Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis

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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

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis.

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Conigliaro, Paola; Ciccacci, Cinzia; Politi, Cristina; Triggianese, Paola; Rufini, Sara; Kroegler, Barbara; Perricone, Carlo; Latini, Andrea; Novelli, Giuseppe; Borgiani, Paola; Perricone, Roberto

2017-01-01

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. 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)]. 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. 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.

Polymorphisms in STAT4, PTPN2, PSORS1C1 and TRAF3IP2 Genes Are Associated with the Response to TNF Inhibitors in Patients with Rheumatoid Arthritis.

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Paola Conigliaro

Full Text Available 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.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].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.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.

Disease duration and age influence CARD15 expression in Crohn’s disease

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Elżbieta Poniewierka

2016-01-01

Full Text Available One of the susceptibility genes in Crohn’s disease (CD is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs with E.Z.N.A. Total RNA Kit (Omega Bio-tek then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFα agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn›s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression.

Protective effect of chlorpromazine on TNF-mediated hapten-induced irritant reaction.

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Erroi, A; Fantuzzi, G; Demitri, M T; Echtenacher, B; Gnocchi, P; Isetta, A; Ghezzi, P

1995-01-01

Picryl chloride-induced irritant reaction (IR) was shown to be mediated by tumor necrosis factor (TNF). Anti-TNF monoclonal antibodies, but not interleukin 1 receptor antagonist (IL-1 Ra), had a protective effect. Chlorpromazine (CPZ), an inhibitor of TNF synthesis, protected against IR and inhibited the IR-associated TNF induction in ear homogenates. Investigation of the role of polymorphonuclear leukocyte (PMN) in neutropenic mice showed that neutropenia did not prevent the development of the IR.

Role of NOD2/CARD15 in coronary heart disease

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Förster Matti

2007-11-01

Full Text Available Abstract Background: Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion. Genetic variation in the CARD15 gene, which encodes NOD2, was previously shown to result in a barrier defect that causes chronic inflammatory disorders (e.g. Crohn disease. In the present study, we investigated the possible involvement of NOD2/CARD15 in the pathology of CHD by i analyzing the local expression of NOD2 in atherectomy versus healthy tissue (n = 5 each using histochemical immunofluorescence and ii by testing the three major functional CARD15 variants (R702W, G908R and 1007fs for association with early-onset CHD in 900 German patients and 632 healthy controls. Results: In atherectomy tissue of CHD patients, NOD2 was detected in inflammatory cells at the luminal sides of the lesions. However, the allele and genotype frequencies of the three major CARD15 polymorphisms did not differ between CHD patients and controls. Conclusion: The NOD2 up-regulation in atheroma lesions indicates an involvement of this protein in the pathology of CHD. Although NOD2 could be important in local immune response mechanisms, none of the analyzed CARD15 variants seem to play a significant role in the etiology of CHD.

Effect of Bizhongxiao decoction and its dismantled formulae on IL-1 and TNF levels in collagen-induced arthritis in rat synovial joints

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Guo Ya-jing

2012-11-01

Full Text Available Abstract Background Rheumatoid arthritis (RA, a chronic autoimmune disease, affects sufferers in many different ways. Treatment of this chronic condition is particularly challenging. Traditional Chinese Medicine (TCM provides alternatives. Bizhongxiao decoction (BZX is a TCM complex, which has been used clinically for many years to treat RA. The purpose of this study is to compare the effects of BZX decoction and its dismantled formulae on IL-1 and TNF-1 levels in rats with RA, and to elucidate its mechanism of action. Methods Ninety healthy normal female SD rats were randomly divided into six groups: normal (control, model, BZX decoction, and the three dismantled formulae (I: heat-clearing and detoxication, II: dissipating dampness, and III: blood circulation promotion. Apart from the normal (control group, the rats in each group were injected subcutaneously with bovine type II collagen and complete Freund adjuvant to establish a collagen-induced arthritis model, so that inhibition of foot swelling in the rats by BZX decoction and its dismantled formulae could be observed. Immunohistochemistry was used to assess the levels of the inflammatory cytokines IL-1 and TNF in synovial joints at various time points. Results Twenty-one days after the model was established, the levels of TNF and IL-1 were significantly higher in the model group, BZX decoction group and dismantled formula groups I, II and III than in the normal controls (P  Conclusions BZX decoction and the three dismantled formulae examined down-regulated the inflammatory factors IL-1 and TNF in collagen-induced arthritis rat models, but BZX exerted the strongest effect.

Systemic blockade of TNF-α does not improve insulin resistance in humans.

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Ferraz-Amaro, I; Arce-Franco, M; Muñiz, J; López-Fernández, J; Hernández-Hernández, V; Franco, A; Quevedo, J; Martínez-Martín, J; Díaz-González, F

2011-10-01

The purpose of this study was to determine whether long-term modulation of inflammatory activity by tumor necrosis factor (TNF)-α inhibitors has some influence on insulin resistance (IR). 16 active rheumatoid arthritis (RA) patients without CV risk factors treated with anti-TNF-α agents were included in this study. RA activity by disease activity score 28, IR by HOMA2-IR, body composition by impedance analysis, physical activity by accelerometry, abdominal fat distribution by magnetic resonance imaging, and serum level of key adipokines by ELISA were measured at baseline and during a 1-year follow-up period. Patient body mass index increased significantly (26.94 ± 3.88 vs. 28.06 ± 4.57 kg/m2, p=0.02) after 1 year of treatment. Body composition, in terms of fat and fat-free mass, remained unchanged except for a significant elevation in body cell mass (25.50 ± 4.60 vs. 26.60 ± 3.17 kg, p=0.02). Basal levels of IR in the RA patients included in this study were significantly higher than healthy controls (1.6 ± 0.8 vs. 1.11 ± 0.56, p=0.011) but did not change during the follow-up. Nor did basal concentrations of adiponectin, visfatin, leptin, ghrelin, resistin, and apelin in response to anti-TNF-α treatment; only retinol-binding protein 4, showed a significant increase (51.7 ± 32.7 vs. 64.9 ± 28.4 μg/ml, p=0.03) at the end of the study. IR, adiposity distribution, and serum levels of most adipokines are not significantly affected by long-term inhibition of TNF-α in RA patients. Our data suggest that although systemic blockade of TNF-α exerts an anticachectic effect in RA patients, it does not seem to play a major role in IR. © Georg Thieme Verlag KG Stuttgart · New York.

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) mediates repression of TNF-α by decreasing levels of acetylated histone H3 and H4 at its promoter

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Engdahl, Ryan; Monroy, M. Alexandra; Daly, John M.

2007-01-01

Prostaglandin metabolite 15-Deoxy-Δ 12,14 -prostaglandin J2 (15d-PGJ2) is known to inhibit a number of pro-inflammatory cytokines as well as being a ligand for nuclear receptor PPARγ. We investigated the ability of 15d-PGJ2 to inhibit TNF-α gene expression through mechanisms that involve histone modification. Pretreatment with 15d-PGJ2 (10 μM) inhibited LPS-stimulated TNF-α mRNA in THP-1 monocytes or PMA-differentiated cells to nearly basal levels. A specific PPARγ ligand, GW1929, failed to inhibit LPS-induced TNF-α mRNA expression nor did a PPARγ antagonist, GW9662, alter the repression of TNF-α mRNA in LPS-stimulated cells pretreated with 15d-PGJ2 suggesting a PPARγ-independent inhibition of TNF-α mRNA in THP-1 cells. Transfection studies with a reporter construct and subsequent treatment with 15d-PGJ2 demonstrated a dose-dependent inhibition of the TNF-α promoter. Additional studies demonstrated that inhibition of histone deacetylases with trichostatin A (TSA) or overexpression of histone acetyltransferase CBP could overcome 15d-PGJ2-mediated repression of the TNF-α promoter, suggesting that an important mechanism whereby 15d-PGJ2 suppresses a cytokine is through factors that regulate histone modifications. To examine the endogenous TNF-α promoter, chromatin immunoprecipitations (ChIP) were performed. ChIP assays demonstrated that LPS stimulation induced an increase in histone H3 and H4 acetylation at the TNF-α promoter, which was reduced in cells pretreated with 15d-PGJ2. These results highlight the ability of acetylation and deacetylation factors to affect the TNF-α promoter and demonstrate that an additional important mechanism whereby 15d-PGJ2 mediates TNF-α transcriptional repression by altering levels of acetylated histone H3 and H4 at its promoter

Circulating cytokines and cytokine receptors in infliximab treatment failure due to TNF-α independent Crohn disease

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Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine

2016-01-01

-IFX antibodies. Circulating cytokines and cytokine receptors were assessed by enzyme-linked immunosorbent assay: granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1α, IL-1β, IL-1Ra, IL-6, IL-10, IL-12p70, soluble TNF receptor (sTNF-R) 1, sTNF-R2, IL-17A, and monocyte chemotactic...

The risk of familial Mediterranean fever in MEFV heterozygotes: a statistical approach.

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Jéru, Isabelle; Hentgen, Véronique; Cochet, Emmanuelle; Duquesnoy, Philippe; Le Borgne, Gaëlle; Grimprel, Emmanuel; Stojanovic, Katia Stankovic; Karabina, Sonia; Grateau, Gilles; Amselem, Serge

2013-01-01

Familial Mediterranean fever (FMF) is an autosomal recessive autoinflammatory disorder due to MEFV mutations and one of the most frequent Mediterranean genetic diseases. The observation of many heterozygous patients in whom a second mutated allele was excluded led to the proposal that heterozygosity could be causal. However, heterozygosity might be coincidental in many patients due to the very high rate of mutations in Mediterranean populations. To better delineate the pathogenicity of heterozygosity in order to improve genetic counselling and disease management. Complementary statistical approaches were used: estimation of FMF prevalence at population levels, genotype comparison in siblings from 63 familial forms, and genotype study in 557 patients from four Mediterranean populations. At the population level, we did not observe any contribution of heterozygosity to disease prevalence. In affected siblings of patients carrying two MEFV mutations, 92% carry two mutated alleles, whereas 4% are heterozygous with typical FMF diagnosis. We demonstrated statistically that patients are more likely to be heterozygous than healthy individuals, as shown by the higher ratio heterozygous carriers/non carriers in patients (pclassical Mendelian FMF per se, but constitutes a susceptibility factor for clinically-similar multifactorial forms of the disease. We also provide a first estimate of the risk for heterozygotes to develop FMF.

IL-15 expression on RA synovial fibroblasts promotes B cell survival.

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Marta Benito-Miguel

Full Text Available INTRODUCTION: The purpose of this study was to examine the role of RA Synovial Fibroblast (RASFib IL-15 expression on B cell survival. METHODS: Magnetically sorted peripheral blood memory B cells from 15 healthy subjects were cocultured with RASFib. RESULTS: RASFib constitutively expressed membrane IL-15. Survival of isolated B cells cultured for 6 days, below 5%, was extended in coculture with RASFib to 52+/-8% (p<0.001. IL-15 neutralizing agents but not isotype controls, reduced this rate to 31+/-6% (p<0.05. Interestingly, rhIL-15 had no effect on isolated B cells but significantly increased their survival in coculture with RASFib. In parallel, B cell IL-15R chains were upregulated in cocultures. BAFF and VCAM-1, that are expressed on RASFib, were tested as potential candidates involved in upregulating B cell IL-15R. Culture of B cells in the presence of rhBAFF or rhVCAM-1 resulted in significantly increased survival, together with upregulation of all three IL-15R chains; in parallel, rhIL-15 potentiated the anti-apoptotic effect of BAFF and VCAM-1. Both BAFF and VCAM-1 neutralizing agents downmodulated the effect of RASFib on B cell survival and IL-15R expression. In parallel, rhIL-15 had a lower effect on the survival of B cells cocultured with RASFib in the presence of BAFF or VCAM-1 neutralizing agents. Peripheral blood B cells from 15 early RA patients demonstrated an upregulated IL-15R and increased survival in cocultures. CONCLUSION: IL-15 expression on RASFib significantly contributes to the anti-apoptotic effect of RASFib on B cells. IL-15 action is facilitated by BAFF and VCAM-1 expressed on RASFib, through an upregulation of IL-15R chains.

CARD15 single nucleotide polymorphisms 8, 12 and 13 are not increased in ethnic Danes with sarcoidosis

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Milman, Nils; Nielsen, Ole Haagen; Hviid, Thomas Vauvert F

2007-01-01

and SNP13, respectively, were performed by capillary electrophoresis single-strand confirmation polymorphism in 53 patients with histologically verified sarcoidosis and in 103 healthy controls. RESULTS: The frequencies of CARD15 mutations in sarcoidosis patients were: SNP8, 4/106 chromosomes (3.8%); SNP12...... with Crohn's disease. OBJECTIVES: To evaluate whether ethnic Danes with sarcoidosis have an increased frequency of CARD15 mutations compared to healthy control subjects. METHODS: Genotyping for CARD15 mutations R702W, G908R, and L1007fsinsC, also designated single nucleotide polymorphism (SNP) SNP8, SNP12......, 2/106 chromosomes (1.9%); SNP13, 2/106 chromosomes (1.9%); SNP8+SNP12+SNP13, 8/106 chromosomes (7.6%). All 8 patients were heterozygous. The frequencies in controls were: SNP8, 9/206 chromosomes (4.4%); SNP12, 2/206 chromosomes (1.0%); SNP13, 4/206 chromosomes (1.9%); SNP8+SNP12+SNP13, 15...

The Analysis Mutation Of The CARD 15 Gene Variants In Chronic Periodontis

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Bahruddin Thalib, Dr.drg. M.Kes,Sp.Pros.

2014-01-01

As Conclusion, CARD 15 gene mutation with chronic periodontitis was found to have heterozygote mutation and homozygote mutation variants, and also found genetics variation that changed the composition of C??? T nucleotide at codon 802 in exon 4 amino acid changed from alanine to valine. Purpose of This study was to determine the variant of card 15 gene mutation with periodontitis chronic.

Estradiol increases the expression of TNF-α and TNF receptor 1 in lactotropes.

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Zaldivar, Verónica; Magri, María Laura; Zárate, Sandra; Jaita, Gabriela; Eijo, Guadalupe; Radl, Daniela; Ferraris, Jimena; Pisera, Daniel; Seilicovich, Adriana

2011-01-01

Estrogens are recognized modulators of pituitary cell renewal, sensitizing cells to mitogenic and apoptotic signals. Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays an important role in tissue homeostasis modulating cell proliferation, differentiation and death. We previously demonstrated that TNF-α-induced apoptosis of anterior pituitary cells from female rats is estrogen-dependent and predominant in cells from rats at proestrus when estradiol levels are the highest. Considering that one of the mechanisms involved in the apoptotic action of estrogens can result from increased expression of cytokines and/or their receptors, the aim of the present study was to evaluate the effect of estrogens on the expression of TNF-α and its receptor, TNF receptor 1 (TNFR1), in anterior pituitary cells. TNFR1 expression, determined by Western blot, was higher in anterior pituitary glands from rats at proestrus than at diestrus. Incubation of anterior pituitary cells from ovariectomized rats with 17β-estradiol enhanced TNFR1 protein expression. As determined by double immunocytochemistry, the expression of TNF-α and TNFR1 was detected in prolactin-, GH-, LH- and ACTH-bearing cells. 17β-estradiol increased the percentage of TNF-α and TNFR1-immunoreactive lactotropes but did not modify the number of GH-bearing cells expressing TNF-α or TNFR1. Our results demonstrate that estradiol increases the expression of TNF-α and TNFR1 in anterior pituitary cells, especially in lactotropes. The sensitizing action of estrogens to proapoptotic stimuli at proestrus in the anterior pituitary gland may involve changes in the expression of the TNF-α/TNFR1 system. Copyright © 2011 S. Karger AG, Basel.

The Janus kinase inhibitor tofacitinib inhibits TNF-α-induced gliostatin expression in rheumatoid fibroblast-like synoviocytes.

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Kawaguchi, Yohei; Waguri-Nagaya, Yuko; Tatematsu, Naoe; Oguri, Yusuke; Kobayashi, Masaaki; Nozaki, Masahiro; Asai, Kiyofumi; Aoyama, Mineyoshi; Otsuka, Takanobu

2018-01-15

Gliostatin (GLS) is known to have angiogenic and arthritogenic activity, and GLS expression levels in serum from patients with rheumatoid arthritis (RA) are significantly correlated with the disease activity. Tofacitinib is a novel oral Janus kinase (JAK) inhibitor and is effective in treating RA. However, the mechanism of action of tofacitinib in fibroblast-like synoviocytes (FLSs) has not been elucidated. The purpose of this study was to investigate the modulatory effects of tofacitinib on serum GLS levels in patients with RA and GLS production in FLSs derived from patients with RA. Six patients with RA who had failed therapy with at least one TNF inhibitor and were receiving tofacitinib therapy were included in the study. Serum samples were collected to measure CRP, MMP-3 and GLS expression. FLSs derived from patients with RA were cultured and stimulated by TNFα with or without tofacitinib. GLS expression levels were determined using reverse transcription-polymerase chain reaction (RT-PCR), EIA and immunocytochemistry, and signal transducer and activator of transcription (STAT) protein phosphorylation levels were determined by western blotting. Treatment with tofacitinib decreased serum GLS levels in all patients. GLS mRNA and protein expression levels were significantly increased by treatment with TNF-α alone, and these increases were suppressed by treatment with tofacitinib, which also inhibited TNF-α-induced STAT1 phosphorylation. JAK/STAT activation plays a pivotal role in TNF-α-mediated GLS up-regulation in RA. Suppression of GLS expression in FLSs has been suggested to be one of the mechanisms through which tofacitinib exerts its anti-inflammatory effects.

Discontinuation of Biologic Therapy in Rheumatoid Arthritis: Analysis from the Corrona RA Registry.

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Strand, Vibeke; Miller, Paul; Williams, Setareh A; Saunders, Katherine; Grant, Shannon; Kremer, Joel

2017-12-01

Despite the availability of multiple effective therapies, discontinuation/switching of treatment is common for many patients with rheumatoid arthritis (RA). This study was designed to examine initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs) within the Consortium of Rheumatology Researchers of North America (Corrona) RA Registry, and characterize reasons for discontinuation. Inclusion criteria were: Corrona-registered adults (≥18 years) with RA (2002-2011); age of RA onset: ≥16 years; ≥6 months' follow-up after initiation of first/subsequent bDMARD. Patients receiving both tumor necrosis factor antagonists and non-TNF antagonists were included. Treatment discontinuation was defined as first report of stopping initial therapy or initiation of new bDMARD at/between visits, using a follow-up physician questionnaire. Overall, 6209 patients met inclusion criteria and 80.7% received TNF antagonists. Median time to discontinuation/change of therapy was 25.1 months (26.5 months with TNF antagonists vs. 20.5 months with non-TNF antagonists; log-rank p < 0.0001); 82.2, 67.3, and 51.1% of patients remained on therapy at 6, 12, and 24 months, respectively. Reasons for discontinuation were captured for 49.2% of patients, including: loss of efficacy (35.8%); physician preference (27.8%); safety (20.1%); patient preference (17.9%); and no access to treatment (9.0%). Baseline factors with greatest correlation to discontinuation were modified Health Assessment Questionnaire scores, patient-reported anxiety/depression, initiation of bDMARD treatment in 2007-2010 versus 2002-2003, and Clinical Disease Activity Index scores. Almost one-third of patients in the US discontinue currently available bDMARD therapies for RA by 12 months and almost half by 24 months, most commonly due to loss of efficacy. Corrona LLC and MedImmune.

Loss-of-function CARD8 mutation causes NLRP3 inflammasome activation and Crohn's disease.

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Mao, Liming; Kitani, Atsushi; Similuk, Morgan; Oler, Andrew J; Albenberg, Lindsey; Kelsen, Judith; Aktay, Atiye; Quezado, Martha; Yao, Michael; Montgomery-Recht, Kim; Fuss, Ivan J; Strober, Warren

2018-05-01

In these studies, we evaluated the contribution of the NLRP3 inflammasome to Crohn's disease (CD) in a kindred containing individuals having a missense mutation in CARD8, a protein known to inhibit this inflammasome. Whole exome sequencing and PCR studies identified the affected individuals as having a V44I mutation in a single allele of the T60 isoform of CARD8. The serum levels of IL-1β in the affected individuals were increased compared with those in healthy controls, and their peripheral monocytes produced increased amounts of IL-1β when stimulated by NLRP3 activators. Immunoblot studies probing the basis of these findings showed that mutated T60 CARD8 failed to downregulate the NLRP3 inflammasome because it did not bind to NLRP3 and inhibit its oligomerization. In addition, these studies showed that mutated T60 CARD8 exerted a dominant-negative effect by its capacity to bind to and form oligomers with unmutated T60 or T48 CARD8 that impeded their binding to NLRP3. Finally, inflammasome activation studies revealed that intact but not mutated CARD8 prevented NLRP3 deubiquitination and serine dephosphorylation. CD due to a CARD8 mutation was not effectively treated by anti-TNF-α, but did respond to IL-1β inhibitors. Thus, patients with anti-TNF-α-resistant CD may respond to this treatment option.

Opium addiction increases interleukin 1 receptor antagonist (IL-1Ra) in the coronary artery disease patients.

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Saadat, Habibollah; Ziai, Seyed Ali; Ghanemnia, Maryam; Namazi, Mohammad Hasan; Safi, Morteza; Vakili, Hosein; Dabbagh, Ali; Gholami, Omid

2012-01-01

There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD) is a condition resulted from atherosclerosis which is dependent on the immune response. To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients. The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6) and interleukin-1Ra (IL-1Ra) were evaluated with ELISA method before, just after and 4 hours after the test. IL-1Ra (2183 pg/ml) tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that), although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes. Consumption of opium in CAD patients is associated with higher IL-1Ra levels.

Opium addiction increases interleukin 1 receptor antagonist (IL-1Ra in the coronary artery disease patients.

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Habibollah Saadat

Full Text Available BACKGROUND: There is evidence that opium addiction has immunosuppressant effects. Coronary artery disease (CAD is a condition resulted from atherosclerosis which is dependent on the immune response. PURPOSE: To evaluate plasma levels of interleukin-6 and interleukin-1Ra in 30 patients with three-vessel coronary artery disease, ejection fraction of more than 35% and to evaluate their changes after prognostic treadmill test in 15 opium addicted and 15 non-addicted patients. METHODS: The participants underwent prognostic treadmill test and plasma levels of interleukin-6 (IL-6 and interleukin-1Ra (IL-1Ra were evaluated with ELISA method before, just after and 4 hours after the test. RESULTS: IL-1Ra (2183 pg/ml tended to decrease over time in the opium addicted group (1372 pg/ml after prognostic treadmill test and 1034 pg/ml 4 hours after that, although such decrease did not reach the statistical significance. IL-1Ra levels were significantly higher in opium addicted than in non addicted patients. Opium addiction had no significant effect on IL-6 changes. CONCLUSION: Consumption of opium in CAD patients is associated with higher IL-1Ra levels.

Lack of association of variants previously associated with anti-TNF medication response in rheumatoid arthritis patients: results from a homogeneous Greek population.

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Zervou, Maria I; Myrthianou, Efsevia; Flouri, Irene; Plant, Darren; Chlouverakis, Gregory; Castro-Giner, Francesc; Rapsomaniki, Panayiota; Barton, Anne; Boumpas, Dimitrios T; Sidiropoulos, Prodromos; Goulielmos, George N

2013-01-01

Treatment strategies blocking tumor necrosis factor (anti-TNF) have proven very successful in patients with rheumatoid arthritis (RA), showing beneficial effects in approximately 50-60% of the patients. However, a significant subset of patients does not respond to anti-TNF agents, for reasons that are still unknown. The aim of this study was to validate five single nucleotide polymorphisms (SNPs) of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been reported to predict anti-TNF outcome. In addition, two markers of RA susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF-treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA patient cohort consisted of 183 patients treated with either of 3 anti-TNF biologic agents (infliximab, adalimumab and etanercept) from the Clinic of Rheumatology of the University Hospital of Crete. The SNPs were genotyped by TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs) approach. Disease activity score in 28 joints (DAS28) at baseline and after 6 months were available for all patients and analysis of good versus poor response at 6 months was performed for each SNP. None of the 7 genetic markers correlated with treatment response. We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Greece.

The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis.

NARCIS (Netherlands)

Blom, M.; Kievit, W.; Fransen, J.; Kuper, I.H.; Broeder, A. den; Gendt, C.M. de; Jansen, T.L.Th.A.; Brus, H.L.; Laar, M.A. van der; Riel, P.L.C.M. van

2009-01-01

OBJECTIVE: To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS: Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

The reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent does not influence the effect of a second TNF blocking agent in patients with rheumatoid arthritis

NARCIS (Netherlands)

Blom, Marlies; Kievit, Wietske; Fransen, Jaap; Kuper, Ina H.; den Broeder, Alfons A.; De Gendt, Carla M.A.; Jansen, Tim L.; Brus, Herman L.M.; van de Laar, Mart A.F.J.; van Riel, Piet L.C.M.

2009-01-01

OBJECTIVE:To investigate whether the reason for discontinuation of the first tumor necrosis factor (TNF) blocking agent influences the effect of a second TNF blocking agent. METHODS:Data were used from 2 Dutch registries including patients with rheumatoid arthritis (RA) treated with TNF blocking

Lack of association of variants previously associated with anti-TNF medication response in rheumatoid arthritis patients: results from a homogeneous Greek population.

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Maria I Zervou

Full Text Available Treatment strategies blocking tumor necrosis factor (anti-TNF have proven very successful in patients with rheumatoid arthritis (RA, showing beneficial effects in approximately 50-60% of the patients. However, a significant subset of patients does not respond to anti-TNF agents, for reasons that are still unknown. The aim of this study was to validate five single nucleotide polymorphisms (SNPs of PTPRC, CD226, AFF3, MyD88 and CHUK gene loci that have previously been reported to predict anti-TNF outcome. In addition, two markers of RA susceptibility, namely TRAF1/C5 and STAT4 were assessed, in a cohort of anti-TNF-treated RA patients, from the homogeneous Greek island of Crete, Greece. The RA patient cohort consisted of 183 patients treated with either of 3 anti-TNF biologic agents (infliximab, adalimumab and etanercept from the Clinic of Rheumatology of the University Hospital of Crete. The SNPs were genotyped by TaqMan assays or following the Restriction Fragments Length Polymorphisms (RFLPs approach. Disease activity score in 28 joints (DAS28 at baseline and after 6 months were available for all patients and analysis of good versus poor response at 6 months was performed for each SNP. None of the 7 genetic markers correlated with treatment response. We conclude that the gene polymorphisms under investigation are not strongly predictive of anti-TNF response in RA patients from Greece.

NOD2/CARD15 genotype, cardiovascular disease and cancer in 43 600 individuals from the general population

DEFF Research Database (Denmark)

Yazdanyar, S.; Nordestgaard, B.G.

2010-01-01

from two large Danish general population cohorts followed for 31 years: the Copenhagen City Heart Study (n = 10 597) and the Copenhagen General Population Study (n = 32 999). We examined the risk of cardiovascular disease (2743 and 3890, respectively, in the two studies) and cancer (2144 and 3241......, respectively) by NOD2/CARD15 genotype using Cox and logistic regressions in both studies. To maximize statistical power, the three NOD2/CARD15 genetic variants were analysed together as follows: noncarriers for all three variants, heterozygotes for one of the three variants and homozygotes for one of the three...... variants pooled with compound heterozygotes for two variants. Results. Multifactorially adjusted hazard ratios for cardiovascular disease and cancer in NOD2/CARD15 heterozygotes or homozygotes/compound heterozygotes versus noncarries did not differ from 1.0 in the Copenhagen City Heart Study...

NOD1CARD Might Be Using Multiple Interfaces for RIP2-Mediated CARD-CARD Interaction: Insights from Molecular Dynamics Simulation.

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Jitendra Maharana

Full Text Available The nucleotide-binding and oligomerization domain (NOD-containing protein 1 (NOD1 plays the pivotal role in host-pathogen interface of innate immunity and triggers immune signalling pathways for the maturation and release of pro-inflammatory cytokines. Upon the recognition of iE-DAP, NOD1 self-oligomerizes in an ATP-dependent fashion and interacts with adaptor molecule receptor-interacting protein 2 (RIP2 for the propagation of innate immune signalling and initiation of pro-inflammatory immune responses. This interaction (mediated by NOD1 and RIP2 helps in transmitting the downstream signals for the activation of NF-κB signalling pathway, and has been arbitrated by respective caspase-recruitment domains (CARDs. The so-called CARD-CARD interaction still remained contradictory due to inconsistent results. Henceforth, to understand the mode and the nature of the interaction, structural bioinformatics approaches were employed. MD simulation of modelled 1:1 heterodimeric complexes revealed that the type-Ia interface of NOD1CARD and the type-Ib interface of RIP2CARD might be the suitable interfaces for the said interaction. Moreover, we perceived three dynamically stable heterotrimeric complexes with an NOD1:RIP2 ratio of 1:2 (two numbers and 2:1. Out of which, in the first trimeric complex, a type-I NOD1-RIP2 heterodimer was found interacting with an RIP2CARD using their type-IIa and IIIa interfaces. However, in the second and third heterotrimer, we observed type-I homodimers of NOD1 and RIP2 CARDs were interacting individually with RIP2CARD and NOD1CARD (in type-II and type-III interface, respectively. Overall, this study provides structural and dynamic insights into the NOD1-RIP2 oligomer formation, which will be crucial in understanding the molecular basis of NOD1-mediated CARD-CARD interaction in higher and lower eukaryotes.

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

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de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

2014-01-01

To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Anti-TNF-alpha therapy does not modulate leptin in patients with severe rheumatoid arthritis.

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Gonzalez-Gay, M A; Garcia-Unzueta, M T; Berja, A; Gonzalez-Juanatey, C; Miranda-Filloy, J A; Vazquez-Rodriguez, T R; de Matias, J M; Martin, J; Dessein, P H; Llorca, J

2009-01-01

The adipocytokine leptin regulates weight centrally and participates in the regulation of the immune and inflammatory responses. Chronic systemic inflammation is of major importance in the development of atherosclerosis in rheumatoid arthritis (RA). In the present study we investigated whether inflammation, obesity or both of these characteristics are potential determinants of circulating leptin concentrations in a group of RA patients on periodical treatment with the TNF-alpha-blocker-infliximab due to severe disease. We also assessed whether the infusion of infliximab may alter circulating leptin concentrations in patients with severe RA. We investigated 33 patients with RA on periodical treatment with infliximab. Serum leptin levels were determined immediately prior to and after infliximab infusion. There was a positive correlation between body mass index of RA patients and baseline serum level of leptin (rho=0.665, pghrelin or the cumulative prednisone dose at the time of the study were found. Leptin levels did not change upon infliximab infusion (p=0.48). In RA patients on TNF-alpha blocker treatment, circulating leptin levels are unrelated to disease activity but constitute a manifestation of adiposity. The beneficial effect of anti-TNF-alpha therapy on cardiovascular mortality in RA does not seem to be mediated by reduction in serum levels of leptin.

The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T).

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Gumus, Evren

2018-05-07

Familial Mediterranean Fever (FMF) is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV) gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January⁻December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T) mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP), do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS) analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

Effect of 1-year anti-TNF-α therapy on aortic stiffness, carotid atherosclerosis, and calprotectin in inflammatory arthropathies: a controlled study.

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Angel, Kristin; Provan, Sella A; Fagerhol, Magne K; Mowinckel, Petter; Kvien, Tore K; Atar, Dan

2012-06-01

Premature arterial stiffening and atherosclerosis are increased in patients with inflammatory arthropathies such as rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The proinflammatory protein calprotectin is associated with inflammatory arthropathies, vascular pathology, and acute coronary events. We examined the long-term effects of treatment with tumor necrosis factor (TNF)-α antagonists on aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies, and the relationships to the levels of calprotectin. Fifty-five patients with RA, AS, or PsA and a clinical indication for anti-TNF-α therapy were included and followed with regular examinations for 1 year. Thirty-six patients starting with anti-TNF-α therapy were compared with a nontreatment group of 19 patients. Examinations included assessments of aortic stiffness (aortic pulse wave velocity, aPWV), CIMT, and plasma calprotectin. After 1 year, aPWV (mean (s.d.)) was improved in the treatment group, but not in the control group (-0.54 [0.79] m/s vs. 0.06 [0.61] m/s, respectively; P = 0.004), and CIMT progression (median (quartile cut-points, 25th and 75th percentiles)) was reduced in the treatment group compared to the control group (-0.002 [-0.038, 0.030] mm vs. 0.030 [0.011, 0.043] mm, respectively; P = 0.01). In multivariable analyses, anti-TNF-α therapy over time was associated with improved aPWV (P = 0.02) and reduced CIMT progression (P = 0.04), and calprotectin was longitudinally associated with aPWV (P = 0.02). Long-term anti-TNF-α therapy improved aortic stiffness and CIMT progression in patients with inflammatory arthropathies. Calprotectin may be a soluble biomarker reflecting aortic stiffening in these patients.

Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis.

