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1.
ObjectiveTo study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA).MethodsOne hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression.ResultsAmong the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p<0.001). According to univariate logistic regression analysis, age at diagnosis, HLA-B27 positivity, the presence of fat metaplasia, erosion, and ankyloses on SIJ MRI, increased baseline CRP levels, and the presence of syndesmophytes at baseline were associated with spinal progression over 2 years. Multivariate analysis identified syndesmophytes and severe fat metaplasia on baseline SIJ MRI as predictive of spinal radiographic progression (OR, 14.74 and 5.66, respectively).ConclusionInflammatory lesions in the SIJs on baseline MRI were not associated with spinal radiographic progression. However, fat metaplasia at baseline was significantly associated with spinal progression after 2 years. 相似文献
2.
John M Davis III Keith L Knutson Michael A Strausbauch Abigail B Green Cynthia S Crowson Terry M Therneau Eric L Matteson Sherine E Gabriel 《Arthritis research & therapy》2013,15(6):R199
Introduction
It remains challenging to predict the outcomes of therapy in patients with rheumatoid arthritis (RA). The objective of this study was to identify immune response signatures that correlate with clinical treatment outcomes in patients with RA.Methods
A cohort of 71 consecutive patients with early RA starting treatment with disease-modifying antirheumatic drugs (DMARDs) was recruited. Disease activity at baseline and after 21 to 24 weeks of follow-up was measured using the Disease Activity Score in 28 joints (DAS28). Immune response profiling was performed by analyzing multi-cytokine production from peripheral blood cells following incubation with a panel of stimuli, including a mixture of human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) lysates. Profiles identified via principal components analysis (PCA) for each stimulus were then correlated with the ΔDAS28 from baseline to follow-up. A clinically meaningful improvement in the DAS28 was defined as a decrease of ≥1.2.Results
A profile of T-cell cytokines (IL-13, IL-4, IL-5, IL-2, IL-12, and IFN-γ) produced in response to CMV/EBV was found to correlate with the ΔDAS28 from baseline to follow-up. At baseline, a higher magnitude of the CMV/EBV immune response profile predicted inadequate DAS28 improvement (mean PCA-1 scores: 65.6 versus 50.2; P = 0.029). The baseline CMV/EBV response was particularly driven by IFN-γ (P = 0.039) and IL-4 (P = 0.027). Among patients who attained clinically meaningful DAS28 improvement, the CMV/EBV PCA-1 score increased from baseline to follow-up (mean +11.6, SD 25.5), whereas among patients who responded inadequately to DMARD therapy, the CMV/EBV PCA-1 score decreased (mean -12.8, SD 25.4; P = 0.002). Irrespective of the ΔDAS28, methotrexate use was associated with up-regulation of the CMV/EBV response. The CMV/EBV profile was associated with positive CMV IgG (P <0.001), but not EBV IgG (P = 0.32), suggesting this response was related to CMV exposure.Conclusions
A profile of T-cell immunity associated with CMV exposure influences the clinical response to DMARD therapy in patients with early RA. Because CMV latency is associated with greater joint destruction, our findings suggest that changes in T-cell immunity mediated by viral persistence may affect treatment response and possibly long-term outcomes of RA. 相似文献3.
4.
Anja Wei? In-Ho Song Hildrun Haibel Joachim Listing Joachim Sieper 《Arthritis research & therapy》2014,16(1):R35
Introduction
The aim of this study was to investigate the influence of symptom duration on treatment response and on the correlation between improvements in patient reported outcomes (PRO) and objective inflammation in patients with axial spondylarthritis (SpA) treated with etanercept (ETA) or adalimumab (ADA).Methods
Data from 112 patients with axial SpA originally enrolled in two randomized controlled clinical trials were pooled and analyzed after one year of treatment with ETA (n = 66) or ADA (n = 46). Patients with <4 years and ≥4 years of disease were compared for improvement in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Ankylosing Spondylitis Disease Activity Score (ASDAS), C-reactive protein (CRP) and magnetic resonance imaging (MRI) score for sacroiliac joints (SIJ).Results
Patients with <4 years of disease showed a significantly better improvement than longer diseased patients in BASDAI (3.2 (95% confidence interval (CI): 2.7 to 3.7) vs. 1.7 (1.1 to 2.2)), BASFI, BASMI and ASDAS (1.6 (1.4 to 1.8) vs. 0.9 (0.7 to 1.1)). The change in BASDAI showed a significant correlation with the change in SIJ score (Spearman’s rank correlation coefficient (rho) = 0.37, P = 0.01) and the change in CRP (rho = 0.45, P = 0.001) in patients with <4 years of disease. For long diseased patients this correlation was poor and did not achieve statistical significance (rho = 0.13, P = 0.46; rho = 0.22, P = 0.13 respectively).Conclusion
The low correlation between change of PROs and change of objective signs of inflammation seen in axial SpA patients with longer symptom duration treated with tumor necrosis factor-blocker seems to indicate that inflammation is not the only cause of the patients’ symptoms, while inflammation seems to be the major cause in short diseased patients.Trial registration
Clinical Trials.gov NCT00844142 (Trial 1); NCT00235105 (Trial 2) 相似文献5.
