ABSTRACT
Solar systems complexity, multiscale, and nonlinearity are governed by numerous and continuous changes where the sun magnetic fields can successfully represent many of these phenomena. Thus, nonlinear tools to study these challenging systems are required. The dynamic system recurrence approach has been successfully used to deal with this kind challenge in many scientific areas, objectively improving the recognition of state changes, randomness, and degrees of complexity that are not easily identified by traditional techniques. In this work we introduce the use of these techniques in photospheric magnetogram series. We employ a combination of recurrence quantification analysis with a preprocessing denoising wavelet analysis to characterize the complexity of the magnetic flux emergence in the solar photosphere. In particular, with the developed approach, we identify regions of evolving magnetic flux and where they present a large degree of complexity, i.e., where predictability is low, intermittence is high, and low organization is present.
ABSTRACT
The yeast Saccharomyces boulardii is a biotherapeutic agent used for the prevention and treatment of several gastrointestinal diseases, such as diarrhoea caused by Clostridium difficile, in addition to the antibiotic therapy. In this study we report a case of Saccharomyces cerevisiae fungemia in a patient with Clostridium difficile-associated diarrhoea (CDAD) treated orally with S. boulardii in association with vancomycin. The identification of the S. cerevisiae was confirmed by molecular technique. Fungemia is a rare, but a serious complication to treatment with probiotics. We believe it is important to remind the clinicians of this risk when prescribing probiotics, especially to immunocompromised patients.
Subject(s)
Clostridioides difficile/drug effects , Enterocolitis, Pseudomembranous/drug therapy , Fungemia/chemically induced , Probiotics/adverse effects , Saccharomyces cerevisiae/growth & development , Aged, 80 and over , Antifungal Agents/administration & dosage , Antifungal Agents/therapeutic use , Caspofungin , Catheters, Indwelling/microbiology , Echinocandins/administration & dosage , Echinocandins/therapeutic use , Fungemia/blood , Fungemia/drug therapy , Fungemia/microbiology , Humans , Lipopeptides , Male , Probiotics/administration & dosage , Probiotics/therapeutic use , Saccharomyces cerevisiae/isolation & purification , Treatment OutcomeABSTRACT
Atrial fibrillation (AF) is the most common cardiac dysrhythmia and occurs in 3.3%-10% of emergency admissions. It is frequently quoted for people over the age of 75, but the cases of AF in young subjects without structural heart disease are also increasing, therefore, leading to the evaluation of "lonely atrial fibrillation" as a new challenge for the clinician. The first diagnosis and treatment often occur in the emergency room and the emergency physician has therefore to evaluate the initial step towards the therapeutic decisions. Although international standard guidelines are available, AF treatment in the Emergency Department (ED) is still heterogeneous in terms of the management strategy chosen. There are two main strategies for the management of AF: rate and rhythm control. Moreover, antithrombotic treatment is pivotal in AF to prevent cardioembolic stroke and it is considered a primary objective after an accurate assessment of antithrombotic treatment risks and benefits. The introduction of innovative echocardiographic approach, directly in ED, seems to improve the management and risk stratification of patients with AF. This review aims to provide an overview about the current approach and the future expectations in the management of AF in ED. This manuscript represents a synopsis of the lectures on AF management in the ED of the Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012. We decided to use only the most relevant references for each contribution as suggested by each participant at this review.
Subject(s)
Atrial Fibrillation/therapy , Cardiology Service, Hospital/trends , Emergency Service, Hospital/trends , Algorithms , Atrial Fibrillation/diagnosis , Cardiology Service, Hospital/standards , Emergency Service, Hospital/standards , Forecasting , Humans , Practice Guidelines as Topic , Predictive Value of Tests , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND AIM: To evaluate the diagnostic and prognostic usefulness of procalcitonin (PCT) in patients admitted to the Emergency Department (ED) with signs of infections and to assess the prognostic value of repeated measurements in predicting hospital mortality. MATERIALS AND METHODS: A prospective, observational study was conducted in our 400-bed General Teaching Hospital. 261 patients arriving in ED with signs/symptoms of infection were enrolled. PCT was performed upon arrival in the ED (T0), and 5 days after antibiotic therapy (T5). Blood cultures were performed in all patients upon arrival in the ED. RESULTS: Mean T0 PCT value was 7.1±17.9 ng/ml, and at T5 3±9.1 ng/ml (p < 0.0001). Mean PCT in septic non-survivors was increased at T5 compared to T0 but not significantly. The PCT increase at T5 was an independent factor of mortality (OR = 1.29, p < 0.02) in septic patients. Compared to baseline mean delta % PCT decrease at T5 was 28%. Patients with a decrease delta % PCT > 28% showed a lower number of deaths, with a statistical significant difference if compared to those patients with a < 28% decrease (p < 0.004). ROC curve of delta % PCT for prediction of death has an AUC = 0.82 (p < 0.03). CONCLUSIONS: PCT is a useful marker for diagnosis of systemic and local infections, and for prognostic stratification in patients with acute infectious diseases at their arrival in ED. PCT variations after antibiotic therapy are highly predictive for in-hospital mortality. PCT normalization during antibiotic therapy suggests a good response to infection possibly leading to less infection-related deaths.
