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ID PMID Title PublicationDate abstract
20216016 Psychological vulnerability predicts increases in depressive symptoms in individuals with 2010 Mar BACKGROUND: Efficient measures are needed to identify individuals at risk for depression to optimize intervention efforts that can enhance health-related outcomes. OBJECTIVES: The purpose of this study was to examine the effectiveness of the six-item Psychological Vulnerability Scale (PVS) as a predictor of depressive symptoms and change in depressive symptoms while controlling for two established predictors of depression-arthritis helplessness (AHI) and functional impairment (FI). METHODS: Data from 125 patients with rheumatoid arthritis (73% women) were used in hierarchical regression analyses to examine whether the PVS could be used to predict unique variance in depressive symptoms (Center for Epidemiological Studies-Depression [CES-D]) cross sectionally (N = 125) and change in depressive symptoms (N = 93). RESULTS: The three-predictor cross-sectional model was highly significant, F(3, 121) = 25.6; p < .001, explaining 39% of the variance in CES-D scores assessed at the same point in time. Controlling for both AHI and FI, the PVS explained an additional 9.3% of the variance in CES-D scores. To examine changes in CES-D scores over a 1-year period, CES-D scores at the later time were regressed on CES-D scores from a year earlier. On the next two steps, AHI, FI, and PVS scores assessed a year earlier were entered into the model. The full model predicted 56% of the variance in depressive symptoms, F(4, 88) = 27.7, p < .001, with the PVS accounting for a unique 5.6% of the variance in change in CES-D scores. DISCUSSION: Because of its brevity, the PVS can be an efficient screening tool for individuals at risk for depression. More research is needed to substantiate the value of the PVS for identifying individuals who could benefit from interventions designed to prevent depression.
20360042 Distinct bacterial colonization patterns of Escherichia coli subtypes associate with rheum 2010 Jul OBJECTIVES: The aetiology of RA is unknown; however, bacterial exposure, particularly to Escherichia coli, Proteus mirabilis and Klebsiella pneumoniae, has been linked to disease pathogenesis. The strongest association was observed for RF(+) RA. We compare colonization patterns of these bacteria, and the anti-bacterial antibody levels in early onset RF(+) and RF(-) inflammatory arthritis. METHODS: Bacteria isolated from stool and urine of early-stage RF(+) and RF(-) patients recruited to the Early Arthritis Registry were biochemically identified and genotyped. IgM and IgA anti-bacterial and RF antibodies were assessed by ELISA. RESULTS: Differences in the types of colonizing pathogenic E. coli were identified. RF(+) patients were more commonly colonized with phylogenetic Group D E. coli, whereas RF(-) patients were more commonly colonized with phylogenetic Group B2 E. coli and these individuals also had lower joint scores and inflammatory markers yet higher IgA anti-E. coli antibody responses. CONCLUSIONS: These studies link the type of colonizing bacteria in the gut and urine with the immune response (anti-bacterial and RF) in early-onset inflammatory arthritis and provide evidence for a role of the host-pathogen response in the aetiology of RF.
19812228 Response of elderly patients with rheumatoid arthritis to methotrexate or TNF inhibitors c 2009 Dec OBJECTIVE: To compare the efficacy of MTX and MTX+TNF inhibitors (TNFis) in elderly patients with RA with that in patients of younger age. METHODS: Data from two large, randomized, controlled, double-blind trials in patients with early RA using adalimumab or infliximab+MTX or MTX alone were obtained and pooled. Composite disease activity indices were calculated at baseline and 1 year of treatment, and compared in groups of patients classified by quartiles of age with the highest age group comprising 61-82 years using analysis of variance or Kruskal-Wallis test. RESULTS: Across all age quartiles, improvement on MTX was similar with respect to changes of composite disease activity indices, assessment of physical function and X-ray progression. Likewise, TNFi+MTX had similar effects across all age groups, but the effects of the combination were more profound than those of MTX monotherapy. Also in 10% of the patients with the highest age, primarily septuagenarians, improvement was seen to a similar degree as in the younger ones. CONCLUSIONS: Responsiveness of elderly patients with RA to MTX or TNFi+MTX is similar to that observed in patients of younger age.