Diana C Sanchez-Ramirez Marike van der Leeden Martin van der Esch Leo D Roorda Sabine Verschueren Jaap H van Die?n Joost Dekker Willem F Lems 《Arthritis research & therapy》2014,16(3):R123
Introduction
The aim of this study was to examine the associations of elevated serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) with change in muscle strength in patients with established knee osteoarthritis (OA), at 2 years.Methods
Data from 186 patients with knee OA were gathered at baseline and at 2-year follow-up. CRP (in milligrams per liter) and ESR (in millimeters per hour) were measured in serum from patients’ blood. Strength of quadriceps and hamstrings muscles was assessed by using an isokinetic dynamometer. The association of inflammatory markers with change in knee muscle strength was analyzed by using uni- and multi-variate linear regression models.Results
Patients with elevated CRP values at both baseline and 2-year follow-up exhibited a lower increase in knee muscle strength for a period of 2 years (β = -0.22; P = 0.01) compared with the group with non-elevated levels at both times of assessment. The association persisted after adjustment for relevant confounders. Elevated ESR values at both times of assessment were not significantly associated with change in knee muscle strength (β = -0.05; P = 0.49).Conclusions
Our results indicate that elevated CRP values are related to a lower gain in muscle strength over time in patients with established knee OA. Although the mechanism to explain this relationship is not fully elucidated, these results suggest inflammation as a relevant factor influencing muscle strength in this group of patients. 相似文献6.
Carole Bougault Sabrina Priam Xavier Houard Audrey Pigenet Laure Sudre Rik J Lories Claire Jacques Francis Berenbaum 《Arthritis research & therapy》2014,16(4):R137
Introduction
Our objective was to investigate whether a lack of frizzled-related protein B (FrzB), an extracellular antagonist of the Wnt signaling pathways, could enhance cartilage degradation by facilitating the expression, release and activation of matrix metalloproteinases (MMPs) by chondrocytes in response to tissue-damaging stimuli.Methods
Cartilage explants from FrzB−/− and wild-type mice were challenged by excessive dynamic compression (0.5 Hz and 1 MPa for 6 hours). Load-induced glycosaminoglycan (GAG) release and MMP enzymatic activity were assessed. Interleukin-1β (IL-1β) (10, 100 and 1000 pg/mL for 24 hours) was used to stimulate primary cultures of articular chondrocytes from FrzB−/− and wild-type mice. The expression and release of MMP-3 and −13 were determined by RT-PCR, western blot and ELISA. The accumulation of β-catenin was assessed by RT-PCR and western blot.Results
Cartilage degradation, as revealed by a significant increase in GAG release (2.8-fold, P = 0.014) and MMP activity (4.5-fold, P = 0.014) by explants, was induced by an excessive load. Load-induced MMP activity appeared to be enhanced in FrzB−/− cartilage explants compared to wild-type (P = 0.17). IL-1β dose-dependently induced Mmp-13 and −3 gene expression and protein release by cultured chondrocytes. IL-1β-mediated increase in MMP-13 and −3 was slightly enhanced in FrzB−/− chondrocytes compared to wild-type (P = 0.05 and P = 0.10 at gene level, P = 0.17 and P = 0.10 at protein level, respectively). Analysis of Ctnn1b and Lef1 gene expression and β-catenin accumulation at protein level suggests that the enhanced catabolic response of FrzB−/− chondrocytes to IL-1β and load may be associated with an over-stimulation of the canonical Wnt/β-catenin pathway.Conclusions
Our results suggest that FrzB may have a protective role on cartilage degradation and MMP induction in mouse chondrocytes by attenuating deleterious effects of the activation of the canonical Wnt/β-catenin pathway. 相似文献7.