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Jacob Sode

Full Text Available To determine whether genetic variation within genes related to the Toll-like receptor, inflammasome and interferon-γ pathways contributes to the differences in treatment response to tumour necrosis factor inhibitors (anti-TNF in patients with rheumatoid arthritis (RA.In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value<0.05 between genotypes and European League Against Rheumatism (EULAR treatment responses. False Discovery Rate corrections for multiple testing (q-value and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF status.Six of twenty successfully genotyped polymorphisms were nominally associated with EULAR treatment response. Three of these were in weak to moderate linkage disequilibrium with polymorphisms previously reported associated with anti-TNF treatment response. TLR5(rs5744174 variant allele carriers (odds ratio(OR = 1.7(1.1-2.5,p = 0.010,q = 0.46 and TLR1(rs4833095 homozygous variant carriers (OR = 2.8(1.1-7.4,p = 0.037,q = 0.46 had higher odds for a positive treatment response. NLRP3(rs10754558 variant allele carriers (odds ratio(OR = 0.6(0.4-1.0,p = 0.045,q = 0.46 were more likely to have a negative treatment response. The association in TLR5(rs5744174 remained significant after correction for multiple comparisons among patients negative for RF (OR = 6.2(2.4-16.3,p = 0.0002,q = 0.024. No other association withstood correction for multiple testing. Post hoc analyses showed that change in Patient Global score on a visual analogue scale (VAS and change in pain VAS were the main factors responsible for the association.We reproduced previously reported associations between genetic variation in the TLR10/1/6 gene cluster, TLR5

Blau syndrome-associated mutations in exon 4 of the caspase activating recruitment domain 15 (CARD 15) gene are not found in ethnic Danes with sarcoidosis

DEFF Research Database (Denmark)

Milman, Nils; Nielsen, Finn Cilius; Hviid, Thomas Vauvert F

2007-01-01

BACKGROUND: Distinct mutations of the caspase activating recruitment domain 15 (CARD15) gene (also known as nucleotide-binding oligomerisation domain protein 2) on chromosome 16q are associated with the chronic granulomatous disease called Blau syndrome. Sarcoidosis is a systemic granulomatous...... disease, which has features in common with Blau syndrome. AIM: The aim of this study was to evaluate whether ethnic Danes with sarcoidosis have CARD15 mutations associated with Blau syndrome. METHODS: Analysis of exon 4 of the CARD15 gene containing mutations associated with Blau syndrome was performed...

The Frequency of MEFV Gene Mutations and Genotypes in Sanliurfa Province, South-Eastern Region of Turkey, after the Syrian Civil War by Using Next Generation Sequencing and Report of a Novel Exon 4 Mutation (I423T

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Evren Gumus

2018-05-01

Full Text Available Background: Familial Mediterranean Fever (FMF is a genetic disorder characterized by recurrent episodes of fever and abdominal pain. Mutations in the Mediterranean fever (MEFV gene are localized on the p arm of chromosome 16. Over 333 MEFV sequence variants have been identified so far in FMF patients, which occur mostly in the 2nd and 10th exons of the gene. Methods: In this study, 296 unrelated patients with clinical suspicion of FMF, which were admitted during January–December 2017, were retrospectively reviewed to identify the frequency of MEFV gene mutations by using next generation sequencing. Results: Eighteen different mutations, 45 different genotypes and a novel exon 4 (I423T mutation were identified in this study. This mutation is the fourth mutation identified in exon 4.The most frequent mutation was R202Q, followed by M694V, E148Q, M680I, R761H, V726A and R354W. Conclusions: One of the most important aims of this study is to investigate the MEFV mutation type and genotype of migrants coming to Sanliurfa after the civil war of Syria. This study also examines the effect of the condition on the region’s gene pool and the distribution of different types of mutations. Our results indicated that MEFV mutations are highly heterogeneous in our patient population, which is consistent with the findings of other studies in our region. Previously used methods, such as Restriction Fragment Length Polymorphism (RFLP, do not define uncommon or especially novel mutations. Therefore, Next Generation Sequencing (NGS analysis of the MEFV gene could be useful for finding novel mutations, except for those located on exon 2 and 10.

Astrocyte reactivity to unconjugated bilirubin requires TNF-α and IL-1β receptor signaling pathways.

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Fernandes, Adelaide; Barateiro, Andreia; Falcão, Ana Sofia; Silva, Sandra Leit-Ao; Vaz, Ana Rita; Brito, Maria Alexandra; Silva, Rui Fernando Marques; Brites, Dora

2011-01-01

Jaundice and sepsis are common neonatal conditions that can lead to neurodevelopment sequelae, namely if present at the same time. We have reported that tumor necrosis factor (TNF)-α and interleukin (IL)-1β are produced by cultured neurons and mainly by glial cells exposed to unconjugated bilirubin (UCB). The effects of these cytokines are mediated by cell surface receptors through a nuclear factor (NF)-κB-dependent pathway that we have showed to be activated by UCB. The present study was designed to evaluate the role of TNF-α and IL-1β signaling on astrocyte reactivity to UCB in rat cortical astrocytes. Exposure of astrocytes to UCB increased the expression of both TNF-α receptor (TNFR)1 and IL-1β receptor (IL-1R)1, but not TNFR2, as well as their activation, observed by augmented binding of receptors' molecular adaptors, TRAF2 and TRAF6, respectively. Silencing of TNFR1, using siRNA technology, or blockade of IL-1β cascade, using its endogenous antagonist, IL-1 receptor antagonist (IL-1ra), prevented UCB-induced cytokine release and NF-κB activation. Interestingly, lack of TNF-α signal transduction reduced UCB-induced cell death for short periods of incubation, although an increase was observed after extended exposure; in contrast, inhibition of IL-1β cascade produced a sustained blockade of astrocyte injury by UCB. Together, our data show that inflammatory pathways are activated during in vitro exposure of rat cortical astrocytes to UCB and that this activation is prolonged in time. This supports the concept that inflammatory pathways play a role in brain damage by UCB, and that they may represent important pharmacological targets. Copyright © 2010 Wiley-Liss, Inc.

New Onset of Dermatomyositis/Polymyositis during Anti-TNF-α Therapies: A Systematic Literature Review

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Alexandra Maria Giovanna Brunasso

2014-01-01

Full Text Available We performed a systematic search of databases from 1990 to 2013 to identify articles concerning the new onset of dermatomyositis/polymyositis (DM/PM in patients treated with anti-TNF-α therapy. We retrieved 13 publications describing 20 patients where the new onset of DM/PM after anti-TNF-α therapy was recorded. 17 patients were affected by rheumatoid arthritis (RA, one by Crohn’s disease, one by ankylosing spondilytis, and one by seronegative arthritis. In 91% of the cases antinuclear autoantibodies were detected after the introduction of anti-TNF-α therapy. In 6 patients antisynthetase antibodies were detected and other clinical findings as interstitial lung disease (ILD were recorded. Improvement of DM/PM after anti-TNF suspension (with the concomitant use of other immunosuppressors was recorded in 94% of cases. The emergence of DM/PM and antisynthetase syndrome seem to be associated with the use of anti-TNF-α agents, especially in patients with chronic inflammatory diseases (mainly RA with positive autoantibodies before therapy initiation. In particular, physicians should pay attention to patients affected by RA with positive antisynthetase antibodies and/or history of ILD. In those cases, the use of the TNF-α blocking agents may trigger the onset of PM/DM or antisynthetase syndrome or may aggravate/trigger the lung disease.

NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease.

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Barreiro-de-Acosta, M; Mendoza, J L; Lana, R; Domínguez-Muñoz, J E; Díaz-Rubio, M

2010-05-01

Crohn's disease (CD) is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide), though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, at present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.

Biologics beyond TNF-α inhibitors and the effect of targeting the homologues TL1A-DR3 pathway in chronic inflammatory disorders

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Tougaard, Peter; Zervides, Kristoffer Alexander; Skov, Søren

2016-01-01

novel drugs that target TNF-α signaling are still being developed. Indeed, blockade of this pathway seems so important amongst immune-targets that TNF-α targeted therapies will continue to have a significant role in the treatment of chronic inflammation. However, up to 40% of RA and IBD patients do...... as a highly promising strategy for treatment of chronic inflammatory disorders....

Mycobacterium tuberculosis Upregulates TNF-α Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells.

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Wei-Lin Chen

Full Text Available Tumor necrosis factor (TNF-α and matrix metalloproteinases (MMPs are elevated in pleural fluids of tuberculous pleuritis (TBP where pleural mesothelial cells (PMCs conduct the first-line defense against Mycobacterium tuberculosis (MTB. However, the clinical implication of TNF-α and MMPs in TBP and the response of PMCs to MTB infection remain unclear.We measured pleural fluid levels of TNF-α and MMPs in patients with TBP (n = 18 or heart failure (n = 18 as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa on the expression of TNF-α and MMPs.As compared with controls, the effusion levels of TNF-α, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-α and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-α had positive correlation with those of MMP-1 and MMP-9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-α mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-α expression. Additionally, both MTBRa and TNF-α markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-α neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation.MTBRa activates TLR2/ERK signalings to induce TNF-α and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-α and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP.

Cost-effectiveness of drug monitoring of anti-TNF therapy in inflammatory bowel disease and rheumatoid arthritis: a systematic review.

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Martelli, Laura; Olivera, Pablo; Roblin, Xavier; Attar, Alain; Peyrin-Biroulet, Laurent

2017-01-01

Therapeutic drug monitoring (TDM) of anti-TNF is increasingly used to manage inflammatory bowel diseases (IBD) and rheumatoid arthritis (RA). The cost-effectiveness of this strategy is debated. All studies comparing the cost-effectiveness of a TDM-based strategy and an empirical dose management of anti-TNF in IBD or RA were screened. Studies were identified through the MEDLINE electronic database (up to July 2016), and annual international meeting abstracts were also manually reviewed. Seven studies were included: two randomized controlled trials (RCTs) enrolling 332 patients [247 Crohn's disease (CD) and 85 ulcerative colitis (UC)] and five modeling approaches. Four studies included only CD patients, one included both CD and UC patients, and two included only RA patients. Three studies compared the cost-effectiveness of the two strategies in patients with secondary infliximab (IFX) failure (dose-escalation strategy), one in patients in remission on optimized IFX (de-escalation strategy), one in patients starting adalimumab, and two in patients with clinical response to maintenance anti-TNF therapy. The two RCTs demonstrated that a TDM strategy led to major cost savings, ranging from 28 to 34 %. The three modeling approaches with regard to CD patients demonstrated cost savings ranging from $5396 over a 1-year period to €13,130 per patient at 5 years of follow-up. A TDM strategy also led to major cost savings in the two modeling approaches in RA patients. Available evidence indicates that a TDM strategy leads to major cost savings related to anti-TNF therapy in both IBD and RA patients, with no negative impact on efficacy.

[A case of colchicine-responsive Mollaret's meningitis with MEFV gene mutation].

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Kinohshita, Tomomi; Matsushima, Akira; Satoh, Shunichi; Hoshi, Kenichi; Kishida, Dai; Yahikozawa, Hiroyuki

2014-01-01

A 66-year-old woman was admitted to our hospital with recurrent meningitis. She presented with 10 episodes of meningitis in 10 months. Examination of cerebrospinal fluid demonstrated pleocytosis, with neutrophils dominant at the early stage, and lymphocytes dominant at the late stage. Mollaret cells were found and the level of IL-6 was increased in cerebrospinal fluid. Several antibiotics and antiviral agents failed to prevent relapse. However, colchicine therapy successfully prevented the recurrence of meningitis. Genetic testing for familial Mediterranean fever (FMF) showed a mutation in the MEFV gene. It is difficult to diagnose the cause of Mollaret's meningitis in some patients. FMF, neuro-Behçet's disease, and neuro-Sweet disease should be included in the differential diagnosis of recurrent meningitis. In addition, colchicine therapy can prevent the relapse of meningitis in such cases.

The ratio Neutrophil/Lymphocyte and Platelet/Lymphocyte in patient with Rheumatoid Arthritis that are Treating with Anti-TNF

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İsmail Boyraz

2014-06-01

Full Text Available OBJECTIVES: Rheumatoid arthritis (RA is a chronic inflammatory disorder with unknown etiology. RA is characterized by a variable course of remissions and relapses, and subclinical inflammation persists between the disease exacerbations. Anti-TNF therapies have become more often preferred in recent years in the treatment of RA. The aim of the present study was to determine the relationship between N/L and P/L ratios and subclinical inflammation in patients with RA who achieved remission with anti-TNF therapy. METHODS: The present study was a retrospective, controlled and multicenter study. The present study reviewed the medical records of the patients who were on follow-up in the outpatient clinics of the Department of Physical Therapy in Abant İzzet Baysal University and Harran University due to rheumatoid arthritis (RA and who achieved remission with anti-TNF therapy.A total of 80 patients in the inactive phase of RA and 45 healthy subjects in the control group were included in the study. Hemogram results of the people were examined retrospectively. RESULTS: There was significant difference between the patient and the control group in terms of platelet ratio and lymphocyte and neutrophil ratio. There was no significant difference between the group in terms of N/L and P/L ratios.CONCLUSIONS:  In the current study, we found significant differences between the patient and the control group in terms of neutrophil, lymphocyte, and platelet counts; however, there was no significant difference between the two groups in terms of N/L and P/L ratios. These findings suggest that therapies with anti-TNF agents in patients with RA achieved complete control of inflammation. 

TNF promoter polymorphisms and modulation of growth retardation and disease severity in pediatric Crohn's disease.

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Levine, Arie; Shamir, Raanan; Wine, Eytan; Weiss, Batya; Karban, Amir; Shaoul, Ron R; Reif, Shimon S; Yakir, Benjamin; Friedlander, Marcello; Kaniel, Yael; Leshinsky-Silver, Esther

2005-07-01

Delayed growth is common in pediatric Crohn's disease (CD). Multiple factors have been shown to affect growth in this situation, the most prominent being the presence and severity of inflammation and inadequate nutritional intake. Inflammation, anorexia, and weight loss are all manifestations of circulating TNF-alpha, which is elevated in CD. The ability to secrete TNF-alpha may be affected by polymorphisms in the TNF-alpha promoter. The aim of our study was to determine whether growth retardation and disease severity in pediatric onset CD are affected by TNF promoter genotype. Genotyping for TNF-alpha and NOD2/CARD15 single nucleotide polymorphisms was performed in 87 patients with detailed growth records. Parameters including disease location and disease severity were recorded, and the effect of these polymorphisms on Z-scores for height and weight at disease onset and during follow-up were analyzed. Lower age of onset was linked to more height retardation, while the presence of colonic disease and the absence of ileal disease were more likely to predict the absence of growth retardation. The presence of two polymorphisms thought to decrease circulating TNF-alpha was associated with higher mean Z-scores for height and a trend toward less growth retardation. Two other polymorphisms were modestly associated with disease severity. Polymorphisms in the TNF-alpha promoter may independently modulate growth and disease severity in pediatric onset CD. The effect of these polymorphisms does not appear to be mediated via weight loss, and is relatively modest.

THE IMMUNOLOGICAL CHARACTERISTIC OF RA PATIENTS WITH ANAEMIA

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A. E. Sizikov

2014-07-01

Full Text Available Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

CD147 promotes IKK/IκB/NF-κB pathway to resist TNF-induced apoptosis in rheumatoid arthritis synovial fibroblasts.

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Zhai, Yue; Wu, Bo; Li, Jia; Yao, Xi-ying; Zhu, Ping; Chen, Zhi-nan

2016-01-01

TNF is highly expressed in synovial tissue of rheumatoid arthritis (RA) patients, where it induces proinflammatory cytokine secretion. However, in other cases, TNF will cause cell death. Considering the abnormal proliferation and activation of rheumatoid arthritis synovioblasts, the proper rate of synovioblast apoptosis could possibly relieve arthritis. However, the mechanism mediating TNF-induced synovioblast survival versus cell death in RA is not fully understood. Our objective was to study the role of CD147 in TNF downstream pathway preference in RA synovioblasts. We found that overexpressing TNF in synovial tissue did not increase the apoptotic level and, in vitro, TNF-induced mild synovioblast apoptosis and promoted IL-6 secretion. CD147, which was highly expressed in rheumatoid arthritis synovial fibroblasts (RASFs), increased the resistance of synovioblasts to apoptosis under TNF stimulation. Downregulating CD147 both increased the apoptotic rate and inhibited IκB kinase (IKK)/IκB/NF-κB pathway-dependent proinflammatory cytokine secretion. Further, we determined that it was the extracellular portion of CD147 and not the intracellular portion that was responsible for synovioblast apoptosis resistance. CD147 monoclonal antibody inhibited TNF-induced proinflammatory cytokine production but had no effect on apoptotic rates. Thus, our study indicates that CD147 is resistant to TNF-induced apoptosis by promoting IKK/IκB/NF-κB pathway, and the extracellular portion of CD147 is the functional region. CD147 inhibits TNF-stimulated RASF apoptosis. CD147 knockdown decreases IKK expression and inhibits NF-κB-related cytokine secretion. CD147's extracellular portion is responsible for apoptosis resistance. CD147 antibody inhibits TNF-related cytokine secretion without additional apoptosis.

Relative activities of 212Bi (thorium-C) and 228Ra (mesothorium-1) in former radium dial workers

International Nuclear Information System (INIS)

Keane, A.T.; Essling, M.A.; Lucas, H.F.

1984-01-01

From analyses of bones, estimates were made of the relative intakes of 228 Ra and 226 Ra by the employees of a dial-painting studio that used luminous compounds activated with technical mesothorium. These data, in turn, were used to derive estimates of 228 Ra activity from activities of 226 Ra in living colleagues whose body contents of 226 Ra and 212 Bi had been measured. The indirectly determined 212 Bi to 228 Ra activity ratios in the living workers averaged 1.56 +- 0.10 (S.E.) at a median of 42 yr post intake. If no 228 Ra decay products are excreted, the expected 212 Bi to 228 Ra activity ratio at 42 yr after intake is 1.59 according to the simple power function of radium retention of Norris et al., and 1.72 according to the alkaline earth model of ICRP No. 20. 15 references, 2 tables

Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti-TNF therapy

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Dewbury Keith

2010-06-01

Full Text Available Abstract Background Inhibition of tumour necrosis factor (TNF is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA, yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability. Methods Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI. Results 31 patients (24 female, 7 male with RA (12 seronegative, 19 seropositive completed the study: mean age 59.6 (SD 10.1 years, disease duration 11.1 (SD 10.5 years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6. Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar this was not significant. Conclusions Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.

Evaluation of the effects of active fractions of chinese medicine formulas on IL-1β, IL-6, and TNF-α release from ANA-1 murine macrophages.

Science.gov (United States)

Ni, Li-Jun; Wang, Nan-Nan; Zhang, Li-Guo; Guo, Yan-Zi; Shi, Wan-Zhong

2016-02-17

Yaotongning (YTN) is a traditional Chinese Medicine (TCM) that contains ten component medicinal materials (CMMs) and uses Chinese rice wine as a vehicle to enhance its efficacy. YTN has been used for rheumatoid arthritis (RA) treatment in China for decades and has been reported to have anti-inflammatory and analgesic effects, as well as to strengthen the immune system. The present work quantitatively evaluated the in vitro effects of active fractions from the ten CMMs that make up YTN and eight additional herbs commonly used in TCM formulas for RA treatment, as well as different combinations of these active fractions, on cellular immune response; the findings were used to determine which active fractions are responsible for promoting an immune response, and to assess whether YTN is superior to other similar formulas and whether YTN can be improved by simplifying its formula from the point of its cellular immunomodulatory activity. Using the YTN formulation principles and some concepts in combinatorial chemistry, 27 TCM samples were designed by combining some or all of the active fractions of YTN and other eight herbs used for RA treatment. Release of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) from ANA-1 murine macrophages was measured using an enzyme-linked immunosorbent assay (ELISA). The immunoregulatory effects of the TCM samples were evaluated by comparing their half-effective concentrations (EC50) for stimulating the release of these cytokines. Among the investigated active fractions, the flavonoids from Carthamus tinctorius (Fct), Davallia mariesii (Fdm), and Cinnamomum cassia Twig volatile oils (Vca) from the eight selected herbs effectively promoted IL-1β and IL-6 release from ANA-1 cells. Saponins from the YTN CMM Glycyrrhiza uralensis (Sgu) were the most potent promoters of IL-1β and TNF-α release. The aqueous extract of YTN CMM Eupolyphaga sinensis (Ves) strongly enhanced the release of IL-1β, IL-6, and

Weight Gain and Hair Loss during Anti-TNF Therapy

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Abdo Lutf

2012-01-01

Full Text Available Objectives. To investigate the incidence of weight gain and hair loss as adverse effects of anti-TNF therapy in rheumatic diseases. Methods. Patients using anti-TNF therapy, who are followed in rheumatology clinic, were interviewed using a questionnaire to investigate the side effects of anti-TNF therapy. Patients who complained of hair loss and weight gain were asked additional questions concerning the relationship of these adverse effects to anti-TNF use, whether therapy was stopped because of these adverse effects and if the adverse effects reversed after stopping therapy. The files were reviewed to follow the weight change before, during, and after discontinuation of anti-TNF. Results. One hundred fifty consecutive patients (82 RA, 34 ankylosing spondylitis, 32 psoriatic arthritis, and 4 for other indications were interviewed .Weight gain was observed in 20 patients (13.3% with average gain of 5.5 Kg. Anti-TNF was stopped in five patients because of this adverse effect. Hair loss during anti-TNf therapy was reported in five females (3.3% and anti-TNF therapy was stopped in all of them. Conclusion. Weight gain and hair loss appear to be associated with anti-TNF therapy and may be one reason for discontinuing the therapy.

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.

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Eric Toussirot

Full Text Available 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.

Targeting sTNF/TNFR1 Signaling as a New Therapeutic Strategy

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Roman Fischer

2015-03-01

Full Text Available Deregulation of the tumor necrosis factor (TNF plays an important role in the initiation and perpetuation of chronic inflammation and has been implicated in the development of various autoimmune diseases. Accordingly, TNF-inhibitors are successfully used for the treatment of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, total inhibition of TNF can cause severe side effects such as an increased risk of inflammation and reactivation of tuberculosis. This is likely due to the different actions of the two TNF receptors. Whereas TNFR1 predominantly promotes inflammatory signaling pathways, TNFR2 mediates immune modulatory functions and promotes tissue homeostasis and regeneration. Therefore, the specific blockage of TNFR1 signaling, either by direct inhibition with TNFR1-selective antagonists or by targeting soluble TNF, which predominantly activates TNFR1, may prevent the detrimental effects associated with total TNF-inhibitors and constitute a next-generation approach to interfere with TNF.

Nuclear Reactor RA Safety Report, Vol. 15, Analysis of significant accidents; Izvestaj o sigurnosti nuklearnog reaktora RA, Knjiga 15, Analiza znacajnih akcidenata

Energy Technology Data Exchange (ETDEWEB)

NONE

1986-11-01

Power excursions of the RA reactor a mathematical model of reactor kinetic behaviour was formulated to describe power and temperature coefficients for both reactor fuel and moderator. Computer code TM-1 was written for analysis of possible reactor accidents. Power excursions caused by uncontrolled control rod removal and heavy water flow into the central vertical experimental channel were analyzed. Accidents caused by fuel elements handling were discussed including possible fuel element damage. Although the probability for uncontrolled radioactive materials release into the environment is very low, this type of accidents are analyzed as well including the impact on the personnel and the environment. A separate chapter describes analysis of the loss of flow accident. Safety analysis covers the possible damage of the outer steel Ra reactor vessel and the water screens which are part of the water biological shield. [Serbo-Croat] Radi analize dinamickog ponasanja reaktora RA u toku ekskurzije snage formulisan je matematicki model koji opisuje promene snage i temperature goriva i moderatora. Za analizu predpostavljenih akcidenata realizovan je racunarski program TM-1. Analizirane su ekskurzije snage usled nekontrolisanog izvlacenja kontrolnih sipki i punjenja centralnog vertikalnog eksperimentalnog kanala teskom vodom. Analizirani su akcidenti pri rukovanju nuklearnim gorivom ukljucujuci ostecenje nuklearnog goriva. Iako je verovatnoca za nekontrolisano rasturanje radioaktivnog materijala mala, analizirani su i ovakvi moguci akcidenti koji mogu uticati kako na osoblje reaktora tako i na okolinu. Posebno poglavlje obuhvata analizu akcidenta u slucaju prestanka cirkulacije primarnog hladioca. Analiza sigurnosti reaktora obuhvata i moguce ostecenje spoljasnjeg celicnog suda reaktora RA kao i vodenih ekrana koji su deo vodenog bioloskog stita.

CAC-RA1 1958-1998. The first years of the Constituyentes Atomic Center (CAC). History of the first Argentine nuclear reactor (RA-1); CAC-RA-1 1958-1998. Los primeros anios del CAC. Historia del primer reactor nuclear argentino (RA-1)

Energy Technology Data Exchange (ETDEWEB)

Forlerer, Elena; Palacios, Tulio A [comps.

1998-07-01

After giving the milestones of the development of the Constituyentes Atomic Center since 1957, the history of the construction of the first nuclear reactor (RA-1) in Argentina, including the local fabrication of its fuel elements, is surveyed. The RA-1 reached criticality on January 17, 1958. The booklet commemorates the 40th year of the reactor operation.

Allogeneic Transplant in ELANE and MEFV Mutation Positive Severe Cyclic Neutropenia: Review of Prognostic Factors for Secondary Severe Events

OpenAIRE

Okolo, Onyemaechi N.; Katsanis, Emmanuel; Yun, Seongseok; Reveles, Candace Y.; Anwer, Faiz

2017-01-01

Objective and Importance. Cyclic neutropenia (CyN) is a rare autosomal dominant inherited disorder due to the mutation ELANE primarily affecting bone marrow stem cells and is characterized by recurrent neutropenia every 2 to 4 weeks. Symptoms vary from benign to severe, including death. Postulations on the cause of wide spectrum in symptom presentation include the possibility of other genetic mutations, such as MEFV. Recommended treatment for CyN is G-CSF to keep ANC higher to minimize risk o...

Local TNF causes NFATc1-dependent cholesterol-mediated podocyte injury

OpenAIRE

Pedigo, Christopher E.; Ducasa, Gloria Michelle; Leclercq, Farah; Sloan, Alexis; Mitrofanova, Alla; Hashmi, Tahreem; Molina-David, Judith; Ge, Mengyuan; Lassenius, Mariann I.; Forsblom, Carol; Lehto, Markku; Groop, Per-Henrik; Kretzler, Matthias; Eddy, Sean; Martini, Sebastian

2016-01-01

High levels of circulating TNF and its receptors, TNFR1 and TNFR2, predict the progression of diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated the function of local and systemic TNF in podocyte injury. We cultured human podocytes with sera collected from DKD patients, who displayed elevated TNF levels, and focal segmental glomerulosclerosis (FSGS) patients, whose TNF levels resembled those of healthy patients. Exogenou...

Concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal

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Juliano Magalhães Guedes

2015-08-01

Full Text Available O objetivo desta revisão sistemática foi verificar a relação das concentrações de IL-6, TNF-α e MCP-1 em crianças com excesso de massa corporal. As bases de dados investigadas PUBMED, SciELO, LILACS e Periódico Capes foram consultadas retrospectivamente para os últimos seis anos (2009 a 2014 utilizando combinações de palavras chaves como inflamação, IL-6, TNF-α, MCP-1 combinadas com crianças e escolares. Foram analisados 21 artigos. Foi encontrado associação entre sobrepeso/obesidade com IL-6, TNF-α e MCP-1 em 73,3% (11/15, 80% (12/15 e 60% (3/5 dos estudos que analisaram tais marcadores, respectivamente. Crianças com excesso de massa corporal possuem concentrações elevadas de IL-6, TNF-α e MCP-1 resultando em inflamação sistêmica crônica e aumentando o risco de desenvolvimento de outras doenças cardiovasculares. 

Cardiovascular safety of biologic therapies for the treatment of RA.

Science.gov (United States)

Greenberg, Jeffrey D; Furer, Victoria; Farkouh, Michael E

2011-11-15

Cardiovascular disease represents a major source of extra-articular comorbidity in patients with rheumatoid arthritis (RA). A combination of traditional cardiovascular risk factors and RA-related factors accounts for the excess risk in RA. Among RA-related factors, chronic systemic inflammation has been implicated in the pathogenesis and progression of atherosclerosis. A growing body of evidence--mainly derived from observational databases and registries--suggests that specific RA therapies, including methotrexate and anti-TNF biologic agents, can reduce the risk of future cardiovascular events in patients with RA. The cardiovascular profile of other biologic therapies for the treatment of RA has not been adequately studied, including of investigational drugs that improve systemic inflammation but alter traditional cardiovascular risk factors. In the absence of large clinical trials adequately powered to detect differences in cardiovascular events between biologic drugs in RA, deriving firm conclusions on cardiovascular safety is challenging. Nevertheless, observational research using large registries has emerged as a promising approach to study the cardiovascular risk of emerging RA biologic therapies.

Plasma TNF binding capacity profiles during treatment with etanercept in rheumatoid arthritis

DEFF Research Database (Denmark)

Gudbrandsdottir, S; Bliddal, H; Petri, A

2004-01-01

occurring soluble TNF receptors. However, the clinical response to treatment with etanercept may vary. Previously, pharmacokinetic studies have focused on the molar concentrations of etanercept, but very little is known about the kinetics of bioactive etanercept in patients treated with etanercept....... The purpose of this study was to evaluate kinetics, including inter- and intraindividual variations of the total TNF binding capacity, in RA patients who were on a standard treatment schedule with etanercept....

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort.

Science.gov (United States)

Patente, Thiago A; Monteiro, Maria B; Vieira, Suzana M; Rossi da Silva, Maria E; Nery, Márcia; Queiroz, Márcia; Azevedo, Mirela J; Canani, Luis H; Parisi, Maria C; Pavin, Elizabeth J; Mainardi, Débora; Javor, Juraj; Velho, Gilberto; Coimbra, Cássio N; Corrêa-Giannella, Maria Lúcia

2015-08-15

A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D. Copyright © 2015 Elsevier B.V. All rights reserved.

Longitudinal micro-CT as an outcome measure of interstitial lung disease in TNF-transgenic mice.

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Richard D Bell

Full Text Available Rheumatoid arthritis associated interstitial lung disease (RA-ILD is a debilitating condition with poor survival prognosis. High resolution computed tomography (CT is a common clinical tool to diagnose RA-ILD, and is increasingly being adopted in pre-clinical studies. However, murine models recapitulating RA-ILD are lacking, and CT outcomes for inflammatory lung disease have yet to be formally validated. To address this, we validate μCT outcomes for ILD in the tumor necrosis factor transgenic (TNF-Tg mouse model of RA.Cross sectional μCT was performed on cohorts of male TNF-Tg mice and their WT littermates at 3, 4, 5.5 and 12 months of age (n = 4-6. Lung μCT outcomes measures were determined by segmentation of the μCT datasets to generate Aerated and Tissue volumes. After each scan, lungs were obtained for histopathology and 3 sections stained with hematoxylin and eosin. Automated histomorphometry was performed to quantify the tissue area (nuclei, cytoplasm, and extracellular matrix and aerated area (white space within the tissue sections. Spearman's correlation coefficients were used to evaluate the extent of association between μCT imaging and histopathology endpoints.TNF-Tg mice had significantly greater tissue volume, total lung volume and mean intensity at all timepoints compared to age matched WT littermates. Histomorphometry also demonstrated a significant increase in tissue area at 3, 4, and 5.5 months of age in TNF-Tg mice. Lung tissue volume was correlated with lung tissue area (ρ = 0.81, p<0.0001, and normalize lung aerated volume was correlated with normalized lung air area (ρ = 0.73, p<0.0001.We have validated in vivo μCT as a quantitative biomarker of ILD in mice. Further, development of longitudinal measures is critical for dissecting pathologic progression of ILD, and μCT is a useful non-invasive method to study lung inflammation in the TNF-Tg mouse model.

Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors

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Lea A. Koch

2014-01-01

Full Text Available There is evidence that plasminogen K1-5 (PlgK1-5 directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5 on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF and tumour necrosis factor alpha (TNF-alpha expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

ANTI-HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1 (ANTI-RA33 ANTIBODIES IN RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS

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P. A. Kuznetsova

2017-01-01

Full Text Available Anti-heterogeneous nuclear ribonucleoprotein (RNP autoantibodies (AAbs are encountered in many autoimmune rheumatic diseases (ARDs. The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA, ankylosing spondylitis (AS, systemic lupus erythematosus (SLE, systemic sclerosis (SSc, and Sjö gren's syndrome (SS and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6% and 8/53 (13% patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144 of the patients with RA; 40.3% (23/57 of those with AS, in 67.5% (27/40 of those with SSc, in 36.4% (16/44 of those with SLE, and in 13.3% (2/15 of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml, but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.

