Browse

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

ID PMID Title PublicationDate abstract
22293812 Tophaceous gout in the cervical spine. 2012 A 58-year-old woman with a three-year progressive history of chronic arthritis, had become disabled due to general malaise and fever. Her laboratory data revealed hyperuricemia and elevated levels of C-reactive protein. Neither rheumatoid factor nor anti-citrullinated peptide antibodies were present. We diagnosed her with tophaceous gout with uric crystalline revealed by the arthrocentesis of the elbow. (99m)Tc scintigraphy also disclosed a significant uptake in the cervical spine. The CT of the patient's cervical spine revealed significant bone erosion and destruction. We diagnosed the cervical involvement of gout based on the exclusion of infections and sarcoidosis. Rheumatologists should be aware of this rare association.
22415625 [Gout as a systemic disease. Manifestations, complications and comorbidities of hyperurica 2012 Apr Of all inflammatory rheumatic diseases gout has the highest prevalence. Patients with intermittent acute gout attacks are usually treated by primary care physicians. However, in cases of insufficient long-term control of serum uric acid levels, complications or atypical clinical manifestations may necessitate consultation with a rheumatologist in the further course of the disease. An oligoarticular or polyarticular presentation can give rise to the initial suspicion of rheumatoid or psoriatic arthritis. In these cases a careful clinical work-up supported by laboratory and imaging investigations is necessary and synovial fluid analysis is usually required. As in other rheumatic diseases extra-articular manifestations are of utmost importance for morbidity and mortality. Gout is a complex metabolic and inflammatory disease and besides articular symptoms the renal and cardiovascular effects of hyperuricemia are particularly relevant for the overall prognosis.
23069002 Minor salivary gland biopsy and Sjögren's syndrome: comparative analysis of biopsies amon 2012 Nov OBJECTIVES: The minor salivary gland biopsy (MSGB) is widely considered an important component of the diagnostic algorithm of primary Sjögren's syndrome (pSS) and is mentioned in all the classification criteria sets for the disease. The aim of this study, coordinated by the Italian Society of Rheumatology, was to verify the inter-observer agreement on the evaluation of MSGB among different experienced Italian rheumatologic centres, in order to better standardise the diagnostic methodology. METHODS: Seven centres participated in the study, providing a total of 50 MSGB samples. Each center blindly classified all the samples according to the Chisholm and Mason (CM) grading. The results were collected and analysed. RESULTS: The inter-observer agreement was satisfactory when the samples were stratified as consistent and non-consistent with the final diagnosis of pSS (median κ =0.75; mean κ =0.70). Nonetheless, significant discrepancies in the histopathologic evaluation of MSGB emerged when the agreement was assessed on the single scores. Considering the modal CM grading for each sample as the correct grading, upon re-examination, a potential bias in the final clinical diagnosis was detected in 7 out of 50 samples. CONCLUSIONS: This study has shown significant discrepancies in the evaluation of MSGB among different rheumatologic centres in the same country. Greater standardisation of the procedure is clearly necessary, both to improve the diagnostic performance and scientific communication.
23068303 IgG4-related disease in the head and neck. 2012 Nov Lymphoid infiltrates are relatively common in the ocular adnexa and the salivary glands. They are of a variety of types and include both reactive processes and lymphomas. Within the ocular adnexa in years past, lymphoid proliferations were classified as inflammatory pseudotumor, reactive lymphoid hyperplasia, atypical lymphoid hyperplasia, and lymphoma. With improvements in diagnostic techniques and with advances in lymphoma subclassification, it became clear that many of the dense lymphoid infiltrates, including cases classified as lymphoma and likely some classified as atypical lymphoid hyperplasia, represented low-grade B-cell lymphomas, the most common of which by far were extranodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT) lymphomas. Ocular adnexal inflammatory pseudotumor, reactive lymphoid hyperplasia, and chronic sclerosing sialadenitis were recognized, but the focus in diagnosis had been on avoiding misdiagnosis as a neoplastic process and in planning appropriate therapy. Recently, it has become clear that many cases of these reactive processes fall into the spectrum of immunoglobulin G4 (IgG4)-related disease, offering new insight into the pathogenesis of inflammatory lesions occurring in the ocular adnexa and the salivary glands. The majority of entities previously classified as chronic sclerosing sialadenitis, Mikulicz disease, orbital pseudolymphoma, and eosinophilic angiocentric fibrosis are now considered a part of the IgG4-related disease spectrum. In this review, we discuss the histologic and immunohistochemical features of IgG4-related disease of the head and neck and provide guidance for distinguishing this disease from its many mimics.