Tomas ML Eagan Esteban C Gabazza Corina D’Alessandro-Gabazza Paloma Gil-Bernabe Shinya Aoki Jon A Hardie Per S Bakke Peter D Wagner 《Respiratory research》2012,13(1):48
Background
Systemic inflammation may contribute to cachexia in patients with chronic obstructive pulmonary disease (COPD). In this longitudinal study we assessed the association between circulating C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 levels and subsequent loss of fat free mass and fat mass in more than 400 COPD patients over three years.Methods
The patients, aged 40–76, GOLD stage II-IV, were enrolled in 2006/07, and followed annually. Fat free mass and fat mass indexes (FFMI & FMI) were calculated using bioelectrical impedance, and CRP, TNF-α, IL-1ß, and IL-6 were measured using enzyme immunoassays. Associations with mean change in FFMI and FMI of the four inflammatory plasma markers, sex, age, smoking, FEV1, inhaled steroids, arterial hypoxemia, and Charlson comorbidity score were analyzed with linear mixed models.Results
At baseline, only CRP was significantly (but weakly) associated with FFMI (r = 0.18, p < 0.01) and FMI (r = 0.27, p < 0.01). Univariately, higher age, lower FEV1, and use of beta2-agonists were the only significant predictors of decline in FFMI, whereas smoking, hypoxemia, Charlson score, and use of inhaled steroids predicted increased loss in FMI. Multivariately, high levels of TNF-α (but not CRP, IL-1ß or IL-6) significantly predicted loss of FFMI, however only in patients with established cachexia at entry.Conclusion
This study does not support the hypothesis that systemic inflammation is the cause of accelerated loss of fat free mass in COPD patients, but suggests a role for TNF-α in already cachectic COPD patients. 相似文献8.
Marco Rodríguez-Castellanos Alberto Tlacuilo-Parra Sergio Sánchez-Enríquez Ezequiel Vélez-Gómez Elizabeth Guevara-Gutiérrez 《Arthritis research & therapy》2014,16(6)
Introduction
Localized scleroderma is an inflammatory disease in its first stages and a fibrotic process in later stages, principally mediated by the transforming growth factor β. To date, there is no standard treatment. The objective of this study was to determine the effectiveness and safety of 8% pirfenidone gel in patients with localized scleroderma.Methods
This was an open phase II clinical trial that included 12 patients. Treatment with pirfenidone was indicated, three times daily for 6 months. Patients were evaluated clinically with the modified Localized Scleroderma Skin Severity Index (mLoSSI), as well with a durometer and histologically using hematoxylin and eosin stain and Masson’s trichrome stain.Results
The baseline mLoSSI average scores were 5.83 ± 4.80 vs. 0.83 ± 1.75 (P = 0.002) at 6 months. The initial durometer induration of the scleroderma plaques was 35.79 ± 9.10 vs. 32.47 ± 8.97 at 6 months (P = 0.05). We observed histopathological improvement with respect to epidermal atrophy, inflammation, dermal or adipose tissue fibrosis and annex atrophy from 12.25 ± 3.25 to 9.75 ± 4.35 (P = 0.032). The 8% pirfenidone gel application was well tolerated, and no side effects were detected.Conclusions
This is the first study on the therapeutic use of pirfenidone gel in localized scleroderma. It acts on both the inflammatory and the fibrotic phases. Considering its effectiveness, good safety profile and the advantage of topical application, pirfenidone is a treatment option in this condition. 相似文献9.