NOD2/CARD15: geographic differences in the Spanish population and clinical applications in Crohn's disease NOD2/CARD15: diferencias geográficas en la población española y su aplicación clínica en la enfermedad de Crohn

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M. Barreiro-de-Acosta

2010-05-01

Full Text Available Crohn's disease (CD is a genetically complex disease in which both genetic susceptibility and environmental factors play key roles in the development of the disorder. NOD2/CARD15 mutations are associated with CD. NOD2 encodes for a protein that is an intracellular receptor for a bacterial product (muramyl dipeptide, though the exact functional consequences of these mutations remain the subject of debate. NOD2/CARD15 mutations are associated with ileal CD, with stricturing behavior, and possibly with a more complicated course of CD. NOD2/CARD15 mutations associated with CD have demonstrated heterogeneity across ethnicities and populations throughout the world, with regional variations across Europe and Spain. However, "NOD2/CARD15 testing" is not yet ready for use in the clinical setting. One of the reasons is that we know that these genetic variants increase the risk of disease only marginally, and many healthy individuals carry the risk alleles, At present it is not recommended to screen first-degree relatives, because we do not have the ability to prevent the disease at the present time.La enfermedad de Crohn (EC es una enfermedad compleja desde el punto de vista de la genética puesto que para el desarrollo de la enfermedad se tiene que producir una interacción entre factores genéticos y ambientales. Las mutaciones del gen NOD2/CARD15 se han asociado con la susceptibilidad a padecer la EC. El gen NOD2/CARD15 codifica una proteína que actúa como un receptor intracelular de la proteína dipeptidomuramil que se encuentran en la pared de cubierta de algunas bacterias. Actualmente se desconoce cuál es el papel exacto de estas mutaciones en el funcionamiento de la proteína NOD2/CARD15. Estas mutaciones se han asociado con la localización en intestino delgado de la enfermedad, el comportamiento fibroestenosante y con un curso más grave de la enfermedad. Las tres mutaciones asociadas con la EC presentan una distribución desigual entre las

Comparison of TNF-α and TGF-β1 level in radicular cyst and odontogenic keratocyst fluid and its association with histopathological findings

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Safoura Seifi

2013-09-01

Full Text Available Background: TNF-α is a multifunctional proinflammatory cytokine and TGF-β1 is a secretory protein controlling epithelial proliferation and differentiation. Keratocyst presents an aggressive behavior and a growth mechanism different from that of radicular cyst. Aim: In this line, the present study aimed at evaluating TNF-α and TGF-β1 level and its association with histopathological findings in the two odontogenic lesions of different origins. Materials and Methods: In this case-control study, aspirated fluid of 15 cases of radicular cyst and 15 cases of keratocyst were investigated using ELISA method. The grade of inflammation and the mean number of blood vessels in three microscopic fields were provided with a magnification of 40 times on microscope slides. T-test, x2, Mann Whitney, and Pearson correlation tests were used for the comparison of TNF-α and TGF-β1 levels in the mentioned lesions and the association between cytokine levels and grade of inflammation and angiogenesis.Results: TNF-α and TGF-β1 were observed in aspirated fluid of all radicular cysts and keratocysts. Levels of TNF-α and TGF-β1 were found to be 6.72 ± 2.985 and 5.882 ± 2.985 respectively in radicular cyst fluid and 24.759 ± 94.849 and 63.38 ± 30.069 in keratocyst fluid however, no statistically significant difference was observed in terms of TNF-α (P=0.450 increasing trend in TNF-α level in radicular cyst and keratocyst was accompanied by increased inflammation and angiogenesis (P<0.001 and P=0.001. Conclusion: TNF-α and TGF-β1 are involved in the pathogenesis of radicular cyst and keratocyst. TGF-β1 level was higher in radicular cyst when compared with keratocyst however, TNF-α level was similar in the two lesions. A positive correlation was found between TNF-α level and grade of inflammation and angiogenesis.

Evaluation of pGL1-TNF-alpha therapy in combination with radiation

Science.gov (United States)

Li, J.; Andres, M. L.; Fodor, I.; Nelson, G. A.; Gridley, D. S.

1998-01-01

Long-term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. In this study a new plasmid-based human tumor necrosis factor-alpha (TNF-alpha) expression vector was synthesized (pGL1-TNF-alpha) and evaluated together with radiation in the aggressive, rapidly growing C6 rat glioma model. pGL1-TNF-alpha was successfully transfected into C6 cells in vitro using a cationic polyamine method. Expression was detected up to 7 days and averaged 0.4 ng of TNF-alpha in the culture medium from 1x10(5) cells. The expressed protein was biologically functional, as evidenced by growth inhibition of L929, a TNF-alpha-susceptible cell line. Using fluorescence-labeled monoclonal antibodies and laser scanning cytometry, we confirmed that both the P55 and P75 receptors for TNF-alpha were present on the C6 cell membrane. However, the receptors were present at low density and P55 was expressed more than the P75 receptor. These findings were in contrast to results obtained with TNF-alpha-susceptible L929 cells. Tests in athymic mice showed that pGL1-TNF-alpha administered intratumorally 16-18 h before radiation (each modality given three times) significantly inhibited C6 tumor progression (Palpha alone did not slow tumor growth and radiation alone had little effect on tumor growth. These results indicate that pGL1-TNF-alpha has potential to augment the antitumor effects of radiation against a tumor type that is virtually incurable.

Crowdsourced assessment of common genetic contribution to predicting anti-TNF treatment response in rheumatoid arthritis.

Science.gov (United States)

Sieberts, Solveig K; Zhu, Fan; García-García, Javier; Stahl, Eli; Pratap, Abhishek; Pandey, Gaurav; Pappas, Dimitrios; Aguilar, Daniel; Anton, Bernat; Bonet, Jaume; Eksi, Ridvan; Fornés, Oriol; Guney, Emre; Li, Hongdong; Marín, Manuel Alejandro; Panwar, Bharat; Planas-Iglesias, Joan; Poglayen, Daniel; Cui, Jing; Falcao, Andre O; Suver, Christine; Hoff, Bruce; Balagurusamy, Venkat S K; Dillenberger, Donna; Neto, Elias Chaibub; Norman, Thea; Aittokallio, Tero; Ammad-Ud-Din, Muhammad; Azencott, Chloe-Agathe; Bellón, Víctor; Boeva, Valentina; Bunte, Kerstin; Chheda, Himanshu; Cheng, Lu; Corander, Jukka; Dumontier, Michel; Goldenberg, Anna; Gopalacharyulu, Peddinti; Hajiloo, Mohsen; Hidru, Daniel; Jaiswal, Alok; Kaski, Samuel; Khalfaoui, Beyrem; Khan, Suleiman Ali; Kramer, Eric R; Marttinen, Pekka; Mezlini, Aziz M; Molparia, Bhuvan; Pirinen, Matti; Saarela, Janna; Samwald, Matthias; Stoven, Véronique; Tang, Hao; Tang, Jing; Torkamani, Ali; Vert, Jean-Phillipe; Wang, Bo; Wang, Tao; Wennerberg, Krister; Wineinger, Nathan E; Xiao, Guanghua; Xie, Yang; Yeung, Rae; Zhan, Xiaowei; Zhao, Cheng; Greenberg, Jeff; Kremer, Joel; Michaud, Kaleb; Barton, Anne; Coenen, Marieke; Mariette, Xavier; Miceli, Corinne; Shadick, Nancy; Weinblatt, Michael; de Vries, Niek; Tak, Paul P; Gerlag, Danielle; Huizinga, Tom W J; Kurreeman, Fina; Allaart, Cornelia F; Louis Bridges, S; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M; Bridges, S Louis; Criswell, Lindsey; Moreland, Larry; Klareskog, Lars; Saevarsdottir, Saedis; Padyukov, Leonid; Gregersen, Peter K; Friend, Stephen; Plenge, Robert; Stolovitzky, Gustavo; Oliva, Baldo; Guan, Yuanfang; Mangravite, Lara M

2016-08-23

Rheumatoid arthritis (RA) affects millions world-wide. While anti-TNF treatment is widely used to reduce disease progression, treatment fails in ∼one-third of patients. No biomarker currently exists that identifies non-responders before treatment. A rigorous community-based assessment of the utility of SNP data for predicting anti-TNF treatment efficacy in RA patients was performed in the context of a DREAM Challenge (http://www.synapse.org/RA_Challenge). An open challenge framework enabled the comparative evaluation of predictions developed by 73 research groups using the most comprehensive available data and covering a wide range of state-of-the-art modelling methodologies. Despite a significant genetic heritability estimate of treatment non-response trait (h(2)=0.18, P value=0.02), no significant genetic contribution to prediction accuracy is observed. Results formally confirm the expectations of the rheumatology community that SNP information does not significantly improve predictive performance relative to standard clinical traits, thereby justifying a refocusing of future efforts on collection of other data.

TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosis

DEFF Research Database (Denmark)

Gregory, Adam P; Dendrou, Calliope A; Attfield, Kathrine E

2012-01-01

), but not with other autoimmune conditions such as rheumatoid arthritis, psoriasis and Crohn’s disease. By analysing MS GWAS data in conjunction with the 1000 Genomes Project data we provide genetic evidence that strongly implicates this SNP, rs1800693, as the causal variant in the TNFRSF1A region. We further...... make to disease risk has raised questions regarding their medical relevance. Here we have investigated a single nucleotide polymorphism (SNP) in the TNFRSF1A gene, that encodes tumour necrosis factor receptor 1 (TNFR1), which was discovered through GWAS to be associated with multiple sclerosis (MS...... substantiate this through functional studies showing that the MS risk allele directs expression of a novel, soluble form of TNFR1 that can block TNF. Importantly, TNF-blocking drugs can promote onset or exacerbation of MS, but they have proven highly efficacious in the treatment of autoimmune diseases...

Genetic Variations in Pattern Recognition Receptor Loci Are Associated with Anti-TNF Response in Patients with Rheumatoid Arthritis

DEFF Research Database (Denmark)

Sode, Jacob; Vogel, Ulla; Bank, Steffen

2015-01-01

: In a retrospective case-case study, we assessed 23 functional single nucleotide polymorphisms (SNPs) in 15 genes. We included 538 anti-TNF naïve Danish RA patients from the nationwide DANBIO database. Multivariable logistic regression analyses were performed to detect associations (p-value... and European League Against Rheumatism (EULAR) treatment responses. False Discovery Rate corrections for multiple testing (q-value) and stratified analyses were performed to investigate association with individual therapies and IgM-rheumatoid factor (RF) status. RESULTS: Six of twenty successfully genotyped...

Predictors of work disability after start of anti-TNF therapy in a national cohort of Swedish patients with rheumatoid arthritis: does early anti-TNF therapy bring patients back to work?

Science.gov (United States)

Olofsson, T; Petersson, I F; Eriksson, J K; Englund, M; Nilsson, J A; Geborek, P; Jacobsson, L T H; Askling, J; Neovius, M

2017-07-01

To examine predictors of work ability gain and loss after anti-tumour necrosis factor (TNF) start, respectively, in working-age patients with rheumatoid arthritis (RA) with a special focus on disease duration. Patients with RA, aged 19-62 years, starting their first TNF inhibitor 2006-2009 with full work ability (0 sick leave/disability pension days during 3 months before bio-start; n=1048) or no work ability (90 days; n=753) were identified in the Swedish biologics register (Anti-Rheumatic Treatment In Sweden, ARTIS) and sick leave/disability pension days retrieved from the Social Insurance Agency. Outcome was defined as work ability gain ≥50% for patients without work ability at bio-start and work ability loss ≥50% for patients with full work ability, and survival analyses conducted. Baseline predictors including disease duration, age, sex, education level, employment, Health Assessment Questionnaire, Disease Activity Score 28 and relevant comorbidities were estimated using Cox regression. During 3 years after anti-TNF start, the probability of regaining work ability for totally work-disabled patients was 35% for those with disease duration start, disease duration did not predict work ability loss. Baseline disability pension was also a strong predictor of work ability gain after treatment start. A substantial proportion of work-disabled patients with RA who start anti-TNF therapy regain work ability. Those initiating treatment within 5 years of symptom onset have a more than doubled 3-year probability of regaining work ability compared with later treatment starts. This effect seems largely due to the impact of disease duration on disability pension status. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Níveis de Treonina em Rações para Leitões dos 6 aos 15 kg

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Rodrigues Nair Elizabeth Barreto

2001-01-01

Full Text Available Foram utilizados 75 suínos com peso inicial médio de 5,8 ± 0,4 kg, com o objetivo de avaliar níveis de treonina em rações para leitões com alto potencial genético para deposição de carne magra dos 6 aos 15 kg. Foi usado o delineamento experimental de blocos ao acaso com cinco tratamentos (níveis de treonina, cinco repetições e três animais por unidade experimental. Os tratamentos corresponderam a uma ração basal com 18% PB e 1,108% lisina total, suplementada com cinco níveis de L-treonina, resultando em dietas com níveis de 0,682; 0,732; 0,782; 0,832; e 0,883% de treonina total. Observou-se variação quadrática para ganho de peso diário (GDP, que aumentou até o nível de 0,77%, e para consumo de ração (CR, que aumentou até o nível estimado de 0,73%. Os níveis de treonina também influenciaram de forma quadrática a conversão alimentar (CA, que melhorou até o nível de 0,82%. A relação da lisina digestível verdadeira:treonina digestível verdadeira, no nível que proporcionou os melhores resultados de CA, correspondeu a 100:73. Concluiu-se que leitões com alto potencial genético para carne magra dos 6 aos 15 kg exigem 0,77% de treonina total na ração para máximo ganho de peso e 0,82% para melhor conversão alimentar.

Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke

DEFF Research Database (Denmark)

Clausen, Bettina Hjelm; Lambertsen, Kate Lykke; Dagnæs-Hansen, Frederik

2016-01-01

), a known neuroprotectant in stroke, can promote neuroprotection, by modulating the detrimental inflammatory response in the tissue at risk. We show by the use of IL-1Ra-overexpressing and IL-1Ra-deficient mice that IL-1Ra is neuroprotective in stroke. Characterization of the cellular and spatiotemporal...... irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving...... by demonstration of IL-1Ra-producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes...

Mammography screening credit card and compliance.

Science.gov (United States)

Schapira, D V; Kumar, N B; Clark, R A; Yag, C

1992-07-15

Screening for breast cancer using mammography has been shown to be effective in reducing mortality from breast cancer. The authors attempted to determine if use of a wallet-size plastic screening "credit" card would increase participants' compliance for subsequent mammograms when compared with traditional methods of increasing compliance. Two hundred and twenty consecutive women, ages 40-70 years, undergoing their first screening mammography were recruited and assigned randomly to four groups receiving (1) a reminder plastic credit card (2) reminder credit card with written reminder; (3) appointment card; and (4) verbal recommendation. Return rates of the four groups were determined after 15 months. The return rate for subsequent mammograms was significantly higher for participants (72.4%) using the credit card than for participants (39.8%) exposed to traditional encouragement/reminders (P less than 0.0001). The credit card was designed to show the participant's screening anniversary, and the durability of the card may have been a factor in increasing the return rate. The use of reminder credit cards may increase compliance for periodic screening examinations for other cancers and other chronic diseases.

Intake of Moringa oleifera Leaf Extract Decreases IL-1 and TNF-α Levels in Dyslipidemic Wistar Rat Model

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Sri Wahyuni

2017-05-01

Full Text Available Changes in consumption behavior to instant food cause various health problems, such as obesity, dislipidemia, and atherosclerosis. A study was conducted to investigate Moringa oleifera extract as an anti-inflammation product that decreases the levels of biochemical markers IL-1 and TNF-a. This experiment was done with randomized pre- and posttest control-group design, employing 40 Wistar rats separated into five groups: control group 0% M. oleifera leaf extract (P0, treatment group 1 with 10% M. oleifera leaf extract (P1, treatment group 2 with 15% M. oleifera leaf extract (P2, treatment group 3 with 20% M. oleifera leaf extract (P3, and treatment group 4 with 25% M. oleifera leaf extract (P4. This research observed that intake of 20% M. oleifera leaf extract results in the highest significant decrease of 15.42% of IL-1 level (134.64 ± 1.98 to 113.87 ± 4.30 pg/mL and decrease of 45.63% of TNF-α level (28.62 ± 1.25 to 15.56 ± 7.20 pg/mL. Therefore, it can be concluded that intake of M. oleifera leaf extract by Wistar rat has anti-inflammatory effects on chronic dyslipidemia through decrease of IL-1 and TNF-α levels and histopathology profile. Further research is required to determine whether the application of M. oleifera leaf extract (daun kelor in humans will have similar anti-inflammation effects.

RA Research nuclear reactor Part 1, RA Reactor operation and maintenance in 1987; Istrazivacki nuklearni reaktor RA Deo 1 - Pogon i odrzavanje nuklearnog reaktora RA u 1987. godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Martinc, R; Cupac, S; Sulem, B; Badrljica, R; Majstorovic, D; Sanovic, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1987-12-15

RA research reacto was not operated due to the prohibition issued in 1984 by the Government of Serbia. Three major tasks were finished in order to fulfill the licensing regulations about safety of nuclear facilities which is the condition for obtaining permanent operation licence. These projects involved construction of the emergency cooling system, reconstruction of the existing special ventilation system, and renewal of the system for electric power supply of the reactor systems. Renewal of the RA reactor instrumentation system was initiated. Design project was done by the Russian Atomenergoeksport, and is foreseen to be completed by the end of 1988. The RA reactor safety report was finished in 1987. This annual report includes 8 annexes concerning reactor operation, activities of services and financial issues, and three special annexes: report on testing the emergency cooling system, report on renewal of the RA reactor and design specifications for reactor renewal and reconstruction. [Serbo-Croat] Reaktor RA nije radio usled zabrane Izvsnog veca Skupstine Srbije od 27. avgusta 1984. U cilju povecanja pouzdanosti rada reaktora a da bi se udovoljilo zakonskim propisima sto je uslov za dobijanje stalne dozvole za rad realizovana su tri velika zahvata na reaktoru RA. Ovi zahvati obuhvatili su izgradnju sistema za hladjenje jezgra reaktora u slucaju nuzde, rekonstukciju postojeceg sistema specijalne ventilacije i rekonstrukciju sistema napajanja elektricnom energijom neophodnih potrosaca reaktora RA. Zapoceti su radovi na modernizaciji intrumentacije reaktora RA, projekat je izradjen u sovjetskoj organizaciji Atomenergoeksport, a trebalo bi da se realizuje do kraja 1989. godine. U cilju povecanja prostora za skladistenje ozracenog nuklearnog goriva i njegovog efikasnijeg koriscenja, izradjen je su projekti za rekonstrukciju postojecih uredjaja za rukovanje gorivom, povecanje smestajnog kapaciteta i preciscavanje vode u bazenima za odlezavanje. Realizaija ovih

Mutations in CARD15 and smoking confer susceptibility to Crohn's disease in the Danish population

DEFF Research Database (Denmark)

Ernst, Anja; Jacobsen, Bent Ascanius; Østergaard, Mette

2007-01-01

Three CAspase Recruitment Domain (CARD15) mutations have shown to predispose to Crohn's disease in Caucasian populations. The aim of this study was to investigate the mutation frequency in patients with inflammatory bowel disease and in healthy controls in Denmark....

The decay scheme of 229Ra

International Nuclear Information System (INIS)

Yang, W.F.; Yuan, S.G.; Fang, K.M.; Shen, S.F.; Mou, W.T.; Zhang, X.Q.; Li, Z.Q.

1997-01-01

By bombarding the natural thorium targets with 14 MeV neutrons, 229 Ra was produced through the reaction 232 Th(n,α) 229 Ra. The radium activities were separated from the irradiated targets by coprecipitation with the BaCl 2 . A total of 18 new weak γ rays with energies of 14.5, 15.6, 18.8, 21.8, 22.5, 44.0, 47.5, 55.0, 63.0, 69.6, 93.6, 94.1, 98.5, 102.2, 104.5, 106.1, 161.1, and 171.5 keV which could be assigned to the decay of 229 Ra were observed in the isolated radium fractions employing high resolution HPGe detectors and γ(X)-γ coincidence methods. A decay scheme of 229 Ra based on these observations is proposed. (orig.). With 2 figs

Synovial features of patients with rheumatoid arthritis and psoriatic arthritis in clinical and ultrasound remission differ under anti-TNF therapy: a clue to interpret different chances of relapse after clinical remission?

Science.gov (United States)

Alivernini, Stefano; Tolusso, Barbara; Petricca, Luca; Bui, Laura; Di Sante, Gabriele; Peluso, Giusy; Benvenuto, Roberta; Fedele, Anna Laura; Federico, Franco; Ferraccioli, Gianfranco; Gremese, Elisa

2017-07-01

To define the synovial characteristics of patients with rheumatoid arthritis (RA) and psoriatic arthritis (PsA) in clinical and ultrasound remission achieved by combination therapy with methotrexate (MTX) and tumour necrosis factor (TNF) blockers. Patients with RA in remission (n=25) (disease activity score (DAS)<1.6 for at least 6 months), patients with RA in low disease activity (LDA) (n=10) (1.61.6 and Psoriasis Area Severity Index (PASI)=0 for at least 6 months) achieved by MTX+anti-TNF (adalimumab 40 mg or etanercept 50 mg) with power Doppler (PDUS)-negative synovial hypertrophy underwent synovial tissue biopsy. Patients with RA with high/moderate disease naïve to treatment (n=50) were included as a comparison group. Immunostaining for cluster designation (CD)68, CD21, CD20, CD3, CD31 and collagen was performed. PDUS-negative patients with RA in remission showed lower histological scores for synovial CD68 + , CD20 + , CD3 + cells and CD31 + vessels and collagen deposition (p<0.05 for both lining and sublining) compared with PDUS-positive patients with RA with high/moderate disease. In addition, there was no significant difference in terms of lining and sublining CD68 + , CD20 + , CD3 + , CD31 + cells and collagen comparing PDUS-negative patients with RA in remission and in LDA, respectively. On the contrary, PDUS-negative patients with PsA in remission showed higher histological scores for sublining CD68 + (p=0.02) and CD3 + cells (p=0.04) as well as CD31 + vessels (p<0.001) than PDUS-negative patients with RA in remission. PDUS-negative patients with RA in remission have comparable synovial histological features than PDUS-negative patients with RA in LDA. However, patients with PsA in remission are characterised by a higher degree of residual synovial inflammation than patients with RA in remission, despite PDUS negativity under TNF inhibition. Published by the BMJ

Factors affecting receipt of a medical card in a cohort of colorectal cancer patients, 2002-2006.

Science.gov (United States)

McDevitt, J; Sharp, L; MacDonald, D; Dwane, F; Comber, H

2013-04-01

The criteria for allocation of medical cards to colorectal cancer patients master file to determine medical card status. Determinants of medical card possession before diagnosis were; age 65-69yr vs. 15-54 yr (OR = 3.95 (95% CI); 3.20-4.88), other status vs. married (OR = 1.89; 1.61-2.23), most vs. least deprived (OR = 3.65; 2.89-4.61), smoker vs. non-smoker (OR = 1.98; 1.64-2.37), ED population density ( 15/ha; OR = 1.47; 1.20-1.80). Determinants of medical card possession after diagnosis were; age 65-69 yr vs. 15-54 yr (OR = 0.77; 0.62-0.96), most vs. least deprived (OR = 2.15; 1.72-2.70), stage IV vs. 1: OR = 2.49; 1.85-3.36), chemotherapy (OR = 2.30; 1.87-2.83), radiotherapy (OR = 1.40; 1.13-1.72), ED population density ( 15/ha; OR = 1.47; 1.19-1.82), HSE South vs. DNML (OR = 1.76; 1.40-2.21). Medical card possession among colorectal cancer patients was determined by greater age and deprivation before diagnosis; and younger age, greater deprivation, advanced stage and treatments warranted by extent of disease after diagnosis. Low population density of ED of residence also predicted card receipt.

Use of anti-tumor necrosis factor biologics in the treatment of rheumatoid arthritis does not change human T-lymphotropic virus type 1 markers: a case series.

Science.gov (United States)

Umekita, Kunihiko; Umeki, Kazumi; Miyauchi, Shunichi; Ueno, Shiro; Kubo, Kazuyoshi; Kusumoto, Norio; Takajo, Ichiro; Nagatomo, Yasuhiro; Okayama, Akihiko

2015-09-01

Anti-tumor necrosis factor (anti-TNF) biologics are effective in the treatment of rheumatoid arthritis (RA); however, it is still not clear whether this treatment promotes the development of malignancies such as lymphoma. Human T-lymphotropic virus type 1 (HTLV-1), which is a causative agent of adult T-cell lymphoma (ATL), is prevalent in Japan. Many HTLV-1-positive patients with RA are assumed to exist; however, there have thus far been no reports on the effect of anti-TNF biologics on HTLV-1-positive patients. We analyzed the response to treatment with anti-TNF biologics and change of HTLV-1 markers in two cases of RA. The two cases showed no response based on the European League Against of Rheumatism response criteria 60-96 weeks after administration of anti-TNF biologics (infliximab and etanercept). No signs of ATL were observed and HTLV-1 markers, such as proviral load and clonality of HTLV-1-infected cells, showed no significant change in either of two cases. Therefore, treatment with anti-TNF biologics did not induce activation of HTLV-1, although the effect on RA was not as effective as in HTLV-1-negative patients in this limited study. Further long-term study with a greater number of patients is necessary to clarify the safety and efficacy of anti-TNF biologics in HTLV-1-positive patients with RA.

Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology.

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Marcela Montes de Oca

2016-01-01

Full Text Available Tumor necrosis factor (TNF is critical for controlling many intracellular infections, but can also contribute to inflammation. It can promote the destruction of important cell populations and trigger dramatic tissue remodeling following establishment of chronic disease. Therefore, a better understanding of TNF regulation is needed to allow pathogen control without causing or exacerbating disease. IL-10 is an important regulatory cytokine with broad activities, including the suppression of inflammation. IL-10 is produced by different immune cells; however, its regulation and function appears to be cell-specific and context-dependent. Recently, IL-10 produced by Th1 (Tr1 cells was shown to protect host tissues from inflammation induced following infection. Here, we identify a novel pathway of TNF regulation by IL-10 from Tr1 cells during parasitic infection. We report elevated Blimp-1 mRNA levels in CD4+ T cells from visceral leishmaniasis (VL patients, and demonstrate IL-12 was essential for Blimp-1 expression and Tr1 cell development in experimental VL. Critically, we show Blimp-1-dependent IL-10 production by Tr1 cells prevents tissue damage caused by IFNγ-dependent TNF production. Therefore, we identify Blimp-1-dependent IL-10 produced by Tr1 cells as a key regulator of TNF-mediated pathology and identify Tr1 cells as potential therapeutic tools to control inflammation.

Hematologic interactions of endotoxin, tumor necrosis factor alpha (TNF alpha), interleukin 1, and adrenal hormones and the hematologic effects of TNF alpha in Corynebacterium parvum-primed rats.

Science.gov (United States)

Ulich, T R; del Castillo, J; Ni, R X; Bikhazi, N

1989-06-01

Endotoxin reduces the release among other cytokines of tumor necrosis factor (TNF) and interleukin 1 (IL-1) and causes peripheral lymphopenia and a dose-response-dependent initial neutropenia followed by a monophasic neutrophilia. TNF alone induces lymphopenia and an initial neutropenia followed by a biphasic neutrophilia. IL-1 alone induces lymphopenia and a monophasic neutrophilia. TNF-plus-IL-1 caused a greater lymphopenia than either monokine alone, suggesting that both monokines contribute to LPS-induced lymphopenia. TNF-plus-IL-1 induced neutropenia similar in magnitude to that induced by TNF alone and induced a neutrophilia significantly greater than that induced by either monokine alone, suggesting that LPS-induced neutropenia is caused by TNF, while LPS-induced neutrophilia is due to the combined effects of TNF and II-1. TNF and IL-1 were administered together with LPS to simulate the in vivo condition of endogenous monokine release during gram-negative bacteremia. TNF combined with LPS increased both the duration and magnitude of LPS-induced lymphopenia, LPS-induced neutropenia, and LPS-induced neutrophilia. TNF-plus-LPS treated rats at 2 hours after injection exhibited a striking 93% decrease in bone marrow neutrophils even though no peripheral neutrophilia was yet apparent, suggesting that the subsequent neutrophilia was due to demargination and recirculation of neutrophils sequestered in the peripheral vasculature immediately after their release from the bone marrow. Epinephrine, which causes neutrophilia by demargination but not by release of marrow neutrophils, reversed the initial neutropenia in TNF-plus-LPS-treated rats and increased the neutrophilia. IL-1 combined with LPS increased LPS-induced neutrophilia, suggesting that endogenous IL-1 also contributed to LPS-induced neutrophilia. Corynebacterium parvum-primed rats with hyperplasia of the monocyte-macrophage system and treated with TNF differed from naive rats treated with TNF in that the

Post-stroke infection: a role for IL-1ra?

Science.gov (United States)

Tanzi, Pat; Cain, Kevin; Kalil, Angela; Zierath, Dannielle; Savos, Anna; Gee, J Michael; Shibata, Dean; Hadwin, Jessica; Carter, Kelly; Becker, Kyra

2011-04-01

Infection is common following stroke and is independently associated with worse outcome. Clinical studies suggest that infections occur more frequently in those individuals with stroke-induced immunologic dysfunction. This study sought to explore the contribution of immunomodulatory cytokines and hormones to lymphocyte function and infection risk. Patients (N = 112) were enrolled as soon as possible after the onset of ischemic stroke. Blood was drawn to assess plasma cortisol, IL-10, IL-1ra, lymphocyte numbers, and lymphocyte function at 72 h after stroke onset; infections were censored through 21 days after stroke onset. Infection occurred in 25% of patients. Stroke severity was the most important predictor of infection risk. Increased plasma cortisol, IL-10, and IL-1ra, as well as decreased lymphocyte numbers, at 72 h after stroke onset were associated with risk of subsequent infection. After controlling for stroke severity, only IL-1ra was independently associated with infection risk, and the degree of risk was consistent throughout the post-stroke period. Infection, but not IL-1ra itself, was associated with worse outcome at 3 months. In this study cohort, increased plasma IL-1ra was independently associated with the risk of post-stroke infection. Further studies are needed to validate this finding, which could have important implications for stroke therapy.

IL-1Ra (recombinant human IL-1 receptor antagonist in the treatment of rheumatoid arthritis: the efficacy

Directory of Open Access Journals (Sweden)

L. Cozzi

2011-09-01

Full Text Available Interleukin 1 receptor antagonist (IL-1Ra is a naturally occurring IL-1 inhibitor, acting as a “receptor antagonist”, which blocks IL-1 mediated signal transduction. In 1990 IL-1Ra was cloned and later on, a large numbers of studies led to disclosure of the crucial importance of the imbalance between IL-1 and IL-1Ra in the pathogenesis of rheumatoid arthritis (RA. In 1991, almost 8 years after the initial isolation of IL-1, recombinant IL-1Ra (IL-1ra, Kineret was introduced in clinical trials involving patients with RA. Between 2001 and 2002 IL-1ra was approved by the US Food and Drug Administration and by the European Agency for the Evaluation of the Medicinal Products and in 2003 it was registered in Italy, too. In RA recombinant IL-1ra has been evaluated in 5 randomized, placebo-controlled clinical trials involving more than 2900 patients. Two of the trials involved the use of IL-1ra as monotherapy versus placebo and two trials in combination with methotrexate (MTX; the last trial explored the use of a fixed 100 mg/day IL-1ra dosage in a RA patient population including a wide array of co-morbid conditions as well as concomitant medications. The studies confirmed both the efficacy and the safety of IL-1ra in patients with active and severe RA. 43% of patients receiving 150 mg/day IL-1ra achieved a 20% response according to the American College of Rheumatology criteria (ACR20, compared to 27% in the placebo group. In the MTX combination therapy study, 42% of the patients receiving 1 mg/Kg/day of IL-1ra achieved an ACR20, 24% an ACR50 and 10% an ACR70. In each study, significant improvements in the Health Assessment Questionnaire scores (HAQ were observed. There were rapid gains in the number of days at work or domestic activity in the treated patients, and the increases in productivity were dose related. At early 24 weeks, there was significant reduction of both the score for progression of joint space narrowing (JSN and the Total modified

High titers of both rheumatoid factor and anti-CCP antibodies at baseline in patients with rheumatoid arthritis are associated with increased circulating baseline TNF level, low drug levels, and reduced clinical responses: a post hoc analysis of the RISING study.

Science.gov (United States)

Takeuchi, Tsutomu; Miyasaka, Nobuyuki; Inui, Takashi; Yano, Toshiro; Yoshinari, Toru; Abe, Tohru; Koike, Takao

2017-09-02

Although both rheumatoid factor (RF) and anticyclic citrullinated peptide antibodies (anti-CCP) are useful for diagnosing rheumatoid arthritis (RA), the impact of these autoantibodies on the efficacy of tumor necrosis factor (TNF) inhibitors has been controversial. The aim of this post hoc analysis of a randomized double-blind study (the RISING study) was to investigate the influences of RF and anti-CCP on the clinical response to infliximab in patients with RA. Methotrexate-refractory patients with RA received 3 mg/kg of infliximab from weeks 0 to 6 and then 3, 6, or 10 mg/kg every 8 weeks from weeks 14 to 46. In this post hoc analysis, patients were stratified into three classes on the basis of baseline RF/anti-CCP titers: "low/low-C" (RF < 55 IU/ml, anti-CCP < 42 U/ml), "high/high-C" (RF ≥ 160 IU/ml, anti-CCP ≥ 100 U/ml), and "middle-C" (neither low/low-C nor high/high-C). Baseline plasma TNF level, serum infliximab level, and disease activity were compared between the three classes. Baseline RF and anti-CCP titers showed significant correlations with baseline TNF and infliximab levels in weeks 2-14. Comparison of the three classes showed that baseline TNF level was lowest in the low/low-C group and highest in the high/high-C group (median 0.73 versus 1.15 pg/ml), that infliximab levels at week 14 were highest in the low/low-C group and lowest in the high/high-C group (median 1.0 versus 0.1 μg/ml), and that Disease Activity Score in 28 joints based on C-reactive protein at week 14 was lowest in the low/low-C group and highest in the high/high-C group (median 3.17 versus 3.82). A similar correlation was observed at week 54 in the 3 mg/kg dosing group, but not in the 6 or 10 mg/kg group. Significant decreases in both RF and anti-CCP were observed during infliximab treatment. RF/anti-CCP titers correlated with TNF level. This might explain the association of RF/anti-CCP with infliximab level and clinical response in patients with RA

Cost per responder of TNF-α therapies in Germany.