19950293 A critical role of Cyr61 in interleukin-17-dependent proliferation of fibroblast-like syno 2009 Dec OBJECTIVE: Fibroblast-like synoviocytes (FLS) are a major component of the hyperplastic synovial pannus that aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Cyr61 (CCN1) is a product of a growth factor-inducible immediate early gene and is involved in cell adhesion, proliferation, and differentiation. However, the role that Cyr61 plays in FLS proliferation has remained undetermined. The aim of this study was to identify the role of Cyr61 in regulating the proliferation of FLS derived from patients with RA. METHODS: Expression of Cyr61 in synovial tissue (ST) and in FLS was determined simultaneously using immunohistochemistry, real-time polymerase chain reaction, and Western blotting. Cyr61 levels in synovial fluid (SF) were determined by enzyme-linked immunosorbent assay. FLS proliferation stimulated by SF, Cyr61, and interleukin-17 (IL-17) was measured by thymidine incorporation. Activation of signal transduction pathways was determined by Western blotting and confocal microscopy. RESULTS: Cyr61 was overexpressed in ST, FLS, and SF samples from RA patients as compared with samples from normal controls. Elevated levels of Cyr61 in RA SF promoted the proliferation of FLS, an effect that was abrogated by a neutralizing monoclonal antibody against human Cyr61. Furthermore, in samples from RA patients, Cyr61 was found to protect FLS from apoptosis and to sustain the expression of Bcl-2 in FLS. Most importantly, the expression of Cyr61 in FLS was regulated by IL-17 mainly via the p38 MAPK and NF-kappaB signaling pathways. Knockdown of expression of the Cyr61 gene inhibited IL-17-stimulated FLS proliferation. CONCLUSION: Our findings indicate that Cyr61 plays a critical role in IL-17-mediated proliferation of FLS in RA and likely contributes to hyperplasia of synovial lining cells and eventually to joint destruction in patients with RA.
19798032 Dendritic cells as targets for therapy in rheumatoid arthritis. 2009 Oct Dendritic cells (DCs) are central in inducing immunity and in mediating immune tolerance in their role as professional antigen-presenting cells. In the absence of DCs, a fatal autoimmunity develops in animal models. Although the role of DCs has been investigated extensively in the pathogenesis of rheumatoid arthritis (RA), it remains unclear whether DCs initiate autoimmunity in this disease. Nevertheless, evidence points towards a significant role for DCs in disease maintenance and progression. Current biologic therapies target cytokine products of antigen-presenting cells, such as tumor necrosis factor, interleukin-1 and interleukin-6. Emerging therapies for RA exploit the tolerogenic capacity of DCs. 'Tolerogenic' DCs can be generated from myeloid precursors ex vivo, loaded with antigen, and manipulated to suppress autoimmune responses in vivo, through the induction of activation-induced cell death, anergy, and/or regulatory T cells. Cells that are primed by DCs, such as B cells, type 1 and type 17 T helper cells, and that have been implicated in certain models of autoimmunity, are also being considered as additional targets for immune-based therapy. Studies to validate these approaches to ameliorate autoimmunity will be necessary before their application in the clinic.
19933784 Early referral to the rheumatologist for early arthritis patients: evidence for suboptimal 2010 Jan OBJECTIVE: To assess the time to access a rheumatologist (TTAR) by early arthritis (EA) patients participating in a nationwide incidental cohort (ESPOIR) and compare it with European League Against Rheumatism (EULAR) recommendations, which recommends rapid referral, ideally within 6 weeks, to a rheumatologist for patients presenting with EA. METHODS: Eight hundred and thirteen patients with EA were included in the cohort between 2002 and 2005. The inclusion criteria were 18-70 years old, two or more swollen joints, symptom duration from 6 weeks to 6 months and possible RA diagnosis. TTAR was defined as the time between the first synovitis and first visit to a rheumatologist. TTAR and satisfaction of the EULAR guidelines were investigated by multiple linear and logistic regressions. RESULTS: Mean TTAR was 76 days; only 46.2% of patients were seen by a rheumatologist within the EULAR-recommended time frame. Patients' patterns of accessing medical care substantially affected access to specialized care: mean TTAR was 58 days for patients who directly scheduled an appointment with the rheumatologist and 78 days for those referred by their general practitioner (P < 0.0007). Only 57.2 and 44.5%, respectively, were able to consult a rheumatologist within 6 weeks. Multivariate analysis confirmed the significant impact of indirect access on TTAR, after adjustment for EA characteristics and medical density in the region. CONCLUSIONS: Significant disparities were identified in the care of EA patients in terms of early access to a rheumatologist. More effort is needed to optimize the physicians' knowledge about EA and to improve the efficiency of medical networks.