Pranav K Gandhi Kelly M Kenzik Lindsay A Thompson Darren A DeWalt Dennis A Revicki Elizabeth A Shenkman I-Chan Huang 《Respiratory research》2013,14(1):26
Background
Little is known about factors contributing to children’s asthma control status and health-related quality of life (HRQoL). The study objectives were to assess the relationship between asthma control and asthma-specific HRQoL in asthmatic children, and to examine the extent to which parental health literacy, perceived self-efficacy with patient-physician interaction, and satisfaction with shared decision-making (SDM) contribute to children’s asthma control and asthma-specific HRQoL.Methods
This cross-sectional study utilized data collected from a sample of asthmatic children (n = 160) aged 8–17 years and their parents (n = 160) who visited a university medical center. Asthma-specific HRQoL was self-reported by children using the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Asthma Impact Scale. Satisfaction with SDM, perceived self-efficacy with patient-physician interaction, parental health literacy, and asthma control were reported by parents using standardized measures. Structural equation modeling (SEM) was performed to test the hypothesized pathways.Results
Path analysis revealed that children with better asthma control reported higher asthma-specific HRQoL (β = 0.4, P < 0.001). Parents with higher health literacy and greater perceived self-efficacy with patient-physician interactions were associated with higher satisfaction with SDM (β = 0.38, P < 0.05; β = 0.58, P < 0.001, respectively). Greater satisfaction with SDM was in turn associated with better asthma control (β = −0.26, P < 0.01).Conclusion
Children’s asthma control status influenced their asthma-specific HRQoL. However, parental factors such as perceived self-efficacy with patient-physician interaction and satisfaction with shared decision-making indirectly influenced children’s asthma control status and asthma-specific HRQoL. 相似文献10.
Stefano Stagi Loredana Cavalli Carla Signorini Federico Bertini Marco Matucci Cerinic Maria Luisa Brandi Fernanda Falcini 《Arthritis research & therapy》2014,16(2):R83
Introduction
Our objective was to evaluate longitudinally the main bone-mass and quality predictors in young juvenile idiopathic arthritis (JIA) patients by using lumbar spine dual-energy X-ray absorptiometry (DXA) scan, radius peripheral quantitative computed tomography (pQCT), and phalangeal quantitative ultrasonography (QUS) at the same time.Methods
In total, 245 patients (172 females, 73 males; median age, 15.6 years: 148 oligoarticular, 55 polyarticular, 20 systemic, and 22 enthesitis-related-arthritis (ERA) onset) entered the study. Of these, 166 patients were evaluated longitudinally. Data were compared with two age- and sex-matched control groups.Results
In comparison with controls, JIA patients, but not with ERA, had a reduced spine bone-mineral apparent density (BMAD) standard deviation score (P < 0.001) and musculoskeletal deficits, with significantly lower levels of trabecular bone mineral density (TrabBMD) (P < 0.0001), muscle cross-sectional area (CSA) (P < 0.005), and density-weighted polar section modulus (SSIp) (P < 0.05). In contrast, JIA showed fat CSA significantly higher than controls (P < 0.0001). Finally, JIA patients had a significant reduced amplitude-dependent speed of sound (AD-SoS) (P < 0.001), and QUS z score (P < 0.005).Longitudinally, we did not find any difference in all JIA patients in comparison with baseline, except for the SSIp value that normalized. Analyzing the treatments, a significant negative correlation among spine BMAD values, TrabBMD, AD-SoS, and systemic and/or intraarticular corticosteroids, and a positive correlation among TNF-α-blocking agents and spine BMAD, TrabBMD, and AD-SoS were observed.Conclusions
JIA patients have a low bone mass that, after a first increase due to the therapy, does not reach the normal condition over time. The pronounced bone deficits in JIA are greater than would be expected because of reduction in muscle cross-sectional area. Thus, bone alterations in JIA likely represent a mixed defect of bone accrual and lower muscle forces. 相似文献11.