21737184 Coexistence of two different types of lymphoma in a patient with Sjögren's syndrome. The 2012 Jan Sjögren syndrome is a chronic systemic autoimmune disease in which there is an increased risk of developing non-Hodgkin's lymphoma. Neoplastic lung involvement and the coexistence of different histological types of lymphoma are uncommon in these patients. These patients frequently have associated infectious processes, most of them due to oral candidiasis. When there is immunodeficiency, the hematogenous spread of the fungus may affect the lungs. We present the case of a female patient diagnosed with follicular non- Hodgkin lymphoma within the context of long-term Sjögren syndrome. In addition to the neoplastic nodal and splenic disease, the PET-CT study showed extensive lung involvement. Due to suspicion of a false positive result for pulmonary Candida infection, antifungal treatment was initiated, with no response. A further histological study showed the presence of a second and different type of lymphoma.
21601495 A screening test for capsaicin-stimulated salivary flow using filter paper: a study for di 2011 Jul OBJECTIVE: The purpose of this study was to develop a simple screening technique for diagnosis of hyposalivation with dry mouth by estimation of capsaicin-stimulated salivary flow using filter paper. STUDY DESIGN: An assay system comprising 5 spots containing starch and potassium iodide on filter paper incorporating or without capsaicin and a coloring reagent was designed. We investigated whether the number of colored spots using the filter paper incorporating capsaicin could distinguish between healthy subjects and subjects with hyposalivation and dry mouth. RESULTS: In the healthy group (>200 μL/min; n = 33), the capsaicin-stimulated salivary flow significantly increased as compared with the resting salivary flow, from 1.2 ± 1.4 to 2.9 ± 1.3 colored spots (P < .05). In contrast, the hyposalivation group with dry mouth (<100 μL/min; n = 32) hardly changed (4.4 ± 1.0 vs 4.9 ± 0.2), except for 3 subjects who had considerable elevated secretion on capsaicin stimulation. CONCLUSION: By measuring resting and stimulated salivary flows, this method should be useful for evaluating retained functional ability of salivary glands and screening of hyposalivation with dry mouth.
22050355 Sialochemistry and cortisol levels in patients with Sjogren's syndrome. 2012 Apr OBJECTIVES: (i) To determine whether salivary cortisol and electrolyte levels differ between patients with Sjogren's syndrome (SjS) and healthy individuals. (ii) To assess correlations between whole-saliva cortisol and some clinical manifestations in patients with SjS. METHODS: A total of 24 healthy women (mean age 49.3±9.8) served as controls (C) vis-à-vis 17 patients with SjS (mean age 55.5±15.7). Salivary cortisol concentration was determined, and sialochemistry analysis was performed. RESULTS: Significantly lower saliva flow rates and higher salivary chloride (Cl(-) ), potassium (K(+) ), and Ca(2+) levels were found in the SjS group. No significant differences or correlations were found in other parameters, including sodium (Na(+) ), magnesium (Mg(2+) ), phosphate ((-) ), urea (U), and salivary cortisol levels. CONCLUSION: Increased whole-salivary output of Cl(-) and K(+) in SjS may reflect release from apoptotic rests of acinar cells after secondary necrosis. Normal levels of salivary Na(+) , Mg(2+) , and (-) argue against concentration effect, deranged tubular function or cortisol (mineralocorticosteroid) effect as the cause for these findings. Increased salivary Ca(2+) levels probably reflect leakage of plasma Ca(2+) through the injured oral mucosa in SjS. In spite of disease-associated stress, salivary cortisol, a stress biomarker, was not increased, suggesting insufficient hypothalamus-pituitary-adrenal (HPA) axis response and/or local consumption of cortisol by lymphocyte infiltrates.