Subject(s)
Calcitonin/blood , Communicable Diseases/mortality , Emergency Service, Hospital , Hospital Mortality , Patient Admission , Protein Precursors/blood , Sepsis/mortality , Acute Disease , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Calcitonin Gene-Related Peptide , Communicable Diseases/blood , Communicable Diseases/diagnosis , Communicable Diseases/drug therapy , Communicable Diseases/microbiology , Female , Hospitals, General , Hospitals, Teaching , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Predictive Value of Tests , Prospective Studies , ROC Curve , Risk Factors , Rome , Sepsis/blood , Sepsis/diagnosis , Sepsis/drug therapy , Sepsis/microbiology , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: The use of biomarkers has been demonstrated useful in many acute diseases both for diagnosis, prognosis and risk stratification. OBJECTIVES: The purpose of this review is to analyze several biomarkers of potential use in patients referring to Emergency Department with acute dyspnea. STATE OF THE ART: The role of natriuretic peptides has a proven utility in the diagnosis, risk stratification, patient management and prediction of outcome in acute and chronic heart failure (HF). New immunoassays are available for the detection of mid-region prohormones in patients with acute dyspnea such as Mid-region pro-adrenomedullin (MR-proADM) and Mid-region pro-atrial natriuretic peptide (MR-proANP). Also procalcitonin, copeptin and D-dimer, which are markers of inflammation, bacterial infections and sepsis, seem to be useful in the differential diagnosis of dyspnea. Conventional and high-sensitivity troponins are fundamental, not only in the diagnosis of acute coronary syndromes, but also as indicators of mortality in patients with acute decompensated heart failure. PERSPECTIVES: Further studies with randomized controlled clinical trials will be needed to prove the theoretical clinical advantages offered by a shortness of breath biomarkers in terms of diagnostic, prognostic, cost effective work-up and management of patients with acute dyspnea. CONCLUSIONS: A multimarker pannel approach performed by rapid and accurate assays could be useful for emergency physicians to promptly identify different causes of dyspnea thus managing to improve diagnosis, treatment and risk stratification.
Subject(s)
Biomarkers/blood , Dyspnea/diagnosis , Acute Disease , Adrenomedullin/blood , Atrial Natriuretic Factor/blood , Calcitonin/blood , Calcitonin Gene-Related Peptide , Dyspnea/blood , Fibrin Fibrinogen Degradation Products/analysis , Humans , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Protein Precursors/blood , Troponin T/bloodABSTRACT
It has recently been suggested that galaxies in the early Universe could have grown through the accretion of cold gas, and that this may have been the main driver of star formation and stellar mass growth. Because the cold gas is essentially primordial, it has a very low abundance of elements heavier than helium (referred to as metallicity). If funnelled to the centre of a galaxy, it will result in the central gas having an overall lower metallicity than gas further from the centre, because the gas further out has been enriched by supernovae and stellar winds, and not diluted by the primordial gas. Here we report chemical abundances across three rotationally supported star-forming galaxies at redshift z ≈ 3, only 2 Gyr after the Big Bang. We find 'inverse' gradients, with the central, star-forming regions having lower metallicities than less active ones, which is opposite to what is seen in local galaxies. We conclude that the central gas has been diluted by the accretion of primordial gas, as predicted by 'cold flow' models.