Science.gov (United States)

Gissel, Christian; Repp, Holger

2013-12-01

Tumor necrosis factor α (TNF-α) inhibitors ranked highest in German pharmaceutical expenditure in 2011. Their most important application is the treatment of rheumatoid arthritis (RA). Our objective is to analyze cost per responder of TNF-α inhibitors for RA from the German Statutory Health Insurance funds' perspective. We aim to conduct the analysis based on randomized comparative effectiveness studies of the relevant treatments for the German setting. For inclusion of effectiveness studies, we require results in terms of response rates as defined by European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) criteria. We identify conventional triple therapy as the relevant comparator. We calculate cost per responder based on German direct medical costs. Direct clinical comparisons could be identified for both etanercept and infliximab compared to triple therapy. For infliximab, cost per responder was 216,392 euros for ACR50 and 432,784 euros for ACR70 responses. For etanercept, cost per ACR70 responder was 321,527 euros. Cost was lower for response defined by EULAR criteria, but data was only available for infliximab. Cost per responder is overestimated by 40% due to inclusion of taxes and mandatory rebates in German drugs' list prices. Our analysis shows specific requirements for cost-effectiveness analysis in Germany. Cost per responder for TNF-α treatment in the German setting is more than double the cost estimated in a similar analysis for the USA, which measured against placebo. The difference in results shows the critical role of the correct comparator for a specific setting.

Paradoxical arthritis occurring during anti-TNF in patients with inflammatory bowel disease: histological and immunological features of a complex synovitis.

Science.gov (United States)

Alivernini, Stefano; Pugliese, Daniela; Tolusso, Barbara; Bui, Laura; Petricca, Luca; Guidi, Luisa; Mirone, Luisa; Rapaccini, Gian Ludovico; Federico, Francesco; Ferraccioli, Gianfranco; Armuzzi, Alessandro; Gremese, Elisa

2018-01-01

Paradoxical arthritis under tumour necrosis factor inhibitor (TNF-i) for inflammatory bowel disease (IBD) has been described. This study aims to evaluate the histological features of paired synovial tissue (ST) and colonic mucosa (CM) tissue in patients with IBD developing paradoxical arthritis under TNF-i. Patients with IBD without history of coexisting joint involvement who developed arthritis under TNF-i were enrolled. Each patient underwent ST biopsy and ileocolonoscopy with CM biopsies. ST and CM paired samples were stained through immunohistochemistry (IHC) for CD68, CD21, CD20, CD3 and CD117. Clinical and immunological parameters (anticitrullinated peptides antibodies (ACPA)-immunoglobulin (Ig)M/IgA rheumatoid factor (RF)) were collected. Psoriatic arthritis (PsA) and ACPA/IgM-RF/IgA-RF negative rheumatoid arthritis (RA) were enrolled as comparison. 10 patients with IBD (age 46.0±9.7 years, 13.2±9.9 years of disease duration, 2.5±1.6 years of TNF-i exposure, six with Crohn's disease and four with ulcerative colitis, respectively) were studied. At ST level, IHC revealed that patients with IBD with paradoxical arthritis showed more similar histological findings in terms of synovial CD68 + , CD21 + , CD20 + , CD3 + and CD117 + cells compared with PsA than ACPA/IgM-RF/IgA-RF negative RA. Analysing the CM specimens, patients with IBD showed the presence of CD68 + , CD3 + , CD117 + and CD20 + cells in 100%, 70%, 60% and 50% of cases, respectively, despite endoscopic remission. Finally, addition of conventional disease-modifying antirheumatic drugs and switch to ustekinumab were more effective than swapping into different TNF-i in patients with IBD with paradoxical arthritis. Patients with IBD may develop histologically proven synovitis during TNF-i, comparable to PsA. The inhibition of inflammatory pathways alternative to TNF (IL12/1L23) may be an effective therapeutic option for severe paradoxical articular manifestations.

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

Science.gov (United States)

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.

Anti-TNF treatment response in rheumatoid arthritis patients is associated with genetic variation in the NLRP3-inflammasome

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Sode, Jacob; Vogel, Ulla; Bank, Steffen

2014-01-01

OBJECTIVE: Many patients with rheumatoid arthritis (RA) benefit from tumor necrosis factor-α blocking treatment (anti-TNF), but about one third do not respond. The objective of this study was to replicate and extend previously found associations between anti-TNF treatment response and genetic...... logistic regression analyses were performed to test associations between genotypes and treatment response at 3-6 months using the European League Against Rheumatism (EULAR) response criterion. American College of Rheumatology treatment response (ACR50) and relative change in 28-joint disease activity score.......36-0.98), p = 0.040, q = 0.76). Current smokers who carried the NLRP3(rs4612666) variant allele were less likely to benefit from anti-TNF treatment (OR = 0.24 (0.10-0.56), p = 0.001, q = 0.04). CONCLUSIONS: In a population of Danish RA patients, we confirm the NLRP3 gene as associated with EULAR anti...

The impacts of smart cards on hospital information systems--an investigation of the first phase of the national health insurance smart card project in Taiwan.

Science.gov (United States)

Liu, Chien-Tsai; Yang, Pei-Tun; Yeh, Yu-Ting; Wang, Bin-Long

2006-02-01

To investigate the impacts of the first phase of Taiwan's Bureau of National Health Insurance (TBNHI) smart card project on existing hospital information systems. TBNHI has launched a nationwide project for replacement of its paper-based health insurance cards by smart cards (or NHI-IC cards) since November 1999. The NHI-IC cards have been used since 1 July 2003, and they have fully replaced the paper-based cards since 1 January 2004. Hospitals must support the cards in order to provide medical services for insured patients. We made a comprehensive study of the current phase of the NHI-IC card system, and conducted a questionnaire survey (from 1 October to 30 November, 2003) to investigate the impacts of NHI-IC cards on the existing hospital information systems. A questionnaire was distributed by mail to 479 hospitals, including 23 medical centers, 71 regional hospitals, and 355 district hospitals. The returned questionnaires were also collected by prepaid mail. The questionnaire return rates of the medical centers, regional hospitals and district hospitals were 39.1, 29.6 and 20.9%, respectively. In phase 1 of the project, the average number of card readers purchased per medical center, regional hospital, and district hospital were 202, 45 and 10, respectively. The average person-days for the enhancement of existing information systems of a medical center, regional hospital and district hospital were 175, 74 and 58, respectively. Three months after using the NHI-IC cards most hospitals (60.6%) experienced prolonged service time for their patients due to more interruptions caused mainly by: (1) impairment of the NHI-IC cards (31.2%), (2) failure in authentication of the SAMs (17.0%), (3) malfunction in card readers (15.3%) and (4) problems with interfaces between the card readers and hospital information systems (15.8%). The overall hospital satisfaction on the 5-point Likert scale was 2.86. Although most hospitals were OK with the project, there was about 22

Observation of unexpectedly small E1 moments in sup 224 Ra

Energy Technology Data Exchange (ETDEWEB)

Poynter, R.J.; Butler, P.A.; Clarkson, N.; Hoare, T.H.; Jones, G.D.; White, C.A. (Liverpool Univ. (UK). Oliver Lodge Lab.); Cline, D. (Rochester Univ., NY (USA). Nuclear Structure Research Lab.); Connell, K.A.; Cunningham, R.A.; Simpson, J. (Science and Engineering Research Council, Daresbury (UK). Daresbury Lab.); Goettig, L. (Warsaw Univ. (Poland). Inst. Fizyki Doswiadczalnej); Hughes, J.R.; Jarvis, N.S.; Mullins, S.M.; Wadsworth, R.; Watson, D.L. (York Univ. (UK). Dept. of Physics); Juutinen, S. (Jyvaeskylae Univ. (Finland). Dept. of Physics); Pass, C.N. (Oxford Univ. (UK). Dept. of Nuclear Physics)

1989-12-14

The {alpha}-decay of {sup 228}Th and the reaction {sup 226}Ra({sup 58}Ni, {sup 60}Ni){sup 224}Ra have been employed to populate states in {sup 224}Ra up to I{sup {pi}}=12{sup +}. Values of the intrinsic electric dipole moment vertical strokeQ{sub 1}vertical stroke have been deduced from the observed B(E1)/B(E2) branching ratios. These values are < or approx.0.1 e fm for spins up to I{sup {pi}}=9{sup -}, and are thus smaller than those in {sup 218,220}Ra or {sup 226}Ra. The behaviour of Q{sub 1} suggests that shell effects are important in this mass region, although theoretical calculations which include these effects do not reproduce the observed pattern. (orig.).

Exploring the Inflammatory Metabolomic Profile to Predict Response to TNF-α Inhibitors in Rheumatoid Arthritis.

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Bart V J Cuppen

Full Text Available In clinical practice, approximately one-third of patients with rheumatoid arthritis (RA respond insufficiently to TNF-α inhibitors (TNFis. The aim of the study was to explore the use of a metabolomics to identify predictors for the outcome of TNFi therapy, and study the metabolomic fingerprint in active RA irrespective of patients' response. In the metabolomic profiling, lipids, oxylipins, and amines were measured in serum samples of RA patients from the observational BiOCURA cohort, before start of biological treatment. Multivariable logistic regression models were established to identify predictors for good- and non-response in patients receiving TNFi (n = 124. The added value of metabolites over prediction using clinical parameters only was determined by comparing the area under receiver operating characteristic curve (AUC-ROC, sensitivity, specificity, positive- and negative predictive value and by the net reclassification index (NRI. The models were further validated by 10-fold cross validation and tested on the complete TNFi treatment cohort including moderate responders. Additionally, metabolites were identified that cross-sectionally associated with the RA disease activity score based on a 28-joint count (DAS28, erythrocyte sedimentation rate (ESR or C-reactive protein (CRP. Out of 139 metabolites, the best-performing predictors were sn1-LPC(18:3-ω3/ω6, sn1-LPC(15:0, ethanolamine, and lysine. The model that combined the selected metabolites with clinical parameters showed a significant larger AUC-ROC than that of the model containing only clinical parameters (p = 0.01. The combined model was able to discriminate good- and non-responders with good accuracy and to reclassify non-responders with an improvement of 30% (total NRI = 0.23 and showed a prediction error of 0.27. For the complete TNFi cohort, the NRI was 0.22. In addition, 88 metabolites were associated with DAS28, ESR or CRP (p<0.05. Our study established an accurate

FRENCH PROTOCOL CARDS

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Human Resources Division

2000-01-01

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.2000, are requested to return these cards and those of family members, for extension to: Bureau des cartes, Bât 33.1-009/1-015 Should the three spaces for authentication on the back of the card be full, please enclose two passport photographs for a new card. In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.

FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy.

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Dawn L Cooper

Full Text Available OBJECTIVE: The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC. We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA, associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. METHODS: FcγRIIIa/CD16 expression on CD14(low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease. Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. RESULTS: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002 with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001. The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003 and was significantly increased in EULAR non-responders compared to moderate (p = 0.01 or good responders (p = 0.003. FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. CONCLUSION: Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.

FcγRIIIa Expression on Monocytes in Rheumatoid Arthritis: Role in Immune-Complex Stimulated TNF Production and Non-Response to Methotrexate Therapy

Science.gov (United States)

Cooper, Dawn L.; Martin, Stephen G.; Robinson, James I.; Mackie, Sarah L.; Charles, Christopher J.; Nam, Jackie; Consortium, YEAR; Isaacs, John D.; Emery, Paul; Morgan, Ann W.

2012-01-01

Objective The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. Methods FcγRIIIa/CD16 expression on CD14low and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. Results Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. Conclusion Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy. PMID:22235253

26 CFR 301.6311-2 - Payment by credit card and debit card.

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2010-04-01

... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Payment by credit card and debit card. 301.6311....6311-2 Payment by credit card and debit card. (a) Authority to receive—(1) Payments by credit card and debit card. Internal revenue taxes may be paid by credit card or debit card as authorized by this...

Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis.

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Kalle J Aaltonen

Full Text Available Five-tumour necrosis factor (TNF-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT.A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE, Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX, in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias.Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo.No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

CAC-RA1 1958-1998. The first years of the Constituyentes Atomic Center (CAC). History of the first Argentine nuclear reactor (RA-1)

International Nuclear Information System (INIS)

Forlerer, Elena; Palacios, Tulio A.

1998-01-01

After giving the milestones of the development of the Constituyentes Atomic Center since 1957, the history of the construction of the first nuclear reactor (RA-1) in Argentina, including the local fabrication of its fuel elements, is surveyed. The RA-1 reached criticality on January 17, 1958. The booklet commemorates the 40th year of the reactor operation

Association of TNF promoter polymorphisms with type 1 diabetes in the South Croatian population

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VESNA BORASKA

2008-01-01

Full Text Available Type 1 diabetes mellitus (TIDM is an autoimmune disease characterized by the destruction of pancreatic p cells. Tumor necrosis factor (TNF is a pleotropic cytokine with potent immunomodulatory and inflammatory activity. Association studies of TNF polymorphisms and type 1 diabetes (TIDM frequently demonstrated TNF involvement with TIDM. Although TNF may play an important role in the pathogenesis of TIDM, the genetic association of TNF región with the disease has not been conclusive because of the strong linkage disequilibrium with HLA genes. In this study, we examined two TNF promoter variants (rs 1800629 at position -308, and rs361525 at position -238 for TIDM association in 233 patients and 144 controls from the population of South Croatia. A higher frequency of TNF -308 A alíele and also, a more frequent specific -308A -238G haplotype in TIDM patients were observed with a limited significance. However, we did not find strong evidence of association of TNF promoter polymorphisms with TIDM. In order to elucidate the trae contribution of TNF to TIDM susceptibility in our population, more comprehensive studies with HLA adjustment in a larger sample are required.

CHIS – New insurance cards and phone numbers valid from 1 January 2015

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HR Department

2014-01-01

New health insurance cards will be posted to CHIS members by mid-December. The new cards are valid from 1 January 2015 and will no longer indicate an end date. You may use the card as long as you are member; if lost, a new card will be delivered on request. From 1 January 2015, please use the telephone numbers printed on your new insurance card: +41 (0)22 718 63 00 for UNIQA’s Head Office, available during office hours +41 (0)22 819 44 77 for UNIQA medical assistance and telemedicine, available 24/7 +1 844 477 0777 in the event of hospitalisation in the USA, available 24/7   Further information on the new services (UNIQA assistance and telemedicine) is available in the CHIS Bulletin 39, which you will receive at your home address during the second half of December. Please note that from 1 January 2015: You should not call the emergency number 24/24 on your old insurance card, as this service will be discontinued. You no longer need to obtain a separate insurance card from Meds...

Ubiquitous hazardous metal lead induces TNF-{alpha} in human phagocytic THP-1 cells: Primary role of ERK 1/2

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Khan, Mohd Imran [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Islam, Najmul [Department of Biochemistry, J.N Medical College, Aligarh Muslim University, Aligarh (India); Sahasrabuddhe, Amogh A. [Molecular and Structural Biology Division, Central Drug Research Institute, Lucknow (India); Mahdi, Abbas Ali [Department of Biochemistry, C.S.M. Medical University, Lucknow (India); Siddiqui, Huma; Ashquin, Mohd [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India); Ahmad, Iqbal, E-mail: ahmadi@sify.com [Fiber Toxicology Division, Indian Institute of Toxicology Research, Council of Scientific and Industrial Research (CSIR), Mahatma Gandhi Marg, P.O Box 80, Lucknow 226001, U.P. (India)

2011-05-15

Induction of tumor necrosis factor-{alpha} (TNF-{alpha}) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-{alpha} is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-{alpha} induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-{alpha} m-RNA and protein secretion. Moreover, the stability of TNF-{alpha} m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-{alpha} m-RNA. However, SB 203580 partially inhibited production and stability of TNF-{alpha} m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-{alpha} m-RNA. Data tends to suggest that expression and stability of TNF-{alpha} induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

Ubiquitous hazardous metal lead induces TNF-α in human phagocytic THP-1 cells: Primary role of ERK 1/2

International Nuclear Information System (INIS)

Khan, Mohd Imran; Islam, Najmul; Sahasrabuddhe, Amogh A.; Mahdi, Abbas Ali; Siddiqui, Huma; Ashquin, Mohd; Ahmad, Iqbal

2011-01-01

Induction of tumor necrosis factor-α (TNF-α) in response to lead (Pb) exposure has been implicated in its immunotoxicity. However, the molecular mechanism by which Pb upregulates the level of TNF-α is wagely known. An attempt was therefore made to elucidate the mechanistic aspect of TNF-α induction, mainly focusing transcriptional and post transcriptional regulation via mitogen activated protein kinases (MAPKs) activation. We observed that exposure of Pb to human monocytic THP-1 cells resulted in significant enhanced production of TNF-α m-RNA and protein secretion. Moreover, the stability of TNF-α m-RNA was also increased as indicated by its half life. Notably, activation of ERK 1/2, p38 and JNK in Pb exposed THP-1 was also evident. Specific inhibitor of ERK1/2, PD 98059 caused significant inhibition in production and stability of TNF-α m-RNA. However, SB 203580 partially inhibited production and stability of TNF-α m-RNA. Interestingly, a combined exposure of these two inhibitors completely blocked modulation of TNF-α m-RNA. Data tends to suggest that expression and stability of TNF-α induction due to Pb exposure is mainly regulated through ERK. Briefly, these observations are useful in understanding some mechanistic aspects of proinflammatory and immunotoxicity of Pb, a globally acknowledged key environmental contaminant.

Penetrance of NOD2/CARD15 genetic variants in the general population

DEFF Research Database (Denmark)

Yazdanyar, Shiva; Kamstrup, Pia R; Tybjaerg-Hansen, Anne

2010-01-01

In case-control studies of Europeans, heterozygosity for Arg702Trp(rs2066844), Gly908Arg(rs2066845) and Leu1007fsinsC(rs5743293) on the NOD2/CARD15 gene is associated with a 2-fold greater risk of Crohn disease, whereas homozygosity or compound heterozygosity is associated with a 17-fold greater ...... risk. However, the importance of these genetic variants if identified in particular individuals within the general population is unknown. We undertook this study to estimate the penetrance of these variants in the general population....

Basal cell carcinoma is associated with high TNF-alpha release but nor with TNF-alpha polymorphism at position--308

DEFF Research Database (Denmark)

Skov, Lone; Allen, Michael H; Bang, Bo

2003-01-01

secretion of TNF-alpha has been identified in humans. We have therefore investigated the association of the --308 polymorphism with the risk of basal cell carcinoma (BCC) in humans. The frequency of TNF G and TNF A alleles among Caucasian patients with a previous BCC (n=191) and health adults (n-107) were...... compared. For the TNF--308 polymorphism there was significant association between the genotype or allele frequencies and having BCC. To determine whether patients with a previous BCC had an increased capacity to secrete TNF-alpha, mononuclear cells were stimulated with lipopolysaccharide. Mononuclear cells...... from patients with a previous BCC (n=15) demonstrated a significantly increased release of TNF-alpha upon stimulation with lipopolysaccharide (Pcells age-matched control subjects (n=16). Further studies of other polymorphisms of the TNF-alpha gene associated...

Effects of Anti-TNF Alpha Drugs on Disability in Patients with Rheumatoid Arthritis: Long-Term Real-Life Data from the Lorhen Registry

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Matteo Filippini

2014-01-01

Full Text Available This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.

Análise da variabilidade da frequência cardíaca em cordeiros da raça Bergamácia, do nascimento aos 35 dias de idade

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K. Koether

2016-08-01

Full Text Available RESUMO A atividade do sistema nervoso autônomo sobre o coração pode ser verificada pela variabilidade da frequência cardíaca (VFC, método que quantifica e assim infere sobre a modulação autonômica cardíaca, refletindo o funcionamento do sistema nervoso autônomo. Durante o período neonatal, diferenças significativas no que se refere à maturação autonômica são descritas em diversas espécies. Embora a espécie ovina venha sendo utilizada como modelo experimental em diversos protocolos em neonatologia e cardiologia em humanos, estudos descritivos sobre a VFC utilizando animais saudáveis e não sedados são escassos na literatura. O objetivo do estudo foi descrever a VFC em cordeiros da raça Bergamácia durante os primeiros 35 dias de idade. Foram realizados exames eletrocardiográficos em 20 cordeiros da raça Bergamácia a partir do nascimento e semanalmente até o 35° dia de idade. A VFC foi analisada pelo intervalo RR normal (batimentos sinusais, pela frequência cardíaca, pelo índice de tônus vasovagal (iTVV, pela raiz quadrada da média do quadrado das diferenças entre intervalos RR normais adjacentes (RMSSD e pela raiz quadrada da somatória do quadrado das diferenças dos valores individuais em relação ao valor médio, dividido pelo número de iR-R em 90 segundos - VFC global (RMSM. Todos os parâmetros se alteraram ao longo das semanas. A frequência cardíaca média elevou-se entre o nascimento e os primeiros sete dias de idade, com decréscimo nas quatro semanas subsequentes, sendo o menor valor encontrado aos 35 dias de idade (145,63±37,80bpm. Entre 21, 28 e 35 dias de idade, o iTVV elevou-se significativamente, o RMSM a partir do 28º dia, e, aos 35 dias, o RMSSD, reflexo da ativação parassimpática, exibiu diferenças em relação aos momentos subsequentes. O início da predominância parassimpática, refletida nos índices da VFC, particularmente o iTVV, ocorre aos 21 dias de idade. A partir dos 35 dias

Clinical significance of measurement of serum NO/NOS and TNF-α levels after treatment in patients with schizophrenia

International Nuclear Information System (INIS)

Nan Deqi; Du Liang; Yang Sixue; Qin Yong

2007-01-01

Objective: To explore the significance of changes of serum NO/NOS and TNF-α levels in patients with schizophrenia. Methods: Serum TNF-α (with R/A) and NO/NOS (with bio-chemistry) levels were determined in 41 patients with schizophrenia both before and after treatment as well as in 35 controls. Results:Before treatment the serum NOS, TNF-α levels in the patients were significantly higher than those in controls (P <0.01 ). After six weeks treatment, the levels in patients, though dropped markedly, remained significantly higher (P<0.05). Conclusion: Serum NO/NOS and TNF-α levels were closely related to the diseases process of schizophrenia and were of prognostic values. (authors)

Radiographic changes and factors associated with subsequent progression of damage in weight-bearing joints of patients with rheumatoid arthritis under TNF-blocking therapies-three-year observational study.

Science.gov (United States)

Matsushita, Isao; Motomura, Hiraku; Seki, Eiko; Kimura, Tomoatsu

2017-07-01

The long-term effects of tumor necrosis factor (TNF)-blocking therapies on weight-bearing joints in patients with rheumatoid arthritis (RA) have not been fully characterized. The purpose of this study was to assess the radiographic changes of weight-bearing joints in patients with RA during 3-year of TNF-blocking therapies and to identify factors related to the progression of joint damage. Changes in clinical variables and radiological findings in 243 weight-bearing joints (63 hips, 54 knees, 71 ankles, and 55 subtalar joints) in 38 consecutive patients were investigated during three years of treatment with TNF-blocking agents. Multivariate logistic regression analysis was used to identify risk factors for the progression of weight-bearing joint damage. Seventeen (14.5%) of proximal weight-bearing joints (hips and knees) showed apparent radiographic progression during three years of treatment, whereas none of the proximal weight-bearing joints showed radiographic evidence of improvement or repair. In contrast, distal weight-bearing joints (ankle and subtalar joints) displayed radiographic progression and improvement in 20 (15.9%) and 8 (6.3%) joints, respectively. Multivariate logistic analysis for proximal weight-bearing joints identified the baseline Larsen grade (p bearing joints identified disease activity at one year after treatment (p bearing joints. Disease activity after treatment was an independent factor for progression of damage in proximal and distal weight-bearing joints. Early treatment with TNF-blocking agents and tight control of disease activity are necessary to prevent the progression of damage of the weight-bearing joints.

Superior serum half life of albumin tagged TNF ligands

International Nuclear Information System (INIS)

Mueller, Nicole; Schneider, Britta; Pfizenmaier, Klaus; Wajant, Harald

2010-01-01

Due to their immune stimulating and apoptosis inducing properties, ligands of the TNF family attract increasing interest as therapeutic proteins. A general limitation of in vivo applications of recombinant soluble TNF ligands is their notoriously rapid clearance from circulation. To improve the serum half life of the TNF family members TNF, TWEAK and TRAIL, we genetically fused soluble variants of these molecules to human serum albumin (HSA). The serum albumin-TNF ligand fusion proteins were found to be of similar bioactivity as the corresponding HSA-less counterparts. Upon intravenous injection (i.v.), serum half life of HSA-TNF ligand fusion proteins, as determined by ELISA, was around 15 h as compared to approximately 1 h for all of the recombinant control TNF ligands without HSA domain. Moreover, serum samples collected 6 or 24 h after i.v. injection still contained high TNF ligand bioactivity, demonstrating that there is only limited degradation/inactivation of circulating HSA-TNF ligand fusion proteins in vivo. In a xenotransplantation model, significantly less of the HSA-TRAIL fusion protein compared to the respective control TRAIL protein was required to achieve inhibition of tumor growth indicating that the increased half life of HSA-TNF ligand fusion proteins translates into better therapeutic action in vivo. In conclusion, our data suggest that genetic fusion to serum albumin is a powerful and generally applicable mean to improve bioavailability and in vivo activity of TNF ligands.

Anti-inflammatory effect of resveratrol on TNF-α-induced MCP-1 expression in adipocytes

International Nuclear Information System (INIS)

Zhu Jian; Yong Wei; Wu Xiaohong; Yu Ying; Lv Jinghuan; Liu Cuiping; Mao Xiaodong; Zhu Yunxia; Xu Kuanfeng; Han Xiao; Liu Chao

2008-01-01

Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-α-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-α-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-α-induced MCP-1 transcription. Nuclear factor (NF)-κB was determined to play a major role in the TNF-α-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-κB complex and subsequently suppressed NF-κB transcriptional activity in TNF-α-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies

Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Milena Iwaszko

2018-01-01

Full Text Available A natural killer group 2 member D (NKG2D acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF therapy is in rheumatoid arthritis (RA patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G, rs1049174 (C > G, and rs1154831 (C > A. Clinical response was evaluated according to the European League against Rheumatism (EULAR criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively. The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively. Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively. Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients.

IL-1 receptor-antagonist (IL-1Ra) knockout mice show anxiety-like behavior by aging.

Science.gov (United States)

Wakabayashi, Chisato; Numakawa, Tadahiro; Odaka, Haruki; Ooshima, Yoshiko; Kiyama, Yuji; Manabe, Toshiya; Kunugi, Hiroshi; Iwakura, Yoichiro

2015-07-10

Interleukin 1 (IL-1) plays a critical role in stress responses, and its mRNA is induced in the brain by restraint stress. Previously, we reported that IL-1 receptor antagonist (IL-1Ra) knockout (KO) mice, which lacked IL-1Ra molecules that antagonize the IL-1 receptor, showed anti-depression-like behavior via adrenergic modulation at the age of 8 weeks. Here, we report that IL-1Ra KO mice display an anxiety-like phenotype that is induced spontaneously by aging in the elevated plus-maze (EPM) test. This anxiety-like phenotype was improved by the administration of diazepam. The expression of the anxiety-related molecule glucocorticoid receptor (GR) was significantly reduced in 20-week-old but not in 11-week-old IL-1Ra KO mice compared to wild-type (WT) littermates. The expression of the mineralocorticoid receptor (MR) was not altered between IL-1Ra KO mice and WT littermates at either 11 or 20 weeks old. Analysis of monoamine concentration in the hippocampus revealed that tryptophan, the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), and the dopamine metabolite homovanillic acid (HVA) were significantly increased in 20-week-old IL-1Ra KO mice compared to littermate WT mice. These findings strongly suggest that the anxiety-like behavior observed in older mice was caused by the complicated alteration of monoamine metabolism and/or GR expression in the hippocampus. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clinical significance of determination of serum IL-1β, TNF-α levels in patients with periodontitis

International Nuclear Information System (INIS)

Wei Dong; Zhang Xiaolei

2006-01-01

Objective: To investigate the changes of serum IL-1β and TNF-α levels in patients with periodontitis. Methods: Serum IL-1β and TNF-α levels were measured with RIA in 42 patients with periodontitis and 35 controls. Results: Serum IL-1β and TNF-α levels in the patients were significantly higher than those in controls (P<0.01). Serum IL-1β level was positively correlated with TNF-α level (r=0.4182, P<0.01). Conclusion: Increase of serum IL-1β and TNF-α levels in patients with periodontitis was closely related to the pathogenesis of the disease. (authors)

A disintegrin and metalloprotease-17 and galectin-9 are important regulators of local 4-1BB activity and disease outcome in rheumatoid arthritis

DEFF Research Database (Denmark)

Nielsen, Morten Aagaard; Andersen, Thomas; Etzerodt, Anders

2016-01-01

OBJECTIVE: Co-stimulatory T cell cytokines are important in the progression of RA. This study investigates the interplay between 4-1BB, a disintegrin and metalloprotease-17 (ADAM17) and galectin-9 (Gal-9) in RA. METHODS: Stimulated mononuclear cells from patients with chronic RA (n = 12) were co...... treatment outcome serially over a 2-year period. RESULTS: RA CD4(+) and CD8(+) synovial T cells express high levels of 4-1BB. The addition of TNF-α to cultured synovial mononuclear cells increased shedding of 4-1BB. 4-1BB ligand only increased TNF-α shedding in combination with Gal-9. RNA interference...

Vibration induced hearing loss in guinea pig cochlea: expression of TNF-alpha and VEGF.

Science.gov (United States)

Zou, Jing; Pyykkö, Ilmari; Sutinen, Päivi; Toppila, Esko

2005-04-01

Transcranial vibration was applied for seven animals at a frequency of 250 Hz for 15 min, and five animals were used as normal controls to investigate cellular and molecular mechanism linked to vibration-induced hearing loss in animal model. Compound action potential (CAP) thresholds were measured by round window niche electrode. The expression of tumour necrosis factor alpha (TNF-alpha) and its receptors (TNF R1, TNF R2), vascular endothelium growth factor (VEGF) and its receptors (VEGF R1, VEGF R2) were analysed by immunohistochemistry. Transcranial vibration caused expression of TNF-alpha, TNF R1 and TNF R2 in the cochlea and the expression of TNF R2 was stronger than that of TNF R1. Vibration also induced VEGF and VEGF R2 expression in the cochlea. The average immediate hearing loss was 62 dB and after three days still 48 dB. It is concluded that transcranial vibration as during temporal bone drilling produces cochlear shear stress that is connected with up-regulation of TNF-alpha and its receptors. Also VEGF and VEGF R2 are up-regulated. These responses may be linked to both the damage and repair process of the cochlea.

Thy-1 attenuates TNF-alpha-activated gene expression in mouse embryonic fibroblasts via Src family kinase.

Directory of Open Access Journals (Sweden)

Bin Shan

Full Text Available Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-alpha. Our study demonstrates distinct profiles of TNF-alpha-activated gene expression in Thy-1 positive (Thy-1+ and negative (Thy-1- subsets of mouse embryonic fibroblasts (MEF. TNF-alpha induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1- MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1- MEFs significantly attenuated TNF-alpha-activated gene expression. Mechanistically, TNF-alpha activated Src family kinase (SFK only in Thy-1- MEFs. Blockade of SFK activation abrogated TNF-alpha-activated gene expression in Thy-1- MEFs, whereas restoration of SFK activation rescued the TNF-alpha response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-alpha-activated gene expression via interfering with SFK- and NF-kappaB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation.