21327929 A case of slowly progressive scleroderma kidney. 2011 Jun A rapidly progressive renal deterioration accompanied by acute-onset/uncontrolled hypertension characterizes scleroderma renal crisis (SRC), a life-threatening complication that occurs in patients with systemic sclerosis (SSc). To date, however, SSc with advanced renal failure has only rarely been reported in the absence of SRC. We report here an atypical case of diffuse cutaneous SSc where renal insufficiency progressed slowly to end-stage renal failure over a 14-year follow-up period after the diagnosis of SSc. In the renal biopsy, which was obtained at a relatively early stage of renal impairment, we found histological findings consistent with those of scleroderma kidneys. Unlike typical SRC, however, the larger renal arteries seemed to be unaffected. These histological findings were probably responsible for the "slowly progressive" renal impairment over the years without causing typical SRC.
21159832 Cortisol during the day in patients with systemic lupus erythematosus or primary Sjogren's 2011 Feb OBJECTIVE: To compare the level and change of cortisol during the day of patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) with low and high erythrocyte sedimentation rate (ESR). METHODS: Saliva was collected in the real-life environment of 21 women with SLE, 16 women with pSS, and 30 age-matched healthy women at 9 fixed timepoints during 2 consecutive days. Repeated measures ANOVA was performed to examine whether cortisol levels during the day were different for the patients with low ESR (≤ 20 mm/h) versus those with high ESR (> 20 mm/h). RESULTS: The groups with low and high ESR showed the characteristic change of cortisol during the day (time-of-day effect, F = 124.9, p < 0.001). The cortisol awakening level was lower for patients with high ESR than for patients with low ESR (group*time effect, F = 3.1, p = 0.02). CONCLUSION: The cortisol awakening level differs for patients with low and high ESR, which indicates the usefulness of further studies of hypothalamic-pituitary-adrenal axis dynamics in patients with SLE and pSS.
21846107 Gold nanoparticles: a revival in precious metal administration to patients. 2011 Oct 12 Gold has been used as a therapeutic agent to treat a wide variety of rheumatic diseases including psoriatic arthritis, juvenile arthritis, and discoid lupus erythematosus. Although the use of gold has been largely superseded by newer drugs, gold nanoparticles are being used effectively in laboratory based clinical diagnostic methods while concurrently showing great promise in vivo either as a diagnostic imaging agent or a therapeutic agent. For these reasons, gold nanoparticles are therefore well placed to enter mainstream clinical practice in the near future. Hence, the present review summarizes the chemistry, pharmacokinetics, biodistribution, metabolism, and toxicity of bulk gold in humans based on decades of clinical observation and experiments in which gold was used to treat patients with rheumatoid arthritis. The beneficial attributes of gold nanoparticles, such as their ease of synthesis, functionalization, and shape control are also highlighted demonstrating why gold nanoparticles are an attractive target for further development and optimization. The importance of controlling the size and shape of gold nanoparticles to minimize any potential toxic side effects is also discussed.
21698592 Chylous hip joint effusion and bone absorption after total hip arthroplasty in a patient w 2011 May Chyle is a sterile, milky fluid consisting of lymph and emulsified fats that is formed in the small intestines and taken up by lymph vessels. Chylous effusions usually occur after destruction or obstruction of lymphatic channels, and chylous joint effusions have been reported in association with rheumatoid and/or septic arthritis, and as the result of penetrating trauma to subsynovial fatty tissue and the intra-articular fat pad. We report a case of bone absorption and lytic change in the femur associated with a chylous hip joint effusion after a total hip arthroplasty (THA) in a patient with chylocolporrhoea and a history of chylous ascites.
21735459 Are the Ro RNP-associated Y RNAs concealing microRNAs? Y RNA-derived miRNAs may be involve 2011 Sep Here we discuss the hypothesis that the RNA components of the Ro ribonucleoproteins (RNPs), the Y RNAs, can be processed into microRNAs (miRNAs). Although Ro RNPs, whose main protein components Ro60 and La are targeted by the immune system in several autoimmune diseases, were discovered many years ago, their function is still poorly understood. Indeed, recent data show that miRNA-sized small RNAs can be generated from Y RNAs. This hypothesis leads also to a model in which Ro60 acts as a modulator in the Y RNA-derived miRNA biogenesis pathway. The implications of these Y RNA-derived miRNAs, which may be specifically produced under pathological circumstances such as in autoimmunity or during viral infections, for the enigmatic function of Ro RNPs are discussed.