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , C-Reactive Protein/metabolism , Nucleosomes/metabolism , Adalimumab , Antibodies, Antinuclear/biosynthesis , Antibodies, Monoclonal, Humanized , Etanercept , Humans , Immunoglobulin G/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic useSubject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Immunoglobulin G/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adolescent , Adult , Aged , Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal, Humanized , Drug Tolerance , Etanercept , Humans , Immunoglobulin G/adverse effects , Longitudinal Studies , Middle Aged , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To evaluate the clinical response after switching to another TNFalpha antagonist in patients with rheumatoid arthritis (RA) and provide a review of the literature on this topic. METHODS: In this ongoing, longitudinal, observational study we have prospectively collected data of patients starting biological treatments since 2000. The present analysis is restricted to RA patients who switched to another anti-TNFalpha due to lack of efficacy (LaE), loss of efficacy (LoE), or adverse events (AEs) by the end of December 2007. Disease activity score (ESR-based DAS28) was calculated and the clinical response (none, moderate, good) was evaluated according to the European League Against Rheumatism (EULAR) criteria. Clinical remission (DAS28 <2.6) and low disease activity (DAS28 =3.2) were also evaluated. RESULTS: A total of 692 anti-TNFalpha-naïve patients has been registered, of whom 395 with a diagnosis of RA. Thirtyseven RA patients switched to another TNFalpha antagonist. Three months after switching, the proportion of patients with remission, low disease activity, good and moderate/good EULAR responses grew from 0%, 2.7%, 0%, and 5.4% (baseline before switching) to 16.2%, 35.1%, 27%, and 62.2% (p<0.05, p<0.001, p<0.001, p<0.000001, respectively). Of the patients who switched because of LaE, LoE, and AEs a moderate/good EULAR response was achieved in 38.4%, 66.6%, and 88.8% of patients, respectively. Mean treatment duration with the second anti-TNFalpha was significantly longer in patients switching for LoE and AEs than in those switching for LaE (p<0.05). CONCLUSIONS: The findings of this study suggest that RA patients may be successfully treated with another TNFalpha antagonist, especially those withdrawing for LoE or AEs.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Adalimumab , Adolescent , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Biomarkers/blood , Blood Sedimentation , C-Reactive Protein/metabolism , Disease Progression , Dose-Response Relationship, Drug , Drug Therapy, Combination , Etanercept , Female , Humans , Immunoglobulin G/therapeutic use , Infliximab , Male , Medical Records , Middle Aged , Prospective Studies , Quality of Life , Receptors, Tumor Necrosis Factor/therapeutic use , Severity of Illness Index , Surveys and Questionnaires , Treatment OutcomeABSTRACT
The aim of this study was to inventory the species of small mammals in Uberlândia, Minas Gerais, Brazil, based on regurgitated pellets of the barn owl and to compare the frequency of rodent species in the diet and in the environment. Since in the region there is a high incidence of hantavirus infection, we also evaluate the importance of the barn owl in the control of rodents that transmit the hantavirus. Data on richness and relative abundance of rodents in the municipality were provided by the Centro de Controle de Zoonoses, from three half-yearly samplings with live traps. In total, 736 food items were found from the analysis of 214 pellets and fragments. Mammals corresponded to 86.0 percent of food items and were represented by one species of marsupial (Gracilinanus agilis) and seven species of rodents, with Calomys tener (70.9 percent) and Necromys lasiurus (6.7 percent) being the most frequent. The proportion of rodent species in barn owl pellets differed from that observed in trap samplings, with Calomys expulsus, C. tener and Oligoryzomys nigripes being consumed more frequently than expected. Although restricted to a single place and based on few individuals, the present study allowed the inventory of eight species of small mammals in Uberlândia. The comparison of the relative frequencies of rodent species in the diet and in the environment indicated selectivity. The second most preyed upon species was N. lasiurus, the main hantavirus reservoir in the Cerrado biome. In this way, the barn owl might play an important role in the control of this rodent in the region, contributing to the avoidance of a higher number of cases of hantavirus infection.