19719812 Spread of spinal block in patients with rheumatoid arthritis. 2010 Jan BACKGROUND: In clinical practice, we noticed a greater than expected spread of sensory spinal block in patients with rheumatoid arthritis. We decided to test this impression and compared the spread of standard spinal anaesthesia in rheumatoid and non-rheumatoid control patients. METHODS: Spinal anaesthesia with 3.4 ml (17 mg) of plain bupivacaine was administered to 50 patients with seropositive rheumatioid arthritis and to 50 non-rheumatoid control patients. The protocol was standardised for all patients. All the patients were undergoing lower limb surgery and the rheumatoid patients were operated on due to their rheumatoid disease. The spread of sensory block was recorded 30 min from the dural puncture using a pin prick test and a cold ice-filled container. The impact of body mass index (BMI), height and age on the spread were analysed. RESULTS: The spread of sensory block was greater in patients with rheumatoid arthritis (15.6+/-3.1 dermatomes) than in non-rheumatoid patients (14.1+/-3.3 dermatomes) (P<0.05). Increasing BMI was related to cephalad spread of block in the rheumatoid group (P<0.05), but not in the control group. CONCLUSION: The mean spread of sensory block 30 min after the injection of plain bupivacaine was 1.5 segments cephalad in patients with rheumatoid arthritis than in those without this disease. BMI might be a patient-related factor contributing to the extent of the block in rheumatoid patients. These findings should be considered when performing a spinal block in rheumatoid patients.
20191031 Serum pro-hepcidin could reflect disease activity in patients with rheumatoid arthritis. 2010 Mar The aim of this study was to analyze the relationship between serum pro-hepcidin concentration and the anemia profiles of rheumatoid arthritis (RA) and to estimate the pro-hepcidin could reflect the disease activity of RA. RA disease activities were measured using Disease Activity Score 28 (DAS28), tender/swollen joint counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Anemia profiles such as hemoglobin, iron, total iron binding capacity (TIBC), ferritin, and transferrin levels were measured. Serum concentration of pro-hepcidin, the prohormone of hepcidin, was measured using enzyme-linked immunosorbent assay (ELISA). Mean concentration of serum pro-hepcidin was 237.6+/-67.9 ng/mL in 40 RA patients. The pro-hepcidin concentration was correlated with rheumatoid factor, CRP, ESR, and DAS28. There was a significant correlation between pro-hepcidin with tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. The pro-hepcidin concentration was significantly higher in the patients with active RA (DAS28>5.1) than those with inactive to moderate RA (DAS28< or =5.1). However, the pro-hepcidin concentration did not correlate with the anemia profiles except hemoglobin level. There was no difference of pro-hepcidin concentration between the patients with anemia of chronic disease and those without. In conclusion, serum concentration of pro-hepcidin reflects the disease activity, regardless of the anemia states in RA patients, thus it may be another potential marker for disease activity of RA.
19996846 A case of sclerosing mesenteritis with rheumatoid arthritis. 2010 Jan Sclerosing mesenteritis (SM) is an uncommon disorder characterized by chronic nonspecific inflammation involving the adipose tissue of the mesentery. The etiology remains unclear. It has been reported in association with and as an initial presentation in some autoimmune diseases. Its clinical presentation and laboratory findings are typically nonspecific and definitive diagnosis usually requires biopsy or surgical excision. We report a patient with a history of rheumatoid arthritis who was found to have an intra-abdominal mass suspicious for malignancy. A biopsy revealed the diagnosis of SM.
20074443 Health-related quality of life in fibromyalgia patients: a comparison with rheumatoid arth 2009 Sep OBJECTIVES: To compare health-related quality of life (HRQL) in fibromyalgia (FM) patients with that of patients with rheumatoid arthritis (RA) and the general population, and investigate if the factors are associated with the greater impact of FM. METHODS: This cross-sectional study involved 380 patients with FM, 693 patients with RA and 1579 healthy controls. HRQL was evaluated using the Medical Outcome Study Short-Form 36 (SF-36), and the measures included disease-related characteristics, demographic variables and comorbidities. S-scores were calculated for comparisons with the norm, and multivariate analyses were used to assess the relationships between HRQL and clinical and demographic variables. RESULTS: In comparison with the general population, the FM patients showed significant impairment in relation to all of the eight scales of the SF-36 (p<0.0001), as well as the physical and mental component summary scores (PCS and MCS) (p<0.0001). The mean PCS and MCS of the FM patients were 38.5 (SD=6.9) and 32.8 (SD=10.9), whereas those of the RA patients were 33.5 (SD=6.4) (p<0.01) and 40.2 (SD=11.9) (p<0.001). The dimensions typically affected by FM were vitality (s-score -1.61), mental health (s-score -1.46) and general health (s-score-1.47), whereas physical functioning (s-score-1.63) and role limitations due to physical function (s -score -0.94) were more impaired in the RA patients; the bodily pain scores were similar in the two groups. The PCS was lower than the MCS in the RA patients (s-scores -1.80 vs. -0.62), but the two scores were similar in the FM patients (s-scores -1.20 vs. -1.08). Multiple regression models showed that the physical component of the SF-36 was associated with widespread pain (the SAPS score) (p<0.0001), educational level (p=0.0017), and the body mass index (p=0.007), and the mental component was associated with the widespread pain (p=0.0005), sleep abnormalities (p=0.0033), physical function (p=0.015), fatigue (p=0.029), gender (p=0.014) and a low educational level (p=0.0007). CONCLUSION: Patients with FM see the disease as having a worse health than RA patients and the general population, especially in terms of mental health.
