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Sample records for active ra patients

  1. Lenalidomide enhances antigen-specific activity and decreases CD45RA expression of T cells from patients with multiple myeloma.

    PubMed

    Neuber, Brigitte; Herth, Isabelle; Tolliver, Claudia; Schoenland, Stefan; Hegenbart, Ute; Hose, Dirk; Witzens-Harig, Mathias; Ho, Anthony D; Goldschmidt, Hartmut; Klein, Bernard; Hundemer, Michael

    2011-07-15

    The aim of this study was to investigate whether the specific T cell response against the multiple myeloma Ag HM1.24 is enhanced by the immunomodulatory drug lenalidomide (Revlimid). Ag-specific CD3(+)CD8(+) T cells against the HM1.24 Ag were expanded in vitro by dendritic cells in 29 healthy donors and 26 patients with plasma cell dyscrasias. Ag-specific activation was analyzed by IFN-γ, granzyme B, and perforin secretion using ELISA, ELISPOT assay, and intracellular staining, and generation of Ag-specific T cells was analyzed by tetramer staining. Expression of T cell maturation markers (CD45RA, CD45R0, CCR7, and CD28) was investigated by flow cytometry. We found that activation of HM1.24-specific T cells from healthy donors and patients with plasma cell dyscrasias was enhanced significantly by lenalidomide and furthermore that the impact of lenalidomide on T cells depends on the duration of the exposure. Notably, lenalidomide supports the downregulation of CD45RA on T cells upon activation, observed in healthy donors and in patients in vitro and also in patients during lenalidomide therapy in vivo. We showed for the first time, to our knowledge, that lenalidomide enhances the Ag-specific activation of T cells and the subsequent downregulation of CD45RA expression of T cells in vitro and in vivo.

  2. Assessment of global disease activity in RA patients monitored in the METEOR database: the patient's versus the rheumatologist's opinion.

    PubMed

    Gvozdenović, Emilia; Koevoets, Rosanne; Wolterbeek, Ron; van der Heijde, Désirée; Huizinga, Tom W J; Allaart, Cornelia F; Landewé, Robert B M

    2014-04-01

    The objectives of this study were to compare the patient's (PtGDA) and physician's (PhGDA) assessment of global disease activity and to identify factors that might influence these differences as well as factors that may influence the patient's and the physician's scores separately. Anonymous data were used from 2,117 Dutch patients included in the Measurement of efficacy of Treatment in the Era of Rheumatology database. PtGDA and PhGDA were scored independently on a 100-mm visual analog scale (VAS) with 0 and 100 as extremes. The agreement, intraclass correlation coefficients (ICC), was calculated and a Bland-Altman plot was created to visualize the differences between PtGDA and PhGDA. Linear mixed model analysis was used to model PtGDA and PhGDA. Logistic repeated measurements were used to model the difference in PtGDA and PhGDA (PtGDA > PhGDA versus PtGDA ≤ PhGDA). Gender patient, gender physician, age, swollen joint count (SJC), tender joint count, VAS pain, disease duration, and erythrocyte sedimentation rate (ESR) were considered as possible determinants in both models. Mean (standard deviation) age was 57 (15) years and 67 % of the patients were female. Agreement between PtGDA and PhGDA was moderate (ICC, 0.57). Patients scored on average 11 units higher (worse) than rheumatologists (95 % limits of agreement, -25.2 to 47.6). Patient's perception of pain (VAS) was positively associated with a PtGDA being higher than PhGDA. Similarly, ESR and swollen joint counts were positively associated with a PtGDA being lower or equal to the PhGDA. Patients rate global disease activity consistently higher than their rheumatologists. Patients base their judgment primarily on the level of pain, physicians on the level of SJC and ESR.

  3. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA

    PubMed Central

    Hutchinson, D; Shepstone, L; Moots, R; Lear, J; Lynch, M

    2001-01-01

    OBJECTIVES—To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease.
METHODS—239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset.
RESULTS—An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003).
CONCLUSIONS—Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

 PMID:11171682

  4. Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases.

    PubMed

    Yoshida, Yuji; Takahashi, Yuko; Minemura, Nobuyoshi; Ueda, Yo; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2012-08-01

    Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.

  5. Measurement of 224Ra and 226Ra activities in natural waters using a radon-in-air monitor

    USGS Publications Warehouse

    Kim, G.; Burnett, W.C.; Dulaiova, H.; Swarzenski, P.W.; Moore, W.S.

    2001-01-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn (218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  6. Factors influencing quality of life (QOL) for Korean patients with rheumatoid arthritis (RA).

    PubMed

    Cho, Soo-Kyung; Kim, Dam; Jun, Jae-Bum; Bae, Sang-Cheol; Sung, Yoon-Kyoung

    2013-01-01

    The aim of the study was to identify factors influencing the health-related quality of life (HR-QOL) for Korean RA patients and factors associated with each dimension of the EQ-5D. Two hundred and twenty-five RA patients were recruited from one University Hospital in Seoul, South Korea. Their clinical and socio-demographic data were widely collected by means of interviews, self-administered questionnaires, and clinical examinations. Multiple logistic regression analyses were performed to determine the factors influencing QOL and factors associated with each dimension of the EQ-5D. The mean EQ-5D utility observed for Korean RA patients was 0.60 (-0.29 to 1.0). Functional disability measured with Health Assessment Questionnaire (OR = 10.0, CI 2.8-34.5), disease activity score (DAS) 28 (OR = 2.6, CI 1.4-4.9), and pain VAS (OR = 2.2, CI 1.2-4.1) was three main factors influencing on QOL of RA patients. Although the functional disability consistently showed significant associations with all dimensions, various factors were associated with the each five specific dimension of EQ-5D. Pain (OR = 2.5, CI 1.4-4.6), history of hospitalization (OR = 2.1, CI 1.0-4.3), and men (OR = 2.6, CI 1.0-6.8) were associated with lower QOL in mobility. Use of alternative medicine (OR = 2.0, CI 1.1-3.7) and disease activity (OR = 3.1, CI 1.7-5.7) were associated with lower self-care QOL. For the patients with discomfort in usual activity, pain (OR = 4.7, CI 2.4-9.2) and the presence of anemia (OR = 2.3, CI 1.2-4.5) were major influencing factors. Higher disease activity (OR = 4.5, CI 1.0-21.2) and pain (OR = 3.3, CI 1.9-5.8) were associated with the pain/discomfort dimension of EQ-5D, and the pain (OR = 3.3, CI 1.9-5.8) was an independent associating factor of anxiety/depression. The strongest determinants of lower QOL in Korean RA patients were functional disability, higher disease activity, and subjective pain. However, various factors are influencing on the QOL for RA patients according

  7. Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking water using a single sample preparation procedure.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail P

    2005-12-01

    The current federal and New Jersey State regulations have greatly increased the number of gross alpha and radium tests for public and private drinking water supplies. The determination of radium isotopes in water generally involves lengthy and complicated processes. In this study, a new approach is presented for the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water samples. The method includes a single sample preparation procedure followed by alpha counting and gamma-ray spectroscopy. The sample preparation technique incorporates an EPA-approved co-precipitation methodology for gross alpha determination with a few alterations and improvements. Using 3-L aliquots of sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle activity of the sample is measured with a low-background gas-flow proportional counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the sample are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is required, the gamma-ray counting should be performed within 2-4 d from sample collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy can be repeated 21 d after sample preparation to ensure that 226Ra and its progeny have reached the equilibrium state. At this point, the 228Ac equilibration with parent 228Ra is already established. Analysis of aliquots of de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra standards demonstrated the accuracy and precision of this method. Various performance evaluation samples were also assayed for gross alpha as well as radium isotope activity determination using this procedure and the

  8. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  9. Drugs or disease: evaluating salivary function in RA patients.

    PubMed

    Torres, Sandra Regina; Pedrazas, Carlos Henrique Silva; Correia, Marcos Paulo Veloso; Azevedo, Mario Newton Leitão de; Zamprogno, Thaís; Silva, Arley; Gonçalves, Lucio Souza; Papi, José Angelo de Souza

    2016-10-10

    Oral complications of RA may include temporomandibular joint disorders, mucosa alterations and symptoms of dry mouth. The aim of this study was to evaluate the salivary gland function of subjects with rheumatoid arthritis (RA) comparing it to healthy controls. Subjects with other systemic conditions known to affect salivary functions were excluded. A questionnaire was applied for the evaluation of xerostomia. Resting and chewing-stimulated salivary flow rates (SFR) were obtained under standard conditions. There were 145 subjects included of the study (104 RA and 38 controls). About 66.7% of the RA subjects and 2.4% in control group presented xerostomia. The median resting SFR were 0.24 ml/min for RA subjects and 0.40 mL/min for controls (p = 0.04). The median stimulated SFR were 1.31 mL/min for RA subjects and 1.52 ml/min for controls (p = 0.33). No significant differences were found between resting and stimulated SFR of RA subjects not using xerogenic medications and controls. There was significantly higher number of subjects presenting hyposalivation in the RA group than among controls, even when subjects using xerogenic medications were eliminated from the analysis. In conclusion, hyposalivation and xerostomia were more frequent among RA subjects not using xerogenic medication than among controls, although there were no significant differences in the median SFR between groups.

  10. Increased extracellular water measured by bioimpedance and by increased serum levels of atrial natriuretic peptide in RA patients-signs of volume overload.

    PubMed

    Straub, Rainer H; Ehrenstein, Boris; Günther, Florian; Rauch, Luise; Trendafilova, Nadezhda; Boschiero, Dario; Grifka, Joachim; Fleck, Martin

    2016-04-26

    The aim of the study is to investigate water compartments in patients with rheumatoid arthritis (RA). Acute inflammatory episodes such as infection stimulate water retention, chiefly implemented by the sympathetic nervous system (SNS) and hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism due to expected water loss (sweating etc.). Since SNS and HPA axis are activated in RA, inflammation might be accompanied by water retention. Using bioimpedance analysis, body composition was investigated in 429 controls and 156 treatment-naïve RA patients between January 2008 and December 2014. A group of 34 RA patients was tested before and after 10 days of intensified therapy. Levels of pro-atrial natriuretic peptide (proANP) and expression of atrial natriuretic peptide in synovial tissue were investigated in 15 controls and 14 RA patients. Extracellular water was higher in RA patients than controls (mean ± SEM: 49.5 ± 0.3 vs. 36.7 ± 0.1, % of total body water, p < 0.0001). Plasma levels of proANP were higher in RA than controls. RA patients expressed ANP in synovial tissue, but synovial fluid levels and synovial tissue superfusate levels were much lower than plasma levels indicating systemic origin. Systolic/diastolic blood pressure was higher in RA patients than controls. Extracellular water levels did not change in RA patients despite 10 days of intensified treatment. This study demonstrates signs of intravascular overload in RA patients. Short-term intensification of anti-inflammatory therapy induced no change of a longer-lasting imprinting of water retention indicating the requirement of additional treatment. The study can direct attention to the area of volume overload.

  11. Opening of the closed water area and consequent changes of ²²⁸Ra/²²⁶Ra activity ratios in coastal lagoon Nakaumi, southwest Japan.

    PubMed

    Nomura, Ritsuo; Nakamura, Kosaku; Seto, Koji; Inoue, Mutsuo; Kofuji, Hisaki

    2013-11-01

    In Lake Nakaumi, the second largest coastal lagoon in Japan, artificially closed (Honjyo) area, which was left untouched for 28 years, was partly opened in May, 2009. (228)Ra/(226)Ra ratio of waters in Honjyo area and Lake Nakaumi showed a well-tuned seasonal variation exhibiting high value in summer. After the opening event, however, the (228)Ra/(226)Ra ratios in the Honjyo water showed an unclear seasonal variation in both surface and deep water. This opening event caused the change of active movement of lake and marine water.

  12. (226) RA AND (228) RA ACTIVITIES ASSOCIATED WITH AGRICULTURAL DRAINAGE PONDS AND WETLAND PONDS IN THE KANKAKEE WATERSHED, IL-IN, USA

    EPA Science Inventory

    Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-a and -B activities were measured up to 455 and 1650 mBq L-1, respectively. 226Ra and 228Ra averaged 139 and 192 mBq L-01...

  13. Carbachol-Induced Reduction in the Activity of Adult Male Zebra Finch RA Projection Neurons

    PubMed Central

    Meng, Wei; Wang, Song-Hua; Li, Dong-Feng

    2016-01-01

    Cholinergic mechanism is involved in motor behavior. In songbirds, the robust nucleus of the arcopallium (RA) is a song premotor nucleus in the pallium and receives cholinergic inputs from the basal forebrain. The activity of projection neurons in RA determines song motor behavior. Although many evidences suggest that cholinergic system is implicated in song production, the cholinergic modulation of RA is not clear until now. In the present study, the electrophysiological effects of carbachol, a nonselective cholinergic receptor agonist, were investigated on the RA projection neurons of adult male zebra finches through whole-cell patch-clamp techniques in vitro. Our results show that carbachol produced a significant decrease in the spontaneous and evoked action potential (AP) firing frequency of RA projection neurons, accompanying a hyperpolarization of the membrane potential, an increase in the evoked AP latency, afterhyperpolarization (AHP) peak amplitude, and AHP time to peak, and a decrease in the membrane input resistance, membrane time constant, and membrane capacitance. These results indicate that carbachol reduces the activity of RA projection neurons by hyperpolarizing the resting membrane potential and increasing the AHP and the membrane conductance, suggesting that the cholinergic modulation of RA may play an important role in song production. PMID:26904300

  14. PADI4 haplotypes in association with RA Mexican patients, a new prospect for antigen modulation.

    PubMed

    Zavala-Cerna, Maria Guadalupe; Gonzalez-Montoya, Norma Guadalupe; Nava, Arnulfo; Gamez-Nava, Jorge I; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Gonzalez-Lopez, Laura; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity.

  15. PADI4 Haplotypes in Association with RA Mexican Patients, a New Prospect for Antigen Modulation

    PubMed Central

    Gonzalez-Montoya, Norma Guadalupe; Gamez-Nava, Jorge I.; Moran-Moguel, Maria Cristina; Rosales-Gomez, Roberto Carlos; Gutierrez-Rubio, Susan Andrea; Sanchez-Corona, Jose; Davalos-Rodriguez, Ingrid Patricia; Salazar-Paramo, Mario

    2013-01-01

    Peptidyl arginine deiminase IV (PAD 4) is the responsible enzyme for a posttranslational modification called citrullination, originating the antigenic determinant recognized by anti-cyclic citrullinated peptide antibodies (ACPA). Four SNPs (single nucleotide polymorphisms) have been described in PADI4 gene to form a susceptibility haplotype for rheumatoid arthritis (RA); nevertheless, results in association studies appear contradictory in different populations. The aim of the study was to analyze if the presence of three SNPs in PADI4 gene susceptibility haplotype (GTG) is associated with ACPA positivity in patients with RA. This was a cross-sectional study that included 86 RA patients and 98 healthy controls. Polymorphisms PADI4_89, PADI4_90, and PADI4_92 in the PADI4 gene were genotyped. The susceptibility haplotype (GTG) was more frequent in RA patients; interestingly, we found a new haplotype associated with RA with a higher frequency (GTC). There were no associations between polymorphisms and high scores in Spanish HAQ-DI and DAS-28, but we did find an association between RARBIS index and PADI4_89, PADI4_90 polymorphisms. We could not confirm an association between susceptibility haplotype presence and ACPA positivity. Further evidence about proteomic expression of this gene will determine its participation in antigenic generation and autoimmunity. PMID:24454473

  16. Effects of tiaprofenic acid on plasminogen activators and inhibitors in human OA and RA synovium.

    PubMed

    Pelletier, J P; McCollum, R; Cloutier, J M; Martel-Pelletier, J

    1992-01-01

    The effect of therapeutic and pharmacological concentrations of tiaprofenic acid, a non-steroidal anti-inflammatory drug (NSAID), on the synthesis of the plasminogen activators, urokinase plasminogen activator (uPA) and tissue plasminogen activator (tPA), and the plasminogen activator inhibitors 1 and 2 (PAI-1 and PAI-2), by human synovial membranes isolated from osteoarthritis (OA) and rheumatoid arthritis (RA) sufferers was evaluated. Both forms of plasminogen activator (PA) and PA inhibitor (PAI) were synthesized by the arthritic synovium. PAI-1 and PAI-2 were both synthesized in greater amounts than the plasminogen activators. Tiaprofenic acid induced a dose-dependent decrease in uPA synthesis in both OA and RA, particularly in OA synovium, but had no true effect on tPA. Tiaprofenic acid also exerted a suppressive effect on the synthesis of PAI-1 in both OA and RA synovial membranes, and on the release of PAI-2 in RA synovium. The results of this study indicate that a decrease in uPA synthesis may be one of the mechanisms by which tiaprofenic acid could exert its effects on the arthritic process. The suppressive action of tiaprofenic acid on PAI is not likely to have a significant impact on the balance of plasminogen activators and plasminogen activator inhibitors, as plasminogen activator inhibitors are synthesized in greater amounts than plasminogen activators.

  17. The Impact of Statin Use on Lipid Levels in Statin-Naive Patients with Rheumatoid Arthritis (RA) vs. non-RA Subjects: Results from a Population-Based Study

    PubMed Central

    Myasoedova, Elena; Gabriel, Sherine E.; Green, Abigail B.; Matteson, Eric L.; Crowson, Cynthia S.

    2013-01-01

    Objectives To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins. Methods Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 ACR criteria first met between 1/1/1988 and 1/1/2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included. Results The study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non-RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) were lower in RA vs non-RA cohort (p<0.001 and p=0.003, respectively). The absolute and percent change in LDL after at least 90 days of statin use tended to be smaller in RA vs non-RA cohort (p=0.03 and p=0.09). After at least 90 days of statin use patients with RA were less likely to achieve therapeutic goals for LDL than the non-RA subjects (p=0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (OR 0.47; 95% CI 0.26, 0.85) was associated with lower likelihood of achieving therapeutic LDL goals. Conclusion Patients with RA had lower TC and LDL levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non-RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals. PMID:23592565

  18. Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity.

    PubMed

    Chan, W K; Suwannasaen, D; Throm, R E; Li, Y; Eldridge, P W; Houston, J; Gray, J T; Pui, C-H; Leung, W

    2015-02-01

    Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19(+) MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA(-) cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR(+)CD45RA(-) cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR(+) cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA(-) cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA(+) cells, CD45RA(-) cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR(+)CD45RA(-) cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells.

  19. 226Ra activity in the mullet species Liza aurata and South Adriatic Sea marine.

    PubMed

    Antovic, N M; Antovic, I; Svrkota, N

    2010-08-01

    (226)Ra activity in the South Adriatic Sea-water, surface sediment, mud with detritus, seagrass (Posidonia oceanica) samples and the mullet (Mugilidae) species Liza aurata, as well as soil and sand from the Montenegrin Coast-was measured using the six-crystal gamma-coincidence spectrometer PRIPYAT-2M. The results are used for calculation of the absorbed (and annual effective) dose rates in air due to the (226)Ra gamma radiation. The absorbed dose rates ranged from 5.94 to 97.16 nGy h(-1) (soil) and from 0.65 to 7.65 nGy h(-1) (sand). In seawater (226)Ra activity is found to be from 0.08 to 0.15 Bq l(-1), while in whole L. aurata individuals from 0.58 to 1.97 Bq kg(-1). Annual intake of (226)Ra by human consumers of this fish species has been estimated to provide an effective dose of 0.006 mSv y(-1).

  20. Investigations on the activity concentrations of 238U, 226RA, 228RA, 210PB and 40K in Jordan phosphogypsum and fertilizers.

    PubMed

    Al-Jundi, J; Al-Ahmad, N; Shehadeh, H; Afaneh, F; Maghrabi, M; Gerstmann, U; Höllriegl, V; Oeh, U

    2008-01-01

    The activity concentrations of naturally occurring radionuclides ((238)U, (226)Ra, (228)Ra, (210)Pb and (40)K) in Jordanian phosphate ore, fertilizer material and phosphogypsum piles were investigated. The results show the partitioning of radionuclides in fertilizer products and phosphogypsum piles. The outcome of this study will enrich the Jordanian radiological map database, and will be useful for an estimation of the radiological impact of this industrial complex on the immediate environment. The activity concentration of (210)Pb was found to vary from 95 +/- 8 to 129 +/- 8 Bq kg(-1) with a mean value of 111 +/- 14 Bq kg(-1) in fertilizer samples, and from 364 +/- 8 to 428 +/- 10 Bq kg(-1) with a mean value of 391 +/- 30 Bq kg(-1) in phosphogypsum samples; while in phosphate wet rock samples, it was found to vary between 621 +/- 9 and 637 +/- 10 Bq kg(-1), with a mean value of 628 +/- 7 Bq kg(-1). The activity concentration of (226)Ra in fertilizer samples (between 31 +/- 4 and 42 +/- 5 Bq kg(-1) with a mean value of 37 +/- 6 Bq kg(-1)) was found to be much smaller than the activity concentration of (226)Ra in phosphogypsum samples (between 302 +/- 8 and 442 +/- 8 Bq kg(-1) with a mean value of 376 +/- 62 Bq kg(-1)). In contrast, the activity concentration of (238)U in fertilizer samples (between 1011 +/- 13 and 1061 +/- 14 Bq kg(-1) with a mean value of 1033 +/- 22 Bq kg(-1)) was found to be much higher than the activity concentration of (238)U in phosphogypsum samples (between 14 +/- 5 and 37 +/- 7 Bq kg(-1) with a mean value of 22 +/- 11 Bq kg(-1)). This indicates that (210)Pb and (226)Ra show similar behaviour, and are concentrated in phosphogypsum piles. In addition, both isotopes enhanced the activity concentration in phosphogypsum piles, while (238)U enhanced the activity concentration in the fertilizer. Due to the radioactivity released from the phosphate rock processing plants into the environment, the highest collective dose commitment for the lungs

  1. Ultrasound-detected joint inflammation and B cell count: related variables for rituximab-treated RA patients?

    PubMed

    Valor, Lara; Martínez-Estupiñán, Lina; Janta, Iustina; Nieto, Juan Carlos; Ovalles-Bonilla, Juan Gabriel; González-Fernández, Carlos; Del Rio, Tamara; Hernández-Flórez, Diana; Monteagudo, Indalecio; López-Longo, Francisco Javier; Naredo, Esperanza

    2016-06-01

    This cross-sectional observational study aimed to explore the relationship between B cell count and ultrasound (US)-detected synovitis, in patients with rheumatoid arthritis treated with rituximab. Thirty-seven consecutive RA patients treated with RTX were recruited for the study. The patients underwent clinical [i.e., Disease Activity Score 28 joints (DAS28)], laboratory, and US assessment of 12 joints. Each joint was semiquantitatively (0-3) scored on B-mode and power Doppler mode. The scores were summed, and a global index was created for BM (BMS) and PD scores (PDI) synovitis. BM subclinical synovitis was evident in all patients, with PD synovial signal detected in 16 patients (43.2 %). No correlation was found between DAS28 and US scores. B cells were detected in 27 (72.9 %) patients, but there was no association in the mean B cell count and disease activity as measured by DAS28 (DAS28 < 2.6 = 34.53, DAS28 > 2.6 = 49.45, p = 0.52) and PDI score (PDI < 1 = 49.48, PDI > 1 = 35.44, p = 0.54). There was no correlation between the B cell count and DAS28, BMS, and PDI (r = 0.020, p = 0.907; r = -0.151, p = 0.371; r = -0.099, p = 0.558, respectively). In RTX-treated RA patients, no relationship could be established between US-detected synovitis and peripheral blood B cell count.

  2. Long-term blood pressure variability in patients with rheumatoid arthritis (RA) and its impact on cardiovascular events and all-cause mortality in RA: a population-based comparative cohort study

    PubMed Central

    Myasoedova, Elena; Crowson, Cynthia S.; Green, Abigail B.; Matteson, Eric L.; Gabriel, Sherine E.

    2014-01-01

    Objectives To examine long-term visit-to-visit blood pressure (BP) variability in rheumatoid arthritis (RA) vs non-RA subjects and to assess its impact on cardiovascular events and mortality in RA. Methods Clinic BP measures were collected in a population-based incident cohort of RA patients (1987 ACR criteria met between 1/1/1995 and 1/1/2008) and non-RA subjects. BP variability was defined as within-subject standard deviation (SD) in systolic and diastolic BP. Results Study included 442 RA patients (mean age 55.5 years, 70% females) and 424 non-RA subjects (mean age 55.7 years, 69% females). RA patients had higher visit-to-visit variability in systolic BP (13.8±4.7 mm Hg), than non-RA subjects (13.0±5.2 mm Hg, p=0.004). Systolic BP variability declined after the index date in RA (p<0.001), but not in the non-RA cohort (p=0.73), adjusting for age, sex and calendar year of RA. During the mean follow-up of 7.1 years, 33 cardiovascular events and 57 deaths occurred in RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of cardiovascular events (hazard ratio [HR] per 1 mm Hg increase in BP variability 1.12, 95% confidence interval [CI] 1.01-1.25); diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95%CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, use of antihypertensives. Conclusion Patients with RA had higher visit-to-visit systolic BP variability vs non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse cardiovascular outcomes and all-cause mortality in RA. PMID:24986852

  3. Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.

    PubMed

    Lévy, Romain; Okada, Satoshi; Béziat, Vivien; Moriya, Kunihiko; Liu, Caini; Chai, Louis Yi Ann; Migaud, Mélanie; Hauck, Fabian; Al Ali, Amein; Cyrus, Cyril; Vatte, Chittibabu; Patiroglu, Turkan; Unal, Ekrem; Ferneiny, Marie; Hyakuna, Nobuyuki; Nepesov, Serdar; Oleastro, Matias; Ikinciogullari, Aydan; Dogu, Figen; Asano, Takaki; Ohara, Osamu; Yun, Ling; Della Mina, Erika; Bronnimann, Didier; Itan, Yuval; Gothe, Florian; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Tahuil, Natalia; Aytekin, Caner; Salhi, Aicha; Al Muhsen, Saleh; Kobayashi, Masao; Toubiana, Julie; Abel, Laurent; Li, Xiaoxia; Camcioglu, Yildiz; Celmeli, Fatih; Klein, Christoph; AlKhater, Suzan A; Casanova, Jean-Laurent; Puel, Anne

    2016-12-20

    Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

  4. Noradrenergic and GABAB Receptor Activation Differentially Modulate Inputs to the Premotor Nucleus RA in Zebra Finches

    PubMed Central

    Sizemore, Max; Perkel, David J.

    2008-01-01

    Neuromodulators can rapidly modify neural circuits, altering behavior. Songbirds provide an excellent system for studying the role of neuromodulation in modifying circuits that underlie behavior because song learning and production are mediated by a discrete set of interconnected nuclei. We examined the neuromodulatory effects of noradrenergic and GABAB receptor activation on synaptic inputs to the premotor robust nucleus of the arcopallium (RA) in zebra finches using whole cell voltage-clamp recording in vitro. In adults, norepinephrine strongly reduced input from the lateral magnocellular nucleus of the anterior nidopallium (LMAN) but only slightly reduced the input from nucleus HVC (proper name), the excitatory input from axon collaterals of other RA neurons, and input from GABAergic interneurons. The effect of norepinephrine was mimicked by the α2 adrenoceptor agonist UK14,304 and blocked by the α2 antagonist yohimbine. Conversely, the GABAB receptor agonist baclofen strongly decreased HVC, collateral, and GABAergic inputs to RA neurons while causing little reduction in the LMAN input. In juveniles undergoing song learning, norepinephrine reduced the LMAN input, caused only a small reduction in the HVC input, and greatly reduced the collateral and GABAergic inputs. Baclofen caused similar results in juvenile and adult birds, reducing HVC, collateral, and GABAergic inputs significantly more than the LMAN input. Significant increases in paired-pulse ratio accompanied all reductions in synaptic transmission, suggesting a presynaptic locus. The reduction in the LMAN input by norepinephrine may be important for mediating changes in song elicited by different social contexts and is well-placed to play a role in song learning. PMID:18463188

  5. Ottawa Panel Evidence-Based Clinical Practice Guidelines for Patient Education in the Management of Rheumatoid Arthritis (RA)

    ERIC Educational Resources Information Center

    Brosseau, Lucie; Wells, George A.; Tugwell, Peter; Egan, Mary; Dubouloz, Claire-Jehanne; Welch, Vivian A.; Trafford, Laura; Sredic, Danjiel; Pohran, Kathryn; Smoljanic, Jovana; Vukosavljevic, Ivan; De Angelis, Gino; Loew, Laurianne; McEwan, Jessica; Bell, Mary; Finestone, Hillel M.; Lineker, Sydney; King, Judy; Jelly, Wilma; Casimiro, Lynn; Haines-Wangda, Angela; Russell-Doreleyers, Marion; Laferriere, Lucie; Lambert, Kim

    2012-01-01

    Background and purpose: The objective of this article is to create guidelines for education interventions in the management of patients ([greater than] 18 years old) with rheumatoid arthritis (RA). Methods: The Ottawa Methods Group identified and synthesized evidence from comparative controlled trials using Cochrane Collaboration methods. The…

  6. Composition and Antioxidant Activity of Geopropolis Collected by Melipona subnitida (Jandaíra) Bees

    PubMed Central

    Alves de Souza, Silvana; Camara, Celso Amorim; Monica Sarmento da Silva, Eva; Silva, Tania Maria Sarmento

    2013-01-01

    An investigation of the geopropolis collected by Melipona subnitida (jandaíra) stingless bee led to the isolation and characterization of two phenylpropanoids, 6-O-p-coumaroyl-D-galactopyranose (1) and 6-O-cinnamoyl-1-O-p-coumaroyl-β-D-glucopyranose (2), and seven flavonoids, 7-O-methyl-naringenin (3), 7-O-methyl aromadendrin (4), 7,4′-di-O-methyl aromadendrin (5), 4′-O-methyl kaempferol (6), 3-O-methyl quercetin (7), 5-O-methyl aromadendrin (8), and 5-O-methyl kaempferol (9). The structure of the new phenylpropanoid (1) was established from IR, LC-ESI-MS, and NMR spectral data, including 2D NMR experiments. The extract and fractions demonstrated significant antioxidant activity in DPPH, ABTS, and β-carotene/linoleic acid tests. PMID:23935683

  7. CD45RA-Foxp3(low) non-regulatory T cells in the CCR7-CD45RA-CD27+CD28+ effector memory subset are increased in synovial fluid from patients with rheumatoid arthritis.

    PubMed

    Matsuki, Fumichika; Saegusa, Jun; Nishimura, Keisuke; Miura, Yasushi; Kurosaka, Masahiro; Kumagai, Shunichi; Morinobu, Akio

    2014-07-01

    Increased numbers of regulatory T (Treg) cells are found in synovial fluid from patients with rheumatoid arthritis (RASF) compared with peripheral blood. However, Treg cells in RASF have been shown to have a decreased capacity to suppress T cells. Here we phenotypically classified CD4+ T cells in RASF into six subsets based on the expression of CD45RA, CCR7, CD27 and CD28, and demonstrated that the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in synovial fluid compared with peripheral blood. In addition, the proportion of Foxp3+ Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Furthermore, most of the Foxp3+ Treg cells in RASF were non-suppressive CD45RA-Foxp3(low) non-Treg cells, and the frequency of the non-Treg cells in the CCR7-CD45RA-CD27+CD28+ TEM subset was significantly increased in RASF. Our findings suggest that the pro-inflammatory environment in RA joints may induce the increase of CD45RA-Foxp3(low) non-Treg cells in synovial fluid.

  8. Power of national economy, disease control and employment status in patients with RA-an analytical multi-site ecological study.

    PubMed

    Pieringer, Herwig; Puchner, Rudolf; Pohanka, Erich; Danninger, Kathrin

    2016-02-01

    In rheumatology, sufficient disease control is a central part of the treatment concept. However, modern treatment strategies are associated with a substantial economic burden for health care systems. Ecological studies offer the unique opportunity to analyse differences between groups as well as group level effects. In the present analytical multi-site ecological study, we investigated whether more powerful national economies as measured by the gross domestic product per capita (GDPpc) are associated with better disease control in RA patients as measured by the disease activity score 28 (DAS28). We used aggregated data on RA patients from the recently published COMORA study as well as the World Health Organization database. There was a strong negative correlation between DAS28 and GDPpc (r = -0.815; p = 0.0002). Adjustment for sex, smoking status, disease duration or current employment status did not significantly change this association. There was a strong, negative correlation between DAS28 and age (r = -0.870; p < 0.001) and a strong, positive correlation between GDPpc and age (r = 0.737; p = 0.002). Adjustment for age reduced the regression coefficient (DAS28/GDPpc) to -0.000018 (p = 0.054). There was a negative correlation between DAS28 and current employment status (r = -0.642; p = 0.008) and a positive correlation between GDPpc and employment status (r = 0.722; p = 0.002). In conclusion, there is evidence of an association between disease control and GDPpc. This association is alleviated after adjustment for age. Of note, in countries with higher GDPpc, a higher proportion of RA patients are currently employed. This is true despite the fact that RA patients in countries with higher GDPpc are also older.

  9. Ra5G, a homologue of Ra5 in giant ragweed pollen: isolation, HLA-DR-associated activity and amino acid sequence.

    PubMed

    Goodfriend, L; Choudhury, A M; Klapper, D G; Coulter, K M; Dorval, G; Del Carpio, J; Osterland, C K

    1985-08-01

    Recent studies [Marsh et al. (1982) J. exp. Med. 155, 1439-1451; Coulter (1983) M.Sc. thesis, McGill University, Montreal, Canada; Coulter et al. (1983) in Genetic and Environmental Factors in Clinical Allergy (Edited by Marsh D.G., Blumenthal M.N. and Santilli J., Jr), University of Minnesota Press, Minneapolis, MN] have shown a highly significant association between HLA-Dw2/DR2 and host sensitivity to the 5000-D, 4-disulfide bonded protein Ra5S of short ragweed pollen. To extend these findings, we isolated Ra5G, an Ra5S-like protein, from giant ragweed pollen by gel and ion-exchange chromatography. The protein was homogeneous by polyacrylamide gel electrophoresis (pH 4.3), reverse-phase high-performance liquid chromatography, and antigenic assays. Its mol. wt and amino acid composition (including 8 half-cystine residues) were closely similar to Ra5S, but the two proteins had little or no antigenic or allergenic cross-reactivity. In a study of 200 ragweed-sensitive individuals, host sensitivity simultaneously to Ra5G and Ra5S was significantly associated with the DR2 allele. The amino acid sequence of Ra5G was determined and showed close homology with Ra5S. The potential function of a highly homologous decapeptidyl sequence stretch is discussed in relation to Ir gene control of immune response to the 2 proteins.

  10. GLP1-RA Add-on Therapy in Patients with Type 2 Diabetes Currently on a Bolus Containing Insulin Regimen.

    PubMed

    Davies, Marie L; Pham, David Q; Drab, Scott R

    2016-08-01

    Adding glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin regimens has become a guideline-recommended treatment option for uncontrolled type 2 diabetes. However, limited data exist to support the use of GLP-1 RAs with insulin regimens, including bolus insulin in patients with type 2 diabetes. The primary objectives of this review were to identify if the combination of a GLP-1 RA and an insulin regimen containing bolus insulin resulted in improvements in HbA1c , weight loss, reduction in insulin doses, and to evaluate the side effect profile of this combination in terms of nausea and hypoglycemia risk. Eight studies using exenatide twice/day, liraglutide, and dulaglutide were reviewed ranging in average duration of follow-up from 3 to 15 months. Seven studies showed that addition of a GLP-1 RA was associated with significant HbA1c reductions ranging from 0.4% to 1.64% from baseline to follow-up. Patients in all eight studies had significant weight loss in the GLP-1 RA arm from baseline to follow-up ranging from 0.87 to 10.2 kg. In all the studies, total daily bolus insulin doses decreased 25-67% from baseline to follow-up. In some studies, a portion of patients were able to discontinue bolus insulin all together after initiation of a GLP-1 RA. In addition, in two randomized trials included in the review, the GLP-1 RA arm showed significant improvement in HbA1c and weight compared with the control group who received basal/bolus regimens. Nausea was identified in 7-42% of participants using GLP-1 RAs with insulin. Data support the use of GLP-1 RAs added to insulin regimens already containing bolus insulin for glycemic control, weight loss, and reduction or discontinuation of bolus insulin.

  11. Effects of a new heterocyclic glucocorticoid, deflazacort (DFC), on the functions of lymphocytes from patients with rheumatoid arthritis (RA).

    PubMed

    Scudeletti, M; Piccardo, C; Piovano, P; Imbimbo, B; Indiveri, F

    1987-01-01

    Deflazacort (DFC) is a new glucocorticoid which, when compared with prednisone (PDN), has similar anti-inflammatory actions, but lacks several unwanted side effects on mineral and carbohydrate metabolism. DFC is more efficient than PDN in inducing immunomodulatory effects. This study concerns twelve patients with classical RA who required corticosteroid therapy because of the ineffectiveness of other drugs. Six patients received 12 mg/day of PDN from day 1 to day 21 and 15 mg/day of DFC from day 29 to day 50. The second group of six patients received DFC initially followed by the PDN dosing regimen. At various times (4, 8, 24, 48 and 72 h) after the first administration of steroid, and 7, 14 and 21 days after the beginning of the treatment with PDN or DFC the following tests were performed the phenotype of T lymphocytes isolated from peripheral blood; the evaluation of the expression of HLA Class 2 antigens by PHA primed T cells; and the analysis of cell behavior in mixed lymphocyte reactions. The data reported in this paper show that the oral administration of DFC to patients with RA affects the in vitro behavior of their lymphocytes. This immunomodulatory effect of DFC concerns both the phenotype and function of RA lymphocytes. Moreover it differs in both intensity and kinetic characteristics from the immunomodulating effect observed with PDN (control).

  12. Expression of interferon-gamma (IFN-δ), IL-10, IL-12 and transforming growth factor-beta (TGF-β) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA)

    PubMed Central

    BUCHT, A.; LARSSON, P.; WEISBROT, L.; THORNE, C.; PISA, P.; SMEDEGÅRD, G.; KEYSTONE, E C; GRÖNBERG, A.

    1996-01-01

    The expression of immunoregulatory cytokines was investigated in freshly isolated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with RA, using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN-γ, TGF-β, IL-10 and IL-12 (p40) transcripts were detected in SFMC of patients with early disease (<1 year duration) as well as in patients with long standing arthritis (>1 year). The expression of IFN-γ, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from healthy control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with levels found in serum from RA patients and control individuals. High levels of TGF-β mRNA were found in SFMC, but a significantly decreased TGF-β/β2-microglobulin (β2-M) ratio was found compared with PBMC from both patients and control individuals. IL-4 mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBMC did not differ from control PBMC, with the exception of a decreased TGF-β/β2-M ratio in RA patients with early disease. Our findings of IFN-7 mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune response. The presence of TGF-β and IL-10 mRNA indicates that immunosuppressive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immune activation. PMID:8608632

  13. TLRs, future potential therapeutic targets for RA.

    PubMed

    Elshabrawy, Hatem A; Essani, Abdul E; Szekanecz, Zoltán; Fox, David A; Shahrara, Shiva

    2017-02-01

    Toll like receptors (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients.

  14. In Patients with Established RA, Positive Effects of a Randomised Three Month WBV Therapy Intervention on Functional Ability, Bone Mineral Density and Fatigue Are Sustained for up to Six Months

    PubMed Central

    Prioreschi, Alessandra; Makda, Mohamed A.; Tikly, Mohammed; McVeigh, Joanne A.

    2016-01-01

    Functional ability is often impaired for people with rheumatoid arthritis (RA), rendering these patients highly sedentary. Additionally, patients with RA often take medication known to negatively affect bone mass. Thus improving functional ability and bone health in this group of patients is important. The aim of this study was to investigate the effects of whole body vibration (WBV) therapy in patients with stable, established RA. Thirty one females with RA were randomly assigned to a control group (CON, n = 15) who continued with their normal activities or a WBV group (n = 16) who underwent a three month WBV therapy intervention, consisting of 15 minutes of intermittent vibration, performed twice per week. Patients were assessed at baseline, three months, and three months post intervention for functional ability using the modified Health Assessment Questionnaire; for RA disease activity using the Clinical Disease Activity Index, for quality of life using self-report fatigue and pain scores; for physical activity profiles using accelerometry, and for BMD and body composition using DXA. Patients in both groups were matched for all variables at baseline. After the intervention period, functional ability was significantly improved in the WBV group (1.22(0.19) to 0.92(0.19), p = 0.02). Hip BMD was significantly reduced in the CON group (0.97(0.05) to 0.84(0.05) g.cm-2, p = 0.01), while no decreases were seen in the WBV group (1.01(0.05) to 0.94(0.05) g.cm-2, p = 0.50). Despite no change in RA disease activity in either group at either follow up, fatigue levels were improved in the WBV group (4.4(0.63) to 1.1(0.65), yet remained unchanged in the CON group at both follow ups (p = 0.01). Ten minute bouts of light to moderate physical activity were significantly reduced in the CON group after the intervention (2.8(0.61) to 1.8(0.64) bouts per day, p = 0.01), and were preserved in the WBV group (3.1(0.59) to 3.0(0.61) bouts per day, p = 0.70). Intermittent WBV shows

  15. Activity ratios of (234)U/(238)U and (226)Ra/(228)Ra for transport mechanisms of elevated uranium in alluvial aquifers of groundwater in south-western (SW) Punjab, India.

    PubMed

    Kumar, A; Karpe, R K; Rout, S; Gautam, Y P; Mishra, M K; Ravi, P M; Tripathi, R M

    2016-01-01

    The concentrations of total dissolved uranium (U), its isotopic composition ((234)U, (235)U, (238)U) and two long lived Ra isotopes ((226)Ra and (228)Ra) in alluvial aquifers of groundwater were determined to investigate the groundwater flow pattern in the south-western (SW) Punjab, India. Particular attention was given to the spatial variability of activity ratios (ARs) of (234)U/(238)U and (226)Ra/(228)Ra to predict the possible sources and supply process of U into the water from the solid phase. The measured groundwater (234)U/(238)U ARs were ∼1 or >1 in the shallow zone (depth < 30 m) with high U concentration and <1 in the deeper zone (depth > 30 m) with relatively low U concentration. The simultaneous elevated U concentration and (234)U/(238)U ARs in waters were possibly due to differences in imprints of rock-water interactions under hydrologic conditions. However, (234)U/(238)U ARs < 1 clearly indicate the lack of recharge from surface water to groundwater leading to (234)U deficit in groundwater. This deficit might be also attributed to alpha recoil processes under strong dissolution. Overall, the decreasing pattern of (234)U/(238)U ARs observed from SE to SW or NW ward clearly indicates a groundwater flow paths from SE to SW/NW. Similarly, (226)Ra/(238)U ARs < 1 for all water samples reflect that the precursor (238)U is fairly mobile relative to (226)Ra. This might be due to unusually high amount of (238)U in groundwaters and subsequently the different geochemistry of the two isotopes. On the other hand, (226)Ra/(228)Ra ARs in groundwaters varied widely and observed about 50-300 times higher than (238)U/(232)Th ARs in granitic rocks or soils. Such elevation in ARs might be attributed to different dissolution properties of their parents during water-rock interactions or lattice damage during decay or local enrichments of uranium in the aquifers.

  16. Factors that influence fatigue status in patients with severe rheumatoid arthritis (RA) and good disease outcome following 6 months of TNF inhibitor therapy: a comparative analysis.

    PubMed

    Minnock, Patricia; Veale, Douglas J; Bresnihan, Barry; FitzGerald, Oliver; McKee, Gabrielle

    2015-11-01

    The objective of the present study is to determine the factors associated with persistent fatigue in patients with severe rheumatoid arthritis (RA) and good disease response to 6 months of tumour necrosis factor inhibitor therapy. Eligible patients with either persistent (PF) or no fatigue (NF) were compared. Using validated questionnaires and bivariate analysis, this cross-sectional survey explored if clinical characteristics, pain, self-efficacy, sleep and mood/depression differed between groups. Patients with PF (PF; NF) (n = 28; 28) reported significantly more overall pain (11.3 ± 9.4 (0-33); 6.9 ± 8.9 (0-33)), more recent and current pain intensity (41.4 ± 26.6 (0-80) 24.4 ± 26.6 (0-100) and depression (11.8 ± 7.5 (1-35); 8.2 ± 6.6 (0-26)), than the NF group. There was no significant difference between groups in self-efficacy and both groups experienced poor sleep quality (Pittsburgh Sleep Quality Index >5). Despite having good disease response, the PF group had significantly higher rheumatoid factor incidence, disease activity score-28, early morning stiffness duration and lower incidence of ever-failing disease-modifying anti-rheumatic drugs than the NF group. These findings enhance the fatigue literature in patients with RA prescribed tumour necrosis factor (TNF) inhibition therapy, identifying the potentially modifiable factors of pain and depression, previously demonstrated to be strongly associated with fatigue in non-biologic populations. In addition, this study highlights the association between persistent fatigue and an on-going state of low disease activity. This infers that more judicious disease management could minimise the symptom burden of pain and depression and consequentially fatigue.

  17. Identification and functional characterization of T cells reactive to citrullinated-vimentin in HLA-DRB1*0401 humanized mice and RA patients

    PubMed Central

    Snir, Omri; Rieck, Mary; Gebe, John A.; Yue, Betty B.; Rawlings, Crystal A.; Nepom, Gerald; Malmström, Vivianne; Buckner, Jane H.

    2011-01-01

    Objective Antibodies towards the citrullinated form of the synovial antigen vimentin are specific for rheumatoid arthritis (RA) and associated with HLADRB1*0401. This suggests that T cells specific for peptides derived from citrullinated-vimentin presented in the context of HLA-DRB1*0401 may contribute to the etiopathogenesis of RA. Here, we aimed to identify immunodominant epitopes from citrullinated-vimentin presented by HLADRB1*0401 and characterize the resulting T cell responses. Methods We first predicted an HLA-binding T cell epitope from citrullinated vimentin based on the binding motif of DRB1*0401, and then confirmed its affinity. An MHC class-II tetramer loaded with cit-vim59-78 was constructed and used to screen for specific T cells in DRB1*0401 transgenic mice, RA patients and healthy controls. Additionally, the cytokine output following cit-vim59-78 challenge was analyzed in patients and healthy subjects by multicolor flow cytometry and luminex-based analysis. Results The citrullinated form of vim59-78 bound to HLA-DRB1*0401 while the native version could not. Subsequently, cit-vim59-78-specific T cells were detected in immunized mice and in the periphery of both HLA-DR*0401 healthy controls and RA subjects, using MHC class-II tetramers, CD154 upregulation and intracellular cytokine measurements. Cell culture supernatants demonstrated an enhanced production of cytokines, most prominent of which was IFNγ from RA-derived cells in response to cit-vim59-78 in comparison to healthy controls. Conclusions Here, we describe a posttranslational modification of an RA candidate autoantigen towards which DRB1*0401-restricted, T cells can be found in both RA patients and healthy controls, but for which a proinflammatory response is uniquely found among subjects with RA. PMID:21567378

  18. Efficacy and safety of subcutaneous tocilizumab versus intravenous tocilizumab in combination with traditional DMARDs in patients with RA at week 97 (SUMMACTA)

    PubMed Central

    Burmester, Gerd R; Rubbert-Roth, Andrea; Cantagrel, Alain; Hall, Stephen; Leszczynski, Piotr; Feldman, Daniel; Rangaraj, Madura J; Roane, Georgia; Ludivico, Charles; Bao, Min; Rowell, Lucy; Davies, Claire; Mysler, Eduardo F

    2016-01-01

    Objectives To evaluate the long-term efficacy and safety of subcutaneous (SC) tocilizumab (TCZ) versus intravenous (IV) TCZ, including switching formulations, in patients with rheumatoid arthritis (RA) and inadequate response to disease-modifying antirheumatic drugs (DMARDs). Methods Patients (n=1262) were randomised 1:1 to receive TCZ-SC 162 mg weekly (qw)+placebo-IV every four weeks (q4w) or TCZ-IV 8 mg/kg q4w+placebo-SC qw in combination with DMARD(s). After a 24-week double-blind period, patients receiving TCZ-SC were re-randomised 11:1 to TCZ-SC (n=521) or TCZ-IV (TCZ-SC–IV, n=48), and patients receiving TCZ-IV were re-randomised 2:1 to TCZ-IV (n=372) or TCZ-SC (TCZ-IV–SC; n=186). Maintenance of clinical responses and safety through week 97 were assessed. Results The proportions of patients who achieved American College of Rheumatology (ACR)20/50/70 responses, Disease Activity Score in 28 joints remission and improvement from baseline in Health Assessment Questionnaire Disability Index ≥0.3 were sustained through week 97 and comparable across arms. TCZ-SC had a comparable safety profile to TCZ-IV through week 97, except that injection site reactions (ISRs) were more common with TCZ-SC. Safety profiles in patients who switched were similar to those in patients who received continuous TCZ-SC or TCZ-IV treatment. The proportion of patients who developed anti-TCZ antibodies remained low across treatment arms. No association between anti-TCZ antibody development and clinical response or adverse events was observed. Conclusions The long-term efficacy and safety of TCZ-SC was maintained and comparable to that of TCZ-IV, except for ISRs. Profiles in patients who switched formulations were comparable to those in patients who received TCZ-IV or TCZ-SC. TCZ-SC provides additional treatment options for patients with RA. Trial registration number NCT01194414. PMID:26056119

  19. Draft genome sequence of Xanthomonas axonopodis pv. glycines 8ra possessing transcription activator-like effectors used for genetic engineering.

    PubMed

    Lee, Ju-Hoon; Shin, Hakdong; Park, Hye-Jee; Ryu, Sangryeol; Han, Sang-Wook

    2014-06-10

    Xanthomonas axonopodis pv. glycines 8ra is a causal agent of bacterial pustule disease in soybean. This bacterium possesses transcription activator-like (TAL) effectors which are useful for genetic/protein engineering applications in higher organisms including plants and humans. Here, we report that the draft genome sequence consists of 5,337,885-bp double-stranded DNA encoding 4674 open reading frames (ORFs) in 13 different contigs. This genome sequence would be useful in applications of TAL effectors in genetic engineering and in elucidating virulence factors against plants.

  20. Identification of a HERV-K env surface peptide highly recognized in RA patients: A cross-sectional case-control study.

    PubMed

    Mameli, G; Erre, G L; Caggiu, E; Mura, S; Cossu, D; Bo, Marco; Cadoni, M L; Piras, A; Mundula, N; Colombo, E; Buscetta, G; Passiu, G; Sechi, L A

    2017-03-21

    Endogenous Retroviruses (HERV) are believed to be pathogenic in several autoimmune diseases. Among them, HERV-K viruses have been recently reported to be involved in the pathogenesis of rheumatoid arthritis (RA). In this study we have explored the role of humoral immune response against HERV-K as a potential pathogenetic mechanism in RA. Four different peptides from the extracellular portion of the env protein of HERV-K (env-su 19-37 , env-su 109-26 , env-su 164-186 , env-su 209-226 ) were selected by bioinformatic analysis on the basis of their putative immunogenicity. Indirect ELISA was then carried out to quantify antibodies against those peptides on blood samples of seventy consecutive RA patients and seventy-one healthy controls (HC). Differences between the two groups were analysed using the Mann-Whitney test. Potential correlations between RA laboratory, clinical descriptors and IgGs levels were explored by bivariate regression analysis. Serum autoantibodies against one out of four tested peptides of HERV-K (env-su 19-37 ) were significantly higher in RA than in HC (19% vs 3%, p=0.0025). Subgroup analysis showed no association between anti-HERV-K peptide humoral response and clinical, serological and clinimetric RA disease descriptors. Serum from RA patients in our series significantly reacted against HERV-K env-su 19-37 peptide in comparison to the general population suggesting a role for the HERV-K related, secondary antigenic driven immune response in the pathogenesis of RA. Further studies are needed to confirm these results and to explore the role of this HERV-K surface peptide as a potential therapeutic target. This article is protected by copyright. All rights reserved.

  1. Activation of CpxRA in Haemophilus ducreyi primarily inhibits the expression of its targets, including major virulence determinants.

    PubMed

    Gangaiah, Dharanesh; Zhang, Xinjun; Fortney, Kate R; Baker, Beth; Liu, Yunlong; Munson, Robert S; Spinola, Stanley M

    2013-08-01

    Haemophilus ducreyi causes chancroid, a genital ulcer disease that facilitates the transmission of human immunodeficiency virus type 1. In humans, H. ducreyi is surrounded by phagocytes and must adapt to a hostile environment to survive. To sense and respond to environmental cues, bacteria frequently use two-component signal transduction (2CST) systems. The only obvious 2CST system in H. ducreyi is CpxRA; CpxR is a response regulator, and CpxA is a sensor kinase. Previous studies by Hansen and coworkers showed that CpxR directly represses the expression of dsrA, the lspB-lspA2 operon, and the flp operon, which are required for virulence in humans. They further showed that CpxA functions predominantly as a phosphatase in vitro to maintain the expression of virulence determinants. Since a cpxA mutant is avirulent while a cpxR mutant is fully virulent in humans, CpxA also likely functions predominantly as a phosphatase in vivo. To better understand the role of H. ducreyi CpxRA in controlling virulence determinants, here we defined genes potentially regulated by CpxRA by using RNA-Seq. Activation of CpxR by deletion of cpxA repressed nearly 70% of its targets, including seven established virulence determinants. Inactivation of CpxR by deletion of cpxR differentially regulated few genes and increased the expression of one virulence determinant. We identified a CpxR binding motif that was enriched in downregulated but not upregulated targets. These data reinforce the hypothesis that CpxA phosphatase activity plays a critical role in controlling H. ducreyi virulence in vivo. Characterization of the downregulated genes may offer new insights into pathogenesis.

  2. 226Ra and 228Ra in Iowa drinking water.

    PubMed

    Kriege, L B; Hahne, R M

    1982-10-01

    The University Hygienic Laboratory has been performing radiochemical analyses on drinking water in the state of Iowa for over 20 yr. Approximately one half of the 1250 community water supplies that exist in Iowa have been sampled roughly once every 3 yr for the past decade. Originally, raw and finished waters that showed a gross alpha activity of greater than or equal to 3.0 pCi/L were analyzed for 226Ra, but starting in July 1976, finished waters were analyzed for both 226Ra and 228Ra if the gross alpha activity was greater than or equal to 2.0 pCi/L. As of 10 June 1981, 604 community water supplies had submitted composited samples that have been analyzed for gross alpha, 226Ra, and 228Ra concentrations in compliance with the federal Safe Drinking Water Act (Public Law 93-523). Approximately 10% of these supplies were found to exceed the EPA-established maximum contaminant level (MCL) for 226Ra plus 228Ra of 5 pCi/L. The results revealed, consistent with several other investigators (Mc81; Mi80; Mic80), that some supplies had higher concentrations of 228Ra than of 226Ra. It was also concluded, in agreement with McCurdy and Mellor (Mc81), that some ground water samples cannot be accurately measured for gross alpha activity due to their high dissolved solids content.

  3. Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis

    PubMed Central

    Crotti, T; Smith, M; Weedon, H; Ahern, M; Findlay, D; Kraan, M; Tak, P; Haynes, D

    2002-01-01

    Objectives: To compare receptor activator of NF-κB ligand (RANKL) production in the synovial tissue from patients with active rheumatoid arthritis (RA), inactive RA, spondyloarthropathies (SpA), osteoarthritis, and from normal subjects. In addition, to establish the cell lineages expressing RANKL in these tissues. Methods: Immunohistological analysis of frozen synovial tissue biopsy specimens was performed using a monoclonal antibody (mAb) to detect RANKL. Sections were evaluated by computer assisted image analysis and semiquantitative analysis to compare RANKL expression between groups. Dual and sequential labelling with mAb RANKL and cell lineage specific monoclonal antibodies were used to determine the types of cells expressing RANKL. Results: Higher levels of RANKL were expressed in tissues from patients with active RA and SpA than in tissues from patients with inactive RA, osteoarthritis, and from normal subjects. RANKL protein was associated with CD3 antigen-positive lymphocytes and some macrophages. RANKL was predominantly associated with activated, memory T cells (CD45Ro positive cells) in patients with active RA and spondyloarthropathy (SpA). Conclusions: The highest levels of RANKL were detected in patients with RA with active synovitis and in some patients with SpA. An increase in RANKL in the inflamed joint of patients with RA, produced by infiltrating activated T cells and macrophages, is likely to be an important cause of joint erosions in RA. PMID:12429533

  4. Patients with Multidrug-Resistant Tuberculosis Display Impaired Th1 Responses and Enhanced Regulatory T-Cell Levels in Response to an Outbreak of Multidrug-Resistant Mycobacterium tuberculosis M and Ra Strains▿

    PubMed Central

    Geffner, Laura; Yokobori, Noemí; Basile, Juan; Schierloh, Pablo; Balboa, Luciana; Romero, María Mercedes; Ritacco, Viviana; Vescovo, Marisa; González Montaner, Pablo; Lopez, Beatriz; Barrera, Lucía; Alemán, Mercedes; Abatte, Eduardo; Sasiain, María C.; de la Barrera, Silvia

    2009-01-01

    In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-γ) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4+ and CD8+ T cells from MDR- and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-γ expression and CTL activity in TB patients, with M- and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles. PMID:19720756

  5. 68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer.

    PubMed

    Ahmadzadehfar, Hojjat; Schlenkhoff, Carl Diedrich; Rogenhofer, Sebastian; Yordanova, Anna; Essler, Markus

    2016-09-01

    A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases.

  6. A unique drug distribution process for radium Ra 223 dichloride injection and its implication for product quality, patient privacy, and delineation of professional responsibilities.

    PubMed

    Dansereau, Raymond N

    2014-11-01

    On May 15, 2013, Bayer Healthcare Pharmaceuticals announced that it had received marketing approval for the therapeutic radioactive medication radium Ra 223 dichloride injection (Xofigo; Ra 223). The product acquisition and distribution process for hospital-based nuclear pharmacies and nuclear medicine services is unlike any other. The product is distributed as a low-risk compounded sterile preparation through a single compounding nuclear pharmacy located in Denver, Colorado, pursuant to a prescription. This model for drug distribution and delivery to the user institution has implications for product quality, patient privacy, and delineation of professional responsibilities.

  7. The activity ratio of 228Th to 228Ra in bone tissue of recently deceased humans: a new dating method in forensic examinations.

    PubMed

    Zinka, Bettina; Kandlbinder, Robert; Schupfner, Robert; Haas, Gerald; Wolfbeis, Otto S; Graw, Matthias

    2012-01-01

    Reliable determination of time since death in human skeletons or single bones often is limited by methodically difficulties. Determination of the specific activity ratio of natural radionuclides, in particular of 232Th (Thorium), 228Th and 228Ra (Radium) seems to be a new appropriate method to calculate the post mortem interval. These radionuclides are incorporated by any human being, mainly from food. So with an individual's death the uptake of radionuclides ends. But the decay of 232Th produces 228Ra and 228Th due to its decay series, whereas 228Th is continuously built up in the human's bones. Thus, it can be concluded that in all deceased humans at different times after death different activity ratios of 228Th to 228Ra will develop in bone. According to this fact it should be possible to calculate time since death of an individual by first analysing the specific activities of 228Th and 228Ra in bones of deceased and then determining the 228Th/228Ra activity ratio, which can be assigned to a certain post-mortem interval.

  8. Pharmacokinetic-pharmacodynamic modeling of fostamatinib efficacy on ACR20 to support dose selection in patients with rheumatoid arthritis (RA).

    PubMed

    Maringwa, John; Kågedal, Matts; Hamrén, Ulrika Wählby; Martin, Paul; Cox, Eugène; Hamrén, Bengt

    2015-03-01

    R788 (fostamatinib) is an oral prodrug that is rapidly converted into a relatively selective spleen tyrosine kinase (SYK) inhibitor R406, evaluated for the treatment of rheumatoid arthritis (RA). This analysis aimed at developing a pharmacodynamic model for efficacy using pooled ACR20 data from two phase II studies in patients with rheumatoid arthritis (TASKi1 and TASKi2), describing the effect of fostamatinib as a function of fostamatinib exposure (dose, R406 plasma concentration) and other explanatory variables. The exposure-response relationship of fostamatinib was implemented into a continuous time Markov model describing the time course of transition probabilities between the three possible states of ACR20 non-responder, responder, and dropout at each visit. The probability of transition to the ACR20 response state was linearly (at the rate constant level) related to average R406 plasma concentrations and the onset of this drug effect was fast. Further, increases of fostamatinib dose resulted in increased dropout and subsequent loss of efficacy. This analysis provided an increased understanding of the exposure-response relationship, and provided support for fostamatinib 100 mg BID an appropriate dose regimen for further clinical evaluation.

  9. Regulation of TAK1 activation by epigallocatechin-3-gallate in RA synovial fibroblasts: suppression of K63-linked autoubiquitination of TRAF6

    PubMed Central

    Singh, Anil K.; Umar, Sadiq; Riegsecker, Sharayah; Chourasia, Mukesh; Ahmed, Salahuddin

    2017-01-01

    Background/Purpose Transforming growth factor β activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), or toll-like receptor signaling. We examined the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA). Methods The effect of TAK1, IRAK-1, or TRAF6 inhibition was evaluated in IL-1β-induced human RA synovial fibroblasts (RA-FLS). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RA-FLS. The efficacy of epigallocatechin-3-gallate (EGCG), a potent anti-inflammatory molecule, in regulating these processes in RA-FLS was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were validated using a rat adjuvant-induced arthritis (AIA) model. Results Inhibition of TAK1, not IRAK-1 or TRAF6, completely abrogates IL-1β-induced IL-6 and IL-8 synthesis in RA-FLS. EGCG inhibits TAK1 phosphorylation at Thr184/187 and occupies the C174 position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibits K63-autoubiquitination of TRAF6, a post-translational modification essential for TAK1 autophosphorylation, by forming stable hydrogen-bond at the K124 position on TRAF6. Furthermore, EGCG enhances associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses on the joint homogenates from rat AIA show a significant increase in K48-linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to the naïve group. Administration of EGCG (50 mg/kg/day) for 10 days ameliorates AIA by reducing TAK1 phosphorylation and K48 polyubiquitination. Conclusions This study provides rationale for targeting TAK1 for RA treatment by EGCG. PMID:26473505

  10. Rapid Memory T-cell Reconstitution Recapitulating CD45RA-depleted Haploidentical Transplant Graft Content in Patients with Hematologic Malignancies

    PubMed Central

    Triplett, Brandon M; Shook, David R; Eldridge, Paul; Li, Ying; Kang, Guolian; Dallas, Mari; Hartford, Christine; Srinivasan, Ashok; Chan, Wing Keung; Suwannasaen, Duangchan; Inaba, Hiroto; Pui, Ching-Hon; Leung, Wing

    2015-01-01

    T-cell depletion of an HLA-haploidentical graft is often used to prevent graft-vs.-host disease (GvHD), but the procedure may lead to increased graft failure, relapse, and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GvHD through removal of naïve T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA– memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without total body irradiation or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post-transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vβ spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GvHD despite infusion of a median of >100 million per kilogram haploidentical T cells. PMID:25665048

  11. Evaluation of differences in HLA-DR4 gene and its subtypes prevalence among healthy people and RA patients in Isfahan province population

    PubMed Central

    Salesi, Mansour; Boroujeni, Golshan Taghipour; Salehi, Mansoor; Farzamnia, Somaieh

    2016-01-01

    Background: There are a lot of evidences showing that genetic play an important role in RA disease. Inheritance of some subgroups of HLA-DR4 gene increases the propensity to RA disease. In this paper, the impact of HLA-DR4 gene and its subtypes or subgroups, be consistence on RA patient who lived in Isfahan province, has been evaluated. Materials and Methods: In this survey, two groups of people (100 patients in case group and 100 normal persons in control group) have been selected. These two groups were similar in age and gender. Statistical population has been considered among people who visited Al Zahra rheumatology clinic. The participants were from Isfahan province and accepted to participate to the study voluntarily. The prevalence of HLA-DR4 and its 0401-0404 subtypes were evaluated between two groups; DNA was extracted from blood samples and studied using PCR SSCP method. Results: It was found that 35% of RA patients had HLA-DR4 gene, of which 14 persons had 0401, 10 persons had 0404, and 11 persons had other subtypes, whereas 30 people in control group had HLA-DR4 gene, of which 10 people had 0401, 20 people had 0404, and nobody had other subtypes. Conclusion: The observed differences between prevalence of HLA-DR4 gene between the case and control group were not statistically significant (P = 0.45; OR = 1.256; 95% CI = 0.69-2.27), but a relation was between HLA-DR4 0404 subtypes and RA (P = 0.02; OR = 0.44; 95% CI = 0.196-0.992). PMID:26962513

  12. Activity concentrations of ²²⁶Ra, ²³²Th and ⁴⁰K in brands of fertilisers used in Nigeria.

    PubMed

    Jibiri, N N; Fasae, K P

    2012-01-01

    The activity concentration of naturally occurring radionuclides ⁴⁰K, ²²⁶Ra and ²³²Th have been measured in different brands of fertiliser samples sold to farmers in retail markets in six commercial cities in southwestern Nigeria. Gamma ray spectroscopy was employed in the measurements of these radionuclides. The results of measurements showed that the average activity concentration of ⁴⁰K in the nitrogen, phosphorus and potassium fertilisers across the cities varied from 3972.0 ± 416.9 to 5089.3 ± 111.3 Bq kg⁻¹, 9.9 ± 7.3 to 450.6 ± 14.3 Bq kg⁻¹ for ²²⁶Ra, while for ²³²Th it varied from less than lower limit of detection to 15.1 ± 2.8 Bq kg⁻¹. The activity concentrations of ⁴⁰K, ²²⁶Ra and ²³²Th in single super phosphate (SSP) fertilisers and phosphate rocks were also determined. However, high activity concentrations of ²²⁶Ra were obtained in the SSP fertiliser and phosphate rocks and in particular, two brands of fertilisers from ITL/TAK and F & C companies. The values of the activity concentration of the radionuclides in the brands of fertilisers used in Nigeria are within the range of values reported in several other countries except ⁴⁰K.

  13. Vectra DA for the objective measurement of disease activity in patients with rheumatoid arthritis.

    PubMed

    Segurado, O G; Sasso, E H

    2014-01-01

    Quantitative and regular assessment of disease activity in rheumatoid arthritis (RA) is required to achieve treatment targets such as remission and to optimize clinical outcomes. To assess inflammation accurately, predict joint damage and monitor treatment response, a measure of disease activity in RA should reflect the pathological processes resulting in irreversible joint damage and functional disability. The Vectra DA blood test is an objective measure of disease activity for patients with RA. Vectra DA provides an accurate, reproducible score on a scale of 1 to 100 based on the concentrations of 12 biomarkers that reflect the pathophysiologic diversity of RA. The analytical validity, clinical validity, and clinical utility of Vectra DA have been evaluated for patients with RA in registries and prospective and retrospective clinical studies. As a biomarker-based instrument for assessing disease activity in RA, the Vectra DA test can help monitor therapeutic response to methotrexate and biologic agents and assess clinically challenging situations, such as when clinical measures are confounded by non-inflammatory pain from fibromyalgia. Vectra DA scores correlate with imaging of joint inflammation and are predictive for radiographic progression, with high Vectra DA scores being associated with more frequent and severe progression and low scores being predictive for non-progression. In summary, the Vectra DA score is an objective measure of RA disease activity that quantifies inflammatory status. By predicting risk for joint damage more effectively than conventional clinical and laboratory measures, it has the potential to complement these measures and optimise clinical decision making.