22674286 Thrombin induces epidermal growth factor receptor transactivation and CCL2 expression in h 2012 Oct OBJECTIVE: Thrombin is a key factor involved in the stimulation of fibrin deposition, angiogenesis, and proinflammatory processes. Abnormalities in these processes are primary features of rheumatoid arthritis (RA). The aim of this study was to investigate the intracellular signaling pathways involved in thrombin-induced CCL2 expression in human osteoblasts. METHODS: Thrombin-mediated CCL2 expression was assessed by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. The mechanisms of action of thrombin in different signaling pathways were studied using Western blotting. Knockdown of protease-activated receptor (PAR) protein was achieved by small interfering RNA (siRNA) transfection. Chromatin immunoprecipitation assays were used to study in vivo binding of c-Jun to the CCL2 promoter. Transient transfection was used to examine activator protein 1 (AP-1) activity. RESULTS: Stimulation of human primary osteoblasts and MG-63 cells with thrombin induced CCL2 expression. PAR-1-specific siRNA (but not other PAR siRNA) was involved in thrombin-mediated up-regulation of CCL2. Thrombin-mediated CCL2 production was attenuated by the thrombin inhibitor PPACK, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the c-Src inhibitor PP2, epidermal growth factor receptor (EGFR) inhibitor AG-1478, MEK inhibitors PD98059 and U0126, or AP-1 inhibitors curcumin and tanshinone IIA. Stimulation of cells with thrombin increased PKCδ, c-Src, EGFR, MEK, and ERK activation. Treatment of osteoblasts with thrombin also increased c-Jun phosphorylation, AP-1 luciferase activity, and c-Jun binding to the AP-1 element on the CCL2 promoter. CONCLUSION: Our results suggest that the interaction between thrombin and PAR-1 increases CCL2 expression in human osteoblasts via the PKCδ/c-Src/ EGFR transactivation/MEK/ERK/c-Jun/AP-1 pathway.
22275150 Prevalence of axial spondylarthritis in the United States: estimates from a cross-sectiona 2012 Jun OBJECTIVE: The US national prevalence of spondylarthritis (SpA) was estimated for 2 published sets of classification criteria: the Amor criteria and the European Spondylarthropathy Study Group (ESSG) criteria. These 2 SpA criteria sets have been the most widely utilized in previous population-based studies of SpA. METHODS: The US SpA prevalence estimates were based on a representative sample of 5,013 US adults ages 20-69 years who were examined in the US National Health and Nutrition Examination Survey (NHANES) 2009-2010. RESULTS: The overall age-adjusted prevalence of definite and probable SpA by the Amor criteria was 0.9% (95% confidence interval [95% CI] 0.7-1.1%), corresponding to an estimated 1.7 million persons (95% CI 1.4-2.1 million persons). The age-adjusted prevalence of SpA by the ESSG criteria was 1.4% (95% CI 1.0-1.9%), corresponding to an estimated 2.7 million persons (95% CI 1.9-3.7 million persons). There were no statistically significant sex differences in SpA prevalence. The SpA prevalence among non-Hispanic white persons was 1.0% (95% CI 0.7-1.5%) by the Amor criteria and 1.5% (95% CI 1.0-2.3%) by the ESSG criteria. SpA prevalence could not be reliably estimated in other race/ethnicity subgroups due to sample size imitations. CONCLUSION: The SpA prevalence estimates are in the range of SpA prevalence estimates reported elsewhere in population-based surveys and it is likely that SpA may affect up to 1% of US adults, a prevalence similar to that reported for rheumatoid arthritis. The current US SpA prevalence estimates may be lower than the true value because the NHANES 2009-2010 data collection did not capture a complete set of the elements specified in the 2 SpA criteria sets.