O objetivo deste estudo foi inventariar as espécies de pequenos mamíferos em Uberlândia, Minas Gerais, Brasil, com base em pelotas regurgitadas de suindara e comparar a freqüência das espécies de roedores na dieta e no ambiente. Como na região ocorre grande incidência de casos de hantavirose, também se avaliou a importância da suindara no controle de roedores que transmitem o hantavírus. Os dados de riqueza e abundância relativa de roedores no município foram fornecidos pelo Centro de Controle de Zoonoses, a partir de três amostragens semestrais com armadilhas. No total, foram encontrados 736 itens alimentares a partir da análise de 214 pelotas e fragmentos de regurgitação. Os mamíferos corresponderam a 86,0 por cento dos itens alimentares e estiveram representados por uma espécie de marsupial (Gracilinanus agilis) e sete espécies de roedores, sendo os mais freqüentes Calomys tener (70,9 por cento) e Necromys lasiurus (6,7 por cento). A proporção das espécies de roedores nas pelotas da suindara diferiu daquela observada nas coletas com armadilhas, sendo que as espécies Calomys expulsus, C. tener e Oligoryzomys nigripes foram consumidas com maior freqüência do que o esperado. Apesar de restrito a um único local e baseado em poucos indivíduos, o presente estudo permitiu inventariar oito espécies de pequenos mamíferos em Uberlândia. A comparação da freqüência relativa das espécies de roedores na dieta e no ambiente indicou a existência de seletividade. A segunda espécie mais predada foi N. lasiurus, o principal reservatório de hantavírus no bioma Cerrado. Desta forma, a suindara parece desempenhar um importante papel no controle desse roedor na região, contribuindo para evitar um maior número de casos de hantavirose.
Subject(s)
Animals , Disease Reservoirs/classification , Hantavirus Infections , Marsupialia/classification , Predatory Behavior/physiology , Rodentia/classification , Strigiformes/physiology , Brazil , Hantavirus Infections/prevention & control , Hantavirus Infections/transmission , Population DensityABSTRACT
The aim of this study was to inventory the species of small mammals in Uberlândia, Minas Gerais, Brazil, based on regurgitated pellets of the barn owl and to compare the frequency of rodent species in the diet and in the environment. Since in the region there is a high incidence of hantavirus infection, we also evaluate the importance of the barn owl in the control of rodents that transmit the hantavirus. Data on richness and relative abundance of rodents in the municipality were provided by the Centro de Controle de Zoonoses, from three half-yearly samplings with live traps. In total, 736 food items were found from the analysis of 214 pellets and fragments. Mammals corresponded to 86.0% of food items and were represented by one species of marsupial (Gracilinanus agilis) and seven species of rodents, with Calomys tener (70.9%) and Necromys lasiurus (6.7%) being the most frequent. The proportion of rodent species in barn owl pellets differed from that observed in trap samplings, with Calomys expulsus, C. tener and Oligoryzomys nigripes being consumed more frequently than expected. Although restricted to a single place and based on few individuals, the present study allowed the inventory of eight species of small mammals in Uberlândia. The comparison of the relative frequencies of rodent species in the diet and in the environment indicated selectivity. The second most preyed upon species was N. lasiurus, the main hantavirus reservoir in the Cerrado biome. In this way, the barn owl might play an important role in the control of this rodent in the region, contributing to the avoidance of a higher number of cases of hantavirus infection.
Subject(s)
Disease Reservoirs/classification , Hantavirus Infections , Marsupialia/classification , Predatory Behavior/physiology , Rodentia/classification , Strigiformes/physiology , Animals , Brazil , Hantavirus Infections/prevention & control , Hantavirus Infections/transmission , Population DensityABSTRACT
OBJECTIVE: To assess the effect of occupational therapy (OT) in rheumatoid arthritis (RA) patients treated with anti-TNF-alpha drugs in a short-term open controlled prospective study. METHODS: 31 RA subjects [(M/F=5/26; mean age= 56 (range=28-73) years; mean disease duration= 165 (range =15-432) months], treated with anti- TNF-alpha drugs, were allocated to OT (n=15) or control (n=16) group. We evaluated at entry and 12 weeks the following outcome parameters including Health Assessment Questionnaire (HAQ), Short-Form Health Survey (SF-36), Global Health (GH), Ritchie index, number of swollen or tender joints, pain, patient and physician disease activity, Disease Activity Score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein CRP) and the correct adherence to items regarding activity daily living (ADL). RESULTS: At baseline, OT and control group had similar demographic and clinical features. After 12 weeks, the changes from baseline of main outcome parameters were not significantly different between the two groups. After 12 weeks, in 7 out of 11 items regarding ADL, the percentage of patients showing a correct adherence was significantly increased in OT group only. Moreover at the end of the study, the OT group showed a correct adherence to 8 out of 11 ADL items in an higher percentage of patients respect to the control group. CONCLUSION: Our study sustains that OT improves self-management but not main parameters of disease activity or functional capacity. Nevertheless educational intervention should be considered as a useful tool in conjunction with pharmacological treatment.