  14. Plant/soil concentration ratios of 226Ra for contrasting sites around an active U mine-mill.

    PubMed

    Ibrahim, S A; Whicker, F W

    1988-12-01

    Concentrations of 226Ra were determined in native vegetation and underlying substrate (soil and tailings) at various sites around a conventional open-pit, acid leach U production operation in Wyoming. Plant/soil concentration ratios (CRs) for 226Ra were estimated for various sites, including weathered tailings; a tailings impoundment shoreline; downwind from exposed tailings; a mine overburden reclamation area; and several background locations. Radium-226 concentrations for vegetation and substrate and CR values from the perturbed sites were elevated above background. The highest vegetation concentration (1.3 Bq g-1) was found in a grass which had invaded exposed, weathered tailings. Levels of 226Ra in soil and vegetation and CR values decreased with distance from the tailings impoundment edge. CR values varied significantly among sites, but few differences were found between plant species groups. The observed CR values ranged from 0.07 at the background and reclamation areas to 0.4 downwind from the tailings area. Average CR values for plants growing on exposed tailings and within one meter from the impoundment edge were 0.15 and 0.3, respectively. CR values of 226Ra for plants on tailings substrates were comparatively low in contrast to other radionuclides in the U chain. We speculate that in the case of sulfuric acid leached tailings-derived material, 226Ra is sequestered as sulfate, which is highly insoluble relative to the sulfates of the other elements (e.g., U and Th) resulting in reduced availability for plant uptake.

  15. Determination of ²²⁶Ra, ²²⁸Ra and ²¹⁰Pb in NORM products from oil and gas exploration: problems in activity underestimation due to the presence of metals and self-absorption of photons.

    PubMed

    Landsberger, S; Brabec, C; Canion, B; Hashem, J; Lu, C; Millsap, D; George, G

    2013-11-01

    Typical calibration of solid environmental samples for the determination of (226)Ra, (228)Ra and (210)Pb entails the use of standard reference materials which have a very similar matrix. However, TENORM samples from the oil and gas exploration contain unusually high amounts of calcium, strontium and barium which can severely attenuate the photons of (210)Pb and (226)Ra with their characteristic 46.1 keV and 186.2 keV gamma-rays, respectively and to some extent (228)Ra with the characteristic gamma-rays of 911.2 keV and 969.0 keV. We used neutron activation analysis to evaluate the content of TENORM for calcium, barium and strontium and then used a software program SELABS to determine the self-absorption. Our results confirm that even in Petrie containers with small dimensions the (210)Pb can be underestimated by almost by a factor of four while (226)Ra can be underestimated by 5%. The (228)Ra activities are virtually unaffected due to the higher energy gamma-rays. However, the implications for TENORM studies that employ large Marinelli containers having sample sizes between 0.25 and 1.0 L may be severely compromised by the presence of high Z elements in elevated concentrations. The usual spectral interferences on (226)Ra, (228)Ra and (210)Pb coming from other radionuclides in the (234)U, (235)U and (238)U decay chains are virtually nonexistent due the very high activity levels of (226)Ra, (228)Ra and (210)Pb in the tens of thousands of Bq/kg.

  16. Mapping the spatial distribution and activity of (226)Ra at legacy sites through Machine Learning interpretation of gamma-ray spectrometry data.

    PubMed

    Varley, Adam; Tyler, Andrew; Smith, Leslie; Dale, Paul; Davies, Mike

    2016-03-01

    Radium ((226)Ra) contamination derived from military, industrial, and pharmaceutical products can be found at a number of historical sites across the world posing a risk to human health. The analysis of spectral data derived using gamma-ray spectrometry can offer a powerful tool to rapidly estimate and map the activity, depth, and lateral distribution of (226)Ra contamination covering an extensive area. Subsequently, reliable risk assessments can be developed for individual sites in a fraction of the timeframe compared to traditional labour-intensive sampling techniques: for example soil coring. However, local heterogeneity of the natural background, statistical counting uncertainty, and non-linear source response are confounding problems associated with gamma-ray spectral analysis. This is particularly challenging, when attempting to deal with enhanced concentrations of a naturally occurring radionuclide such as (226)Ra. As a result, conventional surveys tend to attribute the highest activities to the largest total signal received by a detector (Gross counts): an assumption that tends to neglect higher activities at depth. To overcome these limitations, a methodology was developed making use of Monte Carlo simulations, Principal Component Analysis and Machine Learning based algorithms to derive depth and activity estimates for (226)Ra contamination. The approach was applied on spectra taken using two gamma-ray detectors (Lanthanum Bromide and Sodium Iodide), with the aim of identifying an optimised combination of detector and spectral processing routine. It was confirmed that, through a combination of Neural Networks and Lanthanum Bromide, the most accurate depth and activity estimates could be found. The advantage of the method was demonstrated by mapping depth and activity estimates at a case study site in Scotland. There the method identified significantly higher activity (<3 Bq g(-1)) occurring at depth (>0.4m), that conventional gross counting algorithms

  17. The Peroxisome Proliferator Activated Receptor‐γ Pioglitazone Improves Vascular Function and Decreases Disease Activity in Patients With Rheumatoid Arthritis

    PubMed Central

    Marder, Wendy; Khalatbari, Shokoufeh; Myles, James D.; Hench, Rita; Lustig, Susan; Yalavarthi, Srilakshmi; Parameswaran, Aishwarya; Brook, Robert D.; Kaplan, Mariana J.

    2013-01-01

    Background Rheumatoid arthritis (RA) is associated with heightened mortality due to atherosclerotic cardiovascular disease (CVD). Inflammatory pathways in RA negatively affect vascular physiology and promote metabolic disturbances that contribute to CVD. We hypothesized that the peroxisome proliferator activated receptor‐γ (PPAR‐γ) pioglitazone could promote potent vasculoprotective and anti‐inflammatory effects in RA. Methods and Results One hundred forty‐three non‐diabetic adult RA patients (76.2% female, age 55.2±12.1 [mean±SD]) on stable RA standard of care treatment were enrolled in a randomized, double‐blind placebo controlled crossover trial of 45 mg daily pioglitazone versus placebo, with a 3‐month duration/arm and a 2‐month washout period. Pulse wave velocity of the aorta (PWV), brachial artery flow mediated dilatation (FMD), nitroglycerin mediated dilatation (NMD), microvascular endothelial function (reactive hyperemia index [RHI]), and circulating biomarkers of inflammation, insulin resistance, and atherosclerosis risk all were quantified. RA disease activity was assessed with the 28‐Joint Count Disease Activity Score (DAS‐28) C‐reactive protein (CRP) and the Short Form (36) Health Survey quality of life questionnaire. When added to standard of care RA treatment, pioglitazone significantly decreased pulse wave velocity (ie, aortic stiffness) (P=0.01), while FMD and RHI remained unchanged when compared to treatment with placebo. Further, pioglitazone significantly reduced RA disease activity (P=0.02) and CRP levels (P=0.001), while improving lipid profiles. The drug was well tolerated. Conclusions Addition of pioglitazone to RA standard of care significantly improves aortic elasticity and decreases inflammation and disease activity with minimal safety issues. The clinical implications of these findings remain to be established. Clinical Trial Registration URL: ClinicalTrials.gov Unique Identifier: NCT00554853. PMID:24252844

  18. The Th17/Treg Ratio, IL-1RA and sCD14 Levels in Primary HIV Infection Predict the T-cell Activation Set Point in the Absence of Systemic Microbial Translocation

    PubMed Central

    Chevalier, Mathieu F.; Petitjean, Gaël; Dunyach-Rémy, Catherine; Didier, Céline; Girard, Pierre-Marie; Manea, Maria Elena; Campa, Pauline; Meyer, Laurence; Rouzioux, Christine; Lavigne, Jean-Philippe; Barré-Sinoussi, Françoise; Scott-Algara, Daniel; Weiss, Laurence

    2013-01-01

    Impairment of the intestinal barrier and subsequent microbial translocation (MT) may be involved in chronic immune activation, which plays a central role in HIV pathogenesis. Th17 cells are critical to prevent MT. The aim of the study was to investigate, in patients with primary HIV infection (PHI), the early relationship between the Th17/Treg ratio, monocyte activation and MT and their impact on the T-cell activation set point, which is known to predict disease progression. 27 patients with early PHI were included in a prospective longitudinal study and followed-up for 6 months. At baseline, the Th17/Treg ratio strongly negatively correlated with the proportion of activated CD8 T cells expressing CD38/HLA-DR or Ki-67. Also, the Th17/Treg ratio was negatively related to viral load and plasma levels of sCD14 and IL-1RA, two markers of monocyte activation. In untreated patients, the Th17/Treg ratio at baseline negatively correlated with CD8 T-cell activation at month 6 defining the T-cell activation set point (% HLA-DR+CD38+ and %Ki-67+). Soluble CD14 and IL-1RA plasma levels also predicted the T-cell activation set point. Levels of I-FABP, a marker of mucosal damages, were similar to healthy controls at baseline but increased at month 6. No decrease in anti-endotoxin core antibody (EndoCAb) and no peptidoglycan were detected during PHI. In addition, 16S rDNA was only detected at low levels in 2 out 27 patients at baseline and in one additional patient at M6. Altogether, data support the hypothesis that T-cell and monocyte activation in PHI are not primarily driven by systemic MT but rather by viral replication. Moreover, the “innate immune set point” defined by the early levels of sCD14 and IL-1RA might be powerful early surrogate markers for disease progression and should be considered for use in clinical practice. PMID:23818854

  19. Increased FcγRII expression and aberrant tumour necrosis factor α production by mature dendritic cells from patients with active rheumatoid arthritis

    PubMed Central

    Radstake, T; Blom, A; Sloetjes, A; van Gorselen, E O F; Pesman, G; Engelen, L; Torensma, R; van den Berg, W B; Figdor, C; van Lent, P L E M; Adema, G; Barrera, P

    2004-01-01

    Objectives: To investigate potential differences in phenotype and behaviour of immature (iDC) and mature dendritic cells (mDC) from patients with RA and healthy subjects. Methods: iDC and mDC were derived from blood monocytes of patients with RA and healthy controls following standardised protocols. FACS was used to analyse expression of FcγRI, II, and III and molecules to characterise DC. Discrimination between FcγRIIa and FcγRIIb was achieved by RT-PCR. Immunohistochemistry was performed on synovial biopsy specimens of three patients with RA and three healthy controls. TNFα production by iDC and mDC upon FcγR dependent stimulation was compared between patients with RA and controls by ELISA. Results: iDC from patients with active RA but not from patients with inactive RA or healthy controls markedly up regulated FcγRII. mDC from patients with active RA also lacked the physiological down regulation of FcγRII that occurs upon maturation in both control groups. RT-PCR analysis confirmed the increased expression of FcγRII in RA—especially marked for FcγRIIb. FcγR dependent stimulation of DC using antigen-IgG immune complexes (IC) significantly increased TNFα production by DC from healthy subjects, but significantly decreased TNFα by DC from patients with RA. Overlapping expression patterns between FcγRII and DC-LAMP in the synovial tissue of patients with RA imply that in vivo, also, mature DC express increased levels of FcγRIIb. Conclusion: The presence and altered characteristics of DC during active RA suggest that DC help to modulate autoimmunity in RA. Further studies should elucidate the role of local factors in altering the function of DC in RA and in increasing expression of FcγRII. PMID:15547078

  20. The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years.

    PubMed

    da Mota, Licia Maria Henrique; Dos Santos Neto, Leopoldo Luiz; de Carvalho, Jozélio Freire; Pereira, Ivânio Alves; Burlingame, Rufus; Ménard, Henri A; Laurindo, Ieda Maria Magalhães

    2012-12-01

    Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (<12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of

  1. Dynamics of Rifting in two Active Rift Segments in Afar - Geodetic and Structural Studies - DoRA Project

    NASA Astrophysics Data System (ADS)

    Doubre, C.; Socquet, A.; Masson, F.; Jacques, E.; Grandin, R.; Nercessian, A.; Kassim, M.; Vergne, J.; Diament, M.; Hinderer, J.; Ayele, A.; Lewi, E.; Calais, E.; Peltzer, G.; Toussaint, R.; de Chaballier, J.; Ballu, V. S.; Luck, B.; King, G. C.; Vigny, C.; Cattin, R.; Tiberi, C.; Kidane, T.; Jalludin, M.; Maggi, A.; Dorbath, C.; Manatschal, G.; Schmittbuhl, J.; Le Moigne, N.; Deroussi, S.

    2009-12-01

    The DoRA project aims to conduct complementary studies in two volcano-tectonic rifts in the Afar Depression. In Northern Afar, the Wal’is Dabbahu Rift (WD, Ethiopia) is currently undergoing a major rifting episode. This event started in September 2005 with a significant seismic activity. InSAR data revealed the injection of a 65 km-long mega-dyke that opened by up to 8 m, the slip of numerous normal faults and opening of fissures, and a rhyolitic eruption. Similarly, the Asal-Ghoubbet Rift (AG, Djibouti) was affected in 1978 by a smaller episode of rifting associated with the intrusion of a 2 m wide dyke into the crust. Since then, a large catalog of geodetic data that includes recent InSAR time series reveals the importance of non-steady deformation controlling the rift dynamics. Our goal is to gain an understanding of such volcano-tectonic segments on several time scales, including the dyking period itself and the post-event period. The study of the behavior of the AG Rift during its whole post-rifting period offers an image at t+30 years of the WD segment, while keeping in mind important structural and scale differences. First, we propose to build a complete and accurate set of geodetic data (InSAR, cGPS, GPS), covering the period under study. With a narrow temporal sample window, we will precisely describe the aseismic slip affecting the normal faults of these rifts, the periods of sudden slip and/or slip acceleration but also measure the deformation associated with probable future dyke intrusion. Second, we aim to constrain the origin of these displacements and their relation with mass transfers within the crust. Series of gravity measurements will be pursue or initiated in both rifts. Third, the recording of seismic activity is essential to constrain the relative importance of seismic and aseismic deformation. This will also help to evaluate the thickness of the seismogenic layer. Together with structural data collected during a seismic survey in the AG

  2. Baricitinib in patients with inadequate response or intolerance to conventional synthetic DMARDs: results from the RA-BUILD study

    PubMed Central

    Dougados, Maxime; Chen, Ying-Chou; Greenwald, Maria; Drescher, Edit; Liu, Jiajun; Beattie, Scott; Witt, Sarah; de la Torre, Inmaculada; Gaich, Carol; Rooney, Terence; Schlichting, Douglas; de Bono, Stephanie; Emery, Paul

    2017-01-01

    Background Baricitinib is an oral, reversible, selective Janus kinase 1 and 2 inhibitor. Methods In this phase III, double-blind 24-week study, 684 biologic disease-modifying antirheumatic drug (DMARD)-naïve patients with rheumatoid arthritis and inadequate response or intolerance to ≥1 conventional synthetic DMARDs were randomly assigned 1:1:1 to placebo or baricitinib (2 or 4 mg) once daily, stratified by region and the presence of joint erosions. Endpoint measures included American College of Rheumatology 20% response (ACR20, primary endpoint), Disease Activity Score (DAS28) and Simplified Disease Activity Index (SDAI) score ≤3.3. Results More patients achieved ACR20 response at week 12 with baricitinib 4 mg than with placebo (62% vs 39%, p≤0.001). Compared with placebo, statistically significant improvements in DAS28, SDAI remission, Health Assessment Questionnaire-Disability Index, morning joint stiffness, worst joint pain and worst tiredness were observed. In a supportive analysis, radiographic progression of structural joint damage at week 24 was reduced with baricitinib versus placebo. Rates of adverse events during the treatment period and serious adverse events (SAEs), including serious infections, were similar among groups (SAEs: 5% for baricitinib 4 mg and placebo). One patient had an adverse event of tuberculosis (baricitinib 4 mg); one patient had an adverse event of non-melanoma skin cancer (baricitinib 4 mg). Two deaths and three major adverse cardiovascular events occurred (placebo). Baricitinib was associated with a decrease in neutrophils and increases in low-density and high-density lipoprotein. Conclusions In patients with rheumatoid arthritis and an inadequate response or intolerance to conventional synthetic DMARDs, baricitinib was associated with clinical improvement and inhibition of progression of radiographic joint damage. Trial registration number NCT01721057; Results. PMID:27689735

  3. Expression of CCR7 and CD45RA in CD4+ and CD8+ subsets in cerebrospinal fluid of 134 patients with inflammatory and non-inflammatory neurological diseases

    PubMed Central

    Mullen, Katherine M.; Gocke, Anne R.; Allie, Rameeza; Ntranos, Achilles; Grishkan, Inna V.; Pardo, Carlos; Calabresi, Peter A.

    2012-01-01

    We investigated CD45RA and CCR7 expression in CD4+ and CD8+ subsets of cerebrospinal fluid (CSF) lymphocytes, both immediately ex vivo and after stimulation, from 134 patients with a variety of inflammatory and non-inflammatory neurological diseases. Most inflammatory diseases had a higher CD4+: CD8+ ratio and higher percentage of effector memory T cells (TEM) than non-inflammatory controls, excluding active infection. Moreover, we found that patients with highly elevated cell counts in the CSF tended to have a lower percentage of central memory T cells (TCM) than patients with low or absent pleiocytosis, with a concomitant increase in TEM. We also found that samples with elevated IgG index or presence of oligoclonal bands had a significantly higher CD4+:CD8+ ratio than normal samples, consistent with increased CD4+ help for intrathecal IgG synthesis by B cells. PMID:22633193

  4. Activity concentration, transfer factors and resultant radiological risk of 226Ra, 232Th, and 40K in soil and some vegetables consumed in Selangor, Malaysia

    NASA Astrophysics Data System (ADS)

    Solehah, A. R.; Yasir, M. S.; Samat, S. B.

    2016-11-01

    The activity concentrations of the natural radionuclides 226Ra, 232Th, and 40K were determined in vegetable crops consumed by Malaysian people in Sungai Besar, Selangor. Sample of vegetables and the soil where the crops were cultivated and collected at five different location. The activity concentrations in Bq/kg of 226Ra, 232Th, and 40K were measured by the gamma-ray spectroscopy using the high purity germanium detector. The range activity concentration in soil is between 51.81 and 71.84 Bq/kg, 64.18 and 78.00 Bq/kg, and 210.49 and 244.29 Bq/kg for 226Ra, 232Th, and 40K, respectively. The activity concentration of 226Ra, 232Th, and 40K in vegetables were found to be in the range of 2.06 to 5.44 Bq/kg, Not Detectable to 0.61 Bq/kg, and 101.00 to 1223.09 Bq/kg, respectively. The activity concentration in both soil and vegetables were all less than lower limit stated by UNSCEAR. The Transfer Factors range value for 226Ra, 232Th, and 40K varied from 0.02 to 0.06, 0.003 to 0.008, and 1.79 to 5.19 respectively. Radium equivalent for soil range from 165.57 to 194.84 Bq/kg. It was within the international accepted value (370 Bq/kg). Absorb dose rate for soil range between 73.5 to 86.40 nGyh-1, in safe range from limit of international accepted value (55nGyh-1). Effective dose rate is found to be in range of 0.09 to 0.11 mSvy-1 for soil which is less than 2.4 mSv/y. External and Internal Hazard indices of soil was all below 1, within agreement of other researcher and UNSCEAR. The estimation of the consequent radiological risk due to the presence of those radionuclides is significantly low.

  5. Drug-specific risk and characteristics of lupus and vasculitis-like events in patients with rheumatoid arthritis treated with TNFi: results from BSRBR-RA

    PubMed Central

    Dixon, William G; Kersley-Fleet, Lianne; Bruce, Ian N; Chinoy, Hector; Barton, Anne; Lunt, Mark; Watson, Kath; Hyrich, Kimme L

    2017-01-01

    Objective To compare the risk of lupus-like events (LLEs) and vasculitis-like events (VLEs) in tumour necrosis factor-α inhibitor (TNFi)-treated patients with rheumatoid arthritis (RA) to those receiving non-biological disease-modifying antirheumatic drugs (nbDMARDs). Methods Patients were recruited to the British Society for Rheumatology Biologics Register—RA, a national prospective cohort study. Two cohorts recruited between 2001 and 2015: (1) patients starting first TNFi (adalimumab, etanercept, infliximab and certolizumab) (n=12 937) and (2) biological-naïve comparison cohort receiving nbDMARDs (n=3673). The risk of an event was compared between the two cohorts using Cox proportional-hazard models, adjusted using propensity scores. Rates of LLE/VLE were compared between TNFi and nbDMARD patients. Results The crude incidence rates for LLEs were: TNFi 10/10 000 patient-years (pyrs) (95% CI 8 to 13) and nbDMARD 2/10 000 pyrs (95% CI 1 to 6); for VLEs: TNFi 15/10 000 pyrs (95% CI 12 to 19) and nbDMARD 7/10 000 pyrs (95% CI 4 to 12). The risk of both events was highest in the first year of TNFi treatment. After adjusting for differences in baseline characteristics, there was no difference in risk of LLEs (adjHR 1.86; 95% CI 0.52 to 6.58) or VLEs (adjHR 1.27; 95% CI 0.40 to 4.04) for TNFi compared to nbDMARD-treated patients. Infliximab conferred the highest overall risk, followed by etanercept, although 95% CIs overlapped following adjustment. Conclusions In one of the largest biological registers, the absolute risk of both events is low. The addition of TNFi to nbDMARD does not alter the risk of either event in patients with RA selected for TNFi. This is the first study to assess the risk of these outcomes in a prospective, observational cohort. PMID:28123776

  6. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    PubMed Central

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  7. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.

    PubMed

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.

  8. Pharmacological properties of S1RA, a new sigma-1 receptor antagonist that inhibits neuropathic pain and activity-induced spinal sensitization

    PubMed Central

    Romero, L; Zamanillo, D; Nadal, X; Sánchez-Arroyos, R; Rivera-Arconada, I; Dordal, A; Montero, A; Muro, A; Bura, A; Segalés, C; Laloya, M; Hernández, E; Portillo-Salido, E; Escriche, M; Codony, X; Encina, G; Burgueño, J; Merlos, M; Baeyens, JM; Giraldo, J; López-García, JA; Maldonado, R; Plata-Salamán, CR; Vela, JM

    2012-01-01

    BACKGROUND AND PURPOSE The sigma-1 (σ1) receptor is a ligand-regulated molecular chaperone that has been involved in pain, but there is limited understanding of the actions associated with its pharmacological modulation. Indeed, the selectivity and pharmacological properties of σ1 receptor ligands used as pharmacological tools are unclear and the demonstration that σ1 receptor antagonists have efficacy in reversing central sensitization-related pain sensitivity is still missing. EXPERIMENTAL APPROACH The pharmacological properties of a novel σ1 receptor antagonist (S1RA) were first characterized. S1RA was then used to investigate the effect of pharmacological antagonism of σ1 receptors on in vivo nociception in sensitizing conditions and on in vitro spinal cord sensitization in mice. Drug levels and autoradiographic, ex vivo binding for σ1 receptor occupancy were measured to substantiate behavioural data. KEY RESULTS Formalin-induced nociception (both phases), capsaicin-induced mechanical hypersensitivity and sciatic nerve injury-induced mechanical and thermal hypersensitivity were dose-dependently inhibited by systemic administration of S1RA. Occupancy of σ1 receptors in the CNS was significantly correlated with the antinociceptive effects. No pharmacodynamic tolerance to the antiallodynic and antihyperalgesic effect developed following repeated administration of S1RA to nerve-injured mice. As a mechanistic correlate, electrophysiological recordings demonstrated that pharmacological antagonism of σ1 receptors attenuated the wind-up responses in spinal cords sensitized by repetitive nociceptive stimulation. CONCLUSIONS AND IMPLICATIONS These findings contribute to evidence identifying the σ1 receptor as a modulator of activity-induced spinal sensitization and pain hypersensitivity, and suggest σ1 receptor antagonists as potential novel treatments for neuropathic pain. PMID:22404321

  9. Deletion of mtrC in Haemophilus ducreyi increases sensitivity to human antimicrobial peptides and activates the CpxRA regulon.

    PubMed

    Rinker, Sherri D; Trombley, Michael P; Gu, Xiaoping; Fortney, Kate R; Bauer, Margaret E

    2011-06-01

    Haemophilus ducreyi resists killing by antimicrobial peptides encountered during human infection, including cathelicidin LL-37, α-defensins, and β-defensins. In this study, we examined the role of the proton motive force-dependent multiple transferable resistance (MTR) transporter in antimicrobial peptide resistance in H. ducreyi. We found a proton motive force-dependent effect on H. ducreyi's resistance to LL-37 and β-defensin HBD-3, but not α-defensin HNP-2. Deletion of the membrane fusion protein MtrC rendered H. ducreyi more sensitive to LL-37 and human β-defensins but had relatively little effect on α-defensin resistance. The mtrC mutant 35000HPmtrC exhibited phenotypic changes in outer membrane protein profiles, colony morphology, and serum sensitivity, which were restored to wild type by trans-complementation with mtrC. Similar phenotypes were reported in a cpxA mutant; activation of the two-component CpxRA regulator was confirmed by showing transcriptional effects on CpxRA-regulated genes in 35000HPmtrC. A cpxR mutant had wild-type levels of antimicrobial peptide resistance; a cpxA mutation had little effect on defensin resistance but led to increased sensitivity to LL-37. 35000HPmtrC was more sensitive than the cpxA mutant to LL-37, indicating that MTR contributed to LL-37 resistance independent of the CpxRA regulon. The CpxRA regulon did not affect proton motive force-dependent antimicrobial peptide resistance; however, 35000HPmtrC had lost proton motive force-dependent peptide resistance, suggesting that the MTR transporter promotes proton motive force-dependent resistance to LL-37 and human β-defensins. This is the first report of a β-defensin resistance mechanism in H. ducreyi and shows that LL-37 resistance in H. ducreyi is multifactorial.

  10. Activation of the CpxRA system by deletion of cpxA impairs the ability of Haemophilus ducreyi to infect humans.

    PubMed

    Spinola, Stanley M; Fortney, Kate R; Baker, Beth; Janowicz, Diane M; Zwickl, Beth; Katz, Barry P; Blick, Robert J; Munson, Robert S

    2010-09-01

    Haemophilus ducreyi must adapt to the environment of the human host to establish and maintain infection in the skin. Bacteria generally utilize stress response systems, such as the CpxRA two-component system, to adapt to hostile environments. CpxRA is the only obvious two-component system contained in the H. ducreyi genome and negatively regulates the lspB-lspA2 operon, which encodes proteins that enable the organism to resist phagocytosis. We constructed an unmarked, in-frame H. ducreyi cpxA deletion mutant, 35000HPDeltacpxA. In human inoculation experiments, 35000HPDeltacpxA formed papules at a rate and size that were significantly less than its parent and was unable to form pustules compared to the parent. CpxA usually has kinase and phosphatase activities for CpxR, and the deletion of CpxA leads to the accumulation of activated CpxR due to the loss of phosphatase activity and the ability of CpxR to accept phosphate groups from other donors. Using a reporter construct, the lspB-lspA2 promoter was downregulated in 35000HPDeltacpxA, confirming that CpxR was activated. Deletion of cpxA downregulated DsrA, the major determinant of serum resistance in the organism, causing the mutant to become serum susceptible. Complementation in trans restored parental phenotypes. 35000HPDeltacpxA is the first H. ducreyi mutant that is impaired in its ability to form both papules and pustules in humans. Since a major function of CpxRA is to control the flow of protein traffic across the periplasm, uncontrolled activation of this system likely causes dysregulated expression of multiple virulence determinants and cripples the ability of the organism to adapt to the host.

  11. An alternative method for Ra determinations in water

    SciTech Connect

    Loyd, D.H.; Drake, E.N. 2d.

    1989-07-01

    Concentrations of /sup 226/Ra and /sup 224/Ra in 13 wells distributed throughout McCulloch and Mason counties in the Hickory Aquifer of the Llano Uplift Region of West-Central Texas are reported. Measurable alpha-particle activity is present in all wells, with seven wells having /sup 226/Ra radioactivity concentrations greater than 185 Bq m-3 (5 pCi L-1). An alternative methodology for measuring /sup 226/Ra, /sup 224/Ra and /sup 228/Ra is described. The EPA-approved methodology for estimating total Ra is shown to be invalid for aquifers containing significant levels of /sup 224/Ra. Alpha-particle activity measurements made in the interval of 12 to 300 h after Ra isolation lead to self-consistent solutions for radioactivity concentrations of /sup 226/Ra and /sup 224/Ra, with negligible contributions from /sup 228/Ra. Radioactivity concentrations of /sup 228/Ra can be calculated from grow-in terms for this isotope used with alpha-particle activity measurements at post-isolation times significantly longer than 800 h. Comparison of the /sup 226/Ra radioactivity concentration with that reported previously by the Texas Department of Health for a single well indicates acceptable agreement. However, the radioactivity concentration attributable to /sup 228/Ra for the same well was found to be in significant disagreement with the Texas Department of Health value.

  12. "Redefining RA": The RA Tool Kit

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    No one likes being two steps behind, and the fastest way to fall off the pace is by not keeping up with major titles and hot authors. Fortunately, there are numerous resources, both prepublication and postpublication, that can help. It is best when readers' advisory (RA) librarians know what is coming out months ahead of time--in order to think…

  13. Determination of specific activity of (226)Ra, (232)Th and (40)K for assessment of radiation hazards from Turkish pumice samples.

    PubMed

    Turhan, Seref; Gündüz, Lüfullah

    2008-02-01

    The specific activity of (226)Ra, (232)Th and (40)K in 52 Turkish pumice samples collected from 11 geographical areas located in Central Anatolia, Eastern Anatolia, Mediterranean and Aegean regions was determined by gamma-ray spectrometry with a high-purity germanium (HPGe) detector. The specific activity of (226)Ra, (232)Th and (40)K ranged from 12.7+/-0.5 to 256.2+/-9.1Bqkg(-1) with a mean of 89.1+/-65.2Bqkg(-1), 12.3+/-1.0 to 237.9+/-12.2Bqkg(-1) with a mean of 87.0+/-61.4Bqkg(-1) and 300.1+/-5.5 to 1899.0+/-30.8Bqkg(-1) with a mean of 1211.9+/-419.8Bqkg(-1), respectively. Elemental concentrations were determined for U (from 1.0 to 20.7ppm with a mean of 7.2+/-5.3ppm), Th (from 3.0 to 58.6ppm with a mean of 21.4+/-15.1ppm) and K (from 1.0 to 6.1% with a mean of 3.9+/-1.3%). The radium equivalent activity (Ra(eq)), the activity index, the emanation coefficient, the (222)Rn mass exhalation rate, the indoor absorbed dose rate and the effective dose rate were estimated for the radiation hazard of the natural radioactivity in all samples. The calculated mean Ra(eq) value was 306.6+/-177.7Bqkg(-1) (54.6+/-5.5 to 737.6+/-49.0Bqkg(-1)) for all pumice samples. This value is lower than the recommended limit value of 370Bqkg(-1) for building raws and products. The emanation coefficient and the (222)Rn mass exhalation rate of all samples ranged from 29.4 to 42.9% with a mean of 36.2% and from 11.0 to 196.4microBqkg(-1)s(-1) with a mean of 73.5microBqkg(-1)s(-1), respectively. The mean indoor absorbed dose rate and the corresponding mean effective dose rate were 274.6+/-153.6nGyh(-1) (50.4-644.6nGyh(-1)) and 1.35+/-0.75mSvy(-1) (0.24-3.16mSvy(-1)), respectively. For all pumice samples the mean indoor absorbed dose rate is about three times higher than the population-weighted average of 84nGyh(-1), while the mean effective dose rate values except for PUM 05, PUM 06, PUM 10 and PUM 15 exceed the dose criterion of 1mSvy(-1).

  14. Martin RA-30 Baltimore

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Martin RA-30 Baltimore: The Martin RA-30 Baltimore was a light bomber ordered by the Royal Air Force. Some examples were retained in the United States as part of a 'Reverse Lend-Lease.' This example was flown by the NACA from June 1943 until March 1944.

  15. Effects of copper supplementation on erythrocyte superoxide dismutase activity levels in rheumatoid arthritis patients

    SciTech Connect

    Marten, J.T.; DiSilvestro, R.A. )

    1989-02-09

    Rheumatoid arthritis (RA) patients are reported to possess lower than normal levels of Cu-Zn superoxide dismutase (SOD) activity. The contribution of copper status to these low values has not been examined. To address this issue, blood samples were obtained from 10 RA patients before and after 28 days of daily oral copper supplementation (2 mg/day). All patients were receiving gold therapy. Each RA subject, before supplementation, displayed lower erythrocyte SOD values than any of 25 age matched controls. The mean value for the RA subjects was about 40% lower than the control mean, whether expressed as units per ml packed cells or per mg hemoglobin. Erythrocyte SOD activity levels were increased in all subjects by the 4 week copper supplementation, with 7 of the patients showing at least a 22% increase. Presupplement SOD activities showed no correlation with serum C-reactive protein contents, an indicator of acute phase response. Serum levels of the copper containing acute phase protein ceruloplasmin, showed variable responses to copper supplementation. The studies described here are currently being extended to include RA subjects not being treated with gold and to include supplemented controls.

  16. Systematic review of patient-reported outcome measures (PROMs) for assessing disease activity in rheumatoid arthritis

    PubMed Central

    de Jonge, Marieke J; Fransen, Jaap; Kievit, Wietske; van Riel, Piet LCM

    2016-01-01

    Patient assessment of disease activity in rheumatoid arthritis (RA) may be useful in clinical practice, offering a patient-friendly, location independent, and a time-efficient and cost-efficient means of monitoring the disease. The objective of this study was to identify patient-reported outcome measures (PROMs) to assess disease activity in RA and to evaluate the measurement properties of these measures. Systematic literature searches were performed in the PubMed and EMBASE databases to identify articles reporting on clinimetric development or evaluation of PROM-based instruments to monitor disease activity in patients with RA. 2 reviewers independently selected articles for review and assessed their methodological quality based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) recommendations. A total of 424 abstracts were retrieved for review. Of these abstracts, 56 were selected for reviewing the full article and 34 articles, presenting 17 different PROMs, were finally included. Identified were: Rheumatoid Arthritis Disease Activity Index (RADAI), RADAI-5, Patient-based Disease Activity Score (PDAS) I & II, Patient-derived Disease Activity Score with 28-joint counts (Pt-DAS28), Patient-derived Simplified Disease Activity Index (Pt-SDAI), Global Arthritis Score (GAS), Patient Activity Score (PAS) I & II, Routine Assessment of Patient Index Data (RAPID) 2–5, Patient Reported Outcome-index (PRO-index) continuous (C) & majority (M), Patient Reported Outcome CLinical ARthritis Activity (PRO-CLARA). The quality of reports varied from poor to good. Typically 5 out of 10 clinimetric domains were covered in the validations of the different instruments. The quality and extent of clinimetric validation varied among PROMs of RA disease activity. The Pt-DAS28, RADAI, RADAI-5 and RAPID 3 had the strongest and most extensive validation. The measurement properties least reported and in need of more evidence were: reliability

  17. Evidence for B cell activation in patients with active rheumatoid arthritis.

    PubMed Central

    Youinou, P Y; Irving, W L; Shipley, M; Hayes, J; Lydyard, P M

    1984-01-01

    Peripheral blood lymphocytes and in some cases synovial eluate cells from 51 patients with rheumatoid arthritis (RA), were analysed for the percentages of cells bearing surface light chains (total B cells), IgM and IgD. In addition, their capacity to form rosettes with mouse erythrocytes (mRFC)--a property of a B cell subpopulation--was determined. Activity of the disease was assessed by clinical and laboratory criteria and classified as very active, moderately active and inactive. Normal, age and sex matched individuals and a group of patients with a variety of other rheumatological disorders, were used as control populations. Although there was no significant difference in percentages of total B cells in any of the groups compared with normal controls, there was a small but significant increase in the ratio of cells bearing IgM to those bearing IgD in patients with very active disease. This was paralleled by a significant decrease in the mRFC in this disease activity group. Patients with inactive disease showed no change in their proportions of IgM:IgD, but did show a significant increase in mRFC. These results are discussed in terms of the presence of activated B cells in patients with very active RA. PMID:6607144

  18. Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of ASP2408, a Potent Selective T-Cell Costimulation Modulator After Single and Multiple Ascending Doses in Healthy Volunteers and RA Patients.

    PubMed

    Zhu, Tong; Keirns, James; Howieson, Corrie; Kaibara, Atsunori; Goldwater, Ronald; Kivitz, Alan J; Chindalore, Vishala; Cohen, Stanley; Santos, Vicki; Akinlade, Bolanle; Kernstock, Robert; Delgado-Herrera, Leticia; Blahunka, Paul C; Karrer, Erik E; Garg, Jay P; Samberg, Nancy; Zeiher, Bernhardt G

    2016-09-01

    ASP2408 is a next-generation anti-cytotoxic T lymphocyte antigen-4 fusion protein engineered for improved CD86 binding affinity as a treatment for rheumatoid arthritis (RA). In 72 healthy subjects (n = 6/treatment), ASP2408 was administered as single ascending doses intravenously at 0.003 to 10.0 mg/kg or subcutaneously at 0.3 to 3.0 mg/kg. It showed decreased clearance and prolonged half-life with increasing doses, consistent with target-mediated disposition. The apparent bioavailability was 36.3%-56.7% across single subcutaneous doses. Sixteen RA patients (n = 8/treatment) on stable methotrexate received 3 × 3.0 mg/kg subcutaneously every 4 weeks or every 2 weeks. Similar to single-dose treatment, ASP2408 concentrations peaked 2 to 3 days postdose, with a median t1/2 of approximately 8 days. Using CD86 receptor occupancy (RO) as a mechanistic biomarker, ASP2408 demonstrated dose-dependent binding to its target. ASP2408 3.0 mg/kg subcutaneously every 4 weeks and every 2 weeks led to a mean %CD86 RO ≥ 74.7% and ≥ 81.5%, respectively, within each dosing interval. ASP2408 was well tolerated across studies with no evidence of dose-limiting toxicity or clinically significant changes in clinical laboratory test results, vital signs, or 12-lead electrocardiograms. ASP2408 elicited antidrug antibodies in the majority of patients, but with no clinical sequelae.

  19. Measurement of activity concentrations of 40K, 226Ra and 232Th for assessment of radiation hazards from soils of the southwestern region of Nigeria.

    PubMed

    Ajayi, Oladele Samuel

    2009-08-01

    Activity concentrations of the selected radionuclides (40)K, (226)Ra and (232)Th were measured in surface soil samples collected from 38 cities in the southwest region of Nigeria by means of gamma spectroscopy with a high-purity germanium detector. Measured activity concentration values of (40)K varied from 34.9 +/- 4.4 to 1,358.6 +/- 28.5 Bq kg(-1) (given on a dry mass (DM) basis) with a mean value of 286.5 +/- 308.5 Bq kg(-1); that of (226)Ra varied from 9.3 +/- 3.7 to 198.1 +/- 13.8 Bq kg(-1) with a mean value of 54.5 Bq kg(-1) and a standard deviation of 38.7 Bq kg(-1), while that of (232)Th varied from 5.4 +/- 1.1 to 502.0 +/- 16.5 Bq kg(-1) with a mean value of 91.1 Bq kg(-1) and standard deviation of 100.9 Bq kg(-1). The mean activity concentration values obtained for (226)Ra and (232)Th are greater than the world average values reported by the United Nations Scientific Committee on Effects of Atomic Radiation for areas of normal background radiation. Radiological indices were estimated for the radiation/health hazards of the natural radioactivity of all soil samples. Estimated absorbed dose rates in air varied from 12.42 +/- 2.25 to 451.33 +/- 19.06 nGy h(-1), annual outdoor effective dose rates from 0.015 +/- 0.003 to 0.554 +/- 0.023 mSv year(-1), internal hazard index from 0.10 +/- 0.03 to 3.02 +/- 0.16, external hazard index from 0.07 +/- 0.01 to 2.60 +/- 0.11, representative level index from 0.19 +/- 0.03 to 6.84 +/- 0.29, activity index from 0.09 +/- 0.02 to 3.42 +/- 0.15, and radium equivalent activity from 26.95 +/- 5.04 to 963.15 +/- 41.87 Bq kg(-1). Only the mean value of the representative level index exceeds the limit for areas of normal background radiation. All other indices show mean values that are lower than the recommended limits.

  20. RA Construction KC, LLC Information Sheet

    EPA Pesticide Factsheets

    RA Construction KC, LLC (the Company) is located in Gladstone, Missouri. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Kansas City, Missouri.

  1. RANTES and Chemotactic Activity in Synovial Fluids From Patients With Rheumatoid Arthritis and Osteoarthritis

    PubMed Central

    Stanczyk, Joanna; Kowalski, Marek L.; Grzegorczyk, Janina; Szkudlinska, Barbara; Jarzebska, Marzanna; Marciniak, Marek; Synder, Marek

    2005-01-01

    A massive accumulation of inflammatory cells in synovial tissues is a major pathological feature of rheumatoid arthritis (RA). Neutrophiles dominate synovial fluid while rheumatoid synovium is infiltrated with mononuclear cells. Mechanisms regulating influx of particular subpopulations of leukocytes into articular cavity and synovium compartment are not completely defined. An increasing amount of data supports a crucial role of a C-C chemokine RANTES in the RA pathogenesis. Our objective is to evaluate chemotactic activity for neutrophils (NCA), lymphocytes (LCA), and monocytes (MoCA) in SFs obtained from patients with RA and osteoarthritis (OA). We also aimed to characterise the relation between chemotactic activity, RANTES, and percentage distribution of leukocytes in SF. SFs from 11 patients with RA and 6 with OA were included in the study. Modified microchamber Boyden method was employed to assess chemotactic activity. Cytological and biochemical analysis of SF was performed. RANTES was measured with ELISA. Rheumatoid SFs were rich in cells with predominance of neutrophiles while osteoarthritic fluids were lymphocytic. RA SFs were also characterised by increased lactoferrin level. Both NCA and LCA were higher in SF from patients with RA (62 ± 12 and 24 ± 6 cells/HPF, resp) as compared to patients with OA (23 ± 6; P < .05 and 6 ± 2 cells/HPF; P < 0.05). The chemoattractive effect of RA SF was more pronounced on neutrophiles than on lymphocytes. RA SF expressed high RANTES levels (145 ± 36 pg/mL), while OA SF was characterised by only trace amount of this chemokine (2 ± 1 pg/mL). We found positive correlation of RANTES with chemotactic activity for mononuclear cells (LCA+MoCA; R = 0.61; P < .05). Surprisingly, RANTES correlated also positively with neutrophiles number (R = 0.77; P < 0.001). Rheumatoid SF possesses strong chemotactic potency for leukocytes. RANTES is overexpressed in RA SF and is a potential mediator influencing intensity and composition

  2. Perceived Barriers, Facilitators and Benefits for Regular Physical Activity and Exercise in Patients with Rheumatoid Arthritis: A Review of the Literature.

    PubMed

    Veldhuijzen van Zanten, Jet J C S; Rouse, Peter C; Hale, Elizabeth D; Ntoumanis, Nikos; Metsios, George S; Duda, Joan L; Kitas, George D

    2015-10-01

    Rheumatoid arthritis (RA) is an autoimmune disease, which not only affects the joints but can also impact on general well-being and risk for cardiovascular disease. Regular physical activity and exercise in patients with RA have numerous health benefits. Nevertheless, the majority of patients with RA are physically inactive. This indicates that people with RA might experience additional or more severe barriers to physical activity or exercise than the general population. This narrative review provides an overview of perceived barriers, benefits and facilitators of physical activity and exercise in RA. Databases were searched for articles published until September 2014 using the terms 'rheumatoid arthritis', 'physical activity', 'exercise', 'barriers', 'facilitators', 'benefits', 'motivation', 'motivators' and 'enablers'. Similarities were found between disease-specific barriers and benefits of physical activity and exercise, e.g. pain and fatigue are frequently mentioned as barriers, but reductions in pain and fatigue are perceived benefits of physical activity and exercise. Even though exercise does not influence the existence of barriers, physically active patients appear to be more capable of overcoming them. Therefore, exercise programmes should enhance self-efficacy for exercise in order to achieve long-term physical activity and exercise behaviour. Encouragement from health professionals and friends/family are facilitators for physical activity and exercise. There is a need for interventions that support RA patients in overcoming barriers to physical activity and exercise and help sustain this important health behaviour.

  3. T cell receptor excision circles (TRECs), CD4+, CD8+, and their CD45RO+, and CD45RA+, subpopulations in hepatitis C virus (HCV)-HIV-co-infected patients during treatment with interferon alpha plus ribavirin: analysis in a population on effective antiretroviral therapy.

    PubMed

    Arizcorreta, A; Márquez, M; Fernández-Gutiérrez, C; Guzmán, E Pérez; Brun, F; Rodríguez-Iglesias, M; Girón-González, J A

    2006-11-01

    Interferon (IFN)-alpha induced CD4(+) T lymphopenia is a toxic effect of the treatment of chronic hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-co-infected patients. To increase the knowledge about this secondary effect, we performed an analysis of the evolution of the T cell receptor excision circles (TRECs), CD4(+) and CD8(+) T cells and of their CD45RO(+) and CD45RA(+) subpopulations during the treatment of chronic hepatitis HCV with peginterferon alpha (pegIFN-alpha) + ribavirin. Twenty HCV/HIV-co-infected patients, with undetectable HIV load after highly active antiretroviral therapy (HAART), were treated with pegIFN-alpha + ribavirin. TRECs were determined using real-time polymerase chain reaction. CD4(+) and CD8(+) T cells and their CD45RO(+) and CD45RA(+) subpopulations were analysed by two-colour flow cytometry. Median baseline CD4(+) and CD8(+) T cells were 592 mm(3) and 874 mm(3), respectively. Median baseline CD45RO(+) subpopulation was 48% for CD4(+) T and 57% for CD8(+) T lymphocytes. A progressive decrease in both T cell populations, as well as of their CD45RO(+) and CD45RA(+) subpopulations, was detected, with a difference between the baseline and nadir levels approaching 50%. The evolution of T cell populations and TRECs was independent of the response to the treatment. T lymphocytes and their subpopulations returned to baseline levels at 24 weeks after the end of treatment, with the exception of the T CD4(+) CD45RA(+) subpopulation. The ratio of CD4(+) CD45RO(+)/CD4(+) CD45RA(+) increased from 0.89 (baseline) to 1.44 (24 weeks after the end of the therapy). TRECs/ml did not return to the basal values. In conclusion, a significant reduction of CD4(+) and CD8(+) T cells, and of their CD45RA(+) and CD45RO(+) subpopulations, in HIV/HCV co-infected patients treated with pegIFN-alpha was observed. Both subpopulations increased after the suppression of treatment, but the CD4(+) CD45RA subpopulation did not reach the basal levels as a

  4. Measurement of 226Ra, 232Th, 137Cs and 40K activities of Wheat and Corn Products in Ilam Province – Iran and Resultant Annual Ingestion Radiation Dose

    PubMed Central

    CHANGIZI, Vahid; SHAFIEI, Elham; ZAREH, Mohammad Reza

    2013-01-01

    Background: Background: Natural background radiation is the main source of human exposure to radioactive material. Soils naturally have radioactive mineral contents. The aim of this study is to determine natural (238 U, 232 Th, 40 K) and artificial (137 Cs) radioactivity levels in wheat and corn fields of Eilam province. Methods: HPGe detector was used to measure the concentration activity of 238 U and 232 Th series, 40 K and 137 Cs in wheat and corn samples taken from different regions of Eilam province, in Iran. Results: In wheat and corn samples, the average activity concentrations of 226 Ra, 232 Th, 40 K and 137 Cs were found to be 1, 67, 0.5, 91.73, 0.01 and 0.81, 0.85, 101.52, 0.07 Bq/kg (dry weight), respectively. H ex and H in in the present work are lower than 1. The average value of H ex was found to be 0.02 and 0.025 and average value of H in to be found 0.025 and 0.027 in wheat fields samples and corn samples in Eilam provinces, respectively. The obtained values of AGDE are 30.49 mSv/yr for wheat filed samples and 37.89 mSv/yr for corn samples; the AEDE rate values are 5.28 mSv/yr in wheat filed samples and this average value was found to be 6.13 mSv/yr in corn samples in Eilam. Transfer factors (TFs) of long lived radionuclide such as 137 Cs, 226 Ra, 232 Th and 40 K from soils to corn and wheat plants have been studied by radiotracer experiments. Conclusion: The natural radioactivity levels in Eilam province are not at the range of high risk of morbidity and are under international standards. PMID:26056646

  5. Activity concentrations of 226Ra, 232Th, 40K and 137Cs radionuclides in Turkish medicinal herbs, their ingestion doses and cancer risks

    NASA Astrophysics Data System (ADS)

    Parmaksız, Aydın; Ağuş, Yusuf

    2014-11-01

    Twenty-two medicinal herb samples, each representing a distinct species, were collected from Turkish markets and measured by the gamma spectrometric method. The activity concentration of 226Ra in medicinal herbs was found in the range of minimum detectable activity (MDA) and 15.1 ± 2.2 Bqkg-1. The activity concentration of 232Th ranged from MDA values to 3.5 ± 0.8 Bqkg-1. The activity concentration of 40K varied between 50.0 ± 16.8 and 1311.5 ± 57.3 Bqkg-1. All 137Cs activity concentrations of medicinal herbs were found to have lower than MDA values. The bone surface dose, lower large intestine and colon doses were found to be 182.9, 18.8 and 18.7 µSvy-1, respectively. The highest committed effective dose originated from the annual ingestion of 1 kg medicinal herb was calculated notably low as 9.0 µSv. The cancer risk of ingestion of medicinal herbs was found to be small enough to be neglected. The selected Turkish medicinal herbs are considered safe for human consumption.

  6. Estuarine geochemistry of /sup 224/Ra, /sup 226/Ra, and /sup 222/Rn

    SciTech Connect

    Elsinger, R.J.

    1982-01-01

    Desorption from river borne sediments is the most likely source of the excess /sup 226/Ra. Laboratory mixing experiments on Pee Dee River sediments show an increase in /sup 226/Ra desorption with increasing salinities with maximum desorption occurring at or above 20/sup 0//oo salinity. Desorption and diffusion are the sources for /sup 226/Ra in the estuarine systems. In Winyah Bay the /sup 228/Ra//sup 226/Ra activity ratio does not change significantly with salinity, averaging around 1.4, indicating desorption as the major source of /sup 228/Ra. In the Yangtze River the /sup 228/Ra//sup 226/Ra activity ratio is constant (approx.1.90) until increasing linearly above 16/sup 0//oo. A diffusive flux from regeneration by /sup 232/Th decay in shelf sediments is the source of the increase. In Delaware Bay /sup 228/Ra increases faster than /sup 226/Ra in the less than or equal to22/sup 0//oo water, indicating a source in addition to desorption. The increase can be balanced by a 0.33 dpm/cm/sup 2/-year flux over the upper part of the Bay where fine grained sediments predominate. /sup 224/Ra behavior is controlled by its 3.64 day half-life. In Winyah Bay a flux of around 0.4 dpm/cm/sup 2/-day is necessary to support the standing crop of non-desorbed /sup 224/Ra in the water column. In Delaware Bay the nearly constant /sup 224/Ra in concentration over the 2.5/sup 0//oo to 12/sup 0//oo salinity range are maintained by regeneration from /sup 228/Th in the turbidity maximum zones and diffusion from bottom sediments. Water leaving on ebb tide from a salt marsh on Delaware Bay had increases in all three radium isotopes (/sup 224/Ra > /sup 228/Ra > /sup 226/Ra) compared to water coming in on the flood tide. Excess /sup 222/Rn concentrations in a fresh water section of the Pee Dee River show a decreasing downstream gradient. Using these gradients to determine evasion rates, stagnant film thicknesses range from 21..mu.. to 62..mu...

  7. Asymptomatic Atherosclerosis in Egyptian Rheumatoid Arthritis Patients and Its Relation to Disease Activity

    PubMed Central

    Elshereef, Rawhya R.; Darwish, Aymen; Ali, Amal; Abdel-kadar, Mohammed; Hamdy, Lamiaa

    2015-01-01

    Aim. To detect the frequency of subclinical atherosclerosis in rheumatoid arthritis patients without clinically evident atherosclerosis and to correlate its presence with the disease activity. Patients and Methods. Our study includes 112 RA patients (group 1) and 40 healthy controls (group 11). All patients and controls were subjected to full history taking, clinical examination, and laboratory investigations. Carotid intima media wall thickness (IMT) and carotid plaques were measured in both groups by B-mode ultrasonography; also color duplex Doppler ultrasound of the brachial artery was done to detect endothelial function. Results. There is atherosclerosis in 31.3% of asymptomatic RA patients compared with only 5% in controls (P = 0.003**). A significant difference was detected in patients with and without atherosclerosis regarding duration of the disease (P = 0.0001***) and patient's age (P = 0.01*). There is highly statistical significant correlation between atherosclerosis and disease activity index. Conclusion. The frequency of subclinical atherosclerosis was high in long-term active RA patients. PMID:25737726

  8. Keishibukuryogan (Gui-Zhi-Fu-Ling-Wan), a Kampo Formula, Decreases Disease Activity and Soluble Vascular Adhesion Molecule-1 in Patients with Rheumatoid Arthritis

    PubMed Central

    Nozaki, Kazuya; Hikiami, Hiroaki; Goto, Hirozo; Nakagawa, Takako; Shibahara, Naotoshi; Shimada, Yutaka

    2006-01-01

    An increasing death rate due to cardiovascular disease in patients with rheumatoid arthritis (RA) has been reported. Keishibukuryogan (KBG) is a traditional Chinese/Japanese (Kampo) formula that has been administered to patients with blood stagnation, e.g. thrombotic disease and atherosclerosis. The objective of this study was to evaluate the efficacy of KBG on disease activity and endothelial dysfunction in RA patients. Sixteen RA patients were enrolled and administered KBG (12 g per day) for 12 weeks in addition to continuing other drugs. The disease activity of RA was assessed by modified disease activity scores for 28 joints (DAS28). Plasma levels of adhesion molecules, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were evaluated. C-reactive protein (CRP), inflammatory cytokines (IL-1β, IL-6 and TNF-α) and lipid peroxide (LPO) were also evaluated. Fourteen patients completed the study. The disease activity of RA, tender joint count, swollen joint count and DAS28 decreased significantly. Among adhesion molecules, only sVCAM-1 decreased significantly. LPO also decreased significantly, whereas CRP and inflammatory cytokines remained unchanged. These results suggest that KBG has insufficient anti-inflammatory or immunomodulating effect but does have a beneficial effect on articular symptoms and a protective effect against endothelial dysfunction in RA patients. PMID:16951720

  9. SoRa first flight. Summer 2009

    NASA Astrophysics Data System (ADS)

    Pirrotta, S.; Flamini, E.

    The SoRa (Sounding Radar) experiment was successfully launched from Longyearbyen (Svalbard, Norway) during the summer 2009 campaign managed by the Italian/Norwegian "Nobile Amundsen / Stratospheric Balloon Centre" (NA/SBC). SoRa is part of the Italian Space Agency (ASI) programs for Long Duration Balloon Flights. Carried by the biggest balloon (800.000 m3) ever launched in polar regions, SoRa main experiment and its three piggyback payloads (DUSTER, ISA and SIDERALE) performed a nominal flight of almost 4 days over the North Sea and Greenland, until the separation, landing and recovery in Baffin Island (Canada). Despite the final destructive event that compromise the scientific main goal of SoRa, the 2009 ASI balloon campaign can be considered an important milestone, because of the obtained scientific and technical results but also for the lesson learned by the science, engineering and managerial teams looking at the future ASI scientific balloon-born activities.

  10. Evaluating disease activity in patients with ankylosing spondylitis and rheumatoid arthritis using 99mtc-glucosamine

    PubMed Central

    Manolios, Nicholas; Ali, Marina; Camden, Bradley; Aflaky, Elham; Pavic, Katrina; Markewycz, Andrew; De Costa, Robert; Angelides, Socrates

    2016-01-01

    Objective To evaluate the clinical utility of a novel radiotracer, 99mTc-glucosamine, in assessing disease activity of both rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Material and Methods: Twenty-five patients with RA (nine males and 16 females) and 12 patients with AS (all male) at various stages of disease were recruited for the study. A clinical history and examination was performed, followed by the measurement of hematological, biochemical, and autoimmune serological parameters to assess disease activity. 99mTc-glucosamine was intravenously administered and scans were compared with other imaging modalities, including plain X-ray, magnetic resonance imaging (MRI), and bone scans. Results In patients with AS, 99mTc-glucosamine scans were more capable of identifying active disease and differentiating between inflammatory and non-inflammatory causes. In patients with RA, 99mTc-glucosamine accumulated at all known sites of disease involvement. Uptake was most pronounced in patients with active untreated disease. The relative tracer activity in the involved joints increased with time compared with that in the adjoining soft tissue, liver, and cardiac blood pool. Using Spearman’s correlation coefficient, there was a positive correlation among glucosamine scan scores, C-reactive protein (p=0.048), and clinical assessment (p=0.003), which was not noted with bone scans. Conclusion The radiotracer was well tolerated by all patients, with no adverse reactions. 99mTc-glucosamine imaging could detect spinal inflammation in AS. With respect to RA, 99mTc-glucosamine was a viable alternative to 99mTc-labeled methylene diphosphonate nuclear bone scans for imaging inflamed joints and had the added advantage of demonstrating a significant clinical correlation between disease activity and scan findings. PMID:27708974

  11. Composite Indices Using 3 or 4 Components of the Core Data Set Have Similar Predictive Ability to Measure Disease Activity in RA: Evidence from the DANCER and REFLEX Studies.

    PubMed

    Bergman, Martin J; Reiss, William; Chung, Carol; Wong, Pamela; Turpcu, Adam

    2013-01-01

    Background. Understanding how disease-assessment indices perform in rheumatoid arthritis (RA) clinical trials can inform their use in routine practice. The study objective was to assess the capacity of combinations of RA Core Data Set measures to distinguish rituximab from control treatment. Methods. Post hoc analysis of two randomised clinical trials was used. Composite Efficacy Indices were derived by combining three or four RA Core Data Set measures from three possible sources: physician, patient, and laboratory. Results. All 105 Composite Efficacy Indices evaluated significantly distinguished rituximab from control treatment (P < 10(-7)). Generally, indices containing measures from three different sources had a greater capacity to distinguish rituximab from control treatment than indices containing three measures from one source. Composite Efficacy Indices performed as well as validated indices such as DAS28, RAPID3, and CDAI. Conclusions. All indices composed of three or four RA Core Data Set measures have a similar capacity to detect treatment differences. These results suggest that the precise measurement used is less important than whether any measurement is performed, although selection should be consistent for each patient. Therefore, the choice of assessment tool should not be limited to a prescribed list and should instead be left to the clinician's discretion.

  12. Imbalance between HAT and HDAC Activities in the PBMCs of Patients with Ankylosing Spondylitis or Rheumatoid Arthritis and Influence of HDAC Inhibitors on TNF Alpha Production

    PubMed Central

    Toussirot, Eric; Abbas, Wasim; Khan, Kashif Aziz; Tissot, Marion; Jeudy, Alicia; Baud, Lucile; Bertolini, Ewa; Wendling, Daniel; Herbein, Georges

    2013-01-01

    Objective Acetylation or deacetylation of histone proteins may modulate cytokine gene transcription such as TNF alpha (TNF). We evaluated the balance between histone deacetytlase (HDAC) and histone acetyltransferase (HAT) in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS) compared to healthy controls (HC) and determined the influence of HDAC inhibitors (trichostatin A -TSA- or Sirtinol -Sirt-) on these enzymatic activities and on the PBMC production of TNF. Methods 52 patients with RA, 21 with AS and 38 HC were evaluated. HAT and HDAC activities were measured on nuclear extracts from PBMC using colorimetric assays. Enzymatic activities were determined prior to and after ex vivo treatment of PBMC by TSA or Sirt. TNF levels were evaluated in PBMC culture supernatants in the absence or presence of TSA or Sirt. Results HAT and HDAC activities were significantly reduced in AS, while these activities reached similar levels in RA and HC. Ex vivo treatment of PBMC by HDACi tended to decrease HDAC expression in HC, but Sirt significantly reduced HAT in RA. TNF production by PBMC was significantly down-regulated by Sirt in HC and AS patients. Conclusion HAT and HDAC were disturbed in AS while no major changes were found in RA. HDACi may modulate HDAC and HAT PBMC expression, especially Sirt in RA. Sirtinol was able to down regulate TNF production by PBMC in HC and AS. An imbalance between HAT and HDAC activities might provide the rationale for the development of HDACi in the therapeutic approach to inflammatory rheumatic diseases. PMID:24039666

  13. Gene expression analysis in RA: towards personalized medicine

    PubMed Central

    Burska, A N; Roget, K; Blits, M; Soto Gomez, L; van de Loo, F; Hazelwood, L D; Verweij, C L; Rowe, A; Goulielmos, G N; van Baarsen, L G M; Ponchel, F

    2014-01-01

    Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patient's care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients. PMID:24589910

  14. Does Regular Use of a Complementary Medicine of Olea Europe and Ficus carica Have Adverse Effects on Lipid Profile and Fasting Blood Glucose of Rheumatoid Arthritis (RA) Patients Under Treatment with DMARD Regimens Containing Methotrexate?

    PubMed Central

    Bahadori, Shahnaz; Ahmadzadeh, Arman; Shams Ardekani, Mohammad Reza; Kamalinejad, Mohammad; Keshavarz, Mansoor; Salamzadeh, Jamshid

    2016-01-01

    Rheumatoid arthritis (RA) patients are vulnerable to cardiovascular morbidity and mortality in which atherosclerosis plays a major role. In this study, the lipid profile and fasting blood sugar (FBS) of RA patients receiving a complementary medicine of olive and fig, as add-on therapy for routine disease-modifying antirheumatic drugs (DMARDs) regimen containing low dose methotrexate (MTX), were studied. A randomized controlled clinical trial was designed. Adult RA patients were randomly allocated in two groups receiving routine DMARDs regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), the atherogenic index of plasma (AIP) defined as log(TG/HDL-C), and the fasting blood sugar (FBS) were determined and recorded. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.9 ± 12.3 years completed the study. Average MTX dose received by intervention and control groups were 24.30 ± 18.39 and 17.61 ± 15.53 mg/week, respectively (p = 0.11). Repeated measures analysis of variance (ANOVA) revealed that differences between lipid profile indicators and FBS in the two study groups were not statistically significant (P>0.05). No additional substantial adverse reaction was seen in the study groups. Our findings are more reassuring for patients and their doctors to trust on the safety of the investigated complementary preparation to be used as add-on therapy to manage rheumatoid arthritis. PMID:28243292

  15. Organizing Pneumonia in Rheumatoid Arthritis Patients: A Case-Based Review

    PubMed Central

    Mori, Shunsuke; Koga, Yukinori; Sugimoto, Mineharu

    2015-01-01

    We treated 21 patients with organizing pneumonia (OP) associated with rheumatoid arthritis (RA) or related to biological disease-modifying antirheumatic drugs (DMARDs) at our institution between 2006 and 2014. Among these cases, 3 (14.3%) preceded articular symptoms of RA, 4 (19.0%) developed simultaneously with RA onset, and 14 (66.7%) occurred during follow-up periods for RA. In the case of OP preceding RA, increased levels of anti-cyclic citrullinated peptide antibodies and rheumatoid factor were observed at the OP onset. RA disease activity was related to the development of OP in the simultaneous cases. In the cases of OP developing after RA diagnosis, 10 of 14 patients had maintained low disease activity with biological DMARD therapy at the OP onset, and among them, 6 patients developed OP within the first year of this therapy. In the remaining four patients, RA activity was not controlled at the OP onset. All patients responded well to systemic steroid therapy, but two patients suffered from relapses of articular and pulmonary symptoms upon steroid tapering. In most of the RA patients, DMARD therapy was introduced or restarted during the steroid tapering. We successfully restarted a biological DMARD that had not been previously used for patients whose RA would otherwise have been difficult to control. In this study, we also perform a review of the literature on RA-associated or biological DMARD-related OP and discuss the pathogenesis and management of OP occurring in RA patients. PMID:26543387

  16. Establishing an active patient partnership.

    PubMed

    Herrier, R N; Boyce, R W

    1995-04-01

    Pharmacists face many changes in the coming decade, some of which threaten their professional survival. Although uncertainty may currently prevail, one of these changes, the shift in the patient-health care professional relationship from the patient taking a passive role to an active partnering role, provides pharmacists with many opportunities to realize the vision of patient-centered care that has been advocated by pharmacy innovators and leaders for almost three decades. To take advantage of these changes, pharmacists must modify their practice paradigms and use their existing strengths, such as easy patient access and high levels of patient trust, to help develop a new model of pharmaceutical care. The concern that the magnitude of these changes will prevent successful practice transformations may be exaggerated. In reality, these proposed "new" roles have been in existence for much of this century. Most pharmacists can expand and enhance their traditional roles as self-care advisors and patient educators simply by incremental improvements in interpersonal and clinical skills. Rather than a Star Trek approach to "go where no man has gone before," the profession needs only a pharmaceutical sequel to Back to the Future.

  17. Assessment of disease activity in patients with rheumatoid arthritis using optical spectral transmission measurements, a non-invasive imaging technique

    PubMed Central

    van Onna, M; Ten Cate, D F; Tsoi, K L; Meier, A J L; Jacobs, J W G; Westgeest, A A A; Meijer, P B L; van Beek, M C; Rensen, W H J; Bijlsma, J W J

    2016-01-01

    Objectives In rheumatoid arthritis (RA), treat-to-target strategies require instruments for valid detection of joint inflammation. Therefore, imaging modalities are increasingly used in clinical practice. Optical spectral transmission (OST) measurements are non-invasive and fast and may therefore have benefits over existing imaging modalities. We tested whether OST could measure disease activity validly in patients with RA. Methods In 59 patients with RA and 10 patients with arthralgia, OST, joint counts, Disease Activity Score (DAS) 28 and ultrasonography (US) were performed. Additionally, MRI was performed in patients with DAS28<2.6. We developed and validated within the same cohort an algorithm for detection of joint inflammation by OST with US as reference. Results At the joint level, OST and US performed similarly inproximal interphalangeal-joints (area under the receiver-operating curve (AUC) of 0.79, p<0.0001) andmetacarpophalangeal joints (AUC 0.78, p<0.0001). Performance was less similar in wrists (AUC 0.62, p=0.006). On the patient level, OST correlated moderately with clinical examination (DAS28 r=0.42, p=0.001), and US scores (r=0.64, p<0.0001). Furthermore, in patients with subclinical and low disease activity, there was a correlation between OST and MRI synovitis score (RAMRIS (Rheumatoid Arthritis MRI Scoring) synovitis), r=0.52, p=0.005. Conclusions In this pilot study, OST performed moderately in the detection of joint inflammation in patients with RA. Further studies are needed to determine the diagnostic performance in a new cohort of patients with RA. PMID:26452538

  18. Proportions of several types of plasma and urine microparticles are increased in patients with rheumatoid arthritis with active disease.

    PubMed

    Viñuela-Berni, V; Doníz-Padilla, L; Figueroa-Vega, N; Portillo-Salazar, H; Abud-Mendoza, C; Baranda, L; González-Amaro, R

    2015-06-01

    We analysed the proportions of different microparticles (MPs) in plasma from patients with rheumatoid arthritis (RA), and assessed their relationship with disease activity/therapy and their in-vitro effect on proinflammatory cytokine release. Blood and urine samples were obtained from 55 patients with RA (24 untreated and 31 under conventional therapy) and 20 healthy subjects. Fourteen patients with systemic lupus erythematosus (SLE) were also studied. The proportions of CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs were determined by flow cytometry analysis. The in-vitro effect of plasma MPs on the release of interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α was also analysed. We detected that the proportions of different types of annexin-V(+) MPs were enhanced in plasma (CD3(+) , CD14(+) , CD19(+) , CD41(+) and CD62E(+) MPs) and urine (CD14(+) , CD3(+) and CD19(+) MPs) from RA patients with high disease activity (DAS28 index > 5·1). Accordingly, a significant positive correlation was observed between the levels of MPs and DAS28 score, and these levels diminished significantly at week 4 of immunosuppressive therapy. Finally, MPs isolated from patients with high disease activity induced, in vitro, an enhanced release of IL-1, IL-17 and TNF-α. In SLE, enhanced levels of different types of plasma MPs were also detected, with a tight correlation with disease activity. Our data further support that MPs have a relevant role in the pathogenesis of RA and suggest that the analysis of the proportions of these microvesicles in plasma could be useful to monitor disease activity and therapy response in patients with RA.