20609223 Increased activity and expression of histone deacetylase 1 in relation to tumor necrosis f 2010 INTRODUCTION: The purpose of this study was to investigate the profile of histone deacetylase (HDAC) expression in the synovial tissue of rheumatoid arthritis (RA) compared with that of normal control and osteoarthritis (OA), and to examine whether there is a link between HDAC activity and synovial inflammation. METHODS: HDAC activity and histone acetyltransferase (HAT) activity were determined in nuclear extracts of total synovial tissue surgically obtained from normal, OA and RA joints. The level of cytoplasmic tumor necrosis factor a (TNFα) fraction was measured by ELISA. Total RNA of synovial tissue was used for RT-PCR of HDAC1-8. In synovial fibroblasts from RA (RASFs), the effects of TNFα on nuclear HDAC activity and class I HDACs (1, 2, 3, 8) mRNA expressions were examined by quantitative real-time PCR. The protein expression and distribution of class I HDACs were examined by Western blotting. RESULTS: Nuclear HDAC activity was significantly higher in RA than in OA and normal controls and correlated with the amount of cytoplasmic TNFα. The mRNA expression of HDAC1 in RA synovial tissue was higher than in OA and normal controls, and showed positive correlation with TNFα mRNA expression. The protein level of nuclear HDAC1 was higher in RA synovial tissue compared with OA synovial tissue. Stimulation with TNFα significantly increased the nuclear HDAC activity and HDAC1 mRNA expression at 24 hours and HDAC1 protein expression at 48 hours in RASFs. CONCLUSIONS: Our results showed nuclear HDAC activity and expression of HDAC1 were significantly higher in RA than in OA synovial tissues, and they were upregulated by TNFα stimulation in RASFs. These data might provide important clues for the development of specific small molecule HDAC inhibitors.
18850321 Coexistence of the monostatic Paget's disease, sensorimotor neuropathy and elderly onset r 2009 Mar Paget's disease is a chronic focal disease of the skeleton that affects up to 2-3% of the population over the age of 60. Polymyalgia rheumatica (PMR) is an inflammatory condition of unknown etiology characterized by aching and stiffness in the shoulder, pelvic girdle and the neck. There are two incompletely overlapping subsets of RA that have been recognized: one exhibits the classical RA clinical picture, while the other has a PMR-like onset in later ages of life. We reported a rare case of monostatic Paget's disease, sensorimotor neuropathy and elderly onset rheumatoid arthritis in an elderly women.
18832606 Circulating chromogranin A reveals extra-articular involvement in patients with rheumatoid 2009 Jan TNF-alpha plays an important role in the natural history of rheumatoid arthritis (RA), a systemic disease characterized by endothelial activation and synovial involvement with bone erosions. Neuroendocrine signals contribute as well to RA, but their role is poorly understood. We measured in 104 RA patients and in an equal number of sex- and age-matched, healthy controls the blood levels of chromogranin A (CgA), a candidate marker linking the neuroendocrine system to TNF-alpha-mediated vascular inflammation. CgA levels were significantly higher in patients with RA and remained stable over time. High levels of CgA were significantly associated with severe extra-articular manifestations, namely pulmonary fibrosis, rheumatoid vasculitis, serositis, and peripheral neuropathy. RA sera curbed the response of human microvascular endothelial cells to TNF-alpha, as assessed by the expression of ICAM-1, the release of MCP-1/CCL2, and the export of nuclear high-mobility group box 1; the effect abated in the presence of anti-CgA antibodies. The efficacy of the blockade was significantly correlated with the CgA concentration in the serum. The recombinant aminoterminal portion of CgA, corresponding to residues 1-78, had similar inhibitory effects on endothelial cells challenged with TNF-alpha. Our results suggest that enhanced levels of CgA identify patients with extra-articular involvement and reveal a negative feedback loop that limits the activation of endothelial cells in RA.