A Brief History of IL-1 and IL-1 Ra in Rheumatology

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Jean-Michel Dayer

2017-05-01

Full Text Available The history of what, in 1979, was called interleukin-1 (IL-1, orchestrator of leukocyte inter-communication, began many years before then, initially by the observation of fever induction via the endogenous pyrogen (EP (1974 and then in rheumatology on the role in tissue destruction in rheumatoid diseases via the induction of collagenase and PGE2 in human synovial cells by a mononuclear cell factor (MCF (1977. Since then, the family has exploded to presently 11 members as well as many membrane-bound and soluble receptor forms. The discovery of a natural Interleukin-1 receptor antagonist (IL-1Ra in human biological fluids has highlighted the importance of IL-1 and IL-1Ra in human diseases. Evidence delineating its role in autoinflammatory syndromes and the elucidation of the macromolecular complex referred to as “inflammasome” have been instrumental to our understanding of the link with IL-1. At present, the IL-1blockade as therapeutic approach is crucial for many hereditary autoinflammatory diseases, as well as for adult-onset Still’s disease, crystal-induced arthropathies, certain skin diseases including neutrophil-triggered skin diseases, Behçet’s disease and deficiency of IL-1Ra and other rare fever syndromes. Its role is only marginally important in rheumatoid arthritis and is still under debate with regard to osteoarthritis, type 2 diabetes mellitus, cardiovascular diseases and cancer. This brief historical review focuses on some aspects of IL-1, mainly IL-1β and IL-Ra, in rheumatology. There are many excellent reviews focusing on the IL-1 family in general or with regard to specific diseases or biological discoveries.

FRENCH PROTOCOL CARDS

CERN Multimedia

Division du Personnel

1999-01-01

Senior officials, holders of FRENCH PROTOCOL cards (blue cards) due to expire on 31.12.1999, are requested to return these cards and those of family members, for extension to:Bureau des cartes, bâtiment 33.1-025Should the 3 spaces for authentication on the back of the card be full, please enclose 2 passport photographs for a new card.In the case of children aged 14 and over, an attestation of dependency and a school certificate should be returned with the card.Personnel DivisionTel. 79494/74683

From EuCARD to EuCARD-2

CERN Multimedia

Chaudron, M

2013-01-01

The one word that best describes the spirit of the EuCARD ’13 event (see here) that took place from 10 to 14 June at CERN is "collaboration". The event brought together more than 180 accelerator specialists from all over the world to celebrate the conclusion of the EuCARD project and to kick off its successor, EuCARD-2.   EuCARD-2 brings a global view to particle accelerator research in order to address challenges for future generations of accelerators. The project officially began on 1 May 2013 and will run for four years. With a total budget of €23.4 million, including an €8 million EU contribution, it will build upon the success of EuCARD and push it into an even more innovative regime. EuCARD-2 aims to significantly enhance multidisciplinary R&D for European accelerators and will actively contribute to the development of a European Research Area in accelerator science. This will be accomplished by promoting complementary expertise, cross-d...

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.

LENUS (Irish Health Repository)

Minnock, Patricia

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.

Effects of anti-TNF-α treatment on lipid profile in rheumatic diseases: an analytical cohort study.

Science.gov (United States)

Hassan, Shadi; Milman, Uzi; Feld, Joy; Eder, Lihi; Lavi, Idit; Cohen, Shai; Zisman, Devy

2016-11-10

The aim was to assess the influence of long-term treatment with tumor necrosis factor alpha (TNF-α) inhibitors on total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and atherogenic index (AI) in rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) patients. A retrospective cohort study was conducted on RA, PsA, and AS patients treated with TNF-α inhibitors for at least 270 days between 2001 and 2011. Levels of TC, TG, LDL, and HDL and the AI were compared with baseline values at 0-6, 6-12, 12-18, and 18-24 months. Patients were further subdivided into three groups according to their HMG CoA reductase inhibitor (statin) treatment status in order to assess their effect on the results. The records of 311 patients (152 RA, 90 PsA, and 69 AS) were reviewed. TC and TG increased following treatment with TNF-α inhibitors, from 180.85 ± 2.12 mg/dl and 116.00 ± 3.55 mg/dl at baseline to 188.12 ± 2.35 mg/dl (p = 0.02) and 132.02 ± 4.63 mg/dl at 0-6 months (p < 0.01), respectively, and to 184.88 ± 2.09 mg/dl (p = 0.02) and 129.36 ± 4.32 mg/dl at 18-24 months (p < 0.01), respectively. AI increased following treatment with TNF-α inhibitors, from -0.032 ± 0.017 at baseline to 0.004 ± 0.019 at 18-24 months (p < 0.01). LDL decreased significantly in patients who were treated with statins before and during the entire study period, from 119.97 ± 2.86 mg/dl at baseline to 104.02 ± 3.57 mg/dl at 18-24 months (p < 0.01), in contrast to an increase in LDL values in patients who did not receive statins during the study. TNF-α inhibitor treatment was associated with a significant increase in TC and TG levels and the AI. Adding statins to the treatment was associated with a significant decrease in LDL levels.

The effects of TNF-α on GLP-1-stimulated plasma glucose kinetics

DEFF Research Database (Denmark)

Lehrskov-Schmidt, Louise; Lehrskov-Schmidt, Lars; Nielsen, Signe T

2015-01-01

levels impairs GLP-1's effects on glucose metabolism. Design: Randomized, controlled, cross-over trial. Setting: Hospital clinical research laboratory. Participants: Twelve healthy males (age 24±3 y; BMI 22.9±1.3 kg/m(2)). Interventions: Following an overnight fast, either saline (0.9%) or recombinant......Context: GLP-1 analogues have recently been promoted as anti-hyperglycemic agents in critically ill patients with systemic inflammation, but the effects of TNF-α on glucose metabolism during GLP-1 administration are unknown. Objective: To determine whether infusion of TNF-α at high physiological...... human TNF-α (1000 ng/m(2)/h) was infused from t = 0-6 hours. At t = 2 hours, GLP-1 infusion (0.5 pmol/kg/min) began. From t = 4-6 hours, the GLP-1 infusion rate was increased to 1.2 pmol/kg/min. Plasma glucose was clamped at 5 mmol/L throughout via a variable-rate 20% dextrose infusion. Trials were 7...

The clinical analysis of the TNF-α1 and IL-2 levels in patients with hyperthyroidism

International Nuclear Information System (INIS)

Huang Chunling; Zha Jinshun; Jiang Tingyin

2012-01-01

Objective: To explore the characters of plasma levels of the tumor necrosis factor-α1 (TNF-α1) and interleukin-2 (IL-2) in patients with hyperthyroidism due to multiple etiologies such as Graves disease (GD) and Hashimoto disease (HD) etc. Methods: Two hundred and fifty hyperthyroidism patients were divided into three groups,including GD group (n=109), HD group (n=80) and other causes of hyperthyroidism group (n=61). Ninety-eight healthy individuals served as control group.The TNF-α1 and IL-2 levels in plasma were measured by radioimmunoassay. Results: The TNF-α1 level in plasma of GD group and HD group were significantly higher than that of other causes of hyperthyroidism group (d TNF-α1 =17.638 and 19.248, both P<0.01) and normal group (d TNF-α1 =24.460 and 26.070, both P<0.01). The IL-2 level in plasma of GD group and HD group were significantly lower than that of other causes of hyperthyroidism group (d IL-2 =2.668 and 2.975, both P<0.01) and normal group (d IL-2 =2.649 and 2.955, both P<0.01).There were no significant differences of the TNF-α1 and IL-2 levels in plasma between other causes of hyperthyroidism group and normal group (d TNF-α1 =0.821, d IL-2 =0.194, both P>0.05). Conclusions: Hyperthyroidism due to autoimmune disease such as GD and HD accompanied with changes of TNF-α1 and IL-2 levels in plasma, while hyperthyroidism due to high iodine uptake, toxic multinodular goiter, and toxic adenoma did not accompany with changes of TNF-α1 and IL-2 levels in plasma. The plasma levels of TNF-α1 and IL-2 may play an important role in differential diagnosis and therapeutic effect evaluation in GD and HD. (authors)

Aberrant Expression of TNF-α and TGF-β1 mRNA in Spontaneous Abortion

Institute of Scientific and Technical Information of China (English)

Ji-fen HU; Hong-chu BAO; Feng-chuan ZHU; Cai-ling YOU

2004-01-01

Objective To investigate the aberrant expressions of TNF-α and TGF-β1 in peripheral blood mononuclear cells (PBMCs) and placental tissues in patients with early spontaneous abortionMethods Using the technique of semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR), TNF-α mRNA and TGF-β1 mRNA in PBMCs were measured in spontaneous abortion group (30 cases), normal pregnancy group (25 cases) and nonpregnant group (25 cases). The expressive intension of TNF-α protein and TGF-β1 protein in placental tissues was also identified by immunohistochemistry.Results Both levels of TNF-α mRNA and TGF-β1 mRNA expressed in PBMCs were significantly different between the three groups respectively (P＜0. 05). Levels of TNF-α in syncytiotrophoblastic and cytotrophoblastic cells of the two aborted groups were substantially higher than those of the non-pregnant group (P＜0. 01), but the levels of TGF-β1 in syncytiotrophoblastic cells of the two aborted groups were markedly lower than those of the non-pregnant group (P＜0. 01).Conclusion There is potential relation between TGF-β1 at the fetomaternal interface and spontaneous abortion. TGF-β1 may contribute to the maintenance of pregnancy,and low-level expression of TGF-β1 may be associated with pregnancy failure.

RA Research nuclear reactor Part 1, RA Reactor operation and maintenance in 1987

International Nuclear Information System (INIS)

Sotic, O.; Martinc, R.; Cupac, S.; Sulem, B.; Badrljica, R.; Majstorovic, D.; Sanovic, V.

1987-01-01

RA research reacto was not operated due to the prohibition issued in 1984 by the Government of Serbia. Three major tasks were finished in order to fulfill the licensing regulations about safety of nuclear facilities which is the condition for obtaining permanent operation licence. These projects involved construction of the emergency cooling system, reconstruction of the existing special ventilation system, and renewal of the system for electric power supply of the reactor systems. Renewal of the RA reactor instrumentation system was initiated. Design project was done by the Russian Atomenergoeksport, and is foreseen to be completed by the end of 1988. The RA reactor safety report was finished in 1987. This annual report includes 8 annexes concerning reactor operation, activities of services and financial issues, and three special annexes: report on testing the emergency cooling system, report on renewal of the RA reactor and design specifications for reactor renewal and reconstruction [sr

RA Research reactor Annual report 1981 - Part 1, Operation, maintenance and utilization of the RA reactor; Istrazivacki nuklearni reaktor RA, Deo 1 - Pogon, odrzavanje i eksploatacija reaktora u 1981. godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Milosevic, M; Martinc, R; Kozomara-Maic, S; Cupac, S; Radivojevic, J; Stamenkovic, D; Skoric, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1981-12-15

The RA nuclear reactor stopped operation after March 1979 campaign due to appearance of aluminium oxyhydrates deposits on the surface of fuel element claddings. Relevant decisions of the Sanitary inspection body of the Ministry of health and the Director General of the 'Boris Kidric' Institute of nuclear sciences, Vinca, banned further reactor operation until reasons caused aluminium oxyhydrates deposition are investigated and removed to enable regular reactor operation. Until the end of 1979 and during 1980, after a series of analyses and findings that caused cease of reactor operation, all the preparatory actions needed for restart were performed. Due to the fact that there is no emergency cooling system and no appropriate filtering system at the reactor, and according to the new regulations about start up of nuclear facilities, the Sanitary inspection body made a decision about temporary licence for reactor start-up meaning performance of the 'zero experiment' limiting the operating power to 1% of the nominal power. Accordingly the reactor was restarted on January 21 1981. Criticality was reached with the core made of 80% enriched fuel elements only. After the experiment was finished by the end of March a permission was demanded for operation at higher power levels at full power. Taking into account the state of the reactor components the operating licence was issued limiting the power to 2 MW until reconstruction of the ventilation system and construction of the emergency cooling system are fulfilled. Program of testing operation started on September 15 1981 increasing gradually the operating power. Thus the reactor was operated at 2 MW power for 15 days during November and December. The total production achieved in 1981 was 1698 MWh. This enabled isotopes production at the reactor during last two months. Control and maintenance of the reactor components and systems was done regularly and efficiently within limits imposed by availability of spare parts. The

A similar pro/anti-inflammatory cytokine balance is present in the airways of competitive athletes and non-exercising asthmatics.

Science.gov (United States)

Kurowski, Marcin; Jurczyk, Janusz; Olszewska-Ziąber, Agnieszka; Jarzębska, Marzanna; Krysztofiak, Hubert; Kowalski, Marek L

2018-03-01

Intensive exercise modifies airway inflammation and infection susceptibility. We aimed to determine the effect of exercise on pro- and anti-inflammatory cytokine (TNF-α, IL-1ra, IL-10) and innate immunity protein (HSPA1, sCD14) levels in exhaled breath condensate (EBC) and nasal secretions of competitive athletes, non-exercising asthmatics and healthy controls (HC). The study group consisted of 15 competitive athletes (five speed skaters and ten swimmers) aged 15-25. The control groups comprised 10 mild-to-moderate asthmatics (AC) and seven HC. Athletes were assessed in- and off-training while asthmatics and controls at one time point. Nasal lavages and EBC were collected before and after a treadmill exercise challenge. Protein levels were assessed using ELISA. TNF-α levels in EBC were significantly higher in athletes than HC, but similar to asthmatic patients. In contrast, IL-1ra EBC concentrations were significantly lower in athletes than in HC, but again similar to asthmatics. Significant positive correlations were seen between baseline concentrations of TNF-α in EBC and fall in FEV1 following exercise challenge in athletes during training period (R=0.74, pExercise caused a slight, yet significant, increase in EBC HSPA1 in athletes (p=0.02). The exercise challenge did not considerably influence TNF-α, IL-1ra, HSPA1 and sCD14 in EBC or nasal secretions. Dysregulation of the TNF-α/IL-1ra balance in EBC and nasal secretions from athletes may reflect the presence of airway inflammation induced by repeated strenuous exercise. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

Nuclear Reactor RA Safety Report, Vol. 1, Introduction; Izvestaj o sigurnosti nuklearnog reaktora RA, Knjiga 1, Uvod

Energy Technology Data Exchange (ETDEWEB)

NONE

1986-11-01

Based on the agreement between governments of Socialist Federal Republic of Yugoslavia and USSR of January 28 1956, a contract was signed about construction of RA research reactor in the Boris Kidric Institute of nuclear sciences. Building of the RA reactor started in 1956, and has reached criticality in 1959. Since then it has been in almost permanent operation, except for five longer shutdown periods: in 1963 because of heavy water and primary coolant system contamination with cobalt; in 1970 because of transporting the heavy water to France for isotopic regeneration; in 1979/1980 and 1983 because of aluminium oxyhydrate deposition on the fuel element cladding in reactor active region; in 1985/1986 because of ventilation system reconstruction and construction of emergency core cooling system. RA reactor is a heavy water cooled and heavy water moderated research reactor. Since the beginning of its operation, 2% enriched metal uranium fuel was used. From 1976, 80% enriched uranium oxide fuel elements were used partially in some core regions and since 1981 the complete core was filled with this highly enriched fuel. RA reactor was designed to operate under normal conditions at 6.5 MW power and at 10 MW power under forced regime. As a powerful neutron source the reactor was meant to be used for research in the field of reactor and neutron physics, solid state physics, radiation chemistry, biology and radioactive isotopes production. RA reactor was build by Yugoslav companies based on USSR basic design project. Main components of the systems were produced in USSR. [Serbo-Croat] Na osnovu Sporazuma izmedju vlada SFRJ i SSSR od 28. januara 1956. godine, sklopljen je ugovor o izgradnji istrazivackog reaktora RA u Institutu za nuklearne nauke Boris Kidric u Vinci. Reaktor RA je poceo da se gradi 1956. godine, a kriticnost je postigao 1959. godine. Od tada je takoreci neprekidno bio u radu, izuzev u pet slucajeva duzeg stajanja: 1963. godine - zbog kontaminacije teske vode

Modifications in Lipid Levels Are Independent of Serum TNF-α in Rheumatoid Arthritis: Results of an Observational 24-Week Cohort Study Comparing Patients Receiving Etanercept Plus Methotrexate or Methotrexate as Monotherapy

Directory of Open Access Journals (Sweden)

Norma Alejandra Rodriguez-Jimenez

2014-01-01

Full Text Available Objective. To compare the modifications in lipids between patients with rheumatoid arthritis (RA receiving etanercept plus methotrexate (ETA + MTX versus methotrexate (MTX and their relationship with serum levels of tumor necrosis factor-alpha (TNF-α. Methods. In an observational cohort study, we compared changes in lipid levels in patients receiving ETA + MTX versus MTX in RA. These groups were assessed at baseline and at 4 and 24 weeks, measuring clinical outcomes, total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol, and TNF-α. Results. Baseline values for lipid levels were similar in both groups. HDL-C levels increased significantly only in the ETA + MTX group (from 45.5 to 50.0 mg/dL at 4 weeks, a 10.2% increase, P<0.001, and to 56.0 mg/dL at 24 weeks, a 25.1% increase, P<0.001, while other lipids underwent no significant changes. ETA + MTX also exhibited a significant increase in TNF-α (44.8 pg/mL at baseline versus 281.4 pg/mL at 24 weeks, P<0.001. The MTX group had no significant changes in lipids or TNF-α. Significant differences in HDL-C between groups were observed at 24 weeks (P=0.04 and also in TNF-α  (P=0.01. Conclusion. HDL-C levels increased significantly following treatment with ETA + MTX, without a relationship with decrease of TNF-α.

Estuarine geochemistry of 224Ra, 226Ra, and 222Rn

International Nuclear Information System (INIS)

Elsinger, R.J.

1982-01-01

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

Comparing the lifetime risks of TNF-alpha inhibitor use to common benchmarks of risk.

Science.gov (United States)

Kaminska, Edi; Patel, Isha; Dabade, Tushar S; Chang, Jongwha; Qureshi, Ayub A; O'Neill, Jenna L; Balkrishnan, Rajesh; Feldman, Steven R

2013-04-01

The study aims to illustrate the range of lifetime risks of lymphoma, tuberculosis (TB), and demyelinating diseases with TNF-α inhibitors in psoriasis patients. Previously published data and online resources were used to determine the risk of the TB, demyelinating disease, and lymphoma with and without TNF-α inhibitor treatment. Lifetime risks for heart disease and stroke were collected using a Medline search. All cancer, trauma, and environmental statistics were obtained from the data published by National Cancer Institute, National Safety Council, and the National Oceanic and Atmospheric Administration, respectively. The lifetime risks of TNF-α-inhibitor-linked conditions and comparators are as follows: TNF-α inhibitor-linked conditions: lymphoma with: without TNF-α inhibitors (0.5-4.8%:2.3%), TB with:without TNF-α inhibitors (0-17.1%:0.3%), and demyelinating disease with:without TNF-α inhibitors (0.1-1.7%:0.15%). Comparators: cancer (40.4%), heart disease (36.2%), stroke (18.4%), accidental death (3.0%), motor vehicle death (1.2%), and lightning strike (0.033%). Much of the data on lifetime risks of disease with TNF-α inhibitor were for patients with rheumatoid arthritis and not psoriasis. The risks of lymphoma, demyelinating diseases, and tuberculosis with TNF-α inhibitors are lower than risks patients face on a regular basis. Screening reduces the risk of tuberculosis in patients receiving TNF-α inhibitors.

Role of IL-1β, IL-6 and TNF-α cytokines and TNF-α promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India.

Science.gov (United States)

Singh, Krishn Pratap; Shakeel, Shayan; Naskar, Namrata; Bharti, Aakanksha; Kaul, Asha; Anwar, Shadab; Kumari, Shweta; Kumar, Amod; Singh, Jiv Kant; Kumari, Nutan; Gupta, Birendra Kumar; Manna, Purwa; Roy, Vishwaprakash; Lata, Sneh; Singh, Om P; Sinha, Manoranjan Prasad; Sharma, Ajay Kumar; Sohail, Mohammad

2018-05-01

The combinatorial effects of Plasmodium infection, perturbation of inflammatory responses and the dichotomic role of TNF promoter polymorphism has potential clinical and physiological relevance during pregnancy. This coordinated orchestration instigated us to investigate the circulating level of inflammatory cytokines (IL-1β, TNF-α and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-α -308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. We observed significantly elevated concentrations of IL-1β were observed, followed by IL-6 and TNF-α in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1β, followed by TNF-α and IL-6 were detected in the non-infected pregnancy group. The differential dynamics of inflammatory cytokine concentration during each trimester of pregnancy with and without P. vivax infection were detected. For the first time, a high level of IL-6 was observed in the first trimester of MIP and high IL-1β in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1β in the MIP group compared to a sustained high level of IL-1β in the healthy pregnancy group. In the third trimester, high IL-1β was sustained in the MIP group and healthy pregnancies acquired a high TNF-α level. The genotypic distribution for the TNF-α promoter -308 G/A position was observed to be nonsignificant and mildly associated during MIP (OR = 1.4) and in WWM (OR = 1.2). Moreover, based on genotypic distribution, we observed a well-correlated and significantly elevated TNF-α concentration in the mutant homozygote genotype (AA; p = 0.001) followed by heterozygotes (GA; p = 0.0001) and ancestral genotypes (GG; p = 0.0001) in both MIP and WWM subjects. The observation of elevated IL-1β and IL-6 in MIP and TNF-α in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly

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

International Nuclear Information System (INIS)

Moore, W.S.; Key, R.M.; Sarmiento, J.L.

1985-01-01

Improvements in the analyses of 226 Ra and 228 Ra 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 228 Ra to study mixing processes on a 3-15 year time scale in both the upper and deep North Atlantic. The 228 Ra 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 228 Ra should always respond on a time scale of 8 years. Thus the 228 Ra 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 226 Ra 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 226 Radata

226Ra, 228Ra, 223Ra, and 224Ra in coastal waters with application to coastal dynamics and groundwater input

International Nuclear Information System (INIS)

Moore, W.S.

1997-01-01

Four radium isotopes offer promise in unraveling the complex dynamics of coastal ocean circulation and groundwater input. Each isotope is produced by decay of a thorium parent bound to sediment. The activities of these thorium isotopes and the sediment-water distribution coefficient for radium provide an estimate of the source function of each Ra isotope to the water. In salt marshes that receive little surface water input, Ra activities which exceed coastal ocean values must originate within the marsh. In North Inlet, South Carolina, the activities of 226 Ra exported from the marsh far exceed the activities generated within the marsh. To supply the exported activities, substantial groundwater input is required. In the coastal region itself, 226 Ra activities exceed the amount that can be supplied from rivers. Here also, substantial groundwater input is required. Within the coastal ocean, 223 Ra and 224 Ra may be used to determine mixing rates with offshore waters. Shore-perpendicular profiles of 223 Ra and 224 Ra show consistent trends which may be modeled as eddy diffusion coefficients of 350-540 m 2 s -1 . These coefficients allow an assessment of cross-shelf transport and provide further insight on the importance of groundwater to coastal regions. (author)

De-repression of RaRF-mediated RAR repression by adenovirus E1A in the nucleolus.

Science.gov (United States)

Um, Soo-Jong; Youn, Hye Sook; Kim, Eun-Joo

2014-02-21

Transcriptional activity of the retinoic acid receptor (RAR) is regulated by diverse binding partners, including classical corepressors and coactivators, in response to its ligand retinoic acid (RA). Recently, we identified a novel corepressor of RAR called the retinoic acid resistance factor (RaRF) (manuscript submitted). Here, we report how adenovirus E1A stimulates RAR activity by associating with RaRF. Based on immunoprecipitation (IP) assays, E1A interacts with RaRF through the conserved region 2 (CR2), which is also responsible for pRb binding. The first coiled-coil domain of RaRF was sufficient for this interaction. An in vitro glutathione-S-transferase (GST) pull-down assay was used to confirm the direct interaction between E1A and RaRF. Further fluorescence microscopy indicated that E1A and RaRF were located in the nucleoplasm and nucleolus, respectively. However, RaRF overexpression promoted nucleolar translocation of E1A from the nucleoplasm. Both the RA-dependent interaction of RAR with RaRF and RAR translocation to the nucleolus were disrupted by E1A. RaRF-mediated RAR repression was impaired by wild-type E1A, but not by the RaRF binding-defective E1A mutant. Taken together, our data suggest that E1A is sequestered to the nucleolus by RaRF through a specific interaction, thereby leaving RAR in the nucleoplasm for transcriptional activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Keitel Functional Test for patients with rheumatoid arthritis: translation, reliability, validity, and responsiveness

DEFF Research Database (Denmark)

Holm, Bente; Jacobsen, S.; Skjodt, H.

2008-01-01

) 15 patients with long-lasting (median=6 years) active RA, tested before and after 2, 6, and 14 weeks of anti-tumor necrosis factor alpha (TNF-alpha) inhibitor therapy, and (2) 35 patients with early (median=0.25 year) RA, tested at years 0, 0.5, 1, and 2. Twenty-three patients in the early RA group...

A smart card based student card system

OpenAIRE

2009-01-01

M.Sc. A Smart Card looks like a normal plastic card that we use every day, but its capabilities and advantages are huge. Inside the card there is a small microprocessor capable of doing operations on data. With memory available on the card, data can be stored in a safe and secure location. This card can be used for various applications and is a big improvement on all of its predecessors. These applications can be anything from SIM cards in a cell phone to credit cards and cards used for ac...

TNF-α production in NKT cell hybridoma is regulated by sphingosine-1-phosphate: implications for inflammation in atherosclerosis.

Science.gov (United States)

Ito, Shiori; Iwaki, Soichiro; Kondo, Rie; Satoh, Masashi; Iwabuchi, Kazuya; Ohkawa, Ryunosuke; Mishima, Yuko; Yatomi, Yutaka; Furumoto, Tomoo; Tsutsui, Hiroyuki; Fujii, Satoshi

2014-06-01

Natural killer T (NKT) cells are unique T lymphocytes that recognize glycolipid antigen and produce various cytokines. NKT cells accelerate atherosclerosis in mice. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid and regulates T-lymphocyte trafficking. We aimed to determine the effects of S1P on the production of proinflammatory cytokine, tumor necrosis factor (TNF)-α, in NKT cell hybridomas and mouse NKT cells. NKT cell hybridomas and sorted mouse NKT cells were stimulated with S1P and α-galactosylceramide (α-GalCer), the major ligand to produce cytokines in NKT cells. TNF-α mRNA expression and protein production were determined by real-time PCR and ELISA, respectively. Cell migration was assayed using chemotaxicell. Plasma S1P was measured using HPLC. Hybridomas expressed S1P receptors, S1P1, S1P2, and S1P4. S1P and α-GalCer increased TNF-α mRNA expression and protein production. S1P enhanced TNF-α induction by α-GalCer. S1P receptor antagonists decreased the TNF-α mRNA expression induced by S1P. FTY720, an immunosuppressive S1P receptor modulator, also decreased the TNF-α mRNA expression. The migration of NKT cell hybridomas was increased by S1P. FTY720 reduced the migration induced by S1P. S1P also increased the TNF-α mRNA expression in mouse NKT cells. Plasma TNF-α levels in patients with high plasma S1P (≥500 nmol/l) were higher than those in patients with low S1P (NKT cells and enhances TNF-α production. TNF-α overproduction may induce atherogenic inflammatory responses. S1P may serve as a novel therapeutic target for amelioration of vascular inflammatory diseases.

Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry

International Nuclear Information System (INIS)

Beek, P. van; Souhaut, M.; Reyss, J.-L.

2010-01-01

Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228 Ra and 226 Ra are usually measured using gamma spectrometry, short-lived Ra isotopes ( 224 Ra and 223 Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226 Ra, 228 Ra, 224 Ra, 223 Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccares lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223 Ra and 224 Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224 Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223 Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.

The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

International Nuclear Information System (INIS)

Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda; Granja, Marcelo Gomes; Gonçalves-de-Albuquerque, Cassiano Felippe; Castro-Faria-Neto, Hugo Caire; Giestal-de-Araujo, Elizabeth

2016-01-01

Ouabain is a steroid hormone that binds to the enzyme Na + , K + – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.

The trophic effect of ouabain on retinal ganglion cells is mediated by IL-1β and TNF-α

Energy Technology Data Exchange (ETDEWEB)

Salles von-Held-Ventura, Juliana; Mázala-de-Oliveira, Thalita; Cândida da Rocha Oliveira, Amanda; Granja, Marcelo Gomes [Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ (Brazil); Gonçalves-de-Albuquerque, Cassiano Felippe; Castro-Faria-Neto, Hugo Caire [Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Departamento de Fisiologia e Farmacodinâmica, Av., no 4365, Manguinhos, 21045-900, Rio de Janeiro, RJ (Brazil); Giestal-de-Araujo, Elizabeth, E-mail: egiestal@vm.uff.br [Departamento de Neurobiologia, Programa de Neurociências, Outeiro de São João Batista s/n CEP: 24020-150, Universidade Federal Fluminense, Niterói, RJ (Brazil)

2016-09-09

Ouabain is a steroid hormone that binds to the enzyme Na{sup +}, K{sup +} – ATPase and stimulates different intracellular pathways controlling growth, proliferation and cell survival. IL-1β and TNF-α are pleiotropic molecules, conventionally regarded as pro-inflammatory cytokines with well-known effects in the immune system. In addition, IL-1β and TNF-α also play important roles in the nervous system including neuroprotective effects. Previous data from our group showed that ouabain treatment is able to induce an increase in retinal ganglion cell survival kept in mixed retinal cell cultures. The aim of this work was to investigate if IL-1β and TNF-α could be mediating the trophic effect of ouabain on retinal ganglion cells. Our results show that the trophic effect of ouabain on retinal ganglion cell was inhibited by either anti-IL-1β or anti-TNF-α antibodies. In agreement, IL-1β or TNF-α increased the retinal ganglion cells survival in a dose-dependent manner. Accordingly, ouabain treatment induces a temporal release of TNF-α and IL-1β from retinal cell cultures. Interestingly, TNF-α and IL-1β regulate each other intracellular levels. Our results suggest that ouabain treatment triggers the activation of TNF-α and IL-1β signaling pathways leading to an increase in retinal ganglion cell survival. - Highlights: • Pro-inflammatory cytokines regulates the ouabain effect on RGC survival. • Ouabain treatment modulates the intracellular levels of TNF-α and IL-1β. • Ouabain induces the release of TNF-α and IL-1β in retinal cell cultures.

Membrane type 1-matrix metalloproteinase/Akt signaling axis modulates TNF-α-induced procoagulant activity and apoptosis in endothelial cells.

Directory of Open Access Journals (Sweden)

Hiroshi Ohkawara

Full Text Available Membrane type 1-matrix metalloproteinase (MT1-MMP functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt in tumor necrosis factor (TNF-α-induced signaling pathways of vascular responses, including tissue factor (TF procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs. TNF-α (10 ng/mL induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1-dependent signaling pathway and nuclear factor-kB (NF-kB activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs.

Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema.

Science.gov (United States)

Faggioni, R; Gatti, S; Demitri, M T; Delgado, R; Echtenacher, B; Gnocchi, P; Heremans, H; Ghezzi, P

1994-03-01

We studied the role of reactive oxygen intermediates (ROI) in lipopolysaccharide (LPS)-induced pulmonary edema. LPS treatment (600 micrograms/mouse, IP) was associated with a marked induction of the superoxide-generating enzyme xanthine oxidase (XO) in serum and lung. Pretreatment with the antioxidant N-acetylcysteine (NAC)--1 gm/kg orally, 45 minutes before LPS--or with the XO inhibitor allopurinol (AP)--50 mg/kg orally at -1 hour and +3 hours--was protective. On the other hand nonsteroidal antiinflammatory drugs (ibuprofen, indomethacin, and nordihydroguaiaretic acid) were ineffective. These data suggested that XO might be involved in the induction of pulmonary damage by LPS. However, treatment with the interferon inducer polyriboinosylic-polyribocytidylic acid, although inducing XO to the same extent as LPS, did not cause any pulmonary edema, indicating that XO is not sufficient for this toxicity of LPS. To define the possible role of cytokines, we studied the effect of direct administration of LPS (600 micrograms/mouse, IP), tumor necrosis factor (TNF, 2.5 or 50 micrograms/mouse, IV), interleukin-1 (IL-1 beta, 2.5 micrograms/mouse, IV), interferon-gamma (IFN-gamma, 2.5 micrograms/mouse, IV), or their combination at 2.5 micrograms each. In addition to LPS, only TNF at the highest dose induced pulmonary edema 24 hours later. LPS-induced pulmonary edema was partially inhibited by anti-IFN-gamma antibodies but not by anti-TNF antibodies, anti-IL-1 beta antibodies, or IL-1 receptor antagonist (IL-1Ra).

Studies on the relationship between plasma CRP and TNF-α, IL-1β levels in aged patients with acute coronary syndrome

International Nuclear Information System (INIS)

Luo Nanping; Wang Xiangang; Hu Chengjin; Wang Ruishan

2002-01-01

Objective: To investigate the relationship between plasma TNF-α, IL-1β and CRP levels in aged patients with coronary heart disease and to define the inflammation marker which might recognize and predict acute coronary syndrome. Methods: Radioimmunoassay was used to detect plasma levels of TNF-α, IL-1β and CRP. Results: Plasma levels of TNF-α and IL-β in patients with acute coronary syndrome (ACS) were significantly higher than those in controls (p<0.05; p<0.01) and stable coronary heart disease (SCHD) (p<0.05; p<0.01). Plasma CRP levels in patients with ACS (7.99 +- 11.9 ml/L) were also significantly higher than those in controls (0.99 +- 1.5 mg/L; p<0.01) and patients with SCHD (2.71 +- 5.45 mg/L; p<0.05). There was positive correlation between CRP level and TNF-α (r=0.0545; p<0.01) as well as IL-β (r=0.31, p<0.05). Conclusion: The abnormal expression of cytokines in aged patients with coronary heart disease was correlative to inflammation marker CRP, which suggested that the abnormal expression to the occurrence of acute coronary syndrome and might serve as a marker of unstable atherosclerosis plaque

Smart Cards and Card Operating Systems

NARCIS (Netherlands)

Hartel, Pieter H.; Bartlett, J.; de Jong, Eduard K.