  19. Proportions of several types of plasma and urine microparticles are increased in patients with rheumatoid arthritis with active disease

    PubMed Central

    Viñuela-Berni, V; Doníz-Padilla, L; Figueroa-Vega, N; Portillo-Salazar, H; Abud-Mendoza, C; Baranda, L; González-Amaro, R

    2015-01-01

    We analysed the proportions of different microparticles (MPs) in plasma from patients with rheumatoid arthritis (RA), and assessed their relationship with disease activity/therapy and their in-vitro effect on proinflammatory cytokine release. Blood and urine samples were obtained from 55 patients with RA (24 untreated and 31 under conventional therapy) and 20 healthy subjects. Fourteen patients with systemic lupus erythematosus (SLE) were also studied. The proportions of CD3+, CD14+, CD19+, CD41+ and CD62E+ MPs were determined by flow cytometry analysis. The in-vitro effect of plasma MPs on the release of interleukin (IL)-1, IL-6, IL-17 and tumour necrosis factor (TNF)-α was also analysed. We detected that the proportions of different types of annexin-V+ MPs were enhanced in plasma (CD3+, CD14+, CD19+, CD41+ and CD62E+ MPs) and urine (CD14+, CD3+ and CD19+ MPs) from RA patients with high disease activity (DAS28 index > 5·1). Accordingly, a significant positive correlation was observed between the levels of MPs and DAS28 score, and these levels diminished significantly at week 4 of immunosuppressive therapy. Finally, MPs isolated from patients with high disease activity induced, in vitro, an enhanced release of IL-1, IL-17 and TNF-α. In SLE, enhanced levels of different types of plasma MPs were also detected, with a tight correlation with disease activity. Our data further support that MPs have a relevant role in the pathogenesis of RA and suggest that the analysis of the proportions of these microvesicles in plasma could be useful to monitor disease activity and therapy response in patients with RA. PMID:25639560

  20. Radium Ra 223 dichloride in castration-resistant prostate cancer.

    PubMed

    Joung, J Y; Ha, Y S; Kim, I Y

    2013-08-01

    Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC.

  1. An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis

    PubMed Central

    Martin-Martin, LS; Giovannangeli, F; Bizzi, E; Massafra, U; Ballanti, E; Cassol, M; Migliore, A

    2017-01-01

    Background Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA). One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA). The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL) in patients affected by RA in maintaining LDA or remission obtained after biological therapy. Method This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28), clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. Results The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. Conclusion This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA cytokines may be an opportunity to explore in the management of RA.

  2. Association of disease activity with acute exacerbation of interstitial lung disease during tocilizumab treatment in patients with rheumatoid arthritis: a retrospective, case-control study.

    PubMed

    Akiyama, Mitsuhiro; Kaneko, Yuko; Yamaoka, Kunihiro; Kondo, Harumi; Takeuchi, Tsutomu

    2016-06-01

    The objective of the study was to identify risk factors for acute exacerbation of interstitial lung disease (ILD) during tocilizumab treatment in patients with rheumatoid arthritis (RA). This is a retrospective, case-control study. We reviewed 395 consecutive RA patients who received tocilizumab. First, we divided the patients according to the presence (RA-ILD) or absence of ILD (non-ILD) assessed by chest X-ray or high-resolution computed tomography, and compared them for characteristics relevant to RA-ILD. Subsequently, focusing on the patients with RA-ILD, we assessed their baseline characteristics and clinical courses comparing patients with acute exacerbation to those without. Comparing 78 with ILD and 317 without ILD, the following were identified as factors related to RA-ILD on multivariate analysis: age 60 years or older (OR 4.5, 95 % CI 2.2-9.4, P < 0.0001), smoking habit (OR 2.9, 95 % CI 1.5-5.5, P = 0.002), and high rheumatoid factor levels (OR 2.8, 95 % CI 1.4-5.5, P = 0.002). Of 78 RA-ILD patients, six developed acute exacerbation during tocilizumab treatment. The median duration between the initiation of tocilizumab treatment and the acute exacerbation occurrence was 48 weeks. While baseline characteristics did not differ between acute exacerbation and non-acute exacerbation groups, patients experiencing acute exacerbation had significantly higher Clinical Disease Activity Index (CDAI) at 24 weeks (20.8 vs. 6.2, P = 0.019). Univariate analysis showed that CDAI > 10 at 24 weeks was a risk factor for acute exacerbation (OR 4.7, 95 % CI 2.1-10.4, P = 0.02). Uncontrolled arthritis activity during tocilizumab treatment may be associated with acute exacerbation of RA-ILD, suggesting post-treatment monitoring of disease activity is important not only with respect to RA itself but also for RA-ILD.

  3. Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set

    PubMed Central

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H; Lin, Daming; Alten, Rieke; Christensen, Robin; Furst, Daniel E; Hewlett, Sarah; Leong, Amye; March, Lyn; Woodworth, Thasia; Boire, Gilles; Haraoui, Boulos; Hitchon, Carol; Jamal, Shahin; Keystone, Edward C; Pope, Janet; Tin, Diane; Thorne, J Carter

    2016-01-01

    Objective To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. Methods Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). Results The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16–32% were flaring at the second visit. Agreement of flare status was low–strong (κ's 0.17–0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49–0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29–0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1–3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. Conclusions Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares. PMID

  4. Large-Scale Discovery and Validation Studies Demonstrate Significant Reductions in Circulating Levels of IL8, IL-1Ra, MCP-1, and MIP-1β in Patients With Type 1 Diabetes

    PubMed Central

    Purohit, Sharad; Sharma, Ashok; Hopkins, Diane; Steed, Leigh; Bode, Bruce; Anderson, Stephen W.; Reed, John Chip; Steed, R. Dennis; Yang, Tao

    2015-01-01

    Context: Previous studies have attempted to elucidate the potential role of various cytokines and chemokines in human type 1 diabetes (T1D); however, the precise role of these serum proteins in T1D is still controversial and undetermined primarily due to the small sample sizes of the previous studies. We profiled a panel of serum cytokines and chemokines using a large-scale, two-stage study design for the discovery and validation of the serum proteins associated with T1D. Participants: The participants were patients with T1D and islet autoantibody–negative control subjects from the Phenome and Genome of Diabetes Autoimmunity study. Main Outcome Measures: Thirteen cytokines and chemokines were measured in serum of 4424 subjects using multiplex immunoassays. Results: Using 1378 samples in Stage 1, we found that four of the 13 proteins are significantly lower in patients with T1D than controls (IL8: odds ratio [OR] = 0.40; P = 5.7 × 10−19; IL-1Ra: OR = 0.42; P = 1.1 × 10−13; MCP-1: OR = 0.60; P = 6.7 × 10−9; and MIP-1β: OR = 0.63; P = 4.2 × 10−7). Our confirmation data with 3046 samples in Stage 2 further confirmed the significant negative associations of these four proteins with T1D (IL8: OR = 0.43; P = 8.9 × 10−32; IL-1Ra: OR = 0.56, P = 3.7 × 10−27; MCP-1: OR = 0.61, P = 4.3 × 10−17; and MIP-1β: OR = 0.69, P = 2.4 × 10−13). Quartile analyses also suggested that significantly more T1D cases have protein levels in the bottom quartile than in the top quartile for all four proteins: IL8 (OR = 0.09), IL-1Ra (OR = 0.18), MCP-1 (OR = 0.38), and MIP-1β (OR = 0.44). Furthermore, the negative associations between T1D and serum levels of all four proteins are stronger in genetically high-risk groups compared with the moderate and low-risk groups. Conclusions: IL8, IL-1Ra, MCP-1, and MIP-1β are significantly lower in patients with T1D than controls. PMID:26158606

  5. Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan.

    PubMed

    Tomita, Jumpei; Zhang, Jing; Yamamoto, Masayoshi

    2014-11-01

    A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (δ(2)H and δ(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed.

  6. The Autophagy Level Is Increased in the Synovial Tissues of Patients with Active Rheumatoid Arthritis and Is Correlated with Disease Severity

    PubMed Central

    Zhu, Li; Wang, Huaizhou; Wu, Yu; He, Zhengwen

    2017-01-01

    Rheumatoid arthritis (RA) is a complex and not fully understood autoimmune disease associated with multijoint damage. The main effector cells, the synovial fibroblasts, are apoptosis resistant and hyperplastic which indicate that autophagy level is high in synovial tissue. Real-time PCR, immunocytochemistry, and western blotting were used in this paper to study the autophagy status of the synovial tissues obtained from RA and OA patients at the time of joint replacement surgery. We further evaluated the correlation between autophagy levels with RA activity-associated serum markers with SPSS. The results showed that the expression levels (both in mRNA and in protein level) of autophagy-related proteins (belcin1, Atg5, and LC3) in the synovial tissue of patients with active rheumatoid arthritis (n = 20) were significantly higher than those in OA patients (n = 16). We further showed that the LC3-II/β-actin relative gray value was strongly correlated with the serum levels of several RA activity-related markers: CRP, ESR, CCP, and RF. Our results indicate that evaluating the autophagy level of synovial biopsies might be a useful way to diagnose RA and to estimate the disease activity. Reducing the expression level of autophagy-related genes might become a new therapeutic target for active rheumatoid arthritis. PMID:28255205

  7. Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity

    PubMed Central

    Ristić, Gorica G.; Subota, Vesna; Lepić, Toplica; Stanisavljević, Dejana; Glišić, Branislava; Ristić, Arsen D.; Petronijević, Milan; Stefanović, Dušan Z.

    2015-01-01

    Background To evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk. Methods Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately. Results RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05). Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28–ESR, mDAS28–CRP), modified Health Assessment Questionnaire (p<0.01 for all), duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all), and anti-CCP antibodies (p<0.01). In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05) or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05) than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039). Conclusions We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity

  8. A rapid and inexpensive method for 226Ra and 228Ra measurements of high TDS groundwaters.

    PubMed

    El-Shrakawy, A; Ebaid, Y Y; Burnett, W C; Aldaihan, Soaad K

    2013-07-01

    A series of laboratory-scale studies was conducted by preconcentrating (226)Ra from spiked water test samples using Purolite ion-exchange resin to evaluate the adsorption efficiency of the resin under varying conditions. After removing the resin from the columns, it was sealed in gas-tight containers and measured via gamma spectrometry. The Purolite resin showed high radium uptake and retention from natural waters in the presence of high iron and total dissolved solids (TDS). This procedure allowed us to process a large number of high TDS samples at a typical rate of 15 samples/day using three germanium detectors. Quality assurance and method validation have been achieved by analyzing selected groundwater samples, with different (226)Ra activities and high TDS values, and comparing the results to those using alpha spectrometry with a (133)Ba yield tracer. There was very good agreement between the obtained (226)Ra activities by both methods.

  9. Assessment of (226)Ra, (238)U, (232)Th, (137)Cs and (40)K activities from the northern coastline of Oman Sea (water and sediments).

    PubMed

    Darabi-Golestan, F; Hezarkhani, A; Zare, M R

    2017-02-27

    Water and sediment samples were collected from northern coast of Oman Sea covering from Goatr to Hormoz canyon seaport. Water and sediment quality assessment for naturally or anthropogenic radionuclides at Oman Sea as a main strategic golf for trade and transit, is an important issue. Correspondence analysis (CA) by R-mode analysis represents that sigma(T)-temperature-conductivity-O2 parameters are well-correlated with (226)Ra, (232)Th and (40)K. Accordingly Q-mode analysis revealed an indicator samples of ST13W for different radionuclides, ST03W for O2, and simultaneously ST34W-ST21W-ST08W-ST04W for sigma(T) parameters. The CA results overlapped with factor and cluster analysis results that explained 85.8% of total variance of water samples. Descriptive analysis of sediments indicates more significant variation than water samples. The (232)Th and (226)Ra generally showing that ST13D to ST25D sediments that restricted to Pi Bashk coastline are concentrated from (137)Cs and (40)K. By comparison with reference-values from Iran and other parts of the world, they are acceptable with respect to environmental and radioisotope hazards.

  10. Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment

    PubMed Central

    Rech, Juergen; Hueber, Axel J; Finzel, Stephanie; Englbrecht, Matthias; Haschka, Judith; Manger, Bernhard; Kleyer, Arnd; Reiser, Michaela; Cobra, Jayme Fogagnolo; Figueiredo, Camille; Tony, Hans-Peter; Kleinert, Stefan; Wendler, Joerg; Schuch, Florian; Ronneberger, Monika; Feuchtenberger, Martin; Fleck, Martin; Manger, Karin; Ochs, Wolfgang; Schmitt-Haendle, Matthias; Lorenz, Hanns-Martin; Nuesslein, Hubert; Alten, Rieke; Henes, Joerg; Krueger, Klaus; Schett, Georg

    2016-01-01

    Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1–100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA−/ACPA−, moderate in patients who were MBDA+/ACPA− (33.3%) and MBDA−ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. Trial registration number EudraCT 2009-015740-42. PMID:26483255

  11. Immune memory in CD4+ CD45RA+ T cells.

    PubMed Central

    Richards, D; Chapman, M D; Sasama, J; Lee, T H; Kemeny, D M

    1997-01-01

    This study addresses the question of whether human peripheral CD4+ CD45RA+ T cells possess antigen-specific immune memory. CD4+ CD45RA+ T cells were isolated by a combination of positive and negative selection. Putative CD4+ CD45RA+ cells expressed CD45RA (98.9%) and contained < 0.1% CD4+ CD45RO+ and < 0.5% CD4+ CD45RA+ CD45RO+ cells. Putative CD45RO+ cells expressed CD45RO (90%) and contained 9% CD45RA+ CD45RO+ and < 0.1% CD4+ CD45RA+ cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4+ CD45RA+ and CD4+ CD45RO+ T cells was determined in two atopic donors and found to be 1:11,314 and 1:8031 for CD4+ CD45RA+ and 1:1463 and 1:1408 for CD4+ CD45RO+ T cells. The responder frequencies of CD4+ CD45RA+ and CD4+ CD45RO+ T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176,903 for CD4+ CD45RA+ and 1:9136 and 1:13,136 for CD4+ CD45RO+ T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4+ CD45RO+ and 24 from CD4+ CD45RA+ T cells. All clones were CD3+ CD4+ CD45RO+ and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4+ CD45RA+ and CD4+ CD45RO+ precursors, although freshly isolated and polyclonally activated CD4+ CD45RA+ T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4+ CD45RO+ counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4+ CD45RA+ as well as CD4+ CD45RO+ T cells during the chronic immune response to inhaled antigen. PMID:9301520

  12. Recommendations and the state of the evidence for physical activity interventions for adults with rheumatoid arthritis: 2007 to present

    PubMed Central

    Iversen, Maura D; Brawerman, Marisa; Iversen, Christina N

    2013-01-01

    Patients with rheumatoid arthritis (RA) are twice as likely as their healthy peers to suffer from cardiovascular disease. RA is also a major cause of disability and reduced quality of life. Clinical trials of exercise and physical activity interventions demonstrate positive effects on muscle strength, function, aerobic capacity, mood and disability. While RA management guidelines emphasize the role of exercise and physical activity in the management of RA, the description of physical activity and exercise is vague and patients with RA remain less physically active than their healthy counterparts. This review discusses the benefits of physical activity and current physical activity recommendations in RA, describes measurement techniques to assess physical activity, and synthesizes the data from interventions to promote physical activity and improve health outcomes in adults with RA. PMID:23538738

  13. The multifaceted balance of TNF-α and type I/II interferon responses in SLE and RA: how monocytes manage the impact of cytokines.

    PubMed

    Smiljanovic, Biljana; Grün, Joachim R; Biesen, Robert; Schulte-Wrede, Ursula; Baumgrass, Ria; Stuhlmüller, Bruno; Maslinski, Wlodzimierz; Hiepe, Falk; Burmester, Gerd-R; Radbruch, Andreas; Häupl, Thomas; Grützkau, Andreas

    2012-11-01

    Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as tumor necrosis factor (TNF)-α in rheumatoid arthritis (RA) and interferon (IFN)-α/γ in systemic lupus erythematosus (SLE). To relate the transcriptional imprinting of cytokines in a cell type- and disease-specific manner, we generated gene expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNF-α, IFN-α2a, and IFN-γ. Monocytes from SLE and RA patients revealed disease-specific gene expression profiles. In vitro-generated signatures induced by IFN-α2a and IFN-γ showed similar profiles that only partially overlapped with those induced by TNF-α. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNF-α regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNF-α that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene expression profiles, which can be molecularly dissected when compared with in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.

  14. Patient education, disease activity and physical function: can we be more targeted? A cross sectional study among people with rheumatoid arthritis, psoriatic arthritis and hand osteoarthritis

    PubMed Central

    2013-01-01

    Introduction In order to target educational needs of patients more effectively, an Austrian-German educational needs assessment tool (OENAT) was developed, the educational needs of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and hand osteoarthritis (HOA) were described and the relationships between educational needs, gender, disease activity and function were explored. Methods The English ENAT was adapted into Austrian-German using Beaton's cross-cultural adaptation process. Internal construct validity was assessed by Rasch analysis. Educational needs across diagnostic groups and subgroups of patients were summarized descriptively and their relationship with disease activity and physical functioning explored. Results The sample comprised 130 RA, 125 PsA and 48 HOA patients. Their mean ages ± SD were 56 ± 14, 51 ± 11 and 64 ± 7 years for RA, PsA and HOA; disease duration was 11 ± 9, 11 ± 11 and 14 ± 9 years, respectively. More than 70% in each patient group expressed interest in receiving education about their disease. The educational needs differed significantly between women and men in all 3 groups. In RA and PsA, female patients expressed significantly higher educational needs than men in 'movements’ and 'feelings’ domains (p=0.04 and p=0.03 for RA and p<0.01 and p=0.01 for PsA). Female patients in the HOA group had significantly higher scores on all domains except for the 'movements’. Older patients with PsA scored significantly higher than their younger counterparts in the 'pain’ domain (p=0.05). RA patients with disease duration >5 years), expressed higher educational needs in 'movements’ (p<0.01). Educational background had effects in the PsA group only, patients with basic education had greater scores than those with higher education on 'movements’ and 'arthritis process’ (p=0.01). In the RA group, DAS28 correlated significantly with 'movements’ (r=0.24, p=0.01), 'feelings’ (r=0.22, p

  15. Citrullinated vimentin as an important antigen in immune complexes from synovial fluid of rheumatoid arthritis patients with antibodies against citrullinated proteins

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is an inflammatory disease, which results in destruction of the joint. The presence of immune complexes (IC) in serum and synovial fluid of RA patients might contribute to this articular damage through different mechanisms, such as complement activation. Therefore, identification of the antigens from these IC is important to gain more insight into the pathogenesis of RA. Since RA patients have antibodies against citrullinated proteins (ACPA) in their serum and synovial fluid (SF) and since elevated levels of citrullinated proteins are detected in the joints of RA patients, citrullinated antigens are possibly present in IC from RA patients. Methods IC from serum of healthy persons, serum of RA patients and IC from synovial fluid of RA patients and Spondyloarthropathy (SpA) patients were isolated by immunoprecipitation. Identification of the antigens was performed by SDS-PAGE, mass spectrometry and immunodetection. The presence of citrullinated proteins was evaluated by anti-modified citrulline (AMC) staining. Results Circulating IC in the serum of RA patients and healthy controls contain fibrinogenβ and fibronectin, both in a non-citrullinated form. Additionally, in IC isolated from RA SF, fibrinogenγ and vimentin were identified as well. More importantly, vimentin and a minor portion of fibrinogenβ were found to be citrullinated in the isolated complexes. Moreover these citrullinated antigens were only found in ACPA+ patients. No citrullinated antigens were found in IC from SF of SpA patients. Conclusions Citrullinated fibrinogenβ and citrullinated vimentin were found in IC from SF of ACPA+ RA patients, while no citrullinated antigens were found in IC from SF of ACPA- RA patients or SpA patients or in IC from serum of RA patients or healthy volunteers. The identification of citrullinated vimentin as a prominent citrullinated antigen in IC from SF of ACPA+ RA patients strengthens the hypothesis that citrullinated vimentin

  16. Natural radioactivity of 226Ra and 228Ra in thermal and mineral waters in Croatia.

    PubMed

    Bituh, Tomislav; Marovic, Gordana; Petrinec, Branko; Sencar, Jasminka; Franulovic, Iva

    2009-01-01

    Thermal waters are known as valuable natural resources of a country. They contain certain degree of natural radioactivity attributable to the elements of the uranium and thorium natural decay series. Among these elements, the most radiotoxic and the most important is radium that exists in several isotopic forms (226Ra and 228Ra). The focus of attention was the content of radium in samples of thermal and mineral spring water from several spas in Croatia. These waters are mainly used for medical, bathing and recreational purposes, and some of them are used for drinking. Measured activity concentrations of 226Ra ranged from 87 to 6200 mBq l(-1) which, in some springs, exceed the maximal permissible level of 1 Bq l(-1) for drinking water. Measured activity concentrations of 228Ra ranged from 23 to 3480 mBq l(-1). The study showed that radium content for the investigated thermal and mineral waters is below the levels at which negative consequences would arise due to ingestion.

  17. Seasonal changes in submarine groundwater discharge to coastal salt ponds estimated using 226Ra and 228Ra as tracers

    USGS Publications Warehouse

    Hougham, A.L.; Moran, S.B.; Masterson, J.P.; Kelly, R.P.

    2008-01-01

    Submarine groundwater discharge (SGD) to coastal southern Rhode Island was estimated from measurements of the naturally-occurring radioisotopes 226Ra (t1/2 = 1600??y) and 228Ra (t1/2 = 5.75??y). Surface water and porewater samples were collected quarterly in Winnapaug, Quonochontaug, Ninigret, Green Hill, and Pt. Judith-Potter Ponds, as well as nearly monthly in the surface water of Rhode Island Sound, from January 2002 to August 2003; additional porewater samples were collected in August 2005. Surface water activities ranged from 12-83??dpm 100??L- 1 (60??dpm = 1??Bq) and 21-256??dpm 100??L- 1 for 226Ra and 228Ra, respectively. Porewater 226Ra activities ranged from 16-736??dpm 100??L- 1 (2002-2003) and 95-815??dpm 100??L- 1 (2005), while porewater 228Ra activities ranged from 23-1265??dpm 100??L- 1. Combining these data with a simple box model provided average 226Ra-based submarine groundwater fluxes ranging from 11-159??L m- 2 d- 1 and average 228Ra-derived fluxes of 15-259??L m- 2 d- 1. Seasonal changes in Ra-derived SGD were apparent in all ponds as well as between ponds, with SGD values of 30-472??L m- 2 d- 1 (Winnapaug Pond), 6-20??L m- 2 d- 1 (Quonochontaug Pond), 36-273??L m- 2 d- 1 (Ninigret Pond), 29-76??L m- 2 d- 1 (Green Hill Pond), and 19-83??L m- 2 d- 1 (Pt. Judith-Potter Pond). These Ra-derived fluxes are up to two orders of magnitude higher than results predicted by a numerical model of groundwater flow, estimates of aquifer recharge for the study period, and values published in previous Ra-based SGD studies in Rhode Island. This disparity may result from differences in the type of flow (recirculated seawater versus fresh groundwater) determined using each technique, as well as variability in porewater Ra activity. ?? 2007 Elsevier B.V. All rights reserved.

  18. Patient Activation: Public Libraries and Health Literacy

    ERIC Educational Resources Information Center

    Malachowski, Margot

    2011-01-01

    Patient activation is a new term for a perennial problem. People know what they need to do for their health: exercise, eat right, and get enough rest--but how are they motivated to actually do these things? This is what patient activation is. From this author's vantage point as a medical librarian, public libraries are well-placed to be part of…

  19. Work disability remains a major problem in rheumatoid arthritis in the 2000s: data from 32 countries in the QUEST-RA Study

    PubMed Central

    2010-01-01

    Introduction Work disability is a major consequence of rheumatoid arthritis (RA), associated not only with traditional disease activity variables, but also more significantly with demographic, functional, occupational, and societal variables. Recent reports suggest that the use of biologic agents offers potential for reduced work disability rates, but the conclusions are based on surrogate disease activity measures derived from studies primarily from Western countries. Methods The Quantitative Standard Monitoring of Patients with RA (QUEST-RA) multinational database of 8,039 patients in 86 sites in 32 countries, 16 with high gross domestic product (GDP) (>24K US dollars (USD) per capita) and 16 low-GDP countries (<11K USD), was analyzed for work and disability status at onset and over the course of RA and clinical status of patients who continued working or had stopped working in high-GDP versus low-GDP countries according to all RA Core Data Set measures. Associations of work disability status with RA Core Data Set variables and indices were analyzed using descriptive statistics and regression analyses. Results At the time of first symptoms, 86% of men (range 57%-100% among countries) and 64% (19%-87%) of women <65 years were working. More than one third (37%) of these patients reported subsequent work disability because of RA. Among 1,756 patients whose symptoms had begun during the 2000s, the probabilities of continuing to work were 80% (95% confidence interval (CI) 78%-82%) at 2 years and 68% (95% CI 65%-71%) at 5 years, with similar patterns in high-GDP and low-GDP countries. Patients who continued working versus stopped working had significantly better clinical status for all clinical status measures and patient self-report scores, with similar patterns in high-GDP and low-GDP countries. However, patients who had stopped working in high-GDP countries had better clinical status than patients who continued working in low-GDP countries. The most significant

  20. TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients

    PubMed Central

    MUÑOZ-VALLE, J F; VÁZQUEZ-DEL MERCADO, M; GARCÍA-IGLESIAS, T; OROZCO-BAROCIO, G; BERNARD-MEDINA, G; MARTÍNEZ-BONILLA, G; BASTIDAS-RAMÍREZ, B E; NAVARRO, A D; BUENO, M; MARTÍNEZ-LÓPEZ, E; BEST-AGUILERA, C R; KAMACHI, M; ARMENDÁRIZ-BORUNDA, J

    2003-01-01

    During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-γ was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease. PMID:12562402

  1. Assessment of anti-CarP antibodies, disease activity and quality of life in rheumatoid arthritis patients on conventional and biological disease-modifying antirheumatic drugs

    PubMed Central

    Kumar, Sudhir; Pangtey, Ghanshyam; Gupta, Rachna; Rehan, Harmeet Singh

    2017-01-01

    Objective Good biomarkers are important to guide decisions in the clinical management of rheumatoid arthritis (RA). RA patients harbor antibodies directed against carbamylated proteins which may predict joint damage. This study investigated whether antibodies against carbamylated proteins (anti-CarP) may serve as surrogate prognostic markers. Material and methods Fifty-three patients with a diagnosis of rheumatoid arthritis according to ACR 1987 criteria were included. Blood samples were analyzed for CarP antibody levels using the ELISA method. Quality of life (QoL) was assessed by the WHO SF-36 questionnaire, and disease activity was assessed using the DAS28 calculator. Newly diagnosed patients were assessed at the first visit and at 12 weeks of treatment, while a single assessment was made for patients already on maintenance therapy. Results Out of 53 patients, 22 had titers of anti-CarP above the cut-off range and considered as positive for anti-CarP antibodies. Anti-CarP antibody serum level was significantly higher in patients with deformity of joints and with erosions in comparison to those without any destructive changes (p < 0.05). There was a weak positive correlation between anti-CarP and DAS 28 (p > 0.05). Also there was a weak negative correlation in all domains of quality of life with anti-CarP antibody titers (p > 0.05). There was no significant correlation between titers of anti-CarP antibodies and presence or absence of rheumatoid factor. Conclusions Serum levels of anti-CarP antibodies in RA patients with joint erosions/deformities were much higher than in those without any joint damage. Anti-CarP antibodies may have good prognostic value in RA patients with erosions. Disease activity and QoL of RA patients improved during treatment, but no correlation was found between DAS 28/QoL and anti-CarP antibody serum levels. PMID:28386136

  2. OMERACT 10 Patient Perspective Virtual Campus: valuing health; measuring outcomes in rheumatoid arthritis fatigue, RA sleep, arthroplasty, and systemic sclerosis; and clinical significance of changes in health.

    PubMed

    Kirwan, John R; Boonen, Annelies; Harrison, Mark J; Hewlett, Sarah E; Wells, George A; Singh, Jasvinder A; Furst, Daniel E; Dworkin, Robert H

    2011-08-01

    This workshop reviewed progress in a number of areas related to patient perspective outcomes that were not specifically included within other areas of the program. A substantial review of the work of the valuing health outcomes group (the "QALY" working group) with participation and feedback from the plenary audience resulted in guidance to refocus on the use of patient preferences in the elaboration of more robust outcome measures for patient-reported outcomes and life impact measures. Progress and developments in the areas of fatigue and sleep in rheumatoid arthritis, outcome measures in hip and knee arthroplasty clinical trials, and scleroderma were outlined, and the challenge of truly understanding the nature of clinically important improvement was reviewed.

  3. Carotid Artery Atherosclerosis in Patients with Active Rheumatoid Arthritis: Predictors of Plaque Occurrence and Progression Over 24 Weeks

    PubMed Central

    Pope, Janet E.; Nevskaya, Tatiana; Barra, Lillian; Parraga, Grace

    2016-01-01

    Introduction: This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA). Methods: Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)≥8 OR SJC plus TJC≥4 with elevated acute phase reactants) and were enrolled (27 female; mean age 59.3±9.8years). Patients using lipid lowering drugs and uncontrolled comorbidities were excluded. Results: Atherosclerotic plaque occurred in 35% and arterial wall hypertrophy (IMT≥0.6mm) in 86% of patients. Most (68%) had an abnormal lipid profile characterized by reduced HDL and/or increased total cholesterol/HDL index, which was adversely affected by disease activity. Stepwise binary logistic regression analysis showed that Framingham risk score (OR=1.155, 95%CI:1.002-1.332, p=0.046) and ESR (OR=1.148, 95%CI:1.015-1.299, p=0.028) predicted plaque burden most strongly. Plaque progression was significantly associated with baseline higher hsCRP, ESR, and heavy smoking, but only hsCRP predicted plaque growth in multivariate regression analysis (p=0.004); and hsCRP was related to higher disease activity (r=0.443, p=0.016), LDL (r=0.544, p=0.007), and smoking (r=0.384, p=0.04). Conclusion: RA-related inflammation contributed to augmented CV burden in RA and might mediate its effect on atherosclerosis through hsCRP and modulation of the traditional CV risk factors, such as dyslipidemia. PMID:27857821

  4. The major risk alleles of age-related macular degeneration (AMD) in CFH do not play a major role in rheumatoid arthritis (RA).

    PubMed

    Trouw, L A; Böhringer, S; Daha, N A; Stahl, E A; Raychaudhuri, S; Kurreeman, F A; Stoeken-Rijsbergen, G; Houwing-Duistermaat, J J; Huizinga, T W; Toes, R E

    2011-12-01

    Because activation of the alternative pathway (AP) of the complement system is an important aspect of both age-related macular degeneration (AMD) and rheumatoid arthritis (RA), we wished to address the question whether genetic risk factors of the AP inhibitor complement factor H (CFH) for AMD would also be risk factors for RA. For this purpose we genotyped single nucleotide polymorphisms (SNPs) in a Dutch set of RA patients and controls. Similarly, a meta-analysis using a Spanish cohort of RA as well as six large genome-wide association studies (GWAS) studies was performed. For these SNPs we analysed more than 6000 patients and 20,000 controls. The CFH variants, I62V, Y402H, IVS1 and IVS10, known to associate strongly with AMD, did not show a significant association with the risk of developing RA despite a strong statistical power to detect such differences. In conclusion, the major risk alleles of AMD in CFH do not have a similar effect on developing RA.

  5. What explains the intention to be physically active in cancer patients? Different determinants for active and insufficiently active patients.

    PubMed

    Ungar, Nadine; Sieverding, Monika; Ulrich, Cornelia M; Wiskemann, Joachim

    2015-01-01

    In a qualitative elicitation study with 61 cancer patients, a broad range of attitudes toward physical activity could be obtained, especially negative attitudes among insufficiently active patients. Based on these results, a second quantitative study was conducted; 64 patients [40 men; 42% insufficiently active (<150 minutes/week)] completed a Theory of Planned Behavior (TPB) questionnaire. Regression analyses revealed that different variables of the TPB are relevant for explaining the intention to exercise for physically active (subjective norm) and insufficiently active (attitudes) cancer patients. Health professionals should adapt their support to the special needs of insufficiently active and active cancer patients.

  6. Changes in foot function, disease activity, and disability after forefoot resection arthroplasty in patients with rheumatoid arthritis.

    PubMed

    Sawachika, Fusakazu; Uemura, Hirokazu; Katsuura-Kamano, Sakurako; Yamaguchi, Miwa; Bahari, Tirani; Miki, Keisuke; Todo, Satoshi; Inoo, Masayuki; Onishi, Ikuko; Kurata, Noriyuki; Arisawa, Kokichi

    2016-01-01

    The purpose of this study was to investigate the changes in foot function, disease activity, and disability in patients with RA after resection arthroplasty of the forefoot (arthroplasty). Arthroplasty was performed on 11 patients with RA. All study patients underwent clinical assessment to measure disease activity (Disease Activity Score in 28 Joints-C-reactive protein, DAS28-CRP), disability (Health Assessment Questionnaire-Disability Index, HAQ-DI) and foot function (Foot Function Index, FFI) at the following stages: preoperatively and 1, 3, and 12 months after surgery. Following arthroplasty, foot function improved significantly, as assessed by FFI total and subscales (pain, disability, and limitation of activity) (P<0.001, P<0.001, P<0.001, and P=0.002, respectively). Disease activity was significantly improved in relation to DAS28-CRP and its subscales of number of swollen joints and patient global assessment (PtGA) (P=0.033, P=0.008, and P=0.038, respectively). There was no significant difference in disability, as assessed by the HAQ-DI and its subscale, HAQ-walking (P=0.150 and P=0.597, respectively). Foot function improved significantly after arthroplasty, and was maintained at 12 months postoperatively. Additionally, our study showed that disease activity and its subscale PtGA improved after arthroplasty.

  7. Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Johnson, Cheilonda; Giles, Jon T.; Bathon, Joan; Lederer, David; Hoffman, Eric A.; Barr, R. Graham; Danoff, Sonye K.

    2016-01-01

    A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10–42) and 15(IQR 5–31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007–0.05%) in RA patients and by 0.008% (95% CI, 0.003–0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population. PMID:27050433

  8. Production of Ra225 precursor for Ac225/Bi213 generators. Final CRADA Report.

    SciTech Connect

    Ehst, D. A.; Nuclear Engineering Division

    2009-10-02

    Russian subcontractors shipped two small deliveries of Ra225 to PNNL for evaluation. The activity was close to the requisite amount in the subcontract. The first labeled properly; the second did not. This showed that the Russians could supply Ra225 to the US; however they proved unable to meet future demands for larger amounts of activity. The US DOE attempts to get Ra225 from Russian should be terminated; the Russians, under Rosatom, are not interested in this business.

  9. Alterations of brain activity in fibromyalgia patients.

    PubMed

    Sawaddiruk, Passakorn; Paiboonworachat, Sahattaya; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-04-01

    Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients. Nevertheless, due to few studies, limited knowledge for alterations in brain activities in fibromyalgia is currently available. In this review, the changes in brain activity in various brain areas obtained from reports in fibromyalgia patients are comprehensively summarized. Changes of the grey matter in multiple regions such as the superior temporal gyrus, posterior thalamus, amygdala, basal ganglia, cerebellum, cingulate cortex, SII, caudate and putamen from the MRI as well as the increase of brain activities in the cerebellum, prefrontal cortex, anterior cingulate cortex, thalamus, somatosensory cortex, insula in fMRI studies are presented and discussed. Moreover, evidence from pharmacological interventions offering benefits for fibromyalgia patients by reducing brain activity is presented. Because of limited knowledge regarding the roles of brain activity alterations in fibromyalgia, this summarized review will encourage more future studies to elucidate the underlying mechanisms involved in the brains of these patients.

  10. Single cell cloning and recombinant monoclonal antibodies generation from RA synovial B cells reveal frequent targeting of citrullinated histones of NETs

    PubMed Central

    Corsiero, Elisa; Bombardieri, Michele; Carlotti, Emanuela; Pratesi, Federico; Robinson, William; Migliorini, Paola; Pitzalis, Costantino

    2016-01-01

    Objectives Rheumatoid arthritis (RA) is characterised by breach of self-tolerance towards citrullinated antigens with generation of anti-citrullinated peptide/proteins antibodies (ACPA). Currently, the nature and source of citrullinated antigens driving the humoral autoimmune response within synovial ectopic lymphoid structures (ELS) is a crucial unknown aspect of RA pathogenesis. Here we characterised the autoreactive B-cell response of lesional B cells isolated from ELS+RA synovium. Methods Single synovial tissue CD19+cells were Fluorescence Activated Cell Sorting (FACS)-sorted and VH/VL Ig genes cloned to generate recombinant monoclonal antibodies (rmAbs) from patients with ELS+/ACPA+RA. Results RA-rmAbs immunoreactivity analysis provided the following key findings: (1) in a chIP-based array containing 300 autoantigens and in a ‘citrullinome’ multiplex assay, a strong reactivity against citrullinated histones H2A/H2B (citH2A/H2B) was observed in ∼40% of RA-rmAbs, followed by cit-fibrinogen and cit-vimentin; (2) anti-citH2A/H2B-reactive RA-rmAbs (but not anti-citH2A/H2B negative) selectively recognised neutrophil extracellular traps (NETs) from peripheral blood and/or RA joint neutrophils; (3) anti-citH2A/citH2B and anti-NET immunobinding was dependent on affinity maturation and was completely abrogated following reversion of hypermutated IgVH/VL genes to germline sequences; (4) ELS+ (not ELS−) RA synovial tissues engrafted into Severe Combined ImmunoDeficiency (SCID) mice released human anti-citH2A/citH2B and anti-NET antibodies in association with the intra-graft expression of CXCL13 and lymphotoxin (LT)-β, two master regulators of ELS. Conclusion We provided novel evidence that B cells differentiated within synovial ELS in the RA joints frequent target deiminated proteins which could be generated during NETosis of RA synovial neutrophils including histones. Thus, NETs could represent a source of citrullinated antigens fuelling the ACPA autoimmune

  11. IL2RA — EDRN Public Portal

    Cancer.gov

    The interleukin 2 receptor exists in three forms which differ in their ability to bind interleukin 2. The low affinity form of the receptor is a monomer of IL2RA, the alpha subunit. The alpha/beta subunit heterodimer, formed by IL2RA and IL2RB, is an intermediate affinity form. The alpha/beta/gamma heterotrimer formed by IL2RA, IL2RB, and IL2RG is the high affinity form. IL2RA is normally an integral membrane protein, although soluble IL2RA has been isolated. There are known alternately-spliced versions of IL2RA mRNAs, but their functions are unknown. Mutations in the IL2RA gene are associated with diabetes mellitus insulin-dependent type 10 (IDDM10). Complications of IDDM10 can adversely affect the eyes, kidneys, nerves, and blood vessels.

  12. Secretory activity of subcutaneous abdominal adipose tissue in male patients with rheumatoid arthritis and osteoarthritis – association with clinical and laboratory data

    PubMed Central

    Zielińska, Agnieszka; Księżopolska-Orłowska, Krystyna; Głuszko, Piotr

    2016-01-01

    Introduction Adipose tissue exerts widespread effects on the metabolism and immune system, but its activity differs between the genders. In the general population low-grade adipose tissue inflammation contributes to development of diseases of affluence. Little is known about the systemic impact of peripheral fat tissue in osteoarthritis (OA) and rheumatoid arthritis (RA), characterized by chronic, low- and high-grade systemic inflammation, respectively. To clarify this we evaluated the secretory activity of subcutaneous abdominal adipose tissue (SAAT) obtained from male patients affected with RA (n = 21) and OA (n = 13), and assessed its association with body mass and composition, demographic, clinical and laboratory data. Material and methods Basal and interleukin (IL)-1β-triggered secretion of selected adipocytokines from SAAT explants was measured by specific enzyme-linked immunosorbent assays (ELISA). Patients’ body composition was evaluated by bioelectric impendence technique. Results Rheumatoid SAAT secreted more adiponectin and macrophage migration inhibitory factor (MIF) than respective osteoarthritis tissue. In both RA and OA patient groups, stimulation of SAAT explants with IL-1β (1 ng/ml/100 mg tissue) significantly up-regulated release of pro-(IL-6, IL-8, tumor necrosis factor – TNF) and anti-inflammatory (IL-10) cytokines but had no effect on the secretion of adiponectin, leptin, MIF and hepatocyte growth factor (HGF). Compared with RA, patients with OA were more obese. In RA patients SAAT-released adiponectin and TNF inversely correlated with body mass index (BMI) and visceral fat rating (FVSC). In addition, SAAT-secreted adiponectin and leptin positively correlated with DAS28 and disease duration, respectively. In the OA group tissue-released TNF positively correlated with patients’ age. Conclusions We conclude that in RA male patients adipocytokines originating from SAAT are of clinical importance because: (i) adiponectin and TNF may

  13. Medication persistence over 2 years of follow-up in a cohort of early rheumatoid arthritis patients: associated factors and relationship with disease activity and with disability

    PubMed Central

    Pascual-Ramos, Virginia; Contreras-Yáñez, Irazú; Villa, Antonio R; Cabiedes, Javier; Rull-Gabayet, Marina

    2009-01-01

    Introduction Aggressive treatment with disease-modifying antirheumatic drugs (DMARDs) plays a major role in improving early rheumatoid arthritis (RA) patient outcomes. Persistence and adherence with medication occurs variably (20% to 70%). The objectives of the study were to determine medication persistence (MP) in early RA patients over 13 consecutive visits each 2 months apart, to investigate the relationship between MP and disease activity, disability and structural damage, and to identify baseline prognosticators. Methods Charts from 75 patients of an early RA cohort were reviewed. At each visit, a rheumatologist interviewed patients regarding therapy, scored disease activity with the 28-joint disease activity score (DAS28) and disability with the health assessment questionnaire (HAQ), and recorded comorbidities and treatment. A complete medical history was obtained at baseline. MP was defined as the duration of time from initiation to discontinuation of at least one DMARD and/or corticosteroids for at least 1 week and was reported as a dichotomous variable at consecutive evaluations. Structural damage was defined by detection of new erosions on radiography. Descriptive statistics, Student's t test, the chi-squared test, and logistic regression analyses were used. Results The proportion of MP patients decreased from 98% at 2 months to 34% at 2 years. MP patients (n = 32) had similar DAS28 to non-MP patients (n = 53) at initial visits, lower DAS28 and greater DAS28 improvements at follow-ups (P ≤ 0.05 at visits 4, 6, 7 and 9) and reached sustained remission (≥ 3 consecutive visits with DAS28 < 2.6) more frequently (82.8% versus 46.5%, P = 0.003) and earlier (7.7 ± 4.6 versus 13.6 ± 5.7 months, P = 0.001) than non-MP patients. MP patients had similar baseline HAQ scores, but lower HAQ scores at follow-up (P ≤ 0.05 at visits 3, 5, 6, 7, 9, 10 and 13). More non-MP patients developed erosive disease than MP patients (26.8% versus 17.9%, P = 0.56). Older age

  14. Physical activity in patients with anorexia nervosa.

    PubMed

    Achamrah, Najate; Coëffier, Moïse; Déchelotte, Pierre

    2016-05-01

    Anorexia nervosa (AN) is often associated with physical hyperactivity. Recent studies have established links between anorexia and hyperactivity, suggesting the existence of commonalities in neural pathways. How physical activity should be managed during the clinical care of patients with anorexia remains controversial. This review first focuses on the implication of hyperactivity in the pathophysiology of AN. Hyperactivity during refeeding of patients with AN has been associated with increased energy needs to achieve weight gain, poorer clinical outcome, longer hospitalization, and increased psychiatric comorbidity. This typically leads to the prescription of bed rest. However, current knowledge suggests that preserving some kind of physical activity during refeeding of patients with AN should be safe and beneficial for the restoration of body composition, the preservation of bone mineral density, and the management of mood and anxiety. In the absence of standardized guidelines, it is suggested here that physical activity during refeeding of patients with AN should be personalized according to the physical and mental status of each patient. More research is needed to assess whether programmed physical activity may be a beneficial part of the treatment of AN.

  15. Prolidase activity in chronic plaque psoriasis patients

    PubMed Central

    Aksoy, Nurten; Ozgöztas, Orhan; Sezen, Hatice; Yesilova, Yavuz; Turan, Enver

    2015-01-01

    Introduction Psoriasis is a chronic, inflammatory, T-cell-mediated and hyperproliferative skin disease characterized by erythematous, squamous, sharply circumscribed and infiltrated plaques. The metabolisms of the collagen proteins undergo considerable changes due to the acceleration of their turnovers as a result of increased prolidase activity in psoriasis patients. Aim To determine the level of prolidase activity in psoriasis patients and evaluate its relationship with the oxidative system. Material and methods The serum prolidase enzyme activity, total antioxidant levels and total oxidant levels of 40 psoriasis patients and a control group including 47 healthy individuals were analyzed by using their serum samples, and their oxidative stress indices were calculated. Results The prolidase levels (p < 0.01), total oxidant levels (p < 0.01) and oxidative stress index levels (p < 0.001) of the patient group were higher than the corresponding parameters in the control group. The total antioxidant level was low (p < 0.01). Although a positive correlation was found between the prolidase and total antioxidant levels and the total oxidant level, no correlation was found between prolidase and the oxidative stress index. Conclusions It has been determined that the activity of the prolidase enzyme increases due to the increased collage turnover in psoriasis patients. Increased serum oxidant levels and oxidative stress indices values may play a role in the pathogenesis of psoriasis. PMID:26015776

  16. Serum Calprotectin Discriminates Subclinical Disease Activity from Ultrasound-Defined Remission in Patients with Rheumatoid Arthritis in Clinical Remission

    PubMed Central

    Hulejova, Hana; Zavada, Jakub; Komarc, Martin; Hanova, Petra; Klein, Martin; Mann, Herman; Sleglova, Olga; Olejarova, Marta; Forejtova, Sarka; Ruzickova, Olga; Vencovsky, Jiri; Pavelka, Karel; Senolt, Ladislav

    2016-01-01

    Objective Clinical remission in some patients with rheumatoid arthritis (RA) may be associated with ongoing synovial inflammation that is not always detectable on clinical examination or reflected by laboratory tests but can be visualized by musculoskeletal ultrasound. The goal of our study was to determine the levels of serum calprotectin, a major leukocyte protein, in patients with RA in clinical remission and to investigate the ability of serum calprotectin levels to distinguish patients in ultrasound-defined remission from those with residual ultrasound subclinical inflammation. Methods Seventy RA patients in clinical remission underwent clinical and ultrasound examination. Ultrasound examination was performed according to the German US7 score. Ultrasound remission was defined as grey scale (GS) range 0–1 and power Doppler (PD) range 0. The levels of serum calprotectin and C-reactive protein (CRP) were determined. The discriminatory capacity of calprotectin and CRP in detecting residual ultrasound inflammation was assessed using ROC curves. Results The total number of patients fulfilling the DAS28-ESR, DAS28-CRP, SDAI and CDAI remission criteria was 58, 67, 32 and 31, respectively. Residual synovial inflammation was found in 58–67% of the patients who fulfilled at least one set of clinical remission criteria. Calprotectin levels were significantly higher in patients with residual synovial inflammation than in those with ultrasound-defined remission (mean 2.5±1.3 vs. 1.7±0.8 μg/mL, p<0.005). Using ultrasound-defined remission criteria, calprotectin had an AUC of 0.692, p<0.05 using DAS28-ESR remission criteria and an AUC of 0.712, p<0.005 using DAS28-CRP remission criteria. Calprotectin correctly distinguished ultrasound remission from subclinical activity in 70% of patients. CRP (AUC DAS28-ESR = 0.494, p = NS; AUC DAS28-CRP = 0.498, p = NS) had lower and insignificant discriminatory capacity. Conclusion The present study demonstrates the potential of

  17. The effects of isometric exercise types on pain and muscle activity in patients with low back pain

    PubMed Central

    Rhyu, Hyun-Seung; Park, Hun-Kyung; Park, Jung-Sub; Park, Hye-Sang

    2015-01-01

    The purpose of the present study is to evaluate the effects of isometric exercise types on low back pain (LBP) patients. Isometric exercise types were mat exercise and I-Zer exercise. Subjects were divided into 3 groups: LBP control group, LBP mat exercise group, and LBP I-Zer exercise group in 23–25 aged men. Visual analogue scale (VAS) and electromyography (EMG) were used to evaluate the degree of pain and the muscle activity in LBP patients. Root mean square (RMS), median frequency (MDF), and mean frequency (MNF) were checked by EMG power spectrum analysis on longissimus thoracic (LT), iliocostalis lumborum (IL), mulitifidus (M), and rectus abdominis (RA). LBP mat exercise program and LBP I-Zer exercise program were conducted 5 sets once time, 3 times per week during 6 weeks. The two-way ANOVA with repeated measure was used to check the pain degree and muscle activity. The present results showed that muscle activity in the LBP I-Zer exercise group was increased compared to the LBP mat exercise group and LBP control group (P<0.05). LBP I-Zer exercise group and LBP mat exercise group showed increased mean frequency in LT, IL, M, and RA muscles than the LBP control group. Therefore, LBP patients performed isometric exercise may have positive effect to reduce pain degree and to increase muscle activity. Especially, LBP I-Zer exercise type showed more effectiveness in reducing pain degree and enhancing muscle activity. PMID:26331136

  18. Induction of antinuclear antibodies in patients with rheumatoid arthritis receiving treatment with human recombinant interferon gamma.

    PubMed Central

    Seitz, M; Franke, M; Kirchner, H

    1988-01-01

    Of six patients with rheumatoid arthritis (RA) treated with human recombinant interferon gamma for two to eight months, three developed antinuclear antibodies (ANAs). This was accompanied by a simultaneous clinical exacerbation of the disease activity. In this study both anti-inflammatory and immunostimulatory effects of human recombinant interferon gamma in patients with RA were observed. PMID:3137901

  19. When seeing the same physician, highly activated patients have better care experiences than less activated patients.

    PubMed

    Greene, Jessica; Hibbard, Judith H; Sacks, Rebecca; Overton, Valerie

    2013-07-01

    Measures of the patient care experience are now routinely used in public reports and increasingly influence health provider payment. We examined data from 5,002 patients of forty-nine primary care providers to explore the relationship between patient activation-a term referring to the knowledge, skills, and confidence a patient has for managing his or her health care-and the patient care experience. We found that patients at higher levels of activation had more positive experiences than patients at lower levels seeing the same clinician. The observed differential was maintained when we controlled for demographic characteristics and health status. We did not find evidence that patients at higher levels of activation selected providers who were more patient-centric. The findings suggest that the care experience is transactional, shaped by both providers and patients. Strategies to improve the patient experience, therefore, should focus not only on providers but also on improving patients' ability to elicit what they need from their providers.

  20. Effects of patient education on compliance with basic treatment regimens and health in recent onset active rheumatoid arthritis

    PubMed Central

    Brus, H.; van de Laar, M. A F J; Taal, E.; Rasker, J.; Wiegman, O.

    1998-01-01

    OBJECTIVES—To determine the effects of patient education on compliance and on health in patients with active, recent onset rheumatoid arthritis (RA).
METHODS—A randomised, controlled, assessor blinded, one year trial. The experimental group followed an education programme. All patients started on sulphasalazine therapy. Compliance with sulphasalazine was measured by pill counting. Compliance rates with regimens of physical exercise, endurance activities, and energy conservation were measured by questionnaires. Compliance with prescriptions of joint protection was scored using a test for joint protection performance. Health was measured by a Disease Activity Score (function of erythrocyte sedimentation rate, Ritchie score, and number of swollen joints), C reactive protein, Dutch-AIMS scores, and M-HAQ scores, range of motion of shoulder, elbow, and knee joints. Parameters were scored at baseline and after three, six, and 12 months.
RESULTS—Sixty of 65 patients gave informed consent, five of them withdrew from follow up. Compliance with sulphasalazine exceeded 80% with no differences between groups. Compliance with physical exercise (at three months), energy conservation (at three and at 12 months), and joint protection (at three months) improved significantly more in the experimental group. The improvements of health were not different in the groups.
CONCLUSION—Compliance with sulphasalazine among patients with active, recent onset RA is high, whether formal patient education is followed or not. Compliance with physical exercise, energy conservation, and joint protection was increased by patient education. Formal patient education did not improve health status.

 Keywords: rheumatoid arthritis; compliance; health status; patient education PMID:9640129

  1. Alternative expression pattern of MALT1-A20-NF-κB in patients with rheumatoid arthritis.

    PubMed

    Wang, Xu; Zhu, Lihua; Liao, Ziwei; Zhang, Fan; Xu, Ling; Xu, Yan; Chen, Shaohua; Yang, Lijian; Zhou, Yi; Li, Yangqiu

    2014-01-01

    Rheumatoid arthritis (RA) is an inflammatory autoimmune disorder; abnormal T cell immunity plays a critical role in the development of RA. Recently, A20 was identified as a key negative regulator for T cell activation and inflammatory signaling and may be involved in RA pathogenesis. In this study, we analyzed the expression level of A20, NF-κB, and A20 regulatory factor mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) in patients with RA. Real-time PCR was used to determine the expression level of MALT1, MALT-V1, A20, and NF-κB genes in RA and healthy individuals (HI). Significantly lower A20 expression was found in RA patients compared with those in the healthy group, while NF-κB overexpression could be detected in patients with RA. Moreover, the MALT1 and MALT1-V1 expression level was downregulated in RA patients. A positive correlation between MALT1 and A20 and MALT1-V1 and A20 was found in patients with RA, and a tendency towards a negative correlation was found between MALT1 and NF-κB, MALT1-V1 and NF-κB, and A20 and NF-κB. In conclusion, we first characterized the alternative expression pattern of MALT1, A20, and NF-κB in RA, which may be related to abnormal T cell activation.

  2. The Impact of DMARD and Anti-TNF Therapy on Functional Characterization of Short-Term T-Cell Activation in Patients with Rheumatoid Arthritis – A Follow-Up Study

    PubMed Central

    Szalay, Balázs; Cseh, Áron; Mészáros, Gergő; Kovács, László; Balog, Attila; Vásárhelyi, Barna

    2014-01-01

    Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a systemic dysfunction of T-cells. In this study we tested the impact of DMARD and anti-TNF agents on short-term activation characteristics of T-cells. We enrolled 12 patients with newly diagnosed RA (naïve RA) who were treated with methothrexate (MTX) and glucocorticsteroid (GCS) and 22 patients with established RA non responding to conventional DMARD therapy who were treated with different anti-TNF agents. Nine healthy volunteers served as controls. Blood samples were taken at baseline, then at 4th and 8th week of therapy. The characteristics of several intracellular activation processes during short-term activation of T-cells including cytoplasmic Ca2+ level, mitochondrial Ca2+ level, reactive oxygen species (ROS) and nitric oxide (NO) generation were determined by a novel flow-cytometry technique. At baseline, the tested processes were comparable to controls in naïve RA. During GCS therapy, cytoplasmic Ca2+ level and ROS generation decreased. After the addition of MTX to GCS cytoplasmic Ca2+ level became comparable to controls, while ROS generation decreased further. In DMARD non responders, cytoplasmic Ca2+ level was higher than controls at baseline. The cytoplasmic Ca2+ level became comparable to controls and ROS generation decreased during each of the three anti-TNF-α agent therapies. Mitochondrial Ca2+ level and NO generation were unaltered in all of the patient groups. These results indicate that intracellular machinery is affected in T-cells of RA patients. This may alter the behavior of T-cells during activation. Different therapeutic approaches may modulate the abnormal T-cell functions. PMID:25098248

  3. Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study

    PubMed Central

    Thomsen, Tanja; Beyer, Nina; Aadahl, Mette; Hetland, Merete L.; Løppenthin, Katrine; Midtgaard, Julie; Esbensen, Bente A.

    2015-01-01

    Background Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. Methods Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. Results SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. Conclusions SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients’ motivation towards sustainable change in SB and activity patterns. PMID:26462971

  4. Gamma-N activation of cancer patients

    SciTech Connect

    Wielopolski, L.; Meek, A.G.; Moskowitz, M.; Cohn, S.H.

    1986-01-01

    High energy gamma radiation (8 to 30 MeV) is gaining acceptance for radiation therapy of patients with deep cancers. This radiation is of sufficient energy to induce photonuclear activation of the elements in the human body. Our results of measurements of nitrogen and phosphorus in an anthropomorphic phantom, a cadaver, and a cancer patient with bremsstrahlung radiation from 15 MeV electrons demonstrate the feasibility of a method to monitor these two elements in the human body in vivo by measuring the radioactivity induced in these targets by photonuclear reactions. 14 refs., 3 figs., 2 tabs.

  5. Association of Cardiovascular Risk Factors with Carotid Intima Media Thickness in Patients with Rheumatoid Arthritis with Low Disease Activity Compared to Controls: A Cross-Sectional Study

    PubMed Central

    van Breukelen—van der Stoep, Deborah F.; van Zeben, Derkjen; Klop, Boudewijn; van de Geijn, Gert-Jan M.; Janssen, Hans J. W.; Hazes, Mieke J. M. W.; Birnie, Erwin; van der Meulen, Noelle; De Vries, Marijke A.; Castro Cabezas, Manuel

    2015-01-01

    Objectives Rheumatoid arthritis (RA) has been identified as an independent cardiovascular risk factor. The importance of risk factors such as hypertension and hyperlipidemia in the generation of atherosclerosis in RA patients is unclear. This study analyzed clinical parameters associated with carotid intima media thickness (cIMT) in patients with RA. Methods Subjects with RA and healthy controls without RA, both without known cardiovascular disease, were included. Participants underwent a standard physical examination and laboratory measurements including a lipid profile. cIMT was measured semi-automatically by ultrasound. Results In total 243 RA patients and 117 controls were included. The median RA disease duration was 7 years (IQR 2–14 years). The median DAS28 was 2.4 (IQR 1.6–3.2) and 114 (50.4%) of the RA patients were in remission. The presence of RA and cIMT were not associated (univariate analysis). Multivariable regression analysis showed that cIMT in RA patients was associated with age (B = 0.006, P<0.001) and systolic blood pressure (B = 0.003, P = 0.003). In controls, cIMT was associated with age (B = 0.006, P<0.001) and smoking (B = 0.097, P = 0.001). Conclusion cIMT values were similar between RA patients and controls. Hypertension was strongly associated with cIMT in RA patients. After adjustment, no association between cIMT and specific RA disease characteristics was found in this well treated RA cohort. PMID:26485681

  6. Venous thromboembolism in patients with active cancer.

    PubMed

    Seddighzadeh, Ali; Shetty, Ranjith; Goldhaber, Samuel Z

    2007-09-01

    Patients with cancer have an increased risk of venous thromboembolism (VTE). To further define the demographics, comorbidities, and risk factors of VTE in these patients, we analyzed a prospective registry of 5,451 patients with ultrasound confirmed deep vein thrombosis (DVT) from 183 hospitals in the United States. Cancer was reported in 1,768 (39%), of whom 1,096 (62.0%) had active cancer. Of these, 599 (54.7%) were receiving chemotherapy, and 226 (20.6%) had metastases. Lung (18.5%), colorectal (11.8%), and breast cancer (9.0%) were among the most common cancer types. Cancer patients were younger (median age 66 years vs. 70 years; p < 0.0001), were more likely to be male (50.4% vs. 44.5%; p = 0.0005), and had a lower average body mass index (26.6 kg/m(2) vs. 28.9 kg/m(2); p < 0.0001). Cancer patients less often received VTE prophylaxis prior to development of DVT compared to those with no cancer (308 of 1,096, 28.2% vs. 1,196 of 3,444, 34.6%; p < 0.0001). For DVT therapy, low-molecular-weight heparin (LMWH) as monotherapy without warfarin (142 of 1,086, 13.1% vs. 300 of 3,429, 8.7%; p < 0.0001) and inferior vena caval filters (234 of 1,086, 21.5% vs. 473 of 3,429, 13.8%; p < 0.0001) were utilized more often in cancer patients than in DVT patients without cancer. Cancer patients with DVT and neurological disease were twice as likely to receive inferior vena caval filters than those with no cancer (odds ratio 2.17, p = 0.005). In conclusion, cancer patients who develop DVT receive prophylaxis less often and more often receive filters than patients with no cancer who develop DVT. Future studies should focus on ways to improve implementation of prophylaxis in cancer patients and to further define the indications, efficacy, and safety of inferior vena caval filters in this population.

  7. Rapid determination of 226Ra in environmental samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.

    2012-02-04

    A new rapid method for the determination of {sup 228}Ra in natural water samples has been developed at the SRNL/EBL (Savannah River National Lab/ Environmental Bioassay Laboratory) that can be used for emergency response or routine samples. While gamma spectrometry can be employed with sufficient detection limits to determine {sup 228}Ra in solid samples (via {sup 228}Ac) , radiochemical methods that employ gas flow proportional counting techniques typically provide lower MDA (Minimal Detectable Activity) levels for the determination of {sup 228}Ra in water samples. Most radiochemical methods for {sup 228}Ra collect and purify {sup 228}Ra and allow for {sup 228}Ac daughter ingrowth for ~36 hours. In this new SRNL/EBL approach, {sup 228}Ac is collected and purified from the water sample without waiting to eliminate this delay. The sample preparation requires only about 4 hours so that {sup 228}Ra assay results on water samples can be achieved in < 6 hours. The method uses a rapid calcium carbonate precipitation enhanced with a small amount of phosphate added to enhance chemical yields (typically >90%), followed by rapid cation exchange removal of calcium. Lead, bismuth, uranium, thorium and protactinium isotopes are also removed by the cation exchange separation. {sup 228}Ac is eluted from the cation resin directly onto a DGA Resin cartridge attached to the bottom of the cation column to purify {sup 228}Ac. DGA Resin also removes lead and bismuth isotopes, along with Sr isotopes and {sup 90}Y. La is used to determine {sup 228}Ac chemical yield via ICP-MS, but {sup 133}Ba can also be used instead if ICP-MS assay is not available. Unlike some older methods, no lead or strontium holdback carriers or continual readjustment of sample pH is required.

  8. Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes.

    PubMed

    Mercader, N; Leonardo, E; Piedra, M E; Martínez-A, C; Ros, M A; Torres, M

    2000-09-01

    Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

  9. Optimizing Rheumatoid Arthritis Therapy: Using Objective Measures of Disease Activity to Guide Treatment

    PubMed Central

    Owens, Gary M.

    2015-01-01

    Background Rheumatoid arthritis (RA) affects approximately 1.5 million individuals in the United States, or approximately 1% of the US adult population. In women, RA most often begins between age 30 and 60 years; in men, it often starts later in life. Patients with RA may have rapid declines in physical function that can begin early in the disease course. Disability increases most rapidly during the early years of the disease course, and if patients are not accurately diagnosed and do not receive appropriate care early, substantial functional declines may result. Objective To review strategies and clinical assessment tools that may optimize patient outcomes by using objective measures of disease activity. Discussion The goal of treatment for patients newly diagnosed with RA should be preventing joint damage from developing by employing early and aggressive approaches to therapy that minimize disease activity. Likewise, for established disease, treatment should be aimed at limiting the progression of existing joint damage. Substantial advances have been made in the treatment of RA over the past 2 decades, in large part as a result of better understanding of the biology of RA and the resultant introduction of biologic therapies. In 2010, an international task force published recommendations for a treat-to-target management approach to RA, much of which was based on the use of biologic drugs. This treatment strategy emphasized that the primary target in the treatment of patients with RA should be clinical remission or low disease activity. The tools necessary to measure RA disease activity are often incomplete, imprecise, or rely on a combination of physician and patient subjective evaluations. There is no one symptom, laboratory measure, or clinical tool that provides a truly accurate assessment of disease activity in patients with RA. Conclusion Thus, there is a large gap between what is recommended in clinical guidelines and the actual practice of rheumatologists

  10. Spontaneous release of angiotensin converting enzyme and interleukin 1 beta from peripheral blood monocytes from patients with rheumatoid arthritis under a serum free condition.

    PubMed Central

    Goto, M; Fujisawa, M; Yamada, A; Okabe, T; Takaku, F; Sasano, M; Nishioka, K

    1990-01-01

    Angiotensin converting enzyme (ACE) and interleukin 1 activities were assayed simultaneously in the serum free medium from the unstimulated peripheral blood monocytes from 32 patients with rheumatoid arthritis (RA), 11 patients with osteoarthritis, and 25 normal controls matched for age and sex. Angiotensin converting enzyme activity was raised in most (29/32) patients with RA and interleukin 1 activity (most of which was interleukin 1 beta) was enhanced in 11/32 patients with RA, while monocytes from only two patients with osteoarthritis, but from none of the controls, secreted a small amount of ACE alone in the culture condition. Monocytes from patients with early RA (disease duration less than 3 years) released significantly more ACE and interleukin 1 than those from late stage RA (disease duration greater than or equal to 3 years). PMID:2157375

  11. Mental health status can reflect disease activity in rheumatoid arthritis

    PubMed Central

    Sokolovic, Sekib; Dervisevic, Vedina; Fisekovic, Saida

    2014-01-01

    Objective A significant number of patients with rheumatoid arthritis (RA) link the start of illness with psychological trauma or severe stress. Impaired mental health (IMH), defined as depression and anxiety with psychoneuroimmunological factors, can play a significant role in RA. The main objective of this research was to investigate the mutual correlation of IMH and RA activity, estimated by the laboratory and clinical parameters in RA patients. Material and Methods An open clinical prospective study that lasted for 6 months was designed. There were 72 patients included, 58 women and 14 men, aged 34 to 80 years and screened for mental health status. The study population was randomized following the Brief Symptoms Inventory (BSI) scale, comprised of 53 questions with a range from 0 (no symptoms) to 4 (severe). This mental test was done only once during the study. Following the results from the BSI scale, RA patients were divided into mentally stable and mentally unstable patients to investigate the influence of RA activity on mental health. The following laboratory and clinical parameters were analyzed: sex, age, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide (anti-CCP) antibody, and disease activity score (DAS28). All RA patients did not express extra-articular manifestations or Sjögren’s syndrome. The chi-square test, ANOVA, Pearson’s coefficient, and IBM Statistics - SPSS v19 were used. Results From a total of 72 RA patients, there were 44 mentally stable and 28 mentally unstable patients. All patients had either moderate or severe active disease. The only significant correlation of IMH and activity of RA was found in CRP and DAS28, but no significance was observed in ESR, RF, and anti-CCP. The DAS28 showed high disease activity with an average of 5.3 and CRP of 20.9 mg/L in patients with unstable mental health compared to stable mental health patients, where RA was associated with

  12. Prediction of Large Joint Destruction in Patients With Rheumatoid Arthritis Using 18F-FDG PET/CT and Disease Activity Score.