19458908 Etanercept reduces the serum levels of macrophage chemotactic protein-1 in patients with r 2009 This study was performed to analyze the effect of etanercept, the soluble tumor necrosis factor-alpha (TNF-alpha) receptor, on the serum levels of several chemokines including monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T expressed and presumably secreted (RANTES), and granzyme B in rheumatoid arthritis (RA) patients. Twenty-eight patients with RA were administered etanercept once or twice a week for more than 6 months. Clinical and laboratory parameters were measured and serum levels of MCP-1, RANTES, and granzyme B were determined using enzyme-linked immunosorbent assay (ELISA) kits at baseline and at 3 and 6 months after the initial treatment. In addition, the levels of MCP-1, RANTES, and granzyme B produced by cultured synovial cells stimulated with TNF-alpha were measured. A significant decrease in serum MCP-1 levels was observed at 3 and 6 months after initial treatment with etanercept. Serum RANTES and granzyme B levels did not show significant changes. TNF-alpha induced MCP-1, RANTES, and granzyme B production in cultured synovial cells from RA patients. Serum MCP-1 levels were significantly correlated with the disease activity scores of 28 joints combined with CRP (DAS28-CRP), indicating the role of MCP-1 in the pathogenesis of rheumatoid inflammation. This study demonstrated that a reduction of MCP-1 production in RA patients was a newly determined effect of etanercept. Another cascade not associated with TNF-alpha may induce granzyme B and RANTES production in RA patients.
20810498 Pharmacologic immunomodulation and cutaneous malignancy in rheumatoid arthritis, psoriasis 2010 Nov OBJECTIVE: It is unclear if skin cancer risk is affected by the use of immunomodulatory medications in rheumatoid arthritis (RA), psoriasis, and psoriatic arthritis (PsA). The purpose of this study is to evaluate and summarize the available data pertinent to this question. METHODS: The English language literature on PubMed was searched with a combination of phrases, including "malignancy," "skin cancer," "squamous cell carcinoma," "basal cell carcinoma," "melanoma," "psoriasis," "psoriatic arthritis," and "rheumatoid arthritis" in addition to the generic names of a variety of common immunomodulatory drugs. Relevant articles were identified and data were extracted. RESULTS: In total, 2218 potentially relevant articles were identified through the search process. After further screening, 20 articles relevant to RA were included. An additional 19 articles relevant to either psoriasis or PsA were included as well. RA may be a risk factor for the development of cutaneous malignancy. Treatment with tumor necrosis factor inhibitors increases the rates of non-melanoma skin cancer (NMSC) in RA and psoriasis. This risk doubles when combination methotrexate therapy is used in RA. Methotrexate may increase the risk of malignant melanoma in patients with RA and the risk of NMSC in psoriasis. Cyclosporine and prior phototherapy significantly increase the risk of NMSC. CONCLUSION: RA may potentiate the risk of cutaneous malignancy and therefore dermatologic screening in this population should be considered. The use of immunomodulatory therapy in RA, psoriasis, and PsA may further increase the risk of cutaneous malignancy and therefore dermatologic screening examinations are warranted in these groups. More careful recording of skin cancer development during clinical trials and cohort studies is necessary to further delineate the risks of immunomodulatory therapy.
19432123 [Effects of biologic therapies on systemic osteoporosis in patients with rheumatoid arthri 2009 May Biologic therapies including tumor necrosis factor alpha (TNF-alpha)-blocking therapy have been shown to reduce disease activity measures and joint damage progression. However, effects of biologic therapies on systemic osteoporosis remain to be elucidated in patients with rheumatoid arthritis (RA). In this review article, we reviewed the literature on the issue after we described our hypothesis on the pathogenesis of synovitis in patients with RA.