21855836 Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease 2011 Nov 1 Inflammation predicts risk for cardiovascular disease (CVD) events, but the relation of drugs that directly target inflammation with CVD risk is not established. Methotrexate is a disease-modifying antirheumatic drug broadly used for the treatment of chronic inflammatory disorders. A systematic review and meta-analysis of evidence of relations of methotrexate with CVD occurrence were performed. Cohorts, case-control studies, and randomized trials were included if they reported associations between methotrexate and CVD risk. Inclusions and exclusions were independently adjudicated, and all data were extracted in duplicate. Pooled effects were calculated using inverse variance-weighted meta-analysis. Of 694 identified publications, 10 observational studies in which methotrexate was administered in patients with rheumatoid arthritis, psoriasis, or polyarthritis met the inclusion criteria. Methotrexate was associated with a 21% lower risk for total CVD (n = 10 studies, 95% confidence interval [CI] 0.73 to 0.87, p <0.001) and an 18% lower risk for myocardial infarction (n = 5, 95% CI 0.71 to 0.96, p = 0.01), without evidence for statistical between-study heterogeneity (p = 0.30 and p = 0.33, respectively). Among prespecified sources of heterogeneity explored, stronger associations were observed in studies that adjusted for underlying disease severity (relative risk 0.64, 95% CI 0.43 to 0.96, p <0.01) and for other concomitant medication (relative risk 0.73, 95% CI 0.63 to 0.84, p <0.001). Publication bias was potentially evident (funnel plot, Begg's test, p = 0.06); excluding studies with extreme risk estimates did not, however, alter results (relative risk 0.81, 95% CI 0.74 to 0.89). In conclusion, methotrexate use is associated with a lower risk for CVD in patients with chronic inflammation. These findings suggest that a direct treatment of inflammation may reduce CVD risk.
21521520 Gene expression profiles from discordant monozygotic twins suggest that molecular pathways 2011 Apr 26 INTRODUCTION: The objective of this study is to determine if multiple systemic autoimmune diseases (SAID) share gene expression pathways that could provide insights into pathogenic mechanisms common to these disorders. METHODS: RNA microarray analyses (Agilent Human 1A(V2) 20K oligo arrays) were used to quantify gene expression in peripheral blood cells from 20 monozygotic (MZ) twin pairs discordant for SAID. Six affected probands with systemic lupus erythematosus (SLE), six with rheumatoid arthritis (RA), eight with idiopathic inflammatory myopathies (IIM), and their same-gendered unaffected twins, were enrolled. Comparisons were made between discordant twin pairs and these were also each compared to 40 unrelated control subjects (matched 2:1 to each twin by age, gender and ethnicity) using statistical and molecular pathway analyses. Relative quantitative PCR was used to verify independently measures of differential gene expression assessed by microarray analysis. RESULTS: Probands and unrelated, matched controls differed significantly in gene expression for 104 probes corresponding to 92 identifiable genes (multiple-comparison adjusted P values < 0.1). Differentially expressed genes involved several overlapping pathways including immune responses (16%), signaling pathways (24%), transcription/translation regulators (26%), and metabolic functions (15%). Interferon (IFN)-response genes (IFI27, OASF, PLSCR1, EIF2AK2, TNFAIP6, and TNFSF10) were up-regulated in probands compared to unrelated controls. Many of the abnormally expressed genes played regulatory roles in multiple cellular pathways. We did not detect any probes expressed differentially in comparisons among the three SAID phenotypes. Similarly, we found no significant differences in gene expression when comparing probands to unaffected twins or unaffected twins to unrelated controls. Gene expression levels for unaffected twins appeared intermediate between that of probands and unrelated controls for 6535 probes (32% of the total probes) as would be expected by chance. By contrast, in unaffected twins intermediate ordering was observed for 84 of the 104 probes (81%) whose expression differed significantly between probands and unrelated controls. CONCLUSIONS: Alterations in expression of a limited number of genes may influence the dysregulation of numerous, integrated immune response, cell signaling and regulatory pathways that are common to a number of SAID. Gene expression profiles in peripheral blood suggest that for genes in these critical pathways, unaffected twins may be in a transitional or intermediate state of immune dysregulation between twins with SAID and unrelated controls, perhaps predisposing them to the development of SAID given the necessary and sufficient environmental exposures.