    PubMed

    Suto, Takahito; Okamura, Koichi; Yonemoto, Yukio; Okura, Chisa; Tsushima, Yoshito; Takagishi, Kenji

    2016-02-01

    The assessments of joint damage in patients with rheumatoid arthritis (RA) are mainly restricted to small joints in the hands and feet. However, the development of arthritis in RA patients often involves the large joints, such as the shoulder, elbow, hip, knee, and ankle. Few studies have been reported regarding the degree of large joint destruction in RA patients. F-fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT) visualizes the disease activity in large joints affected by RA. In this study, the associations between destruction of the large joints and the findings of FDG-PET/CT as well as laboratory parameters were investigated, and factors associated with large joint destruction after the administration of biological therapy were identified in RA patients. A total of 264 large joints in 23 RA patients (6 men and 17 women; mean age of 66.9 ± 7.9 years) were assessed in this study. FDG-PET/CT was performed at baseline and 6 months after the initiation of biological therapy. The extent of FDG uptake in large joints (shoulder, elbow, wrist, hip, knee, and ankle) was analyzed using the maximum standardized uptake value (SUVmax). Radiographs of the 12 large joints per patient obtained at baseline and after 2 years were assessed according to Larsen's method. A logistic regression analysis was performed to determine the factors most significantly contributing to the progression of joint destruction within 2 years. Radiographic progression of joint destruction was detected in 33 joints. The SUVmax at baseline and 6 months, and the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) at 6, 12, and 24 months were significantly higher in the group with progressive joint destruction. The SUVmax at baseline and DAS28-ESR at 6 months were found to be factors associated with joint destruction at 2 years (P < 0.05). The FDG uptake in the joints with destruction was higher than that observed in the joints

  13. Nuclear Structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L.M.; Borge, M.J.G.; Aas, A.J.; Fogelberg, B.; Garcia-Raffi, L.M.; Grant, I.S.; Gulda, K.; Hagebo, E.; Kurcewicz, W.; Lopez-Jimenez, M.J.; Lovhoiden, G.; Mach, H.; Martinez, T.; Rubio, B.; Tain, J.L.; Teijeiro, A.G.; Tengblad, O.; Thorsteinsen, T.F.

    1999-12-31

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr - Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  14. Nuclear structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L. M.; Borge, M. J. G.; Lopez-Jimenez, M. J.; Teijeiro, A. G.; Aas, A. J.; Hageboe, E.; Fogelberg, B.; Mach, H.; Garcia-Raffi, L. M.; Martinez, T.; Rubio, B.; Tain, J. L.; Grant, I. S.; Gulda, K.; Kurcewicz, W.; Loevhoeiden, G.; Tengblad, O.; Thorsteinsen, T. F.

    1999-11-16

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr-Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  15. Radium Ra 223 dichloride injection: U.S. Food and Drug Administration drug approval summary.

    PubMed

    Kluetz, Paul G; Pierce, William; Maher, V Ellen; Zhang, Hui; Tang, Shenghui; Song, Pengfei; Liu, Qi; Haber, Martin T; Leutzinger, Eldon E; Al-Hakim, Ali; Chen, Wei; Palmby, Todd; Alebachew, Elleni; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

    2014-01-01

    On May 15, 2013, the U.S. Food and Drug Administration (FDA) approved radium Ra 223 dichloride (Ra-223; Xofigo injection; Bayer HealthCare Pharmaceuticals Inc.) for the treatment of patients with castration-resistant prostate cancer (CRPC), symptomatic bone metastases, and no known visceral metastatic disease. The FDA review was based on clinical trial BC1-06, which randomly allocated patients (2:1) to either Ra-223 plus best standard of care (BSoC) or placebo plus BSoC. The primary endpoint was overall survival (OS) with a key secondary endpoint of time to first symptomatic skeletal event (SSE). A statistically significant improvement in OS was demonstrated [HR, 0.70; 95% confidence interval, 0.55-0.88, P = 0.0019]. At the prespecified interim analysis, the median OS durations were 14.0 and 11.2 months in the Ra-223 and placebo arms, respectively. The improvement in OS was supported by a delay in time to first SSE favoring the Ra-223 arm. The most common (>10%) adverse reactions in patients receiving Ra-223 were nausea, diarrhea, vomiting, and peripheral edema. The most common (>10%) hematologic laboratory abnormalities were anemia, lymphocytopenia, leukopenia, thrombocytopenia, and neutropenia. Ra-223 is the first α-emitting radiotherapeutic and the first radiopharmaceutical to demonstrate an OS advantage in metastatic prostate cancer.

  16. [Autonomy of the patient with chronic diseases: from passive patient to active patient].

    PubMed

    González Mestre, Assumpció

    2014-01-01

    Due to social, economic and cultural changes, there has been a transformation of Health Services around the world. A new figure has emerged from this: the Active Patient, more responsible, with more information and willing to change his life as a chronic patient. In order to respond to this new situation, several countries have established initiatives such as self-reliance programmes for chronic patients. The aim of this article is to underline the Expert Patient Programme Catalonia(®) and to explain its operation and the results obtained up until now. The purpose of this program is to improve the experience of chronic disease by patients, from meetings in which an expert patient provides his knowledge and experiences to a group of patients with the same disease, with the aim of promoting changes in habits and lifestyles that improve the quality of life and the coexistence of the person with his chronic process.

  17. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  18. Positive association between serum thymic stromal lymphopoietin and anti-citrullinated peptide antibodies in patients with rheumatoid arthritis

    PubMed Central

    Koyama, K; Ohba, T; Haro, H; Nakao, A

    2015-01-01

    Thymic stromal lymphopoietin (TSLP) has been suggested recently to play an important role in the pathophysiology of rheumatoid arthritis (RA). However, there is little information on serum TSLP concentrations in RA and its clinical significance. The present study investigated whether serum TSLP concentrations were affected in patients with RA. Using an enzyme-linked immunosorbent assay (ELISA), we measured TSLP concentrations in the serum obtained from 100 patients with RA, 60 patients with osteoarthritis (OA) and 34 healthy volunteers. We also investigated the correlation between serum TSLP concentrations and clinical parameters of disease activity in RA [disease activity score using 28 joint counts (DAS28)-C-reactive protein (CRP), DAS28-erythrocyte sedimentation rate (ESR), Clinical Disease Activity Index (CDAI]), patient’s/-physician’s Visual Analogue Scale (VAS), swollen joints count, tender joints count, CRP, ESR and matrix metalloproteinase-3 (MMP-3) concentrations]. In addition, we investigated the correlation between serum TSLP concentrations and anti-citrullinated peptide antibody (ACPA) and serum tumour necrosis factor (TNF)-α. Serum TSLP levels in patients with RA were significantly higher than those in patients with OA and in healthy volunteers. Interestingly, serum TSLP concentrations were correlated significantly with ACPA titres, but not with other clinical parameters. There was a significant increase in serum TSLP concentrations in patients with RA, which was correlated positively with serum ACPA titres. These findings suggest that in patients with RA, TSLP may play a role in ACPA production by B cells. PMID:25817699

  19. Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra.

    PubMed

    Ikonomidis, I; Tzortzis, S; Lekakis, J; Paraskevaidis, I; Dasou, P; Parissis, J; Nikolaou, M; Markantonis, S L; Katsimbri, P; Skarantavos, G; Andreadou, I; Anastasiou-Nana, M

    2011-11-01

    Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1β, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1β (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.

  20. Bioaccumulation of 226Ra by plants growing in fresh water ecosystem around the uranium industry at Jaduguda, India.

    PubMed

    Jha, V N; Tripathi, R M; Sethy, N K; Sahoo, S K; Shukla, A K; Puranik, V D

    2010-09-01

    A field study has been conducted to evaluate the (226)Ra bioaccumulation among aquatic plants growing in the stream/river adjoining the uranium mining and ore-processing complex at Jaduguda, India. Two types of plant group have been investigated namely free floating algal species submerged into water and plants rooted in stream & riverbed. The highest (226)Ra activity concentration (9850 Bq kg(-1)) was found in filamentous algae growing in the residual water of tailings pond. The concentration ratios of (226)Ra in filamentous algae (activity concentration of (226)Ra in plant Bq kg(-1) fresh weight/activity concentration of (226)Ra in water Bq l(-1)) widely varied i.e. from 1.1 x 10(3) to 8.6 x 10(4). Other aquatic plants were also showing wide variability in the (226)Ra activity concentration. The ln-transformed filamentous algae (226)Ra activity concentration was significantly correlated with that of ln-transformed water concentration (r = 0.89, p < 0.001). There was no correlation between the activity concentrations of (226)Ra in stream/riverbed rooted plants and the substrate. For this group, correlation between (226)Ra activity concentration and Mn, Fe, Cu concentration in plants were statistically significant.

  1. Use of Ra isotopes to deduce rapid transfer of sediment-derived inputs off Kerguelen

    NASA Astrophysics Data System (ADS)

    Sanial, V.; van Beek, P.; Lansard, B.; Souhaut, M.; Kestenare, E.; d'Ovidio, F.; Zhou, M.; Blain, S.

    2015-03-01

    The Southern Ocean is known to be the largest high-nutrient, low-chlorophyll (HNLC) region of the global ocean due to iron limitation. However, a large phytoplankton bloom develops annually downstream of the Kerguelen Islands, a bloom which is sustained partly by iron released from the sediments deposited onto the shelves. In the framework of the KEOPS-2 project, we used radium isotopes (224Ra, T1/2 = 3.66 d; 223Ra, T1/2 = 11.4 d; 228Ra, T1/2 = 5.75 yr) to provide information on the origin of iron fertilization and on the timescales of the transfer of sediment-derived inputs (including iron and other micronutrients) towards offshore waters. Significant 224Ra and 223Ra activities were found in the near vicinity of the Kerguelen Islands, in agreement with the short half-lives of these isotopes. Significant 224Ra and 223Ra activities were also detected up to 200 km downstream of the islands and more unexpectedly in offshore waters south of the polar front. These observations thus clearly indicate (i) that the sediment-derived inputs are rapidly transferred towards offshore waters (on timescales on the order of several days up to several weeks) and (ii) that the polar front is not a physical barrier for the chemical elements released from the sediments of the Kerguelen Plateau. The Ra data set suggests that iron and other micronutrients released by the shelves of the Kerguelen Islands may contribute to fueling the phytoplankton bloom downstream of the islands, despite the presence of the polar front. However, the heterogeneous distribution of the 224Ra and 223Ra activities in surface waters suggests that this supply across the front is not a continuous process but rather a process that is highly variable in space and time.

  2. Use of Ra isotopes to deduce rapid transfer of sediment-derived inputs off Kerguelen

    NASA Astrophysics Data System (ADS)

    Sanial, V.; van Beek, P.; Lansard, B.; Souhaut, M.; Kestenare, E.; d'Ovidio, F.; Zhou, M.; Blain, S.

    2014-09-01

    The Southern Ocean is known as the largest High-Nutrient, Low-Chlorophyll (HNLC) region of the global ocean due to iron limitation. However, a large phytoplankton bloom develops annually downstream of the Kerguelen Islands, which is sustained partly by iron released from the sediments deposited onto the margins. In the framework of the KEOPS-2 project, we used radium isotopes (224Ra, T1/2 = 3.66 d; 223Ra, T1/2 = 11.4 d; 228Ra, T1/2 = 5.75 yr) to provide information on the origin of iron fertilization and on the timescales of the transfer of sediment-derived inputs (including iron and other micronutrients) towards offshore waters. Significant 223Ra and 223Ra activities were found in the near vicinity of the Kerguelen Islands, in agreement with the short half-lives of these isotopes. Significant 224Ra and 223Ra activities were also detected up to 200 km downstream of the islands and more unexpectedly in offshore waters south of the Polar Front. These observations thus clearly indicate (i) that the sediment-derived inputs are rapidly transferred towards offshore waters (on timescales in the order of several days up to several weeks) and (ii) that the Polar Front is not a physical barrier for the chemical elements released from the sediments of Kerguelen Plateau. The Ra dataset suggests that iron and other micronutrients released by the shallow sediments of the Kerguelen margins may contribute to fuel the phytoplankton bloom downstream of the islands, despite the presence of the Polar Front. However, the heterogeneous distribution of the 224Ra and 223Ra activities in surface waters suggests that this supply across the front is not a continuous process, but rather a process that is highly variable in space and time.

  3. Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

    PubMed

    Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

    2015-01-01

    The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture.

  4. Efficacy of tofacitinib monotherapy in methotrexate-naive patients with early or established rheumatoid arthritis

    PubMed Central

    Fleischmann, Roy M; Huizinga, Tom W J; Kavanaugh, Arthur F; Wilkinson, Bethanie; Kwok, Kenneth; DeMasi, Ryan; van Vollenhoven, Ronald F

    2016-01-01

    Introduction Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). Tofacitinib monotherapy was previously shown to inhibit structural damage, reduce clinical signs and symptoms of RA, and improve physical functioning over 24 months in methotrexate (MTX)-naive adult patients with RA. In this post hoc analysis, we compared efficacy and safety of tofacitinib in patients with early (disease duration <1 year) versus established (≥1 year) RA. Methods MTX-naive patients ≥18 years with active RA received tofacitinib monotherapy (5 or 10 mg two times a day, or MTX monotherapy, in a 24-month Phase 3 trial. Results Of 956 patients (tofacitinib 5 mg two times a day, n=373; tofacitinib 10 mg two times a day, n=397; MTX, n=186), 54% had early RA. Baseline disease activity and functional disability were similar in both groups; radiographic damage was greater in patients with established RA. At month 24, clinical response rates were significantly greater in patients with early versus established RA in the tofacitinib 5 mg two times a day group. Both tofacitinib doses had greater effects on clinical, functional and radiographic improvements at 1 and 2 years compared with MTX, independent of disease duration. No new safety signals were observed. Conclusions Treatment response was generally similar in early and established RA; significantly greater improvements were observed at month 24 with tofacitinib 5 mg two times a day in early versus established RA. Tofacitinib 5 and 10 mg two times a day demonstrated greater efficacy versus MTX irrespective of disease duration. No difference in safety profiles was observed between patients with early or established RA. Trial registration number NCT01039688; Results. PMID:27493790

  5. Sanshool on The Fingertip Interferes with Vibration Detection in a Rapidly-Adapting (RA) Tactile Channel

    PubMed Central

    Kuroki, Scinob; Hagura, Nobuhiro; Nishida, Shin’ya; Haggard, Patrick; Watanabe, Junji

    2016-01-01

    An Asian spice, Szechuan pepper (sanshool), is well known for the tingling sensation it induces on the mouth and on the lips. Electrophysiological studies have revealed that its active ingredient can induce firing of mechanoreceptor fibres that typically respond to mechanical vibration. Moreover, a human behavioral study has reported that the perceived frequency of sanshool-induced tingling matches with the preferred frequency range of the tactile rapidly adapting (RA) channel, suggesting the contribution of sanshool-induced RA channel firing to its unique perceptual experience. However, since the RA channel may not be the only channel activated by sanshool, there could be a possibility that the sanshool tingling percept may be caused in whole or in part by other sensory channels. Here, by using a perceptual interference paradigm, we show that the sanshool-induced RA input indeed contributes to the human tactile processing. The absolute detection thresholds for vibrotactile input were measured with and without sanshool application on the fingertip. Sanshool significantly impaired detection of vibrations at 30 Hz (RA channel dominant frequency), but did not impair detection of higher frequency vibrations at 240 Hz (Pacinian-corpuscle (PC) channel dominant frequency) or lower frequency vibrations at 1 Hz (slowly adapting 1 (SA1) channel dominant frequency). These results show that the sanshool induces a peripheral RA channel activation that is relevant for tactile perception. This anomalous activation of RA channels may contribute to the unique tingling experience of sanshool. PMID:27935970

  6. Leachable 226Ra in Philippine phosphogypsum and its implication in groundwater contamination in Isabel, Leyte, Philippines.

    PubMed

    Cañete, Socrates Jose P; Palad, Lorna Jean H; Enriquez, Eliza B; Garcia, Teofilo Y; Yulo-Nazarea, Teresa

    2008-07-01

    Phosphogypsum (PG), the major waste material in phosphate fertilizer processing, has been known to contain enhanced levels of naturally-occurring radionuclides especially (226)Ra. The lack of radioactivity data regarding Philippine phosphogypsum and its environmental behavior in the Philippine setting has brought concern on possible contamination of groundwater beneath the phosphogypsum ponds in Isabel, Leyte, Philippines. The radioactivity of Philippine phosphogypsum was determined and the leaching of (226)Ra from phosphogypsum and through local soil was quantified. Level of (226)Ra in groundwater samples in Isabel, Leyte, Philippines was also quantified to address the primary concern. It was found that the (226)Ra activity in Philippine phosphogypsum is distributed in a wide range from 91.5 to 935 Bq/kg. As much as 5% of (226)Ra can be leached from Philippine PG with deionized water. In vitro soil leach experiments suggest that the soil in the phosphate fertilizer plant area would be able to deter the intrusion of (226)Ra into the water table. Compared to reported values of natural groundwater levels of (226)Ra, the concentration of this radionuclide in Isabel, Leyte groundwater suggest that there is no (226)Ra intrusion brought about by the presence of phosphogypsum ponds in the area.

  7. Upregulated Expression of microRNA-16 Correlates with Th17/Treg Cell Imbalance in Patients with Rheumatoid Arthritis.

    PubMed

    Wu, Yuan-Hao; Liu, Wei; Xue, Bin; Zhang, Lei; Liu, Xiao-Ya; Liu, Bin; Wang, Yi; Cai, Yue; Duan, Ran

    2016-12-01

    To explore the correlation between miR-16 expression in T cells of peripheral blood mononuclear cells (PBMCs) and Th17/Treg imbalance in rheumatoid arthritis (RA) patients. Forty RA patients were recruited as the case group and further grouped as active RA and inactive RA groups; 21 healthy individuals were selected as the control group. Th17 and Treg were measured by flow cytometry, and their related cytokines were measured by FlowCytomix. RORγt, FoxP3 mRNA, and miR-16 expression in T cells was determined by real-time quantitative polymerase chain reaction. Western blotting was performed to measure RORγt and FoxP3 protein expression. RA patients showed upregulated Th17 and RORγt mRNA and protein expression compared with the controls (all p < 0.05); active RA patients showed lower Treg and FoxP3 mRNA and protein expression compared with inactive RA patients and controls (all p < 0.05). Secretion levels of Th17-related cytokines were higher in active RA patients than in inactive RA patients and controls (all p < 0.05); whereas those of Treg-related cytokines were lower in active RA patients than in controls (all p < 0.05). Active RA patients showed increased miR-16 expression in Th17 cells and decreased miR-16 expression in Treg cells of PBMCs (both p < 0.05). Pearson's test showed that in the PBMCs of the RA patients, miR-16 expression in the Th17 cells was positively related with RORγt mRNA expression, and miR-16 expression in the Treg cells was positively related with FoxP3 mRNA expression (both p < 0.05). The expression of miR-16 in Th17 and Treg cells of PBMCs in RA patients was closely associated with the expression of RORγt and FoxP3. MiR-16 may be involved in Th17/Treg imbalance of RA patients by affecting the expression of RORγt and FoxP3.

  8. Increased expression of blood mononuclear cell nitric oxide synthase type 2 in rheumatoid arthritis patients.

    PubMed

    St Clair, E W; Wilkinson, W E; Lang, T; Sanders, L; Misukonis, M A; Gilkeson, G S; Pisetsky, D S; Granger, D I; Weinberg, J B

    1996-09-01

    Nitric oxide (NO) is an important inflammatory mediator in nonhuman animal models of rheumatoid arthritis (RA). The purpose of the present study was to determine whether blood mononuclear cells from patients with active RA (as compared to control subjects) have higher levels of NO synthase type 2 (NOS2) and produce more NO in vitro. Leukocytes from 25 RA patients and 20 normal subjects were examined. Arthritis activity was assessed by tender and swollen joint counts, duration of morning stiffness, patient assessment of pain, physician and patient global assessment of disease activity, the modified Stanford Health Assessment Questionnaire, and by blood levels of acute phase reactants. Blood mononuclear cell NOS enzyme activity/antigen content and nitrite/nitrate formation in vitro were measured. Blood mononuclear cells from RA patients had increased NOS activity and increased NOS2 antigen content as compared to those from normal subjects, and responded to interferon-gamma with increased NOS expression and nitrite/nitrate production in vitro. NOS activity of freshly isolated blood mononuclear cells correlated significantly with disease activity, as assessed by render and swollen joint counts. Our results demonstrate that patients with RA have systemic activation for NOS2 expression, and that the degree of activation correlates with disease activity. Increased NOS2 expression and NO generation may be important in the pathogenesis of RA.

  9. [Physical activities and sports in asthmatic patients].

    PubMed

    Todaro, A

    1983-05-31

    Asthma patients are too often advised to refrain from sport. Enforced sedentariness, especially in children, leads to muscle hypotonia, reduced mechanical efficiency, paramorphisms, and adverse psychological consequences. Not all asthmatics develop airway spasm as a result of exercise. On the other hand, there are subjects whose bronchial hyper-reactivity is stimulated solely by muscular effort. The pathogenesis of exercise-induced bronchospasm is not fully understood. In any event, numerous studies have demonstrated the beneficial and even therapeutic effect of physical exercise and sport in cases of asthma. Provided they are practised with judgment and in accordance with a suitable programme, swimming, activities of an alternating aerobic and anaerobic type, cross-country skiing, gymnastics, and fencing are primarily indicated. Some asthmatics have also won Olympic medals. In the light of the studies carried out so far, it is strongly suggested that asthmatics be encouraged to take up sport suitable to their psychophysical characteristics, and not kept wrapped up in cotton wool.

  10. The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

    PubMed Central

    Silva, Bruna Daniella Souza; Tannus-Silva, Daniela Graner Schuwartz; Rabahi, Marcelo Fouad; Kipnis, Andre; Junqueira-Kipnis, Ana Paula

    2013-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease characterised by the destruction of articular cartilage and bone damage. The chronic treatment of RA patients causes a higher susceptibility to infectious diseases such as tuberculosis (TB); one-third of the world’s population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb). The tuberculin skin test is used to identify individuals LTBI, but many studies have shown that this test is not suitable for RA patients. The goal of this work was to test the specific cellular immune responses to the Mtb malate synthase (GlcB) and heat shock protein X (HspX) antigens of RA patients and to correlate those responses with LTBI status. The T-helper (Th)1, Th17 and Treg-specific immune responses to the GlcB and HspX Mtb antigens were analysed in RA patients candidates for tumour necrosis factor-α blocker treatment. Our results demonstrated that LTBI RA patients had Th1-specific immune responses to GlcB and HspX. Patients were followed up over two years and 14.3% developed active TB. After the development of active TB, RA patients had increased numbers of Th17 and Treg cells, similar to TB patients. These results demonstrate that a GlcB and HspX antigen assay can be used as a diagnostic test to identify LTBI RA patients. PMID:24626307

  11. APL-1, an altered peptide ligand derived from human heat-shock protein 60, selectively induces apoptosis in activated CD4+ CD25+ T cells from peripheral blood of rheumatoid arthritis patients.

    PubMed

    Barberá, Ariana; Lorenzo, Noraylis; Garrido, Greta; Mazola, Yuliet; Falcón, Viviana; Torres, Ana María; Hernández, María Isabel; Hernández, María Victoria; Margry, Bram; de Groot, A Marit; van Roon, Joel; van der Zee, Ruurd; Broere, Femke; van Eden, Willem; Padrón, Gabriel; Domínguez, María del Carmen

    2013-12-01

    Rheumatoid arthritis (RA) is a chronic T-cell mediated autoimmune disease that affects primarily the joints. The induction of immune tolerance through antigen-specific therapies for the blockade of pathogenic CD4+ T cells constitutes a current focus of research. In this focus it is attempted to simultaneously activate multiple regulatory mechanisms, such as: apoptosis and regulatory T cells (Tregs). APL-1 is an altered peptide ligand derived from a novel CD4+ T-cell epitope of human heat-shock protein of 60kDa, an autoantigen involved in the pathogenesis of RA. Previously, we have reported that APL-1 induces CD4+ CD25(high)Foxp3+ Tregs in several systems. Here, we investigated the ability of APL-1 in inducing apoptosis in PBMCs from RA patients, who were classified as active or inactive according to their DAS28 score. APL-1 decreased the viability of PBMCs from active but not from inactive patients. DNA fragmentation assays and typical morphological features clearly demonstrated that APL-1 induced apoptosis in these cells. Activated CD4+ CD25+ T cells but not resting CD4+ CD25- T cells were identified as targets of APL-1. Furthermore, CD4+ T-cell responses to APL-1 were found to be dependent on antigen presentation via the HLA-DR molecule. Thus, APL-1 is a regulatory CD4+ T cell epitope which might modulate inflammatory immune responses in PBMCs from RA patients by inducing CD4+ CD25(high)Foxp3+ Tregs and apoptosis in activated CD4+ T cells. These results support further investigation of this candidate drug for the treatment of RA.

  12. Upper gastrointestinal manifestations in rheumatoid arthritis patients: intrinsic or extrinsic pathogenesis?

    PubMed

    Janssen, M; Dijkmans, B A; Lamers, C B

    1990-01-01

    Apart from the complication of gastrointestinal vasculitis it is not known whether the upper gastrointestinal (UGI) tract has any special disease characteristics in rheumatoid arthritis (RA). However, oesophageal motility disorders have been reported in 30% of RA patients. Hypergastrinaemia has been found in 23-43% of RA patients, usually in combination with a decreased gastric acid output. Another finding suggestive of a decreased secretory state, namely a decreased level of pepsinogen A, was found in RA patients with the sicca syndrome and in patients with active disease. The risk for peptic ulcer disease with regard to nonsteroidal anti-inflammatory drugs (NSAID) is possibly higher in RA patients than in patients with other rheumatic diseases. These findings suggest that in RA patients intrinsic factors play a role in the pathogenesis of the oesophageal motility disorders, in hypergastrinaemia and hypopepsinogenaemia and the related decreased gastric secretory state, and possibly in the increased susceptibility to NSAID-related ulcers. However, there are also indications that oesophageal motility disorders, hypergastrinaemia, and NSAID-related ulcers in RA are the result of extrinsic factors, mainly the use of NSAIDs. The effects of NSAIDs and gold compounds on infection with Helicobacter pylori, a possible pathogenetic factor in ulcer disease, is discussed. It is clear that the discussion about intrinsic and extrinsic factors as a cause of the UGI manifestations in RA remains an intriguing but difficult subject for further studies.

  13. Frequency and significance of parvovirus B19 infection in patients with rheumatoid arthritis

    PubMed Central

    Naciute, Milda; Mieliauskaite, Diana; Rugiene, Rita; Nikitenkiene, Rita; Jancoriene, Ligita; Mauricas, Mykolas; Nora-Krukle, Zaiga; Murovska, Modra

    2016-01-01

    The present study aims to clarify the possible involvement of parvovirus B19 (B19V) infection in rheumatoid arthritis (RA) pathogenesis by investigating the presence of B19V infection markers (genomic sequences and virus-specific antibodies) in association with the level of cytokines and RA clinical activity and aggressiveness. A total of 118 RA patients and 49 age- and sex-matched healthy volunteers were enrolled in the study. Nested PCR was used to detect B19V sequences in whole blood and cell-free plasma DNA, ELISA to detect virus-specific antibodies and cytokine levels in plasma and recomLine dot blot assay for antibodies to separate B19V antigens. The detection frequency of B19V DNA was higher in patients with RA (25.4 %) in comparison with healthy persons (18.4 %). B19V DNA in cell-free plasma (B19+p) was detected significantly often in RA patients in comparison with healthy controls (13.6 vs 2 %; P=0.0002). RA B19+p patients had higher disease activity and aggressiveness, decreased haemoglobin and increased erythrocyte sedimentation rates. IL-6 plasma levels were significantly higher in RA patients than in controls. Within the RA patients’ group the IL-6 level was significantly increased in B19+p patients with disease activity scores of DAS28>5.2, high C-reactive protein and low haemoglobin. Contrary to the healthy controls, the majority of RA B19+p patients did not have antibodies to VP-1S (VP1u) and VP-N (N-terminal half of structural proteins VP1 and VP2), which correspond to the epitopes of neutralizing antibodies. These results indicate that B19V infection at least in some patients is involved in RA pathogenesis. PMID:27902343

  14. Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process

    PubMed Central

    Kim, Jae-Yong; Lee, Eun-Young; Park, Jin Kyun; Song, Yeong Wook; Kim, Jae-Ryong; Cho, Kyung-Hyun

    2016-01-01

    Objective In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age. Methods We analyzed four classes of lipoproteins (VLDL, LDL, HDL2, HDL3) from both male (n = 8, 69±4 year-old) and female (n = 25, 53±7 year-old) rheumatoid arthritis (RA) patients as well as controls with similar age (n = 13). Results Although RA group showed normal levels of total cholesterol (TC), low-density lipoprotein (LDL)-cholesterol, and glucose, however, the RA group showed significantly reduced high-density lipoprotein (HDL)-C level and ratio of HDL-C/TC. The RA group showed significantly elevated levels of blood triglyceride (TG), uric acid, and cholesteryl ester transfer protein (CETP) activity. The RA group also showed elevated levels of advanced glycated end (AGE) products in all lipoproteins and severe aggregation of apoA-I in HDL. As CETP activity and TG contents were 2-fold increased in HDL from RA group, paraoxonase activity was reduced upto 20%. Electron microscopy revealed that RA group showed much less HDL2 particle number than control. LDL from the RA group was severely oxidized and glycated with greater fragmentation of apo-B, especially in female group, it was more atherogenic via phagocytosis. Conclusion Lipoproteins from the RA patients showed severely altered structure with impaired functionality, which is very similar to that observed in coronary heart patients. These dysfunctional properties in lipoproteins from the RA patients might be associated with high incidence of cardiovascular events in RA patients. PMID:27736980

  15. Comparison of Antibodies with Amylase Activity from Cerebrospinal Fluid and Serum of Patients with Multiple Sclerosis

    PubMed Central

    Doronin, Vasilii B.; Parkhomenko, Taisiya A.; Castellazzi, Massimiliano; Cesnik, Edward; Buneva, Valentina N.; Granieri, Enrico; Nevinsky, Georgy A.

    2016-01-01

    We have recently shown that IgGs from serum and cerebrospinal fluid (CSF) of MS patients are active in hydrolysis of DNA and myelin basic protein. According to literature data, anti-DNA and anti-MBP abzymes may promote important neuropathologic mechanisms in this chronic inflammatory disorder and in MS pathogenesis development. At the same time, the involvement of antibodies with amylase activity in the pathogenesis of any autoimmune disease has not yet been identified. Electrophoretically and immunologically homogeneous IgGs were obtained by a sequential affinity chromatography of the CSF proteins on protein G-Sepharose and FPLC gel filtration. We are able to present the first unpredictable evidence showing that IgGs from CSF possess amylase activity and efficiently hydrolyze maltoheptaose; their average specific Ab activity is ~30-fold higher than that of antibodies from sera of the same MS patients. Specific average RA (SAA) for IgGs from healthy volunteers was approximately ~1000 lower than that for MS patients. In addition, it was shown that a relative SAA of total proteins of CSF (including Abs) ~15-fold lower than that for purified IgGs, while the relative SAA of the total sera protein is higher than that of sera IgGs by a factor of 1033. This result speaks in favor of the fact that amylolytic activity of CSF proteins is mainly caused by the activity of amylase abzymes. One cannot exclude, that amylase abzymes of CSF can play a, as yet unknown, role in the pathogenesis of MS. Some possible reasons of these findings are discussed. PMID:27196086

  16. Distribution of (223)Ra and (224)Ra in the Bo Sea embayment in Tianjin and its implication of submarine groundwater discharge.

    PubMed

    Liu, Lingling; Yi, Lixin; Cheng, Xiaoqing; Tang, Guoqiang

    2015-12-01

    Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. In this study, in order to analyze the distribution of naturally occurring short-lived radium isotopes and the relative SGD effect in Bo Sea embayment, (223)Ra and (224)Ra were measured in three parts of the embayment with the radium-delayed coincidence counting (RaDeCC) system. Subsequently, the mixing process was studied by the calculation of diffusion coefficients (Kx and Kz) and advection velocities (Vx and Vz) based on the 2D advection-diffusion model. Additionally, the apparent residence ages and SGD flux were quantified based on the (224)Ra and (223)Ra activities. The results showed that the Ra activities exponentially decreased with the distance offshore, and both the Kx and Vx took the order of northern part > southern part > middle part. In vertical direction, there was the maximum value of Vz and minimum Kz in middle part and the maximum Kz and minimum Vz in southern part. The average ages for the northern, middle and southern parts were 4.28, 7.38 and 3.73 days, respectively. The final SGD flux yielded by (224)Ra was 0.09, 0.01 and 0.03 m d(-1) in the northern, middle and southern parts, respectively. The SGD flux yielded by (223)Ra was 0.08, 0.01 and 0.03 m d(-1) in northern, middle and southern parts, respectively. The result indicates that there is the fastest exchange rate and the biggest SGD flux in the southern part in Bo Sea embayment.

  17. Techniques for precise mapping of 226Ra and 228Ra in the ocean

    NASA Astrophysics Data System (ADS)

    Moore, Willard S.; Key, Robert M.; Sarmiento, Jorge L.

    1985-01-01

    Improvements in the analyses of 226Ra and 228Ra in seawater made possible by better extraction and processing techniques reduce significantly the errors associated with these measurements. These improvements and the extensive sampling for Ra isotopes conducted on the TTO North Atlantic Study should enable us to use the distribution of 228Ra to study mixing processes on a 3-15 year time scale in both the upper and deep North Atlantic. The 228Ra profiles already analyzed show a closer resemblance to GEOSECS tritium data than to TTO tritium data in the upper ocean. This is because the transient tracer tritium was responding on a 10-year time scale during GEOSECS and a 20-year time scale during TTO. The steady state tracer 228Ra should always respond on a time scale of 8 years. Thus the 228Ra data obtained on TTO should provide a means to extend the features of the GEOSECS tritium field to the regions of the TTO study. The 226Ra data are of high enough quality to identify features associated with different water masses. Changes in the positions of the deep-water masses since the GEOSECS cruise are revealed by the 226Radata.

  18. The efficacy and safety of reinstitution of tocilizumab in patients with relapsed active rheumatoid arthritis after long-term withdrawal of tocilizumab: retreatment of patients with rheumatoid arthritis with novel anti-IL-6 receptor antibody after a long-term interval following SAMURAI: the RONIN study.

    PubMed

    Sagawa, Akira

    2011-08-01

    We have evaluated the efficacy and safety of tocilizumab (TCZ) re-administration in patients with active rheumatoid arthritis (RA) who had previously received TCZ treatment for about 31 months. Four patients whose RA had been well-controlled with 8 mg/kg TCZ treatment every 4 weeks and had withdrawn from the treatment were enrolled. They resumed TCZ treatment after TCZ was authorized for RA treatment in Japan. Disease activity was assessed by the Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR), and synovitis in the wrists and elbows was measured by ultrasonography at baseline and during follow-up. The mean DAS28-ESR was 6.32 before the first TCZ infusion. After fewer than 20 months of initial TCZ treatment, the mean DAS28-ESR decreased to 1.87. However, after withdrawal of TCZ treatment, the disease activity could not be sufficiently controlled with conventional disease-modifying antirheumatic drugs or biologic agents. The maximum interval between TCZ treatments was approximately 34 months. Following reinstatement of the TCZ treatment, within 12 months the mean DAS28-ESR improved from 5.21 to 2.87, with the synovitis in the wrists and elbow joints also showing great improvement. These findings demonstrate that TCZ retreatment in active RA patients who had relapsed after long-term discontinuation of TCZ treatment led to an improvement in the signs and symptoms of RA and in synovitis without any severe adverse events.

  19. [Plasma antithrombin III activity in patients with pulmonary thromboembolism].

    PubMed

    Vertun, B; Filipecki, S; Szczepański, M; Wawrzyńska, L; Rózycka, J

    A decreased plasma antithrombin III activity has been noted in 12 out of 20 patients. In 2 patients it was most probably congenital defect, whereas in the remaining 10 patients--acquired. The observed disorders in the activity of antithrombin III with particular reference to anticoagulant therapy have been discussed.

  20. Exploring Contextual Factors and Patient Activation: Evidence from a Nationally Representative Sample of Patients with Depression

    ERIC Educational Resources Information Center

    Chen, Jie; Mortensen, Karoline; Bloodworth, Robin

    2014-01-01

    Patient activation has been considered as a "blockbuster drug of the century." Patients with mental disorders are less activated compared to patients with other chronic diseases. Low activation due to mental disorders can affect the efficiency of treatment of other comorbidities. Contextual factors are significantly associated with…

  1. Interpreting the multi-biomarker disease activity score in the context of tocilizumab treatment for patients with rheumatoid arthritis.

    PubMed

    Reiss, William G; Devenport, Jenny N; Low, Jason M; Wu, George; Sasso, Eric H

    2016-02-01

    The multi-biomarker disease activity (MBDA) score measures 12 proteins involved in the pathophysiology of rheumatoid arthritis (RA) to assess disease activity (DA). Previous studies demonstrated correlations between MBDA and clinical DA scores with some RA therapies. In this analysis, the relationship between DA and MBDA scores and changes in MBDA component biomarkers were evaluated in tocilizumab (TCZ)-treated patients. Patients from the ACT-RAY study were included in this analysis if they had DA measures and serum collected at pre-specified time points with sufficient serum for MBDA testing at ≥1 visit. Descriptive statistics, associations between outcomes, and percentage agreement between DA categories were calculated. Seventy-eight patients were included and were similar to the ACT-RAY population. Correlations between MBDA score and DAS28-CRP were ρ = 0.50 at baseline and ρ = 0.26 at week 24. Agreement between low/moderate/high categories of MBDA score and DAS28-CRP was observed for 77.1 % of patients at baseline and 23.7 % at week 24. Mean changes from baseline to weeks 4, 12, and 24 were proportionately smaller for MBDA score than DAS28-CRP. Unlike some other MBDA biomarkers, interleukin-6 (IL-6) concentrations increased in most patients during TCZ treatment. Correlations and agreement between MBDA and DAS28-CRP or CDAI scores were lower at week 24 versus baseline. The proportionately smaller magnitude of response observed for MBDA score versus DAS28-CRP may be due to the influence of the increase in IL-6 concentrations on MBDA score. Thus, MBDA scores obtained during TCZ treatment should be interpreted cautiously and in the context of available clinical information.

  2. Further Optimization of the Reliability of the 28-Joint Disease Activity Score in Patients with Early Rheumatoid Arthritis

    PubMed Central

    Siemons, Liseth; ten Klooster, Peter M.; Vonkeman, Harald E.; van de Laar, Mart A. F. J.; Glas, Cees A. W.

    2014-01-01

    Background The 28-joint Disease Activity Score (DAS28) combines scores on a 28-tender and swollen joint count (TJC28 and SJC28), a patient-reported measure for general health (GH), and an inflammatory marker (either the erythrocyte sedimentation rate [ESR] or the C-reactive protein [CRP]) into a composite measure of disease activity in rheumatoid arthritis (RA). This study examined the reliability of the DAS28 in patients with early RA using principles from generalizability theory and evaluated whether it could be increased by adjusting individual DAS28 component weights. Methods Patients were drawn from the DREAM registry and classified into a “fast response” group (N = 466) and “slow response” group (N = 80), depending on their pace of reaching remission. Composite reliabilities of the DAS28-ESR and DAS28-CRP were determined with the individual components' reliability, weights, variances, error variances, correlations and covariances. Weight optimization was performed by minimizing the error variance of the index. Results Composite reliabilities of 0.85 and 0.86 were found for the DAS28-ESR and DAS28-CRP, respectively, and were approximately equal across patients groups. Component reliabilities, however, varied widely both within and between sub-groups, ranging from 0.614 for GH (“slow response” group) to 0.912 for ESR (“fast response” group). Weight optimization increased composite reliability even further. In the total and “fast response” groups, this was achieved mostly by decreasing the weight of the TJC28 and GH. In the “slow response” group, though, the weights of the TJC28 and SJC28 were increased, while those of the inflammatory markers and GH were substantially decreased. Conclusions The DAS28-ESR and the DAS28-CRP are reliable instruments for assessing disease activity in early RA and reliability can be increased even further by adjusting component weights. Given the low reliability and weightings of the general health

  3. A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients.

    PubMed

    Afroz, Sumbul; Giddaluru, Jeevan; Vishwakarma, Sandeep; Naz, Saima; Khan, Aleem Ahmed; Khan, Nooruddin

    2017-01-01

    Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.

  4. A multicenter report of biologic agents for the treatment of secondary amyloidosis in Turkish rheumatoid arthritis and ankylosing spondylitis patients.

    PubMed

    Pamuk, Ömer Nuri; Kalyoncu, Umut; Aksu, Kenan; Omma, Ahmet; Pehlivan, Yavuz; Çağatay, Yonca; Küçükşahin, Orhan; Dönmez, Salim; Çetin, Gözde Yıldırım; Mercan, Rıdvan; Bayındır, Özün; Çefle, Ayşe; Yıldız, Fatih; Balkarlı, Ayşe; Kılıç, Levent; Çakır, Necati; Kısacık, Bünyamin; Öksüz, Mustafa Ferhat; Çobankara, Veli; Onat, Ahmet Mesut; Sayarlıoğlu, Mehmet; Öztürk, Mehmet Akif; Pamuk, Gülsüm Emel; Akkoç, Nurullah

    2016-07-01

    In this multicenter, retrospective study, we evaluated the efficacy and safety of biologic therapies, including anti-TNFs, in secondary (AA) amyloidosis patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). In addition, the frequency of secondary amyloidosis in RA and AS patients in a single center was estimated. Fifty-one AS (39M, 12F, mean age: 46.7) and 30 RA patients (11M, 19F, mean age: 51.7) with AA amyloidosis from 16 different centers in Turkey were included. Clinical and demographical features of patients were obtained from medical charts. A composite response index (CRI) to biologic therapy-based on creatinine level, proteinuria and disease activity-was used to evaluate the efficacy of treatment. The mean annual incidence of AA amyloidosis in RA and AS patients was 0.23 and 0.42/1000 patients/year, respectively. The point prevalence in RA and AS groups was 4.59 and 7.58/1000, respectively. In RA group with AA amyloidosis, effective response was obtained in 52.2 % of patients according to CRI. RA patients with RF positivity and more initial disease activity tended to have higher response rates to therapy (p values, 0.069 and 0.056). After biologic therapy (median 17 months), two RA patients died and two developed tuberculosis. In AS group, 45.7 % of patients fulfilled the criteria of good response according to CRI. AS patients with higher CRP levels at the time of AA diagnosis and at the beginning of anti-TNF therapy had higher response rates (p values, 0.011 and 0.017). During follow-up after anti-TNF therapy (median 38 months), one patient died and tuberculosis developed in two patients. Biologic therapy seems to be effective in at least half of RA and AS patients with AA amyloidosis. Tuberculosis was the most important safety concern.

  5. T helper 17 and T helper 1 cells are increased but regulatory T cells are decreased in subchondral bone marrow microenvironment of patients with rheumatoid arthritis

    PubMed Central

    Wang, Ting; Li, Shufeng; Yang, Yun; Zhang, Kaining; Dong, Shixiao; Wang, Xiuhua; Liu, Xinguang; Ren, Yanjun; Zhang, Ming; Yan, Xinfeng; Li, Jianmin; Zhang, Lei

    2016-01-01

    Objectives: The present study is to investigate the profiles of Th17, Th1 and Treg cells in bone marrow of patients with rheumatoid arthritis (RA). Methods: Flow cytometry was used to analyze the frequencies of Th17, Th1 and Treg cells in paired peripheral blood and bone marrow of 26 RA patients and 11 osteoarthritis (OA) patients, as well as 10 healthy controls. In addition, the disease activity was analyzed by the 28-joint disease activity score (DAS28). Results: The frequencies of Th17 and Th1 cells were significantly elevated in bone marrow of RA patients. Importantly, Th17 and Th1 cells were significantly elevated in bone marrow compared with the matched peripheral blood from RA patients. However, Treg cells were significantly decreased in bone marrow of RA patients compared with the matched peripheral blood of RA patients and bone marrow of osteoarthritis patients and healthy controls. Moreover, the frequencies of tumor necrosis factor-α-producing T cells were significantly elevated in bone marrow from RA patients. Additionally, Th17 and Th1 cells in bone marrow were positively correlated with DAS28, while Treg cells were negatively correlated with DAS28. Conclusions: The present study demonstrates that Th17 and Th1 cells are markedly increased in bone marrow from RA patients. By contrast, Treg cells are significantly decreased in bone marrow from RA patients. These results suggest that local abnormality of Th17, Th1 and Treg cells in bone marrow of RA patients may contribute to bone destruction in skeletal system. PMID:27508016

  6. Rheumatoid arthritis in patients with HIV: management challenges

    PubMed Central

    Carroll, Matthew B; Fields, Joshua H; Clerc, Philip G

    2016-01-01

    Over the past few decades, HIV has been transformed from a once-uniformly fatal disease to now a manageable but complex multisystem illness. Before highly active antiretroviral therapy (HAART), reports suggested that HIV-infected patients with rheumatoid arthritis (RA) would experience remission of their disease. It has now become clear that RA can develop in HIV-infected patients at any time, independent of HAART. Choosing the right medication to treat symptoms related to RA while avoiding excess weakening of the immune system remains a clinical challenge. Agents such as hydroxychloroquine and sulfasalazine might best balance safety with efficacy, making them reasonable first choices for therapy in HIV-infected patients with RA. More immune suppressing agents such as methotrexate may balance safety with efficacy, but data are limited. Corticosteroids such as prednisone may also be reasonable but could increase the risk of osteonecrosis. Among biologic response modifiers, tumor necrosis factor α inhibitors may balance safety with efficacy, but perhaps when HIV replication is controlled with HAART. Monitoring RA disease activity remains challenging as only one retrospective study has been published in this area. Those with HIV infection and RA can experience comorbidities such as accelerated heart disease and osteoporosis, a consequence of the chronic inflammatory state that each illness generates. Although HIV-infected patients are at risk for developing the immune reconstitution inflammatory syndrome when starting HAART, it appears that immune reconstitution inflammatory syndrome has a minimal effect on triggering the onset or the worsening of RA. PMID:27843370

  7. 223Ra levels fed in the 223Fr β decay

    NASA Astrophysics Data System (ADS)

    Abdul-Hadi, A.; Barci, V.; Weiss, B.; Maria, H.; Ardisson, G.; Hussonnois, M.; Constantinescu, O.

    1993-01-01

    The 223Fr β decay was reinvestigated using high-resolution single γ spectrometry as well as γ-γ coincidence techniques. For single γ-spectra measurements, radiochemically pure 223Fr sources were obtained by chromatographic separation from a 75 MBq activity 227Ac parent source and continuously purified of 223Ra and daughters. The analysis of the γ spectra of 30 sources showed the existence of 131 γ lines, of which 87 are reported for the first time in the 223Fr β decay although many of them are observed following the 227Th α decay. The 223Fr half-life was remeasured and found to be T1/2=22.00+/-0.07 min. γ-γ-t coincidence measurements were also carried out with 223Fr purified sources. The 223Ra level scheme was built on the basis of our γ data, as well as 227Th α-decay data. Among the 32 excited 223Ra levels, of which 22 were also known from 227Th α decay, 13 are newly reported from 223Fr β decay. Low energy levels (E<400 keV) may be classified as parity doublet bands according to the predictions of the reflection asymmetric rotor model. Above a 700 keV gap, a coexistence of symmetric and asymmetric shapes including both static and dynamic octupole correlations is suggested.

  8. Discovery of radioactive decay of /sup 222/Ra and /sup 224/Ra by /sup 14/C emission

    SciTech Connect

    Price, P.B.; Stevenson, J.D.; Barwick, S.W.; Ravn, H.L.

    1985-01-28

    Using the ISOLDE on-line isotope separator at CERN to produce sources of /sup 221/Fr, /sup 221/Ra, /sup 222/Ra, /sup 223/Ra, and /sup 224/Ra, and using polycarbonate track-recording films sensitive to energetic carbon nuclei but not to alpha particles, we have discovered two new cases of the rare /sup 14/C decay mode: in /sup 222/Ra and /sup 224/Ra. Our results for branching ratios, B, relative to alpha decay are for /sup 221/Fr and /sup 221/Ra, B<4.4 x 10/sup -12/; for /sup 222/Ra, B = (3.7 +- 0.6) x 10/sup -10/; for /sup 223/Ra, B = (6.1 +- 1.0) x 10/sup -10/; for /sup 224/Ra, B = (4.3 +- 1.2) x 10/sup -11/. .AE

  9. Psychosocial problems among newly diagnosed rheumatoid arthritis patients.

    PubMed

    Gåfvels, C; Hägerström, M; Nordmark, B; Wändell, P E

    2012-03-01

    We identified patients with newly diagnosed rheumatoid arthritis (RA) in the ages 18-65 years who needed psychosocial interventions. A total of 123 patients (90 women) were asked to participate, but 19 declined and 4 dropped out early in the study, leaving a total of 100 patients (75 women) in the sample. Questionnaires used were the Epidemiological Investigation on Rheumatoid Arthritis study questionnaire, the Hospital Anxiety and Depression Scale, the Sense of Coherence (SOC) scale, and the General Coping Questionnaire. Interviews showed that 46% of the included 100 patients had psychosocial problems (PSP). One third of them had problems directly related to RA. The rest had problems with their life situation in general, without or reinforced by RA. Compared to patients without psychosocial problems, PSP patients lived in more strained social situations, especially regarding personal finances and social support. More of the PSP patients were anxious, showed lower SOC scores, and also used more emotion-based coping strategies (resignation, protest, isolation and intrusion) and less problem-oriented (minimization). They also had higher scores on depression and more frequently expected that RA would negatively affect their future. PSP patients also experienced a more negative impact of the disease, a finding not confirmed by the sickness activity score judged by the rheumatologist. Thus, early in the course of RA, screening instruments should be used to identify PSP patients. Psychosocial treatment and support by medical social workers skilled in RA care should be offered.

  10. Rapid Method for Ra-226 and Ra-228 in Water Samples

    SciTech Connect

    Maxwell, Sherrod, L. III

    2006-02-10

    The measurement of radium isotopes in natural waters is important for oceanographic studies and for public health reasons. Ra-226 (1620 year half-life) is one of the most toxic of the long-lived alpha emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The analysis of radium-226 and radium-228 in natural waters can be tedious and time-consuming. Different sample preparation methods are often required to prepare Ra-226 and Ra-228 for separate analyses. A rapid method has been developed at the Savannah River Environmental Laboratory that effectively separates both Ra-226 and Ra-228 (via Ac-228) for assay. This method uses MnO{sub 2} Resin from Eichrom Technologies (Darien, IL, USA) to preconcentrate Ra-226 and Ra-228 rapidly from water samples, along with Ba-133 tracer. DGA Resin{reg_sign} (Eichrom) and Ln-Resin{reg_sign} (Eichrom) are employed in tandem to prepare Ra-226 for assay by alpha spectrometry and to determine Ra-228 via the measurement of Ac-228 by gas proportional counting. After preconcentration, the manganese dioxide is dissolved from the resin and passed through stacked Ln-Resin-DGA Resin cartridges that remove uranium and thorium interferences and retain Ac-228 on DGA Resin. The eluate that passed through this column is evaporated, redissolved in a lower acidity and passed through Ln-Resin again to further remove interferences before performing a barium sulfate microprecipitation. The Ac-228 is stripped from the resin, collected using cerium fluoride microprecipitation and counted by gas proportional counting. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  11. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    PubMed Central

    Odashiro, Macanori; Hans Filho, Gunter; Pereira, Patricia Rusa; Castro, Ana Rita Coimbra Motta; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors. PMID:26131861

  12. Correlation Between the Expression of MicroRNA-301a-3p and the Proportion of Th17 Cells in Patients with Rheumatoid Arthritis.

    PubMed

    Tang, Xinyi; Yin, Kai; Zhu, Hongsheng; Tian, Jie; Shen, Dong; Yi, Lixian; Rui, Ke; Ma, Jie; Xu, Huaxi; Wang, Shengjun

    2016-04-01

    Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and subsequent joint destruction. Previous studies have confirmed that Th17 cells play a critical role in the pathogenesis of RA. MicroRNA (miR)-301a-3p is a regulatory factor for Th17 cells differentiation that contributes to the pathogenesis of autoimmune diseases. The purposes of this study were to identify the alteration of Th17 cells and analyze the correlation between the expression of the miR-301a-3p and the proportion of Th17 cells in RA patients. The results showed that the frequency of Th17 cells and the expression of transcription factors (RORγt and STAT3) significantly increased in the peripheral blood mononuclear cells (PBMCs) from RA patients, and the associated proinflammatory cytokines were also upregulated. We also observed that the expression of protein inhibitor of activated STAT3 (PIAS3), the main cellular inhibitor of STAT3, was attenuated in RA patients and negatively correlated with the percentage of Th17 cells in RA. Interestingly, miR-301a-3p, an inhibitor of PIAS3 expression, was overexpressed in the PBMCs from RA patients and positively correlated with the frequency of Th17 cells in patients with RA. Taken together, these data indicated that miR-301a-3p and Th17 cells were augmented in peripheral blood, which may play an important role in the process of RA.

  13. Serum level of DNase1l3 in patients with dermatomyositis/polymyositis, systemic lupus erythematosus and rheumatoid arthritis, and its association with disease activity.

    PubMed

    Zhao, Qi; Yang, Chunshu; Wang, Jianing; Li, Yujia; Yang, Pingting

    2016-12-30

    DNase1l3 is an endonuclease to degrade the chromatin of apoptotic or necrotic cells. Serum DNase1l3 may fulfill the function of clearance of chromatin released into the circulation by dying cells, which can trigger autoimmune responses. To date, it remains unclear whether serum DNase1l3 level associates with the pathogenesis of autoimmune diseases. Sixty-eight patients with dermatomyositis/polymyositis (DM/PM, n = 30), systemic lupus erythematosus (SLE, n = 20) and rheumatoid arthritis (RA, n = 18), as well as 26 healthy blood donors were enrolled in the present study. Serum levels of DNase1l3 were quantified by enzyme-linked immunosorbent assay. DNASE1L3 activity in serum was estimated by the capability of serum to digest nucleosomal DNA. Clinical, biochemical, serological and other markers of disease activity (CRP, ESR, C3, C4, anti-Jo-1 and anti-dsDNA, etc.) were measured by standard laboratory procedure. We found a decrease in DNase1l3 level in the DM/PM and SLE patients, resulting in the reduction in serum activity to digest nucleosome DNA. In contrast, the level and activity of DNase1l3 remained unchanged in the RA patients. The DNase1l3 level was relatively lower in the DM/PM patients with anti-Jo-1 antibody and interstitial lung disease, and in the SLE patients with SLE disease activity index higher than 6, renal involvement and anti-dsDNA antibody. DNase1l3 level negatively correlated with CRP and IgG in the PM/DM patients and correlated with ESR in the SLE patients. We found a significant reduction in serum DNase1l3 level in DM/PM and SLE, which may associate with clinic features and disease activity.

  14. Disequilibrium between [sup 226]Ra and supported [sup 210]Pb in a sediment core from a shallow Florida lake

    SciTech Connect

    Brenner, M.; Peplov, A.J.; Schelske, C.L. )

    1994-07-01

    [sup 210]Pb dating can be used to assign ages in lake sediment cores, calculate rates of sediment accumulation, and determine the timing of recent changes in lake-watershed ecosystems. We used low-background gamma counting to measure [sup 226]Ra and total [sup 210]Pb activity in a core from Lake Rowell, Florida. [sup 226]Ra activity was high and strongly variable throughout the core, even exceeding total [sup 210]Pb activity in recently deposited sediments. We traced one source of Ra-rich sediments to the only inflow, Alligator Creek, where stream-bottom deposits display disequilibrium between [sup 226]Ra and supported [sup 210]Pb. High and variable [sup 226]Ra activity in the Lake Rowell profile argues for direct estimates of in situ Ra in lake sediment cores from disturbed watersheds that have Ra-bearing bedrock. Isotopic disequilibrium between [sup 226]Ra and supported [sup 210]Pb makes it difficult to distinguish between supported and unsupported [sup 210]Pb activity throughout the Lake Rowell core and would require special assumptions and nonconventional dating models to establish age-depth relationships. 78 refs., 3 figs., 1 tab.

  15. A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheumatoid Arthritis Patients

    PubMed Central

    Afroz, Sumbul; Giddaluru, Jeevan; Vishwakarma, Sandeep; Naz, Saima; Khan, Aleem Ahmed; Khan, Nooruddin

    2017-01-01

    Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients’ (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA. PMID:28210261

  16. Prediction of remission and low disease activity in disease-modifying anti-rheumatic drug-refractory patients with rheumatoid arthritis treated with golimumab

    PubMed Central

    Kutzbach, Abraham Garcia; Amital, Howard; Pavelka, Karel; Lazaro, María Alicia; Moots, Robert J.; Wollenhaupt, Jürgen; Zerbini, Cristiano A. F.; Louw, Ingrid; Combe, Bernard; Beaulieu, Andre; Schulze-Koops, Hendrik; Dasgupta, Bhaskar; Fu, Bo; Huyck, Susan; Weng, Haoling H.; Govoni, Marinella; Durez, Patrick

    2016-01-01

    Objective. To create a tool to predict probability of remission and low disease activity (LDA) in patients with RA being considered for anti-TNF treatment in clinical practice. Methods. We analysed data from GO-MORE, an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ⩾3.2) despite DMARD therapy. Patients received 50 mg s.c. golimumab (GLM) once monthly for 6 months. In secondary analyses, regression models were used to determine the best set of baseline factors to predict remission (DAS28-ESR <2.6) at month 6 and LDA (DAS28-ESR ⩽3.2) at month 1. Results. In 3280 efficacy-evaluable patients, of 12 factors included in initial regression models predicting remission or LDA, six were retained in final multivariable models. Greater likelihood of LDA and remission was associated with being male; younger age; lower HAQ, ESR (or CRP) and tender joint count (or swollen joint count) scores; and absence of comorbidities. In models predicting 1-, 3- and 6-month LDA or remission, area under the receiver operating curve was 0.648–0.809 (R2 = 0.0397–0.1078). The models also predicted 6-month HAQ and EuroQoL-5-dimension scores. A series of matrices were developed to easily show predicted rates of remission and LDA. Conclusion. A matrix tool was developed to show predicted GLM treatment outcomes in patients with RA, based on a combination of six baseline characteristics. The tool could help provide practical guidance in selection of candidates for anti-TNF therapy. PMID:27114562

  17. Metrological Determination of Natural Radioactive Isotopes {sup 226}Ra, {sup 228}Ra and {sup 210}Pb by Means of Ge Detector

    SciTech Connect

    Almeida, Maria Candida M. de; Delgado, Jose U.; Poledna, Roberto; Oliveira, Estela Maria de; Silva, Ronaldo L. da

    2008-08-07

    A metrological method to determine the activity per mass unity (activity concentration) of {sup 226}Ra and {sup 210}Pb ({sup 238}U decay series) and {sup 228}Ra ({sup 232}Th series) by gamma-ray spectrometers based on hyper-pure coaxial germanium detector was developed. In the soil the {sup 22}Ra (half-life = 1600 years) exhibits the same level of radioactivity as {sup 238}U (half-life 4.5x10{sup 9} years) because of a natural phenomenon called secular equilibrium. {sup 226}Ra decays into {sup 222}Rn (half-life = 3.8 days), a radioactive inert gas. After several days, the {sup 222}Rn naturally decays to {sup 218}Po (half-life = 3 minutes), where finally {sup 210}Pb (half-life = 22 years) is produced. The metrological capability of high-resolution gamma-ray spectrometry for naturally occurring radionuclides at environmental levels is showed, with emphasis on the use of 2 mL standard sources volume in a glass ampoule. Source preparation and calibration procedures are described. Radionuclide standards in an activity range of 10 to 250 Bq/g were produced which can be applied in a variety of environmental sample analysis (water, plant material, sediment, etc.). Uncertainties for {sup 226}Ra and {sup 210}Pb around 3% (k = 1) were obtained.

  18. Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study.

    PubMed

    Chopra, Arvind; Saluja, Manjit; Tillu, Girish; Venugopalan, Anuradha; Narsimulu, Gumdal; Handa, Rohini; Bichile, Lata; Raut, Ashwinikumar; Sarmukaddam, Sanjeev; Patwardhan, Bhushan

    2012-02-01

    Hydroxychloroquine sulfate (HCQS) is a popular disease-modifying antirheumatic drug (DMARD) despite modest efficacy and toxicity. Ayurveda (ancient India medicinal system) physicians treat rheumatoid arthritis (RA) with allegedly safer herbal formulations. We report a head-to-head comparison in an exploratory drug trial. The objective is to compare standardized Ayurvedic formulations and HCQS in the treatment of RA. One hundred twenty-one patients with active moderately severe RA (ACR 1988 classified) were randomized into a 24-week investigator-blind, parallel efficacy, three-arm (two Ayurvedic and HCQS) multicenter drug trial study; polyherb (Tinospora cordifolia and Zingiber officinale based) and monoherb (Semecarpus anacardium). Study measures included joint counts (pain/tenderness and swelling), pain visual analogue scale, global disease assessments, and health assessment questionnaire. Oral meloxicam (fixed-dosage schedule) was prescribed to all patients during the initial 16 weeks. Patients on prednisolone could continue a fixed stable dose (<7.5 mg daily). Rescue oral use of paracetamol was permitted and monitored. All groups matched well at baseline. An intent-to-treat analysis (ANOVA, significance P < 0.05) did not show significant differences by treatment groups. In the polyherb, monoherb, and HCQS arms, 44%, 36%, and 51%, respectively, showed ACR 20 index improvement. Several efficacy measures improved significantly in the HCQS and polyherb groups with no difference between the groups (corrected P). However, the latter was individually superior to monoherb. Only mild adverse events (gut and skin, and none withdrew) were reported with no differences between the groups. Forty-two patients dropped out. This preliminary drug trial controlled for HCQS demonstrated a standardized Ayurvedic polyherb drug to be effective and safe in controlling active RA. A better-designed study with a longer evaluation period is recommended.

  19. Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Luo, Qing; Deng, Zhen; Xu, Chuxin; Zeng, Lulu; Ye, Jianqing; Li, Xue; Guo, Yang; Huang, Zikun; Li, Junming

    2017-01-01

    Background It is well known that lymphocytes play an important role in rheumatoid arthritis (RA). T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (TIGIT) have immunosuppressive co-stimulatory molecules that mediate inhibitory effects, but their roles in RA are poorly understood. Material/Methods Were recruited 76 patients with RA and 33 healthy controls (HC). Clinical manifestations, laboratory measurements, physical examination, and medical history of RA patients were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes, and CD3+CD8+ T lymphocytes was determined using flow cytometry. The expression of TIGIT on T lymphocytes in patients with RA was further analyzed to investigate its correlations with markers of autoimmune response, inflammation, and disease activity in RA. Results Compared with HC, the expression levels of TIGIT on CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were significantly increased in patients with RA (P < 0.01). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was positively correlated with RF, increased ACPA, ESR, and CRP levels. The frequency of TIGIT-expressing CD3+CD8+ T lymphocytes was positively correlated with RF and ESR levels. Furthermore, the expression level of TIGIT on CD3+CD4+ T lymphocytes was positively correlated with the DAS28 score in RA. Conclusions The expression levels of TIGIT on T lymphocytes were elevated and correlated with disease activity in RA. PMID:28282368

  20. [Possibilities of therapy GLP1 RA for diabetics with nephropathy].

    PubMed

    Adamíková, Alena

    2015-04-01

    The incretin hormone GLP1 (glucagon-like peptide 1) has also systemic effects besides its effects on the pancreas. The renal expression for the receptors GLP1 and DPP4 has been described in a whole line of experimental stu-dies. Activation of the receptors for GLP1 in the kidneys has diuretic and natriuretic effects apparently through the renal tubular cells and sodium transporters. Pre-clinical incretin therapy decreased albuminuria, affected glomerulosclerosis, oxidative stress and fibrosis in the kidneys. Diabetic nephropathy is the major cause of kidney failure. In the course of renal insufficiency the functional possibilities and simultaneous safe compensation of diabetes are limited. The treatment GLP1 RA of patients with type 2 diabetes and nephropathy appear to be effective from the aspect of effectiveness and safety.

  1. Exploring Patient Activation in the Clinic: Measurement from Three Perspectives

    ERIC Educational Resources Information Center

    Ledford, Christy J. W.; Ledford, Christopher C.; Childress, Marc A.

    2013-01-01

    Objective. To further conceptualize and operationalize patient activation (PA), using measures from patient, physician, and researcher perspectives. Data Source/Study Setting. Multimethod observation in 2010 within a family medicine clinic. Study Design. Part of an intervention with 130 patients with type 2 diabetes, this observational study…

  2. Enhancing the Lives of Nursing Home Patients through Reading Activities.

    ERIC Educational Resources Information Center

    Lovelace, Terry

    This study investigated the use of reading activities in the enhancement of the lives of nursing-home patients. A special reading group was led by a reading specialist in weekly sessions. Patients voluntarily attended the one-hour sessions and read short selections supplied by the reading specialist. Patients ranged in age from 54 to 91. The…

  3. Effects of Methotrexate on Carotid Intima-media Thickness in Patients with Rheumatoid Arthritis.

    PubMed

    Kim, Hyun-Je; Kim, Min-Jung; Lee, Choong-Ki; Hong, Young-Hoon

    2015-11-01

    The purpose of this study was to evaluate the effects of rheumatoid arthritis (RA) and antirheumatic drugs on atherosclerosis by comparing carotid intima-media thickness (CIMT) as an indicator for cardiovascular diseases (CVD). This study included 44 female RA patients who met the 2010 ACR/EULAR criteria and age-matched 22 healthy females. CIMT was measured on both carotid arteries using a B-mode ultrasound scan. The mean value of both sides was taken as the CIMT of the subject. The CIMT was evaluated according to the use of drugs, disease activity and CVD risk factors in RA patients as a case-control study. Higher CIMT was observed in RA patients as compared with healthy subjects (0.705 ± 0.198 mm, 0.611 ± 0.093 mm, respectively, P < 0.05). With adjustment for the CVD risk factors, disease activity and the use of anti-rheumatic drugs, methotrexate (MTX) only showed a favorable effect on CIMT in RA. A significantly lower CIMT was observed in RA with MTX as compared with RA without MTX (0.644 ± 0.136 mm, 0.767 ± 0.233 mm, respectively, P < 0.05). The effects were correlated with MTX dosage (β = -0.029, P < 0.01). The use of MTX should be considered in high priority not only to control arthritis but also to reduce the RA-related CVD risk to mortality.

  4. The effect on treatment response of fibromyalgic symptoms in early rheumatoid arthritis patients: results from the ESPOIR cohort

    PubMed Central

    Combe, Bernard; Niu, Jingbo; Rincheval, Nathalie; Gaujoux-Viala, Cécile; Felson, David T.