19153184 Rheumatoid arthritis: a novel radiographic projection for hand assessment. 2009 Jul Rheumatoid arthritis (RA) is the most common form of inflammatory disease, affecting 1-2% of the population. Posteroanterior (PA) and Brewerton projections are well established in radiographic practice for scoring and monitoring RA, but there is little evidence to demonstrate the diagnostic efficacy of these techniques. This work, by varying the positioning of a cadaveric hand, investigates whether an alternative radiographic projection could yield greater diagnostic information than the traditional techniques. Phase I of the study evaluated moving the hand 15 degrees from the anteroposterior position and then in 5 degrees increments in four directions: medial rotation, lateral rotation, flexion of the wrist and extension of the wrist. Phase II of the study took the optimum projections from Phase I and further manipulated these positions in a direction at right angles to the original position. Images were scored based on joint space visualisation in 29 joints. Results demonstrated that significantly higher diagnostic efficacy was evident with 15 degrees lateral rotation of the hand or 15 degrees flexion at the wrist compared to the Brewerton projection. Either projection is recommended, but on the basis of patient comfort, the latter of these novel positions, now known as the UCD projection, was chosen as the optimum procedure to replace the Brewerton projection. The value of using cadavers for the establishment of optimum radiographic procedures is highlighted.
19926672 Genotype at the sIL-6R A358C polymorphism does not influence response to anti-TNF therapy 2010 Jan OBJECTIVES: To investigate the association between genotype at the soluble interleukin 6 receptor (sIL-6R) A358C single nucleotide polymorphism (SNP, rs8192284), previously reported to correlate with soluble receptor levels, and response to anti-TNF therapy in subjects with RA. METHODS: In a large cohort of Caucasian RA patients treated with anti-TNF medications (total, n = 1050; etanercept, n = 455; infliximab, n = 450; and adalimumab, n = 142), the sIL-6R A358C polymorphism was genotyped using a Taqman 5'-allelic discrimination assay. Linear regression analysis adjusted for baseline 28 joint disease activity score (DAS28), baseline HAQ score, gender and use of concurrent DMARDs was used to assess the association of genotype at this polymorphism with response to anti-TNF therapy, defined by change in DAS28 after 6 months of treatment. Analyses were performed in the entire cohort, and also stratified by an anti-TNF agent. Additional analysis according to the EULAR response criteria was also performed, with the chi-squared test used to compare genotype groups. RESULTS: No association between genotype at sIL-6R A358C and response to anti-TNF treatment was detected either in the cohort as a whole or after stratification by anti-TNF agent, in either the linear regression analysis or with response segregated according to EULAR criteria. CONCLUSIONS: This study shows that genotype at the functional sIL-6R A358C SNP is not associated with response to anti-TNF treatment in patients with RA.
20851921 Osteoclast activity and subtypes as a function of physiology and pathology--implications f 2011 Feb Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate that osteoclasts have different subtypes depending on their location, genotype, and possibly in response to drug intervention. The aim of the current review is to describe the subtypes of osteoclasts in four different settings: 1) physiological, in relation to turnover of different bone types; 2) pathological, as exemplified by monogenomic disorders; 3) pathological, as identified by different disorders; and 4) in drug-induced situations. The profiles of these subtypes strongly suggest that these osteoclasts belong to a heterogeneous cell population, namely, a diverse macrophage-associated cell type with bone catabolic and anabolic functions that are dependent on both local and systemic parameters. Further insight into these osteoclast subtypes may be important for understanding cell-cell communication in the bone microenvironment, treatment effects, and ultimately bone quality.
20351705 The role of endothelial function and its assessment in rheumatoid arthritis. 2010 May Patients with rheumatoid arthritis (RA) have a reduced life expectancy when compared with the general population, largely attributable to cardiovascular disease. Factors that contribute to this increased cardiovascular risk include traditional risk factors, which account for only part of the excess, along with manifestations of the disease itself. RA is characterized by inflammation, which also is a key component in the development of atherosclerosis. Inflammation leads to the activation of endothelial cells, which, through an increase in the expression of leukocyte adhesion molecules, promotes a pro-atherosclerotic environment. Endothelial dysfunction is an early preclinical marker of atherosclerosis, and is commonly found in patients with RA. Several methods are available for the assessment of endothelial function, such as flow-mediated dilatation and laser Doppler flowmetry combined with iontophoresis, each with its own advantages and limitations. Studies have shown that endothelial dysfunction in RA is closely associated with inflammation, and therapeutic reduction of inflammation leads to improvements in endothelial function. As such, assessments of endothelial function could prove to be useful tools in the identification and monitoring of cardiovascular risk in patients with RA. Given the increase in cardiovascular mortality associated with RA, effective management must involve prevention of cardiovascular risk, in addition to control of disease activity and inflammation.