-Bil level was marginally lower in the patients treated with immunosuppressants (P = 0.086). AST and ALT levels were lower in the patients treated with immunosuppressants (P = 0.0417 and 0.022, respectively). Conclusions. The frequency of jaundice and AST and ALT levels were lower in the patients treated with immunosuppressive drugs. It is recommended that care be taken to evaluate jaundice, AST level, and ALT level in the diagnosis of AC. | |
| 24268698 | [Autoimmune diseases and cancers. Part I: cancers complicating autoimmune diseases and the | 2014 May | The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjögren's syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs. | |
| 24082899 | In vitro cytotoxic evaluation of some synthesized COX-2 inhibitor derivatives against a pa | 2013 Oct | Celecoxib is a non-steroidal anti-inflammatory drug (NSAID) developed as a selective inhibitor of cyclooxygenase-2 (COX-2) for the treatment of rheumatoid arthritis disease. Recently some other mechanisms have been identified for anti cancer activity of these agents including induction of apoptosis, inhibition of tumor vascularization, stimulation of antitumor immune responses and inhibition of cellular protein synthesis. The cytotoxic effects of four synthesisized analogues of celecoxib (coded as D, E, F and G) were evaluated against Hela, MDA-MB-231, A-2780-s and HT-29 cancer cells, using MTT assay; Also their induction of apoptosis using DNA fragmentation analysis were studied. MTT assay showed that cell survival percent of COX-2 positive cell lines (HT-29, MDA-MB-231 and Hela; p≤0.05) were decreased significantly after exposure to the tested COX-2 inhibitors while little effect was observed on the COX-2 negative cell line (A-2780-s). Results also showed that A-2780-s and Hela were the most resistant and the most sensitive cell lines to these compounds, respectively. Moreover, in DNA fragmentation assay, induction of apoptosis was confirmed by electrophoretic pattern of separated DNA fragments in Hela cell line. Compounds E and G in comparison with D and F exerted more cytotoxic effect on COX-2 positive cell lines (Hela, HT-29 and MDA-MB-231). This could be due to the hydrophobic substituent (Cl, CH3) located at the para position of phenyl ring leading to more lipophilicity and cell uptake. In addition, these COX-2 inhibitors induced apoptosis on Hela cell-line, which could be considered as one of the cytotoxic mechanisms of these compounds as potential anti cancer agents. | |
| 24000597 | [Evaluation of significance of Borrelia garinii spirochete recombinant protein DbpB for se | 2013 May | AIM: Obtaining recombinant protein DbpB of West Siberia Borrelia garinii 20047 isolate and evaluation of its antigen activity for the possible use in serodiagnostics of ixodes tick-borne borreliosis (ITB). MATERIALS AND METHODS: Coding region of dbpB gene of novosibirsk B. garinii 20047 isolate was amplified by PCR and cloned as part of expressing pETm vector in Escherichia coli BL21 (DE3) strain cells. Recombinant protein DbpB produced by the selected clone was studied by EIA method for its ability to react with sera antibodies of ITB patients. RESULTS: E. coli BL21 (DE3) clone producing recombinant protein DbpB in quantity of 30% of total E. coli cell protein was obtained. Homology of amino acid sequence of recombinant protein DbpB of novosibirsk B. garinii 20047 isolate with primary structures of B. garinii, B. afzelii and B. burgdorferi sensu stricto spirochete genospieces DbpB proteins presented in GenBank database was 98.4, 77 and 73%, respectively. Sensitivity of immune enzyme detection in sera of ITB patients with migrating erythema of IgM and IgG reacting with DbpB antigen was 13.9 and 20.0%, respectively. Frequency of detection of IgM and IgG against DbpB in patient sera with disseminated ITB form was 15.7 and 43.8%, respectively. Specificity of immune enzyme detection of antibodies against recombinant antigen DbpB in which sera of syphilis, rheumatoid arthritis patients and healthy donors used as control sera was 100%. CONCLUSION: DbpB recombinant protein of novosibirsk B. garinii 20047 isolate may be used as one of antigens for highly specific serodiagnostics of ITB disseminated stage. | |
| 23986169 | Infliximab-induced psoriasis in treatment of Crohn's disease-associated ankylosing spondyl | 2013 Aug | TNF-alpha inhibitors are used to treat numerous inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Recent reports have illustrated the paradoxical development of psoriasis with TNF-alpha inhibitor therapy. We present here a review of 142 cases of new-onset psoriasis with infliximab, adalimumab, and etanercept therapy. This review illustrates the diverse conditions responsible for TNF-alpha-inhibitor induced psoriasis, the variable time prior to psoriasis development, and the most predominant forms of psoriasis. An analysis of the various therapeutic regimens applied may help provide guidelines for patient management. | |