    2015-01-01

    Objective. To evaluate whether patients with RA who belong to the spectrum of fibromyalgic RA (FRA) have an impaired response to treatment measured by traditional activity scores. Methods. Patients from the ESPOIR cohort were analysed. This prospective cohort included 813 patients with early arthritis not initially receiving DMARDs. Among the 697 patients who met RA classification criteria, we studied two groups, one with and the other without FRA. The following endpoints were compared at 6, 12 and 18 months using a mixed linear regression model: 28-joint DAS (DAS28), Simple Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI) and HAQ. In addition, attainment of low disease activity (LDA; DAS28 <3.2) and remission (DAS28 <2.6, SDAI <3.3, CDAI <2.8) at these time points was analysed. Results. Patients with FRA (n = 120) had higher DAS28, SDAI, CDAI and HAQ scores than patients with RA and no fibromyalgic characteristics (n = 548). DAS28 and other DASs started out higher in subjects with FRA, and while they improved to a similar extent to in the isolated RA group, they remained consistently higher among FRA patients. Achievement of LDA and remission was significantly less likely in subjects with FRA. Conclusion. Patients with FRA and RA will have a similar response to treatment according to the decrease in indexes of disease activity, but may miss the target of remission or LDA. PMID:26175470

  5. The Leisure Activities of Mental Patients Prior to Hospitalization.

    ERIC Educational Resources Information Center

    Babow, Irving; Simkin, Sol

    To study the leisure activities, social participation, and organizational participation of mental patients before hospital admission, a three-part research instrument was developed consisting of a structured interview schedule requesting information on the patient's leisure activities, a self-administered questionnaire entitled Survey of Opinions…

  6. Assessment of (226)Ra age-dependent dose from water intake.

    PubMed

    Porntepkasemsan, Boonsom; Srisuksawad, Kanitha

    2008-11-01

    The radioactivity in canal and ground waters collected in a 2-year long observation from the vicinity of the Rare Earth Research and Development Center (RRDC), Phathumthani Province, Thailand, was measured in order to determine the concentration of (226)Ra and to estimate the age-dependent effective dose to humans due to consumption. (226)Ra activities in both canal and ground waters were well below the WHO guidance level for drinking water quality of 1 Bq L(-1). The highest (226)Ra effective doses per year were found for infants and teens. However, the observed levels of calculated (226)Ra effective doses for all age groups in both canal and ground waters show satisfactory low values (less than 15 microSv yr(-1)). These values are acceptable in accordance with the WHO recommended reference dose level of 100 microSv yr(-1) from water intake of 2 Lday(-1).

  7. 226Ra or 226Ra/Ba dating of Holocene volcanic rocks: application to Mt. Etna and Merapi volcanoes

    NASA Astrophysics Data System (ADS)

    Condomines, M.; Gauthier, P. J.; Tanguy, J. C.; Gertisser, R.; Thouret, J. C.; Berthommier, P.; Camus, G.

    2005-02-01

    This paper shows how 226Ra- 230Th disequilibria can be used to date Holocene volcanic rocks from some well selected volcanoes. A systematic study of these disequilibria on historical or well-dated volcanic samples is indeed first required to test the applicability of this method. Two examples are described here to illustrate its potential. In the case of Mt. Etna, the good correlation observed between ( 226Ra) 0 activities at the time of eruption and Th contents in lava flows from the last two millennia [M. Condomines, J.C. Tanguy, V. Michaud, Magma dynamics at Mt. Etna: constraints from U-Th-Ra-Pb radioactive disequilibria and Sr isotopes in historical lavas, Earth Planet. Sci. Lett. 132 (1995) 25-41] is used to infer the ages of several newly analysed lava flows. The calculated ages are in good agreement with those deduced from the archaeomagnetic curve describing the variation of the geomagnetic field direction in southern Italy [J.C. Tanguy, I. Bucur, J.F.C. Thompson, Geomagnetic secular variation in Sicily and revised ages of historic lavas from Mt. Etna, Nature 318 (1985) 453-455, J.C. Tanguy, M. Le Goff, V. Chillemi, A. Paiotti, C. Principe, S. La Delfa, G. Patane, Variation séculaire de la direction du champ géomagnétique enregistrée par les laves de l'Etna et du Vésuve pendant les deux derniers millénaires, C. R. Acad. Sci. Paris 329 (1999) 557-564, J.C. Tanguy, M. Le Goff, C. Principe, S. Arrighi, V. Chillemi, A. Paiotti, S. La Delfa, G. Patane, Archaeomagnetic dating of Mediterranean volcanics of the last 2100 years: validity and limits. Earth Planet. Sci. Lett. 211 (2003) 111-124]. We also present a whole set of new U-series data on historical, recent, and older samples from Merapi (Indonesia), and show that the ( 226Ra)/Ba ratio has probably maintained a quasi-steady state value during at least the past four millennia, and can be used to infer the ( 226Ra) 0/Ba ratio of old volcanics at the time of eruption, and thus their ages. Comparison with

  8. Ra: The Sun for Science and Humanity

    NASA Technical Reports Server (NTRS)

    1996-01-01

    To guide the development of the Ra Strategic Framework, we defined scientific and applications objectives. For our primary areas of scientific interest, we choose the corona, the solar wind, the Sun's effect on the Earth, and solar theory and model development. For secondary areas of scientific interest, we selected sunspots, the solar constant, the Sun's gravitational field, helioseismology and the galactic cosmic rays. We stress the importance of stereoscopic imaging, observations at high spatial, spectral, and temporal resolutions, as well as of long duration measurements. Further exploration of the Sun's polar regions is also important, as shown already by the Ulysses mission. From an applications perspective, we adopted three broad objectives that would derive complementary inputs for the Strategic Framework. These were to identify and investigate: possible application spin-offs from science missions, possible solar-terrestrial missions dedicated to a particular application, and possible future applications that require technology development. The Sun can be viewed as both a source of resources and of threats. Our principal applications focus was that of threat mitigation, by examining ways to improve solar threat monitoring and early warning systems. We compared these objectives to the mission objectives of past, current, and planned international solar missions. Past missions (1962-1980) seem to have been focused on improvement of scientific knowledge, using multiple instrument spacecraft. A ten year gap followed this period, during which the results from previous missions were analyzed and solar study programmes were prepared in international organizations. Current missions (1990-1996) focus on particular topics such as the corona, solar flares, and coronal mass ejections. In planned missions, Sun/Earth interactions and environmental effects of solar activity are becoming more important. The corona is the centre of interest of almost all planned missions

  9. Glycan Biomarkers for Rheumatoid Arthritis and Its Remission Status in Han Chinese Patients.

    PubMed

    Sebastian, Andrea; Alzain, Mohamed Ali; Asweto, Collins Otieno; Song, Haicheng; Cui, Liufu; Yu, Xinwei; Ge, Siqi; Dong, Hao; Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; He, Dian; Guo, Xiuhua; Song, Manshu; Wang, Youxin; Wang, Wei

    2016-06-01

    Rheumatoid arthritis (RA), a systemic, chronic, and progressive inflammatory autoimmune disease, affects up to 1.0% of the world population doubling mortality rate of patients and is a major global health burden. Worrisomely, we lack robust diagnostics of RA and its remission status. Research with the next-generation biomarker technology platforms such as glycomics offers new promises in this context. We report here a clinical case-control study comprising 128 patients suffering from chronic RA (80.22% in remission, 19.78% active clinically) and 195 gender- and age-matched controls, with a view to the putative glycan biomarkers of RA as well as its activity or remission status in Han Chinese RA patients. Hydrophilic interaction liquid chromatography-ultra-performance liquid chromatography (HILIC-UPLC) was used for the analysis of IgG glycans. The regression model identified the glycans that predict RA status, while a receiver operating characteristic (ROC) curve analysis validated the sensitivity and prediction power. Among the total 24 glycan peaks (GP1-GP24), ROC analysis showed only GP1 prediction to be highly sensitive with an area under the curve (AUC) = 0.881. Even though GP21 and GP22 could predict active status among the RA cases (p < 0.05), they had lower sensitivity of prediction with an AUC = 0.658. Taken together, these observations suggest that GP1 might have potential as a putative biomarker for RA in the Han Chinese population, while the change in IgG glycosylation shows association with the RA active and remission states. To the best of our knowledge, this is the first glycomics study with respect to disease activity and remission states in RA.

  10. Comparative Analysis Of 226Ra Soil-To-Plant Transfer In Cabbage Grown In Various Regions

    NASA Astrophysics Data System (ADS)

    Madruga, M. J.; Carvalho, F. P.; Silva, L.; Gouveia, J.

    2008-08-01

    The transfer of 226Ra from soil to cabbage was compared amongst regions, namely the surroundings of Urgeiriça uranium milling tailings (GE), regions with past uranium mining activities (GN1), and regions with no uranium mining activities and no uranium deposits (GN2). Results show a slight increase of the concentration ratio values at low radium concentration in soils. Statistical analysis of the mean 226Ra activity concentrations in soil and cabbage for the three regions was carried out. The comparison of 226Ra activity concentrations in soils indicated no difference (p>0.05), between GE and GN2 and significant differences (p<0.05) between GE and GN1 and between GN1 and GN2. Similar statistical results were obtained for 226Ra activity concentrations in cabbage from the same regions. It was concluded that radium Concentration Ratio (CR) for cabbage grown in the region of the main uranium milling site (GE) is of the same order of magnitude of CR in cabagge grown in background regions (GN2). However, 226Ra CR was higher in cabagge from the region with past uranium mining activities (GN1).

  11. Ra isotopes in trees: Their application to the estimation of heartwood growth rates and tree ages

    NASA Astrophysics Data System (ADS)

    Hancock, Gary J.; Murray, Andrew S.; Brunskill, Gregg J.; Argent, Robert M.

    2006-12-01

    The difficulty in estimating growth rates and ages of tropical and warm-temperate tree species is well known. However, this information has many important environmental applications, including the proper management of native forests and calculating uptake and release of atmospheric carbon. We report the activities of Ra isotopes in the heartwood, sapwood and leaves of six tree species, and use the radial distribution of the 228Ra/226Ra activity ratio in the stem of the tree to estimate the rate of accretion of heartwood. A model is presented in which dissolved Ra in groundwater is taken up by tree roots, translocated to sapwood in a chemically mobile (ion-exchangeable) form, and rendered immobile as it is transferred to heartwood. Uptake of 232Th and 230Th (the parents of 228Ra and 226Ra) is negligible. The rate of heartwood accretion is determined from the radioactive decay of 228Ra (half-life 5.8 years) relative to long-lived 226Ra (half-life 1600 years), and is relevant to growth periods of up to 50 years. By extrapolating the heartwood accretion rate to the entire tree ring record the method also appears to provide realistic estimates of tree age. Eight trees were studied (three of known age, 72, 66 and 35 years), including three Australian hardwood eucalypt species, two mangrove species, and a softwood pine (P. radiata). The method indicates that the rate of growth ring formation is species and climate dependent, varying from 0.7 rings yr-1 for a river red gum (E. camaldulensis) to around 3 rings yr-1 for a tropical mangrove (X. mekongensis).

  12. Increasing Patient Activation Could Improve Outcomes for Patients with Inflammatory Bowel Disease.

    PubMed

    Shah, Shawn L; Siegel, Corey A

    2015-12-01

    Inflammatory bowel disease (IBD) is a complex disease process that often requires the integration of skills from various health care providers to adequately meet the needs of patients with IBD. The medical and surgical treatment options for IBD have become more complicated and are frequently a source of angst for both the patient and provider. However, it has become more important than ever to engage patients in navigating the treatment algorithm. Although novel in the IBD world, the concept of patients' becoming more active and effective managers of their care has been well studied in other disease processes such as diabetes mellitus and mental illness. This idea of patient activation refers to a patient understanding his or her role in the care process and having the skill sets and self-reliance necessary to manage his or her own health care. Over the past decade, evidence supporting the role of patient activation in chronic illness has grown, revealing improved health outcomes, enhanced patient experiences, and lower overall costs. Patient activation can be measured, and interventions have been shown to improve levels of activation over time and influence outcomes. A focus on patient activation is very appropriate for patients with IBD because this may potentially serve as a tool for IBD providers to not only improve patient outcomes and experience but also reduce health care costs.

  13. Clonal heterogeneity of synovial fluid T lymphocytes from patients with rheumatoid arthritis

    SciTech Connect

    Duby, A.D.; Sinclair, A.K.; Osborne-Lawrence, S.L. ); Zeldes, W.; Kan, Li; Fox, D.A. )

    1989-08-01

    Although substantial evidence suggests that synovial T lymphocytes are critical in the pathogenesis of rheumatoid arthritis (RA), little is known regarding their antigenic specificities, antigen receptor gene rearrangements, and mechanisms of activation. To assess the extend of expansion of specific clones among RA synovial fluid T cells, Southern blot analyses of T-cell receptor (TCR) gene rearrangements were performed on 40 RA synovial fluid T-cell clones, as well as on fresh and polyclonally activated T cells from RA synovial fluid, RA peripheral blood, and normal peripheral blood. Two of the clones had identical TCR rearrangement patterns, but the remainder were unique. The nonclonal RA T-cell samples showed the same pattern of TCR {beta}-chain rearrangement that was observed among normal peripheral blood T cells, indicating no dominant clonal T-cell population in these samples. It was noted that with sufficient exposure of autoradiograms of the Southern blots, discrete TCR gene rearrangements, representing in some cases common D{sub {beta}}J{sub {beta}} (D, diversity; J, joining) rearrangements, were evident in T cells from peripheral blood of normal individuals and patients with RA, as well as T cells from RA synovial fluid. Taken together, the findings indicate that only a minor degree of oligoclonality can be demonstrated among T lymphocytes from RA synovial fluid.

  14. Baseline serum interleukin-34 levels independently predict radiographic progression in patients with rheumatoid arthritis.

    PubMed

    Chang, Sung Hae; Choi, Byoong Yong; Choi, Jungbum; Yoo, Jong Jin; Ha, You-Jung; Cho, Hyon Joung; Kang, Eun Ha; Song, Yeong Wook; Lee, Yun Jong

    2015-01-01

    The aim of our observational study was to investigate the clinical significance of interleukin (IL)-34, a novel osteoclastogenic cytokine, for predicting structural damage in patients with rheumatoid arthritis (RA). Serum IL-34 levels were measured in 100 RA patients, 36 patients with ankylosing spondylitis (AS), and 59 gender- and age-matched healthy individuals using an enzyme-linked immunosorbent assay. We also measured IL-34 concentrations in synovial fluid (SF) samples from 18 RA patients and 19 osteoarthritis (OA) patients. Progression of structural damage was assessed in 81 patients with RA by plain radiographs using the modified Sharp/van der Heijde score (SHS) at baseline and after an average 1.6-year follow-up period. Serum IL-34 levels were significantly higher in patients with RA (p < 0.001) or AS (p < 0.001) than in healthy controls. SF IL-34 levels were also significantly higher in RA patients than in OA patients (p < 0.001). In RA, serum IL-34 levels were associated with rheumatoid factor positivity (p = 0.01), current smoking (p < 0.01), erythrocyte sedimentation rate (p = 0.01), and C-reactive protein levels (p < 0.01), but not with disease activity score 28. ΔSHS/year was positively correlated with serum IL-34 levels (r = 0.443, p < 0.001). In multivariate logistic regression analyses, serum IL-34 level was an independent risk factor for radiographic progression. These results suggest that IL-34, a novel osteoclastogenic cytokine, plays a role in RA-associated joint damage and is a potential biomarker for predicting subsequent radiographic progression in patients with RA.

  15. Long-term study of the impact of methotrexate on serum cytokines and lymphocyte subsets in patients with active rheumatoid arthritis: correlation with pharmacokinetic measures

    PubMed Central

    Kremer, Joel M; Lawrence, David A; Hamilton, Robert; McInnes, Iain B

    2016-01-01

    Objective To describe changes in immune parameters observed during long-term methotrexate (MTX) therapy in patients with active rheumatoid arthritis (RA) and explore correlations with simultaneously measured MTX pharmacokinetic (PKC) parameters. Design Prospective, open-label, long-term mechanism of action study. Setting University clinic. Methods MTX was initiated at a single weekly oral dose of 7.5 mg and dose adjusted for efficacy and toxicity for the duration of the study. Standard measures of disease activity were performed at baseline and every 6–36 months. Serum cytokine measurements in blood together with lymphocyte surface immunophenotypes and stimulated peripheral blood mononuclear cell (PBMC) cytokine production were assessed at each clinical evaluation. Results Cytokine concentrations exhibited multiple significant correlations with disease activity measures over time. The strongest correlations observed were for interleukin (IL)-6 (r=0.45, p<0.0001 for swollen joints and r=0.32, p=0.002 for tender joints) and IL-8 (r=0.25, p=0.01 for swollen joints). Significant decreases from baseline were observed in serum IL-1B, IL-6 and IL-8 concentrations. The most significant changes were observed for IL-6 (p<0.001). Significant increases from baseline were observed in IL-2 release from PBMCs ex vivo (p<0.01). In parallel, multiple statistically significant correlations were observed between MTX PKC measures and immune parameters. The change in swollen joint count correlated inversely with the change in area under the curve (AUC) for MTX (r=−0.63, p=0.007). Conclusions MTX therapy of patients with RA is accompanied by a variety of changes in serum cytokine expression, which in turn correlate strongly with clinical disease activity and MTX pharmacokinetics (PKCs). These data strongly support the notion that MTX mediates profound and functionally relevant effects on the immunological hierarchy in the RA lesion. PMID:27335660

  16. Activity recognition in patients with lower limb impairments: do we need training data from each patient?

    PubMed

    Lonini, Luca; Gupta, Aakash; Kording, Konrad; Jayaraman, Arun

    2016-08-01

    Machine learning allows detecting specific physical activities using data from wearable sensors. Such a quantification of patient mobility over time promises to accurately inform clinical decisions for physical rehabilitation. There are two strategies of setting up the machine learning problem: detect one patient's activities using data from the same patient (personal model) or detect their activities using data from other patients (global model), and we currently do not know if personal models are necessary. Here we consider the problem of detecting physical activities from a waist-worn accelerometer in patients who use a knee-ankle-foot orthosis (KAFO) to walk. We show that while a model based on healthy subjects has low accuracy, the global model performs as well as the personal model. This is encouraging because it suggests that condition-specific activity recognition algorithms are sufficient and that no data from individual patients is necessary.

  17. Effects of an Individualized Activity Program on Elderly Patients

    ERIC Educational Resources Information Center

    Salter, Carlota de Lerma; Salter, Charles A.

    1975-01-01

    A combined program of Reality Orientation, Activities of Daily Living, and Recreational Activities, together with environmental stimulation, was applied on an individualized basis to 21 elderly patients suffering from both psychological disorders and long-term physical illness. The motivation to participate in the available activities increased…

  18. 226Ra bioavailability to plants at the Urgeiriça uranium mill tailings site.

    PubMed

    Madruga, M J; Brogueira, A; Alberto, G; Cardoso, F

    2001-01-01

    Large amounts of solid wastes (tailings) resulting from the exploitation and treatment of uranium ore at the Urgeiriça mine (north of Portugal) have been accumulated in dams (tailing ponds). To reduce the dispersion of natural radionuclides into the environment, some dams were revegetated with eucalyptus (Eucalyptus globolus) and pines (Pinus pinea). Besides these plants, some shrubs (Cytisus spp.) are growing in some of the dams. The objective of this study is to determine the 226Ra bioavailability from uranium mill tailings by quantifying the total and available fraction of radium in the tailings and to estimate its transfer to plants growing on the tailing piles. Plant and tailing samples were randomly collected and the activity concentration of 226Ra in plants (aerial part and roots) and tailings was measured by gamma-spectrometry. The exchangeable fraction of radium in tailings was quantified using one single step extraction with 1 mol dm-3 ammonium acetate (pH = 7) or 1 mol dm-3 calcium chloride solutions. The results obtained for 226Ra uptake by plants show that 226Ra concentration ratios for eucalyptus and pines decrease at low 226Ra concentrations in the tailings and appear relatively constant at higher radium concentrations. For shrubs, the concentration ratios increase at higher 226Ra solid waste concentrations approaching a saturation value. Percentage values of 16.0 +/- 8.3 and 12.9 +/- 8.9, for the fraction of radium extracted from the tailings, using 1 mol dm-3 ammonium acetate or calcium chloride solutions, respectively, were obtained. The 226Ra concentration ratios determined on the basis of exchangeable radium are one order of magnitude higher than those based on total radium. It can be concluded that, at a 95% confidence level, more consistent 226Ra concentration ratios were obtained when calculated on the basis of available radium than when total radium was considered, for all the dams.

  19. Mutations in the interleukin receptor IL11RA cause autosomal recessive Crouzon-like craniosynostosis

    PubMed Central

    Keupp, Katharina; Li, Yun; Vargel, Ibrahim; Hoischen, Alexander; Richardson, Rebecca; Neveling, Kornelia; Alanay, Yasemin; Uz, Elif; Elcioğlu, Nursel; Rachwalski, Martin; Kamaci, Soner; Tunçbilek, Gökhan; Akin, Burcu; Grötzinger, Joachim; Konas, Ersoy; Mavili, Emin; Müller-Newen, Gerhard; Collmann, Hartmut; Roscioli, Tony; Buckley, Michael F; Yigit, Gökhan; Gilissen, Christian; Kress, Wolfram; Veltman, Joris; Hammerschmidt, Matthias; Akarsu, Nurten A; Wollnik, Bernd

    2013-01-01

    We have characterized a novel autosomal recessive Crouzon-like craniosynostosis syndrome in a 12-affected member family from Antakya, Turkey, the presenting features of which include: multiple suture synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next-generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice-site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon-like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11-mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon-like craniosynostosis. PMID:24498618

  20. Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex.

    PubMed Central

    Steiner, G; Hartmuth, K; Skriner, K; Maurer-Fogy, I; Sinski, A; Thalmann, E; Hassfeld, W; Barta, A; Smolen, J S

    1992-01-01

    RA33 is a nuclear autoantigen with an apparent molecular mass of 33 kD. Autoantibodies against RA33 are found in about 30% of sera from RA patients, but only occasionally in sera from patients with other connective tissue diseases. To characterize RA33, the antigen was purified from HeLa cell nuclear extracts to more than 90% homogeneity by affinity chromatography on heparin-Sepharose and by chromatofocusing. Sequence analysis of five tryptic peptides revealed that their sequences matched corresponding sequences of the A2 protein of the heterogeneous nuclear ribonucleoprotein (hnRNP) complex. Furthermore, RA33 was shown to be present in the 40S hnRNP complex and to behave indistinguishably from A2 in binding to single stranded DNA. In summary, these data strongly indicate that RA33 and A2 are the same protein, and thus identify on a molecular level a new autoantigen. Images PMID:1522214

  1. Increased detection of latent tuberculosis by tuberculin skin test and booster phenomenon in early rheumatoid arthritis patients.

    PubMed

    Pérez-Barbosa, L; Esquivel-Valerio, J A; Arana-Guajardo, A C; Vega-Morales, D; Riega-Torres, J; Garza-Elizondo, M A

    2015-09-01

    The incidence of tuberculosis (TB) in rheumatoid arthritis (RA) patients is up to four times higher when compared to the general population, but their risk increases with the use of TNF-a drugs. Appropriate screening of latent tuberculosis infection (LTBI) and proper management of such cases substantially reduce the incidence of active TB. Tuberculin skin test (TST) is a widely used method for the detection of LTBI. The time of diagnosis of RA as well as the age of the patient might modify the TST performance. We did an observational, comparative study of RA patients with early and established disease, with the objective to know the prevalence of LTBI using the TST and booster test; an induration ≥5 mm was considered reactive. We evaluated 143 patients (83 [58 %] early RA patients). We found 31.3 and 21.7 % TST positivity in early and established RA patients, respectively. With the use of booster test, the positivity increased to 46.5 and 28.8 %, respectively (p = 0.048, OR 1.33, 95 % CI 1.01-1.75). In conclusion, we found that TST and booster test increased LTBI detection in early RA patients, which may suggest that time of RA diagnosis might affect cellular immunity and therefore the TST response.

  2. RA-XII inhibits tumour growth and metastasis in breast tumour-bearing mice via reducing cell adhesion and invasion and promoting matrix degradation

    PubMed Central

    Leung, Hoi-Wing; Zhao, Si-Meng; Yue, Grace Gar-Lee; Lee, Julia Kin-Ming; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara Bik-San

    2015-01-01

    Cancer cells acquire invasive ability to degrade and adhere to extracellular matrix (ECM) and migrate to adjacent tissues. This ultimately results metastasis. Hence, the present study investigated the in vitro effects of cyclopeptide glycoside, RA-XII on cell adhesion, invasion, proliferation and matrix degradation, and its underlying mechanism in murine breast tumour cells, 4T1. The effect of RA-XII on tumour growth and metastasis in 4T1-bearing mice was also investigated. Our results showed that RA-XII inhibited tumour cell adhesion to collagen, fibronectin and laminin, RA-XII also reduced the expressions of vascular cell adhesion molecule, intracellular adhesion molecule and integrins, and integrin binding. In addition, RA-XII significantly inhibited breast tumour cell migration via interfering cofilin signaling and chemokine receptors. The activities of matrix metalloproteinase-9 and urokinase-type of plasminogen activator, and the expressions of ECM-associated proteinases were attenuated significantly by RA-XII. Furthermore, RA-XII induced G1 phase arrest and inhibited the expressions of cyclins and cyclin-dependent kinases. RA-XII inhibited the expressions of molecules in PI3K/AKT, NF-kappaB, FAK/pSRC, MAPK and EGFR signaling. RA-XII was also shown to have anti-tumour, anti-angiogenic and anti-metastatic activities in metastatic breast tumour-bearing mice. These findings strongly suggested that RA-XII is a potential anti-metastatic agent for breast cancer. PMID:26592552

  3. Management of Hypertension: Adapting New Guidelines for Active Patients.

    ERIC Educational Resources Information Center

    Tanji, Jeffrey L.; Batt, Mark E.

    1995-01-01

    Discusses recent guidelines on hypertension from the National Heart, Lung, and Blood Institute and details the latest management protocols for patients with high blood pressure. The article helps physicians interpret the guidelines for treating active patients, highlighting diagnosis, step care revision, pharmacology, and sports participation…

  4. Decreased Prolidase Activity in Patients with Posttraumatic Stress Disorder

    PubMed Central

    Bulut, Mahmut; Atli, Abdullah; Kaplan, İbrahim; Kaya, Mehmet Cemal; Bez, Yasin; Özdemir, Pınar Güzel; Sır, Aytekin

    2016-01-01

    Objective Many neurochemical systems have been implicated in the development of Posttraumatic Stress Disorder (PTSD). The prolidase enzyme is a cytosolic exopeptidase that detaches proline or hydroxyproline from the carboxyl terminal position of dipeptides. Prolidase has important biological effects, and to date, its role in the etiology of PTSD has not been studied. In the present study, we aimed to evaluate prolidase activity in patients with PTSD. Methods The study group consisted of patients who were diagnosed with PTSD after the earthquake that occurred in the province of Van in Turkey in 2011 (n=25); the first control group consisted of patients who experienced the earthquake but did not show PTSD symptoms (n=26) and the second control group consisted of patients who have never been exposed to a traumatic event (n=25). Prolidase activities in the patients and the control groups were determined by the ELISA method using commercial kits. Results Prolidase activity in the patient group was significantly lower when compared to the control groups. Prolidase activity was also significantly lower in the traumatized healthy subjects compared to the other healthy group (p<0.01). Conclusion The findings of the present study suggest that the decrease in prolidase activity may have neuroprotective effects in patients with PTSD. PMID:27482243

  5. Incidence of active mycobacterial infections in Brazilian patients with chronic inflammatory arthritis and negative evaluation for latent tuberculosis infection at baseline - A longitudinal analysis after using TNFα blockers

    PubMed Central

    Gomes, Carina Mori Frade; Terreri, Maria Teresa; de Moraes-Pinto, Maria Isabel; Barbosa, Cássia; Machado, Natália Pereira; Melo, Maria Roberta; Pinheiro, Marcelo Medeiros

    2015-01-01

    Several studies point to the increased risk of reactivation of latent tuberculosis infection (LTBI) in patients with chronic inflammatory arthritis (CIAs) after using tumour necrosis factor (TNF)α blockers. To study the incidence of active mycobacterial infections (aMI) in patients starting TNF α blockers, 262 patients were included in this study: 109 with rheumatoid arthritis (RA), 93 with ankylosing spondylitis (AS), 44 with juvenile idiopathic arthritis (JIA) and 16 with psoriatic arthritis (PsA). All patients had indication for anti-TNF α therapy. Epidemiologic and clinical data were evaluated and a simple X-ray and tuberculin skin test (TST) were performed. The control group included 215 healthy individuals. The follow-up was 48 months to identify cases of aMI. TST positivity was higher in patients with AS (37.6%) than in RA (12.8%), PsA (18.8%) and JIA (6.8%) (p < 0.001). In the control group, TST positivity was 32.7%. Nine (3.43%) patients were diagnosed with aMI. The overall incidence rate of aMI was 86.93/100,000 person-years [95% confidence interval (CI) 23.6-217.9] for patients and 35.79/100,000 person-years (95% CI 12.4-69.6) for control group (p < 0.001). All patients who developed aMI had no evidence of LTBI at the baseline evaluation. Patients with CIA starting TNF α blockers and no evidence of LTBI at baseline, particularly with nonreactive TST, may have higher risk of aMI. PMID:26560983

  6. Enhanced gastric nitric oxide synthase activity in duodenal ulcer patients.

    PubMed Central

    Rachmilewitz, D; Karmeli, F; Eliakim, R; Stalnikowicz, R; Ackerman, Z; Amir, G; Stamler, J S

    1994-01-01

    Nitric oxide, the product of nitric oxide synthase in inflammatory cells, may have a role in tissue injury through its oxidative metabolism. Nitric oxide may have a role in the pathogenesis of duodenal ulcer and may be one of the mechanisms responsible for the association between gastric infection with Helicobacter pylori and peptic disease. In this study, calcium independent nitric oxide synthase activity was detected in human gastric mucosa suggesting expression of the inducible isoform. In 17 duodenal ulcer patients gastric antral and fundic nitric oxide synthase activity was found to be two and 1.5-fold respectively higher than its activity in the antrum and fundus of 14 normal subjects (p < 0.05). H pylori was detected in the antrum of 15 of 17 duodenal ulcer patients and only in 7 of 14 of the control subjects. Antral nitric oxide synthase activity in H pylori positive duodenal ulcer patients was twofold higher than in H pylori positive normal subjects (p < 0.05). In duodenal ulcer patients antral and fundic nitric oxide synthase activity resumed normal values after induction of ulcer healing with ranitidine. Eradication of H pylori did not further affect gastric nitric oxide synthase activity. These findings suggest that in duodenal ulcer patients stimulated gastric mucosal nitric oxide synthase activity, though independent of the H pylori state, may contribute to the pathogenesis of the disease. PMID:7525417

  7. Management of patients with active caries.

    PubMed

    Milgrom, Peter

    2014-07-01

    This paper reports on a mechanism to manage caries as a disease and to medically intervene in the disease process to halt progression. The goal of this paper is to provide this alternative to a surgical-only approach. The management of caries begins with assessing lesion activity and the potential for arrest. This requires a clinical and radiological assessment and evaluation of risk. Hopeless teeth are extracted and large cavities filled to reduce infection. Risk reduction strategies are employed so efforts to arrest lesions can be successful. Teeth with lesions in the enamel or outer third of the dentin should be sealed, not restored, as restorations can weaken teeth and can be traumatic to pulps.

  8. Synchronization of EEG activity in patients with bipolar disorder

    NASA Astrophysics Data System (ADS)

    Panischev, O. Yu; Demin, S. A.; Muhametshin, I. G.; Demina, N. Yu

    2015-12-01

    In paper we apply the method based on the Flicker-Noise Spectroscopy (FNS) to determine the differences in frequency-phase synchronization of the cortical electroencephalographic (EEG) activities in patients with bipolar disorder (BD). We found that for healthy subjects the frequency-phase synchronization of EEGs from long-range electrodes was significantly better for BD patients. In BD patients a high synchronization of EEGs was observed only for short-range electrodes. Thus, the FNS is a simple graphical method for qualitative analysis can be applied to identify the synchronization effects in EEG activity and, probably, may be used for the diagnosis of this syndrome.

  9. The Frequency of anti-CCP antibodies in patients with rheumatoid arthritis and psoriatic arthritis and their relationship with clinical features and parameters of angiogenesis: A comparative study

    PubMed Central

    Eker, Yeliz Özkaya; Pamuk, Ömer Nuri; Pamuk, Gülsüm Emel; Dönmez, Salim; Çakır, Necati

    2014-01-01

    Objective Macrophage migration inhibitory factor (MIF) and vascular endothelial growth factor (VEGF), as crucial parameters of angiogenesis and inflammation, were evaluated to identify the role of cyclic citrullinated peptide antibodies (anti-CCP) during angiogenesis in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Material and Methods A total of 145 patients with RA, 44 patients with PsA, and 73 healthy subjects were included in this study. The clinical features, total blood counts, and acute phase parameters of RA and PsA patients were recorded. Anti-CCP antibody, VEGF, and MIF levels were determined with enzyme-linked immunosorbent assay (ELISA). Results Anti-CCP positivity was significantly higher in the RA group (69%) than in both PsA (20.6%) and controls (8.2%) (p values<0.001). There was no difference between anti-CCP-positive and -negative RA patients regarding the extra-articular manifestations (p>0.05). VEGF and MIF levels were similar in anti-CCP-positive and -negative RA patients (all p values>0.05). The specificity of anti-CCP antibodies for RA was found to be 87.2%. No relationship was found between anti-CCP antibody positivity and clinical features, disease activity, functional disability as assessed by health assessment questionnaire scores, and extra-articular manifestations. There was no relationship between parameters of angiogenesis and anti-CCP antibody positivity. Both RF and anti-CCP antibodies were observed to be positive in most patients with RA. Conclusion Either RF or anti-CCP antibody was positive in a considerable proportion of our RA patients. Therefore, anti-CCP antibodies are important in the diagnosis of RF-negative patients who present with clinical findings of RA. PMID:27708878

  10. Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy

    PubMed Central

    Seisen, Thomas; Klotz, Caroline; Mazeron, Renaud; Maroun, Pierre; Petit, Claire; Deutsch, Eric; Bossi, Alberto; Haie-Meder, Christine; Chargari, Cyrus; Blanchard, Pierre

    2017-01-01

    Background Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD). Methods From 1989 to 2015, a single center retrospective analysis was performed including all IBD patients who received pelvic external beam radiation therapy (EBRT) or brachytherapy (BT) for a pelvic malignancy. Treatment characteristics, IBD activity and gastrointestinal (GI) toxicity were examined. Results Overall, 28 patients with Crohn’s disease (CD) (n=13) or ulcerative colitis (n=15) were included in the present study. Median follow-up time after irradiation was 5.9 years. Regarding IBD activity, only one and two patients experienced a severe episode within and after 6 months of follow-up, respectively. Grade 3/4 acute GI toxicity occurred in 3 (11%) patients, whereas one (3.6%) patient experienced late grade 3/4 GI toxicity. Only patients with rectal IBD location (P=0.016) or low body mass index (BMI) (P=0.012) experienced more severe IBD activity within or after 6 months following RT, respectively. Conclusions We report an acceptable tolerance of RT in IBD patients with pelvic malignancies. Specifically, a low risk of uncontrolled flare-up was observed. PMID:28280621

  11. Characteristics of daily arm activities in patients with COPD.

    PubMed

    Meijer, Kenneth; Annegarn, Janneke; Lima Passos, Valéria; Savelberg, Hans H; Schols, Annemie M; Wouters, Emiel F; Spruit, Martijn A

    2014-06-01

    Arm activities are required for maintenance of self-care and independent living. This study aimed to investigate whether and to what extent arm activities of daily living (ADL) in chronic obstructive pulmonary disease (COPD) patients differ compared to healthy controls and the extent to which they perform arm ADL at a relatively higher upper limb muscle effort. Daily arm and leg activities were assessed using accelerometers in the home environment (COPD: n=21, healthy: n=24; part 1). The relative efforts of the trapezius, deltoid and biceps muscles were studied using electromyography during domestic arm ADL in a laboratory setting (COPD: n=17, healthy: n=15; part 2). After correction for walking time, the time spent on arm ADL was similar between COPD patients and healthy control subjects (p=0.52), while the intensity of arm activities was lower in COPD patients (p=0.041). In the laboratory setting, arm ADL were performed at a lower intensity by COPD patients, while the trapezius muscle effort was significantly higher during several arm ADL compared to healthy control subjects (p<0.05). COPD patients have a similar duration of arm ADL compared to healthy subjects after correction for walking time, but perform arm activities at a lower intensity. Moreover, patients perform some arm ADL at a relatively higher muscle effort.

  12. [Problems connected with sexual activity in patients with heart disease].

    PubMed

    Rembek, Magdalena; Tylkowski, Michał; Piestrzeniewicz, Katarzyna; Goch, Jan Henryk

    2007-08-01

    The paper presents some basic data on sexual activity in patients with heart disease. The most typical problems of people with stable angina or after myocardial infarction connected with sexual intercourse have been presented. Modulation of risk of heart attack during sexual activity and main problems of sexual dysfunction after acute coronary syndromes have been described.

  13. Influence of Insulin Resistance and TNF-α on the Inflammatory Process, Oxidative Stress, and Disease Activity in Patients with Rheumatoid Arthritis

    PubMed Central

    Delongui, Francieli; Alfieri, Daniela Frizon; Lozovoy, Marcell Alysson Batisti; Amin, Ricardo Braga; Dichi, Isaias; Simão, Andréa Name Colado

    2016-01-01

    The aim of this study was to evaluate the involvement of TNF-α and insulin resistance (IR) in the inflammatory process, oxidative stress, and disease activity in patients with rheumatoid arthritis (RA). This cross-sectional study included 270 subjects (control group, n = 97) and RA patients (n = 173). RA patients were divided into four groups: the first group without IR and not using antitumor necrosis factor-α (TNF−) (G1, IR− TNF−); the second group without IR and using anti-TNF-α (G2, IR− TNF+); the third group with IR and not using anti-TNF-α (G3, IR+ TNF−); and the fourth group with IR and using anti-TNF-α (G4, IR+ TNF+). G3 and G4 had higher (p < 0.05) advanced oxidation protein products (AOPPs) and oxidative stress index (OSI) compared to G1. G4 group presented higher (p < 0.05) AOPPs and OSI than G2. TRAP was significantly lower in G3 compared to G1. Plasma TNF-α levels were significantly higher in G4 and G2 compared to G1 (p < 0.0001) and G3 (p < 0.0001 and p < 0.01, resp.). The presence of insulin resistance was robustly associated with both oxidative stress and TNF-α levels. More studies are warranted to verify if IR can be involved in therapeutic failure with TNF-α inhibitors. This trial is registered with Brazilian Clinical Trials Registry Register number RBR-2jvj92. PMID:27340510

  14. SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly.

    PubMed

    Singh, Dipty; Bhattacharya, Anusri; Rai, Ankit; Dhaked, Hemendra Pal Singh; Awasthi, Divya; Ojima, Iwao; Panda, Dulal

    2014-05-13

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials.

  15. [Effects of a low calorie vegan diet on disease activity and general conditions in patients with rheumatoid arthritis].

    PubMed

    Fujita, A; Hashimoto, Y; Nakahara, K; Tanaka, T; Okuda, T; Koda, M

    1999-06-01

    There is little objective information about diet therapy for rheumatoid arthritis (RA) in Japan. We studied 14 patients with RA who stayed in the Koda hospital for 55 days. They basically took a 1200 kcal vegan diet consisting of unpolished rice gruel, juice of raw vegetables, soya bean curd and sesame seeds, and undertook a 3-5-day fast three times. During the 55-day stay, average body weight decreased by 5.1kg. Lansbury index and ESR decreased whereas CRP did not change. WBC decreased and the differential cell counts showed a decrease of neutrophils, eosinophils and monocytes without a change in lymphocytes or basophils. RBC, hemoglobin and MCV increased. LDL-C decreased, while HDL-C increased. There was no change in total protein or albumin. These data suggest that this combination of a low calorie vegan diet and fasting may contribute to improve RA with little undesirable effects on the patient's general conditions.

  16. The consent process: Enabling or disabling patients' active participation?

    PubMed

    Doherty, Carole; Stavropoulou, Charitini; Saunders, Mark Nk; Brown, Tracey

    2015-10-20

    Standards expected by doctors' regulatory bodies in respect of the process of consent to treatment have arguably sought to restructure the nature of the doctor-patient relationship from one of the paternalism to that of shared decision-making. Yet, few studies have explored empirically, from patients' perspectives, the extent to which the process of consent to treatment enables or disables patients' participation in medical decision-making. Our article examines patients' attitudes towards the consent process, exploring how and why these attitudes influence patients' active participation in decision-making and considering possible consequent medico-legal issues. Data were collected longitudinally using semi-structured interviews and field observations involving 35 patients and 19 of their caregivers, in an English hospital between February and November 2014. These indicate that generally patients defer to the doctor in respect of treatment decision-making. Although most patients and their caregivers wanted detailed information and discussion, they did not necessarily expect that this would be provided. Furthermore, patients perceived that signing the consent form was an obligatory routine principally to protect doctors from legal action should something go wrong. Our study suggests that patients' predominantly paternalistic perceptions of the consent process can not only undermine attempts by doctors to involve them in decision-making but, as patients are now considered in law as informed actors, their perceptions of the consent form as not being in their interests could be a self-fulfilling prophecy if signing is undertaken without due consideration to the content.

  17. Development of the Patient Activation Measure for mental health.

    PubMed

    Green, Carla A; Perrin, Nancy A; Polen, Michael R; Leo, Michael C; Hibbard, Judith H; Tusler, Martin

    2010-07-01

    Our objective was to adapt the physical health Patient Activation Measure (PAM) for use among people with mental health conditions (PAM-MH). Data came from three studies among people with chronic mental health conditions and were combined in Rasch analyses. The PAM-MH's psychometric properties equal those of the original 13-item PAM. Test-retest reliability and concurrent validity were good, and the PAM-MH showed sensitivity to change. The PAM-MH appears to be a reliable and valid measure of patient activation among individuals with mental health problems. It appears to have potential for use in assessing change in activation.

  18. Physical Activity in Patients Treated With Peritoneal Dialysis

    PubMed Central

    Thangarasa, Tharshika; Imtiaz, Rameez; Hiremath, Swapnil; Zimmerman, Deborah

    2017-01-01

    Background: Patients with chronic diseases are known to benefit from exercise. Despite a lack of compelling evidence, patients with end-stage kidney disease treated with peritoneal dialysis are often discouraged from participating in exercise programs that include resistance training due to concerns about the development of hernias and leaks. The actual effects of physical activity with or without structured exercise programs for these patients remain unclear. The purpose of this study is to more completely define the risks and benefits of physical activity in the end-stage kidney disease population treated with peritoneal dialysis. Methods/design: We will conduct a systematic review examining the effects of physical activity on end-stage kidney disease patients treated with peritoneal dialysis. For the purposes of this review, exercise will be considered a purposive subcategory of physical activity. The primary objective is to determine if physical activity in this patient population is associated with improvements in mental health, physical functioning, fatigue and quality of life and if there is an increase in adverse outcomes. With the help of a skilled librarian, we will search MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials for randomized trials and observational studies. We will include adult end-stage kidney disease patients treated with peritoneal dialysis that have participated in an exercise training program or had their level of physical activity assessed directly or by self-report. The study must include an assessment of the association between physical activity and one of our primary or secondary outcomes measures. We will report study quality using the Cochrane Risk of Bias Assessment Tool for randomized controlled trials and the Newcastle–Ottawa Scale for observational studies. Quality across studies will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The

  19. Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients.

    PubMed

    Ruscitti, P; Cipriani, P; Di Benedetto, P; Liakouli, V; Berardicurti, O; Carubbi, F; Ciccia, F; Alvaro, S; Triolo, G; Giacomelli, R

    2015-10-01

    A better understanding about the mechanisms involved in the pathogenesis of type 2 diabetes mellitus (T2D) showed that inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin (IL)-1β play a pivotal role, mirroring data largely reported in rheumatoid arthritis (RA). IL-1β is produced mainly by monocytes (MO), and hyperglycaemia may be able to modulate, in the cytoplasm of these cells, the assembly of a nucleotide-binding domain and leucine-rich repeat containing family pyrin (NLRP3)-inflammosome, a cytosolic multi-protein platform where the inactive pro-IL-1β is cleaved into active form, via caspase-1 activity. In this paper, we evaluated the production of IL-1 β and TNF, in peripheral blood MO of patients affected by RA or T2D or both diseases, in order to understand if an alteration of the glucose metabolism may influence their proinflammatory status. Our data showed, after 24 h of incubation with different glucose concentrations, a significantly increased production of IL-1β and TNF in all evaluated groups when compared with healthy controls. However, a significant increase of IL-1β secretion by T2D/RA was observed when compared with other groups. The analysis of relative mRNA expression confirmed these data. After 24 h of incubation with different concentrations of glucose, our results showed a significant increase in NLRP3 expression. In this work, an increased production of IL-1β by MO obtained from patients affected by both RA and T2D via NLRP3-inflammasome activation may suggest a potential IL-1β targeted therapy in these patients.

  20. Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study: rationale and design for a randomized controlled trial evaluating rheumatoid arthritis risk education to first-degree relatives.

    PubMed

    Sparks, Jeffrey A; Iversen, Maura D; Miller Kroouze, Rachel; Mahmoud, Taysir G; Triedman, Nellie A; Kalia, Sarah S; Atkinson, Michael L; Lu, Bing; Deane, Kevin D; Costenbader, Karen H; Green, Robert C; Karlson, Elizabeth W

    2014-09-01

    We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention.

  1. The Reliability of Disease Activity Score in 28 Joints–C-Reactive Protein Might Be Overestimated in a Subgroup of Rheumatoid Arthritis Patients, When the Score Is Solely Based on Subjective Parameters

    PubMed Central

    Jensen Hansen, Inger Marie; Asmussen Andreasen, Rikke; van Bui Hansen, Mark Nam; Emamifar, Amir

    2017-01-01

    Background Disease Activity Score in 28 Joints (DAS28) is a scoring system to evaluate disease activity and treatment response in rheumatoid arthritis (RA). A DAS28 score of greater than 3.2 is a well-described limit for treatment intensification; however, the reliability of DAS28 might be overestimated. Objective The aim of this study was to evaluate the reliability of DAS28 in RA, especially focusing on a subgroup of patients with a DAS28 score of greater than 3.2. Methods Data from RA patients registered in the local part of Danish DANBIO Registry were collected in May 2015. Patients were categorized into 2 groups: First, those with DAS28 >3.2 with at least one swollen joint (SJ) or elevated C-reactive protein (CRP) (“objective group”), and second, patients with a DAS28 >3.2 who had no SJ, and CRP values were within the reference range (“subjective group”). Disease Activity Score in 28 Joints, Clinical Disease Activity Index, and Health Assessment Questionnaire scores were calculated for each group. We defined new score, DAS28 subjective, to focus on subjective parameters. Results Two hundred thirty patients were included; 198 (86.1%) and 32 (13.9%) patients were in the objective and subjective groups, respectively. Patients in the subjective group had lower mean values of DAS28 (P < 0.001) and Evaluator Global Assessment (P < 0.001) with less common immunoglobulin M rheumatoid factor (P < 0.001) and anti–cyclic citrullinated peptide positivity (P = 0.02) and contrarily higher mean values of tender joints (P = 0.04) and DAS28 based on subjective parameters (P = 0.003) compared with the objective group. Conclusions Rheumatoid arthritis scoring systems should be used cautiously in patients who are considered for treatment intensification. Patients with central sensitization and psychological problems and those with false-positive diagnosis of RA are at high risk of overtreatment. PMID:27870649

  2. RRD-251 enhances all-trans retinoic acid (RA)-induced differentiation of HL-60 myeloblastic leukemia cells

    PubMed Central

    Bunaciu, Rodica P.; Yen, Andrew

    2016-01-01

    All-trans-retinoic acid (RA) is known to induce terminal granulocytic differentiation and cell cycle arrest of HL-60 cells. Responding to an RA-induced cytosolic signaling machine, c-Raf translocates to the nucleus, providing propulsion for RA-induced differentiation. This novel mechanism is not understood, but presumably reflects c-Raf binding with nuclear gene regulatory proteins. RRD-251 is a small molecule that prevents the interaction of c-Raf and RB, the retinoblastoma tumor suppressor protein. The involvement of c-Raf and RB in RA-induced differentiation motivates interest in the effects of combined RA and RRD-251 treatment on leukemic cell differentiation. We demonstrate that RRD-251 enhances RA-induced differentiation. Mechanistically, we find that nuclear translocated c-Raf associates with pS608 RB. RA causes loss of pS608 RB, where cells with hypophosphorylated S608 RB are G0/G1 restricted. Corroborating the pS608 RB hypophosphorylation, RB sequestration of E2F increased with concomitant loss of cdc6 expression, which is known to be driven by E2F. Hypophosphorylation of S608 RB releases c-Raf from RB sequestration to bind other nuclear targets. Release of c-Raf from RB sequestration results in enhanced association with GSK-3 which is phosphorylated at its S21/9 inhibitory sites. c-Raf binding to GSK-3 is associated with dissociation of GSK-3 and RARα, thereby relieving RARα of GSK-3 inhibition. RRD-251 amplifies each of these RA-induced events. Consistent with the posited enhancement of RARα transcriptional activity by RRD-251, RRD-251 increases the RARE-driven CD38 expression per cell. The RA/c-Raf/GSK-3/RARα axis emerges as a novel differentiation regulatory mechanism susceptible to RRD-251, suggesting enhancing RA-effects with RRD-251 in therapy. PMID:27331409

  3. Relationship between disease activity and infection in patients with spondyloarthropathies

    PubMed Central

    Martinez, A; Pacheco-Tena, C; Vazquez-Mellado, J; Burgos-Vargas, R

    2004-01-01

    Methods: A cross sectional study of 95 non-selected patients with SpA (62 men; mean age 26.4 years), who were examined for signs and symptoms of infection and their association with disease activity. 52 had ankylosing spondylitis (AS), 32 undifferentiated SpA (uSpA), 6 chronic reactive arthritis (ReA), and 5 psoriatic arthritis (PsA). Categorical data were analysed by χ2 or Fisher's tests. Results: 53 (56%) patients had infections: 41 (43%) upper respiratory tract (URT), 34 (36%) enteric, and 20 (21%) genitourinary infections. More infections occurred in HLA-B27 positive patients as a whole (39 v 5; p = 0.003) and in uSpA (12 v 2; p = 0.005). In AS and uSpA, infections occurred in ∼50%. 30/39 (77%) patients with active disease (group A) and 23/56 (41%) (group B) (p = 0.001) had infection. There were more enteric infections in group A (47%; p<0.001) and more URT infections in group B (52%; p = NS). 22/30 (73%) patients attributed disease activity to infection. Conclusion: Enteric, and less commonly, URT infections in Mexican patients with SpA, particularly those who were HLA-B27 positive, seem to have a role in the active phase of AS and uSpA. PMID:15361397

  4. Chewing pattern and muscular activation in open bite patients.

    PubMed

    Piancino, Maria Grazia; Isola, Gaetano; Merlo, Andrea; Dalessandri, Domenico; Debernardi, Cesare; Bracco, Pietro

    2012-04-01

    Different studies have indicated, in open bite patients, that masticatory muscles tend to generate a small maximum bite force and to show a reduced cross-sectional area with a lower EMG activity. The aim of this study was to evaluate the kinematics parameters of the chewing cycles and the activation of masseters and anterior temporalis muscles of patients with anterior dental open bite malocclusion. There have been no previous reports evaluating both kinematic values and EMG activity of patients with anterior open bite during chewing. Fifty-two young patients (23 boys and 29 girls; mean age±SD 11.5±1.2 and 10.2±1.6years, respectively) with anterior open bite malocclusion and 21 subjects with normal occlusion were selected for the study. Kinematics parameters and surface electromyography (EMG) were simultaneously recorded during chewing a hard bolus with a kinesiograph K7-I Myotronics-Usa. The results showed a statistically significant difference between the open bite patients and the control group for a narrower chewing pattern, a shorter total and closing duration of the chewing pattern, a lower peak of both the anterior temporalis and the masseter of the bolus side. In this study, it has been observed that open bite patients, lacking the inputs from the anterior guidance, that are considered important information for establishing the motor scheme of the chewing pattern, show narrower chewing pattern, shorter lasting chewing cycles and lower muscular activation with respect to the control group.

  5. Physical activity in patients with axial spondyloarthritis: a cross-sectional study of 203 patients.

    PubMed

    Fabre, Stéphanie; Molto, Anna; Dadoun, Sabrina; Rein, Christopher; Hudry, Christophe; Kreis, Sarah; Fautrel, Bruno; Pertuiset, Edouard; Gossec, Laure

    2016-12-01

    Physical activity is recommended in axial spondyloarthritis (axSpA) but may be insufficiently performed. The objective of this study was to assess physical activity in axial spondyloarthritis and to explore its explanatory factors. This was a cross-sectional study of patients with definite axSpA. The level of physical activity (International Physical Activity Questionnaire-Long form, IPAQ-L), type of aerobic exercise and the Exercise Benefits and Barriers Score were collected. Multivariate logistic regression analyses were performed to explain levels of exercise at least as recommended by the World Health Organization. In all, 203 patients were included: mean age 46.0 ± 11.6 years, 108 (53.2 %) males, mean Bath Ankylosing Spondylitis Activity Index (0-100) 37.8 ± 19.9; 137 (68.8 %) were treated with TNF-inhibitors. In all, 111 patients (54.7 %) were exercising at least as recommended; 96 (47.2 %) were in the 'high physical activity' category. Aerobic exercise >30 min was performed at least once a week by 61 (30.0 %) patients; the most frequent activities were energetic walking (31.0 %) and swimming (21.2 %). Main perceived benefits of exercising were improving physical fitness and functioning of the cardiovascular system, and the main barrier was physical exertion. Patients with paid employment had lower levels of physical activity whereas other demographic variables, disease activity/severity or TNF-inhibitor treatment were not predictive. One half of these patients performed enough physical activity according to the recommendations, similarly to the French population. Levels of physical activity did not appear to be explained by disease-related variables. Physical activity should be encouraged in axSpA.

  6. Imaging of Ra-223 with a small-pixel CdTe detector

    NASA Astrophysics Data System (ADS)

    Scuffham, J. W.; Pani, S.; Seller, P.; Sellin, P. J.; Veale, M. C.; Wilson, M. D.; Cernik, R. J.

    2015-01-01

    Ra-223 Dichloride (Xofigo™) is a promising new radiopharmaceutical offering survival benefit and palliation of painful bone metastases in patients with hormone-refractory prostate cancer [1]. The response to radionuclide therapy and toxicity are directly linked to the absorbed radiation doses to the tumour and organs at risk respectively. Accurate dosimetry necessitates quantitative imaging of the biodistribution and kinetics of the radiopharmaceutical. Although primarily an alpha-emitter, Ra-223 also has some low-abundance X-ray and gamma emissions, which enable imaging of the biodistribution in the patient. However, the low spectral resolution of conventional gamma camera detectors makes in-vivo imaging of Ra-223 challenging. In this work, we present spectra and image data of anthropomorphic phantoms containing Ra-223 acquired with a small-pixel CdTe detector (HEXITEC) [2] with a pinhole collimator. Comparison is made with similar data acquired using a clinical gamma camera. The results demonstrate the advantages of the solid state detector in terms of scatter rejection and quantitative accuracy of the images. However, optimised collimation is needed in order for the sensitivity to rival current clinical systems. As different dosage levels and administration regimens for this drug are explored in current clinical trials, there is a clear need to develop improved imaging technologies that will enable personalised treatments to be designed for patients.

  7. Investigation of the association between metabolic syndrome and disease activity in rheumatoid arthritis.

    PubMed

    Sahebari, Maryam; Goshayeshi, Ladan; Mirfeizi, Zahra; Rezaieyazdi, Zahra; Hatef, Mohammad R; Ghayour-Mobarhan, Majid; Akhlaghi, Saeed; Sahebkar, Amirhossein; Ferns, Gordon A

    2011-06-09

    Rheumatoid arthritis (RA) is the most common form of autoimmune arthritis. Increased prevalence of metabolic syndrome (MetS) in RA may occur secondary to specific drug treatment and reduced physical activity associated with this condition. However, some recent studies suggest contradictory theories about the association of RA with MetS. This study was designed to evaluate the frequency of MetS in RA patients and the relationship between MetS with RA disease activity and body mass index (BMI). The study was conducted on 120 RA patients and 431 age- and sex-matched apparently healthy controls. A considerable proportion of patients were being treated with prednisolone and/or methotrexate and/or hydroxychloroquine. Disease activity was measured by the 28 joint count of disease activity score-Cerythrocyte sedimentation rate (DAS28ESR). MetS was evaluated according to International Diabetic Federation (IDF) and Adult Treatment Panel III (ATP III) criteria. The prevalence of MetS was significantly higher in the control group (p = 0.005). We did not find any difference in the prevalence of MetS between the patients with DAS < 3.2 and DAS ≥ 3.2. There was no association between the DAS28 score and the presence of MetS components by either definition. Multiple logistic regression analysis showed that the odds of a DAS > 3.2 in patients with BMI between 25 and 30 kg/m2 (OR = 0.1, p = 0.01) and BMI > 30 kg/m2 (OR = 0.3, p = 0.1), in comparison to BMI < 25 kg/m2, was 1/5 and 1/3, respectively. RA was not found to increase the risk of MetS. In addition, disease activity in RA patients was not influenced by the presence of MetS.

  8. Using Health Information Technology to Foster Engagement: Patients' Experiences with an Active Patient Health Record.

    PubMed

    Rief, John J; Hamm, Megan E; Zickmund, Susan L; Nikolajski, Cara; Lesky, Dan; Hess, Rachel; Fischer, Gary S; Weimer, Melissa; Clark, Sunday; Zieth, Caroline; Roberts, Mark S

    2017-03-01

    Personal health records (PHRs) typically employ "passive" communication strategies, such as non-personalized medical text, rather than direct patient engagement in care. Currently there is a call for more active PHRs that directly engage patients in an effort to improve their health by offering elements such as personalized medical information, health coaches, and secure messaging with primary care providers. As part of a randomized clinical trial comparing "passive" with "active" PHRs, we explore patients' experiences with using an "active" PHR known as HealthTrak. The "passive" elements of this PHR included problem lists, medication lists, information about patient allergies and immunizations, medical and surgical histories, lab test results, health reminders, and secure messaging. The active arm included all of these elements and added personalized alerts delivered through the secure messaging platform to patients for services coming due based on various demographic features (including age and sex) and chronic medical conditions. Our participants were part of the larger clinical trial and were eligible if they had been randomized to the active PHR arm, one that included regular personalized alerts. We conducted focus group discussions on the benefits of this active PHR for patients who are at risk for cardiovascular disease. Forty-one patients agreed to participate and were organized into five separate focus group sessions. Three main themes emerged from the qualitatively analyzed focus groups: participants reported that the active PHR promoted better communication with providers; enabled them to more effectively partner with their providers; and helped them become more proactive about tracking their health information. In conclusion, patients reported improved communication, partnership with their providers, and a sense of self-management, thus adding insights for PHR designers hoping to address low adoption rates and other patient barriers to the development

  9. Ongoing Contact Activation in Patients with Hereditary Angioedema

    PubMed Central

    Konings, Joke; Cugno, Massimo; Suffritti, Chiara; ten Cate, Hugo; Cicardi, Marco; Govers-Riemslag, José W. P.

    2013-01-01

    Hereditary angioedema (HAE) is predominantly caused by a deficiency in C1 esterase inhibitor (C1INH) (HAE-C1INH). C1INH inhibits activated factor XII (FXIIa), activated factor XI (FXIa), and kallikrein. In HAE-C1INH patients the thrombotic risk is not increased even though activation of the contact system is poorly regulated. Therefore, we hypothesized that contact activation preferentially leads to kallikrein formation and less to activation of the coagulation cascade in HAE-C1INH patients. We measured the levels of C1INH in complex with activated contact factors in plasma samples of HAE-C1INH patients (N=30, 17 during remission and 13 during acute attack) and healthy controls (N=10). We did not detect differences in enzyme-inhibitor complexes between samples of controls, patients during remission and patients during an acute attack. Reconstitution with C1INH did not change this result. Next, we determined the potential to form enzyme-inhibitory complexes after complete in vitro activation of the plasma samples with a FXII trigger. In all samples, enzyme-C1INH levels increased after activation even in patients during an acute attack. However, the levels of FXIIa-C1INH, FXIa-C1INH and kallikrein-C1INH were at least 52% lower in samples taken during remission and 70% lower in samples taken during attack compared to samples from controls (p<0.05). Addition of C1INH after activation led to an increase in levels of FXIIa-C1INH and FXIa-C1INH (p<0.05), which were still lower than in controls (p<0.05), while the levels of kallikrein-C1INH did not change. These results are consistent with constitutive activation and attenuated depletion of the contact system and show that the ongoing activation of the contact system, which is present in HAE-C1INH patients both during remission and during acute attacks, is not associated with preferential generation of kallikrein over FXIa. PMID:24013493

  10. Rapid Response Team Activations in Pediatric Surgical Patients.

    PubMed

    Acker, Shannon N; Wathen, Beth; Roosevelt, Genie E; Hill, Lauren R S; Schubert, Anna; Reese, Jenny; Bensard, Denis D; Kulungowski, Ann M

    2017-02-01

    Introduction The rapid response team (RRT) is a multidisciplinary team who evaluates hospitalized patients for concerns of nonemergent clinical deterioration. RRT evaluations are mandatory for children whose Pediatric Early Warning System (PEWS) score (assessment of child's behavior, cardiovascular and respiratory status) is ≥4. We aimed to determine if there were differences in characteristics of RRT calls between children who were admitted primarily to either medical or surgical services. We hypothesized that RRT activations would be called for less severely ill children with lower PEWS score on surgical services compared with children admitted to a medical service. Materials and Methods We performed a retrospective review of all children with RRT activations between January 2008 and April 2015 at a tertiary care pediatric hospital. We evaluated the characteristics of RRT calls and made comparisons between RRT calls made for children admitted primarily to medical or surgical services. Results A total of 2,991 RRT activations were called, and 324 (11%) involved surgical patients. Surgical patients were older than medical patients (median: 7 vs. 4 years; p < 0.001). RRT evaluations were called for lower PEWS score in surgical patients compared with medical (median: 3 vs. 4, p < 0.001). Surgical patients were more likely to remain on the inpatient ward following the RRT (51 vs. 39%, p < 0.001) and were less likely to require an advanced airway than medical patients (0.9 vs. 2.1%; p = 0.412). RRT evaluations did not differ between day and night shifts (52% day vs. 48% night; p = 0.17). All surgical patients and all but one medical patient survived the event; surgical patients were more likely to survive to hospital discharge (97 vs. 91%, p < 0.001) Conclusions RRT activations are rare events among pediatric surgical patients. When compared with medical patients, RRT evaluation is requested for surgical patients with a lower PEWS

  11. The promise of wearable activity sensors to define patient recovery.

    PubMed

    Appelboom, Geoff; Yang, Annie H; Christophe, Brandon R; Bruce, Eliza M; Slomian, Justine; Bruyère, Olivier; Bruce, Samuel S; Zacharia, Brad E; Reginster, Jean-Yves; Connolly, E Sander

    2014-07-01

    The recent emergence of mobile health--the use of mobile telecommunication and wireless devices to improve health outcomes, services, and research--has inspired a patient-centric approach to monitor health metrics. Sensors embedded in wearable devices are utilized to acquire greater self-knowledge by tracking basic parameters such as blood pressure, heart rate, and body temperature as well as data related to exercise, diet, and psychological state. To that end, recent studies on utilizing wireless fitness activity trackers to monitor and promote functional recovery in patients suggest that collecting up-to-date performance data could help patients regain functional independence and help hospitals determine the appropriate length of stay for a patient. This manuscript examines existing functional assessment scales, discusses the use of activity tracking sensors in evaluating functional independence, and explores the growing application of wireless technology in measuring and promoting functional recovery.

  12. RA-RAR-β counteracts myelin-dependent inhibition of neurite outgrowth via Lingo-1 repression.

    PubMed

    Puttagunta, Radhika; Schmandke, André; Floriddia, Elisa; Gaub, Perrine; Fomin, Natalie; Ghyselinck, Norbert B; Di Giovanni, Simone

    2011-06-27

    After an acute central nervous system injury, axonal regeneration is limited as the result of a lack of neuronal intrinsic competence and the presence of extrinsic inhibitory signals. The injury fragments the myelin neuronal insulating layer, releasing extrinsic inhibitory molecules to signal through the neuronal membrane-bound Nogo receptor (NgR) complex. In this paper, we show that a neuronal transcriptional pathway can interfere with extrinsic inhibitory myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting through the RA receptor β (RAR-β), inhibited myelin-activated NgR signaling through the transcriptional repression of the NgR complex member Lingo-1. We show that suppression of Lingo-1 was required for RA-RAR-β to counteract extrinsic inhibition of neurite outgrowth. Furthermore, we confirm in vivo that RA treatment after a dorsal column overhemisection injury inhibited Lingo-1 expression, specifically through RAR-β. Our findings identify a novel link between RA-RAR-β-dependent proaxonal outgrowth and inhibitory NgR complex-dependent signaling, potentially allowing for the development of molecular strategies to enhance axonal regeneration after a central nervous system injury.

  13. Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.

    PubMed

    Pham, Tu Anh N; Clare, Simon; Goulding, David; Arasteh, Julia M; Stares, Mark D; Browne, Hilary P; Keane, Jacqueline A; Page, Andrew J; Kumasaka, Natsuhiko; Kane, Leanne; Mottram, Lynda; Harcourt, Katherine; Hale, Christine; Arends, Mark J; Gaffney, Daniel J; Dougan, Gordon; Lawley, Trevor D

    2014-10-08

    Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22RA1 protects against lethal Citrobacter rodentium infection and chemical-induced colitis by promoting colonization resistance against an intestinal opportunistic bacterium, Enterococcus faecalis. Susceptibility of Il22ra1(-/-) mice to C. rodentium was associated with preferential expansion and epithelial translocation of pathogenic E. faecalis during severe microbial dysbiosis and was ameloriated with antibiotics active against E. faecalis. RNA sequencing analyses of primary colonic organoids showed that IL-22RA1 signaling promotes intestinal fucosylation via induction of the fucosyltransferase Fut2. Additionally, administration of fucosylated oligosaccharides to C. rodentium-challenged Il22ra1(-/-) mice attenuated infection and promoted E. faecalis colonization resistance by restoring the diversity of anaerobic commensal symbionts. These results support a model whereby IL-22RA1 enhances host-microbiota mutualism to limit detrimental overcolonization by opportunistic pathogens.

  14. Epithelial IL-22RA1-Mediated Fucosylation Promotes Intestinal Colonization Resistance to an Opportunistic Pathogen

    PubMed Central

    Pham, Tu Anh N.; Clare, Simon; Goulding, David; Arasteh, Julia M.; Stares, Mark D.; Browne, Hilary P.; Keane, Jacqueline A.; Page, Andrew J.; Kumasaka, Natsuhiko; Kane, Leanne; Mottram, Lynda; Harcourt, Katherine; Hale, Christine; Arends, Mark J.; Gaffney, Daniel J.; Dougan, Gordon; Lawley, Trevor D.