21479939 Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswelli 2011 Aug There is significant number of evidences suggesting the anti-inflammatory properties of gum resin extracts of Boswellia serrata containing 3-O-acetyl-11-keto-β-boswellic acid (AKBA) and their promising potential as therapeutic interventions against inflammatory diseases such as osteoarthritis (OA). Unfortunately, the poor bioavailability of AKBA following oral administration might limit the anti-inflammatory efficacy of standardized Boswellia extract(s). To address this issue, we describe a novel composition called Aflapin, which contains B. serrata extract enriched in AKBA and non-volatile oil portion of B. serrata gum resin. Our observations show that the availability of AKBA in systemic circulation of experimental animals is increased by 51.78% in Aflapin-supplemented animals, in comparison with that of 30% AKBA standardized extract or BE-30 (5-Loxin(®)). Consistently, Aflapin confers better anti-inflammatory efficacy in Freund's Complete Adjuvant (FCA)-induced inflammation model of Sprague-Dawley rats. Interestingly, in comparison with BE-30, Aflapin(®) also provides significantly better protection from IL-1β-induced death of human primary chondrocytes and improves glycosaminoglycans production in human chondrocytes. In Tumor necrosis factor alpha (TNFα)-induced human synovial cells, the inhibitory potential of Aflapin (IC(50) 44.736 ng/ml) on matrix metalloproteinase-3 (MMP-3) production is 14.83% better than that of BE-30 (IC(50) 52.528 ng/ml). In summary, our observations collectively suggest that both the Boswellia products, BE-30 (5-Loxin(®)) and Aflapin, exhibit powerful anti-inflammatory efficacy and anti-arthritic potential. In particular, in comparison with BE-30, Aflapin provides more potential benefits in recovering articular cartilage damage or protection from proteolytic degradation due to inflammatory insult in arthritis such as osteoarthritis or rheumatoid arthritis.
21388454 Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk fa 2011 May BACKGROUND/AIM: To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. OBJECTIVE: To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. RESULTS: Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. CONCLUSIONS: Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.
22082370 Feedback inhibition of osteoclastogenesis during inflammation by IL-10, M-CSF receptor she 2011 Nov Inflammation plays a key role in excessive bone loss in conditions such as rheumatoid arthritis and periodontitis. An important paradigm in immunology is that inflammatory factors activate feedback inhibition mechanisms to restrain inflammation and limit associated tissue damage. We hypothesized that inflammatory factors would activate similar feedback mechanisms to restrain bone loss in inflammatory settings. We have identified three mechanisms that inhibit osteoclastogenesis and are induced by inflammatory factors such as toll-like receptor ligands and cytokines; downregulation of expression of costimulatory molecules such as TREM-2; induction of shedding, and thereby inactivation of the M-CSF receptor c-Fms, leading to decreased RANK transcription; and induction of transcriptional repressors such as interferon regulatory factor 8. It is likely that these mechanisms work in a complementary and cooperative manner to fine tune the extent of osteoclastogenesis in inflammatory settings, and their augmentation may represent an alternative therapeutic approach to suppress bone resorption.
22670774 Cytokine/chemokine profiles contribute to understanding the pathogenesis and diagnosis of 2012 Jul To investigate the pathogenesis of localized autoimmune damage in Sjögren's syndrome (SS) by examining the expression patterns of cytokines, chemokines and chemokine receptors at sites of autoimmune damage. mRNA expression of these molecules in the labial salivary glands (LSGs) and peripheral blood mononuclear cells (PBMCs) from 36 SS patients was examined using a real-time polymerase chain reaction-based method. Subsets of the infiltrating lymphocytes and chemokines/chemokine receptors expression in the LSG specimens were examined by immunohistochemistry. Cytokines/chemokine concentrations in the saliva were analysed using flow cytometry or enzyme-linked immunosorbent assay. mRNA expression of T helper type 1 (Th1) cytokines, chemokines and chemokine receptors was higher in LSGs than in PBMCs. In contrast, mRNA expression of Th2 cytokines, chemokines [thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22)] and chemokine receptor (CCR4) was associated closely with strong lymphocytic accumulation in LSGs. Furthermore, TARC and MDC were detected immunohistochemically in/around the ductal epithelial cells in LSGs, whereas CCR4 was detected on infiltrating lymphocytes. The concentrations of these cytokines/chemokines were significantly higher in the saliva from SS patients than those from controls, and the concentrations of Th2 cytokines/chemokines were associated closely with strong lymphocytic accumulation in LSGs. These results suggest that SS might be initiated and/or maintained by Th1 and Th17 cells and progress in association with Th2 cells via the interaction between particular chemokines/chemokine receptors. Furthermore, the measurement of cytokines/chemokines in saliva is suggested to be useful for diagnosis and also to reveal disease status.