| 23959445 | Efficacy and safety of rituximab as maintenance therapy for relapsing granulomatosis with | 2014 Jun | The objective of this work was to study the efficacy and safety of pre-emptive rituximab (RTX) in a series of patients with severe relapsing granulomatosis with polyangiitis (GPA). GPA is a systemic vasculitis with a high relapse rate despite successful remission induction. Drug toxicity with repeated induction treatments and long-standing immunosuppression poses a problem. Based on the findings in reports on RTX for rheumatoid arthritis, we treated patients with severe relapsing GPA with pre-emptive RTX, 1,000 mg 2 weeks apart every 6 months, aiming at achieving sustainable remission. All patients at one centre with relapsing GPA in spite of traditional maintenance treatment, who had received more than or equal to three cycles of RTX as regularly repeated pre-emptive maintenance therapy every 6 months, were included in this retrospective study. Information on disease manifestations and activity, treatments, lab parameters and adverse events was extracted from the medical files. Of the 12 included patients, all with a positive proteinase 3–anti-neutrophil cytoplasmic antibodies, generalised disease and a median disease duration of 35 months (21–270), 92% (11/12) achieved sustainable remission during a median follow-up time of 32 months (range 21–111) from first RTX treatment. Concomitant immunosuppressants were reduced. Infections were the most common adverse events, but infections were an issue also before the start of RTX. RTX administered every 6 months seems to be an effective maintenance treatment in a population with severe, relapsing long-standing GPA. Granulomatous as well as vasculitic manifestations responded equally well. Infections are a problem in this patient group but no new safety problems were identified. | |
| 23945674 | Impact of docosahexaenoic acid on gene expression during osteoclastogenesis in vitro--a co | 2013 Aug 13 | Polyunsaturated fatty acids (PUFAs), especially n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are known to protect against inflammation-induced bone loss in chronic inflammatory diseases, such as rheumatoid arthritis, periodontitis and osteoporosis. We previously reported that DHA, not EPA, inhibited osteoclastogenesis induced by the receptor activator of nuclear factor-κB ligand (sRANKL) in vitro. In this study, we performed gene expression analysis using microarrays to identify genes affected by the DHA treatment during osteoclastogenesis. DHA strongly inhibited osteoclastogenesis at the late stage. Among the genes upregulated by the sRANKL treatment, 4779 genes were downregulated by DHA and upregulated by the EPA treatment. Gene ontology analysis identified sets of genes related to cell motility, cell adhesion, cell-cell signaling and cell morphogenesis. Quantitative PCR analysis confirmed that DC-STAMP, an essential gene for the cell fusion process in osteoclastogenesis, and other osteoclast-related genes, such as Siglec-15, Tspan7 and Mst1r, were inhibited by DHA. | |
| 23942768 | Cytomegalovirus disease of the upper gastrointestinal tract in patients with rheumatic dis | 2013 Nov | Cytomegalovirus disease of the upper gastrointestinal tract (CMV-UGT) is a rare but significant complication in patients with rheumatic diseases. We reviewed records for January 2004 to December 2012 and investigated the occurrence of CMV-UGT in patients with rheumatic diseases to evaluate clinical characteristics, the value of the CMV antigenemia assay, and the association between immunosuppressive therapy and CMV-UGT. Ten CMV-UGT events (six gastric ulcer, two esophagitis, one gastritis, and one duodenal ulcer) in nine patients (three rheumatoid arthritis, three systemic lupus erythematosus, one dermatomyositis, one systemic sclerosis, and one overlap syndrome) were identified based on pathology. Mean age was 66.5 (range, 53-76) years. The CMV antigenemia assay was negative in five cases (50 %). All ten cases received glucocorticoids and six (60 %) received pulsed glucocorticoids. Mean prednisolone dose was 31.3 (range, 7.5-40) mg/day at diagnosis. Concomitant immunosuppressive agents were used in eight cases (80 %). Considering other published cases, the most common immunosuppressive drug was cyclophosphamide (ten cases; 45 %). Notably, two of our patients who were treated with low-dose glucocorticoids plus other milder immunosuppressive drugs (methotrexate and cyclosporine) also developed CMV-UGT. Life-threatening complications such as massive bleeding or perforated ulcer occurred in two patients. These results suggest that patients receiving intensive immunosuppressive therapy such as high-dose glucocorticoids and cyclophosphamide are at higher risk for developing CMV-UGT. Moreover, CMV-UGT can occur even with low-dose glucocorticoid therapy and relatively mild immunosuppressive agents. The value of the CMV antigenemia assay for predicting CMV-UGT appears to be limited. |