    2014-01-01

    Summary Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22RA1 protects against lethal Citrobacter rodentium infection and chemical-induced colitis by promoting colonization resistance against an intestinal opportunistic bacterium, Enterococcus faecalis. Susceptibility of Il22ra1−/− mice to C. rodentium was associated with preferential expansion and epithelial translocation of pathogenic E. faecalis during severe microbial dysbiosis and was ameloriated with antibiotics active against E. faecalis. RNA sequencing analyses of primary colonic organoids showed that IL-22RA1 signaling promotes intestinal fucosylation via induction of the fucosyltransferase Fut2. Additionally, administration of fucosylated oligosaccharides to C. rodentium-challenged Il22ra1−/− mice attenuated infection and promoted E. faecalis colonization resistance by restoring the diversity of anaerobic commensal symbionts. These results support a model whereby IL-22RA1 enhances host-microbiota mutualism to limit detrimental overcolonization by opportunistic pathogens. PMID:25263220

  15. Increased expression of CCL18, CCL19, and CCL17 by dendritic cells from patients with rheumatoid arthritis, and regulation by Fc gamma receptors

    PubMed Central

    Radstake, T; van der Voort, R; ten, B; de Waal, Malefijt M; Looman, M; Figdor, C; van den Berg, W B; Barrera, P; Adema, G

    2005-01-01

    Background: Dendritic cells (DC) have a role in the regulation of immunity and tolerance, attracting inflammatory cells by the production of various chemokines (CK). Fc gamma receptors (FcγR) may be involved in regulation of the DC function. Objective: To assess the expression of CK by immature (iDC) and mature DC (mDC) and its regulation by FcγR in patients with RA and healthy donors (HC). Methods: Expression of CK by DC from patients with RA and from HC was determined by real time quantitative PCR and ELISA. DC were derived from monocytes following standardised protocols. To study the potential regulation by FcγR, iDC were stimulated with immune complexes (IC) during lipopolysaccharide (LPS) induced maturation. The presence of CK was studied in synovial tissue from patients with RA, osteoarthritis, and healthy subjects by RT-PCR and immunohistochemistry. Results: iDC from patients with RA had markedly increased mRNA levels of the CK CCL18 and CXCL8. Upon maturation with LPS, expression of CCL18, CCL19, CXCL8, CCL3, and CCL17 increased dramatically, reaching significantly higher levels in patients with RA. Monocytes failed to express these CK, except for CXCL8 and CCL3. IC-mediated triggering of the FcγR on DC from patients with highly active RA down regulated all CK, whereas the reverse was seen when DC from patients with low disease activity and healthy donors were stimulated. CCL18 was significantly increased in RA synovial tissue. Conclusion: Increased CK expression by DC was found in patients with RA. This expression is partly regulated by FcγR triggering and results in an inhibitory DC subtype in RA upon FcγR-mediated triggering. PMID:15331393

  16. Motoneuron activity in patients with different types of tremor.

    PubMed

    Milanov, I

    2001-12-01

    The aim of this work was to examine the segmental motoneuron activity as a possible mechanism of tremor generation. Eighty-three patients with different types of tremor (25 with Parkinsonian, 29 with essential, and 30 with enhanced physiological tremor due to anxiety), 25 Parkinsonian patients without tremor and 30 healthy volunteers were examined. The tremor was studied clinically and by electromyography in all limb positions. The F wave was examined for assessment of motoneuron activity. The wave was recorded after stimulation of the ulnar, median, tibial and fibular nerves. The maximal and mean F wave amplitudes, frequency of occurrence and number of phases were increased, and the duration was prolonged in all group of patients as compared to the healthy persons. The maximal and the mean F/M amplitude ratios, as well as the Fmean./Fmax amplitude ratio were increased in all groups of patients. All F wave parameters were most altered in Parkinsonian tremor patients followed by patients with rigidity. In conclusion increased motoneuron activity participates in generation of different types of tremor and in Parkinsonian rigidity.

  17. Concentrations of (226)Ra, (232)Th and (4)(0)K in industrial kaolinized granite.

    PubMed

    Todorović, Nataša; Hansman, Jan; Mrđa, Dušan; Nikolov, Jovana; Kardos, Richárd; Krmar, Miodrag

    2017-03-01

    Activity concentrations of (226)Ra, (232)Th and (4)(0)K in 120 kaolinized granite samples imported in Serbia from the Motajica mine, Bosnia and Herzegovina, were measured. The (226)Ra concentration ranged from 61 to 319 Bq kg(-1), the (232)Th from 44 to 272 Bq kg(-1), and the (4)(0)K from 590 to 1470 Bq kg(-1). The frequency distribution of (4)(0)K concentrations was near-Gaussian, where those of (226)Ra and (232)Th were right-skewed. In 6 samples, the gamma index, I, was higher than 2, which exceeds the exemption dose criterion (0.3 mSv y(-1)). The absorbed dose rate and annual effective doses for workers in the ceramic industries in Serbia who worked with kaolinized granite were below levels of concern.

  18. Geology and Topography of Ra Patera, Io, in the Voyager era: Prelude to Eruption

    NASA Technical Reports Server (NTRS)

    Schenk, Paul M.; McEwen, Alfred; Davies, A. G.; Davenport, Trevor; Jones, Kevin; Fessler, Brian

    1997-01-01

    Voyager era stereo images are used to map the geology and topography of Ra Patera (a major active volcanic center and possible site of sulfur eruptions on Io). The summit of Ra Patera reaches only approx.1 km above the surrounding plains. Pre-Voyager-era lava flows occur on slopes of 0.1-0.3 deg, comparable to the lunar mare. These flows were emplaced at either low viscosities, high eruption rates, or both. A 600- km-long ridged mountain unit (rising to approx. 8 km near Carancho Patera) forms a 60 by 90 km wide plateau approx. 0.5 km high 50 km east of Ra Patera. The new lava flows observed by Galileo flowed around the southern edge of this plateau.

  19. The Relationship Between Race, Patient Activation, and Working Alliance: Implications for Patient Engagement in Mental Health Care.

    PubMed

    Eliacin, Johanne; Coffing, Jessica M; Matthias, Marianne S; Burgess, Diana J; Bair, Matthew J; Rollins, Angela L

    2016-12-01

    This study explored the relationship between race and two key aspects of patient engagement-patient activation and working alliance-among a sample of African-American and White veterans (N = 152) seeking medication management for mental health conditions. After adjusting for demographics, race was significantly associated with patient activation, working alliance, and medication adherence scores. Patient activation was also associated with working alliance. These results provide support for the consideration of race and ethnicity in facilitating patient engagement and patient activation in mental healthcare. Minority patients may benefit from targeted efforts to improve their active engagement in mental healthcare.

  20. Patterns of Spontaneous Magnetoencephalographic Activity in Schizophrenic Patients

    PubMed Central

    Siekmeier, Peter J.; Stufflebeam, Steven M.

    2010-01-01

    Magnetoencephalography (MEG) non-invasively measures the magnetic fields produced by the brain. Pertinent research articles from 1993 to 2009 that measured spontaneous, whole-head MEG activity in schizophrenic patients were reviewed. Data on localization of oscillatory activity and correlation of these findings with psychotic symptoms are summarized. While the variety of measures used by different research groups makes a quantitative meta-analysis difficult, it appears that MEG activity in patients may exhibit identifiable patterns, defined by topographic organization and frequency band. Specifically, 11 of the 12 studies showed increased theta (4–8 Hz) and delta (1–4 Hz) band oscillations in the temporal lobes of patients; of the 10 studies that examined the relationship between oscillatory activity and symptomatology, 8 found a positive correlation between temporal lobe theta activity and positive schizophrenic symptoms. Abnormally high frontal delta activity was not seen. These findings are analyzed in comparison to the EEG literature on schizophrenics, and possible confounds (e.g., medication effects) are discussed. In the future, MEG might be used to assist in diagnosis, or might be fruitfully used in conjunction with new neuroscience research approaches such as computational modeling, which may be able to link oscillatory activity and cellular-level pathology. PMID:20461010

  1. Patterns of spontaneous magnetoencephalographic activity in patients with schizophrenia.

    PubMed

    Siekmeier, Peter J; Stufflebeam, Steven M

    2010-06-01

    Magnetoencephalography noninvasively measures the magnetic fields produced by the brain. Pertinent research articles from 1993 to 2009 that measured spontaneous, whole-head magnetoencephalography activity in patients with schizophrenia were reviewed. Data on localization of oscillatory activity and correlation of these findings with psychotic symptoms are summarized. Although the variety of measures used by different research groups makes a quantitative meta-analysis difficult, it appears that magnetoencephalography activity in patients may exhibit identifiable patterns, defined by topographic organization and frequency band. Specifically, 11 of the 12 studies showed increased theta (4-8 Hz) and delta (1-4 Hz) band oscillations in the temporal lobes of patients; of the 10 studies that examined the relationship between oscillatory activity and symptomatology, 8 found a positive correlation between temporal lobe theta activity and positive schizophrenic symptoms. Abnormally high frontal delta activity was not seen. These findings are analyzed in comparison with the electroencephalogram literature on schizophrenics, and possible confounds (e.g., medication effects) are discussed. In the future, magnetoencephalography might be used to assist in diagnosis or might be fruitfully used in conjunction with new neuroscience research approaches such as computational modeling, which may be able to link oscillatory activity and cellular-level pathology.

  2. Serum paraoxonase 1 activity in patients with iron deficiency anemia

    PubMed Central

    Gedikbasi, Asuman; Akalin, Nilgul; Gunaldi, Meral; Yilmaz, Deniz; Mert, Meral; Harmankaya, Ozlem; Soylu, Aliye; Karakaya, Pinar; Kumbasar, Abdulbaki

    2016-01-01

    Introduction In this study we aimed to detect paraoxonase 1 (PON-1) activity in iron deficiency anemia (IDA) and to compare it with healthy controls by observing the change after iron therapy. Material and methods In this study, 50 adult patients with IDA and 40 healthy subjects were enrolled. All patients were analyzed at the beginning and after treatment according to laboratory assessments. Results Mean paraoxonase and arylesterase activities in the iron deficiency anemia group were significantly lower than mean activities of the control group (102.4 ±19.2 U/l and 163.3 ±13.68 U/l, respectively and 157.3 ±26.4 U/l and 256.1 ±24.6 U/l, respectively; p = 0.0001 for both). Paraoxonase and arylesterase activities significantly increased after treatment for IDA (143.2 ±13.9 and 197.6 ±27.9 U/l, respectively, p = 0.0001). Mean activities after treatment with iron were significantly lower than mean activities in the control group (p = 0.002; p = 0.0001 respectively). Conclusions Paraoxonase and arylesterase activities in patients with IDA significantly increased after treatment with iron therapy. In adults IDA may also be one of the factors associated with increased risk of atherosclerosis. PMID:27478448

  3. Active rehabilitation in a pediatric extracorporeal membrane oxygenation patient.

    PubMed

    Zebuhr, Carleen; Sinha, Amit; Skillman, Heather; Buckvold, Shannon

    2014-05-01

    Decreased intensive care unit (ICU) mortality has led to an increase in ICU morbidity. ICU-induced immobilization plays a major role in this morbidity. Recently, ICU mobility has been shown to be safe and effective in adolescent and adult patients. We report the successful rehabilitation of an 8-year-old boy with severe acute respiratory distress syndrome on extracorporeal membrane oxygenation. A child who is critically ill may safely perform active rehabilitation while on venovenous extracorporeal membrane oxygenation. The gains achieved through active rehabilitation and optimal nutrition can facilitate recovery from severe acute respiratory distress syndrome in select pediatric patients on extracorporeal membrane oxygenation.

  4. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  5. [Baroreflex behavior in patients with vasovagal syncope during active standing].

    PubMed

    Malamud-Kessler, Caroline; Estañol-Vidal, Bruno; Infante-Vázquez, Óscar; Campos-Sánchez, Miguel; Chiquete, Erwin

    2013-09-01

    INTRODUCTION. Neurally-mediated syncope, also known as vasovagal syncope, is defined as sudden and transient loss of consciousness due to a sudden and deep fall in arterial pressure. AIM. To determine the differences on the hemodynamic parameters mediating the baroreflex during active standing in patients with clinical diagnosis of vasovagal syncope as well as in healthy subjects. SUBJECTS AND METHODS. Cross-sectional, observational and comparative study. We included 20 patients diagnosed with neurally-mediated syncope and 30 controls, who underwent active orthostatic test, recording by finometry the systolic blood pressure (SBP) and heart rate (interbeat interval) in a continuous (beat to beat) and noninvasive fashion. RESULTS. Patients with syncope had a mean supine baseline SBP significantly higher than that of the healthy controls. The measured values of SBP from baseline showed a significant difference between groups, being also lower in the control group. No differences were found between groups in the fall of SBP from the first peak of heart rate to the trough. The recovery time of the SBP to the baseline was no different in controls and in patients. CONCLUSIONS. The baseline SBP and SBP drop measured from baseline in supine position was higher in patients than in healthy subjects. The magnitude of the elevation of heart rate has a tendency to be higher in the patient group compared with the control group. This suggests a sympathetic hyperactivity in patients with syncope.

  6. Reduced Arylsulfatase B Activity in Leukocytes from Cystic Fibrosis Patients

    PubMed Central

    Sharma, Girish; Burke, Jenifer; Bhattacharyya, Sumit; Sharma, Neha; Katyal, Shivani; Park, R. Lucy; Tobacman, Joanne

    2013-01-01

    Summary The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) removes 4-sulfate groups from chondroitin-4-sulfate and dermatan sulfate and is required for the degradation of these sulfated glycosaminoglycans (GAGs). Since these GAGs accumulate in patients with Cystic Fibrosis (CF), we investigated the activity of ARSB in leukocytes of patients with CF, to consider if reduced activity of ARSB might contribute to the pathophysiology of CF. Previous cell-based experiments had demonstrated that when the deficiency of the cystic fibrosis transmembrane regulator (CFTR) was corrected in bronchial epithelial cells, the ARSB activity increased significantly. De-identified, citrated blood samples were collected from 16 children with cystic fibrosis and 31 control subjects, seen in the Pediatric Clinic at Rush University Medical Center. Polymorphonuclear (PMN) and mononuclear cell (MC) populations were separated by density gradient, and blinded determinations of ARSB activity were performed using the exogenous substrate 4-methylumbilliferyl sulfate. Interleukin-6 was measured in the plasma samples by ELISA. ARSB activity was significantly less in the PMN and MC from the CF patients than controls (p<0.0001, unpaired t-test, two-tailed). Interleukin-6 levels in plasma were significantly greater in the CF population (p<0.001). Mean age, age range, and male:female ratio of CF patients and controls were similar, and no association of ARSB activity with age, gender, or CFTR genotype was evident. Since recombinant human ARSB is used successfully for replacement therapy in Mucopolysaccharidosis VI, it may be useful to restore ARSB activity to normal levels and increase degradation of sulfated GAGs in CF patients. PMID:22550062

  7. Low density of sympathetic nerve fibres and increased density of brain derived neurotrophic factor positive cells in RA synovium

    PubMed Central

    Weidler, C; Holzer, C; Harbuz, M; Hofbauer, R; Angele, P; Scholmerich, J; Straub, R

    2005-01-01

    Objective: To investigate the correlation between density of nerve fibres and the presence of BDNF+ cells. Methods: Densities of nerve fibres and BDNF+ cells were detected by quantitative immunohistochemistry in fresh synovial tissue from 52 patients with RA, 59 with OA, and 26 controls (Co). BDNF was also detected by in situ hybridisation. Results: Sympathetic nerve fibre density was similar in Co and OA but markedly reduced in RA (p = 0.002), whereas density of substance P positive (SP+) sensory nerve fibres was lower in OA than in Co and RA (p = 0.002). The ratio of sympathetic/SP+ sensory nerve fibre density was highest in OA and Co, followed by RA. The correlation between density of sympathetic nerve fibres and SP+ sensory nerve fibres in OA (R = 0.425, p = 0.001) was strongly positive, had a positive trend in Co (R = 0.243, NS), but was negative in RA (R = –0.292, p = 0.040). In RA and OA tissue the density of BDNF+ cells was high in sublining areas but markedly lower in Co (p = 0.001). BDNF+ cell density correlated positively with the ratio of sympathetic/SP+ sensory nerve fibre density in Co (R = 0.433, p = 0.045) and in OA (R = 0.613, p = 0.015), but not in RA (R = 0.101, NS). Immunohistochemical double staining demonstrated that some macrophages and fibroblasts were positive for BDNF. Conclusions: The correlation of density of SP+ sensory with sympathetic nerve fibres was positive in Co and OA but negative in RA. BDNF may have a stimulatory role on growth of sympathetic in relation to SP+ sensory nerve fibres in Co and OA, but not in RA. PMID:15608299

  8. (223)Ra-dichloride spectrometric characterization: Searching for the presence of long-lived isotopes with radiological protection implications.

    PubMed

    Sánchez-Jiménez, J; López-Montes, A; Núñez-Martínez, L; Villa-Abaunza, A; Fraile, L M; Sánchez-Tembleque, V; Udías, J M

    2017-03-01

    (223)Ra-dichloride was approved with the commercial name of Xofigo in 2014 for treatment of metastatic castration-resistant prostate cancer. (223)Ra is obtained by neutron irradiation of (226)Ra yielding (227)Ac, which decays to (227)Th and (223)Fr, both decaying to (223)Ra. Since (223)Ra is predominantly (95.3%) an alpha emitter with a 11.42days long half-life, the radiopharmaceutical, its remnants, the patient, and waste material can be managed and disposed with low radiation protection requirements. (227)Ac is a long-lived (T1/2=21.77years) beta emitter that demands strong radiation protection measures. In particular waste disposal has to follow the International Atomic Energy Agency (IAEA) and European Commission (EC) regulations. Since (227)Ac is involved in the production of (223)Ra, an impurity analysis of each batch is required after production. Due to time restrictions, the manufacturer's detection limit (<0.001%) exceeds the one required to assure that (227)Ac concentrations are below direct disposal levels. To improve the detection limit, long-term accurate spectroscopy is required. Alpha and gamma spectroscopy measurements were carried out at the Complutense University Nuclear Physics Laboratory. After twelve months follow up of a sample, (227)Ac concentration was found to be smaller than 10(-9). This allows for direct waste disposal and no additional radiation protection restrictions than those required for (223)Ra. The presence of contamination by other radioisotopes was also ruled out by this experiment. Specifically (226)Ra, involved in (223)Ra production as the original parent and with a very long-lived (T1/2=1577years) alpha emitter, was also below the experimental detection limit.

  9. Release of Active Peptidyl Arginine Deiminases by Neutrophils Can Explain Production of Extracellular Citrullinated Autoantigens in Rheumatoid Arthritis Synovial Fluid

    PubMed Central

    Spengler, Julia; Lugonja, Božo; Jimmy Ytterberg, A.; Zubarev, Roman A.; Creese, Andrew J.; Pearson, Mark J.; Grant, Melissa M.; Milward, Michael; Lundberg, Karin; Buckley, Christopher D.; Filer, Andrew; Raza, Karim; Cooper, Paul R.; Chapple, Iain L.

    2015-01-01

    Objective In the majority of patients with rheumatoid arthritis (RA), antibodies specifically recognize citrullinated autoantigens that are generated by peptidylarginine deiminases (PADs). Neutrophils express high levels of PAD and accumulate in the synovial fluid (SF) of RA patients during disease flares. This study was undertaken to test the hypothesis that neutrophil cell death, induced by either NETosis (extrusion of genomic DNA–protein complexes known as neutrophil extracellular traps [NETs]) or necrosis, can contribute to production of autoantigens in the inflamed joint. Methods Extracellular DNA was quantified in the SF of patients with RA, patients with osteoarthritis (OA), and patients with psoriatic arthritis (PsA). Release of PAD from neutrophils was investigated by Western blotting, mass spectrometry, immunofluorescence staining, and PAD activity assays. PAD2 and PAD4 protein expression, as well as PAD enzymatic activity, were assessed in the SF of patients with RA and those with OA. Results Extracellular DNA was detected at significantly higher levels in RA SF than in OA SF (P < 0.001) or PsA SF (P < 0.05), and its expression levels correlated with neutrophil concentrations and PAD activity in RA SF. Necrotic neutrophils released less soluble extracellular DNA compared to NETotic cells in vitro (P < 0.05). Higher PAD activity was detected in RA SF than in OA SF (P < 0.05). The citrullinated proteins PAD2 and PAD4 were found attached to NETs and also freely diffused in the supernatant. PAD enzymatic activity was detected in supernatants of neutrophils undergoing either NETosis or necrosis. Conclusion Release of active PAD isoforms into the SF by neutrophil cell death is a plausible explanation for the generation of extracellular autoantigens in RA. PMID:26245941

  10. NLRP3 Inflammasome Activation in Dialyzed Chronic Kidney Disease Patients

    PubMed Central

    Granata, Simona; Masola, Valentina; Zoratti, Elisa; Scupoli, Maria Teresa; Baruzzi, Anna; Messa, Michele; Sallustio, Fabio; Gesualdo, Loreto; Lupo, Antonio; Zaza, Gianluigi

    2015-01-01

    To assess whether NLR pyrin domain-containing protein 3 (NLRP3) inflammasome, a multiprotein complex that mediates the activation of caspase-1 (CASP-1) and pro-inflammatory cytokines IL-18 and IL-1β, could be involved in the chronic inflammatory state observed in chronic kidney disease patients undergoing hemodialysis treatment (CKD-HD), we employed several biomolecular techniques including RT-PCR, western blot, FACS analysis, confocal microscopy and microarray. Interestingly, peripheral blood mononuclear cells from 15 CKD-HD patients showed higher mRNA levels of NLRP3, CASP-1, ASC, IL-1β, IL-18 and P2X7receptor compared to 15 healthy subjects. Western blotting analysis confirmed the above results. In particular, active forms of CASP-1, IL1-β and IL-18 resulted significantly up-regulated in CKD-HD versus controls. Additionally, elevated mitochondrial ROS level, colocalization of NLRP3/ASC/mitochondria in peripheral blood mononuclear cells from CKD-HD patients and down-regulation of CASP-1, IL1-β and IL-18 protein levels in immune-cells of CKD-HD patients stimulated with LPS/ATP in presence of mitoTEMPO, inhibitor of mitochondrial ROS production, suggested a possible role of this organelle in the aforementioned CKD-associated inflammasome activation. Then, microarray analysis confirmed, in an independent microarray study cohort, that NLRP3 and CASP-1, along with other inflammasome-related genes, were up-regulated in 17 CKD-HD patients and they were able to clearly discriminate these patients from 5 healthy subjects. All together these data showed, for the first time, that NLRP3 inflammasome was activated in uremic patients undergoing dialysis treatment and they suggested that this unphysiological condition could be possibly induced by mitochondrial dysfunction. PMID:25798846

  11. Non-inflammatory Causes of Pain in Patients with Rheumatoid Arthritis.

    PubMed

    Boyden, Sean D; Hossain, Imtiyaz N; Wohlfahrt, Alyssa; Lee, Yvonne C

    2016-06-01

    Although pain in rheumatoid arthritis (RA) is frequently thought to be inflammatory in nature, the association between measures of inflammation and pain intensity is low. This observation is likely due to the multifactorial nature of pain. In addition to pain from joint inflammation, RA patients may also have pain due to structural damage or central etiologies, such as aberrancies in the central nervous system (CNS) pain regulatory pathways. These CNS pathways include mechanisms that facilitate pain, as well as mechanisms that inhibit pain. Other factors, such as sleep disturbances, depression, anxiety, and catastrophizing, may also impact the perception of pain in RA patients. Since pain is frequently used as a proxy for inflammation in the assessment of RA disease activity, it is important that patients and physicians recognize that not all pain is inflammatory, and alternative management strategies, other than escalating disease-modifying antirheumatic drug treatment, may need to be considered.

  12. Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease

    PubMed Central

    Curto‐Barredo, Laia; Yelamos, Jose; Gimeno, Ramon; Mojal, Sergi; Pujol, Ramon M.

    2016-01-01

    Abstract Introduction The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. Methods We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. Results Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). Conclusions The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life. PMID:27980778

  13. Study of the distribution of ²²⁶Ra in ground water near the uranium industry of Jharkhand, India.

    PubMed

    Tripathi, R M; Jha, V N; Sahoo, S K; Sethy, N K; Shukla, A K; Puranik, V D; Kushwaha, H S

    2012-01-01

    Ground water is the principal source of drinking water in the rural areas of India. With the aim of determining, the contribution of (226)Ra to natural background radiation through drinking water exposure pathway near an operating uranium mining industry at Jaduguda, Jharkhand state of eastern India, the (226)Ra activity concentrations were measured in potable ground water. The water analysed, both tube well and well water, was collected in areas near the uranium industry and away. The (226)Ra concentration was measured by emanometric technique. The (226)Ra level in ground water was ranging between minimum detection limit of 3.5 mBq l(-1) and a maximum of 208 mBq l(-1). The analysis of variance reveals that there is insignificant statistical variation in the median (226)Ra concentration up to a distance of >10 km from the mining complex. Variation in concentration of (226)Ra in sources is attributed to the local geochemistry and environmental factors. The (226)Ra concentration was significantly elevated in natural artesian wells in the vicinity of uranium mineralised hill and it varies from 53.4 to 754 mBq l(-1). The WHO [Guidelines for Drinking Water Quality. Third Edition, Vol. 1, Recommendation (2004)] guideline value of 1000 mBq l(-1) has not been exceeded in any of the sources investigated.

  14. [Rheumatoid factor activity, age at manifestation and roentgenologic progression of rheumatoid arthritis--a retrospective study].

    PubMed

    Hein, G; Eidner, G; Eidner, T; Marzoll, I; Klinner, M

    1993-01-01

    The outcome of RF-activity (measured by hemagglutination in the modification of Podliachouk-Harboe) was investigated in 95 patients with RA. In 52 of these patients the radiological progression (modification of Larsen index for hands and feet) in correlation to the outcome of RF was assessed. The results can be summarized in the following way: 1. Elderly RA patients show a significant elevation of RF titer. 2. There is a statistically insignificant correlation between age of RA manifestation and RF level. 3. The investigation of individual RF outcome shows that 54% of the patients have a relatively constant RF level, 15% tend to a decrease of the level of RF activity. Increased RF activity could only be demonstrated in 31% of the patients in the follow-up. 4. We more often observed a decrease of RF activity in RA cases with a disease manifestation < 30 y. We found no significant decrease in the follow-up in cases with manifestation > 60 y. 5. RA patients with a high level of RF activity (HAR > 1:512) have a significantly higher radiological progression index than cases with a low RF activity (HAR < 1:512).

  15. The association of anti-CCP antibodies with disease activity in rheumatoid arthritis

    PubMed Central

    Çakırbay, Haşim; Değer, Orhan; Cengiz, Sevil; Kul, Sibel

    2008-01-01

    Antibodies to citrullinated proteins have been described in patients with rheumatoid arthritis (RA) and these appear to be the most specific markers of the disease. Our objective was to determine the frequency of antibodies to cyclic citrullinated peptides (CCPs) in patients with RA and the association of anti-CCP antibodies with disease activity, radiological erosions and HLA DR genotype. Forty patients with RA and 38 patients with fibromyalgia were included in this study. Serum samples were collected from both patient groups with RA and fibromyalgia. Anti-CCP was measured by the corresponding enzyme-linked immunosorbent assay. Additionally, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), disease activity score (DAS), visual analog scala (VAS), HLA genotype and radiographic information were determined in patients with RA. The rate of sensitivity and specificity of anti-CCP reactivity for the diagnosis RA were measured (sensitivity 50%, specificity100%). There is no significant difference between anti-CCP (+) and anti-CCP (−) RA patients for DAS28, VAS, ESR, CRP, disease duration, HLA genotype, and radiological assessment of hand. However, there was a significant difference between anti-CCP (+) and anti-CCP (−) RA patients for RF and the radiological assessment of left and right wrists (respectively, P < 0.05, P = 0.04, P = 0.01). There was no significant correlation between anti-CCP antibody and ESR, CRP, VAS, DAS 28 or radiological assessment. A small but significant correlation was found between RF and anti-CCP antibody (P = 0.02, r = 0.35). PMID:18418600

  16. Active cytomegalovirus infection in patients with atopic dermatitis.

    PubMed

    Hafez, Shereen F; Shehata, Iman H; Abdel Aziz, Ghada A; Kamal, Mahmoud M

    2005-01-01

    Atopic dermatitis (AD) is a complex immunologic skin disorder that is expressed when genetically predisposed individuals are exposed to certain environmental stimuli. Inspite of the high prevalence of cytomegalovirus (CMV) infection and its potent immunomodulatory activities, the relation of CMV to AD is still poorly understood and is still to be clarified. The aim of the present study was to evaluate the frequency of active CMV infection in patients with AD and its possible etiologic role in the pathogenesis of the disease. Also, we tried to find if a relation between active CMV infection and disease severity exists. The present study was carried on 31 patients with AD with various degrees of disease severity. Ten apparently healthy subjects were enrolled in the study as a control group. Anti CMV IgG antibodies were estimated by quantitative enzyme immunoassay to discriminate between recent CMV infection and CMV reactivation. Active CMV infection was diagnosed by using nested PCR to detect CMV DNA in the sera of the studied subjects. The detection rate of CMV genome was higher in patients with AD in comparison to the control group. Cytomegalovirus genome was detected in the sera of 52% (16/31) of patients with AD (87.5% of them were seropositive for anti-CMV IgG antibodies). On the other hand no CMV DNA was detected in any of the serum samples of the control subjects. The difference was statistically significant. No significant relation was found between active CMV infection and disease severity. Also, no significant statistical difference was found between the two studied groups as regards the prevalence of latent CMV infection. In addition, no significant difference was detected between anti-CMV IgG antibody levels in all seropositive subjects. Our results denote that active subclinical CMV infection is more frequent in patients with AD and may have possible immunomodulatory role in the etiopathogenesis of AD but it is not related to disease severity.

  17. Demoralization, Patient Activation, and the Outcome of Spine Surgery

    PubMed Central

    Block, Andrew R

    2016-01-01

    It is now well established that psychosocial factors can adversely impact the outcome of spine surgery. This article discusses in detail one such recently-identified “risk” factor: demoralization. Several studies conducted by the author indicate that demoralization, an emotional construct distinct from depression, is associated with poorer pain reduction, less functional improvement and decreased satisfaction among spine surgery patients. However, there are indications that the adverse impact of risk factors such as demoralization can be mitigated by psychosocial “maximizing” factors—characteristics that propel the patient towards positive surgical results. One of these maximizing factors, patient activation, is discussed in depth. The patient activation measure (PAM), an inventory assessing the extent to which patients are active and engaged in their health care, is associated not only with improved spine surgery results, but with better outcomes across a broad range of medical conditions. Other maximizing factors are discussed in this article. The author concludes that the past research focus on psychosocial risk factors has limited the value of presurgical psychological screening, and that future research, as well as clinical assessment, should recognize that the importance of evaluating patients’ strengths as well as their vulnerabilities. PMID:27417599

  18. Pregnancy in patients with rheumatic disease: anti-inflammatory cytokines increase in pregnancy and decrease post partum

    PubMed Central

    Ostensen, M; Forger, F; Nelson, J; Schuhmacher, A; Hebisch, G; Villiger, P

    2005-01-01

    Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). Methods: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon γ (IFNγ), interleukin (IL) 1ß, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. Results: Low levels of IL10 were found sporadically, whereas IFNγ and IL1ß were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. Conclusions: IFNγ and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity. PMID:15539410

  19. Exercise in Treating Hypertension: Tailoring Therapies for Active Patients.

    ERIC Educational Resources Information Center

    Chintanadilok, Jirayos

    2002-01-01

    Exercise can be definitive therapy for some, and adjunctive therapy for many, people with hypertension, though people with secondary hypertension may not derive as much benefit. Low-to- moderate-intensity aerobic exercise can help with mild hypertension and reduce drug dosages in more severe cases. For active patients requiring medication,…

  20. Optimizing perioperative outcomes for older patients with rheumatoid arthritis undergoing arthroplasty: emphasis on medication management.

    PubMed

    Goodman, Susan M

    2015-05-01

    Patients with rheumatoid arthritis continue to undergo arthroplasty despite widespread use of potent disease-modifying drugs (DMARDs), including the biologic tumor necrosis-α inhibitors. In fact, over 80 % of RA patients are taking DMARDs or biologics at the time of arthroplasty. While many RA-specific factors including disease activity and disability may contribute to the increase in infection in RA patients undergoing arthroplasty, immunosuppressant medications may also play a role. As the age of patients with RA undergoing arthroplasty is rising, and the incidence of arthroplasty among the older population is increasing, optimal perioperative management of DMARDs and biologics in older patients with RA is an increasing challenge. Although evidence is sparse, most evidence supports withholding tumor necrosis-α inhibitors and other biologics prior to surgery based on the dosing interval, and continuing methotrexate and hydroxychloroquine through the perioperative period. There is no consensus regarding leflunomide, and rituximab risk does not appear related to the interval between infusion and surgery. This paper reviews arthroplasty outcomes including complications in patients with RA, and discusses the rationale for strategies for the optimal medication management of DMARDs and biologics in the perioperative period to minimize complications and improve outcomes.

  1. Advanced glycation endproducts are increased in rheumatoid arthritis patients with controlled disease

    PubMed Central

    2011-01-01

    Introduction Advanced glycation end products (AGEs) are produced and can accumulate during chronic inflammation, as might be present in patients with rheumatoid arthritis (RA). AGEs are involved in the development of cardiovascular disease. The aim of this study is to evaluate whether AGEs are increased in patients with long-standing RA and whether AGE accumulation is related to disease activity, disease severity and measures of (premature) atherosclerosis, such as endothelial activation, endothelial dysfunction and intima media thickness (IMT). Methods In a cross-sectional study, 49 consecutive RA patients with longstanding disease (median disease duration of 12.3 years (range 9.3 to 15.1)), receiving standard of care, were included and compared with 49 age- and sex-matched healthy controls (HC). AGEs were determined by skin autofluorescence. Disease activity was evaluated by the Disease Activity Score of 28 joints (DAS-28) score and joint damage by modified Sharp-v.d. Heijde score. Endothelial activation (soluble vascular cellular adhesion molecule-1) sVCAM-1, von Willebrand factor (vWF), thrombomodulin), endothelial dysfunction (determined by small artery elasticity (SAE)) and IMT were measured and related to AGE accumulation. Results AGEs were increased in RA patients (median 2.4 arbitrary units (a.u.), range 1.6 to 4.2) compared to HC (2.2, 1.3 to 3.8). RA patients had a DAS-28 score of 2.9 (0.8 to 6.9) and a modified Sharp-v.d. Heijde score of 19 (0 to 103). sVCAM-1 and vWF levels were higher in RA patients. SAE was significantly decreased in RA (3.9 ml/mmHg (1.4 to 12.2) vs. 6.1 in HC (1.7 to 12.9). IMT did not differ between the two groups. Combining both groups' AGEs correlated with vWF, sVCAM-1 and IMT, and was inversely related to SAE. In RA, AGEs had an inverse relation with SAE, but did not relate to disease activity or radiological damage. In multivariate analysis for both groups, smoking, glucose levels, vWF, SAE and male gender were significantly

  2. Interleukin-19 impairment in active Crohn's disease patients.

    PubMed

    Cantó, Elisabet; Garcia Planella, Esther; Zamora-Atenza, Carlos; Nieto, Juan Camilo; Gordillo, Jordi; Ortiz, Ma Angels; Metón, Isidoro; Serrano, Elena; Vegas, Esteban; García-Bosch, Orlando; Juárez, Cándido; Vidal, Sílvia

    2014-01-01

    The exact function of interleukin-19 (IL-19) on immune response is poorly understood. In mice, IL-19 up-regulates TNFα and IL-6 expression and its deficiency increases susceptibility to DSS-induced colitis. In humans, IL-19 favors a Th2 response and is elevated in several diseases. We here investigate the expression and effects of IL-19 on cells from active Crohn's disease (CD) patient. Twenty-three active CD patients and 20 healthy controls (HC) were included. mRNA and protein IL-19 levels were analyzed in monocytes. IL-19 effects were determined in vitro on the T cell phenotype and in the production of cytokines by immune cells. We observed that unstimulated and TLR-activated monocytes expressed significantly lower IL-19 mRNA in active CD patients than in HC (logFC = -1.97 unstimulated; -1.88 with Pam3CSK4; and -1.91 with FSL-1; p<0.001). These results were confirmed at protein level. Exogenous IL-19 had an anti-inflammatory effect on HC but not on CD patients. IL-19 decreased TNFα production in PBMC (850.7 ± 75.29 pg/ml vs 2626.0 ± 350 pg/ml; p<0.01) and increased CTLA4 expression (22.04 ± 1.55% vs 13.98 ± 2.05%; p<0.05) and IL-4 production (32.5 ± 8.9 pg/ml vs 13.5 ± 2.9 pg/ml; p<0.05) in T cells from HC. IL-10 regulated IL-19 production in both active CD patients and HC. We observed that three of the miRNAs that can modulate IL-19 mRNA expression, were up-regulated in monocytes from active CD patients. These results suggested that IL-19 had an anti-inflammatory role in this study. Defects in IL-19 expression and the lack of response to this cytokine could contribute to inflammatory mechanisms in active CD patients.

  3. Rainfall Manipulation Plot Study (RaMPS)

    DOE Data Explorer

    Blair, John [Kansas State University; Fay, Phillip [USDA-ARS; Knapp, Alan [Colorado State University; Collins, Scott [University of New Mexico; Smith, Melinda [Yale University

    Rainfall Manipulation Plots facility (RaMPs) is a unique experimental infrastructure that allows us to manipulate precipitation events and temperature, and assess population community, and ecosystem responses in native grassland. This facility allows us to manipulate the amount and timing of individual precipitation events in replicated field plots at the Konza Prairie Long-Term Ecological Research (LTER) site. Questions we are addressing include: • What is the relative importance of more extreme precipitation patterns (increased climatic variability) vs. increased temperatures (increased climatic mean) with regard to their impact on grassland ecosystem structure and function? Both projected climate change factors are predicted to decrease soil water availability, but the mechanisms by which this resource depletion occurs differ. • Will altered precipitation patterns, increased temperatures and their interaction increase opportunities for invasion by exotic species? • Will long-term (6-10 yr) trajectories of community and ecosystem change in response to more extreme precipitation patterns continue at the same rate as initial responses from years 1-6? Or will non-linear change occur as potential ecological thresholds are crossed? And will increased temperatures accelerate these responses? Data sets are available as ASCII files, in Excel spreadsheets, and in SAS format. (Taken from http://www.konza.ksu.edu/ramps/backgrnd.html

  4. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents.

    PubMed

    Ghanima, Waleed; Junker, Peter; Hasselbalch, Hans Carl; Boiocchi, Leonardo; Geyer, Julia T; Feng, Xingmin; Gudbrandsdottir, Sif; Orazi, Attilio; Bussel, James B

    2011-10-01

    This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on-treatment BM biopsies revealed statistically significant increases in reticulin. Reticulin in biopsies performed after a median of 1·4 years of treatment was graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment Procollagen III N-propeptide (PIIINP) (6·6 μg/l) was significantly higher than on-treatment levels (5·6 μg/l); both were higher than controls (3·4 μg/l; P < 0·001). PIIINP was negatively correlated with treatment duration (r = -0·49) suggesting a decelerated reticulin production over time. There was a trend towards an association between grade of reticulin and PIIINP. Transforming growth factor (GF)-beta and basic-Fibroblast GF were not different between patients and controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated HGF need further investigation to explore their significance in BM fibrogenesis.

  5. Improved limit on the Ra225 electric dipole moment

    DOE PAGES

    Bishof, Michael; Parker, Richard H.; Bailey, Kevin G.; ...

    2016-08-03

    In this study, octupole-deformed nuclei, such as that of 225Ra, are expected to amplify observable atomic electric dipole moments (EDMs) that arise from time-reversal and parity-violating interactions in the nuclear medium. In 2015 we reported the first “proof-of-principle” measurement of the 225Ra atomic EDM.

  6. 226Ra determination in phosphogypsum by alpha-particle spectrometry

    NASA Astrophysics Data System (ADS)

    Aguado, J. L.; Bolívar, J. P.; García-Tenorio, R.

    1999-01-01

    A radiochemical method for226Ra determination by alpha-particle spectrometry in environmental samples has been developed in our laboratory. The method has been validated by measurements in samples with known concentrations of this radionuclide and it has been applied in studies related to226Ra behaviour in phosphogypsum (the main by-product of producing phosphoric acid from phosphate rocks).

  7. Infrared sauna in patients with rheumatoid arthritis and ankylosing spondylitis. A pilot study showing good tolerance, short-term improvement of pain and stiffness, and a trend towards long-term beneficial effects.

    PubMed

    Oosterveld, Fredrikus G J; Rasker, Johannes J; Floors, Mark; Landkroon, Robert; van Rennes, Bob; Zwijnenberg, Jan; van de Laar, Mart A F J; Koel, Gerard J

    2009-01-01

    To study the effects of infrared (IR) Sauna, a form of total-body hyperthermia in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients were treated for a 4-week period with a series of eight IR treatments. Seventeen RA patients and 17 AS patients were studied. IR was well tolerated, and no adverse effects were reported, no exacerbation of disease. Pain and stiffness decreased clinically, and improvements were statistically significant (p < 0.05 and p < 0.001 in RA and AS patients, respectively) during an IR session. Fatigue also decreased. Both RA and AS patients felt comfortable on average during and especially after treatment. In the RA and AS patients, pain, stiffness, and fatigue also showed clinical improvements during the 4-week treatment period, but these did not reach statistical significance. No relevant changes in disease activity scores were found, indicating no exacerbation of disease activity. In conclusion, infrared treatment has statistically significant short-term beneficial effects and clinically relevant period effects during treatment in RA and AS patients without enhancing disease activity. IR has good tolerability and no adverse effects.

  8. Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms.

    PubMed

    Li, Ping; Yang, Li; Ma, Cui-Li; Liu, Bo; Zhang, Xin; Ding, Rui; Bi, Li-qi

    2015-06-01

    Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the number of adiponectin molecules but also in their biological activity. There are conflicting findings regarding the role of adiponectin in rheumatoid arthritis (RA). Moreover, few reports have described the relationships between serum adiponectin multimers levels and RA. Therefore, we examined the association of total adiponectin and its multimers with RA. Two study groups were examined: 180 recently diagnosed untreated RA patients with disease duration less than 1 year (RA group) and 160 age- and sex-matched control subjects (control group). RA-related factors, blood pressure, body mass index, glucose, complete lipid profile, and adiponectin multimers were measured. The levels of total adiponectin and each multimer of adiponectin were significantly lower in the RA than in the control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively correlated with triglycerides levels and negatively correlated with the Disease Activity Score for 28 joints (DAS28). Multivariate regression analysis showed that total, HMW, and MMW adiponectin were independently associated with serum triglycerides level. LMW adiponectin was independently correlated with serum triglycerides level and DAS28. The decreased LMW adiponectin levels may be associated with disease activity of RA.

  9. Brain activation induced by psychological stress in patients with schizophrenia.

    PubMed

    Castro, M N; Villarreal, M F; Bolotinsky, N; Papávero, E; Goldschmidt, M G; Costanzo, E Y; Drucaroff, L; Wainsztein, A; de Achával, D; Pahissa, J; Bär, K-J; Nemeroff, C B; Guinjoan, S M

    2015-10-01

    Environmental influences are critical for the expression of genes putatively related to the behavioral and cognitive phenotypes of schizophrenia. Among such factors, psychosocial stress has been proposed to play a major role in the expression of symptoms. However, it is unsettled how stress interacts with pathophysiological pathways to produce the disease. We studied 21 patients with schizophrenia and 21 healthy controls aged 18 to 50years with 3T-fMRI, in which a period of 6min of resting state acquisition was followed by a block design, with three blocks of 1-min control-task, 1-min stress-task and 1-min rest after-task. Self-report of stress and PANSS were measured. Limbic structures were activated in schizophrenia patients by simple tasks and remained active during, and shortly after stress. In controls, stress-related brain activation was more time-focused, and restricted to the stressful task itself. Negative symptom severity was inversely related to activation of anterior cingulum and orbitofrontal cortex. Results might represent the neurobiological aspect of hyper-reactivity to normal stressful situations previously described in schizophrenia, thus providing evidence on the involvement of limbic areas in the response to stress in schizophrenia. Patients present a pattern of persistent limbic activation probably contributing to hypervigilance and subsequent psychotic thought distortions.

  10. Patient activation and advocacy: which literacy skills matter most?

    PubMed

    Martin, Laurie T; Schonlau, Matthias; Haas, Ann; Derose, Kathryn Pitkin; Rosenfeld, Lindsay; Buka, Stephen L; Rudd, Rima

    2011-01-01

    Attention to the effect of a patient's literacy skills on health care interactions is relatively new. So, too, are studies of either structural or personal factors that inhibit or support a patient's ability to navigate health services and systems and to advocate for their own needs within a service delivery system. Contributions of the structural environment, of interpersonal dynamics, and of a variety of psychological and sociological factors in the relationship between patients and providers have long been under study. Less frequently examined is the advocacy role expected of patients. However, the complex nature of health care in the United States increasingly requires a proactive stance. This study examined whether four literacy skills (reading, numeracy, speaking, and listening) were associated with patient self-advocacy--a component of health literacy itself--when faced with a hypothetical barrier to scheduling a medical appointment. Although all literacy skills were significantly associated with advocacy when examined in isolation, greater speaking and listening skills remained significantly associated with better patient advocacy when all four skills were examined simultaneously. These findings suggest that speaking and listening skills and support for such skills may be important factors to consider when developing patient activation and advocacy skills.

  11. The multiple sclerosis susceptibility genes TAGAP and IL2RA are regulated by vitamin D in CD4+ T cells

    PubMed Central

    Berge, T; Leikfoss, I S; Brorson, I S; Bos, S D; Page, C M; Gustavsen, M W; Bjølgerud, A; Holmøy, T; Celius, E G; Damoiseaux, J; Smolders, J; Harbo, H F; Spurkland, A

    2016-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disorder of the central nervous system that develops in genetically susceptible individuals. The majority of the MS-associated gene variants are located in genetic regions with importance for T-cell differentiation. Vitamin D is a potent immunomodulator, and vitamin D deficiency has been suggested to be associated with increased MS disease susceptibility and activity. In CD4+ T cells, we have analyzed in vitro vitamin D responsiveness of genes that contain an MS-associated single-nucleotide polymorphism (SNP) and with one or more vitamin D response elements in their regulatory regions. We identify IL2RA and TAGAP as novel vitamin D target genes. The vitamin D response is observed in samples from both MS patients and controls, and is not dependent on the genotype of MS-associated SNPs in the respective genes. PMID:26765264

  12. Plasma ADAMTS13 activity and von Willebrand Factor Antigen and Activity In Patients with Subarachnoid Hemorrhage

    PubMed Central

    Kumar, Monisha; Cao, Wenjing; McDaniel, Jenny K.; Pham, Huy P.; Raju, Dheeraj; Nawalinski, Kelsey; Frangos, Suzanne; Kung, David; Zager, Eric E.; Kasner, Scott E.; Levine, Joshua M.; Zheng, X. Long

    2017-01-01

    Summary Background Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage (SAH). Objective To determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Methods 40 consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Results Mean age of SAH patients was 52.4 years (26–84 years) and 30 (75%) were women. 12/40 (30%) had a high Hunt and Hess grade (IV–V) and 25 (62.5%) were treated with coil embolization. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. Conclusions The relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome. PMID:28102428

  13. Plasma ADAMTS13 activity and von Willebrand factor antigen and activity in patients with subarachnoid haemorrhage.

    PubMed

    Kumar, Monisha; Cao, Wenjing; McDaniel, Jenny K; Pham, Huy P; Raju, Dheeraj; Nawalinski, Kelsey; Frangos, Suzanne; Kung, David; Zager, Eric; Kasner, Scott E; Levine, Joshua M; Zheng, X Long

    2017-01-19

    Increased von Willebrand factor (VWF) and reduced ADAMTS13 activity are associated with arterial thrombosis. This may also be the culprit mechanism implicated in delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage (SAH). It was our objective to determine plasma VWF and ADAMTS13 in patients with SAH and healthy subjects; and to explore the levels of those markers and outcome after SAH. Forty consecutive patients were enrolled between September 2007 and April 2014 in a pilot study. Plasma samples were collected from SAH patients on post-bleed day (PBD) 0, 1, 3, 5, 7 and 10 and healthy controls. VWF antigen (VWFAg) and VWF activity (VWFAc) were determined by enzyme-linked immunoassay and collagen binding assay, respectively. ADAMTS13 activity was determined by the cleavage of a fluorescent substrate. Univariate descriptive statistics and cluster analyses were performed based on outcomes in the group with SAH only. Mean age of SAH patients was 52.4 years (26-84 years) and 30 (75 %) were women. 12/40 (30 %) had a high Hunt and Hess grade (IV-V) and 25 (62.5 %) were treated with coil embolisation. Plasma VWFAg and VWFAc were significantly higher in SAH patients than those in healthy subjects on each PBD (p<0.0001). Concurrently, plasma ADAMTS13 activity in SAH patients was significantly lower than that in healthy subjects (p<0.0001). Among those with SAH, cluster analysis demonstrated that patients with higher VWFAg and VWFAc and/or lower ADAMTS13 activity might be at risk of increased mortality. In conclusion, the relative deficiency of plasma ADAMTS13 activity in SAH patients may associate with worse outcome.

  14. Barriers associated with reduced physical activity in COPD patients*

    PubMed Central

    Amorim, Priscila Batista; Stelmach, Rafael; Carvalho, Celso Ricardo Fernandes; Fernandes, Frederico Leon Arrabal; Carvalho-Pinto, Regina Maria; Cukier, Alberto

    2014-01-01

    OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001), as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001). The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures. PMID:25410838

  15. Restoration of peripheral blood natural killer and B cell levels in patients affected by rheumatoid and psoriatic arthritis during etanercept treatment.

    PubMed

    Conigliaro, P; Triggianese, P; Perricone, C; Chimenti, M S; Di Muzio, G; Ballanti, E; Guarino, M D; Kroegler, B; Gigliucci, G; Grelli, S; Perricone, R

    2014-07-01

    Etanercept (ETN) is an anti-tumour necrosis factor (TNF)-α agent used in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Few studies focused on the effects of anti-TNF-α on peripheral blood cells. We aimed to evaluate peripheral blood cells in RA and PsA patients during ETN treatment and to explore their relationships with disease activity. RA (n = 82) and PsA (n = 32) patients who started ETN were included into the study and evaluated prospectively before the beginning of ETN therapy and after 14, 22, 54 and 102 weeks. Patients were studied in terms of disease activity score on 28 joints (DAS28), clinical response and laboratory findings. Natural killer (NK) cells, B cells and T cells were characterized by immunophenotyping. Both the RA and the PsA patients showed reduced NK and B cell count before ETN treatment compared with controls. A negative correlation was demonstrated between DAS28 and B cell count in RA patients at baseline. Sustained significant increase of NK and B cells up to normal levels was observed in RA and PsA patients along ETN treatment. Increase of NK cell count was associated with a good-moderate clinical response to ETN in both RA and PsA patients. During ETN treatment peripheral blood NK and B cells levels were restored in RA and PsA patients. Correlations between NK and B cells with disease activity were observed, suggesting that those effects could be mediated by ETN treatment.

  16. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    PubMed

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  17. Immunoregulation in arthritis. A review on synovial immune reactions in RA and in some experimental animal models for arthritis.

    PubMed

    Klareskog, L; Holmdahl, R; Goldschmidt, T; Björk, J

    1987-01-01

    Local synovial immune reactions have during recent years been characterized both in human arthritides, particularly in rheumatoid arthritis (RA), and in animal models for arthritis. Common characteristics of human RA on one hand and experimental adjuvant arthritis and collagen arthritis on the other hand, are induced expression of class II transplantation antigens on synovial cells close to the cartilage and presence of activated T lymphocytes in close proximity to these class II expressing cells. The present review aims to describe some implications of these and subsequent findings both concerning the analysis of the pathogenesis of RA and concerning some therapeutic implications derived from parallel studies on relevant features of the human RA and the respective animal models for arthritis.

  18. Characteristics of physical activity in patients with critical limb ischemia

    PubMed Central

    Sakaki, Satoko; Takahashi, Tetsuya; Matsumoto, Junichi; Kubo, Kasuya; Matsumoto, Takuya; Hishinuma, Ryo; Terabe, Yuuta; Ando, Hiroshi

    2016-01-01

    [Purpose] The purpose of this study was to evaluate the amount of physical activity of the patients with critical limb ischemia consecutively in order to clarify the characteristics of physical activity of critical limb ischemia. [Subjects and Methods] Twelve patients who were eligible for the 2 months of consecutive evaluation of the amount of physical activity were enrolled in the study (men: 11; woman: 1; mean age: 64.4 [range: 44–80]). A pedometer with an accelerometer was used for the measurement of the number of steps walked as an index of the amount of physical activity. Participants were asked to lead a regular life and no instruction was given as to the number of steps. [Results] The average number of daily steps walked was 2,323 steps (range: 404–6,505). There was no clear tendency in the number of amputation site-specific steps walked. There was also no correlation between the number of steps walked and age as well as the maximum strength of the knee-extension muscle, skin perfusion pressure of the sole and the dorsum, and QOL scores. [Conclusion] The number of steps walked of the patients with critical limb ischemia was remarkably low and no significant association with health-related QOL. PMID:28174472

  19. Basophil activation test with food additives in chronic urticaria patients.

    PubMed

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  20. Cytokine Patterns in Tuberculosis Infection; IL-1ra, IL-2 and IP-10 Differentiate Borderline QuantiFERON-TB Samples from Uninfected Controls

    PubMed Central

    Wergeland, Ida; Assmus, Jörg; Dyrhol-Riise, Anne Ma

    2016-01-01

    Background Interferon gamma release assays (IGRAs) do not discriminate between active tuberculosis (TB) and latent TB infection (LTBI), which limit their use in TB endemic areas. Subjects with QuantiFERON-TB (QFT) results around the diagnostic cut-off more likely show inconsistent results on serial testing which makes the interpretation of the assay difficult. We have studied potential biomarkers in patients with various stages of TB infection and with borderline QFT tests compared to those with higher values. Methods 27 soluble biomarkers were analysed in QFT supernatants from patients with active TB (n = 18), individuals with LTBI (n = 48) and from QFT negative controls (n = 16) by the Multiplex bead assay. The LTBI group was classified into two groups according to QFT IFN-γ levels; QFT borderline (0.35–0.70 IU/mL, n = 11) or QFT high (>0.70 IU/mL, n = 36). Results The levels of IL-1ra, IL-2, IL-13, IL-15, IFN-γ, IP-10 and MCP-1 in background corrected TB antigen stimulated supernatants (TBAg-Nil) significantly distinguished both active TB and LTBI QFT high groups from the QFT negative controls (p≤0.004). In addition, IL-1ra, IL-2 and IP-10 significantly differentiated the QFT borderline group from the controls (p≤0.001). Still, in the QFT borderline group the IL-1ra and IP-10 levels were not significant different from neither the QFT high nor the active TB group, whereas the IL-2 levels were lower (p≤0.003). The level of IP-10 showed the best separation between the QFT borderline group and the QFT negative controls (AUC 0.92) and offered 100% sensitivity for active TB. Conclusion IL-1ra, IL-2 and IP-10 differentiate QFT borderline samples from uninfected controls and the majority of QFT borderline subjects were classified as LTBI by these markers. Still, inconsistency was seen, and further studies are needed to examine the performance of alternative markers before concluded if they could be used as diagnostics tools. PMID:27685462

  1. Comparative Analysis Of {sup 226}Ra Soil-To-Plant Transfer In Cabbage Grown In Various Regions

    SciTech Connect

    Madruga, M. J.; Carvalho, F. P.; Silva, L.; Gouveia, J.

    2008-08-07

    The transfer of {sup 226}Ra from soil to cabbage was compared amongst regions, namely the surroundings of Urgeirica uranium milling tailings (GE), regions with past uranium mining activities (GN1), and regions with no uranium mining activities and no uranium deposits (GN2). Results show a slight increase of the concentration ratio values at low radium concentration in soils. Statistical analysis of the mean {sup 226}Ra activity concentrations in soil and cabbage for the three regions was carried out. The comparison of {sup 226}Ra activity concentrations in soils indicated no difference (p>0.05), between GE and GN2 and significant differences (p<0.05) between GE and GN1 and between GN1 and GN2. Similar statistical results were obtained for {sup 226}Ra activity concentrations in cabbage from the same regions. It was concluded that radium Concentration Ratio (CR) for cabbage grown in the region of the main uranium milling site (GE) is of the same order of magnitude of CR in cabagge grown in background regions (GN2). However, {sup 226}Ra CR was higher in cabagge from the region with past uranium mining activities (GN1)

  2. Smartphone application for rheumatoid arthritis self-management: cross-sectional study revealed the usefulness, willingness to use and patients' needs.

    PubMed

    Azevedo, Rita; Bernardes, Miguel; Fonseca, João; Lima, Aurea

    2015-10-01

    Patient-centered smartphone applications have potential to support rheumatoid arthritis (RA) self-management but remain almost unexplored in literature. Therefore, this study evaluated the usefulness of a smartphone application to support RA self-management, the willingness of RA patients to use and pay for it and the features the application should have. In this cross-sectional study, a questionnaire was developed to collect information on population, device ownership, usefulness and willingness to use and pay for a RA self-management application and application features. Descriptive statistics, Chi-square, Fisher's exact test, t test or Mann-Whitney's test and multivariate analysis were used. One hundred RA patients answered the questionnaire. Patients' mean age was 57 ± 11.9 years, most were females (91 %), with multiple drug regimens and a 40 % treatment non-compliance rate. Most patients believed that could have a more active role in self-management (94 %) and reported it would be useful to develop a RA self-management application (86 %). Patients willing to use an application (83 %) were younger, with a possible more active role in self-management, with access to a smartphone, and using short message service, electronic mail and Internet. Multivariate analysis confirmed these results, except the associations regarding access to a smartphone and use of electronic mail and Internet. Fifty-eight patients (82 %) were willing to pay for a RA self-management application and the most requested feature for it was information in a simple format. This study suggested the usefulness and patients' willingness to use and pay for a RA self-management application and provided insight on patients' needs.

  3. Real-world experiences of folic acid supplementation (5 versus 30 mg/week) with methotrexate in rheumatoid arthritis patients: a comparison study.

    PubMed

    Koh, K T; Teh, C L; Cheah, C K; Ling, G R; Yong, M C; Hong, H C; Gun, S C

    2016-09-09

    The objective of this study was to compare the tolerability of methotrexate in two different regimes of folic acid (FA) supplementation in rheumatoid arthritis (RA). We performed a multicenter, cross-sectional observational cohort study on 240 RA patients with 120 patients each in 5 mg of FA weekly and 30 mg of FA weekly supplementation. There were no significant differences for side effects (14.2 versus 22.5%, P=0.523) and discontinuation of methotrexate (3.6 versus 13.3%, P=0.085). RA patients given 5 mg of FA weekly supplementation had a lower disease activity score 28 compared to 30 mg of FA weekly supplementation [3.44 (1.10) versus 3.85 (1.40), P=0.014]. FA supplementation of 5 mg per week and 30 mg per week was associated with similar tolerability of methotrexate in RA patients.

  4. [Activity of antioxidant enzymes in patients with liver cirrhosis].

    PubMed

    Czeczot, Hanna; Scibior, Dorota; Skrzycki, Michał; Podsiad, Małgorzata

    2006-01-01

    The aim of our studies was the estimation of activities of antioxidant enzymes in patients with liver cirrhosis. We investigated activities of superoxide dismutases (CuZnSOD, MnSOD), catalase (CAT), selenium dependent GSH peroxidase (Se-GSH-Px), selenium independent GSH peroxidase (non-Se-GSH-Px), GSH-S-transferase (GST), GSH reductase (GSHR) and the level ofreduced gutathione (GSH) in cirrhotic and healthy liver tissues. The activities of CuZnSOD, MnSOD, CAT and GSH-dependent enzymes (except GSHR) were found to be lower in cirrhotic tissue compared to healthy liver. Those changes were associated with decrease of GSH level in cirrhotic tissue compared with control liver tissue. Our results show that antioxidant barrier in liver cirrhosis is impaired. It is associated with decrease of glutathione level and changes of activities of antioxidant enzymes (SOD, CAT, GSHPx, GST, GSHR) in liver cirrhosis compared with healthy liver.

  5. Simultaneous determination of gross alpha, gross beta and ²²⁶Ra in natural water by liquid scintillation counting.

    PubMed

    Fons, J; Zapata-García, D; Tent, J; Llauradó, M

    2013-11-01

    The determination of gross alpha, gross beta and (226)Ra activity in natural waters is useful in a wide range of environmental studies. Furthermore, gross alpha and gross beta parameters are included in international legislation on the quality of drinking water [Council Directive 98/83/EC]. In this work, a low-background liquid scintillation counter (Wallac, Quantulus 1220) was used to simultaneously determine gross alpha, gross beta and (226)Ra activity in natural water samples. Sample preparation involved evaporation to remove (222)Rn and its short-lived decay daughters. The evaporation process concentrated the sample ten-fold. Afterwards, a sample aliquot of 8 mL was mixed with 12 mL of Ultima Gold AB scintillation cocktail in low-diffusion vials. In this study, a theoretical mathematical model based on secular equilibrium conditions between (226)Ra and its short-lived decay daughters is presented. The proposed model makes it possible to determine (226)Ra activity from two measurements. These measurements also allow determining gross alpha and gross beta simultaneously. To validate the proposed model, spiked samples with different activity levels for each parameter were analysed. Additionally, to evaluate the model's applicability in natural water, eight natural water samples from different parts of Spain were analysed. The eight natural water samples were also characterised by alpha spectrometry for the naturally occurring isotopes of uranium ((234)U, (235)U and (238)U), radium ((224)Ra and (226)Ra), (210)Po and (232)Th. The results for gross alpha and (226)Ra activity were compared with alpha spectrometry characterization, and an acceptable concordance was obtained.

  6. Exogenous IL-1Ra attenuates intestinal mucositis induced by oxaliplatin and 5-fluorouracil through suppression of p53-dependent apoptosis.

    PubMed

    Wang, Xia; Gao, Jin; Qian, Lan; Gao, Jing; Zhu, Shunying; Wu, Mingyuan; Zhang, Yang; Guan, Wen; Ye, Hao; Yu, Yan; Han, Wei

    2015-01-01

    Chemotherapy-induced intestinal mucositis (CIM) is a major dose-limiting side effect of many chemoagents, resulting in weight loss, diarrhea, and even death. The current treatments for CIM are palliative and have limited benefit. Interleukin-1 receptor antagonist is a natural antagonist of interleukin-1. Our previous studies showed the protective effect of recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) on the intestine in mice after 5-fluorouracil chemotherapy. In this study, we further evaluated rhIL-1Ra in the treatment of CIM induced by different chemoagents and their combination. Normal as well as tumor-bearing mice were administered oxaliplatin (L-OHP), 5-fluorouracil, or their combination to induce intestinal mucositis and mortality. rhIL-1Ra administered after the chemotherapy, but not after the onset of diarrhea, significantly improved mouse survival, attenuated body weight loss, and reduced the incidence, severity, and duration of diarrhea. Histological examination showed that rhIL-1Ra-treated mice had a relatively intact mucosa structure, more proliferating crypt cells, and higher acid mucin content than the vehicle-treated mice. rhIL-1Ra suppressed crypt apoptosis by reducing the levels of proapoptotic proteins in wild-type, but not in IL-1RI or p53 mice. In addition, rhIL-1Ra was as effective as octreotide acetate in the treatment of chemotherapy-induced diarrhea, but with the advantage of reducing the epithelial apoptosis, the major cause of CIM. Importantly, the tumor sensitivity to chemotherapy was not affected by rhIL-1Ra. Thus, our data strongly suggest that rhIL-1Ra may be useful for the treatment of intestinal mucositis and improving the quality of life for cancer patients on chemotherapy.

  7. Neutrophil activation in ivermectin-treated onchocerciasis patients.

    PubMed Central

    Njoo, F L; Hack, C E; Oosting, J; Stilma, J S; Kijlstra, A

    1993-01-01

    Ivermectin is a safe and effective drug for onchocerciasis treatment. In certain individuals, however, therapy is accompanied by adverse reactions. The mechanisms underlying these reactions are not yet known. The aim of the present study was to investigate whether neutrophils are involved in the development of these adverse reactions. Elastase and lactoferrin, two markers for the release of neutrophil azurophilic and specific granule contents respectively, were measured by radioimmunoassays in plasma of onchocerciasis patients with varying degrees of side effects, as well as in control subjects before and 1 and 2 days after ivermectin treatment. A considerable increase of elastase levels after treatment was observed, whereas lactoferrin levels did not change. The percentage of patients with elevated elastase levels was significantly correlated with the degree of side effects. These findings suggest that neutrophil activation may be involved in the development of adverse reactions in these patients. PMID:8222324

  8. Paraoxonase Activity and Oxidative Status in Patients with Tinnitus

    PubMed Central

    Akyüz, Servet; Somuk, Battal Tahsin; Soyalic, Harun; Yılmaz, Beyhan; Taskin, Abdullah; Bilinc, Hasan; Aksoy, Nurten

    2016-01-01

    Background and Objectives The aim of this study was to investigate serum paraoxanase-1 (PON) activity, total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) in tinnitus; and to compare the results with data from healthy subjects. Subjects and Methods A total of 114 subjects-54 patients with tinnitus and 60 healthy controls were enrolled in this study. Serum PON activity, TOS, TAS, and OSI levels were measured. Results In the tinnitus group, TAS, and PON were significantly lower than in the control group (p<0.001). However, the TOS, and OSI levels were significantly higher in the tinnitus group than in the control group (p<0.001). Conclusions According to the data obtained from the present study, patients with tinnitus were exposed to potent oxidative stress. Oxidative stress may be the key contributing factor to the pathogenesis of tinnitus. PMID:27144229

  9. Assessing physical function and physical activity in patients with CKD.

    PubMed

    Painter, Patricia; Marcus, Robin L

    2013-05-01

    Patients with CKD are characterized by low levels of physical functioning, which, along with low physical activity, predict poor outcomes in those treated with dialysis. The hallmark of clinical care in geriatric practice and geriatric research is the orientation to and assessment of physical function and functional limitations. Although there is increasing interest in physical function and physical activity in patients with CKD, the nephrology field has not focused on this aspect of care. This paper provides an in-depth review of the measurement of physical function and physical activity. It focuses on physiologic impairments and physical performance limitations (impaired mobility and functional limitations). The review is based on established frameworks of physical impairment and functional limitations that have guided research in physical function in the aging population. Definitions and measures for physiologic impairments, physical performance limitations, self-reported function, and physical activity are presented. On the basis of the information presented, recommendations for incorporating routine assessment of physical function and encouragement for physical activity in clinical care are provided.

  10. Arterial stiffness is not increased in patients with short duration rheumatoid arthritis and ankylosing spondylitis.

    PubMed

    Dzieża-Grudnik, Anna; Sulicka, Joanna; Strach, Magdalena; Siga, Olga; Klimek, Ewa; Korkosz, Mariusz; Grodzicki, Tomasz

    2017-04-01

    Patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have increased cardiovascular (CV) morbidity and mortality. Arterial stiffness is an independent predictor of CV events. The aim of the study was to assess arterial stiffness and inflammatory markers in patients with short duration chronic arthritis. We assessed carotid-femoral pulse wave velocity (PWV), augmentation index (AIx), traditional CV risk factors and inflammatory and endothelial markers in 71 chronic arthritis patients (RA and AS) and in 29 healthy controls. We did not find differences in PWV (for RA, AS and controls, respectively: 10 [8.8-10.9] versus 10.7 [9.1-11.8] versus 9.2 [8.3-11.4] m/s; p = .14) and AIx (for RA, AS and controls, respectively: 24.3 ± 11.5 versus 5.7 ± 12.4 versus 10 ± 12.8%; p = .22). Both groups of arthritis patients had active disease with significantly elevated inflammatory markers compared to controls. There were no correlations between endothelial and inflammatory markers and parameters of arterial stiffness in arthritis patients. When analyzing arthritis patients according to median of PVW, there were no significant differences in inflammatory and endothelial markers. We found that in patients with short duration active RA and AS arterial stiffness was not increased and furthermore, there was no association between markers of systemic inflammation and arterial stiffness.