The operating system of an IC card should provide an appropriate interface to applications using IC cards. An incorrect choice of operations and data renders the card inefficient and cumbersome. The design principles of the UNIX operating system are most appropriate for IC card operating system

CMS Tracker Readout Prototype Front-End Driver PCI Mezzanine Card (Mk1) (connector side)

CERN Multimedia

J.Coughlan

1998-01-01

The tracking system of the CMS detector at the LHC employs Front End Driver (FED) cards to digitise, buffer and sparsify analogue data arriving via optical links from on detector pipeline chips. This paper describes a prototype version of the FED based upon the popular commercial PCI bus Mezzanine Card (PMC) form factor. The FED-PMC consists of an 8 channel, 9 bit ADC, card, providing a 1 MByte data buffer and operating at the LHC design frequency of 40 MHz. The core of the card is a re-programmable FPGA which allows the functionality of the card to be conveniently modified. The card is supplied with a comprehensive library of C routines.The PMC form factor allows the card to be plugged onto a wide variety of processor carrier boards and even directly into PCI based PCs. The flexibility of the FPGA based design permits the card to be used in a variety of ADC based applications.

1,25-Dihydroxyvitamin D3 Inhibits the RANKL Pathway and Impacts on the Production of Pathway-Associated Cytokines in Early Rheumatoid Arthritis

Directory of Open Access Journals (Sweden)

Jing Luo

2013-01-01

Full Text Available Objectives. To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH2D3 on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA. Methods. Receptor activator of nuclear factor-kappa B ligand (RANKL, osteoprotegerin (OPG, IFN-γ, IL-6, TNF-α, IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA or an enzyme-linked immunosorbent assay (ELISA. Results. After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs with 1,25(OH2D3 in RA patients, the levels of RANKL, TNF-α, IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH2D3 had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. Conclusions. The present study demonstrated that 1,25(OH2D3 reduced the production of RANKL and the secretion of TNF-α, IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH2D3 might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.

Assessment of 226Ra age-dependent dose from water intake

International Nuclear Information System (INIS)

Porntepkasemsan, Boonsom; Srisuksawad, Kanitha

2008-01-01

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 μSv yr -1 ). These values are acceptable in accordance with the WHO recommended reference dose level of 100 μSv yr -1 from water intake of 2 L day -1

Addition of the Neurokinin-1-Receptor Antagonist (RA) Aprepitant to a 5-Hydroxytryptamine-RA and Dexamethasone in the Prophylaxis of Nausea and Vomiting Due to Radiation Therapy With Concomitant Cisplatin

Energy Technology Data Exchange (ETDEWEB)

Jahn, Franziska, E-mail: franziska.jahn@uk-halle.de [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Riesner, Anica [Department of Gastroenterology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jahn, Patrick [Nursing Research Unit, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Sieker, Frank; Vordermark, Dirk [Department of Radiation Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany); Jordan, Karin [Department of Hematology/Oncology, Martin-Luther-University Halle-Wittenberg, Halle (Saale) (Germany)

2015-08-01

Purpose: To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy–induced nausea and vomiting. Patients and Methods: This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period. Results: Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03). Conclusion: This is the first study of an NK1-RA–containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

Evaluation of Four Bedside Test Systems for Card Performance, Handling and Safety.

Science.gov (United States)

Giebel, Felix; Picker, Susanne M; Gathof, Birgit S

2008-01-01

SUMMARY: OBJECTIVE: Pretransfusion ABO compatibility testing is a simple and required precaution against ABO-incompatible transfusion, which is one of the greatest threats in transfusion medicine. While distinct agglutination is most important for correct test interpretation, protection against infectious diseases and ease of handling are crucial for accurate test performance. Therefore, the aim of this study was to evaluate differences in test card design, handling, and user safety. DESIGN: Four different bedside test cards with pre-applied antibodies were evaluated by 100 medical students using packed red blood cells of different ABO blood groups. Criteria of evaluation were: agglutination, labelling, handling, and safety regarding possible user injuries. Criteria were rated subjectively according to German school notes ranging from 1 = very good to 6 = very bad/insufficient. RESULTS: Overall, all cards received very good/good marks. The ABO blood group was identified correctly in all cases. Three cards (no. 1, no. 3, no. 4) received statistically significant (p labelling (1.5 vs. 2.2-2.4), handling (1.9-2.0 vs. 2.5), and user safety (2.5 vs. 3.4). Analysis of card self-explanation revealed no remarkable differences. CONCLUSION: Despite good performance of all card systems tested, the best results when including all criteria evaluated were obtained with card no. 4 (particularly concerning clear agglutination), followed by cards no. 2, no. 1, and no. 3.

Mind Bomb Regulates Cell Death during TNF Signaling by Suppressing RIPK1’s Cytotoxic Potential

Directory of Open Access Journals (Sweden)

Rebecca Feltham

2018-04-01

Full Text Available Summary: Tumor necrosis factor (TNF is an inflammatory cytokine that can signal cell survival or cell death. The mechanisms that switch between these distinct outcomes remain poorly defined. Here, we show that the E3 ubiquitin ligase Mind Bomb-2 (MIB2 regulates TNF-induced cell death by inactivating RIPK1 via inhibitory ubiquitylation. Although depletion of MIB2 has little effect on NF-κB activation, it sensitizes cells to RIPK1- and caspase-8-dependent cell death. We find that MIB2 represses the cytotoxic potential of RIPK1 by ubiquitylating lysine residues in the C-terminal portion of RIPK1. Our data suggest that ubiquitin conjugation of RIPK1 interferes with RIPK1 oligomerization and RIPK1-FADD association. Disruption of MIB2-mediated ubiquitylation, either by mutation of MIB2’s E3 activity or RIPK1’s ubiquitin-acceptor lysines, sensitizes cells to RIPK1-mediated cell death. Together, our findings demonstrate that Mind Bomb E3 ubiquitin ligases can function as additional checkpoint of cytokine-induced cell death, selectively protecting cells from the cytotoxic effects of TNF. : Feltham et al. show that MIB2 directly ubiquitylates RIPK1 upon TNF stimulation, suppressing the cytotoxic potential of RIPK1 and acting as a checkpoint within the TNF signaling pathway. Keywords: MIB2, RIPK1, TNF, cell death, caspase-8, IAPs, ubiquitin

Claudin-1 promotes TNF-α-induced epithelial-mesenchymal transition and migration in colorectal adenocarcinoma cells

International Nuclear Information System (INIS)

Bhat, Ajaz A.; Ahmad, Rizwan; Uppada, SrijayaPrakash B.; Singh, Amar B.; Dhawan, Punita

2016-01-01

Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer progression and malignancy including colorectal cancer (CRC). Importantly, inflammatory mediators are critical constituents of the local tumor environment and an intimate link between CRC progression and inflammation is now validated. We and others have reported key role of the deregulated claudin-1 expression in colon carcinogenesis including colitis-associated colon cancer (CAC). However, the causal association between claudin-1 expression and inflammation-induced colon cancer progression remains unclear. Here we demonstrate, TNF-α, a pro-inflammatory cytokine, regulates claudin-1 to modulate epithelial to mesenchymal transition (EMT) and migration in colon adenocarcinoma cells. Importantly, colon cancer cells cultured in the presence of TNF-α (10 ng/ml), demonstrated a sharp decrease in E-cadherin expression and an increase in vimentin expression (versus control cells). Interestingly, TNF-α treatment also upregulated (and delocalized) claudin-1 expression in a time-dependent manner accompanied by increase in proliferation and wound healing. Furthermore, similar to our previous observation that claudin-1 overexpression in CRC cells induces ERK1/2 and Src- activation, signaling associated with colon cancer cell survival and transformation, TNF-α-treatment induced upregulation of phospho-ERK1/2 and -Src expression. The shRNA-mediated inhibition of claudin-1 expression largely abrogated the TNF-α-induced changes in EMT, proliferation, migration, p-Erk and p-Src expression. Taken together, our data demonstrate TNF-α mediated regulation of claudin-1 and tumorigenic abilities of colon cancer cells and highlights a key role of deregulated claudin-1 expression in inflammation-induced colorectal cancer growth and progression, through the regulation of the ERK and Src-signaling.

Claudin-1 promotes TNF-α-induced epithelial-mesenchymal transition and migration in colorectal adenocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Bhat, Ajaz A. [Surgery, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Ahmad, Rizwan; Uppada, SrijayaPrakash B. [Departments of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Singh, Amar B. [From the Department of Veterans Affairs, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Departments of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Dhawan, Punita, E-mail: punita.dhawan@unmc.edu [From the Department of Veterans Affairs, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Departments of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68022 (United States); Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE 68022 (United States)

2016-11-15

Epithelial-mesenchymal transition (EMT) is an important mechanism in cancer progression and malignancy including colorectal cancer (CRC). Importantly, inflammatory mediators are critical constituents of the local tumor environment and an intimate link between CRC progression and inflammation is now validated. We and others have reported key role of the deregulated claudin-1 expression in colon carcinogenesis including colitis-associated colon cancer (CAC). However, the causal association between claudin-1 expression and inflammation-induced colon cancer progression remains unclear. Here we demonstrate, TNF-α, a pro-inflammatory cytokine, regulates claudin-1 to modulate epithelial to mesenchymal transition (EMT) and migration in colon adenocarcinoma cells. Importantly, colon cancer cells cultured in the presence of TNF-α (10 ng/ml), demonstrated a sharp decrease in E-cadherin expression and an increase in vimentin expression (versus control cells). Interestingly, TNF-α treatment also upregulated (and delocalized) claudin-1 expression in a time-dependent manner accompanied by increase in proliferation and wound healing. Furthermore, similar to our previous observation that claudin-1 overexpression in CRC cells induces ERK1/2 and Src- activation, signaling associated with colon cancer cell survival and transformation, TNF-α-treatment induced upregulation of phospho-ERK1/2 and -Src expression. The shRNA-mediated inhibition of claudin-1 expression largely abrogated the TNF-α-induced changes in EMT, proliferation, migration, p-Erk and p-Src expression. Taken together, our data demonstrate TNF-α mediated regulation of claudin-1 and tumorigenic abilities of colon cancer cells and highlights a key role of deregulated claudin-1 expression in inflammation-induced colorectal cancer growth and progression, through the regulation of the ERK and Src-signaling.

Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America

International Nuclear Information System (INIS)

Bonotto, D.M.

2004-01-01

Groundwater samples were analysed for 222 Rn, 226 Ra, and 228 Ra in Guarani aquifer spreading around 1 million km 2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay

Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America.

Science.gov (United States)

Bonotto, D M

2004-01-01

Groundwater samples were analysed for 222Rn, 226Ra, and 228Ra in Guarani aquifer spreading around 1 million km2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay.

RA Research reactor, Part 1, Operation and maintenance of the RA nuclear reactor for 1986; Istrazivacki nuklearni reaktor RA, deo 1, pogon i odrzavanje nukleanog reaktora RA u 1986. godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Martinc, R; Cupac, S; Sulem, B; Badrljica, R; Majstorovic, D; Sanovic, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1986-12-01

In order to enable future reliable operation of the RA reactor, according to new licensing regulations, three major tasks started in 1984 were fulfilled: building of the new emergency system, reconstruction of the existing ventilation system, and reconstruction of the power supply system. Simultaneously in 1985/1986 renewal of the instrumentation and reconstruction of the system for handling and storage of the spent fuel in the reactor building have started. Design projects for these tasks are almost finished and the reconstruction of both systems is expected to be finished until 1988 and mid 1989 respectively. RA reactor Safety report was finished according to the recommendations of the IAEA. Investments in 1986 were used for 8000 kg of heavy water, maintenance of reactor systems and supply of new components, reconstruction of reactor systems. This report includes 8 annexes concerning reactor operation, activities of services and financial issues. [Serbo-Croat] Sa ciljem da se obezbedi pouzdan rad reaktora RA a u skladu sa zakonskim propisima, zavrsena su tri velika zahvata zapoceta 1984: izgradnja novog sistema za udesno hladjenje, rekonstrukcija postojeceg sistema za ventilaciju, i modernizacija reaktorske instrumentacije. Istovremeno tokom 1985/1986. zapoceta je modernizacija instrumentacije i rekonstrukcija sistema za rukovanje i skladistenje iskoriscenog goriva u zgradi reaktora. Projekti za navedene radove su vec zavrseni ili su u zavrsnoj fazi, a ocekuje se da ce rekonstrukcija oba sistema biti zavrsena do kraja 1988. odnosno sredine 1989. godine. Izrada izvestaja o sigurnosti reaktora RA, prema preporukama MAAE zavrsena je 1986. Investiciona ulaganja na reaktoru Ra u 1986. iskoriscena su za: nabavku 8000 kg teske vode, za investiciono odrzavanje reaktorskih sistema i nabavku opreme, za rekonstrukciju reaktorskih sistema. Ovaj izvestaj sadrzi 8 priloga koji opisuju rad reaktora, rad strucnih sluzbi i finansiranje.

Study of natural radionuclides - "2"2"6Ra, "2"2"8Ra and "2"1"0PB - in marine sediment cores from Southwest Atlantic during the Holocene

International Nuclear Information System (INIS)

Costa, Alice Miranda Ribeiro

2016-01-01

Natural radionuclides from "2"3"8U and "2"3"2Th series have been successfully applied as tracers of environmental process and climate changes. The "2"1"0Pb (half-life of 22.2 years) is used in the geochronological dating technique of sediment cores of the last 100-150 years, and its respective sedimentation rate determination. The study of "2"2"6Ra and "2"2"8Ra concentrations (half-lives of 1,600 years and 5.75 years, respectively) helps calculate the activity of "2"1"0Pb in excess in the environment, besides being important tracers of marine processes, as ground water discharge. In this work it was determined the activity concentrations of "2"2"6Ra, "2"2"8Ra and "2"1"0Pb in four short marine cores collected since the continental platform to upper slope of Southwest Atlantic Ocean. Taking into account the results obtained, sedimentation rates and the ages of each sediment layer were determined using the geochronological dating method with "2"1"0Pb. All sediment samples were total acid digested in microwave. The sequential radiochemical separation of "2"2"6Ra, "2"2"8Ra, "2"1"0Pb were performed, obtaining in the end the precipitation of Ba(Ra)SO_4 and PbCrO_4. The gross α measurements of "2"2"6Ra and gross β measurements of "2"2"8Ra and "2"1"0Pb from the precipitates were carried out in a gas-flow low background proportional counter. Concerning all cores analyzed, the activities concentrations of "2"2"6Ra ranged from 14 Bq.kg"-"1 to 154 Bq.kg"-"1; the concentrations of "2"2"8Ra ranged from 17 Bq.kg"-"1 to 45 Bq.kg"-"1; and the concentrations of "2"1"0Pb ranged from 20 Bq.kg"-"1 to 2,073 Bq.kg"-"1. High values of "2"1"0Pb were observed on the top of all the cores studied, mainly related to atmospheric deposition. The results obtained in this work were of the same order of magnitude of those reported in the literature available on non contaminated areas of Southeast Brazilian Coast. Sedimentation rates fall with the increase of water column depth and ranged from 0

Both anti-TNF and CTLA4 Ig treatments attenuate the disease severity of staphylococcal dermatitis in mice.

Directory of Open Access Journals (Sweden)

Manli Na

Full Text Available RA patients being treated with biologics are known to have an increased risk of infections. We recently demonstrated that both CTLA4 Ig and anti-TNF treatment aggravate systemic Staphylococcus aureus (S. aureus infection in mice, but with distinct clinical manifestations. However, the effects of CTLA4 Ig and anti-TNF treatments on a local S. aureus infection (e.g., skin infection might differ from their effects on a systemic infection.The aim of this study was to examine the differential effects of anti-TNF versus CTLA4 Ig treatment on S. aureus skin infections in mice.Abatacept (CTLA4 Ig, etanercept (anti-TNF treatment or PBS was given to NMRI mice subcutaneously inoculated with S. aureus strain SH1000. The clinical signs of dermatitis, along with histopathological changes due to skin infection, were compared between the groups.Both CTLA4 Ig and anti-TNF treatment resulted in less severe skin infections and smaller post-infectious hyperpigmentation compared with controls. Consistent with the clinical signs of dermatitis, smaller lesion size, more epithelial hyperplasia and more granulation were found in skin biopsies from mice receiving anti-TNF compared with PBS controls. However, both CTLA4 Ig and anti-TNF therapy tended to prolong the healing time, although this finding was not statistically significant. Serum MCP-1 levels were elevated in the anti-TNF group relative to the CTLA4 Ig and PBS groups, whereas IL-6 levels were higher in PBS controls than in the other two groups. Both anti-TNF and CTLA4 Ig treatments tended to down-regulate the necrosis/apoptosis ratio in the locally infected skin tissue. Importantly, no tangible difference was found in the bacterial burden among groups.Both CTLA4 Ig and anti-TNF therapies attenuate disease severity but may prolong the healing time required for S. aureus skin infections. Neither treatment has an impact on bacterial clearance in skin tissues.

Disruption - Access cards service

CERN Multimedia

2014-01-01

We would like to inform you that between 10 November and 15 December 2014, the access cards service in Building 55 will be disrupted, as the GS Department has decided to improve the facilities for users of this building. During the work, you will find the registration, biometric registration and dosimeter exchange services on the second floor of Building 55 and the vehicle sticker service on the ground floor along with the access cards service. We thank you for your understanding and apologise for any inconvenience caused.

Raf-1/CK2 and RhoA/ROCK signaling promote TNF-α-mediated endothelial apoptosis via regulating vimentin cytoskeleton.

Science.gov (United States)

Yang, Lifeng; Tang, Lian; Dai, Fan; Meng, Guoliang; Yin, Runting; Xu, Xiaole; Yao, Wenjuan

2017-08-15

Both RhoA/ROCK and Raf-1/CK2 pathway play essential roles in cell proliferation, apoptosis, differentiation, and multiple other common cellular functions. We previously reported that vimentin is responsible for TNF-α-induced cell apoptosis. Herein, we investigated the regulation of RhoA/ROCK and Raf-1/CK2 signaling on vimentin filaments and endothelial apoptosis mediated by TNF-α. Treatment with TNF-α significantly induced the activation of RhoA and ROCK, and the expression of ROCK1. RhoA deficiency could obviously inhibit ROCK activation and ROCK1 expression induced by TNF-α. Both RhoA deficiency and ROCK activity inhibition (Y-27632) greatly inhibited endothelial apoptosis and preserved cell viability in TNF-α-induced human umbilical vein endothelial cells (HUVECs). Also vimentin phosphorylation and the remodeling of vimentin or phospho-vimentin induced by TNF-α were obviously attenuated by RhoA suppression and ROCK inhibition. TNF-α-mediated vimentin cleavage was significantly inhibited by RhoA suppression and ROCK inhibition through decreasing the activation of caspase3 and 8. Furthermore, TNF-α treatment greatly enhanced the activation of Raf-1. Suppression of Raf-1 or CK2 by its inhibitor (GW5074 or TBB) blocked vimentin phosphorylation, remodeling and endothelial apoptosis, and preserved cell viability in TNF-α-induced HUVECs. However, Raf-1 inhibition showed no significant effect on TNF-α-induced ROCK expression and activation, suggesting that the regulation of Raf-1/CK2 signaling on vimentin was independent of ROCK. Taken together, these results indicate that both RhoA/ROCK and Raf-1/CK2 pathway are responsible for TNF-α-mediated endothelial cytotoxicity via regulating vimentin cytoskeleton. Copyright © 2017 Elsevier B.V. All rights reserved.

Radiological sacroiliitis, a hallmark of spondylitis, is linked with CARD15 gene polymorphisms in patients with Crohn's disease

OpenAIRE

Peeters, Harald; Vander Cruyssen, Bert; Laukens, Debby; Coucke, Paul; MARICHAL, DENIS; VAN DEN BERGHE, MARTINA; Cuvelier, Claude; Remaut, Erik; Mielants, Herman; De Keyser, Filip; De Vos, Martine

2004-01-01

Background: Sacroiliitis is a common extraintestinal manifestation of Crohn's disease but its association with the HLA-B27 phenotype is less evident. Polymorphisms in the CARD15 gene have been linked to higher susceptibility for Crohn's disease. In particular, associations have been found with ileal and fibrostenosing disease, young age at onset of disease, and familial cases.

Membrane Type 1–Matrix Metalloproteinase/Akt Signaling Axis Modulates TNF-α-Induced Procoagulant Activity and Apoptosis in Endothelial Cells

Science.gov (United States)

Ohkawara, Hiroshi; Ishibashi, Toshiyuki; Sugimoto, Koichi; Ikeda, Kazuhiko; Ogawa, Kazuei; Takeishi, Yasuchika

2014-01-01

Membrane type 1–matrix metalloproteinase (MT1-MMP) functions as a signaling molecule in addition to a proteolytic enzyme. Our hypothesis was that MT1-MMP cooperates with protein kinase B (Akt) in tumor necrosis factor (TNF)-α-induced signaling pathways of vascular responses, including tissue factor (TF) procoagulant activity and endothelial apoptosis, in cultured human aortic endothelial cells (ECs). TNF-α (10 ng/mL) induced a decrease in Akt phosphorylation within 60 minutes in ECs. A chemical inhibitor of MMP, TIMP-2 and selective small interfering RNA (siRNA)-mediated suppression of MT1-MMP reversed TNF-α-triggered transient decrease of Akt phosphorylation within 60 minutes, suggesting that MT1-MMP may be a key regulator of Akt phosphorylation in TNF-α-stimulated ECs. In the downstream events, TNF-α increased TF antigen and activity, and suppressed the expression of thrombomodulin (TM) antigen. Inhibition of Akt markedly enhanced TNF-α-induced expression of TF antigen and activity, and further reduced the expression of TM antigen. Silencing of MT1-MMP by siRNA also reversed the changed expression of TF and TM induced by TNF-α. Moreover, TNF-α induced apoptosis of ECs through Akt- and forkhead box protein O1 (FoxO1)-dependent signaling pathway and nuclear factor-kB (NF-kB) activation. Knockdown of MT1-MMP by siRNA reversed apoptosis of ECs by inhibiting TNF-α-induced Akt-dependent regulation of FoxO1 in TNF-α-stimulated ECs. Immunoprecipitation demonstrated that TNF-α induced the changes in the associations between the cytoplasmic fraction of MT1-MMP and Akt in ECs. In conclusion, we show new evidence that MT1-MMP/Akt signaling axis is a key modifier for TNF-α-induced signaling pathways for modulation of procoagulant activity and apoptosis of ECs. PMID:25162582

Poxvirus-encoded TNF decoy receptors inhibit the biological activity of transmembrane TNF.

Science.gov (United States)

Pontejo, Sergio M; Alejo, Ali; Alcami, Antonio

2015-10-01

Poxviruses encode up to four different soluble TNF receptors, named cytokine response modifier B (CrmB), CrmC, CrmD and CrmE. These proteins mimic the extracellular domain of the cellular TNF receptors to bind and inhibit the activity of TNF and, in some cases, other TNF superfamily ligands. Most of these ligands are released after the enzymic cleavage of a membrane precursor. However, transmembrane TNF (tmTNF) is not only a precursor of soluble TNF but also exerts specific pro-inflammatory and immunological activities. Here, we report that viral TNF receptors bound and inhibited tmTNF and describe some interesting differences in their activity against the soluble cytokine. Thus, CrmE, which does not inhibit mouse soluble TNF, could block murine tmTNF-induced cytotoxicity. We propose that this anti-tmTNF effect should be taken into consideration when assessing the role of viral TNF decoy receptors in the pathogenesis of poxvirus.

Smart City Pilot Projects Using LoRa and IEEE802.15.4 Technologies.

Science.gov (United States)

Pasolini, Gianni; Buratti, Chiara; Feltrin, Luca; Zabini, Flavio; De Castro, Cristina; Verdone, Roberto; Andrisano, Oreste

2018-04-06

Information and Communication Technologies (ICTs), through wireless communications and the Internet of Things (IoT) paradigm, are the enabling keys for transforming traditional cities into smart cities, since they provide the core infrastructure behind public utilities and services. However, to be effective, IoT-based services could require different technologies and network topologies, even when addressing the same urban scenario. In this paper, we highlight this aspect and present two smart city testbeds developed in Italy. The first one concerns a smart infrastructure for public lighting and relies on a heterogeneous network using the IEEE 802.15.4 short-range communication technology, whereas the second one addresses smart-building applications and is based on the LoRa low-rate, long-range communication technology. The smart lighting scenario is discussed providing the technical details and the economic benefits of a large-scale (around 3000 light poles) flexible and modular implementation of a public lighting infrastructure, while the smart-building testbed is investigated, through measurement campaigns and simulations, assessing the coverage and the performance of the LoRa technology in a real urban scenario. Results show that a proper parameter setting is needed to cover large urban areas while maintaining the airtime sufficiently low to keep packet losses at satisfactory levels.

Smart City Pilot Projects Using LoRa and IEEE802.15.4 Technologies

Directory of Open Access Journals (Sweden)

Gianni Pasolini

2018-04-01

Full Text Available Information and Communication Technologies (ICTs, through wireless communications and the Internet of Things (IoT paradigm, are the enabling keys for transforming traditional cities into smart cities, since they provide the core infrastructure behind public utilities and services. However, to be effective, IoT-based services could require different technologies and network topologies, even when addressing the same urban scenario. In this paper, we highlight this aspect and present two smart city testbeds developed in Italy. The first one concerns a smart infrastructure for public lighting and relies on a heterogeneous network using the IEEE 802.15.4 short-range communication technology, whereas the second one addresses smart-building applications and is based on the LoRa low-rate, long-range communication technology. The smart lighting scenario is discussed providing the technical details and the economic benefits of a large-scale (around 3000 light poles flexible and modular implementation of a public lighting infrastructure, while the smart-building testbed is investigated, through measurement campaigns and simulations, assessing the coverage and the performance of the LoRa technology in a real urban scenario. Results show that a proper parameter setting is needed to cover large urban areas while maintaining the airtime sufficiently low to keep packet losses at satisfactory levels.

Expression of TNF-α and IL-6 cytokines in the choroid and sclera of hypercholesterolemic rabbits

Directory of Open Access Journals (Sweden)

Rogil José de Almeida Torres

2014-06-01

Full Text Available Objetivo: Avaliar a expressão das citocinas inflamatórias TNF-α e IL-6 na esclera e coroide de coelhos hipercolesterolêmicos. Método: Coelhos New Zealand foram organizados em dois grupos: GN recebeu ração padrão para coelhos; GH recebeu dieta rica em colesterol a 1%. Foi realizada a dosagem sérica de colesterol total, triglicerídeos, HDL colesterol, glicemia de jejum no início do experimento e no momento da eutanásia. Ao final da 4ª semana para o GN e 8ª semana para o GH foi realizada a eutanásia dos animais. Os olhos foram submetidos à análise imuno-histoquímica com os anticorpos TNF-α e IL-6. Resultados: O GH manifestou significativo aumento do colesterol total e triglicerídeos em relação ao GN (p<0,001. Houve significativo aumento da expressão da TNF-α (p<0,001 e da IL-6 (p=0,002 na coroide e esclera dos animais do GH em relação ao GN. Conclusão: Este estudo demonstra que a dieta hipercolesterolêmica induz ao aumento da expressão das citocinas TNF-α e IL-6 na coroide e esclera de coelhos.

A microprocessor card software server to support the Quebec health microprocessor card project.

Science.gov (United States)

Durant, P; Bérubé, J; Lavoie, G; Gamache, A; Ardouin, P; Papillon, M J; Fortin, J P

1995-01-01

The Quebec Health Smart Card Project is advocating the use of a memory card software server[1] (SCAM) to implement a portable medical record (PMR) on a smart card. The PMR is viewed as an object that can be manipulated by SCAM's services. In fact, we can talk about a pseudo-object-oriented approach. This software architecture provides a flexible and evolutive way to manage and optimize the PMR. SCAM is a generic software server; it can manage smart cards as well as optical (laser) cards or other types of memory cards. But, in the specific case of the Quebec Health Card Project, SCAM is used to provide services between physicians' or pharmacists' software and IBM smart card technology. We propose to expose the concepts and techniques used to provide a generic environment to deal with smart cards (and more generally with memory cards), to obtain a dynamic an evolutive PMR, to raise the system global security level and the data integrity, to optimize significantly the management of the PMR, and to provide statistic information about the use of the PMR.

Differential regulation of TNF-α and IL-1β production from endotoxin stimulated human monocytes by phosphodiesterase inhibitors

Directory of Open Access Journals (Sweden)

K. L. Molnar-Kimber

1992-01-01

Full Text Available The effect of selective PDE-I (vinpocetine, PDE-III (milrinone, CI-930, PDE-IV (rolipram, nitroquazone, and PDE-V (zaprinast isozyme inhibitors on TNF-α and IL-1β production from LPS stimulated human monocytes was investigated. The PDE-IV inhibitors caused a concentration dependent inhibition of TNF-α production, but only partially inhibited IL-1β at high concentrations. High concentrations of the PDE-III inhibitors weakly inhibited TNF-α, but had no effect on IL-1β production. PDE-V inhibition was associated with an augmentation of cytokine secretion. Studies with combinations of PDE isozyme inhibitors indicated that PDE-III and PDE-V inhibitors modulate rolipram's suppression of TNF production in an additive manner. These data confirm that TNF-α and IL-1β production from LPS stimulated human monocytes are differentially regulated, and suggest that PDE-IV inhibitors have the potential to suppress TNF levels in man.

Digitizing Olin Eggen's Card Database

Science.gov (United States)

Crast, J.; Silvis, G.

2017-06-01

The goal of the Eggen Card Database Project is to recover as many of the photometric observations from Olin Eggen's Card Database as possible and preserve these observations, in digital forms that are accessible by anyone. Any observations of interest to the AAVSO will be added to the AAVSO International Database (AID). Given to the AAVSO on long-term loan by the Cerro Tololo Inter-American Observatory, the database is a collection of over 78,000 index cards holding all Eggen's observations made between 1960 and 1990. The cards were electronically scanned and the resulting 108,000 card images have been published as a series of 2,216 PDF files, which are available from the AAVSO web site. The same images are also stored in an AAVSO online database where they are indexed by star name and card content. These images can be viewed using the eggen card portal online tool. Eggen made observations using filter bands from five different photometric systems. He documented these observations using 15 different data recording formats. Each format represents a combination of filter magnitudes and color indexes. These observations are being transcribed onto spreadsheets, from which observations of value to the AAVSO are added to the AID. A total of 506 U, B, V, R, and I observations were added to the AID for the variable stars S Car and l Car. We would like the reader to search through the card database using the eggen card portal for stars of particular interest. If such stars are found and retrieval of the observations is desired, e-mail the authors, and we will be happy to help retrieve those data for the reader.

Distribution of 226Ra and 228Ra in drinking water and dose assessment

International Nuclear Information System (INIS)

Ajay Kumar; Sugandhi, S.; Usha, N.; Rupali, K.; Gurg, R.P.

2002-01-01

The radioactivity concentrations of 226 Ra and 228 Ra have been analysed in 123 drinking water samples received from different regions of India. The maximum concentrations of 226 Ra and 228 Ra in drinking water are 8 mBq/l and 11.5 mBq/l respectively. The higher doses due to intake of 228 Ra through drinking water suggests that 228 Ra should also be measured in the assessment of ingestion dose to the population. The estimated committed effective doses range from 0.082 to 2.45 μSv/year and from 1.53 to 8.81 μSv/year for the ingestion of 226 Ra and 228 Ra respectively. (author)

Taraxacum officinale induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

Science.gov (United States)

Koo, Hyun-Na; Hong, Seung-Heon; Song, Bong-Keun; Kim, Cheorl-Ho; Yoo, Young-Hyun; Kim, Hyung-Min

2004-01-16

Taraxacum officinale (TO) has been frequently used as a remedy for women's disease (e.g. breast and uterus cancer) and disorders of the liver and gallbladder. Several earlier studies have indicated that TO exhibits anti-tumor properties, but its mechanism remains to be elucidated. In this study, we investigated the effect of TO on the cytotoxicity and production of cytokines in human hepatoma cell line, Hep G2. Our results show that TO decreased the cell viability by 26%, and significantly increased the tumor necrosis factor (TNF)-alpha and interleukin (IL)-1alpha production compared with media control (about 1.6-fold for TNF-alpha, and 2.4-fold for IL-1alpha, P < 0.05). Also, TO strongly induced apoptosis of Hep G2 cells as determined by flow cytometry. Increased amounts of TNF-alpha and IL-1alpha contributed to TO-induced apoptosis. Anti-TNF-alpha and IL-1alpha antibodies almost abolished it. These results suggest that TO induces cytotoxicity through TNF-alpha and IL-1alpha secretion in Hep G2 cells.

[TNF-α, diabetes type 1 and regulatory T cells].