Subject(s)
Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/rehabilitation , Occupational Therapy , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Activities of Daily Living , Adalimumab , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antirheumatic Agents/administration & dosage , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/diagnosis , Blood Sedimentation , C-Reactive Protein/analysis , Cortisone/administration & dosage , Cortisone/therapeutic use , Data Interpretation, Statistical , Etanercept , Female , Health Status , Health Surveys , Humans , Immunoglobulin G/administration & dosage , Immunoglobulin G/therapeutic use , Infliximab , Male , Middle Aged , Patient Compliance , Prospective Studies , Receptors, Tumor Necrosis Factor/administration & dosage , Receptors, Tumor Necrosis Factor/therapeutic use , Socioeconomic Factors , Surveys and Questionnaires , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVES: To evaluate, using musculoskeletal ultrasound (MSUS), the effects of Etanercept therapy in patients with rheumatoid arthritis (RA) over 3 months of treatment. METHODS: Eighteen consecutive patients, 3 male and 15 female, affected by RA (ACR criteria) who were non-responders or partial responders to DMARDs therapy were commenced on Etanercept treatment. MSUS was performed bilaterally in the 2nd and 5th metacarpophalangeal, 3rd interphalangeal, wrist and knee joints, using a Philips/HP Image Point HX machine with a 7,5 MHz linear probe for knee joints and a 14 MHz probe for the hands and wrists. In addition, power Doppler was used with the following settings: PRF 700-1000Hz, gain 60-65 dB, low filter. For all the changes a semi-quantitative score (0-3) was used to indicate the presence of a localised inflammatory process (synovitis, tenosynovitis). An overall score was then calculated based on the sum of the single scores in order to obtain a comprehensive score indicative of the global pathological change. RESULTS: The overall score significantly (p<10-5) reduced between T0 (8,5) and T3 (5). Even the most part of the local joint scores significantly reduced. CONCLUSIONS: A positive response to treatment with Etanercept was demonstrated by MSUS examination of several joints. The results of our study are supportive of those presented in other reports where MSUS was used to monitor disease activity. We were able however to demonstrate this in a wider range of anatomical targets than in previous studies. MSUS is a useful tool in the monitoring of biologic therapy in RA.
Subject(s)
Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/drug therapy , Immunoglobulin G/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Ultrasonography, Doppler/methods , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antirheumatic Agents/administration & dosage , Drug Combinations , Drug Therapy, Combination , Etanercept , Female , Follow-Up Studies , Glucosamine/administration & dosage , Glucosamine/analogs & derivatives , Glucosamine/therapeutic use , Humans , Hydroxychloroquine/administration & dosage , Hydroxychloroquine/therapeutic use , Immunoglobulin G/administration & dosage , Joints/diagnostic imaging , Male , Methotrexate/administration & dosage , Methotrexate/therapeutic use , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Receptors, Tumor Necrosis Factor/administration & dosage , Sulfasalazine/administration & dosage , Sulfasalazine/therapeutic use , Tenosynovitis/diagnostic imaging , Time FactorsABSTRACT
OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions. METHODS: Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea. CONCLUSIONS: The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.