Camille Roubille Jean-Pierre Raynauld Fran?ois Abram Patrice Paiement Marc Dorais Philippe Delorme Louis Bessette André D Beaulieu Johanne Martel-Pelletier Jean-Pierre Pelletier 《Arthritis research & therapy》2014,16(6)
Introduction
Pain in osteoarthritis (OA) has been classically attributed to joint structural damage. Disparity between the degree of radiographic structural damage and the severity of symptoms implies that factors other than the joint pathology itself contribute to the pain. Peripheral and central sensitization have been suggested as two of the underlying mechanisms that contribute to pain in OA. The aim of this study was to explore in symptomatic knee OA patients, the structural changes assessed by magnetic resonance imaging (MRI) that could be used as markers of neuropathic pain (NP).Methods
This cross-sectional observational pilot study included 50 knee OA patients with moderate to severe pain (VAS ≥40) in the target knee. The presence of NP was determined based on the PainDETECT questionnaire. Among the 50 patients included, 25 had PainDETECT score ≤12 (unlikely NP), 9 had PainDETECT score between 13 and 18 (uncertain NP) and 16 had PainDETECT score ≥19 (likely NP). WOMAC, PainDETECT, and VAS pain scores as well as knee MRI were assessed.Results
Data showed no significant difference in demographic characteristics between the three groups. However, a positive and statistically significant association was found between the WOMAC pain (P <0.001), function (P <0.001), stiffness (P = 0.007) and total (P <0.001) scores as well as higher VAS pain score (P = 0.023), and PainDETECT scores. Although no difference was found in the cartilage volume between groups, the presence of meniscal extrusion in both medial (P = 0.006) and lateral (P = 0.023) compartments, and presence of meniscal tears in the lateral compartment (P = 0.011), were significantly associated with increasing PainDETECT score. Moreover, the presence of bone marrow lesions in the lateral plateau and the extent of the synovial membrane thickness in the lateral recess were associated with increasing PainDETECT scores (P = 0.032, P = 0.027, respectively).Conclusions
In this study, meniscal lesions, particularly extrusion, were found to be among the strongest risk factors for NP in knee OA patients.Trial registration
ClinicalTrials.gov . Registered 16 November 2012. NCT01733277相似文献12.
Magali Meyer Jérémie Sellam Soraya Fellahi Salma Kotti Jean-Philippe Bastard Olivier Meyer Frédéric Lioté Tabassome Simon Jacqueline Capeau Francis Berenbaum 《Arthritis research & therapy》2013,15(6):R210
Introduction
Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA.Methods
In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion).Results
Adiponectin level was independently associated with baseline total SHS (adjusted β = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 μg/ml for ∆SHS ≥1 and 6.04 μg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively).Conclusion
Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status. 相似文献13.
Erik H. Van Iterson Stephen R. Karpen Sarah E. Baker Courtney M. Wheatley Wayne J. Morgan Eric M. Snyder 《Respiratory research》2015,16(1)
Background
Pulmonary system dysfunction is a hallmark of cystic fibrosis (CF) disease. In addition to impaired cystic fibrosis transmembrane conductance regulator protein, dysfunctional β2-adrenergic receptors (β2AR) contribute to low airway function in CF. Recent observations suggest CF may also be associated with impaired cardiac function that is demonstrated by attenuated cardiac output (Q), stroke volume (SV), and cardiac power (CP) at both rest and during exercise. However, β2AR regulation of cardiac and peripheral vascular tissue, in-vivo, is unknown in CF. We have previously demonstrated that the administration of an inhaled β-agonist increases SV and Q while also decreasing SVR in healthy individuals. Therefore, we aimed to assess cardiac and peripheral hemodynamic responses to the selective β2AR agonist albuterol in individuals with CF.Methods
18 CF and 30 control (CTL) subjects participated (ages 22 ± 2 versus 27 ± 2 and BSA = 1.7 ± 0.1 versus 1.8 ± 0.0 m2, both p < 0.05). We assessed the following at baseline and at 30- and 60-minutes following nebulized albuterol (2.5mg diluted in 3.0mL of normal saline) inhalation: 12-lead ECG for HR, manual sphygmomanometry for systolic and diastolic blood pressure (SBP and DBP, respectively), acetylene rebreathe for Q and SV. We calculated MAP = DBP + 1/3(SBP–DBP); systemic vascular resistance (SVR) = (MAP/Q)•80; CP = Q•MAP; stroke work (SW) = SV•MAP; reserve (%change baseline to 30- or 60-minutes). Hemodynamics were indexed to BSA (QI, SVI, SWI, CPI, SVRI).Results
At baseline, CF demonstrated lower SV, SVI, SW, and SWI but higher HR than CTL (p < 0.05); other measures did not differ. At 30-minutes, CF demonstrated higher HR and SVRI, but lower Q, SV, SVI, CP, CPI, SW, and SWI versus CTL (p < 0.05). At 60-minutes, CF demonstrated higher HR, SVR, and SVRI, whereas all cardiac hemodynamics were lower than CTL (p < 0.05). Reserves of CP, SW, and SVR were lower in CF versus CTL at both 30 and 60-minutes (p < 0.05).Conclusions
Cardiac and peripheral hemodynamic responsiveness to acute β2AR stimulation via albuterol is attenuated in individuals with CF, suggesting β2AR located in cardiac and peripheral vascular tissue may be dysfunctional in this population. 相似文献14.