Science.gov (United States)

Ryba, Monika; Myśliwska, Jolanta

2010-01-01

Recent studies on animal models of diabetes as well as human regulatory T cells have shown that α impairs the ability of these cells to prevent the disease. NOD mice treated with α had decreased frequency of regulatory T cells, whereas anti-TNF administration induced the increase in the number of these cells and disease prevention. The action of α also influenced the suppressive potential of Tregs. Increased susceptibility of Tregs to the modulatory effects of α involves signaling through TNFR2 that is expressed on the surface of this cell population. It seems that α neutralization may rescue regulatory T cells and restore their function in several autoimmune and inflammatory diseases. This review describes recent data concerning regulatory T cells in the context of inflammation that is present during diabetes type 1. It describes how TNF contributes to the pathogenesis of type 1 diabetes, what is the impact of this cytokine on regulatory T cell population and therapeutic effects that result from its neutralization in several inflammatory and autoimmune diseases.

FBCT fast intensity measurement using TRIC cards

CERN Document Server

Allica, J C; Belohrad, D; Jensen, L; Lenardon, F; SØby, L

2015-01-01

At the CERN PS complex, precise fast intensity measurements are very important in order to optimize the transfer efficiencies between the different accelerators. Over the last two years a complete renovation has been ongoing, where the old electronics, based on analogue integrators, have been replaced by a fully digital system enclosed in a single VME based card. This new system called TRIC (Transformer Integration Card) is based on a 12 bit, 212 MS/s ADC and an FPGA for the signal processing. Also located on the same board one finds a 250 V/1.5 W DCDC converter used to generate precise calibration pulses.

RA reactor operation and maintenance in 1992, Part 1; Deo 1 - Pogon i odrzavanje nuklearnog reaktoro RA u 1992. Godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Cupac, S; Sulem, B; Zivotic, Z; Majstorovic, D; Tanaskovic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1992-12-01

During 1992 Ra reactor was not in operation. All the activities were fulfilled according to the previously adopted plan. Basic activities were concerned with revitalisation of the RA reactor and maintenance of reactor components. All the reactor personnel was busy with reconstruction and renewal of the existing reactor systems and building of the new systems, maintenance of the reactor devices. Part of the staff was trained for relevant tasks and maintenance of reactor systems. [Serbo-Croat] U toku 1992 godine poslovi u okviru projekta 'Istrazivacki nuklearni reaktor RA' obavljani su u skladu sa programom i planom rada. Osnovne aktivnosti na kojima je radjeno odnosile su se na revitalizaciju reaktora RA, kao i na odrzavanje opreme. U ovom periodu reaktor nije bio u pogonu. Svo osoblje je bilo angazovano na poslovima rekonstrukcije i modernizacije postojecih i dogradnje novih reaktorskih sistema, na odrzavanju opreme a deo tehnickog osoblja je bio obucavan za vrsenje odgovarajucih poslova u pogonu i odrzavanju opreme.

TNF induction of EL4 hyposensitivity to lysis by recombinant (soluble) and membrane-associated TNFs: TNF binding, internalization, and degradation.

Science.gov (United States)

Fishman, M; Costlow, M

1994-04-01

EL4 mouse thymoma cells sensitive to TNF-mediated lysis only in the presence of cycloheximide (S-EL4) or in the presence or absence of cycloheximide (N-EL4) were used in these experiments. Murine tumor cell line (S-EL4) sensitivity to TNF cytotoxicity is augmented when cycloheximide is added together with TNF or when cycloheximide is added 1 hr before or after TNF. No enhanced sensitivity is observed when target cells are incubated with cycloheximide 2-4 hr before or after the addition of TNF. In the absence of cycloheximide, S-EL4 cells preexposed to murine TNF are less susceptible to lysis by TNF and TNF receptor-conjugated TNF but are lysed by integral membrane TNF. TNF-induced hyposensitivity is partially reversed by actinomycin D or by culturing the preexposed cells for 4 hr prior to TNF lytic assay. TNF preincubation of N- and S-EL4 cells results in an immediate decrease in 125I-TNF binding due to TNF receptor occupancy. Recovery of TNF-R occupancy and TNF internalization were subsequently noted.

Measuring the radium quartet ({sup 228}Ra, {sup 226}Ra, {sup 224}Ra, {sup 223}Ra) in seawater samples using gamma spectrometry

Energy Technology Data Exchange (ETDEWEB)

Beek, P. van, E-mail: vanbeek@legos.obs-mip.f [LEGOS, Laboratoire d' Etudes en Geophysique et Oceanographie Spatiales (CNRS/CNES/IRD/UPS), Observatoire Midi Pyrenees, 14 Avenue Edouard Belin, 31400 Toulouse (France); Souhaut, M. [LEGOS, Laboratoire d' Etudes en Geophysique et Oceanographie Spatiales (CNRS/CNES/IRD/UPS), Observatoire Midi Pyrenees, 14 Avenue Edouard Belin, 31400 Toulouse (France); Reyss, J.-L. [LSCE, Laboratoire des Sciences du Climat et de l' Environnement (CNRS/CEA/UVSQ), Avenue de la Terrasse, 91198 Gif-sur-Yvette (France)

2010-07-15

Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While {sup 228}Ra and {sup 226}Ra are usually measured using gamma spectrometry, short-lived Ra isotopes ({sup 224}Ra and {sup 223}Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report {sup 226}Ra, {sup 228}Ra, {sup 224}Ra, {sup 223}Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccares lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The {sup 223}Ra and {sup 224}Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the {sup 224}Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low {sup 223}Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes.

Effect of Novel Marine Nutraceuticals on IL-1α-Mediated TNF-α Release from UVB-Irradiated Human Melanocyte-Derived Cells

Directory of Open Access Journals (Sweden)

Visalini Muthusamy

2011-01-01

Full Text Available UV-induced inflammation and reactive oxygen species formation are involved in the development of melanoma. Natural products like 5β-scymnol and CO2-supercritical fluid extract (CO2-SFE of mussel oil contain anti-inflammatory and antioxidant properties that may aid in reducing the deleterious effects of UV radiation. Therefore, their effect on the release of the proinflammatory cytokine, tumour necrosis factor-α (TNF-α, from UVB-irradiated human melanocytic cells was examined. Human epidermal melanocytes (HEM and MM96L melanoma cells were exposed to UVB radiation and IL-1α. Cell viability and TNF-α levels were determined 24 hours after-irradiation while p38 mitogen-activated protein kinase (MAPK activation was observed at 15 min after-irradiation. When α-tocopherol, CO2-SFE mussel oil, and 5β-scymnol were added to the UVB-irradiated HEM cells treated with IL-1α, TNF-α levels fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L cells. This effect was not due to inhibition of the intracellular p38 MAPK signalling pathway. These compounds may be useful in preventing inflammation-induced damage to normal melanocytes.

Evaluation and comparison of FTA card and CTAB DNA extraction methods for non-agricultural taxa1

Science.gov (United States)

Siegel, Chloe S.; Stevenson, Florence O.; Zimmer, Elizabeth A.

2017-01-01

Premise of the study: An efficient, effective DNA extraction method is necessary for comprehensive analysis of plant genomes. This study analyzed the quality of DNA obtained using paper FTA cards prepared directly in the field when compared to the more traditional cetyltrimethylammonium bromide (CTAB)–based extraction methods from silica-dried samples. Methods: DNA was extracted using FTA cards according to the manufacturer’s protocol. In parallel, CTAB-based extractions were done using the automated AutoGen DNA isolation system. DNA quality for both methods was determined for 15 non-agricultural species collected in situ, by gel separation, spectrophotometry, fluorometry, and successful amplification and sequencing of nuclear and chloroplast gene markers. Results: The FTA card extraction method yielded less concentrated, but also less fragmented samples than the CTAB-based technique. The card-extracted samples provided DNA that could be successfully amplified and sequenced. The FTA cards are also useful because the collected samples do not require refrigeration, extensive laboratory expertise, or as many hazardous chemicals as extractions using the CTAB-based technique. Discussion: The relative success of the FTA card method in our study suggested that this method could be a valuable tool for studies in plant population genetics and conservation biology that may involve screening of hundreds of individual plants. The FTA cards, like the silica gel samples, do not contain plant material capable of propagation, and therefore do not require permits from the U.S. Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) for transportation. PMID:28224056

Systemic and localized infection by Candida species in patients with rheumatic diseases receiving anti-TNF therapy

Directory of Open Access Journals (Sweden)

Nadia E. Aikawa

Full Text Available ABSTRACT Objective: To evaluate the prevalence of systemic and localized infection by Candida species and its possible association with demographic, clinical and laboratory manifestations and therapy in patients with rheumatic diseases taking TNF blockers. Methods: Consecutive patients with rheumatic diseases receiving anti-TNF agents were included. The following risk factors up to four weeks prior to the study were analyzed: use of antibiotics, immunosuppressant drugs, hospitalization and invasive procedures. All subjects were evaluated for clinical complaints; specific blood cultures were obtained for fungi and blood samples were collected for Candida spp. detection by polymerase chain reaction. Results: 194 patients [67 with rheumatoid arthritis (RA, 47 with ankylosing spondylitis (AS, 36 with juvenile idiopathic arthritis (JIA, 28 with psoriatic arthritis and 16 with other conditions] were included. The average age of patients was 42 ± 16 years, with 68 (35% male and mean disease duration of 15 ± 10 years. Sixty-four (33% patients were receiving adalimumab, 59 (30% etanercept and 71 (36% infliximab. Eighty-one percent of patients were concomitantly taking immunosuppressant drugs. At the time of the study, only one (0.5% patient had localized fungal infection (vaginal candidiasis. None of the patients included had systemic candidiasis with positive blood cultures for fungi or PCR positive for Candida spp. in peripheral blood sample. Conclusions: This was the first study to assess the prevalence of invasive and localized fungal disease by Candida in a significant number of patients with rheumatic diseases on anti-TNF therapy, and demonstrated low risk of candidiasis, despite the high prevalence of immunosuppressive drug use.

1,5-Anhydro-D-fructose attenuates lipopolysaccharide-induced cytokine release via suppression of NF-κB p65 phosphorylation

International Nuclear Information System (INIS)

Meng Xiaojie; Kawahara, Ko-ichi; Nawa, Yuko; Miura, Naoki; Shrestha, Binita; Tancharoen, Salunya; Sameshima, Hisayo; Hashiguchi, Teruto; Maruyama, Ikuro

2009-01-01

Lipopolysaccharide (LPS) stimulates macrophages by activating NF-κB, which contributes to the release of tumor necrosis factor (TNF)-α and interleukin (IL)-6. 1,5-anhydro-D-fructose (1,5-AF), a monosaccharide formed from starch and glycogen, exhibits anti-oxidant activity and enhances insulin secretion. This study examined the effects of 1,5-AF on LPS-induced inflammatory reactions and elucidated its molecular mechanisms. Before LPS challenge, mice were pretreated with 1,5-AF (38.5 mg/kg). We found that 1,5-AF pretreatment attenuated cytokine release into the serum, including TNF-α, IL-6 and macrophage chemoattractant protein (MCP)-1. Furthermore, pretreatment with 1,5-AF (500 μg/ml) attenuated cytokine release, and 1,5-AF directly inhibited the nuclear translocalization of the NF-κB p65 subunit in LPS-stimulated murine macrophage-like RAW264.7 cells. This inhibition was responsible for decreased LPS-induced phosphorylation on Ser536 of the NF-κB p65 subunit, which is a posttranslational modification involved in the non-canonical pathway. Collectively, these findings indicate that the anti-inflammatory activity of 1,5-AF occurs via inactivation of NF-κB.

In vivo evidence for a functional role of both tumor necrosis factor (TNF) receptors and transmembrane TNF in experimental hepatitis.

Science.gov (United States)

Küsters, S; Tiegs, G; Alexopoulou, L; Pasparakis, M; Douni, E; Künstle, G; Bluethmann, H; Wendel, A; Pfizenmaier, K; Kollias, G; Grell, M

1997-11-01

The significance of tumor necrosis factor receptor 1 (TNFR1) for TNF function in vivo is well documented, whereas the role of TNFR2 so far remains obscure. In a model of concanavalin A (Con A)-induced, CD4+ T cell-dependent experimental hepatitis in mice, in which TNF is a central mediator of apoptotic and necrotic liver damage, we now provide evidence for an essential in vivo function of TNFR2 in this pathophysiological process. We demonstrate that a cooperation of TNFR1 and TNFR2 is required for hepatotoxicity as mice deficient of either receptor were resistant against Con A. A significant role of TNFR2 for Con A-induced hepatitis is also shown by the enhanced sensitivity of transgenic mice overexpressing the human TNFR2. The ligand for cytotoxic signaling via both TNF receptors is the precursor of soluble TNF, i.e. transmembrane TNF. Indeed, transmembrane TNF is sufficient to mediate hepatic damage, as transgenic mice deficient in wild-type soluble TNF but expressing a mutated nonsecretable form of TNF developed inflammatory liver disease.

rs1004819 is the main disease-associated IL23R variant in German Crohn's disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants.

Directory of Open Access Journals (Sweden)

Jürgen Glas

Full Text Available BACKGROUND: The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants. METHODS: Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD, 456 patients with ulcerative colitis (UC, and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T and SLC22A5/OCTN2 (-207 G-->C. RESULTS: All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11; OR 1.56; 95 % CI (1.37-1.78]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34]. The coding SNP rs11209026 (p.Arg381Gln was protective for CD [P = 8.04x10(-8; OR 0.43; CI (0.31-0.59]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5. CONCLUSION: IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.

Increased levels of circulating (TNF-α) is associated with (-308G/A) promoter polymorphism of TNF-α gene in Diabetic Nephropathy.

Science.gov (United States)

Umapathy, Dhamodharan; Krishnamoorthy, Ezhilarasi; Mariappanadar, Vairamani; Viswanathan, Vijay; Ramkumar, Kunka Mohanram

2018-02-01

The crucial role of Tumor Necrosis Factor-α (TNF-α) on renal function in patients with Diabetic Nephropathy (DN) has been well documented. The present study was designed to investigate the association of TNF-α [-308G/A, (rs1800629)] single nucleotide polymorphism (SNP) on the susceptibility to DN subjects and to correlate it with the plasma levels of TNF-α along with circulatory TNF-α receptor super family cytokines (sTNFR-1 and sTNFR-2). A total of 756 subjects, were recruited and divided into groups [Group-I, Control (n=218), Group-II, Normoalbuminuria (n=196), Group-IIIa, Microalbuminuria (n=178), Group-IIIb, Macroalbuminuria (n=164)] and were genotyped by PCR-restriction fragment length polymorphism (RFLP). Circulatory levels of TNF-α and sTNFR-1 & sTNFR-2 were measured using multiplex bead based assay. The 'A' allele of TNF-α (-308 G/A) SNP was associated with a significant risk for macroalbuminuria subjects (OR: 2.1; 95% CI: 0.8-3.7; P<0.001). A marked stepwise increase was observed in the levels of circulatory biomarkers such as TNF-α, sTNF-R1 and sTNF-R2 from normo to macroalbuminuria subjects. In DN subjects, the TNF-α level was higher in individuals who had mutant AA, than the wild GG genotype of TNF-α gene. Our results conclude that rs1800629 polymorphism in TNF-α gene is associated with renal complications in T2DM subjects. Copyright © 2017 Elsevier B.V. All rights reserved.

Thermorewritable card by using dyes; Senryo wo mochiita kakikae kanona card

Energy Technology Data Exchange (ETDEWEB)

Muto, Y.

1998-06-01

Described herein are thermorewritable cards which use dyes. Rewritable cards, mainly used for membership and point cards, are themselves used repeatedly and required to be rewritable repeatedly for information they carry. The dyes and developers used for the conventional heat- and pressure-sensitive papers are colorless, leuco-dye precursors and acidic compounds with a phenolic hydroxyl group or the like. They transfer electrons to each other, opening the lactone ring of the dye precursor to develop the color. Developing and erasing the color are reversible chemical reactions, where the color is developed under heat and maintained by quenching. For erasing the color, it is heated and then slowly cooled to separate the precursor and developer phases from each other. A printer (thermal head) is required for developing and erasing a color. Durability under various conditions is another requirement of the card; it must be adaptable to weather conditions and resistant to sweat. The new thermorewritable card is protected from various adverse effects on its chemical reactions, and made as durable as the conventional cards. 3 refs., 5 figs., 1 tab.

Radium isotope (223Ra, 224Ra, 226Ra and 228Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil

International Nuclear Information System (INIS)

Dias, Thais H.; Oliveira, Joselene de; Sanders, Christian J.; Carvalho, Franciane; Sanders, Luciana M.; Machado, Eunice C.; Sá, Fabian

2016-01-01

This work investigates the 223 Ra, 224 Ra, 226 Ra and 228 Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of 223 Ra, 224 Ra, 226 Ra and 228 Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, 223 Ra/ 224 Ra and 223 Ra/ 228 Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11 days. - Highlights: • Radium isotope concentrations were evaluated along a large estuarine system. • The radioactivity level in river, estuary and sediments was within a normal range. • Spatial distributions of site specific radionuclides have differing activities and sources.

Expressions of TNF-α, IL-1α and IL-6 in bronchiolar epithelium after thoracic irradiation

International Nuclear Information System (INIS)

Yang Kunyu; Hu Yu; Ruebe Claudia; Ruebe Christian

2006-01-01

Objective: To investigate temporal and spatial releases of proinflam matory cytokines TNF-α, IL-1α and IL-6 in the lung tissue after thoracic irradiation in C57BL/6J mice. Methods: Mice were irradiated with 12 Gy to whole lungs, and control mice were sham-irradiated. Mice were sacrificed at hours 0.5, 1, 3, 6, 12, 24, 48 and 72 and weeks 1, 2, 4, 8, 16 and 24 after thoracic irradiation or sham-irradiation. Expressions of TNF-a and IL-1α, IL-6 proteins were detected with immuno-histochemistry. Results: At hour 6 after thoracic irradiation, the expression of TNF-α protein increased significantly, and at hour 12 after thoracic irradiation, the expressions of IL-1α and IL-6 proteins increased significantly, too. The bronchiolar epithelium was the most prominent source of these inflammatory cytokines in the first hours. During the stage of acute pneumonitis, the bronchiolar epithelium, as well as inflammatory cells in the lung interstitium, produced high amounts of TNF-α, IL-1α and IL-6. Conclusions: It was demonstrated that immediate expressions of TNF-α, IL-1α and IL-6 occurred in the bronchiolar epithelium after lung irradiation, and a long-lasting release by the bronchiolar and alveolar epithelium, and inflammatory cells during acute pneumonitis. Therefore, the bronchiolar epithelium is a significant source of proinflammatory cytokines capable of promoting inflammation through recruitment and activation of inflammatory cells after lung irradiation. (authors)

Doses from {sup 222}Rn, {sup 226}Ra, and {sup 228}Ra in groundwater from Guarani aquifer, South America

Energy Technology Data Exchange (ETDEWEB)

Bonotto, D.M. E-mail: dbonotto@rc.unesp.br

2004-07-01

Groundwater samples were analysed for {sup 222}Rn, {sup 226}Ra, and {sup 228}Ra in Guarani aquifer spreading around 1 million km{sup 2} within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay.

Does a family history of RA influence the clinical presentation and treatment response in RA?

Science.gov (United States)

Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

2016-06-01

To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

REPLACEMENT OF FRENCH CARDS

CERN Multimedia

Human Resources Division

2001-01-01

The French Ministry of Foreign Affairs has informed the Organization that it is shortly to replace all diplomatic cards, special cards and employment permits ('attestations de fonctions') now held by members of the personnel and their families. Between 2 July and 31 December 2001, these cards are to be replaced by secure, computerized equivalents. A 'personnel office' stamped photocopy of the old cards may continue to be used until 31 December 2001. For the purposes of the handover, members of the personnel must go personally to the cards office (33/1-015), between 8:30 and 12:30, in order to fill a 'fiche individuelle' form (in black ink only), which has to be personally signed by themselves and another separately signed by members of their family, taking the following documents for themselves and members of their families already in possession of a French card : A recent identity photograph in 4.5 cm x 3.5 cm format (signed on the back) The French card in their possession an A4 photocopy of the same Fre...

The "Negative" Credit Card Effect: Credit Cards as Spending-Limiting Stimuli in New Zealand

Science.gov (United States)

Lie, Celia; Hunt, Maree; Peters, Heather L.; Veliu, Bahrie; Harper, David

2010-01-01

The "credit card effect" describes a finding where greater value is given to consumer items if credit card logos are present. One explanation for the effect is that credit cards elicit spending behavior through associative learning. If this is true, social, economic and historical contexts should alter this effect. In Experiment 1, Year…

RA Research reactor, Annual report 1986; Istrazivacki nuklearni reaktor RA - Izvestaj za 1986. godinu

Energy Technology Data Exchange (ETDEWEB)

Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1986-12-01

Research reactor RA Annual report for year 1985 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1986 godinu sastoji se od dva dela: prvi deo obuhvata pogon i odzavanje reaktora RA, a drugi poslove zastite od zracenja na reaktoru RA.

Effect of interleukin-1 and tumor necrosis factor/cachectin on glucose turnover in the rat

International Nuclear Information System (INIS)

Flores, E.A.; Istfan, N.; Pomposelli, J.J.; Blackburn, G.L.; Bistrian, B.R.

1990-01-01

We studied the effect of recombinant human interleukin-1 beta (IL-1) and recombinant human tumor necrosis factor alpha/cachectin (TNF) on glucose kinetics in healthy rats by means of a primed constant infusion of D-(6-3H)glucose and D-[U- 14 C]glucose. During the isotope (6-hour) and monokine (4-hour) infusion, plasma levels of glucagon and insulin were determined and correlated with changes in glucose metabolism. The rates of glucose appearance (Ra) and disappearance (Rd) were elevated only with IL-1 and were associated with an increase in glucagon and a concomitant decrease in the ratio of insulin to glucagon. Plasma glucose concentration was increased early after IL-1 administration and coincided with the peak in the Ra. The augmentation of the metabolic clearance rate (MCR) and percent of flux oxidized by IL-1 suggest that this monokine induces the utilization of glucose as a substrate. TNF administration failed to modify the Ra or Rd, percent of flux oxidized, or MCR. TNF-treated rats increased the percent of glucose recycling, but not the total rate of glucose production. The results of this experiment suggest that endogenous macrophage products participate in the diverse alterations of carbohydrate metabolism seen during injury and/or infection

β-Hydroxy-β-methylbutyrate (HMB)-free acid attenuates circulating TNF-α and TNFR1 expression postresistance exercise.

Science.gov (United States)

Townsend, Jeremy R; Fragala, Maren S; Jajtner, Adam R; Gonzalez, Adam M; Wells, Adam J; Mangine, Gerald T; Robinson, Edward H; McCormack, William P; Beyer, Kyle S; Pruna, Gabriel J; Boone, Carleigh H; Scanlon, Tyler M; Bohner, Jonathan D; Stout, Jeffrey R; Hoffman, Jay R

2013-10-15

The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyrate-free acid (HMB-FA) and cold-water immersion (CWI) on circulating concentrations of TNF-α and monocyte TNF-α receptor 1 (TNFR1) expression. Forty resistance-trained men (22.3 ± 2.4 yr) were randomized into four groups [placebo (PL), HMB-FA, CWI, and HMB-FA-CWI] and performed an acute, intense exercise protocol (four sets of up to 10 repetitions of the squat, dead lift, and split squat). Participants also performed four sets of up to 10 repetitions of the squat at 24 and 48 h following the initial exercise bout. Blood was sampled before exercise (PRE), immediately postexercise (IP), and 30 min, 24 h, and 48 h postexercise (30P, 24P, and 48P, respectively). Circulating TNF-α was assayed, and TNFR1 expression on CD14+ monocytes was measured by flow cytometry. The exercise protocol significantly elevated TNF-α in only PL (P = 0.006) and CWI (P = 0.045) IP. Mean percent changes show that TNF-α significantly increased from PRE to IP for only PL and CWI groups (P < 0.05), whereas the percent change of TNF-α for HMB-FA and HMB-FA-CWI was not significant. TNFR1 expression was elevated in PL (P = 0.023) and CWI (P = 0.02) at 30P compared with PRE, whereas both HMB-FA-treated groups did not increase significantly. In conclusion, HMB-FA attenuated circulating TNF-α IP and TNFR1 expression during recovery compared with PL and CWI. HMB-FA supplementation may attenuate the initial immune response to intense exercise, which may reduce recovery time following intense exercise.

Effects of interleukin-1 receptor antagonist (IL-1Ra) gene 86 bp VNTR polymorphism on recurrent pregnancy loss: a case-control study.

Science.gov (United States)

Hajizadeh, Yasamin Sayed; Emami, Elina; Nottagh, Marina; Amini, Zahra; Maroufi, Nazila Fathi; Azimian, Saba Haj; Isazadeh, Alireza

2017-05-26

Objective Recurrent pregnancy loss (RPL) is a heterogeneous disease which is defined as two or more consecutive fetal losses during early pregnancy. Interleukin-1 receptor antagonist (IL-1Ra) is a anti-inflammatory cytokine, which inhibits IL-1 activity by binding to its receptors. The aim of this study was to investigate the association between RPL and IL-1Ra intron 2 polymorphism (86 bp VNTR) in Iranian women. Materials and methods In this case control study, genetic polymorphism was studied in 140 RPL patients and 140 healthy women as controls. Genomic DNA was extracted from the blood samples and polymorphism analysis was performed using the polymerase chain reaction (PCR) method. Finally, the data obtained were analyzed by statistical software. Results We found an increased frequency of the IL-1Ra 1/1 genotype in the case group compared to the control group. Whereas, the frequency of IL-1Ra genotype 1/2 was higher in control group than in the case group. However, we did not observe an association between IL-1Ra 86 bp VNTR polymorphism in intron 2 and RPL patients (p > 0.05). Conclusion IL-1Ra VNTR polymorphism may not be a genetic factor for RPL. However, investigation of IL-1Ra polymorphism was recommended in other populations and patients with recurrent pregnancy loss.

226Ra, 228Ra and 228Ra/226Ra in surface marine sediment of Malaysia

International Nuclear Information System (INIS)

Mei-Wo Yii; Zal Uyun Wan-Mahmood

2013-01-01

Surface sediment samples were collected at the West (east coast and west coast of Peninsular Malaysia) and East (Sabah and Sarawak) Malaysia in several expeditions within August 2003 until June 2008 for determining the level of natural radium isotopes. Activity concentrations of 226 Ra and 228 Ra in surface marine sediment at 176 sampling stations were measured. The activity concentrations of both radionuclides in Malaysia (East and West Malaysia) display varied with the range from 9 to 158 Bq/kg dry wt. and 13 to 104 Bq/kg dry wt., respectively. Meanwhile, the ratio distributions of 228 Ra/ 226 Ra were ranged from 0.62 to 3.75. This indicated that the ratios were slightly high at west coast of Peninsular Malaysia compared to other regions (east coast of Peninsular Malaysia, Sabah and Sarawak). The variation of activity concentrations of 226 Ra and 228 Ra and its ratios were also supported by the statistical analyses of one-way ANOVA and t test at 95 % confidence level, whereby there were proved that the measured values were different between the regions. These different were strictly related to their half-life, potential input sources (included their parents, 238 U and 232 Th), parent's characteristic, the geological setting/formation of the study area, environment origin and behavior. (author)

TNF-α and LPS activate angiogenesis via VEGF and SIRT1 signalling in human dental pulp cells.

Science.gov (United States)

Shin, M R; Kang, S K; Kim, Y S; Lee, S Y; Hong, S C; Kim, E-C

2015-07-01

To assess whether SIRT1 and VEGF are responsible for tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS)-induced angiogenesis and to examine the molecular mechanism(s) of action in human dental pulp cells (HDPCs). Immortalized HDPCs obtained from Prof. Takashi Takata (Hiroshima University, Japan) were treated with LPS (1 μg mL(-1) ) and TNF-α (10 ng mL(-1) ) for 24 h. mRNA and protein levels were examined by RT-PCR and Western blotting, respectively. Migration and tube formation were examined in human umbilical vein endothelial cells (HUVECs). The data were analysed by one-way anova. Statistical analysis was performed at α = 0.05. LPS and TNF-α upregulated VEGF and SIRT1 mRNA and protein levels. Inhibition of SIRT1 activity by sirtinol and SIRT1 siRNA or inhibition of the VEGF receptor by CBO-P11 significantly attenuated LPS + TNF-α-stimulated MMPs production in HDPCs, as well as migration and tube formation in HUVECs (P disease. © 2014 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB

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Jin-Xiu Yang

2016-11-01

Full Text Available Background/Aims: Tanshinone IIA (Tan IIA is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α-induced endothelial progenitor cells (EPCs. Methods: EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1/intracellular adhesion molecule-1 (ICAM-1 and activation of Nuclear factor κB (NF-κB signaling pathway were measured. Results: The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/β in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount. Conclusion: This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/β pathway in EPCs.

Rare and Common Variants in CARD14, Encoding an Epidermal Regulator of NF-kappaB, in Psoriasis

Science.gov (United States)

Jordan, Catherine T.; Cao, Li; Roberson, Elisha D.O.; Duan, Shenghui; Helms, Cynthia A.; Nair, Rajan P.; Duffin, Kristina Callis; Stuart, Philip E.; Goldgar, David; Hayashi, Genki; Olfson, Emily H.; Feng, Bing-Jian; Pullinger, Clive R.; Kane, John P.; Wise, Carol A.; Goldbach-Mansky, Raphaela; Lowes, Michelle A.; Peddle, Lynette; Chandran, Vinod; Liao, Wilson; Rahman, Proton; Krueger, Gerald G.; Gladman, Dafna; Elder, James T.; Menter, Alan; Bowcock, Anne M.

2012-01-01

Psoriasis is a common inflammatory disorder of the skin and other organs. We have determined that mutations in CARD14, encoding a nuclear factor of kappa light chain enhancer in B cells (NF-kB) activator within skin epidermis, account for PSORS2. Here, we describe fifteen additional rare missense variants in CARD14, their distribution in seven psoriasis cohorts (>6,000 cases and >4,000 controls), and their effects on NF-kB activation and the transcriptome of keratinocytes. There were more CARD14 rare variants in cases than in controls (burden test p value = 0.0015). Some variants were only seen in a single case, and these included putative pathogenic mutations (c.424G>A [p.Glu142Lys] and c.425A>G [p.Glu142Gly]) and the generalized-pustular-psoriasis mutation, c.413A>C (p.Glu138Ala); these three mutations lie within the coiled-coil domain of CARD14. The c.349G>A (p.Gly117Ser) familial-psoriasis mutation was present at a frequency of 0.0005 in cases of European ancestry. CARD14 variants led to a range of NF-kB activities; in particular, putative pathogenic variants led to levels >2.5× higher than did wild-type CARD14. Two variants (c.511C>A [p.His171Asn] and c.536G>A [p.Arg179His]) required stimulation with tumor necrosis factor alpha (TNF-α) to achieve significant increases in NF-kB levels. Transcriptome profiling of wild-type and variant CARD14 transfectants in keratinocytes differentiated probably pathogenic mutations from neutral variants such as polymorphisms. Over 20 CARD14 polymorphisms were also genotyped, and meta-analysis revealed an association between psoriasis and rs11652075 (c.2458C>T [p.Arg820Trp]; p value = 2.1 × 10−6). In the two largest psoriasis cohorts, evidence for association increased when rs11652075 was conditioned on HLA-Cw∗0602 (PSORS1). These studies contribute to our understanding of the genetic basis of psoriasis and illustrate the challenges faced in identifying pathogenic variants in common disease. PMID:22521419

Valutazione economica dello studio CARDS

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Simona de Portu

2007-10-01

Full Text Available Introduction: cardiovascular diseases (CVD are the major component of premature mortality, generate disability and are a relevant source of cost. The growing incidence of CVD is associated with lifestyle and other modifiable risk factors. Prevention and preclinical detection of CVD reduce morbidity and mortality. Type 2 diabetes is associated with a substantially increased risk of cardiovascular disease. Objective: the aim of the study was to evaluate the health economic consequence of medical therapy with atorvastatin for primary prevention of major cardiovascular events in patients with type 2 diabetes in Italy. Materials and method: in order to reach our objective we drew clinical information from the CARDS study. This economic evaluation was carried out conducting a cost/effectiveness analysis from the perspective of National Health Service (NHS. The analysis was applied to a time horizon in conformity with the observational period adopted in the CARDS study (3.9 years. An incremental cost/effectiveness ratio (ICER was calculated and is expressed as cost per life years gained (LYG. In order to test the robustness of the results, a one-way sensitivity analysis was performed. Results: the total cost of atorvastatin therapy over 3.9 years amounts to around 1.5 million of euros per 1,000 patients. The total cost of adding atorvastatin to standard care in people treated for primary prevention of major cardiovascular events in type 2 diabetes as those involved in the CARDS study would entail an additional cost of about 1,2 million of euros per 1,000 patients treated per 3.9 years, with an incremental cost/effectiveness ratio (ICER equivalent to 36,566 euros per patient per LYG. Discussion: the current study is the first economic evaluation of CARDS study to the Italian situation. The results of the current study show that hypolipemic therapy with atorvastatin 10 mg in diabetic individuals is to be considered cost effective.