Subject(s)
Antiphospholipid Syndrome/immunology , Autoantibodies/blood , Autoimmune Diseases/immunology , Rheumatic Fever/immunology , Acetylglucosamine/immunology , Adolescent , Adult , Antibody Specificity , Antigens, Bacterial/immunology , Autoantigens/immunology , Autoimmunity , Bacterial Outer Membrane Proteins/immunology , Binding, Competitive , Blotting, Western , Carrier Proteins/immunology , Cross Reactions , Dose-Response Relationship, Immunologic , Female , Glycoproteins/immunology , Humans , Male , Middle Aged , beta 2-Glycoprotein IABSTRACT
OBJECTIVES: To evaluate the inflammatory status and the cartilage regenerative potential of pathological synovial fibroblasts from patients with osteoarthritis (OA) compared with non-inflamed synovium (NS)-derived cells from patients with chondropathy. METHODS: The inflammatory cell phenotype was investigated based on the constitutive and inducible surface expression and secretion of various effector molecules using flow cytometry or ELISA assays. The capacity of cells to produce cartilage-like extracellular matrix was assessed using acid Alcian blue staining and type II collagen immunostaining after treatment with transforming growth factor beta1 (TGF-beta1). RESULTS: OA and NS fibroblasts consistently expressed CD29, CD44, CD49e, CD54, CD90 and CD106. Expression of high-affinity receptors for IL-4, IL-15, CXCL8 and CXCL12 was also detected but only intracellularly. All types of fibroblasts spontaneously released abundant amounts of CXCL12, CCL2, IL-6 and tissue inhibitor of metalloproteinase 1, while the production of IL-11, TGF-beta1, matrix metalloproteinase 1 (MMP-1) and MMP-9 was detected at moderate levels. Several other secreted factors remained undetectable. No statistically significant differences were noted between the two groups of fibroblasts. Treatment with the proinflammatory cytokine tumour necrosis factor alpha (TNF-alpha) up-regulated the same set of surface and secreted molecules, including CD54, CD106, membrane IL-15, CCL2 and CCL5. Under TGF-beta1 treatment and adipogenic culture conditions, both OA and NS fibroblasts displayed chondrogenic and adipocytic activities that were reduced in OA compared with NS cells. CONCLUSIONS: OA synovial fibroblasts did not display a distinct activated inflammatory phenotype compared with NS cells. However, they did differ in their reduced ability to produce cartilage-like matrix. This difference may be an additional important factor contributing to OA pathogenesis.
Subject(s)
Cartilage, Articular/growth & development , Fibroblasts/pathology , Joint Diseases/pathology , Knee Joint/pathology , Osteoarthritis, Hip/pathology , Synovial Fluid/cytology , Adipocytes/metabolism , Aged , Antigens, CD/analysis , Cartilage, Articular/pathology , Cell Adhesion Molecules/analysis , Cells, Cultured , Chemokines/analysis , Cytokines/analysis , Female , Humans , Male , Middle Aged , PhenotypeABSTRACT
INTRODUCTION: Antiphospholipid syndrome (APS) is a systemic autoimmune disease, associated not only with a hypercoagulable state and recurrent fetal loss but with many diverse clinical manifestations including heart involvement, neurological manifestations, as well as skin, kidney and hematologic abnormalities. Cardiac manifestations include coronary by-pass graft and angioplasty occlusions, cardiomyopathy, cyanotic congenital heart disease, intracardiac thrombus and complications of cardiovascular surgery. The valvular heart disease was defined as Libman-Sacks nonbacterial endocarditis. Previously, we have shown a linear subendothelial deposition of anti-cardiolipin/beta2 glycoprotein I (beta2GPI) antibodies in the valve specimens derived from APS patients. The involvement of complement C3c in the pathogenesis was documented. We assessed the beta2GPI-related target epitope recognized by the anti-beta2GPI Abs on the valves. MATERIALS AND METHODS: In order to find the beta2GPI-related target epitopes recognized by the anti-beta2GPI antibodies on the valves, we used beta2GPI-related synthetic peptides. The presence of anti-beta2GPI Abs on the studied valves was detected by anti-idiotypic antibody, followed by immunoperoxidase analysis. Biotin attached to the N-terminal of beta2GPI-related synthetic peptides and control peptide were used to identify the epitope addressed by the anti-beta2GPI Abs deposited on the patient's valve. The binding was probed by streptavidin-peroxidase and appropriate substrate. The specificity was confirmed by competition assays with control peptide and anti-idiotypic antibody. RESULTS: Among the beta2GPI-related synthetic peptides, two peptides were found in previous studies to mimic common pathogens either bacteriae or viruses, which raised a possible infectious origin for APS. One of these peptides, TLRVYK, is a specific target for anti-beta2GPI Abs deposited on the APS valves. This synthetic peptide was able to displace the anti-anti-beta2GPI anti-idiotypic Abs for binding the anti-beta2GPI Abs on the valve by a competition assay. CONCLUSION: We point to the possibility that Libman-Sacks nonbacterial endocarditis may have an infectious origin.