Domingo Hernández Javier Tri?anes Eduardo Salido Sergio Pitti Margarita Rufino José Manuel González-Posada Armando Torres 《PloS one》2015,10(6)
Background
Kidney transplant recipients have high cardiovascular risk, and vascular inflammation may play an important role. We explored whether the inflammatory state in the vessel wall was related to carotid intima-media thickness (c-IMT) and patient survival following kidney transplantation.Methods
In this prospective observational cohort study we measured c-IMT and expression of proinflammatory cytokines and adhesion molecules in the inferior epigastric artery in 115 kidney transplant candidates. Another c-IMT measurement was done 1-year post-transplantation in 107. By stepwise multiple regression analysis we explored factors associated with baseline c-IMT and their changes over time. Multivariate Cox regression analysis was constructed to identify risk factors for mortality.Results
A worse cardiovascular profile (older age, smoker, diabetic, carotid plaque, systolic blood pressure and vascular calcification) and higher VCAM-1 levels were found in patients in the highest baseline c-IMT tertile, who also had a worse survival. Factors independently related to baseline c-IMT were age (β=0.369, P<0.0001), fasting glucose (β=0.168, P=0.045), smoking (β=0.228, P=0.003) and VCAM-1 levels (β=0.244, P=0.002). Independent factors associated with c-IMT measurement 1-year post-transplantation were baseline c-IMT (β=-0.677, P<0.0001), post-transplant diabetes (β=0.225, P=0.003) and triglycerides (β=0.302, P=0.023). Vascular VCAM-1 levels were associated with increased risk of mortality in bivariate and multivariate Cox regression. Notably, nearly 50% of patients showed an increase or maintenance of high c-IMT 1 year post-transplantation and these patients experienced a higher mortality (13 versus 3.5%; P=0.021).Conclusion
A worse cardiovascular profile and a higher vascular VCAM-1 protein levels at time of KT are related to subclinical atheromatosis. This could lead to a higher post-transplant mortality. Pre-transplant c IMT, post-transplant diabetes and triglycerides at 1-year post-transplantation may condition a high c-IMT measurement post-transplantation, which may decrease patient survival. 相似文献15.
Masato Nishiwaki Akinori Kuriyama Yumi Ikegami Nana Nakashima Naoyuki Matsumoto 《Journal of physiological anthropology》2014,33(1)
Background
Wearing an activity monitor as a motivational tool and incorporating a behavior-based reward system or a computerized game element might have a synergistic effect on an increase in daily physical activity, thereby inducing body fat reduction. This pilot crossover study aimed to examine the effects of a short-term lifestyle intervention using an activity monitor with computerized game functions on physical activity and body composition.Methods
Twenty healthy volunteers (31 ± 3 years) participated in a 12-week crossover study. The participants were randomly assigned to either Group A (a 6-week game intervention followed by a 6-week normal intervention) or Group B (a 6-week normal intervention followed by a 6-week game intervention). The participants wore both a normal activity monitor (Lifecorder EX) and an activity monitor with computerized game functions (Yuuhokei) during the game intervention, whereas they only wore a normal activity monitor during the normal intervention. Before, during, and after the intervention, body composition was assessed.Results
Significantly more daily steps were recorded for the game intervention than for the normal intervention (10,520 ± 562 versus 8,711 ± 523 steps/day, P < 0.01). The participants performed significantly more physical activity at an intensity of ≥ 3 metabolic equivalents (METs) in the game intervention than in the normal intervention (3.1 ± 0.2 versus 2.4 ± 0.2 METs · hour/day, P < 0.01). Although body mass and fat were significantly reduced in both periods (P < 0.01), the difference in body fat reduction was significantly greater in the game intervention than in the normal intervention (P < 0.05).Conclusions
A short-term intervention using an activity monitor with computerized game functions increases physical activity and reduces body fat more effectively than an intervention using a standard activity monitor. 相似文献16.