  11. Muscular activity may improve in edentulous patients after implant treatment.

    PubMed

    Afrashtehfar, Kelvin I; Schimmel, Martin

    2016-12-01

    Data sourcesMedline via Pubmed and the Cochrane Library were searched from January 1980 to September 2013. This was complemented by a manual search of the magazines Deutsche Zahnaerztliche Zeitung, Quintessenz, Zeitschrift für Zahnärztliche Implantologie, Schweizerische Monatszeitschrift and Implantologie. Additionally, the list of reference s of all selected full-text articles and related reviews were further scrutinised for potential included studies in English or German.Study selectionThree review authors independently searched for clinical trials that assessed the muscular activity in the intervention groups: edentulous patients treated with implant-overdentures (IODs) and implant-supported fixed dental prostheses (ISFDPs) and the comparison groups: dentates and edentulous patients treated with mucosa-borne complete removable dental prostheses (CRDPs).Data extraction and synthesisThe primary outcome was the muscular activity (measured by electromyography [EMG]) in masseter or temporalis muscle of the participants during clenching and chewing. The data extraction of each included study consisted of author, year, age range, treatment, number of participants, number of implants inserted, arch treated, opposite jaw, kind and side of the muscles that were measured. EMG gain or loss (unit measured: volt) was considered by using the effect size. For the meta-analyses only the studies that included masseter muscle measured separately from temporalis were considered. Concerning the side of measurement (right and left side measured together or right and left side measured separately), only the dominant type in each category was included.ResultsSixteen articles, out of the initial 646 retrieved abstracts, were analysed. The muscular activity of edentulous subjects increased after implant support therapy during clenching (effect size [ES]: 2.18 [95% confidence interval [CI]: 1.14, 3.23]) and during chewing (ES: 1.45 [95 % CI: 1.21, 1.69]). In addition, the pooled EMG

  12. Challenges of developing a cardiovascular risk calculator for patients with rheumatoid arthritis

    PubMed Central

    Rollefstad, Silvia; Kitas, George D.; van Riel, Piet L. C. M.; Gabriel, Sherine E.; Semb, Anne Grete

    2017-01-01

    Objective Cardiovascular disease (CVD) risk calculators designed for use in the general population do not accurately predict the risk of CVD among patients with rheumatoid arthritis (RA), who are at increased risk of CVD. The process of developing risk prediction models involves numerous issues. Our goal was to develop a CVD risk calculator for patients with RA. Methods Thirteen cohorts of patients with RA originating from 10 different countries (UK, Norway, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico) were combined. CVD risk factors and RA characteristics at baseline, in addition to information on CVD outcomes were collected. Cox models were used to develop a CVD risk calculator, considering traditional CVD risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration with 10-fold cross-validation. Results A total of 5638 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 76% female). During a mean follow-up of 5.8 years (30139 person years), 389 patients developed a CVD event. Event rates varied between cohorts, necessitating inclusion of high and low risk strata in the models. The multivariable analyses revealed 2 risk prediction models including either a disease activity score including a 28 joint count and erythrocyte sedimentation rate (DAS28ESR) or a health assessment questionnaire (HAQ) along with age, sex, presence of hypertension, current smoking and ratio of total cholesterol to high-density lipoprotein cholesterol. Unfortunately, performance of these models was similar to general population CVD risk calculators. Conclusion Efforts to develop a specific CVD risk calculator for patients with RA yielded 2 potential models including RA disease characteristics, but neither demonstrated improved performance compared to risk calculators designed for use in the general population. Challenges encountered and lessons learned are discussed in detail. PMID

  13. Postmenopausal loss of Ra acquired in adolescence or young adulthood: quantitative relationship to radiation-induced skeletal damage and dosimetric implications

    SciTech Connect

    Keane, A.T.; Rundo, J.; Essling, M.A.

    1988-05-01

    From the results of serial measurements of body /sup 226/Ra activity in 13 former luminous dial workers 30-60 y after relatively brief periods of intake of luminous compounds in adolescence or young adulthood, we determined the postmenopausal rate of elimination of Ra in percent of contemporary body Ra content per year. This rate was negatively correlated with the reduced x-ray score, a measure of radiation osteonecrosis observed radiographically in the 13 subjects (r = -0.85, P less than 0.001). The clearance rates of subjects retaining low Ra activity were greater than predicted by retention models. We conclude that for those members of the Ra-exposed population under study for health effects at our institution who sustained the lesser degrees of macroscopic skeletal damage, present estimates of skeletal absorbed dose are systematically low, by at most a factor of 2.

  14. Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

    SciTech Connect

    Fang, Xian-Ying; Chen, Wei; Fan, Jun-Ting; Song, Ran; Wang, Lu; Gu, Yan-Hong; Zeng, Guang-Zhi; Shen, Yan; Wu, Xue-Feng; Tan, Ning-Hua; Xu, Qiang; Sun, Yang

    2013-02-15

    In the present paper, we examined the effects of a natural cyclopeptide RA-V on human breast cancer cells and the underlying mechanisms. RA-V significantly inhibited the growth of human breast cancer MCF-7, MDA-MB-231 cells and murine breast cancer 4T1 cells. In addition, RA-V triggered mitochondrial apoptotic pathway which was indicated by the loss of mitochondrial membrane potential, the release of cytochrome c, and the activation of caspase cascade. Further study showed that RA-V dramatically inhibited phosphorylation of AKT and 3-phosphoinositide dependent protein kinase 1 (PDK1) in MCF-7 cells. Moreover, RA-V disrupted the interaction between PDK1 and AKT in MCF-7 cells. Furthermore, RA-V-induced apoptosis could be enhanced by phosphatidylinositol 3-kinase inhibitor or attenuated by over-expression of AKT in all the three kinds of breast cancer cells. Taken together, this study shows that RA-V, which can induce mitochondria-mediated apoptosis, exerts strong anti-tumor activity against human breast cancer. The underlying anti-cancer mechanism of RA-V is related to the blockage of the interaction between PDK1 and AKT. - Highlights: ► Plant cyclopeptide RA-V kills human breast cancer cells. ► RA-V triggered mitochondrial apoptotic pathway in human breast cancer cells. ► RA-V inhibited phosphorylation of AKT and PDK1 in breast cancer MCF-7 cells. ► Its mechanism is related to the blockage of the interaction between PDK1 and AKT.

  15. Concurrent determination of 224Ra, 226Ra, 228Ra, and unsupported 212Pb in a single analysis for drinking water and wastewater: dissolved and suspended fractions.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail

    2004-02-01

    A technique has been developed for the measurement of 224Ra, 226Ra, 228Ra, and unsupported 2t2Pb concurrently in a single analysis. The procedure can be applied to both drinking water and wastewater, including the dissolved and suspended fractions of a sample. For drinking water samples, using 3-L aliquots, the radium isotopes are isolated by a fast PbSO4 co-precipitation and then quantified by gamma-ray spectroscopy. The radium isotopes 224Ra, 226Ra, and 228Ra are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb (and/or 214Bi), and 228Ac, respectively. Because of the short half-life of 224Ra (T1/2 = 3.66 d), the precipitate should be counted within 4 d of the sample collection date. In case the measurement of unsupported 212Pb (T1/2 = 10.64 h) is required, the gamma-ray analysis should be initiated as soon as possible, preferably on the same day of collection. The counting is repeated after about 21 d to ensure the 226Ra progeny are in equilibrium with their parent. At this point, the 228Ac equilibration with its 228Ra parent is already established. In the case of samples containing suspended materials, an aliquot of sample is filtered and then the filtrate is treated as described above for drinking water samples. The suspended fraction of sample, collected on the filter, is directly analyzed by gamma-ray spectroscopy with no further chemical separation. Aliquots of de-ionized water spiked with various radium standards were analyzed to check the accuracy and precision of the method. In addition, analysis results of actual samples using this method were compared with the ones performed using U.S. Environmental Protection Agency-approved procedures, and the measured values were in close agreement. This method simplifies the analytical procedures and reduces the labor while achieving the precision, accuracy, and minimum detection concentration requirements of EPA's Regulations.

  16. Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid arthritis using LC-MALDI-TOF/TOF.

    PubMed

    Wang, Fei; Chen, Fang-Fang; Gao, Wen-Bo; Wang, Hai-Yong; Zhao, Ning-Wei; Xu, Min; Gao, De-Yu; Yu, Wei; Yan, Xiao-Ling; Zhao, Jian-Ning; Li, Xiao-Jun

    2016-09-01

    The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA.

  17. Leaching of 226Ra from components of uranium mill tailings

    USGS Publications Warehouse

    Landa, E.R.

    1991-01-01

    A sequential extraction procedure was used to characterize the geochemical forms of 226Ra retained by mixtures of quartz sand and a variety of fine-grained rock and mineral species. These mixtures had previously been exposed to the sulfuric acid milling liquor of a simulated acid-leach uranium milling circuit. For most test cases, the major fraction of the 226Ra was extracted with 1 mol/1 NH4Cl and was deemed to be exchangeable. However, 226Ra retained by the barite-containing mixture was resistant to both 1 mol/1 NH4Cl and 1 mol/HCHCl extraction. ?? 1991.

  18. The Role of Retinoic Acid (RA) in Spermatogonial Differentiation.

    PubMed

    Busada, Jonathan T; Geyer, Christopher B

    2016-01-01

    Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia.

  19. Treatment of rheumatoid arthritis (RA) in India-how and by whom: results from a speciality clinic-use of low-dose methotrexate (MTX) was inexplicably suboptimal.

    PubMed

    Malaviya, Anand N; Gogia, S B

    2016-09-01

    This study was conducted in order to study (a) seropositive RA patients for their prior caregivers, diagnosis makers, drugs and doses taken and (b) the disease status at the first visit and the last visit, from the standpoint of whether they received optimum or suboptimum DMARD treatment. Prospectively entered data were extracted from a rheumatology-specific electronic health record for demography, diagnostic delay, prior caregivers, diagnosis makers, intake of DMARDs and glucocorticoids and disease activity state at first presentation and at the last visit using structured query language. Among 316 patients, prior caregivers were orthopaedicians (73.4 %), alternative systems of medicine practitioners (62 %), internists (38 %), rheumatologists (35.8 %), general practitioners (17 %) and others (12 %). The diagnosis of RA was made by rheumatologists (55.6 %), orthopaedicians (21 %), internists (12.6 %), physiotherapists (3.5 %), homeopaths (2.8 %), general practitioner (2.1 %), neurologists (1.4 %) and Ayurvedic physicians (0.7 %). The mean and the median diagnostic delay among 142 patients where information was available were 18 and 8.5 months, respectively (SD +23.2). Thirty-two percent of the patients had early disease, 48 % established disease and 20 % late disease at presentation. Sixty-six percent of the patients had taken DMARDs-methotrexate (56 %), hydroxychloroquine (46.2 %), leflunomide (18.7 %) and sulfasalazine (20.6 %)-and often in combinations. Different preparations, doses and schedules of glucocorticoids were taken orally or parentally by 51 %. Only one (0.3 %) patient had taken biological DMARDs prior to visiting this clinic. High or moderate disease activity was present in 84 % at the first clinic visit that fell to 14 % at the last clinic visit. The majority of patients with RA were treated by orthopaedicians and practitioners of alternative systems of medicine with only a third by rheumatologists. In 80 % of patients, the

  20. Opsonic activity of blister fluid from burn patients.

    PubMed Central

    Deitch, E A

    1983-01-01

    The combination of skin loss and immune depression after thermal injury predisposes burn patients to an increased risk of infection. Since the commonest site of infection in the burn patient is the burn wound itself, we elected to study the opsonic activity of locally produced blister fluid, from 18 thermally injured patients, for the two most common organisms colonizing the burn wound (Pseudomonas aeruginosa and Staphylococcus aureus). Blister fluid was as good an opsonin source for staphylococcus as normal serum. In contrast, the blister fluid did not support either the phagocytosis of the intracellular killing of P. aeruginosa. The poor opsonic activity of blister fluid for P. aeruginosa did not appear to be due to the presence of an inhibitory factor(s) since the addition of normal serum restored the opsonic activity of the blister fluid to normal. The concentrations of immunoglobulins and the complement components C3 and C4 in the blister fluid samples were less than half the level of those in normal serum. The opsonic activity of the blister fluid could not be restored to normal by the addition of either immunoglobulin or heat-inactivated serum (56 degrees C for 30 min). Thus, the opsonic factor(s) missing from the blister fluid was heat labile and thus probably represents complement components. That blister fluid had impaired opsonic activity for P. aeruginosa but not for S. aureus indicated that a local humoral defect may be responsible, at least in part, for the high incidence of gram-negative organisms, especially pseudomonads, colonizing the burn wound after thermal injury. PMID:6411619

  1. Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products

    PubMed Central

    Paoliello-Paschoalato, Adriana Balbina; Marchi, Larissa Fávaro; de Andrade, Micássio Fernandes; Kabeya, Luciana Mariko; Donadi, Eduardo Antônio; Lucisano-Valim, Yara Maria

    2015-01-01

    Rheumatoid arthritis (RA) is a highly disabling disease that affects all structures of the joint and significantly impacts on morbidity and mortality in RA patients. RA is characterized by persistent inflammation of the synovial membrane lining the joint associated with infiltration of immune cells. Eighty to 90% of the leukocytes infiltrating the synovia are neutrophils. The specific role that neutrophils play in the onset of RA is not clear, but recent studies have evidenced that they have an important participation in joint damage and disease progression through the release of proteolytic enzymes, reactive oxygen species (ROS), cytokines, and neutrophil extracellular traps, in particular during frustrated phagocytosis of immune complexes (ICs). In addition, the local and systemic activation of the complement system contributes to the pathogenesis of RA and other IC-mediated diseases. This review discusses (i) the participation of Fcγ and complement receptors in mediating the effector functions of neutrophils in RA; (ii) the contribution of the complement system and ROS-dependent and ROS-independent mechanisms to joint damage in RA; and (iii) the use of plant extracts, dietary compounds, and isolated natural compounds in the treatment of RA, focusing on modulation of the effector functions of neutrophils and the complement system activity and/or activation. PMID:26346244

  2. Search for possible solar influences in Ra-226 decays

    NASA Astrophysics Data System (ADS)

    Stancil, Daniel D.; Balci Yegen, Sümeyra; Dickey, David A.; Gould, Chris R.

    Measurements of Ra-226 activity from eight HPGe gamma ray detectors at the NC State University PULSTAR Reactor were analyzed for evidence of periodic variations, with particular attention to annual variations. All measurements were made using the same reference source, and data sets were of varying length taken over the time period from September 1996 through August 2014. Clear evidence of annual variations was observed in data from four of the detectors. Short time periodograms from the data sets suggest temporal variability of both the amplitude and frequency of these variations. The annual variations in two of the data sets show peak values near the first of February, while surprisingly, the annual variations in the other two are roughly out of phase with the first two. Three of the four detectors exhibited annual variations over approximately the same time period. A joint statistic constructed by combining spectra from these three shows peaks approximating the frequencies of solar r-mode oscillations with νR = 11.74 cpy, m = 1, and l = 3, 5, 6. The fact that similar variations were not present in all detectors covering similar time periods rules out variations in activity as the cause, and points to differing sensitivities to unspecified environmental parameters instead. In addition to seasonal variations, the modulation of environmental parameters by solar processes remains a possible explanation of periodogram features, but without requiring new physics.

  3. Immune Recognition of Citrullinated Proteoglycan Aggrecan Epitopes in Mice with Proteoglycan-Induced Arthritis and in Patients with Rheumatoid Arthritis

    PubMed Central

    Markovics, Adrienn; Ocskó, Tímea; Katz, Robert S.; Buzás, Edit I.; Glant, Tibor T.

    2016-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune inflammatory disease affecting the joints. Anti-citrullinated protein antibodies (ACPA) are frequently found in RA. Previous studies identified a citrullinated epitope in cartilage proteoglycan (PG) aggrecan that elicited pro-inflammatory cytokine production by RA T cells. We recently reported the presence of ACPA-reactive (citrullinated) PG in RA cartilage. Herein, we sought to identify additional citrullinated epitopes in human PG that are recognized by T cells or antibodies from RA patients. Methods We used mice with PG-induced arthritis (PGIA) as a screening tool to select citrulline (Cit)-containing PG peptides that were more immunogenic than the arginine (R)-containing counterparts. The selected peptide pairs were tested for induction of pro-inflammatory T-cell cytokine production in RA and healthy control peripheral blood mononuclear cell (PBMC) cultures using ELISA and flow cytometry. Anti-Cit and anti-R peptide antibodies were detected by ELISA. Results Splenocytes from mice with PGIA exhibited greater T-cell cytokine secretion in response to the Cit than the R version of PG peptide 49 (P49) and anti-P49 antibodies were found in PGIA serum. PBMC from ACPA+ and ACPA- RA patients, but not from healthy controls, responded to Cit49 with robust cytokine production. High levels of anti-Cit49 antibodies were found in the plasma of a subset of ACPA+ RA patients. Another PG peptide (Cit13) similar to the previously described T-cell epitope induced greater cytokine responses than R13 by control (but not RA) PBMC, however, anti-Cit13 antibodies were rarely detected in human plasma. Conclusions We identified a novel citrullinated PG epitope (Cit49) that is highly immunogenic in mice with PGIA and in RA patients. We also describe T-cell and antibody reactivity with Cit49 in ACPA+ RA. As citrullinated PG might be present in RA articular cartilage, Cit PG epitope-induced T-cell activation or antibody deposition may

  4. Relationship between patient-reported and objective measurements of hand function in patients with rheumatoid arthritis.

    PubMed

    Günay, S M; Tuna, Z; Oskay, D

    2016-12-31

    Rheumatoid arthritis (RA) often results in impairments in upper extremities, especially in the small joints of hand. Involvement of hand brings limitations in activities of daily living. However, it is commonly observed that patient-reported functional status of hand does not always corresponds to their actual physical performance in the clinical setting. The aim of this pilot study is to investigate the relationship between patient self-reported and objectively measured hand functions in patients with RA. Twenty-six patients (51±13 years) with RA diagnosis participated in the study. Hand grip and pinch (lateral, bipod, tripod) strengths were measured and Jebsen Hand Function Test (JHFT) was performed for objective functional performance. Duruöz Hand Index and Beck Depression Inventory - Turkish version were completed by patients. Grip and all three-pinch strength results significantly correlated with Duruöz Hand Index scores (p<0.05). JHFT results except the sentence writing also correlated with the Duruöz scores (p<0.05). Our results showed that self-reported outcome scales might be used for determining functional level of hand in patients with RA in rheumatology practice. Objective quantitative functional tests are the best methods in evaluating functional level of hand, but require valid and reliable equipment with accurate calibration. Therefore, in case of unavailability of objective assessment tools, patient-reported scales may also reflect the real status of hand functions.

  5. Treatment with Dexamethasone and Monophosphoryl Lipid A Removes Disease-Associated Transcriptional Signatures in Monocyte-Derived Dendritic Cells from Rheumatoid Arthritis Patients and Confers Tolerogenic Features

    PubMed Central

    García-González, Paulina A.; Schinnerling, Katina; Sepúlveda-Gutiérrez, Alejandro; Maggi, Jaxaira; Hoyos, Lorena; Morales, Rodrigo A.; Mehdi, Ahmed M.; Nel, Hendrik J.; Soto, Lilian; Pesce, Bárbara; Molina, María Carmen; Cuchacovich, Miguel; Larrondo, Milton L.; Neira, Óscar; Catalán, Diego Francisco; Hilkens, Catharien M.; Thomas, Ranjeny; Verdugo, Ricardo A.; Aguillón, Juan C.

    2016-01-01

    Tolerogenic dendritic cells (TolDCs) are promising tools for therapy of autoimmune diseases, such as rheumatoid arthritis (RA). Here, we characterize monocyte-derived TolDCs from RA patients modulated with dexamethasone and activated with monophosphoryl lipid A (MPLA), referred to as MPLA-tDCs, in terms of gene expression, phenotype, cytokine profile, migratory properties, and T cell-stimulatory capacity in order to explore their suitability for cellular therapy. MPLA-tDCs derived from RA patients displayed an anti-inflammatory profile with reduced expression of co-stimulatory molecules and high IL-10/IL-12 ratio, but were capable of migrating toward the lymphoid chemokines CXCL12 and CCL19. These MPLA-tDCs induced hyporesponsiveness of autologous CD4+ T cells specific for synovial antigens in vitro. Global transcriptome analysis confirmed a unique transcriptional profile of MPLA-tDCs and revealed that RA-associated genes, which were upregulated in untreated DCs from RA patients, returned to expression levels of healthy donor-derived DCs after treatment with dexamethasone and MPLA. Thus, monocyte-derived DCs from RA patients have the capacity to develop tolerogenic features at transcriptional as well as at translational level, when modulated with dexamethasone and MPLA, overcoming disease-related effects. Furthermore, the ability of MPLA-tDCs to impair T cell responses to synovial antigens validates their potential as cellular treatment for RA. PMID:27826300

  6. Cyclopeptide RA-V inhibits angiogenesis by down-regulating ERK1/2 phosphorylation in HUVEC and HMEC-1 endothelial cells

    PubMed Central

    Yue, Grace GL; Fan, Jun-Ting; Lee, Julia KM; Zeng, Guang-Zhi; Ho, Tina WF; Fung, Kwok-Pui; Leung, Ping-Chung; Tan, Ning-Hua; Lau, Clara BS

    2011-01-01

    BACKGROUND AND PURPOSE Anti-angiogenic agents have recently become one of the major adjuvants for cancer therapy. A cyclopeptide, RA-V, has been shown to have anti-tumour activities. Its in vitro anti-angiogenic activities were evaluated in the present study, and the underlying mechanisms were also assessed. EXPERIMENTAL APPROACH Two endothelial cell lines, human umbilical vein endothelial cells (HUVEC) and human microvascular endothelial cells (HMEC-1), were used. The effects of RA-V on the proliferation, cell cycle phase distribution, migration, tube formation and adhesion were assessed. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant molecules. KEY RESULTS RA-V inhibited HUVEC and HMEC-1 proliferation dose-dependently with IC50 values of 1.42 and 4.0 nM respectively. RA-V inhibited migration and tube formation of endothelial cells as well as adhesion to extracellular matrix proteins. RA-V treatment down-regulated the protein and mRNA expression of matrix metalloproteinase-2. Regarding intracellular signal transduction, RA-V interfered with the activation of ERK1/2 in both cell lines. Furthermore, RA-V significantly decreased the phosphorylation of JNK in HUVEC whereas, in HMEC-1, p38 MAPK was decreased. CONCLUSIONS AND IMPLICATIONS RA-V exhibited anti-angiogenic activities in HUVEC and HMEC-1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA-V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA-V has the potential to be further developed as an anti-angiogenic agent. PMID:21518338

  7. Allelic polymorphism in IL-1 beta and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease.

    PubMed Central

    Bioque, G; Crusius, J B; Koutroubakis, I; Bouma, G; Kostense, P J; Meuwissen, S G; Peña, A S

    1995-01-01

    Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra) gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying allele 2 of this gene have increased production of IL-1Ra protein. Since the final outcome of the biological effects of IL-1 beta may depend on the relative proportion of these two cytokines, we have studied if a TaqI polymorphism in the IL-1 beta gene, which is relevant to IL-1 beta protein production, may be involved in the genetic susceptibility to UC and Crohn's disease (CD), in association with the established IL-1Ra gene polymorphism. Polymorphisms in the closely linked genes for IL-1 beta and IL-1Ra were typed in 100 unrelated Dutch patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in exon 5 of the IL-1 beta gene and in intron 2 of the IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based methods. The IL-1 beta allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1 beta gene polymorphism might participate synergistically with the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1 beta and IL-1Ra, in each of the patient groups and controls. Results indicated a significant association of this pair of genes, estimated by the odds ratio (OR) after performing Fisher's exact test, in the UC group (P = 0.023, OR = 2.81), as well as in the CD group (P = 0.01, OR = 3.79). Thus, non-carriers of IL-1 beta allele 2 were more often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the group of healthy controls (P = 1.00, OR = 0.92). These results suggest that the IL-1 beta/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel diseases. PMID:7586694

  8. Study of 223Ra uptake mechanism by Fe3O4 nanoparticles: towards new prospective theranostic SPIONs

    NASA Astrophysics Data System (ADS)

    Mokhodoeva, Olga; Vlk, Martin; Málková, Eva; Kukleva, Ekaterina; Mičolová, Petra; Štamberg, Karel; Šlouf, Miroslav; Dzhenloda, Rustam; Kozempel, Ján

    2016-10-01

    The use of superparamagnetic iron oxide nanoparticles ( SPIONs) and radiolabelled nanoparticles ( NPs) has grown considerably over the recent years, and the SPIONs labelled with medicinal radionuclides offer new opportunities in multimodal diagnostics and in the drug-delivery systems for targeted alpha-particle therapy (TAT) driven by magnetic field gradient or by biologically active moieties bound on NPs shell. However, the mechanisms of NPs radiolabelling are not studied substantially and still remain unclear, even though the way of label attachment directly implies the stability of the label-nanoparticle construct. Since the 223Ra was the first clinically approved alpha-emitter, it is a promising nuclide for further development of its targeted carriers. We report here on the study of 223Ra uptake by the Fe3O4 SPIONs, together with an attempt to propose the 223Ra uptake mechanism by the Fe3O4 NPs in the presence of a phosphate buffer a typical formulation medium, under the pseudo-equilibrium conditions. Further, the in vitro stability tests of the prepared [223Ra]Fe3O4 NPs were performed to estimate the 223Ra label stability. The potential use of 223Ra-labelled SPIONs in theranostic applications is also discussed.

  9. Evidence for brain glial activation in chronic pain patients.

    PubMed

    Loggia, Marco L; Chonde, Daniel B; Akeju, Oluwaseun; Arabasz, Grae; Catana, Ciprian; Edwards, Robert R; Hill, Elena; Hsu, Shirley; Izquierdo-Garcia, David; Ji, Ru-Rong; Riley, Misha; Wasan, Ajay D; Zürcher, Nicole R; Albrecht, Daniel S; Vangel, Mark G; Rosen, Bruce R; Napadow, Vitaly; Hooker, Jacob M

    2015-03-01

    Although substantial evidence has established that microglia and astrocytes play a key role in the establishment and maintenance of persistent pain in animal models, the role of glial cells in human pain disorders remains unknown. Here, using the novel technology of integrated positron emission tomography-magnetic resonance imaging and the recently developed radioligand (11)C-PBR28, we show increased brain levels of the translocator protein (TSPO), a marker of glial activation, in patients with chronic low back pain. As the Ala147Thr polymorphism in the TSPO gene affects binding affinity for (11)C-PBR28, nine patient-control pairs were identified from a larger sample of subjects screened and genotyped, and compared in a matched-pairs design, in which each patient was matched to a TSPO polymorphism-, age- and sex-matched control subject (seven Ala/Ala and two Ala/Thr, five males and four females in each group; median age difference: 1 year; age range: 29-63 for patients and 28-65 for controls). Standardized uptake values normalized to whole brain were significantly higher in patients than controls in multiple brain regions, including thalamus and the putative somatosensory representations of the lumbar spine and leg. The thalamic levels of TSPO were negatively correlated with clinical pain and circulating levels of the proinflammatory citokine interleukin-6, suggesting that TSPO expression exerts pain-protective/anti-inflammatory effects in humans, as predicted by animal studies. Given the putative role of activated glia in the establishment and or maintenance of persistent pain, the present findings offer clinical implications that may serve to guide future studies of the pathophysiology and management of a variety of persistent pain conditions.

  10. RANK Expression and Osteoclastogenesis in Human Monocytes in Peripheral Blood from Rheumatoid Arthritis Patients

    PubMed Central

    Kobashigawa, Tsuyoshi

    2016-01-01

    Rheumatoid arthritis (RA) appears as inflammation of synovial tissue and joint destruction. Receptor activator of NF-κB (RANK) is a member of the TNF receptor superfamily and a receptor for the RANK ligand (RANKL). In this study, we examined the expression of RANKhigh and CCR6 on CD14+ monocytes from patients with RA and healthy volunteers. Peripheral blood samples were obtained from both the RA patients and the healthy volunteers. Osteoclastogenesis from monocytes was induced by RANKL and M-CSF in vitro. To study the expression of RANKhigh and CCR6 on CD14+ monocytes, two-color flow cytometry was performed. Levels of expression of RANK on monocytes were significantly correlated with the level of osteoclastogenesis in the healthy volunteers. The expression of RANKhigh on CD14+ monocyte in RA patients without treatment was elevated and that in those receiving treatment was decreased. In addition, the high-level expression of RANK on CD14+ monocytes was correlated with the high-level expression of CCR6 in healthy volunteers. Monocytes expressing both RANK and CCR6 differentiate into osteoclasts. The expression of CD14+RANKhigh in untreated RA patients was elevated. RANK and CCR6 expressed on monocytes may be novel targets for the regulation of bone resorption in RA and osteoporosis. PMID:27822475

  11. [Gallbladder motor activity in patients with virus hepatitis B].

    PubMed

    Mamos, Arkadiusz; Wichan, Paweł; Chojnacki, Jan; Grzegorczyk, Krzysztof

    2003-12-01

    In acute stage of virus hepatitis B patients often complain of dyspeptic discomfort. They may be a consequence of alimentary tract motor activity disorders including these of gallbladder. Routine ultrasonography in an early phase of virus hepatitis often reveals gallbladder wall thickening what may confirm the above thesis. Thus, a group of 15 patients in an acute phase of virus hepatitis B was subjected to examinations. Gallbladder motor activity was assessed by ultrasonographic method determining its total volume and ejection fraction and volume after test meal stimulus. First examination was performed in the first week since the appearance of yellowing of the walls, successive in 4 and 8 week of the disease. Obtained results were compared to the values obtained in the group of 25 healthy volunteers. It was found out that gallbladder volume was significantly decreased and ejection fraction increased in the acute phase of virus hepatitis B than in the controls. This may speak for gallbladder hyperreactivity in patients in the course of virus hepatitis B. These disorders decreased during two-month observation but even in the 8 week the investigated parameters differed from those found in the control group.

  12. Reduced killer cell activity of lymphocytes from patients with asbestosis.

    PubMed Central

    Kubota, M; Kagamimori, S; Yokoyama, K; Okada, A

    1985-01-01

    Immunological abnormalities in 30 patients with asbestosis were investigated by examining the cytoxicity of natural killer (NK) cells and antibody dependent cellular cytotoxicity by killer (K) cells from peripheral blood lymphocytes; the effects of interferon on NK activity was also examined. Fifteen men and 15 women (mean age 58; range 40-72) with asbestosis but who were free of complications such as tuberculosis, carcinoma, or steroid treatment were the subjects for study. There were nine cases of type 1, 19 cases of type 2, and two cases of type 3 disease as described in the ILO classification of pneumoconiosis. They were all textile workers with a mean duration of 18 years (3-40 years) since first exposure to chrysotile. Controls matched for age and sex were selected from a population without occupational exposure to asbestos. The activity of the NK and K cells in patients with asbestosis was significantly lower than in the control group, but the populations of NK and K cells in the peripheral blood lymphocytes were not significantly different in the two groups. An in vitro experiment showed that the increase in the cytotoxicity of the NK cell after treatment with interferon-alpha was significantly lower in the subjects than in the controls. These results indicate that one of the defence mechanisms in relation to cancer is deficient in patients with asbestosis. PMID:3978049

  13. Bortezomib followed by autologous stem cell transplantation in a patient with rheumatoid arthritis

    PubMed Central

    Liu, Junru; Li, Juan; Chen, Meilan; Kuang, Lifen

    2016-01-01

    Abstract Rationale and Patients concerns: Despite the introduction of varied disease-modifying antirheumatic drugs and biological agents, a substantial proportion of patients remain untreatable. We report a 56-year-old Chinese female patient with a case of refractory rheumatoid arthritis (RA) complicated with multiple myeloma (MM) who was treated successfully with Bortezomib followed by autologous stem cell transplantation (ASCT). Diagnosis and Interventions: We report a 56-year-old Chinese female patient who was diagnosed as RA complicating with MM. She received 4 cycles of Bortezomib-based chemotherapy followed by ASCT. The response of her RA and MM were evaluated after every cycle of Bortezomib-based chemotherapy. Interventions and Outcomes: After the first Bortezomib-based chemotherapy cycle, this patient's symptoms were significantly alleviated and thereafter the RA activity continued to improve. After the 4 courses of Bortezomib-based chemotherapy, the C-reactive protein was <0.5 mg/dL and the disease activity score 28-erythrocyte sedimentation rate was 2.0. No hematological or nonhematological side effects were observed during the treatment of Bortezomib. Lessons: Bortezomib might be a new safe and promising drug for refractory RA patients. PMID:28033292

  14. Rapid determination of 226Ra in emergency urine samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian K.; Hutchison, Jay B.; ...

    2014-02-27

    A new method has been developed at the Savannah River National Laboratory (SRNL) that can be used for the rapid determination of 226Ra in emergency urine samples following a radiological incident. If a radiological dispersive device event or a nuclear accident occurs, there will be an urgent need for rapid analyses of radionuclides in urine samples to ensure the safety of the public. Large numbers of urine samples will have to be analyzed very quickly. This new SRNL method was applied to 100 mL urine aliquots, however this method can be applied to smaller or larger sample aliquots as needed.more » The method was optimized for rapid turnaround times; urine samples may be prepared for counting in <3 h. A rapid calcium phosphate precipitation method was used to pre-concentrate 226Ra from the urine sample matrix, followed by removal of calcium by cation exchange separation. A stacked elution method using DGA Resin was used to purify the 226Ra during the cation exchange elution step. This approach combines the cation resin elution step with the simultaneous purification of 226Ra with DGA Resin, saving time. 133Ba was used instead of 225Ra as tracer to allow immediate counting; however, 225Ra can still be used as an option. The rapid purification of 226Ra to remove interferences using DGA Resin was compared with a slightly longer Ln Resin approach. A final barium sulfate micro-precipitation step was used with isopropanol present to reduce solubility; producing alpha spectrometry sources with peaks typically <40 keV FWHM (full width half max). This new rapid method is fast, has very high tracer yield (>90 %), and removes interferences effectively. The sample preparation method can also be adapted to ICP-MS measurement of 226Ra, with rapid removal of isobaric interferences.« less

  15. Routine Assessment of Patient Index Data 3 score (RAPID3) correlates well with Bath Ankylosing Spondylitis Disease Activity index (BASDAI) in the assessment of disease activity and monitoring progression of axial spondyloarthritis.

    PubMed

    Danve, Abhijeet; Reddy, Anusha; Vakil-Gilani, Kiana; Garg, Neha; Dinno, Alexis; Deodhar, Atul

    2015-01-01

    Routine Assessment of Patient Index Data 3 (RAPID3) is a composite index, very useful for assessment of disease activity of various rheumatic diseases including RA. If RAPID3 can also reliably measure disease activity in axial spondyloarthritis (axSpA), it may prove to be a practical and effective quantitative assessment tool in busy practices. We studied the association of RAPID3 with Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Patients with Ankylosing Spondylitis (AS) seen from 2007 to 2012 were classified as having AS or non-radiographic axial spondyloarthritis (nr-axSpA) using modified New York criteria and Assessment of SpondyloArthritis International Society criteria, respectively. Patients with simultaneous BASDAI and RAPID3 scores were enrolled (N = 112; 105 with AS, seven with nr-axSpA). Multiple regression and nonparametric receiver operating characteristics were used. Baseline mean (SD) BASDAI and RAPID3 were 4.2 (2.5) and 3.8 (2.3), respectively. Multiple linear regressions modeled a quadratic relationship between BASDAI and RAPID3 for 321 observations in 112 patients with axSpA (1) cross-sectionally: BASDAI predicted by RAPID3 (β = 1.171; s.e. = 0.113, p < 0.001) and RAPID3(2) (β = -0.037; s.e. = 0.014, p = 0.011) with an adjusted R (2) of 0.676; and (2) longitudinally: BASDAI predicted by RAPID3 (β = 1.196; s.e. = 0.111, p < 0.001), RAPID3(2) (β = -0.042; s.e. = 0.014, p = 0.004), and visit number (β = -0.142; s.e. = 0.038, p < 0.001) with an adjusted R (2) of 0.689. RAPID3 (correctly classified) corresponded to BASDAI scores of 2, 4, and 6: 1.40 (85.8 %), 3.33 (81.9 %), and 5.43 (87.1 %), respectively. RAPID3 correlates well with BASDAI in monitoring axSpA patients (including AS) in cross-sectional and longitudinal follow-up. Since it also correlates with measures of disease activity of other rheumatic diseases including RA, RAPID3 could be an attractive measure

  16. Concentration of {sup 226}Ra in human teeth

    SciTech Connect

    Yamamoto, Masayoishi; Ueno, Kaoru; Hinoide, Moriyo; Ohkubo, Yoshiteru

    1994-11-01

    {sup 226}Ra concentrations in human teeth from several cities, mainly Tokyo, Japan, were determined with emphasis on the measurement of low-level {sup 226}Ra by alpha-ray spectrometry following chemical separation. No appreciable differences in {sup 226}Ra concentration were found among various permanent teeth samples of different age groups in Tokyo. The mean {sup 226}Ra concentration for Tokyo was 0.51 {+-} 0.06 mBq (g CA){sup -1}. {sup 226}Ra concentration [mean: 0.67 {+-} 0.11 mBq (g Ca){sup -1}] in teeth in western regions of the country was statistically higher than that [mean: 0.48 {+-} 0.09 mBq (g Ca){sup -1}] in eastern ones. The mean {sup 226}Ra concentration [0.51 mBq (g CA){sup -1}] in teeth from Tokyo was less than the concentration [1.11 mBq (g CA){sup -1}] reported for vertebral bone samples of this city. 27 refs., 1 fig., 5 tabs.

  17. Vegetation composition and ²²⁶Ra uptake by native plant species at a uranium mill tailings impoundment in South China.

    PubMed

    Hu, Nan; Ding, Dexin; Li, Guangyue; Zheng, Jifang; Li, Le; Zhao, Weichao; Wang, Yongdong

    2014-03-01

    A field investigation was conducted for the vegetation composition and (226)Ra uptake by native plant species at a uranium mill tailings impoundment in South China. 80 species belonging to 67 genera in 32 families were recorded in the sampling sites. The Poaceae and Asteraceae were the dominant families colonizing the impoundment. The number of the plant species and vegetation community composition in the sampling sites seemed most closely related to the activities of (226)Ra and the pH value of the uranium tailings. The plant species in the sampling sites with relatively low activities of (226)Ra and relatively high pH value formed a relatively stable vegetation community. The plant species in the sampling sites with medium activities of (226)Ra and medium pH value formed the transitional vegetation community. The plant species in the sampling sites with relatively high activities of (226)Ra and relatively low pH value formed a simple unstable vegetation community that was similar to that on the unused grassland. The activities of (226)Ra and transfer factors (TFs) varied greatly with the plant species. The high activities of (226)Ra and TFs were found in the leaves of Pteris multifida (150.6 Bq/g of AW; 9.131), Pteridium aquilinum (122.2 Bq/g of AW; 7.409), and Dryopteris scottii (105.7 Bq/g of AW; 6.408). They satisfied the criteria for a hyperaccumulator for (226)Ra. They may be the candidates for phytoremediation of (226)Ra in the uranium mill tailings impoundment areas and the contaminated soils around.

  18. [Ultrasound densitometry of the heel bone in the diagnosis of osseous tissue metabolic abnormalities in patients with rheumatoid arthritis].

    PubMed

    Iakimenko, E A; Dets', V V; Tbileli, V V

    2001-01-01

    The implication was studied of such factors as occurrence of the affliction, sex, inflammation activity, joint functional inadequacies, intake of steroids in the development of osteopenia and osteoporosis in patients with rheumatoid arthritis (RA). Determined in the above patients were RRF, SOS, BUA with the aid of the ultrasonic densitometer UBIS 5000 of the DMS (FRANCIUM) firm. Of the 42 examined patients, osteoporosis was identified in 28.5 percent, osteopenia in 45.3 percent of cases, the degree associated with RA duration, inflammation activity, function disorders of the joints favored by intensification of processes of osteal resorption in rheumatoid arthritis.

  19. Active core rewarming avoids bioelectrical impedance changes in postanesthetic patients

    PubMed Central

    2011-01-01

    Background Postoperative hypothermia is a common cause of complications in patients who underwent laparoscopic cholecystectomy. Hypothermia is known to elicit electrophysiological, biochemical, and cellular alterations thus leading to changes in the active and passive membrane properties. These changes might influence the bioelectrical impedance (BI). Our aim was to determine whether the BI depends on the core temperature. Methods We studied 60 patients (52 female and 8 male) age 40 to 80 years with an ASA I-II classification that had undergone laparoscopic cholecystectomy under balanced inhalation anesthesia. The experimental group (n = 30) received active core rewarming during the transanesthetic and postanesthesic periods. The control group (n = 30) received passive external rewarming. The BI was recorded by using a 4-contact electrode system to collect dual sets of measurements in the deltoid muscle. The body temperature, hemodynamic variables, respiratory rate, blood-gas levels, biochemical parameters, and shivering were also measured. The Mann-Whitney unpaired t-test was used to determine the differences in shivering between each group at each measurement period. Measurements of body temperature, hemodynamics variables, respiratory rate, and BI were analyzed using the two-way repeated-measures ANOVA. Results The gradual decrease in the body temperature was followed by the BI increase over time. The highest BI values (95 ± 11 Ω) appeared when the lowest values of the temperature (35.5 ± 0.5°C) were reached. The active core rewarming kept the body temperature within the physiological range (over 36.5°C). This effect was accompanied by low stable values (68 ± 3 Ω) of BI. A significant decrease over time in the hemodynamic values, respiratory rate, and shivering was seen in the active core-rewarming group when compared with the controls. The temporal course of shivering was different from those of body temperatue and BI. The control patients showed a

  20. Self-Reported Childhood Maltreatment and Traumatic Events among Israeli Patients Suffering from Fibromyalgia and Rheumatoid Arthritis

    PubMed Central

    Hellou, Raneen; Brenner, Inbal; Buskila, Dan; Jacob, Giris; Elkayam, Ori; Aloush, Valerie

    2017-01-01

    Objective. The association between Fibromyalgia Syndrome (FMS) and childhood maltreatment and adversity has frequently been proposed but limited data exists regarding the transcultural nature of this association. Methods. 75 Israeli FMS patients and 23 Rheumatoid Arthritis (RA) patients were compared. Childhood maltreatment was assessed by the Childhood Trauma Questionnaire (CTQ) and potential depressive and anxiety disorders were assessed by the Patient Health Questionnaire-4. FMS severity was assessed by the Widespread Pain Index (WPI), the Symptom Severity Score (SSS), and the FIQ. PTSD was diagnosed according to the DSM IV. RA severity was assessed by the RA Disease Activity Index. Health status was assessed by the SF-36. Results. Similar to reports in other countries, high levels of self-reported childhood adversity were reported by Israeli FMS patients. PTSD was significantly more common among FMS patients compared with RA patients, as well as childhood emotional abuse and physical and emotional neglect. Levels of depression and anxiety were significantly higher among FMS patients. Conclusion. The study demonstrated the cross cultural association between FMS and childhood maltreatment, including neglect, emotional abuse, and PTSD. Significant differences were demonstrated between FMS patients and patients suffering from RA, a model of an inflammatory chronic rheumatic disease. PMID:28167861

  1. 76 FR 63701 - Culturally Significant Objects Imported for Exhibition Determinations: “Johan Zoffany RA: Society...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-13

    ... for Exhibition Determinations: ``Johan Zoffany RA: Society Observed'' SUMMARY: Notice is hereby given... objects to be included in the exhibition ``Johan Zoffany RA: Society Observed,'' imported from abroad...

  2. In rheumatoid arthritis patients treated with tocilizumab, the rate of clinical disease activity index (CDAI) remission at 24 weeks is superior in those with higher titers of IgM-rheumatoid factor at baseline.

    PubMed

    Kawashiri, Shin-Ya; Kawakami, Atsushi; Iwamoto, Naoki; Fujikawa, Keita; Aramaki, Toshiyuki; Tamai, Mami; Yamasaki, Satoshi; Nakamura, Hideki; Origuchi, Tomoki; Ueki, Yukitaka; Migita, Kiyoshi; Mizokami, Akinari; Aoyagi, Kiyoshi; Eguchi, Katsumi

    2011-08-01

    We aimed to evaluate the efficacy of tocilizumab in patients with rheumatoid arthritis (RA), using the clinical disease activity index (CDAI), and to determine the baseline variables associated with CDAI remission. Fifty-eight patients with active RA were enrolled. We tried to evaluate whether baseline variables were associated with CDAI remission at 24 weeks. Twenty-two of the 58 patients (37.9%) had received tumor necrosis factor (TNF) inhibitors. The continuation rate of tocilizumab at 24 weeks was 87.9%. The seropositivity rates of IgM-rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies at baseline were both 91.4%. The rate of CDAI remission at 24 weeks was 20.7%. We selected baseline variables including age, gender, duration of disease, concomitant use of glucocorticoids, concomitant use of methotrexate (MTX), previous anti-TNF therapy, titer of anti-CCP antibodies (high or low toward median), titer of IgM-RF (high or low toward median), and CDAI, and found that a high titer of IgM-RF was the only variable to be associated with CDAI remission, according to univariate and logistic regression analyses. This is a new finding, and may be specific to tocilizumab as compared with previous observations in anti-TNF therapy.

  3. [Spontaneous activity of cutaneous nociceptors in patients with painful polyneuropathy. Report of three patients].

    PubMed

    Campero, Mario; Campero, Sebastián

    2012-11-01

    Painful polyneuropathy may result from selective impairment of small diameter nerve fibers, while tactile and motor functions are preserved. In these patients clinical and electrophysiological assessment is usually unrevealing. We report three patients with a pure painful polyneuropathy. One of them had neurogenic pruritus additionally. Quantitative sensory analysis disclosed a slight warm hypoesthesia (3/3) and paradoxical hot sensation (2/3) in the feet. Intraneural recordings from the peroneal nerve demonstrated abnormal spontaneous activity in 8 of 17 nociceptive afferents. One of them displayed double firing reflecting impulse multiplication. These results support the notion that patients with pain or pruritus with a distal distribution similar to a polyneuropathy, could have small diameter afferent fiber damage, despite normal function of large diameter fibers.

  4. Adipose-derived mesenchymal stem cells from infrapatellar fat pad of patients with rheumatoid arthritis and osteoarthritis have comparable immunomodulatory properties.

    PubMed

    Skalska, Urszula; Kontny, Ewa

    2016-01-01

    Adipose-derived mesenchymal stem cells (ASCs) possess immunosuppressive properties, but their activity is dependent on stimuli provided by local environment. It is possible that proinflammatory milieu of rheumatoid joint affects ASCs function. To verify this hypothesis, rheumatoid ASCs (RA-ASCs) and osteoarthritic ASCs (OA-ASCs) derived from infrapatellar fat pad (IPFP) of the knee joint have been compared. RA- and OA-ASCs isolated from patients were cultured in vitro. Their secretory and proliferative activity was measured. Peripheral blood mononuclear cells (PBMCs) from healthy donors were co-cultured with ASCs. Then, PBMCs proliferation was measured by (3)H-thymidine incorporation method, cytokines secretion by immunoassays, T cells activation and regulatory T cells (Tregs) percentage - by flow cytometry. RA- and OA-ASCs properties in vitro were comparable, however, some differences in secretory activity occurred. RA- and OA-ASCs inhibited PBMCs proliferation and induced interleukin 10 production but up-regulated interleukin 17 A secretion and failed to limit release of other proinflammatory mediators (tumor necrosis factor [TNF], interferon γ [IFNγ], CCL5) by PBMCs. RA- and OA-ASCs did not suppress activation markers expression on T cells and did not trigger Tregs expansion. The present study shows that IPFP-ASCs from RA and OA patients have comparable functions in vitro. Their immunosuppressive activity seems to be impaired comparing to available data.

  5. Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels.

    PubMed

    Ye, Yun; Li, Su-Liang; Xie, Ming; Jiang, Ping; Liu, Kai-Ge; Li, Ya-Jun

    2013-10-01

    The study aimed to evaluate the levels of serum free kappa (κ) and lambda (λ) light chains in patients with rheumatoid arthritis (RA) as well as exploring the association between serum free κ and λ light chains and activity of RA. For this purpose, healthy individuals and patients with active RA and RA in remission were enrolled, and their serum levels of free κ and λ light chains were measured using rate nephelometry. The diagnostic accuracy of serum free κ and λ light chains was evaluated by receiver operating characteristic curves and 95% confidence intervals for areas under the curve (AUC). The results obtained indicated that the levels of serum free κ and λ light chains in patients with active RA were significantly higher than those of patients in remission and of healthy controls (p < 0.05). Further, the AUC values in patients with active RA were 0.871 for free κ light chain and 0.781 for free λ light chain. When the optimal cut-off point for serum κ light chain was 8.02 g/L, the maximum sensitivity and specificity were 82.5% and 82.5%, respectively, and when the optimal cut-off point for serum λ light chain was 3.57 g/L, the maximum sensitivity and specificity were 80% and 82.5%, respectively. It was thus found that serum levels of free κ and λ light chains were positively correlated with disease activity in RA, the Disease Activity Score 28 (DAS28), and values for C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), platelet count (PLT), rheumatoid factor (RF), and anticitrullinated protein antibody (ACPA) (p < 0.05). In conclusion, high serum levels of free κ and λ light chains in patients with active RA are closely correlated with disease activity parameters including DAS28, CRP, ESR, PLT, RF, and ACPA. Thus, the above-mentioned levels of serum free κ and λ light chains may be used as important indicators of activity of RA.

  6. Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure

    PubMed Central

    Sandip, Chaugai; Tan, Lun; Huang, Jin; Li, Qing; Ni, Li; Cianflone, Katherine; Wang, Dao Wen

    2016-01-01

    Abstract Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it. A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63–0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02–1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class. This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure

  7. Common variants in IL-17A/IL-17RA axis contribute to predisposition to and progression of congestive heart failure.

    PubMed

    Sandip, Chaugai; Tan, Lun; Huang, Jin; Li, Qing; Ni, Li; Cianflone, Katherine; Wang, Dao Wen

    2016-07-01

    Heart failure is characterized by immune activation leading to production and release of proinflammatory cytokines. Interleukin 17A (IL-17A) is a proinflammatory cytokine and multiple lines of evidence from animal and human studies suggest crucial roles of IL-17A in heart failure. Therefore, we investigated whether common polymorphisms of genes IL17A and IL17RA (coding interleukin 17 receptor A) contribute to genetic predisposition to heart failure and adverse clinical outcomes associated with it.A total of 1713 adult patients with congestive heart failure and 1713 age- and sex-matched controls were genotyped for promoter single nucleotide polymorphisms (SNPs), rs2275913 and rs8193037 in IL17A and rs4819554 in IL17RA, to assess the relationship between individual SNPs and the risk of congestive heart failure. Results showed that rs8193037 in IL17A was associated with the risk of congestive heart failure (odds ratio [OR] = 0.76; 95% confidence interval [CI] 0.63-0.90, adjusted P = 0.002) after adjustment for multiple cardiovascular risk factors including age, sex, smoking status, diabetes, hypertension, and dyslipidemia. This association was evident in both ischemic and nonischemic heart failure (P = 0.005 and P = 0.05, respectively). Furthermore, prospective follow-up of 12.7 months for the occurrence of adverse clinical outcomes showed that rs4819554 in IL17RA was significantly associated with cardiovascular mortality (hazard ratio [HR] = 1.28; 95% CI = 1.02-1.59, adjusted P = 0.03) after adjustments for multiple cardiovascular risk factors and New York Heart Association functional class.This study demonstrated associations of rs8193037 in the promoter of IL17A with the risk of congestive heart failure, and of rs4819554 in the promoter of IL17RA with the risk of cardiovascular mortality in patients with congestive heart failure. These data lend further support to the notion that immune activation and genetic polymorphisms contribute to heart failure pathogenesis

  8. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    SciTech Connect

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A. )

    1990-10-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).

  9. New Agents for Targeting of IL-13RA2 Expressed in Primary Human and Canine Brain Tumors

    PubMed Central

    Debinski, Waldemar; Dickinson, Peter; Rossmeisl, John H.; Robertson, John; Gibo, Denise M.

    2013-01-01

    Interleukin 13 receptor alpha 2 (IL-13RA2) is over-expressed in a vast majority of human patients with high-grade astrocytomas like glioblastoma. Spontaneous astrocytomas in dogs resemble human disease and have been proposed as translational model system for investigation of novel therapeutic strategies for brain tumors. We have generated reagents for both detection and therapeutic targeting of IL-13RA2 in human and canine brain tumors. Peptides from three different regions of IL-13RA2 with 100% sequence identity between human and canine receptors were used as immunogens for generation of monoclonal antibodies. Recombinant canine mutant IL-13 (canIL-13.E13K) and canIL-13.E13K based cytotoxin were also produced. The antibodies were examined for their immunoreactivities in western blots, immunohistochemistry, immunofluorescence and cell binding assays using human and canine tumor specimen sections, tissue lysates and established cell lines; the cytotoxin was tested for specific cell killing. Several isolated MAbs were immunoreactive to IL-13RA2 in western blots of cell and tissue lysates from glioblastomas from both human and canine patients. Human and canine astrocytomas and oligodendrogliomas were also positive for IL-13RA2 to various degrees. Interestingly, both human and canine meningiomas also exhibited strong reactivity. Normal human and canine brain samples were virtually negative for IL-13RA2 using the newly generated MAbs. MAb 1E10B9 uniquely worked on tissue specimens and western blots, bound live cells and was internalized in GBM cells over-expressing IL-13RA2. The canIL-13.E13K cytotoxin was very potent and specific in killing canine GBM cell lines. Thus, we have obtained several monoclonal antibodies against IL-13RA2 cross-reacting with human and canine receptors. In addition to GBM, other brain tumors, such as high grade oligodendrogliomas, meningiomas and canine choroid plexus papillomas, appear to express the receptor at high levels and thus may be

  10. Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling.

    PubMed

    Peng, Wei-Xiang; Zhu, Shang-Ling; Zhang, Bai-Yu; Shi, Yi-Ming; Feng, Xiao-Xue; Liu, Fang; Huang, Jian-Lin; Zheng, Song Guo

    2017-01-01

    Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA.

  11. Smoothened Regulates Migration of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via Activation of Rho GTPase Signaling

    PubMed Central

    Peng, Wei-xiang; Zhu, Shang-ling; Zhang, Bai-yu; Shi, Yi-ming; Feng, Xiao-xue; Liu, Fang; Huang, Jian-lin; Zheng, Song Guo

    2017-01-01

    Fibroblast-like synoviocytes (FLSs) acquire aggressive phenotypes characterized with enhanced migration abilities and inherent invasive qualities in rheumatoid arthritis (RA). Smoothened (Smo) is a key component of sonic hedgehog (Shh) signaling and contributes to tumor cell invasion and metastasis. The objective of this study is to investigate the role of Smo in the modulation of cell migration and explore the underlying molecular mechanism(s). FLSs were isolated from RA synovium. Shh levels were regulated by a Smo agonist (purmorphamine), Smo antagonist (KAAD-cyclopamine), or small interfering RNA targeting the Smo gene (Smo-siRNA) in RA-FLSs. Expression of Smo was detected by real-time PCR and western blot analysis. Cell migration was examined by Transwell assay and activation of Rho GTPases was measured by pull-down assays. Incubation with purmorphamine resulted in a significant increase of cell migration and activation of Rho GTPase signaling compared to controls (P < 0.05). However, treatment with KAAD-cyclopamine or transfection with Smo-siRNA suppressed migration of RA-FLSs and showed an inhibitory effect of Rho GTPase signaling. Together, these results suggest that Smo plays an important role in RA-FLSs migration through activation of Rho GTPase signaling and may contribute to progression of RA, thus, targeting Shh signal may have a therapeutic potential in patients with RA. PMID:28261216

  12. Increased autophagy in CD4(+) T cells of rheumatoid arthritis patients results in T-cell hyperactivation and apoptosis resistance.

    PubMed

    van Loosdregt, Jorg; Rossetti, Maura; Spreafico, Roberto; Moshref, Maryam; Olmer, Merissa; Williams, Gary W; Kumar, Pavanish; Copeland, Dana; Pischel, Ken; Lotz, Martin; Albani, Salvatore

    2016-12-01

    Rheumatoid arthritis (RA) is an autoimmune disease hallmarked by aberrant cellular homeostasis, resulting in hyperactive CD4(+) T cells that are more resistant to apoptosis. Both hyperactivation and resistance to apoptosis may contribute to the pathogenicity of CD4(+) T cells in the autoimmune process. A better knowledge of the mechanisms determining such impaired homeostasis could contribute significantly to both the understanding and the treatment of the disease. Here we investigated whether autophagy, is dysregulated in CD4(+) T cells of RA patients, resulting in disturbed T-cell homeostasis. We demonstrate that the rate of autophagy is significantly increased in CD4(+) T cells from RA patients, and that increased autophagy is also a feature of in vitro activated CD4(+) T cells. The increased apoptosis resistance observed in CD4(+) T cells from RA patients was significantly reversed upon autophagy inhibition. These mechanisms may contribute to RA pathogenesis, as autophagy inhibition reduced both arthritis incidence and disease severity in a mouse collagen induced arthritis mouse model. Conversely, in Atg5(flox/flox) -CD4-Cre(+) mice, in which all T cells are autophagy deficient, T cells showed impaired activation and proliferation. These data provide novel insight into the pathogenesis of RA and underscore the relevance of autophagy as a promising therapeutic target.

  13. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    ERIC Educational Resources Information Center

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2016-01-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and…

  14. The WMO RA VI Regional Climate Centre Network - a support to users in Europe

    NASA Astrophysics Data System (ADS)

    Rösner, S.

    2012-04-01

    Climate, like weather, has no limits. Therefore the World Meteorological Organization (WMO), a specialized United Nations organization, has established a three-level infrastructure to better serve its member countries. This structure comprises Global Producing Centres for Long-range Forecasts (GPCs), Regional Climate Centres (RCCs) and National Meteorological or Hydrometeorological Services (NMHSs), in most cases representing their countries in WMO governance bodies. The elements of this infrastructure are also part of and contribute to the Global Framework for Climate Services (GFCS) agreed to be established by World Climate Conference 3 (WCC-3) and last year's Sixteenth World Meteorological Congress (WMO Cg-XVI). RCCs are the core element of this infrastructure at the regional level and are being establish in all WMO Regional Associations (RAs), i.e. Africa (RA I); Asia (II); South America (III); North America, Central America and the Caribbean (IV); South-West Pacific (V); Europe (VI). Addressing inter-regional areas of common interest like the Mediterranean or the Polar Regions may require inter-regional RCCs. For each region the RCCs follow a user driven approach with regard to governance and structure as well as products generated for the users in the respective region. However, there are common guidelines all RCCs do have to follow. This is to make sure that services are provided based on best scientific standards, are routinely and reliably generated and made available in an operational mode. These guidelines are being developed within WMO and make use of decade-long experience gained in the business of operational weather forecast. Based on the requirements of the 50 member countries of WMO RA VI it was agreed to establish the WMO RCC as a network of centres of excellence that create regional products including long-range forecasts that support regional and national climate activities, and thereby strengthen the capacity of WMO Members in the region to

  15. Complement factor B activation in patients with preeclampsia.

    PubMed

    Velickovic, Ivan; Dalloul, Mudar; Wong, Karen A; Bakare, Olufunke; Schweis, Franz; Garala, Maya; Alam, Amit; Medranda, Giorgio; Lekovic, Jovana; Shuaib, Waqas; Tedjasukmana, Andreas; Little, Perry; Hanono, Daniel; Wijetilaka, Ruvini; Weedon, Jeremy; Lin, Jun; Toledano, Roulhac d'Arby; Zhang, Ming

    2015-06-01

    Preeclampsia is a leading cause of maternal and fetal morbidity and mortality. Bb, the active fragment of complement factor B (fB), has been reported to be a predictor of preeclampsia. However, conflicting results have been found by some investigators. We hypothesized that the disagreement in findings may be due to the racial/ethnic differences among various study groups, and that fB activation is significant in women of an ethnic minority with preeclampsia. We investigated the maternal and fetal levels of Bb (the activated fB fragment) in pregnant women of an ethnic minority with or without preeclampsia. We enrolled 291 pregnant women (96% of an ethnic minority, including 78% African-American). Thirteen percent of these were diagnosed with preeclampsia. Maternal venous blood was collected from all participants together with fetal umbilical cord blood samples from 154 deliveries in the 291 women. The results were analyzed using the Mann-Whitney U test and multivariate analyses. Maternal Bb levels were significantly higher in the preeclamptic group than in the nonpreeclamptic group. Levels of Bb in fetal cord blood were similar in both groups. Subgroup analyses of African-American patients' results confirmed the study hypothesis that there would be a significant increase in Bb in the maternal blood of the preeclamptic group and no increase in Bb in the fetal cord blood of this group. These results suggest that a maternal immune response through complement fB might play a role in the development of preeclampsia, particularly in African-American patients.

  16. HtrA2 suppresses autoimmune arthritis and regulates activation of STAT3

    PubMed Central

    Lee, Seung Hoon; Moon, Young-Mee; Seo, Hyeon-Beom; Kim, Se-Young; Kim, Eun-Kyung; Yi, Junyeong; Nam, Min-Kyung; Min, Jun-Ki; Park, Sung-Hwan; Rhim, Hyangshuk; Cho, Mi-La

    2016-01-01

    Rheumatoid arthritis (RA) is an autoimmune disease that is related to the induction of T helper (Th)17 cells, which secrete interleukin-17, and activation of the signal transducer and activator of transcription (STAT) 3. The expression of high-temperature requirement protein A (HtrA) 2, a serine protease involved in apoptosis, was decreased in RA patients nonresponsive to drug treatment of RA. The aim of this study was to determine whether overexpression of HtrA2 has a therapeutic effect on RA. Th17 differentiation, osteoclastogenesis, and lymphocyte activation are increased in motor neuron degeneration (mnd)2 mice, which lack HtrA2 activity because of a missense mutation (Ser276Cys) in the protease domain of HtrA2. The inhibitor of HtrA2 also increased Th17 differentiation. On the other hand, HtrA2 induced cleavage of STAT3 and overexpression of HtrA2 attenuated CIA in a mouse model. HtrA2 overexpression inhibited plaque development as well as the differentiation of Th17 in ApoE−/− mice after immunization with proteoglycans to induce a hyperlipidemia-based RA animal model. The therapeutic function of HtrA2 in inflammatory diseases is linked with Th17 development and the STAT3 pathway in splenocytes. These results suggest that HtrA2 participates in immunomodulatory activity where the upregulation of HtrA2 may shed light on therapeutic approaches to RA and hyperlipidemia. PMID:28008946

  17. Polymorphism in vitamin D receptor and osteoprotegerin genes in Egyptian rheumatoid arthritis patients with and without osteoporosis.

    PubMed

    Hussien, Yousry Mostafa; Shehata, Amal; Karam, Rehab A; Alzahrani, Saad S; Magdy, Hanem; El-Shafey, Abeer M

    2013-05-01

    1α,25-Dihydroxyvitamin D3 upregulates the expression of the receptor activator of nuclear factor kB ligand (RANKL), and downregulates osteoprotegerin (OPG) expression. We tested the effects of polymorphisms in the vitamin D receptor gene (VDR), and OPG gene in rheumatoid arthritis (RA) patients and healthy controls and their relationship to bone mineral density (BMD) and development of osteoporosis. Three hundred and fifty women were evaluated, 200 women having RA and 150 healthy control. The subjects were genotyped for polymorphism at BsmI in VDR and A163G in OPG genes by polymerase chain reaction followed by restriction fragment length polymorphism analysis. BMD was also measured. In A163G, the G allele increased the risk for RA and for the development of osteoporosis. We found a significant association between lower hip (BMD-h) and genotype variants of VDR (BsmI) and OPG A163G in RA patients with osteoporosis. Our results suggested that OPG A163G polymorphism was associated with RA susceptibility and with the development of osteoporosis in these patients. Also, VDR and OPG genes are important candidates for osteoporosis in RA patients.

  18. Bone erosions in rheumatoid arthritis can be repaired through reduction in disease activity with conventional disease-modifying antirheumatic drugs.

    PubMed

    Ideguchi, Haruko; Ohno, Shigeru; Hattori, Hideaki; Senuma, Akiko; Ishigatsubo, Yoshiaki

    2006-01-01

    We conducted the present study to determine whether repair of erosions occurs in patients with rheumatoid arthritis (RA) treated with conventional disease-modifying anti-rheumatic drugs (DMARDs) and to compare clinical characteristics between patients exhibiting and not exhibiting erosion repair. We included in the study a total of 122 RA patients who fulfilled the 1987 American College of Rheumatology criteria for RA; all patients had paired sequential radiographs of both hands and wrists showing erosive changes at baseline. Patients were classified into two groups according to the presence of repair of erosions at follow up, namely the 'repair observed' and 'repair not observed' groups. Clinical characteristics, disease activity, radiographic scores and treatment in the two groups were compared. Forty-four repairs were observed in 13 patients (10.7%). Compared with the repair not observed group, the functional class of the patients in the repair observed group was lower at baseline (P < 0.01) and the mean disease activity was lower at follow up (P < 0.005). The changes in radiographic scores per year (total radiographic score and erosion score) were lower (P < 0.05 and P < 0.01, respectively) in the repair observed group. No difference in treatment was observed. Repair of erosions was detected in 10.7% of RA patients treated with conventional DMARDs. Repairs were associated with low functional class at baseline and low disease activity at follow up. These observations support the importance of reduction in disease activity in RA patients. Because repair of erosions was detected in a substantial number of patients, assessment of erosion repair should be incorporated into the radiographic evaluation and scoring of RA.

  19. The "RA" Expeditions: The Archaeological and Anthropological Background. The "RA" Expeditions: The Coriolis Effect. The "RA" Expeditions: The Papyrus Reed. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 211, 212, 213. [Project COAST].

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Coll. of Education.

    Included are three units related to coastal and oceanic awareness. These are: (1) The "RA" Expeditions: The Archaeological and Anthropological Background; (2) The "RA" Expeditions: The Coriolis Effect; and (3) The "RA" Expeditions: The Papyrus Reed. Each of the three units are designed for students in grades 6-12.…

  20. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

    DOE PAGES

    Rojas, J. V.; Woodward, J. D.; Chen, N.; ...

    2015-03-19

    Targeted alpha therapy (TAT) has the potential for killing specific tumor cells with minimum collateral damage to surrounding healthy tissue. Radionuclides such as 223Ra, 225Ra, and 225Ac are of special interest for radiotherapeutic applications as they emit multiple -particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. Methods. In this work, core and core+2 shells (NPs with 2 additional layers of cold LaPO4 deposited on the core surfaces) LaPO4 nanoparticles (NPs)more » were synthesized containing either 223Ra or 225Ra/225Ac and the retention of the parents and daughters within the NPs in vitro was investigated. Results. The NPs crystallized in rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core+2 shells, respectively. The core LaPO 4 NPs retained up to 88% of 223Ra over 35 days. However, in the core+2 shell NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27 days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~80% for the 221Fr and 213Bi daughters over 35 days for the core+2 shell NPs. Conclusions. These results suggest that LaPO4 NPs are potentially effective carriers of radium isotopes.« less

  1. Relationship between balance and physical activity measured by an activity monitor in elderly COPD patients

    PubMed Central

    Iwakura, Masahiro; Okura, Kazuki; Shibata, Kazuyuki; Kawagoshi, Atsuyoshi; Sugawara, Keiyu; Takahashi, Hitomi; Shioya, Takanobu

    2016-01-01

    Background Little is known regarding the relationship between balance impairments and physical activity in COPD. There has been no study investigating the relationship between balance and objectively measured physical activity. Here we investigated the association between balance and physical activity measured by an activity monitor in elderly COPD patients. Materials and methods Twenty-two outpatients with COPD (mean age, 72±7 years; forced expiratory volume in 1 second, 53%±21% predicted) and 13 age-matched healthy control subjects (mean age, 72±6 years) participated in the study. We assessed all 35 subjects’ balance (one-leg standing test [OLST] times, Short Physical Performance Battery total scores, standing balance test scores, 4 m gait speed, and five-times sit-to-stand test [5STST]) and physical activity (daily steps and time spent in moderate-to-vigorous physical activity per day [MV-PA]). Possible confounders were assessed in the COPD group. The between-group differences in balance test scores and physical activity were analyzed. A correlation analysis and multivariate regression analysis were conducted in the COPD group. Results The COPD patients exhibited significant reductions in OLST times (P=0.033), Short Physical Performance Battery scores (P=0.013), 4 m gait speed (P<0.001), five-times sit-to-stand times (P=0.002), daily steps (P=0.003), and MV-PA (P=0.022) compared to the controls; the exception was the standing balance test scores. The correlation and multivariate regression analyses revealed significant independent associations between OLST times and daily steps (P<0.001) and between OLST times and MV-PA (P=0.014) in the COPD group after adjusting for possible confounding factors. Conclusion Impairments in balance and reductions in physical activity were observed in the COPD group. Deficits in balance are independently associated with physical inactivity. PMID:27445470

  2. Within-day variation and influence of physical exercise on circulating Galectin-3 in patients with rheumatoid arthritis and healthy individuals.