Subject(s)
Antiphospholipid Syndrome/immunology , Endocarditis/immunology , Antibodies, Anticardiolipin/chemistry , Antiphospholipid Syndrome/complications , Endocarditis/complications , Epitopes/chemistry , Glycoproteins/immunology , Heart Valves/metabolism , Humans , Infections/complications , Lupus Erythematosus, Systemic/immunology , Peptides/chemistry , Protein Binding , beta 2-Glycoprotein IABSTRACT
OBJECTIVE: To investigate the effect of infliximab treatment on anti-cyclic citrullinated peptide antibodies (anti-CCP) and rheumatoid factor (RF) in patients with rheumatoid arthritis. METHODS: 43 patients with rheumatoid arthritis not responding to disease modifying anti-rheumatic drugs (DMARD) received intravenous infliximab at a dose of 3 mg/kg at baseline and after two and six weeks, and subsequently bimonthly, in combination with methotrexate. Serum samples were collected at baseline and at week 24. A commercial enzyme linked immunosorbent assay was used to test for anti-CCP antibodies; RF were detected using a quantitative nephelometric assay. RESULTS: At baseline, 38 of the 43 patients (88%) were positive for anti-CCP antibodies, and 41 (95%) were positive for RF. The serum titre of anti-CCP and RF decreased significantly after six months of treatment (p = 0.0001 and p<0.0001, respectively). When the patients were grouped on the basis of their clinical response to infliximab, a significant decrease in serum anti-CCP antibodies and RF was observed only in patients who had clinical improvement (ACR 20 and ACR 50). CONCLUSIONS: Anti-TNFalpha treatment in rheumatoid arthritis results in a decrease in the serum titres of RF and anti-CCP antibodies in patients showing clinical improvement, suggesting that these measurements may be a useful adjunct in assessing treatment efficacy.
Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Autoantibodies/blood , Citrulline/immunology , Rheumatoid Factor/blood , Adult , Aged , Arthritis, Rheumatoid/immunology , Biomarkers/blood , Drug Therapy, Combination , Female , Humans , Infliximab , Male , Methotrexate/therapeutic use , Middle Aged , Severity of Illness Index , Treatment OutcomeABSTRACT
We investigated the circulating levels of the main cytokines involved in bone resorption (IL-1beta, IL-6, TNF-alpha), prostaglandins (PGE2) and metalloproteases (MMP-1), as possible early markers of osteolysis, in the serum of eight patients with periprosthetic osteolysis and ten patients without osteolysis. All had received a cementless hip prosthesis (ABG-1). We also assessed the serum levels of IL-1 and TGF-beta anti-inflammatory cytokines exerting protective effect on bone resorption. The mean serum levels of IL-1beta, IL-6, TNF-alpha, TGF-beta, MMP-1, and PGE2 in patients with periprosthetic osteolysis did not differ significantly from those of patients without osteolysis or from those of normal controls. IL-11 serum levels were not detectable at all in any of the patients, while they were detected within normal reference values in the control subjects (significant inverse correlation). We believe that circulating cytokines cannot be regarded as markers of osteolysis, a condition characterised by a local inflammation without systemic signs of inflammation. On the contrary, the undetectable levels of IL-11 in implanted patients could provide evidence for a lack of balance between pro- and anti-inflammatory cytokines in these patients.
Subject(s)
Cytokines/blood , Hip Prosthesis/adverse effects , Osteolysis/blood , Aged , Aged, 80 and over , Biomarkers/blood , Dinoprostone/blood , Female , Humans , Inflammation/blood , Inflammation Mediators/blood , Interleukin-1/blood , Interleukin-11/blood , Interleukin-6/blood , Male , Matrix Metalloproteinase 1/blood , Middle Aged , Osteolysis/etiology , Polyethylene , Tumor Necrosis Factor-alpha/metabolismABSTRACT
This study examined the hypothesis that the polymorphism of Duffy antigen receptor for chemokines (DARC) predisposes to and/or influences the clinical manifestations of Behçet's disease. The serum levels of IL-8 and monocyte chemotactic peptide (MCP)-1, two DARC-binding chemokines, were investigated and related to this polymorphism. Twenty-eight patients with Behçet's disease and 30 healthy blood donors were included in the study. No null phenotypes were found among the patients studied, and the frequencies of the other phenotypes (Fy((a+b-)), Fy((a+b+)), and Fy((a-b+))) did not significantly differ from those found in the blood donor group or reported in the general Caucasian population. No difference was found between the single phenotypes in terms of IL-8 and MCP-1 serum levels, and no relevant association between the clinical characteristics, Behçet's disease-associated human leukocyte antigen (HLA)-B51, and single phenotypes was observed. This investigation indicates that DARC is not a genetic trait significantly associated with or predisposing to Behçet's disease, at least in Caucasian Italians. However, the role of this polymorphism in the development and in the clinical course of the disease awaits further investigation.