Nguyen Phuong Thao Bui Thi Thuy Luyen Jung Eun Koo Sohyun Kim Young Sang Koh Nguyen Xuan Cuong Nguyen Hoai Nam Phan Van Kiem Young Ho Kim Chau Van Minh 《Biological research》2015,48(1)
Background
In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1–4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA).Results
The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 μg/mL. Four highly pure steroid derivatives (1–4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S) 5α-cholestane-3β,4β,6α,7α,8β,15α,16β,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 μM), and for (25S) 5α-cholestane-3β,6α,8β,15α,16β,26-hexol (1) and (25S) 5α-cholestane-3β,6α,7α,8β,15α,16β,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and 1.02 ± 0.01 μM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production.Conclusion
This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases. 相似文献17.
Jinhyun Kim Ji Yong Choi Sung-Hye Park Seung Hee Yang Ji Ah Park Kichul Shin Eun Young Lee Hiroshi Kawachi Hitoshi Kohsaka Yeong Wook Song 《Arthritis research & therapy》2014,16(3):R126
Introduction
C-X-C motif chemokine 10 (CXCL10) is a chemokine that plays a critical role in the infiltration of T cells in autoimmune diseases and is reported to be expressed in muscle tissue of polymyositis. To determine the therapeutic efficacy of CXCL10 blockade, we investigated the role of CXCL10 and the effect of anti-CXCL10 antibody treatment in C protein-induced myositis (CIM), an animal model of polymyositis.Methods
CIM was induced with human skeletal muscle C protein fragment in female C57BL/6 mice. Immunohistochemistry of CXCL10 and C-X-C motif chemokine receptor 3 (CXCR3) and measurement of serum CXCL10 were performed. Cell surface markers and interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in CIM lymph node cells was investigated by flow cytometry. Mice with CIM were treated with anti-CXCL10 antibody or control antibody (anti-RVG1) and the inflammation in muscle tissue was assessed.Results
Immunohistochemistry showed increased expression of CXCL10 and CXCR3 in the inflammatory lesions of muscle in CIM. Especially, CD8+ T cells invading myofiber expressed CXCR3. Serum level of CXCL10 was increased in CIM compared to the level in normal mice (normal mouse, 14.3 ± 5.3 pg/ml vs. CIM, 368.5 ± 135.6 pg/ml, P < 0.001). CXCR3 positivity in CD8+ T cells was increased compared to that of CD4+ T cells in the lymph node cells of CIM (CXCR3+ among CD8+ T cell, 65.9 ± 2.1% vs. CXCR3+ among CD4+ T cell, 23.5 ± 4.7%, P <0.001). Moreover, IFN-γ+ cells were increased among CXCR3+CD8+ T cells compared to CXCR3–CD8+ T cells (CXCR3+CD8+ T cell, 28.0 ± 4.2% vs. CXCR3-CD8+ T cell, 9.5 ± 1.5%, P = 0.016). Migration of lymph node cells was increased in response to CXCL10 (chemotactic index was 1.91 ± 0.45). CIM mice treated with anti-CXCL10 antibody showed a lower inflammation score in muscles than those with anti-RVG1 (median, anti-CXCL10 treatment group, 0.625 vs. anti-RVG1 treatment group, 1.25, P = 0.007).Conclusions
CXCL10/CXCR3 expression was increased in the inflammation of CIM model and its blockade suppressed inflammation in muscle. 相似文献18.