    PubMed

    Issa, S F; Christensen, A F; Lottenburger, T; Junker, K; Lindegaard, H; Hørslev-Petersen, K; Junker, P

    2015-07-01

    Galectin-3 has been suggested as a pro-inflammatory mediator in rheumatoid arthritis (RA). Previous studies have reported overexpression of Galectin-3 in RA synovitis and increased levels in synovial fluid and serum in long-standing RA compared with osteoarthritis and healthy controls. Our objectives were to study whether serum Galectin-3 (1) exhibits circadian variation and/or (2) responds to exercise in RA and controls. The study on circadian patterns (1) comprised eleven patients with newly diagnosed RA, disease duration less than 6 months (ERA), 10 patients with long-standing RA [5-15 years (LRA)] and 16 self-reportedly healthy control subjects. During 24 h, 7 blood samples were drawn at 3-h intervals starting at 10 a.m. through 10 p.m. and at 7 and 10 a.m. on the following day. The study on the effect of physical activity (2) included 10 patients with ERA, 10 with LRA and 14 controls. The participants underwent a standardized exercise programme and four blood samples were drawn before, during and after exercise. Serum Galectin-3 was quantified by ELISA (R&D systems). (1) Galectin-3 was increased at baseline in both RA subsets (P = 0.08). There were no diurnal oscillations (P = 0.85). Day-to-day variation amounted to 3%. (2) Baseline Galectin-3 was increased in LRA versus controls and ERA (P < 0.01 and 0.05). Physical exercise induced 10-15% Galectin-3 increments in RA and controls (P < 0.001) peaking after 1-3 h. To conclude, Galectin-3 did not exhibit circadian variation. Day-to-day variation was 3%. Exercise elicited comparable increments in patients with RA of short and long duration and controls, approaching normal after 1-3 h.

  3. MEFV, TNF1rA, CARD15 and NLRP3 mutation analysis in PFAPA.

    PubMed

    Dagan, Efrat; Gershoni-Baruch, Ruth; Khatib, Ihab; Mori, Adi; Brik, Riva

    2010-03-01

    PFAPA is a periodic fever disease, of unknown etiology, characterized by aphthous stomatitis, pharyngitis and cervical adenitis. To inquire whether genes implicated in other auto-inflammatory diseases might be involved in its pathogenesis, predominant mutations in the genes causing familial Mediterranean fever, TNF receptor-associated periodic fever syndrome, Crohn's disease and Muckel-Wells syndrome were analyzed in PFAPA patients. Patients (n = 57) with PFAPA, according to previously published criteria were recruited, at the Meyer Children Hospital during 2006-2007. Clinical information was complemented during physicians-parents encounter. Predominant mutations in MEFV, TNF1rA, CARD15/NOD2 and NLRP3 genes were tested. Mean age at diagnosis was 30.64 +/- 16.4 months. Boys (n = 33; 58%) were diagnosed earlier than girls (n = 21; 42%) at 26.18 +/- 13.83 and 36.41 +/- 18.32 months, respectively (P = 0.05). Fifteen patients (27%) carried an MEFV mutation; two patients (3.6%) a CARD15 mutation, one patient (1.8%) a variance in TNF1rA and another had both an MEFV and a CARD15 mutation. Clinical symptoms were equally manifested in carriers and non-carriers. The high carrier rate of MEFV mutations in our PFAPA cases compares well with that of the general population in Israel. It is debated whether MEFV mutations, when mediated by the presence of additional modifiers, may expose a transient fever condition, namely PFAPA.

  4. Sexual function in Moroccan women with rheumatoid arthritis and its relationship with disease activity.

    PubMed

    Hari, Asmae; Rostom, Samira; Lahlou, Racha; Bahiri, Rachid; Hajjaj-Hassouni, Najia

    2015-06-01

    The objective of this study was to evaluate sexual function in women with rheumatoid arthritis (RA) using an auto-questionnaire Female Sexual Function Index (FSFI) and study its correlation with disease activity. Sixty patients with RA and 40 healthy controls were included in this exploratory study. Sociodemographic, clinical, and laboratory characteristics were assessed. The disease activity was assessed by auto-questionnaires Routine Assessment of Patient Index Data 3 (RAPID3) and Rheumatoid Arthritis Disease Activity Index 5 (RADAI5) judged by 28 DAS ESR. Sexual function was assessed by an auto-questionnaire specific for female sexuality: FSFI during the last 4 weeks. The definition of sexual dysfunction was considered by FSFI score less than or equal to 26.5. The mean age of RA patients and controls was 45.95 ± 9.3 and 45.01 ± 9.2, respectively. According to FSFI, the percentage of FSD in women with RA was significantly higher than that in the control group. All dimensions of sexuality were affected (desire, arousal, lubrication, orgasm, and satisfaction) except pain. The multivariate linear regression analysis indicated that the swollen joints and the RADAI5 were the independent variables of disease activity associated with sexual dysfunction in women with RA. This study suggests that sexual dysfunction among women suffering from rheumatoid arthritis is found when a targeted questionnaire is used to identify it and that the increased disease activity has a negative effect of sexual function.

  5. Epithelial neutrophil activating peptide-78: a novel chemotactic cytokine for neutrophils in arthritis.

    PubMed Central

    Koch, A E; Kunkel, S L; Harlow, L A; Mazarakis, D D; Haines, G K; Burdick, M D; Pope, R M; Walz, A; Strieter, R M

    1994-01-01

    We and others have shown that cells obtained from inflamed joints of rheumatoid arthritis (RA) patients produce interleukin-8, a potent chemotactic cytokine for neutrophils (PMNs). However, IL-8 accounted for only 40% of the chemotactic activity for PMNs found in these synovial fluids. Currently, we have examined the production of the novel PMN chemotactic cytokine, epithelial neutrophil activating peptide-78 (ENA-78), using peripheral blood, synovial fluid, and synovial tissue from 70 arthritic patients. RA ENA-78 levels were greater in RA synovial fluid (239 +/- 63 ng/ml) compared with synovial fluid from other forms of arthritis (130 +/- 118 ng/ml) or osteoarthritis (2.6 +/- 1.8 ng/ml) (P < 0.05). RA peripheral blood ENA-78 levels (70 +/- 26 ng/ml) were greater than normal peripheral blood levels (0.12 +/- 0.04 ng/ml) (P < 0.05). Anti-ENA-78 antibodies neutralized 42 +/- 9% (mean +/- SE) of the chemotactic activity for PMNs found in RA synovial fluids. Isolated RA synovial tissue fibroblasts in vitro constitutively produced significant levels of ENA-78, and this production was further augmented when stimulated with tumor necrosis factor-alpha (TNF-alpha). In addition RA and osteoarthritis synovial tissue fibroblasts as well as RA synovial tissue macrophages were found to constitutively produce ENA-78. RA synovial fluid mononuclear cells spontaneously produced ENA-78, which was augmented in the presence of lipopolysaccharide. Immunohistochemical localization of ENA-78 from the synovial tissue of patients with arthritis or normal subjects showed that the predominant cellular source of this chemokine was synovial lining cells, followed by macrophages, endothelial cells, and fibroblasts. Synovial tissue macrophages and fibroblasts were more ENA-78 immunopositive in RA than in normal synovial tissue (P < 0.05). These results, which are the first demonstration of ENA-78 in a human disease state, suggest that ENA-78 may play an important role in the recruitment of PMNs

  6. Long-term clinical outcomes of patients with rheumatoid arthritis and concomitant coronary artery disease

    PubMed Central

    Spartera, Marco; Godino, Cosmo; Baldissera, Elena; Campochiaro, Corrado; La Spina, Ketty; Aiello, Patrizia; Salerno, Anna; Cera, Michela; Magni, Valeria; Jabbour, Richard J; Dagna, Lorenzo; Tresoldi, Moreno; Cappelletti, Alberto; Alfieri, Ottavio; Colombo, Antonio; Sabbadini, Maria Grazia; Margonato, Alberto

    2017-01-01

    Background: Rheumatoid arthritis (RA) is associated with high morbidity and mortality predominately due to increased cardiovascular risk. Few reports are available regarding the management of coronary artery disease (CAD) in RA patients and the long-term clinical outcomes after coronary revascularization. Methods and results: All consecutive patients with RA were identified by retrospective review at a rheumatology tertiary center in Milan, Italy between 2001 and 2013. RA patients affected by significant CAD (RA-CAD+) were prospectively followed for major adverse cardiovascular and cerebrovascular events (MACCE) after percutaneous coronary revascularization (RA-PCI), coronary artery bypass grafting (RA-CABG) or medical therapy (RA-MT). Among 936 patients with RA, the presence of clinically significant CAD was found in 5.6% (53 patients, RA-CAD+). Of these, 32 patients (60%) underwent PCI (RA-PCI), 10 patients (19%) underwent CABG (RA-CABG) and 11 patients (21%) treated with MT (RA-MT). After a mean follow-up of 9±7 years, the rate of MACCE was 56% in RA-PCI patients, 50% in RA-CABG and 27% in RA-MT patients (P=0.184). The high MACCE rate was mainly driven by repeat coronary revascularization (47%) in the RA-PCI group and high rate of strokes (30%) in RA-CABG patients. Conclusion: In patients with rheumatoid arthritis and concomitant coronary artery disease (RA-CAD+), we observed at long-term follow-up a high MACCE rate, predominantly in those who underwent coronary revascularization PMID:28337386

  7. Small-Molecule RA-9 Inhibits Proteasome-Associated DUBs and Ovarian Cancer in Vitro and in Vivo Via Exacerbating Unfolded Protein Responses

    PubMed Central

    Coughlin, Kathleen; Anchoori, Ravi; Iizuka, Yoshie; Meints, Joyce; MacNeill, Lauren; Vogel, Rachel Isaksson; Orlowski, Robert Z.; Lee, Michael K.; Roden, Richard BS; Bazzaro, Martina

    2014-01-01

    Purpose Ovarian cancer is the deadliest of the gynecological malignancies. Carcinogenic progression is accompanied by up-regulation of ubiquitin-dependent protein degradation machinery as a mechanism to compensate with elevated endogenous proteotoxic stress. Recent studies support the notion that deubiquitinating enzymes (DUBs) are essential factors in proteolytic degradation and that their aberrant activity is linked to cancer progression and chemoresistance. Thus, DUBs are an attractive therapeutic target for ovarian cancer. Experimental Design The potency and selectivity of RA-9 inhibitor for proteasome-associated DUBs was determined in ovarian cancer cell lines and primary cells. The anticancer activity of RA-9 and its mechanism of action was evaluated in multiple cancer cell lines in vitro and in vivo in immunodeficient mice bearing an intra-peritoneal ES-2 xenograft model of human ovarian cancer. Results Here we report the characterization of RA-9 as a small-molecule inhibitor of proteasome-associated DUBs. Treatment with RA-9 selectively induces onset of apoptosis, in ovarian cancer cell lines and primary cultures derived from donors. Loss of cell viability following RA-9 exposure is associated with an Unfolded Protein Response (UPR) as mechanism to compensate for unsustainable levels of proteotoxic stress. In vivo treatment with RA-9 retards tumor growth, increases overall survival and was well tolerated by the host. Conclusions Our preclinical studies support further evaluation of RA-9 as an ovarian cancer therapeutic. PMID:24727327

  8. Is a Coded Physical Activity Diary Valid for Assessing Physical Activity Level and Energy Expenditure in Stroke Patients?

    PubMed Central

    Vanroy, Christel; Vanlandewijck, Yves; Cras, Patrick; Feys, Hilde; Truijen, Steven; Michielsen, Marc; Vissers, Dirk

    2014-01-01

    Objectives to determine the concurrent validity of a physical activity diary for measuring physical activity level and total energy expenditure in hospitalized stroke patients. Method Sixteen stroke patients kept coded activity diaries and wore SenseWear Pro2 multi-sensor activity monitors during daytime hours for one day. A researcher observed the patients and completed a diary. Data from the patients' diaries were compared with observed and measured data to determine total activity (METs*minutes), activity level and total energy expenditure. Results Spearman correlations between the patients' and researchers' diaries revealed a high correlation for total METs*minutes (rs = 0.75, p<0.01) for sedentary (rs = 0.74,p<0.01) and moderate activities (rs = 0.71,p<0.01) and a very high correlation (rs = 0.92, p<0.01) for the total energy expenditure. Comparisons between the patients' diaries and activity monitor data revealed a low correlation (rs 0.29) for total METs*minutes and energy expenditure. Conclusion Coded self-monitoring activity diaries appear feasible as a low-tech alternative to labor-intensive observational diaries for determining sedentary, moderate, and total physical activity and for quantifying energy expenditure in hospitalized stroke patients. Given the poor correlation with objective measurements of physical activity, however, further research is needed to validate its use against a gold-standard measure of physical activity intensity and energy expenditure. PMID:24905345

  9. Study of the Effect of an Oral Formulation of Fig and Olive on Rheumatoid Arthritis (RA) Remission Indicators: A Randomized Clinical Trial

    PubMed Central

    Bahadori, Shahnaz; Salamzadeh, Jamshid; Kamalinejad, Mohammad; Shams Ardekani, Mohammad Reza; Keshavarz, Mansoor; Ahmadzadeh, Arman

    2016-01-01

    This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming p<0.05 as significance level. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.91 ± 12.26 years completed the study. Repeated measures analysis revealed that differences between remission indicators in the two study groups were not statistically significant, however, there was a p = 0.03 for the within-subjects contrast test of the Patient Global Assessment (PtGA), approving a nonlinear change for PtGA with respect to time. No between groups differences in adjunct drug therapy pattern for disease flares were seen. In conclusion, although, non-significant changes in the study variable of DAS28_ESR is in agreement with few previous reports, nevertheless, trends in its reduction in the intervention group along with the significant delayed PtGA score improvements occurred in the intervention group convince us to suggest further investigations on the supplementary olive and fig products, with a longer follow up periods. PMID:27980590

  10. Study of the Effect of an Oral Formulation of Fig and Olive on Rheumatoid Arthritis (RA) Remission Indicators: A Randomized Clinical Trial.

    PubMed

    Bahadori, Shahnaz; Salamzadeh, Jamshid; Kamalinejad, Mohammad; Shams Ardekani, Mohammad Reza; Keshavarz, Mansoor; Ahmadzadeh, Arman

    2016-01-01

    This study was designed to explore the complementary effects of a combination formulation of olive oil, olive and fig fruits on RA remission indicators. A randomized controlled clinical trial was designed. Adult RA patients were randomly divided into two groups receiving routine Disease-modifying antirheumatic drugs (DMARDs) regimen (control group) and routine DMARDs regimen plus the herbal supplementary formulation of olive oil, fig and olive fruits (intervention group). Patients were followed every 4 weeks for total study period of 16 weeks. In addition to demographic and medical history of the patients, the Disease Activity Score with 28-joint counts based on Erythrocyte Sedimentation Rate (DAS28_ESR) were recorded. SPSS (version 22.0) software was used to analyze data, assuming p<0.05 as significance level. 56 patients (control = 27 and intervention = 29), with mean ± sd age of 50.91 ± 12.26 years completed the study. Repeated measures analysis revealed that differences between remission indicators in the two study groups were not statistically significant, however, there was a p = 0.03 for the within-subjects contrast test of the Patient Global Assessment (PtGA), approving a nonlinear change for PtGA with respect to time. No between groups differences in adjunct drug therapy pattern for disease flares were seen. In conclusion, although, non-significant changes in the study variable of DAS28_ESR is in agreement with few previous reports, nevertheless, trends in its reduction in the intervention group along with the significant delayed PtGA score improvements occurred in the intervention group convince us to suggest further investigations on the supplementary olive and fig products, with a longer follow up periods.

  11. Greek NHS capacity constraints regarding intravenous treatment for rheumatoid arthritis patients.

    PubMed

    Athanasakis, Kostas; Detsis, Marios; Souliotis, Kyriakos; Golna, Christina; Kyriopoulos, John

    2012-04-01

    Intravenous (iv) infusion of biologic agents is a highly effective therapeutic option for active rheumatoid arthritis (RA). In Greece, it is mandatory that all infusions are administered in a hospital setting; therefore, they are strongly correlated with the system's capacity in terms of resources. The objective of this paper was to assess the capacity of the Greek National Health System (NHS) hospitals to meet current/projected demand for iv treatment of RA patients. Semi-qualitative interviews on the basis of a strictly structured questionnaire were conducted with the Heads of all NHS RA infusion sites to record available resources, service utilization and ability to meet current/projected demand. Out of 31 NHS infusion sites, 28 responded (90.3%). On average, 41.6% of Greek NHS RA patients are treated with a biologic agent and 61.5% of respondents stated that available resources are insufficient to meet current demand. The most important constraints in selection order were as follows: space (93%), staff (89.5%), equipment (61.5%) and working hours (57%). Fifty-six percent of respondents stated that they may decline treatment to patients due to constraints. Overall, respondents estimated that the number of iv patients could be increased by 104%, were there no capacity constraints. An important proportion of the estimated 40.000 RA patients in Greece, for whom iv biologic treatment in the hospital setting is essential for disease control, may be declined treatment due to constraints in RA-specific resources. Rationalization and reallocation of NHS resources is required to ensure equity in access to effective treatment for all RA patients.

  12. RAPID DETERMINATION OF RA-226 IN ENVIRONMENTAL SAMPLES

    SciTech Connect

    Maxwell, S.

    2012-01-03

    A new rapid method for the determination of {sup 226}Ra in environmental samples has been developed at the Savannah River Site Environmental Lab (Aiken, SC, USA) that can be used for emergency response or routine sample analyses. The need for rapid analyses in the event of a Radiological Dispersive Device or Improvised Nuclear Device event is well-known. In addition, the recent accident at Fukushima Nuclear Power Plant in March, 2011 reinforces the need to have rapid analyses for radionuclides in environmental samples in the event of a nuclear accident. {sup 226}Ra (T1/2 = 1,620 years) is one of the most toxic of the long-lived alpha-emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The new method to determine {sup 226}Ra in environmental samples utilizes a rapid sodium hydroxide fusion method for solid samples, calcium carbonate precipitation to preconcentrate Ra, and rapid column separation steps to remove interferences. The column separation process uses cation exchange resin to remove large amounts of calcium, Sr Resin to remove barium and Ln Resin as a final purification step to remove {sup 225}Ac and potential interferences. The purified {sup 226}Ra sample test sources are prepared using barium sulfate microprecipitation in the presence of isopropanol for counting by alpha spectrometry. The method showed good chemical recoveries and effective removal of interferences. The determination of {sup 226}Ra in environmental samples can be performed in less than 16 h for vegetation, concrete, brick, soil, and air filter samples with excellent quality for emergency or routine analyses. The sample preparation work takes less than 6 h. {sup 225}Ra (T1/2 = 14.9 day) tracer is used and the {sup 225}Ra progeny {sup 217}At is used to determine chemical yield via alpha spectrometry. The rapid fusion technique is a rugged sample digestion method that ensures that any

  13. The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28).

    PubMed

    van Riel, P L C M

    2014-01-01

    In rheumatoid arthritis, disease activity cannot be measured using a single variable. The Disease Activity Score (DAS) has been developed as a quantitative index to be able to measure, study and manage disease activity in RA in daily clinical practice, clinical trials, and long term observational studies. The DAS is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and patient self-report of general health. Cut points were developed to classify patients in remission, as well as low, moderate, and severe disease activity in the 1990s. DAS-based EULAR response criteria were primarily developed to be used in clinical trials to classify individual patients as non-, moderate, or good responders, depending on the magnitude of change and absolute level of disease activity at the conclusion of the test.

  14. Somatotropic, lactotropic and adrenocortical responses to insulin-induced hypoglycemia in patients with rheumatoid arthritis.

    PubMed

    Rovensky, Jozef; Bakosová, Jana; Koska, Juraj; Ksinantová, Lucia; Jezová, Daniela; Vigas, Milan

    2002-06-01

    Neuroendocrine mechanisms have been suggested to play an important role in the onset and progression of rheumatoid arthritis (RA). The aim of this study was to evaluate hypothalamic-pituitary functions in RA patients by measurement of hormone responses to insulin-induced hypoglycemia. Insulin-hypoglycemia (Actrapid HM 0.1 IU/kg, i.v. as a bolus) was induced in 17 male patients and in 11 age-, gender-, and weight-matched healthy subjects. Concentrations of growth hormone (GH), prolactin (PRL) and cortisol were analyzed in plasma. PRL release after thyreoliberin stimulation (TRH, 200 g, i.v.) was determined in 21 patients with active forms of RA and in 12 control subjects to evaluate pituitary lactotropic response. In RA patients, basal concentrations of glucose, GH, PRL, and cortisol were in the normal range and they were comparable to those in the control group. Stress of hypoglycemia induced significant elevation of GH, PRL, and cortisol concentrations in all groups. Cortisol responses to hypoglycemia were comparable in patients and in control subjects. GH release during hypoglycemia was increased (p < 0.05) and PRL response was attenuated (p < 0.05) in RA patients versus control subjects. After TRH administration, PRL response was the same in patients as in healthy subjects. In conclusion, the present study revealed an altered hypothalamic-pituitary function in patients with RA, namely, an enhanced somatotropic and reduced lactotropic activation in response to insulin-induced hypoglycemia. Basal hormone levels and cortisol release during hypoglycemia were similar to those in healthy subjects.

  15. Long term treatment with abatacept or tocilizumab does not increase Epstein-Barr virus load in patients with rheumatoid arthritis - A three years retrospective study

    PubMed Central

    Balandraud, Nathalie; Texier, Gaetan; Massy, Emmanuel; Muis-Pistor, Olivier; Martin, Marielle; Auger, Isabelle; Guzian, Marie-Caroline; Guis, Sandrine; Pham, Thao; Roudier, Jean

    2017-01-01

    Background Epstein-Barr Virus (EBV) is a widely disseminated lymphotropic herpes virus implicated in benign and malignant disorders. In transplant patients, immunosuppressive drugs (cyclosporine) diminish control of EBV replication, potentially leading to lymphoproliferative disorders (LPD). Rheumatoid arthritis (RA) patients have impaired control of EBV infection and have EBV load ten times higher than controls. As post transplant patients, patients with RA have increased risk of developing lymphomas. Immunosuppressive drugs used to treat RA (conventional disease modifying drugs cDMARDs or biologics bDMARDs) could enhance the risk of developing LPD in RA patients. We have previously shown that long term treatment with Methotrexate and/or TNF alpha antagonists does not increase EBV load in RA. Our objective was to monitor the Epstein-Barr Virus load in RA patients treated with Abatacept (CTLA4 Ig), a T cell coactivation inhibitor, and Tocilizumab, an anti IL6 receptor antibody. Methods EBV load in the peripheral blood mononuclear cells (PBMCs) of 55 patients under Abatacept (in 34% associated with Methotrexate) and 35 patients under Tocilizumab (in 37% associated with Methotrexate) was monitored for durations ranging from 6 months to 3 years by real time PCR. The influences of treatment duration and disease activity score 28 (DAS28) index on EBV load were analyzed. Results Abatacept did not significantly modify EBV load over time. Tocilizumab significantly diminished EBV load over time. No patient (of 90) developed EBV associated lymphoma. Conclusion Long term treatment with Abatacept or Tocilizumab does not increase EBV load in the PBMNCs of patients with RA. PMID:28199343

  16. Determination of photon emission probabilities for the main gamma-rays of ²²³Ra in equilibrium with its progeny.

    PubMed

    Pibida, L; Zimmerman, B; Fitzgerald, R; King, L; Cessna, J T; Bergeron, D E

    2015-07-01

    The currently published (223)Ra gamma-ray emission probabilities display a wide variation in the values depending on the source of the data. The National Institute of Standards and Technology performed activity measurements on a (223)Ra solution that was used to prepare several sources that were used to determine the photon emission probabilities for the main gamma-rays of (223)Ra in equilibrium with its progeny. Several high purity germanium (HPGe) detectors were used to perform the gamma-ray spectrometry measurements.

  17. Relation between bone mineral density and IL-17 serum levels in Serbian patients with early Rheumatoid arthritis

    PubMed Central

    Dimic, Aleksandar; Milenkovic, Sasa; Krtinic, Dane; Aleksic, Ivana

    2015-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial inflammation and destruction of joint cartilage and bone. Different cytokines play important role in the processes that cause articular destruction and extra-articular manifestations in RA. The contribution of cytokines representing the Th1 (INF-γ), Th2 (IL-4) and IL-17A to the pathogenesis of early RA and bone mineral density (BMD) loss in still poorly understood. Serum samples of 38 early RA patients were evaluated for erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP) and for the tested cytokines (IL-17A, IL-4 and INF-γ). BMD was evaluated by dualenergy X-ray absorptiometry (DXA). Disease activity score (DAS28) calculation was assessed for all patients. Control serum samples were obtained from 34 healthy volunteers. The levels of tested cytokines were significantly higher (IL-17A, p<0.001; INF-γ, P<0.001; IL-4, P<0.01) in patients with early RA, compared to the healthy controls. In early RA patients, strong correlation of serum IL-17A was found with DAS28, ESR and CRP. Also, a significant negative correlation was found between serum INF-γ levels and the DAS28 score. Significantly positive correlation of BMD values and CRP, DAS28 IL-17A were also demonstrated. DXA analysis revealed that the most common site for osteoporosis was the lumbar spine followed by the femoral neck. BMD values significantly correlated with CRP, DAS28 score and IL-17A serum levels. The mean serum IL-17A levels, in patients with early RA, corresponded with disease activity, severity and BMD loss, indicating the potential usefulness of serum IL-17A in defining the disease activity and bone remodeling. PMID:28352685

  18. Precise measurements of the absolute γ-ray emission probabilities of (223)Ra and decay progeny in equilibrium.

    PubMed

    Collins, S M; Pearce, A K; Regan, P H; Keightley, J D

    2015-08-01

    Precise measurements of the absolute γ-ray emission probabilities have been made of radiochemically pure solutions of (223)Ra in equilibrium with its decay progeny, which had been previously standardised by 4π(liquid scintillation)-γ digital coincidence counting techniques. Two high-purity germanium γ-ray spectrometers were used which had been accurately calibrated using a suite of primary and secondary radioactive standards. Comparison of the activity concentration determined by the primary technique against γ-ray spectrometry measurements using the nuclear data evaluations of the Decay Data Evaluation Project exhibited a range of ~18% in the most intense γ-ray emissions (>1% probability) of the (223)Ra decay series. Absolute γ-ray emission probabilities and standard uncertainties have been determined for the decay of (223)Ra, (219)Rn, (215)Po, (211)Pb, (211)Bi and (207)Tl in equilibrium. The standard uncertainties of the measured γ-ray emission probabilities quoted in this work show a significant improvement over previously reported γ-ray emission probabilities. Correlation coefficients for pairs of the measured γ-ray emission probabilities from the decays of the radionuclides (223)Ra, (219)Rn and (211)Pb have been determined and are presented. The α-transition probabilities of the (223)Ra have been deduced from P(γ+ce) balance using the γ-ray emission probabilities determined in this work with some agreement observed with the published experimental values of the α-emission probabilities.

  19. Vhnf1 acts downstream of Bmp, Fgf, and RA signals to regulate endocrine beta cell development in zebrafish.

    PubMed

    Song, Jianbo; Kim, Hyon J; Gong, Zhiyuan; Liu, Ning-Ai; Lin, Shuo

    2007-03-15

    Bmp, Fgf, and retinoic acid (RA) signals have been implicated as regulators of pancreas development. However, the integration of these signaling pathways in vivo is not fully understood. Variant hnf1 (Vhnf1) is a transcription factor involved in pancreas, liver, and kidney development and its mutation in zebrafish causes underdeveloped pancreas and liver. We investigated the signaling pathways that regulate vhnf1 expression during pancreas development. First, we showed that Bmp activity is required for vhnf1 expression in the endoderm. In chordin (a Bmp antagonist) morpholino (MO)-injected embryos, vhnf1 expression in endoderm and in endocrine beta cells is expanded. On the other hand, in alk8 (a type I TGFbeta receptor) MO-injected embryos, vhnf1 expression in the endoderm is significantly reduced. Second, we showed that Fgf signaling participates in regulation of pancreas development through the vhnf1 pathway. Third, we demonstrated that RA fails to rescue reduction of insulin expression in vhnf1 mutants, whereas overexpression of vhnf1 restores insulin expression that is repressed by treatment with a RA receptor inhibitor. And finally, we revealed that both Bmp and Fgf signals act genetically upstream of RA in directing pancreas development. Taken together, our data establish that vhnf1 acts downstream of the signaling pathways of RA, Bmp, and Fgf to regulate pancreas development in zebrafish.

  20. A theoretical model for the production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226.

    PubMed

    Melville, G; Fan Liu, Sau; Allen, B J

    2006-09-01

    Radium needles that were once implanted into tumours as a cancer treatment are now obsolete and constitute a radioactive waste problem, as their half-life is 1600 years. We are investigating the reduction of radium by transmutation on a small scale by bombarding Ra-226 with high-energy photons from a medical linear accelerator (linac) to produce Ra-225, which subsequently decays to Ac-225, which can be used as a generator to produce Bi-213 for use in 'targeted alpha therapy' for cancer. This paper examines the possibility of producing Ac-225 with a linac using an accurate theoretical model in which the bremsstrahlung photon spectrum at 18 MV linac electron energy is convoluted with the corresponding photonuclear cross sections of Ra-226. The total integrated yield can then be obtained and is compared with a computer simulation. This study shows that at 18 MV, the photonuclear reaction on Ra-226 can produce low activities of Ac-225 with a linac. However, a high power linac with high current, pulse length and frequency is needed to produce practical amounts of Ac-225 and a useful reduction of Ra-226.

  1. Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies.

    PubMed

    Ablain, Julien; Leiva, Magdalena; Peres, Laurent; Fonsart, Julien; Anthony, Elodie; de Thé, Hugues

    2013-04-08

    In PML/RARA-driven acute promyelocytic leukemia (APL), retinoic acid (RA) induces leukemia cell differentiation and transiently clears the disease. Molecularly, RA activates PML/RARA-dependent transcription and also initiates its proteasome-mediated degradation. In contrast, arsenic, the other potent anti-APL therapy, only induces PML/RARA degradation by specifically targeting its PML moiety. The respective contributions of RA-triggered transcriptional activation and proteolysis to clinical response remain disputed. Here, we identify synthetic retinoids that potently activate RARA- or PML/RARA-dependent transcription, but fail to down-regulate RARA or PML/RARA protein levels. Similar to RA, these uncoupled retinoids elicit terminal differentiation, but unexpectedly fail to impair leukemia-initiating activity of PML/RARA-transformed cells ex vivo or in vivo. Accordingly, the survival benefit conferred by uncoupled retinoids in APL mice is dramatically lower than the one provided by RA. Differentiated APL blasts sorted from uncoupled retinoid-treated mice retain PML/RARA expression and reinitiate APL in secondary transplants. Thus, differentiation is insufficient for APL eradication, whereas PML/RARA loss is essential. These observations unify the modes of action of RA and arsenic and shed light on the potency of their combination in mice or patients.

  2. Uncoupling RARA transcriptional activation and degradation clarifies the bases for APL response to therapies

    PubMed Central

    Ablain, Julien; Leiva, Magdalena; Peres, Laurent; Fonsart, Julien; Anthony, Elodie

    2013-01-01

    In PML/RARA-driven acute promyelocytic leukemia (APL), retinoic acid (RA) induces leukemia cell differentiation and transiently clears the disease. Molecularly, RA activates PML/RARA-dependent transcription and also initiates its proteasome-mediated degradation. In contrast, arsenic, the other potent anti-APL therapy, only induces PML/RARA degradation by specifically targeting its PML moiety. The respective contributions of RA-triggered transcriptional activation and proteolysis to clinical response remain disputed. Here, we identify synthetic retinoids that potently activate RARA- or PML/RARA-dependent transcription, but fail to down-regulate RARA or PML/RARA protein levels. Similar to RA, these uncoupled retinoids elicit terminal differentiation, but unexpectedly fail to impair leukemia-initiating activity of PML/RARA-transformed cells ex vivo or in vivo. Accordingly, the survival benefit conferred by uncoupled retinoids in APL mice is dramatically lower than the one provided by RA. Differentiated APL blasts sorted from uncoupled retinoid–treated mice retain PML/RARA expression and reinitiate APL in secondary transplants. Thus, differentiation is insufficient for APL eradication, whereas PML/RARA loss is essential. These observations unify the modes of action of RA and arsenic and shed light on the potency of their combination in mice or patients. PMID:23509325

  3. A Study on Association between Common Haematological Parameters and Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Barui, Gopinath; Adhikari, Anjan; Karmakar, Rupam; Ghosh, Udas Chandra; Das, Tushar Kanti

    2017-01-01

    Introduction Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease where assessment of disease activity is essential for management of patient. Currently, many composite scoring systems are used for evaluation of disease activity but they are mainly clinical-based. As several haematological parameters are altered due to systemic inflammatory process in RA, this study was intended to evaluate role of common haematological parameters to assess disease activity in RA. Aim To find out the association of disease activity of Rheumatoid Arthritis (RA) with platelet count, Mean Platelet Volume (MPV) and Haemoglobin (Hb) level so that these cost-effective haematological parameters can be used as additional factors to assess disease activity. Materials and Methods This hospital based cross-sectional study was done on newly diagnosed patients of RA along with age and sex matched healthy control population. Patients suffering from malignancies, renal failure, diabetes mellitus or RA patients on drug therapy were excluded. Clinically, disease activity of RA was measured using DAS 28-3 Score (Modified Disease Activity Score using three variables- tender joint count, swollen joint count and ESR). Haematological parameters were measured by automated cell counter. Results Total 80 cases were selected (60 female and 20 male). 48 patients with high disease activity (DAS 28-3>5.1) were labelled as Group-A and 32 with low to moderate disease activity (DAS 28-3 ≤5.1) as Group- B. Mean platelet count of patients of group A and group B were 4.53 lac/cmm and 2.17 lac/cmm respectively (p <0.001). MPV mean in group A and B were 11.86 fl and 10.19 fl respectively (p <0.001). Mean Hb (g/dl) was 10.05 and 12.25 for group A and B respectively (p=0.001) for male patients while in females it was 10.12 and 11.91 for group A and B, respectively (p=0.003). Mean platelet count and MPV in control population were 2.07 lac/cmm and 9.4 fl, respectively while mean Hb (g/dl) was 13.31 (male

  4. Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis

    PubMed Central

    Politi, Cristina; Triggianese, Paola; Rufini, Sara; Kroegler, Barbara; Perricone, Carlo; Latini, Andrea; Novelli, Giuseppe; Borgiani, Paola; Perricone, Roberto

    2017-01-01

    Objective Rheumatoid Arthritis (RA) is a progressive autoimmune disease characterized by chronic joint inflammation and structural damage. Remission or at least low disease activity (LDA) represent potentially desirable goals of RA treatment. Single nucleotide polymorphisms (SNPs) in several genes might be useful for prediction of response to therapy. We aimed at exploring 4 SNPs in candidate genes (STAT4, PTPN2, PSORS1C1 and TRAF3IP2) in order to investigate their potential role in the response to therapy with tumor necrosis factor inhibitors (TNF-i) in RA patients. Methods In 171 RA patients we investigated the following SNPs: rs7574865 (STAT4), rs2233945 (PSORS1C1), rs7234029 (PTPN2) and rs33980500 (TRAF3IP2). Remission, LDA, and EULAR response were registered at 6 months and 2 years after initiation of first line TNF-i [Adalimumab (ADA) and Etanercept (ETN)]. Results STAT4 variant allele was associated with the absence of a good/moderate EULAR response at 2 years of treatment in the whole RA group and in ETN treated patients. The PTPN2 SNP was associated with no good/moderate EULAR response at 6 months in ADA treated patients. Patients carrying PSORS1C1 variant allele did not reach LDA at 6 months in both the whole RA group and ETN treated patients. TRAF3IP2 variant allele was associated with the lack of LDA and remission achievement at 6 months in all RA cohort while an association with no EULAR response at 2 years of treatment occurred only in ETN treated patients. Conclusions For the first time, we reported that SNPs in STAT4, PTPN2, PSORS1C1, and TRAF3IP2 are associated with response to TNF-i treatment in RA patients; however, these findings should be validated in a larger population. PMID:28107378

  5. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    SciTech Connect

    Nigg, D.W.; Schwint, A.E.; Hartwell, J.K.; Heber, E.M.; Trivillin, V.; Castillo, J.; Wentzeis, L.; Sloan, P.; Wemple, C.A.

    2004-10-04

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  6. Collaborative Physical and Biological Dosimetry Studies for Neutron Capture Therapy at the RA-1 Research Reactor Facility

    SciTech Connect

    David W. Nigg; Amanda E. Schwint; John K. Hartwell; Elisa M. Heber; Veronica Trivillin; Jorge Castillo; Luis Wentzeis; Patrick Sloan; Charles A. Wemple

    2004-10-01

    Initial physical dosimetry measurements have been completed using activation spectrometry and thermoluminiscent dosimeters to characterize the BNCT irradiation facility developed at the RA-1 research reactor operated by the Argentine National Atomic Energy Commission in Buenos Aires. Some biological scoping irradiations have also been completed using a small-animal (hamster) oral mucosa tumor model. Results indicate that the RA-1 neutron source produces useful dose rates but that some improvements in the initial configuration will be needed to optimize the spectrum for thermal-neutron BNCT research applications.

  7. Relationship between VEGF Gene Polymorphisms and Serum VEGF Protein Levels in Patients with Rheumatoid Arthritis

    PubMed Central

    Paradowska-Gorycka, Agnieszka; Pawlik, Andrzej; Romanowska-Prochnicka, Katarzyna; Haladyj, Ewa; Malinowski, Damian; Stypinska, Barbara; Manczak, Malgorzata; Olesinska, Marzena

    2016-01-01

    Background Rheumatoid arthritis (RA) is one of the chronic autoimmune diseases, with genetic and environmental predisposition, and synovial angiogenesis is considered to be a notable stage in its pathogenesis. Angiogenesis or vascular proliferation has been suggested to be a pivotal mechanism involved in both inflammation/immune activation and joint invasion and destruction. RA may be considered an “angiogenic disease” because it is associated with active tissue neovascularization. Vascular endothelial growth factor (VEGF) promotes vascular permeability, regulates angiogenesis, endothelial cell proliferation and migration, chemotaxis, and capillary hyper permeability and therefore is involved in the development of inflammation. VEGF is the most potent proangiogenic molecule promoting the angiogenic phenotype of RA and is upregulated in RA. Objectives The aim of the study was to identify functional VEGF variants and their possible association with VEGF expression, susceptibility to and severity of RA. Methods 581 RA patients and of 341 healthy individuals were examined for -1154 A/G, -2578 A/C VEGF gene polymorphisms by PCR-RFLP method and for -634 G/C VEGF gene polymorphisms by TaqMan SNP genotyping assay. Serum VEGF levels in RA patients and controls were measured by ELISA. Results The -1154 A/G VEGF gene polymorphism under the codominant, recessive (AA+AG vs. GG) and dominant (AA vs. AG+GG) models were associated with RA (p = 0.0009; p = 0.004; p = 0.017, respectively). VEGF -2578 A/C revealed differences in the case-control distribution in codominant, recessive, dominant and overdominant models (all p<0.0001). Furthermore, the -634 G/C VEGF gene SNP was not correlated with susceptibility to RA in Polish population. The genotype-phenotype analysis showed significant association between the VEGF -1154 A/G and -634 G/C and mean value of the hemoglobin (all p = 0.05), additionally they relevated that the number of women with the polymorphic allele -2578 C was

  8. Ratio of Circulating IFNγ (+) "Th17 Cells" in Memory Th Cells Is Inversely Correlated with the Titer of Anti-CCP Antibodies in Early-Onset Rheumatoid Arthritis Patients Based on Flow Cytometry Methods of the Human Immunology Project.

    PubMed

    Kotake, Shigeru; Nanke, Yuki; Yago, Toru; Kawamoto, Manabu; Kobashigawa, Tsuyoshi; Yamanaka, Hisashi

    2016-01-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic joint inflammation characterized by activated T cells. IL-17 and Th17 cells play important roles in the pathogenesis of RA. Recently, plasticity in helper T cells has been demonstrated; Th17 cells can convert to Th1 cells. However, it remains to be elucidated whether this conversion occurs in the early phase of RA. Here, we validated the methods of the Human Immunology Project using only the cell-surface marker through measuring the actual expression of IL-17 and IFNγ. We also evaluated the expression of CD161 in human Th17 cells. We then tried to identify Th17 cells, IL-17(+)Th17 cells, and IFNγ (+)Th17 cells in the peripheral blood of early-onset RA patients using the standardized method of the Human Immunology Project. Our findings validated the method and the expression of CD161. The ratio of IFNγ (+)Th17 cells in memory T cells was inversely correlated to the titers of anti-CCP antibodies in the early-onset RA patients. These findings suggest that Th17 cells play important roles in the early phase of RA and that anti-IL-17 antibodies should be administered to patients with early phase RA, especially those with high titers of CCP antibodies.

  9. Physical Activity Enjoyment and Self-Efficacy As Predictors of Cancer Patients' Physical Activity Level

    PubMed Central

    Ungar, Nadine; Wiskemann, Joachim; Sieverding, Monika

    2016-01-01

    Background: Physical activity (PA) can support cancer patients during medical treatment by reducing side-effects and increasing quality of life. However, PA levels mostly decline after diagnosis. Which factors can explain if patients are able to remain or even increase their PA level? Self-efficacy is an important cognitive factor that has been linked to cancer patients' PA across many studies. In contrast, affective factors such as PA enjoyment have rarely been examined. We compare the influence of self-efficacy and PA enjoyment on cancer patients' PA levels after completion of an exercise or stress-management intervention. Methods: Outpatient cancer patients [N = 72; 54% female; M = 56 years, SD = 12.34; most with breast or colon cancer (34%, 15%)] were enrolled in the MOTIVACTION study, a 4-week intervention (1 h counseling followed by weekly phone calls), with pre-test (T1), post-test (T2), and a 10-week follow-up (T3). Participants were randomized to either an exercise intervention (emphasizing self-regulatory strategies for behavior change) or to a stress management intervention (coping and relaxation techniques). Sixty-seven patients remained in the study and completed the SQUASH assessment of PA, a measure of maintenance self-efficacy (7 items, Cronbach's α = 0.88) and PA enjoyment (2 items, Cronbach's α = 0.89). Regression analyses were calculated with PA level (at T2 and T3) as dependent variable and relative weight analyses were conducted. The study was registered at clinicalTrials.gov (unique identifier:NCT01576107; URL: https://clinicaltrials.gov/ct2/show/NCT01576107?term=motivaction&rank=1). Results: Baseline self-efficacy and change in PA enjoyment significantly predicted cancer patients' PA level at T2 adjusting for baseline PA and type of intervention. Relative weight (RW) analysis revealed that PA enjoyment (baseline and change together) explained 34.3% of the dependent variable, self-efficacy (baseline and change) explained 38.4%. At follow

  10. Cardiovascular risk assessment in patients with rheumatoid arthritis: The relevance of clinical, genetic and serological markers.

    PubMed

    López-Mejías, Raquel; Castañeda, Santos; González-Juanatey, Carlos; Corrales, Alfonso; Ferraz-Amaro, Iván; Genre, Fernanda; Remuzgo-Martínez, Sara; Rodriguez-Rodriguez, Luis; Blanco, Ricardo; Llorca, Javier; Martín, Javier; González-Gay, Miguel A

    2016-11-01

    Cardiovascular disease (CV) is the most common cause of premature mortality in patients with rheumatoid arthritis (RA). This is the result of an accelerated atherosclerotic process. Adequate CV risk stratification has special relevance in RA to identify patients at risk of CV disease. However, current CV risk screening and management strategies underestimate the actual CV risk in RA. Consequently, the search for additional tools that may help to identify those patients at high CV risk has become a key objective in the last years. In this regard, non-invasive surrogates, such as carotid ultrasonography, have been found to be excellent predictors of future CV events. In addition, several studies have revealed the relevance of a genetic component in the development of CV disease in RA patients. Besides an association with HLA-DRB1* shared epitope alleles other gene polymorphisms located inside and outside the HLA seem to influence the risk of cardiovascular disease in RA. Moreover, serum levels of some metabolic syndrome-related biomarkers, adipokines such as adiponectin and biomarkers of endothelial cell activation and inflammation such as Osteoprotegerin and Asymmetric dimethylarginine have recently been found useful for the prediction of CV disease in these patients. An update of the current knowledge on these potential markers, especially focused on new genetic and serological biomarkers is shown in this review.

  11. Lack of association between TLR4 rs4986790 polymorphism and risk of cardiovascular disease in patients with rheumatoid arthritis.

    PubMed

    García-Bermúdez, Mercedes; López-Mejías, Raquel; González-Juanatey, Carlos; Castañeda, Santos; Miranda-Filloy, José A; Blanco, Ricardo; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; González-Alvaro, Isidoro; Gómez-Vaquero, Carmen; Llorca, Javier; Martín, Javier; González-Gay, Miguel A

    2012-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased cardiovascular (CV) mortality. Toll-like receptor-4 (TLR4) activates the innate immune response via NF-kB pathway and mitogen-activated protein kinase signaling, leading to expression of proinflammatory cytokines and chemokines. The G allele of TLR4 rs4986790 (+896A>G, Asp299Gly) gene polymorphism has been implicated in reduction of risk of atherosclerosis. In this study, 1481 RA patients fulfilling the 1987 American College of Rheumatology (ACR) criteria were genotyped for the rs4986790 TLR4 variant to determine the influence of this variant in the risk of CV events in these patients. Also, HLA-DRB1 status was determined using molecular based methods. Moreover, potential influence of rs4986790 variant in the development of subclinical atherosclerosis was assessed in a subgroup of RA patients with no history of CV events by the measurement of surrogate markers of subclinical atherosclerosis. No statistically significant differences in allele or genotype frequencies for the rs4986790 variant between RA patients who experienced CV events or not were found. Likewise, no significant association between this gene variant and any of the surrogate markers of subclinical atherosclerosis was found. In summary, results in our study do not support the hypothesis that the rs4986790 (+896A>G, Asp299Gly) TLR4 variant may influence predisposition for subclinical atherosclerosis and clinically evident CV disease in RA patients.

  12. Ra and Rn isotopes as natural tracers of submarine groundwater discharge in Tampa Bay, Florida

    USGS Publications Warehouse

    Swarzenski, P.W.; Reich, C.; Kroeger, K.D.; Baskaran, M.

    2007-01-01

    A suite of naturally occurring radionuclides in the U/Th decay series (222Rn, 223,224,226,228Ra) were studied during wet and dry conditions in Tampa Bay, Florida, to evaluate their utility as groundwater discharge tracers, both within the bay proper and within the Alafia River/estuary — a prominent free-flowing river that empties into the bay. In Tampa Bay, almost 30% of the combined riverine inputs still remain ungauged. Consequently, groundwater/surface water (hyporheic) exchange in the discharging coastal rivers, as well as submarine groundwater discharge (SGD) within the bay, are still unresolved components of this system's water and material budgets. Based on known inputs and sinks, there exists an excess of 226Ra in the water column of Tampa Bay, which can be evaluated in terms of a submarine groundwater contribution to the bay proper. Submarine groundwater discharge rates calculated using a mass balance of excess 226Ra ranged from 2.2 to 14.5 L m− 2 day− 1, depending on whether the estuarine residence time was calculated using 224Ra/xs228Ra isotope ratios, or whether a long term, averaged model-derived estuarine residence time was used. When extrapolated to the total shoreline length of the bay, such SGD rates ranged from 1.6 to 10.3 m3 m− 1 day− 1. Activities of 222Rn were also elevated in surface water and shallow groundwater of the bay, as well as in the Alafia River estuary, where upstream activities as high as 250 dpm L− 1 indicate enhanced groundwater/surface water exchange, facilitated by an active spring vent. From average nutrient concentrations of 39 shallow, brackish, groundwater samples, rates of nutrient loading into Tampa Bay by SGD rates were estimated, and these ranged from 0.2 to 1.4 × 105 mol day− 1 (PO43−), 0.9–6.2 × 105 mol day− 1 (SiO4−), 0.7–5.0 × 105 mol day− 1 (dissolved organic nitrogen, DON), and 0.2–1.4 × 106 mol day− 1 (total dissolved nitrogen, TDN). Such nutrient loading estimates, when compared

  13. Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

    PubMed Central

    Guillou, Clément; Fréret, Manuel; Fondard, Emeline; Derambure, Céline; Avenel, Gilles; Golinski, Marie-Laure; Verdet, Mathieu; Boyer, Olivier; Caillot, Frédérique; Musette, Philippe; Lequerré, Thierry; Vittecoq, Olivier

    2016-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA. PMID:27025255

  14. Concentration of 210Po, 226Ra and 228Ac in non-siliceous environmental materials

    NASA Astrophysics Data System (ADS)

    Houmani, Zidan Mohamed M.; Bradley, D. A.; Maah, Mohd. Jamil; Ahmed, Zaharuddin

    2001-06-01

    The present interest concerns the possible anthropomorphic enhancement of naturally occurring radioactive material (NORM) in non-siliceous media, in particular, sediment from a river running alongside a crude oil facility and alluvial samples from the site of a now defunct minerals benefication plant. We use gamma spectrometry for 226Ra and 228Ac, and for 210Po we use alpha spectrometry in association with a hydrochloric acid based radiochemical method for the extraction of 210Po. Using 209Po to monitor polonium extraction from samples we find the concentrations of 210Po, 226Ra and 228Ac in river sediments to be in accord with typical background values (˜0.04 Bq g -1 dry), while for sub-surface soils located nearby we find the respective activity concentrations to accord with low background values (˜0.02 Bq g -1dry). For alluvial material from the site of a defunct minerals benefications plant we have found 210Po concentrations of ˜11 Bq g -1 (dry) in two of three samples and 30 Bq g -1 (dry) in the remaining sample; 226Ra and 228Ac were some several times these concentrations. In support of the methods we have adopted in present evaluations we find IAEA-300 Baltic Sea sediment reference material to contain 210Po concentrations that are within the IAEA confidence interval for this material.

  15. [sup 223]Ra levels fed in the [sup 223]Fr [beta] decay

    SciTech Connect

    Abdul-Hadi, A.; Barci, V.; Weiss, B.; Maria, H.; Ardisson, G. ); Hussonnois, M.; Constantinescu, O. )

    1993-01-01

    The [sup 223]Fr [beta] decay was reinvestigated using high-resolution single [gamma] spectrometry as well as [gamma]-[gamma] coincidence techniques. For single [gamma]-spectra measurements, radiochemically pure [sup 223]Fr sources were obtained by chromatographic separation from a 75 MBq activity [sup 227]Ac parent source and continuously purified of [sup 223]Ra and daughters. The analysis of the [gamma] spectra of 30 sources showed the existence of 131 [gamma] lines, of which 87 are reported for the first time in the [sup 223]Fr [beta] decay although many of them are observed following the [sup 227]Th [alpha] decay. The [sup 223]Fr half-life was remeasured and found to be [ital T][sub 1/2]=22.00[plus minus]0.07 min. [gamma]-[gamma]-[ital t] coincidence measurements were also carried out with [sup 223]Fr purified sources. The [sup 223]Ra level scheme was built on the basis of our [gamma] data, as well as [sup 227]Th [alpha]-decay data. Among the 32 excited [sup 223]Ra levels, of which 22 were also known from [sup 227]Th [alpha] decay, 13 are newly reported from [sup 223]Fr [beta] decay. Low energy levels ([ital E][lt]400 keV) may be classified as parity doublet bands according to the predictions of the reflection asymmetric rotor model. Above a 700 keV gap, a coexistence of symmetric and asymmetric shapes including both static and dynamic octupole correlations is suggested.

  16. Prognostic Factors Toward Clinically Relevant Radiographic Progression in Patients With Rheumatoid Arthritis in Clinical Practice

    PubMed Central

    Koga, Tomohiro; Okada, Akitomo; Fukuda, Takaaki; Hidaka, Toshihiko; Ishii, Tomonori; Ueki, Yukitaka; Kodera, Takao; Nakashima, Munetoshi; Takahashi, Yuichi; Honda, Seiyo; Horai, Yoshiro; Watanabe, Ryu; Okuno, Hiroshi; Aramaki, Toshiyuki; Izumiyama, Tomomasa; Takai, Osamu; Miyashita, Taiichiro; Sato, Shuntaro; Kawashiri, Shin-ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Origuchi, Tomoki; Nakamura, Hideki; Aoyagi, Kiyoshi; Eguchi, Katsumi; Kawakami, Atsushi

    2016-01-01

    Abstract To determine prognostic factors of clinically relevant radiographic progression (CRRP) in patients with rheumatoid arthritis (RA) in clinical practice. We performed a multicenter prospective study in Japan of biological disease-modifying antirheumatic drug (bDMARD)-naive RA patients with moderate to high disease activity treated with conventional synthetic DMARDs (csDMARDs) at study entry. We longitudinally observed 408 patients for 1 year and assessed disease activity every 3 months. CRRP was defined as yearly progression of modified total Sharp score (mTSS) > 3.0 U. We also divided the cohort into 2 groups based on disease duration (<3 vs ≥3 years) and performed a subgroup analysis. CRRP was found in 10.3% of the patients. A multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: CRP at baseline (0.30 mg/dL increase, 95% confidence interval [CI] 1.01–1.11), time-integrated Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR) during the 1 year postbaseline (12.4-unit increase, 95%CI 1.17–2.59), RA typical erosion at baseline (95%CI 1.56–21.1), and the introduction of bDMARDs (95%CI 0.06–0.38). The subgroup analysis revealed that time-integrated DAS28-ESR is not a predictor whereas the introduction of bDMARDs is a significant protective factor for CRRP in RA patients with disease duration <3 years. We identified factors that could be used to predict the development of CRRP in RA patients treated with DMARDs. These variables appear to be different based on the RA patients’ disease durations. PMID:27124044

  17. U-isotopes and (226)Ra as tracers of hydrogeochemical processes in carbonated karst aquifers from arid areas.

    PubMed

    Guerrero, José Luis; Vallejos, Ángela; Cerón, Juan Carlos; Sánchez-Martos, Francisco; Pulido-Bosch, Antonio; Bolívar, Juan Pedro

    2016-07-01

    Sierra de Gádor is a karst macrosystem with a highly complex geometry, located in southeastern Spain. In this arid environment, the main economic activities, agriculture and tourism, are supported by water resources from the Sierra de Gádor aquifer system. The aim of this work was to study the levels and behaviour of some of the most significant natural radionuclides in order to improve the knowledge of the hydrogeochemical processes involved in this groundwater system. For this study, 28 groundwater and 7 surface water samples were collected, and the activity concentrations of the natural U-isotopes ((238)U, (235)U and (234)U) and (226)Ra by alpha spectrometry were determined. The activity concentration of (238)U presented a large variation from around 1.1 to 65 mBq L(-1). Elevated groundwater U concentrations were the result of oxidising conditions that likely promoted U dissolution. The PHREEQC modelling code showed that dissolved U mainly existed as uranyl carbonate complexes. The (234)U/(238)U activity ratios were higher than unity for all samples (1.1-3.8). Additionally, these ratios were in greater disequilibrium in groundwater than surface water samples, the likely result of greater water-rock contact time. (226)Ra presented a wide range of activity concentrations, (0.8 up to about 4 × 10(2) mBq L(-1)); greatest concentrations were detected in the thermal area of Alhama. Most of the samples showed (226)Ra/(234)U activity ratios lower than unity (median = 0.3), likely the result of the greater mobility of U than Ra in the aquifer system. The natural U-isotopes concentrations were strongly correlated with dissolution of sulphate evaporites (mainly gypsum). (226)Ra had a more complex behaviour, showing a strong correlation with water salinity, which was particularly evident in locations where thermal anomalies were detected. The most saline samples showed the lowest (234)U/(238)U activity ratios, probably due to fast uniform bulk mineral dissolution

  18. A Single Nucleotide Polymorphism in the Il17ra Promoter Is Associated with Functional Severity of Ankylosing Spondylitis

    PubMed Central

    Vidal-Castiñeira, Jose Ramón; López-Vázquez, Antonio; Diaz-Peña, Roberto; Diaz-Bulnes, Paula; Martinez-Camblor, Pablo; Coto, Eliecer; Coto-Segura, Pablo; Bruges-Armas, Jacome; Pinto, Jose Antonio; Blanco, Francisco Jose; Sánchez, Alejandra; Mulero, Juan; Queiro, Ruben; Lopez-Larrea, Carlos

    2016-01-01

    The aim of this study was to identify new genetic variants associated with the severity of ankylosing spondylitis (AS). We sequenced the exome of eight patients diagnosed with AS, selected on the basis of the severity of their clinical parameters. We identified 27 variants in exons and regulatory regions. The contribution of candidate variants found to AS severity was validated by genotyping two Spanish cohorts consisting of 180 cases/300 controls and 419 cases/656 controls. Relationships of SNPs and clinical variables with the Bath Ankylosing Spondylitis Disease Activity and Functional Indices BASDAI and BASFI were analyzed. BASFI was standardized by adjusting for the duration of the disease since the appearance of the first symptoms. Refining the analysis of SNPs in the two cohorts, we found that the rs4819554 minor allele G in the promoter of the IL17RA gene was associated with AS (p<0.005). This variant was also associated with the BASFI score. Classifying AS patients by the severity of their functional status with respect to BASFI/disease duration of the 60th, 65th, 70th and 75th percentiles, we found the association increased from p60 to p75 (cohort 1: p<0.05 to p<0.01; cohort 2: p<0.01 to p<0.005). Our findings indicate a genetic role for the IL17/ILRA axis in the development of severe forms of AS. PMID:27415816

  19. "LJ" Series "Redefining RA": Keeping up with Genres

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    Genre is a hot issue in readers' advisory (RA) circles right now. Many people are looking at how genre functions and morphs. Studying a genre is not a new idea. Over two decades ago, and even longer in less formal ways, librarians began gathering to study genres--asking such questions as in what genre does this book fit and why, what are its…

  20. Observation of the negative ions: Ra[sup [minus

    SciTech Connect

    Zhao, X.; Nadeau, M.; Garwan, M.A.; Kilius, L.R.; Litherland, A.E. )

    1993-11-01

    The negative ions of the isotopes [sup 226]Ra, [sup 231]Pa, and [sup 244]Pu have been observed by means of accelerator mass spectrometry and their properties compared with the negative ions of Th and U. The electron affinities of all these elements have been estimated to be similar and greater than 50 meV.

  1. The influence of lifestyle habits on quality of life in patients with established rheumatoid arthritis-A constant balancing between ideality and reality.

    PubMed

    Malm, Karina; Bremander, Ann; Arvidsson, Barbro; Andersson, Maria L E; Bergman, Stefan; Larsson, Ingrid

    2016-01-01

    Introduction Rheumatoid arthritis (RA) is a chronic, inflammatory, and systemic disease with symptoms that limit activities and affect quality of life. RA is associated with an increased risk of developing comorbidities, some of which are also known to be associated with lifestyle habits such as physical activity, diet, smoking, and alcohol. There has been an augmented focus on the implementation and maintenance of healthy lifestyle habits even for patients with RA in the past decade, but little is known about the link between patients' experiences of lifestyle habits and quality of life. The aim of the study was thus to describe and explore how patients with established RA experience the influence of lifestyle habits on quality of life. Methods The study had a descriptive and explorative design, based on qualitative content analysis. Strategic sampling was used in order to achieve variations in experiences. Twenty-two patients with RA (14 women and 8 men) from 30 to 84 years old, with a disease duration ranging from 8 to 23 years, were interviewed. Results The analysis of the influence of lifestyle habits on quality of life resulted in the theme balancing between ideality and reality. Three categories emerged about how lifestyle habits influenced quality of life by limitations (including insufficiency and adaptation), self-regulation (including guilt and motivation), and companionship (including belonging and pleasure). Conclusions Quality of life for patients with established RA was influenced by the balance between ideality and reality in the lifestyle habits: physical activity, diet, smoking, and alcohol. This is important new knowledge for health professionals when discussing lifestyle habits with RA patients.

  2. Cancer Prehabilitation for Patients Starting from Active Treatment to Surveillance

    PubMed Central

    Shun, Shiow-Ching

    2016-01-01

    The purpose of this brief summary is to introduce the concept of cancer prehabilitation and the role of oncology nurses in prehabilitation care. Cancer prehabilitation has been defined by Sliver and Baima (2013) as “a process on the cancer continuum of care that occurs between the time of cancer diagnosis and the beginning of acute treatment.” The evidence supports the notion that prehabilitation programs can improve physical and psychological health outcomes and decrease overall health care costs. The care model for cancer prehabilitation should include timely and efficient assessment throughout the care continuum with a focus on improving outcomes in cancer at every stage. During the cancer journey, three types of assessment with different aims are included: (1) prehabilitation assessment pretreatment, (2) rehabilitation assessment at early post treatment, and (3) health promotion assessment at the end of treatment. Specific prehabilitation assessment and interventions for treatment-related complications or major side-effects should be considered. Teaching, counseling, discharge planning, and coordination should also be part of an oncology nurse's role in cancer prehabilitation. It is suggested that cancer care managers or navigators be trained in the assessment of their patients’ physical and psychological status once the cancer diagnosis has been identified and the patient has decided to receive active treatment, especially for those waiting for surgery at home. Oncology nurses could increase their competence with prehabilitation care by gaining knowledge about cancer-related treatments and their outcomes for specific cancers and by strengthening the ability to assess the functional status and psychological distress of their patients. PMID:27981135

  3. Effectiveness of Certolizumab Pegol in Treating Rheumatoid Arthritis Patients with Persistent Inflamed Residual Mono- or Oligosynovitis Resistant to Prior TNF-α Inhibitors

    PubMed Central

    Koarada, Syuichi; Tsuboi, Masahiko; Komine, Mitsunori; Nakao, Yoshinobu; Tokuda, Yukiko; Ono, Yukihide; Tashiro, Satoko; Maruyama, Akihito; Ono, Nobuyuki; Ohta, Akihide; Tada, Yoshifumi

    2015-01-01

    We report four cases of successful treatment with certolizumab pegol (CZP) of rheumatoid arthritis (RA) patients with persistent inflamed residual mono- or oligosynovitis resistant to prior TNF-α inhibitors. Although the patients were in a moderate disease activity, a low activity, or a remission of RA, they sustained inflammatory mono-/oligoarthritis even after treatment with prior TNF inhibitors. They were then all treated with CZP and observed in a serial ultrasonography. In all cases, the positive power Doppler signals in the joint have disappeared promptly and all of the patients were able to retain remission in the long term. The treatment of CZP to the refractory mono-/oligoarthritis of inflammatory synovitis in RA patients has not been previously described. The cases suggest that it may be associated with the feature of CZP, possible effective penetration into the site of inflammation. PMID:26451269

  4. Combined effects of three independent SNPs greatly increase the risk estimate for RA at 6q23.

    PubMed

    Orozco, Gisela; Hinks, Anne; Eyre, Steve; Ke, Xiayi; Gibbons, Laura J; Bowes, John; Flynn, Edward; Martin, Paul; Wilson, Anthony G; Bax, Deborah E; Morgan, Ann W; Emery, Paul; Steer, Sophia; Hocking, Lynne; Reid, David M; Wordsworth, Paul; Harrison, Pille; Thomson, Wendy; Barton, Anne; Worthington, Jane

    2009-07-15

    The most consistent finding derived from the WTCCC GWAS for rheumatoid arthritis (RA) was association to a SNP at 6q23. We performed a fine-mapping of the region in order to search the 6q23 region for additional disease variants. 3962 RA patients and 3531 healthy controls were included in the study. We found 18 SNPs associated with RA. The SNP showing the strongest association was rs6920220 [P = 2.6 x 10(-6), OR (95% CI) 1.22 (1.13-1.33)]. The next most strongly associated SNP was rs13207033 [P = 0.0001, OR (95% CI) 0.86 (0.8-0.93)] which was perfectly correlated with rs10499194, a SNP previously associated with RA in a US/European series. Additionally, we found a number of new potential RA markers, including rs5029937, located in the intron 2 of TNFAIP3. Of the 18 associated SNPs, three polymorphisms, rs6920220, rs13207033 and rs5029937, remained significant after conditional logistic regression analysis. The combination of the carriage of both risk alleles of rs6920220 and rs5029937 together with the absence of the protective allele of rs13207033 was strongly associated with RA when compared with carriage of none [OR of 1.86 (95% CI) (1.51-2.29)]. This equates to an effect size of 1.50 (95% CI 1.21-1.85) compared with controls and is higher than that obtained for any SNP individually. This is the first study to show that the confirmed loci from the GWA studies, that confer only a modest effect size, could harbour a significantly greater effect once the effect of additional risk variants are accounted for.

  5. Use of medication reminders in patients with rheumatoid arthritis.

    PubMed

    Bruera, Sebastian; Barbo, Andrea G; Lopez-Olivo, Maria A

    2016-11-01

    Patients with rheumatoid arthritis (RA) often have difficulties adhering to their medical treatment plans. We determined the characteristics of patients with RA who used reminders and the association between reminders and adherence. A total of 201 patients with RA were asked the frequency of reminders use such as pill containers, calendars, or diaries. Patients completed self-reported adherence questionnaires, and their disease activity and functional ability were measured. Sixty-eight patients (34 %) reported using a reminder. Factors associated with reminder use were older age (yes-mean age 54 vs no-mean age 49, p = 0.004), race (Whites-54 % vs Blacks-30 % vs Hispanics-26 %, p = 0.003), and sex (males-50 % vs females 28 %, p = 0.005). Working patients were less likely to use reminders (employed-21 % vs unemployed-43 %, p = 0.006). Use of calendars was associated with adherence while away from home (ρ = 0.16, p = 0.03), when busy (ρ = 0.16, p = 0.03), and use of any reminder was associated with adherence when running out of pills (ρ = 0.15, p = 0.04). The use of calendar reminders was associated with fewer tender joints (ρ = -0.17, p = 0.02). Few patients with RA used reminders, and whites, males and patients of increasing age were most likely to use reminders. Our findings show that reminders can assist patients with RA in taking medications, particularly when they are most prone to forgetting, such as when they are away from home or busy. Providers should encourage using reminders as a low-cost aid to enhance adherence.

  6. Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways

    PubMed Central

    Shang, Wei; Zhao, Ling-Jie; Dong, Xiao-Lei; Zhao, Zhi-Ming; Li, Jing; Zhang, Bei-Bei; Cai, Hui

    2016-01-01

    The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic pot