Julio Ramírez Virginia Ruíz-Esquide Isaac Pomés Raquel Celis Andrea Cuervo Ma Victoria Hernández Jaume Pomés José L Pablos Raimon Sanmartí Juan D Ca?ete 《Arthritis research & therapy》2014,16(1):R5
Introduction
The aim of this study was to identify and characterize subclinical synovitis in patients with rheumatoid arthritis (RA) in clinical remission using power Doppler ultrasound (PDUS) and serum levels of biomarkers of inflammation and/or angiogenesis.Methods
We selected patients with RA in clinical remission defined as a Disease activity score of 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) <2.6 for more than six months tested by two independent rheumatologists. Clinical, epidemiological, demographic and serological data were analyzed. PDUS of knees and hands was performed by a sonographer. Synovial hypertrophy (SH) and PDUS signal were scored (grades 0 to 3). SH ≥2 and a PDUS signal was classified as active synovitis. Serum levels of biomarkers of inflammation/angiogenesis were determined by Quantibody® Human Array.Results
This study included 55 patients, of whom 25 (45.4%) met criteria for ultrasound-defined active synovitis. Patients with active synovitis had higher DAS28-C reactive protein (P = 0.023), DAS28-ESR (P = 0.06), simplified disease activity score, SDAI (P = 0.064), and only 12% were taking oral glucocorticoids (≤5 mg/day) compared with 40% of patients without active synovitis (P = 0.044). Patients with synovitis also had significantly higher serum levels of the angiogenic biomarkers angiopoietin-2 (P = 0.038), vascular endothelial growth factor-D (P = 0.018), placental growth factor (P = 0.043), stromal cell-derived factor-1 (P = 0.035), matrix metallopeptidase-2 (P = 0.027) and basic fibroblast growth factor (bFGF) (P = 0.007), but not of pro-inflammatory cytokines.In the multivariate logistic regression model used to explore prognostic biomarkers for active synovitis, serum levels of bFGF, DAS28-ESR and not receiving glucocorticoids were the best predictors of active synovitis. The predictive indexes provided by the model were specificity 73.3%, sensitivity 72%, and area under the curve in receiver operating characteristic 81.5% (95% CI: 70.1% to 92.8%).Conclusions
Nearly half of the patients with RA in clinical remission had ultrasound-defined active synovitis, higher disease activity and less frequent oral glucocorticoid consumption than patients without active synovitis. This clinical situation was associated with a specific biological profile characterized by an excess of angiogenic mediators rather than persistent proinflammatory cytokine responses. 相似文献19.
Shee-Chan Lin Wei-Yu Chen Kai-Yuan Lin Sheng-Hsuan Chen Chun-Chao Chang Sey-En Lin Chia-Lang Fang 《PloS one》2013,8(2)
Objectives
This study investigated the PKCα protein expression in gastric carcinoma, and correlated it with clinicopathological parameters. The prognostic significance of PKCα protein expression in gastric carcinoma was analyzed.Methods
Quantitative real-time PCR test was applied to compare the PKCα mRNA expression in tumorous and nontumorous tissues of gastric carcinoma in ten randomly selected cases. Then PKCα protein expression was evaluated in 215 cases of gastric carcinoma using immunohistochemical method. The immunoreactivity was scored semiquantitatively as: 0 = absent; 1 = weak; 2 = moderate; and 3 = strong. All cases were further classified into two groups, namely PKCα overexpression group with score 2 or 3, and non-overexpression group with score 0 or 1. The PKCα protein expression was correlated with clinicopathological parameters. Survival analysis was performed to determine the prognostic significance of PKCα protein expression in patients with gastric carcinoma.Results
PKCα mRNA expression was upregulated in all ten cases of gastric carcinoma via quantitative real-time PCR test. In immunohistochemical study, eighty-eight out of 215 cases (41%) of gastric carcinoma revealed PKCα protein overexpression, which was statistically correlated with age (P = 0.0073), histologic type (P<0.0001), tumor differentiation (P = 0.0110), depth of invasion (P = 0.0003), angiolymphatic invasion (P = 0.0373), pathologic stage (P = 0.0047), and distant metastasis (P = 0.0048). We found no significant difference in overall and disease free survival rates between PKCα overexpression and non-overexpression groups (P = 0.0680 and 0.0587). However, PKCα protein overexpression emerged as a significant independent prognostic factor in multivariate Cox regression analysis (hazard ratio 0.632, P = 0.0415).Conclusions
PKCα protein is upregulated in gastric carcinoma. PKCα protein expression is statistically correlated with age, histologic type, tumor differentiation, depth of invasion, angiolymphatic invasion, pathologic stage, and distant metastasis. The PKCα protein overexpression in patients with gastric carcinoma is a significant independent prognostic factor in multivariate Cox regression analysis. 相似文献20.
Erfan Aref-Eshghi Yuhua Zhang Deborah Hart Ana M. Valdes Andrew Furey Glynn Martin Guang Sun Proton Rahman Nigel Arden Tim D. Spector Guangju Zhai 《PloS one》2014,9(5)