Determination of 226 Ra and 228 Ra in mineral spring waters of the Aguas da Prata region

International Nuclear Information System (INIS)

Oliveira, J. de.

1993-01-01

Concentration levels of 226 Ra and 228 Ra have been analysed in most of the mineral spring waters available in the Aguas da Prata region. The 226 Ra and 228 Ra were determined by coprecipitation with barium sulphate. The 226 Ra was determined by gross alpha counting of the Ba(Ra)SO 4 precipitate. The determination of 228 Ra was done by measuring the gross beta activity of the same precipitate. Both measurements were carried out in a low background gas flow proportional counter. Dose calculations were performed in order to evaluate the relative importance of such radionuclides to the radiation exposure due to the ingestion of these waters. Based upon measured concentrations, committed effective doses up to 5.5 x 10 -1 mSv/y and 1.0 x 10 -2 mSv/y were observed for 226 Ra and 228 Ra, respectively. These results show that 226 Ra is the main contributor to radiation exposure. (author)

Functional analysis RaZIP1 transporter of the ZIP family from the ectomycorrhizal Zn-accumulating Russula atropurpurea.

Science.gov (United States)

Leonhardt, Tereza; Sácký, Jan; Kotrba, Pavel

2018-04-01

A search of R. atropurpurea transcriptome for sequences encoding the transporters of the Zrt-, Irt-like Protein (ZIP) family, which are in eukaryotes integral to Zn supply into cytoplasm, allowed the identification of RaZIP1 cDNA with a predicted product belonging to ZIP I subfamily; it was subjected to functional studies in mutant Saccharomyces cerevisiae strains. The expression of RaZIP1, but not RaZIP1 H208A or RaZIP1 H232A mutants lacking conserved-among-ZIPs transmembrane histidyls, complemented Zn uptake deficiency in zrt1Δzrt2Δ yeasts. RaZIP1 substantially increased cellular Zn uptake in this strain and added to Zn sensitivity in zrc1Δcot1Δ mutant. The Fe uptake deficiency in ftr1Δ strain was not rescued and Mn uptake was insufficient for toxicity in Mn-sensitive pmr1Δ yeasts. By contrast, RaZIP1 increased Cd sensitivity in yap1Δ strain and conferred Cd transport activity in yeasts, albeit with substantially lower efficiency compared to Zn transport. In metal uptake assays, the accumulation of Zn in zrt1Δzrt2Δ strain remained unaffected by Cd, Fe, and Mn present in 20-fold molar excess over Zn. Immunofluorescence microscopy detected functional hemagglutinin-tagged HA::RaZIP1 on the yeast cell protoplast periphery. Altogether, these data indicate that RaZIP1 is a high-affinity plasma membrane transporter specialized in Zn uptake, and improve the understanding of the cellular and molecular biology of Zn in R. atropurpurea that is known for its ability to accumulate remarkably high concentrations of Zn.

Modelling of the RA-1 reactor using a Monte Carlo code; Modelado del reactor RA-1 utilizando un codigo Monte Carlo

Energy Technology Data Exchange (ETDEWEB)

Quinteiro, Guillermo F; Calabrese, Carlos R [Comision Nacional de Energia Atomica, General San Martin (Argentina). Dept. de Reactores y Centrales Nucleares

2000-07-01

It was carried out for the first time, a model of the Argentine RA-1 reactor using the MCNP Monte Carlo code. This model was validated using data for experimental neutron and gamma measurements at different energy ranges and locations. In addition, the resulting fluxes were compared with the data obtained using a 3D diffusion code. (author)

Both IL-1β and TNF-α Regulate NGAL Expression in Polymorphonuclear Granulocytes of Chronic Hemodialysis Patients

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Adriana Arena

2010-01-01

Full Text Available Background. NGAL is involved in modulation of the inflammatory response and is found in the sera of uremic patients. We investigated whether hemodiafiltration (HDF could influence the ability of polymorphonuclear granulocytes (PMGs to release NGAL. The involvement of interleukin- (IL-1β and tumor necrosis factor- (TNF-α on NGAL release was evaluated. Methods. We studied end-stage renal disease (ESRD patients at the start of dialysis (Pre-HDF and at the end of treatment (Post-HDF and 18 healthy subjects (HSs. Peripheral venous blood was taken from HDF patients at the start of dialysis and at the end of treatment. Results. PMGs obtained from ESRD patients were hyporesponsive to LPS treatment, with respect to PMG from HS. IL-1β and TNF-α produced by PMG from post-HDF patients were higher than those obtained by PMG from pre-HDF. Neutralization of IL-1β, but not of TNF-α, determined a clear-cut production of NGAL in PMG from healthy donors. On the contrary, specific induction of NGAL in PMG from uremic patients was dependent on the presence in supernatants of IL-1β and TNF-α. Conclusion. Our data demonstrate that in PMG from healthy subjects, NGAL production was supported solely by IL-1β, whereas in PMG from HDF patients, NGAL production was supported by IL-1β, TNF-α.

Effect of TNF-Alpha on Caveolin-1 Expression and Insulin Signaling During Adipocyte Differentiation and in Mature Adipocytes

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Sara Palacios-Ortega

2015-07-01

Full Text Available Background/Aims: Tumor necrosis factor-α (TNF-α-mediated chronic low-grade inflammation of adipose tissue is associated with obesity and insulin resistance. Caveolin-1 (Cav-1 is the central component of adipocyte caveolae and has an essential role in the regulation of insulin signaling. The effects of TNF-α on Cav-1 expression and insulin signaling during adipocyte differentiation and in mature adipocytes were studied. Methods: 3T3-L1 cells were differentiated (21 days in the presence TNF-α (10 ng/mL and mature adipocytes were also treated with TNF-α for 48 hours. Cav-1 and insulin receptor (IR gene methylation were determined as well as Cav-1, IR, PKB/AKT-2 and Glut-4 expression and activation by real time RT-PCR and western blot. Baseline and insulin-induced glucose uptake was measured by the 2-[C14]-deoxyglucose uptake assay. Results: TNF-α slowed down the differentiation program, hindering the expression of some insulin signaling intermediates without fully eliminating insulin-mediated glucose uptake. In mature adipocytes, TNF-α did not compromise lipid-storage capacity, but downregulated the expression of the insulin signaling intermediates, totally blocking insulin-mediated glucose uptake. Insulin sensitivity correlated with the level of activated phospho-Cav-1 in both situations, strongly suggesting the direct contribution of Cav-1 to the maintenance of this physiological response. Conclusion: Cav-1 activation by phosphorylation seems to be essential for the maintenance of an active and insulin-sensitive glucose uptake.

Necroptosis Mediates TNF-Induced Toxicity of Hippocampal Neurons

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Shan Liu

2014-01-01

Full Text Available Tumor necrosis factor-α (TNF-α is a critical proinflammatory cytokine regulating neuroinflammation. Elevated levels of TNF-α have been associated with various neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. However, the signaling events that lead to TNF-α-initiated neurotoxicity are still unclear. Here, we report that RIP3-mediated necroptosis, a form of regulated necrosis, is activated in the mouse hippocampus after intracerebroventricular injection of TNF-α. RIP3 deficiency attenuates TNF-α-initiated loss of hippocampal neurons. Furthermore, we characterized the molecular mechanism of TNF-α-induced neurotoxicity in HT-22 hippocampal neuronal cells. HT-22 cells are sensitive to TNF-α only upon caspase blockage and subsequently undergo necrosis. The cell death is suppressed by knockdown of CYLD or RIP1 or RIP3 or MLKL, suggesting that this necrosis is necroptosis and mediated by CYLD-RIP1-RIP3-MLKL signaling pathway. TNF-α-induced necroptosis of HT-22 cells is largely independent of both ROS accumulation and calcium influx although these events have been shown to be critical for necroptosis in certain cell lines. Taken together, these data not only provide the first in vivo evidence for a role of RIP3 in TNF-α-induced toxicity of hippocampal neurons, but also demonstrate that TNF-α promotes CYLD-RIP1-RIP3-MLKL-mediated necroptosis of hippocampal neurons largely bypassing ROS accumulation and calcium influx.

226Ra and 228Ra activities associated with agricultural drainage ponds and wetland ponds in the Kankakee Watershed, Illinois-Indiana, USA

International Nuclear Information System (INIS)

Sidle, W.C.; Shanklin, D.; Lee, P.Y.; Roose, D.L.

2001-01-01

Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-α and -β activities were measured up to 455 and 1650 mBq L -1 , respectively. 226 Ra and 228 Ra averaged 139 and 192 mBq L -1 in controlled drainage ponds compared to 53 and 58 mBq L -1 for 226 Ra and 228 Ra, respectively, in native wetland ponds. Analyses of applied ammonium phosphate fertilizers near both native and controlled ponds indicate comparable 226 Ra/ 228 Ra and 228 Ra/ 232 Th activity ratios with only the surface waters in the controlled ponds. For example, 226 Ra/ 228 Ra activity ratios in controlled ponds ranged from 0.79 to 0.91 and group with a local fertilizer batch containing FL phosphate compounds with 226 Ra/ 228 Ra activity ratios of 0.83-1.04. Local soils of the Kankakee watershed have 226 Ra/ 228 Ra activity ratios of 0.54-0.70. Calculated Ra fluxes of waters, in drainage ditches associated with these controlled ponds, for 226 Ra ranged from 0.77 to 9.00 mBq cm -2 d -1 and for 228 Ra ranged from 1.22 to 8.43 mBq cm -2 d -1 . Ra activity gradients were measured beneath these controlled ponds both in agricultural landscapes and in constructed wetlands, all being associated with drainage ditches. Ra had infiltrated to the local water table but was below regulatory maximum contaminant limits. Still, measurable Ra activity was measured downgradient of even the constructed wetlands in the Kankakee watershed, suggesting that the attenuation of Ra was low. However, no Ra excess was observed in the riparian zone or the Kankakee River downgradient of the native wetland ponds

Properties of 15/2- states in 215Ra and 217Th; evaluation of the 15/2- to 9/2+ E3 strength in N=127 isotones

International Nuclear Information System (INIS)

Dracoulis, G.D.; Riess, R.; Stuchbery, A.E.; Bark, R.A.; Gupta, S.L.; Baxter, A.M.; Kruse, M.

1988-01-01

The lifetime of the yrast 15/2 - state in 215 Ra was measured using pulsed beams and γ-ray and electron techniques. Transition multipolarities were established from measured conversion coefficients. The B(E3) of the 15/2 - → 9/2 + transition is found to be considerably larger than previously reported. A candidate for the corresponding transition in 217 Th was also observed. The E3 strength of the 15/2 - → 9/2 + transition in the N=127 isotones is evaluated in the light of these and other recent results. Interpretation in the framework of particle-octupole vibration coupling requires a systematic lowering of the core 3 - vibration as proton pairs are added to 208 Pb

The role of renal function loss on circadian misalignment of cytokines EPO, IGF-1, IL-6 and TNF-alfa in chronic renal disease.

Science.gov (United States)

van der Putten, Karien; Koch, Birgit; van Someren, Eus; Wielders, Jos; Ter Wee, Piet; Nagtegaal, Elsbeth; Gaillard, Carlo

2011-01-01

Chronic inflammation plays a pivotal role in the development of renal disease. Circadian sleep-wake rhythm is disturbed in renal disease. Awareness of other disturbed rhythms, such as inflammation processes, can affect the treatment of patients with renal disease. Knowledge of possibly related circadian misalignment of the cytokines erythropoietin (EPO), Insulin Growth Factor-1 (IGF-1) and interleukins (IL) however is limited. We therefore performed an observational study. The objective of this study was to characterize levels of EPO, IGF-1 and inflammation markers IL-6 and TNF-α, related to renal function. The study population consisted of patients with various degrees of renal function, admitted to our hospital. During 24 hours, blood of 28 subjects with various degrees of renal function was collected every 2 hours. The patients were stable, not acutely ill and they were waiting for a procedure, such as elective surgery. Circadian parameters of EPO, IGF-1, IL-6 and TNF-α were measured in serum and were correlated with glomerular filtration rate (GFR) and Hb, using Pearson correlations. Although diurnal variations in EPO level were found in 15 out of 28 patients, the curves did not show a consistent phase. The presence of an EPO rhythm was not related to GFR. No diurnal rhythm could be detected for IGF-1, IL-6 and TNF-α. Mean levels of IGF-1 were correlated inversely to mean levels of EPO (p=0.03). When divided based on GFR and Hb subjects with GFR 10-30 ml/min and lower Hb had the highest IGF-1 levels (p=0.02). A relationship between Il-6, TNF-α and EPO or GFR was not found. The existence of a circadian (mis)alignment of EPO, IGF-1, IL-6 and TNF-α was not found. The association between high IGF-1 and low Hb suggests that EPO and IGF-1 have an alternating role, dependent on GFR, in stimulating erythropoiesis. These results could have consequences for the treatment of anemia.

Alterations in TNF- and IL-related gene expression in space-flown WI38 human fibroblasts

Science.gov (United States)

Semov, Alexandre; Semova, Nathalia; Lacelle, Chantale; Marcotte, Richard; Petroulakis, Emmanuel; Proestou, Gregory; Wang, Eugenia

2002-01-01

Spaceflight, just like aging, causes profound changes in musculoskeletal parameters, which result in decreased bone density and muscular weakness. As these conditions decrease our ability to conduct long-term manned space missions, and increase bone frailty in the elderly, the identification of genes responsible for the apparition of these physiological changes will be of great benefit. Thus, we developed and implemented a new microarray approach to investigate the changes in normal WI38 human fibroblast gene expression that arise as a consequence of space flight. Using our microarray, we identified changes in the level of expression of 10 genes, belonging to either the tumor necrosis factor- (TNF) or interleukin- (IL) related gene families in fibroblasts when WI38 cells exposed to microgravity during the STS-93 Space Shuttle mission were compared with ground controls. The genes included two ligands from the TNF superfamily, TWEAK and TNFSF15; two TNF receptor-associated proteins, NSMAF and PTPN13; three TNF-inducible genes, ABC50, PTX3, and SCYA13; TNF-alpha converting enzyme, IL-1 receptor antagonist, and IL-15 receptor alpha chain. Most of these are involved in either the regulation of bone density, and as such the development of spaceflight osteopenia, or in the development of proinflammatory status.

Pannus invasion and cartilage degradation in rheumatoid arthritis: involvement of MMP-3 and interleukin-1beta.

Science.gov (United States)

Ainola, M M; Mandelin, J A; Liljeström, M P; Li, T F; Hukkanen, M V J; Konttinen, Y T

2005-01-01

Synovial inflammation in rheumatoid arthritis (RA) leads to pannus tissue invasion and destruction of cartilage/bone matrix by proteinases. Our intention was to analyze some of the key matrix metalloproteinases (MMPs) in pannus tissue overlying evolving cartilage erosions in RA. Frozen tissue samples of pannus and synovium from advanced RA and synovium from osteoarthritic patients were used for immunohistochemical, western blotting and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis of MMP-1, -3, -13 and -14. Synovial fibroblast cultures, stimulated with tumour necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), were analyzed with enzyme-linked immunosorbent assays (ELISA) and quantitative RT-PCR. MMP-3 was highly expressed in pannus tissue compared with significantly lower expression levels of MMP-1, -13 and -14. In fibroblast cultures IL-1beta was a potent stimulus for MMP-3, whereas TNF-alpha was more potent for MMP-1. This is the first study to demonstrate quantitatively in real time that MMP-3 mRNA expression is clearly higher in advanced RA pannus tissue compared to parallel RA or osteoarthritic synovium. MMP-3 mRNA levels were also clearly overexpressed in RA pannus compared to MMP-1, -13 and -14. Advanced RA has previously been found to overexpress IL-1beta. The high expression of MMP-3 in pannus and IL-1beta, mediated stimulation of MMP-3 suggest that MMP-3 plays a significant role in the progression of erosions through the proteoglycan-rich cartilage matrix.

Payment Cards

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Kantnerová Liběna

2016-09-01

Full Text Available The aim of this paper is to analyze the use of payment cards in retail in the Czech Republic from the side of clients (buyers and the side of sellers. Questionnaires for clients examine satisfaction with cards and the service connected with them. Sellers’ satisfaction with the profit and function of cards is analyzed. The data indicated that 92% of the 352 respondents in South Bohemia had a payment card and more than 35% had more than one card. In retail, 70% of sellers had a payment terminal.

Alpha-particle doses to human organs and tissues from internally-deposited 226Ra and 228Ra

International Nuclear Information System (INIS)

Keane, A.T.; Schlenker, R.A.

1981-01-01

Estimation of radiation doses to the soft tissues from internally-deposited 226 Ra and 228 Ra is relevant to an investigation of soft-tissue malignancies in radium-exposed persons being conducted at the Center for Human Radiobiology. Alpha-particle doses in a 50-year period following a single injection of 226 Ra or 228 Ra are presented for 31 soft tissues and organs of the adult human. The dose estimates were derived from the ICRP alkaline earth model fitted to data on retention of 226 Ra in soft tissues and bone, combined with reported ratios of 226 Ra to Ca in soft tissue and bone at natural levels and the distribution of Ca in the tissues of Reference Man (ICRP23). The median of the 31 organ and tissue doses from the α-particles of 226 Ra itself is 0.08 rad per injected μCi. An additional average dose of 0.01 rad per μCi 226 Ra daughter products produced in soft tissue or transferred from bone to soft tissue. Soft-tissue doses from α-particles of the 228 Ra decay series are about six times those from 226 Ra α-particles for equal injected activities of 228 Ra and 226 Ra, with the assumption that 228 Ra daughter products do not transfer from the organ in which they are produced. The 50-year dose to the red marrow of bone from α-particles originating in bone is 0.55 rad per μCi 226 Ra injected and 1.0 rad per μCi 228 Ra injected. For ingestion by dial painters of luminous compound containg 226 Ra or 228 Ra with a daughter-to-parent activity ratio of 0.5, the dose to the mucosal alyer of the lower large intestine from α-particles originating in the gut contents is about 0.1 rad per μCi systemic intake of 226 Ra or 228 Ra

RA reactor operation and maintenance in 1989, Part 1; Deo 1 - Pogon i odrzavanje nuklearnog reaktora RA u 1989. godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Martinc, R; Cupac, S; Sulem, B; Zivotic, Z; Majstorovic, D; Sanovic, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1989-12-15

During the previous period RA reactor was not operated because the Committee of Serbian ministry for health and social care has cancelled the operation licence in July 1984. The reason was the non existing emergency cooling system and lack of appropriate filters in the special ventilation system. The following major tasks were fulfilled: building of the new emergency cooling system, reconstruction of the existing ventilation system, and renewal of the power supply system. Project concerned with renewal of RA reactor complete instrumentation was started at the end of 1988. Contract was signed between the IAEA and Soviet Atomenergoexport for supplying the new instrumentation for the RA reactor. Project concerned with increase of the storage space and the efficiency of handling the spent fuel elements has started in 1988. In 1989, device for water purification designed by the reactor staff started operation and spent fuel handling equipment is being mounted. Training of the existing personnel and was done regularly, but the new staff has no practical training since the reactor is not operated. Lack of financial support influenced strongly the status of RA reactor. [Serbo-Croat] U proteklom periodu reaktor RA nije bio u pogonu zato sto je 30. jula 1984. Republicki komitet za zdravlje i socijalnu politiku republike Srbije, zabranio njegov rad zbog toga sto reaktor ne poseduje sistem za udesno hladjenje i ne poseduje odgovarajuce filtere u sistemu specijalne ventilacije. Zavrseni su radovi na izgradnji sistema za udesno hladjenje, rekonstrukciji postojeceg sistema specijalne ventilacije i rekonstrukciji sistema za napajanje elektricnom energijom. Krajem 1988, medjunarodna agencija za atomsku energiju potpisala je ugovor sa sovjetskom firmom Atomergexport za izradu novog sistema instrumentacije. Sa ciljem da se poveca i efikasnije koristi prostor za skladistenje ozracenog goriva, 1987. godine zapoceta je realizacija projekata preciscavanja vode u bazenima za odlezavanje

The use of FTA cards for preserving unfixed cytological material for high-throughput molecular analysis.

Science.gov (United States)

Saieg, Mauro Ajaj; Geddie, William R; Boerner, Scott L; Liu, Ni; Tsao, Ming; Zhang, Tong; Kamel-Reid, Suzanne; da Cunha Santos, Gilda

2012-06-25

Novel high-throughput molecular technologies have made the collection and storage of cells and small tissue specimens a critical issue. The FTA card provides an alternative to cryopreservation for biobanking fresh unfixed cells. The current study compared the quality and integrity of the DNA obtained from 2 types of FTA cards (Classic and Elute) using 2 different extraction protocols ("Classic" and "Elute") and assessed the feasibility of performing multiplex mutational screening using fine-needle aspiration (FNA) biopsy samples. Residual material from 42 FNA biopsies was collected in the cards (21 Classic and 21 Elute cards). DNA was extracted using the Classic protocol for Classic cards and both protocols for Elute cards. Polymerase chain reaction for p53 (1.5 kilobase) and CARD11 (500 base pair) was performed to assess DNA integrity. Successful p53 amplification was achieved in 95.2% of the samples from the Classic cards and in 80.9% of the samples from the Elute cards using the Classic protocol and 28.5% using the Elute protocol (P = .001). All samples (both cards) could be amplified for CARD11. There was no significant difference in the DNA concentration or 260/280 purity ratio when the 2 types of cards were compared. Five samples were also successfully analyzed by multiplex MassARRAY spectrometry, with a mutation in KRAS found in 1 case. High molecular weight DNA was extracted from the cards in sufficient amounts and quality to perform high-throughput multiplex mutation assays. The results of the current study also suggest that FTA Classic cards preserve better DNA integrity for molecular applications compared with the FTA Elute cards. Copyright © 2012 American Cancer Society.

RA research nuclear reactor - Annual report 1985; Istrazivacki nuklearni reaktor RA - Izvestaj za 1985. godinu

Energy Technology Data Exchange (ETDEWEB)

NONE

1985-12-01

Research reactor RA Annual report for year 1985 is divided into two main parts to cover: (1) operation and maintenance and (2) activities related to radiation protection. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1985 godinu sastoji se od dva dela: prvi deo obuhvata pogon i odzavanje reaktora RA, a drugi poslove zastite od zracenja na reaktoru RA.

A potent and selective p38 inhibitor protects against bone damage in murine collagen-induced arthritis : a comparison with neutralization of mouse TNF alpha

NARCIS (Netherlands)

Mihara, K.; Almansa, C.; Smeets, R. L.; Loomans, E. E. M. G.; Dulos, J.; Vink, P. M. F.; Rooseboom, M.; Kreutzer, H.; Cavalcanti, F.; Boots, A. M.; Nelissen, R. L.

Background and purpose: The p38 kinase regulates the release of proinflammatory cytokines including tumour-necrosis factor-alpha (TNF alpha) and is regarded as a potential therapeutic target in rheumatoid arthritis (RA). Using the novel p38 inhibitor Org 48762-0, we investigated the therapeutic

Anti-TNF-α Activity of Brazilian Medicinal Plants and Compounds from Ouratea semiserrata.

Science.gov (United States)

Campana, Priscilla R V; Mansur, Daniel S; Gusman, Grasielle S; Ferreira, Daneel; Teixeira, Mauro M; Braga, Fernão C

2015-10-01

Several plant species are used in Brazil to treat inflammatory diseases and associated conditions. TNF-α plays a pivotal role on inflammation, and several plant extracts have been assayed against this target, both in vitro and in vivo. The effect of 11 Brazilian medicinal plants on TNF-α release by LPS-activated THP-1 cells was evaluated. The plant materials were percolated with different solvents to afford 15 crude extracts, whose effect on TNF-α release was determined by ELISA. Among the evaluated extracts, only Jacaranda caroba (Bignoniaceae) presented strong toxicity to THP-1 cells. Considering the 14 non-toxic extracts, TNF-α release was significantly reduced by seven of them (inhibition > 80%), originating from six plants, namely Cuphea carthagenensis (Lythraceae), Echinodorus grandiflorus (Alismataceae), Mansoa hirsuta (Bignoniaceae), Ouratea semiserrata (Ochnaceae), Ouratea spectabilis and Remijia ferruginea (Rubiaceae). The ethanol extract from O. semiserrata leaves was fractionated over Sephadex LH-20 and RP-HPLC to give three compounds previously reported for the species, along with agathisflavone and epicatechin, here described for the first time in the plant. Epicatechin and lanceoloside A elicited significant inhibition of TNF-α release, indicating that they may account for the effect produced by O. semiserrata crude extract. Copyright © 2015 John Wiley & Sons, Ltd.

226Ra and 228Ra in scale and sludge samples and their correlation with the chemical composition.

Science.gov (United States)

Godoy, José Marcus; da Cruz, Rosana Petinatti

2003-01-01

In order to contribute to a future waste management policy related to the presence of technologically enhanced natural occurring radioactive material (TENORM) in the Brazilian petroleum industry, the present work presents the chemical composition and the (226)Ra and (228)Ra content of sludge and scales generated during the offshore E and P petroleum activities in the Campos Basin, the primary offshore oil production region in Brazil. The (226)Ra and (228)Ra content on 36 sludge and scales samples were determined by gamma-spectrometry. Based on X-ray diffractometry results, a chemical analysis schema for these samples was developed. The results have shown that scales are 75% barium and strontium sulfates, with a mean (226)Ra and (228)Ra content of 106 kBq kg(-1) and 78 kBq kg(-1), respectively. On the other hand, sludge samples have a much more complex chemical composition than the scales. The (226)Ra and (228)Ra content in sludge also varies much more than the content observed in the scales samples and ranged from 0.36 to 367 kBq kg(-1) and 0.25 to 343 kBq kg(-1), respectively.

RENEWAL OF SWISS LEGITIMATION CARDS

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Division des Ressources Humaines; Human Resources Division; Tel. 79494-74683

2000-01-01

Members of the personnel, holders of SWISS LEGITIMATION CARDS due to expire during the year 2000, need to change them. Those concerned should bring: - a recent passport photo (with NAME and first name on the back) - the expired (or due to expire) card and a recto-verso photocopy on A4 size paper (for certified authentication) to: Bureau des cartes, bldg 33.1-009/1-011. HR Division will notify members of personnel as soon as the new cards are available.Be careful: if you are in possession of expired cards (Swiss or French), or if you present non-certified copies, the Organisation will not take any responsibility in case of difficulties with the customs authorities or the police.

NLRX1 Acts as an Epithelial-Intrinsic Tumor Suppressor through the Modulation of TNF-Mediated Proliferation

Directory of Open Access Journals (Sweden)

Ivan Tattoli

2016-03-01

Full Text Available The mitochondrial Nod-like receptor protein NLRX1 protects against colorectal tumorigenesis through mechanisms that remain unclear. Using mice with an intestinal epithelial cells (IEC-specific deletion of Nlrx1, we find that NLRX1 provides an IEC-intrinsic protection against colitis-associated carcinogenesis in the colon. These Nlrx1 mutant mice have increased expression of Tnf, Egf, and Tgfb1, three factors essential for wound healing, as well as increased epithelial proliferation during the epithelial regeneration phase following injury triggered by dextran sodium sulfate. In primary intestinal organoids lacking Nlrx1, stimulation with TNF resulted in exacerbated proliferation and expression of the intestinal stem cell markers Olfm4 and Myb. This hyper-proliferation response was associated with increased activation of Akt and NF-κB pathways in response to TNF stimulation. Together, these results identify NLRX1 as a suppressor of colonic tumorigenesis that acts by controlling epithelial proliferation in the intestine during the regeneration phase following mucosal injury.

Do mechanical strain and TNF-α interact to amplify pro-inflammatory cytokine production in human annulus fibrosus cells?

Science.gov (United States)

Likhitpanichkul, Morakot; Torre, Olivia M; Gruen, Jadry; Walter, Benjamin A; Hecht, Andrew C; Iatridis, James C

2016-05-03

During intervertebral disc (IVD) injury and degeneration, annulus fibrosus (AF) cells experience large mechanical strains in a pro-inflammatory milieu. We hypothesized that TNF-α, an initiator of IVD inflammation, modifies AF cell mechanobiology via cytoskeletal changes, and interacts with mechanical strain to enhance pro-inflammatory cytokine production. Human AF cells (N=5, Thompson grades 2-4) were stretched uniaxially on collagen-I coated chambers to 0%, 5% (physiological) or 15% (pathologic) strains at 0.5Hz for 24h under hypoxic conditions with or without TNF-α (10ng/mL). AF cells were treated with anti-TNF-α and anti-IL-6. ELISA assessed IL-1β, IL-6, and IL-8 production and immunocytochemistry measured F-actin, vinculin and α-tubulin in AF cells. TNF-α significantly increased AF cell pro-inflammatory cytokine production compared to basal conditions (IL-1β:2.0±1.4-84.0±77.3, IL-6:10.6±9.9-280.9±214.1, IL-8:23.9±26.0-5125.1±4170.8pg/ml for basal and TNF-α treatment, respectively) as expected, but mechanical strain did not. Pathologic strain in combination with TNF-α increased IL-1β, and IL-8 but not IL-6 production of AF cells. TNF-α treatment altered F-actin and α-tubulin in AF cells, suggestive of altered cytoskeletal stiffness. Anti-TNF-α (infliximab) significantly inhibited pro-inflammatory cytokine production while anti-IL-6 (atlizumab) did not. In conclusion, TNF-α altered AF cell mechanobiology with cytoskeletal remodeling that potentially sensitized AF cells to mechanical strain and increased TNF-α-induced pro-inflammatory cytokine production. Results suggest an interaction between TNF-α and mechanical strain and future mechanistic studies are required to validate these observations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fine structures in 14C emission of 223Ra and 224Ra

International Nuclear Information System (INIS)

Hourani, E.; Rosier, L.; Berrier-Ronsin, G.; Elayi, A.; Mueller, A.C.; Rappenecker, G.; Rotbard, G.; Renou, G.; Liebe, A.; Stab, L.

1991-01-01

The measurement of the energy spectrum of 14 C nuclei emitted in the spontaneous radioactivity from 223 Ra and 224 Ra has been carried out, using thin and intense sources (480 MBq for 223 Ra and 3550 MBq for 224 Ra). The sources were obtained by implanting mass-separated beams from ISOLDE (CERN) into Al and vitreous C catchers. The measurement was performed with the supraconducting solenoidal spectrometer SOLENO installed at Orsay. The discovery, of a fine structure in the energy spectrum of 14 C emission from 223 Ra, which is analogous to the one known for α emission, is confirmed. Only 13% of the branching ratio in 14 C decay leads to the ground state of the residual nucleus, while 8l% to the first excited state. For 14 C emission of 224 Ra, a lower limit of 2 for the hindrance factor has been measured for the transition to the first excited state in the residual nucleus. Also, a precise identification in Z with a E·ΔE telescope has been performed for the radiation from the 223 Ra source. (author) 22 refs., 11 figs., 1 tab

Experimental transmission of AA amyloidosis by injecting the AA amyloid protein into interleukin-1 receptor antagonist knockout (IL-1raKO) mice.

Science.gov (United States)

Watanabe, K; Uchida, K; Chambers, J K; Tei, M; Shoji, A; Ushio, N; Nakayama, H

2015-05-01

The incidence of AA amyloidosis is high in humans with rheumatoid arthritis and several animal species, including cats and cattle with prolonged inflammation. AA amyloidosis can be experimentally induced in mice using severe inflammatory stimuli and a coinjection of AA amyloid; however, difficulties have been associated with transmitting AA amyloidosis to a different animal species, and this has been attributed to the "species barrier." The interleukin-1 receptor antagonist knockout (IL-1raKO) mouse, a rodent model of human rheumatoid arthritis, has been used in the transmission of AA amyloid. When IL-1raKO and BALB/c mice were intraperitoneally injected with mouse AA amyloid together with a subcutaneous pretreatment of 2% AgNO3, all mice from both strains that were injected with crude or purified murine AA amyloid developed AA amyloidosis. However, the amyloid index, which was determined by the intensity of AA amyloid deposition, was significantly higher in IL-1raKO mice than in BALB/c mice. When IL-1raKO and BALB/c mice were injected with crude or purified bovine AA amyloid together with the pretreatment, 83% (5/6 cases) and 38% (3/8 cases) of IL-1raKO mice and 17% (1/6 cases) and 0% (0/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. Similarly, when IL-1raKO and BALB/c mice were injected with crude or purified feline AA amyloid, 33% (2/6 cases) and 88% (7/8 cases) of IL-1raKO mice and 0% (0/6 cases) and 29% (2/6 cases) of BALB/c mice, respectively, developed AA amyloidosis. These results indicated that IL-1raKO mice are a useful animal model for investigating AA amyloidogenesis. © The Author(s) 2014.

Playing the Smart Card.

Science.gov (United States)

Zuzack, Christine A.

1997-01-01

Enhanced magnetic strip cards and "smart cards" offer varied service options to college students. Enhanced magnetic strip cards serve as cash cards and provide access to services. Smart cards, which resemble credit cards but contain a microchip, can be used as phone cards, bus passes, library cards, admission tickets, point-of-sale debit…

Migration of 226 Ra, 228 Ra, 210 Pb, U and Th from phosphogypsum

International Nuclear Information System (INIS)

Silva, Nivaldo Carlos da; Cipriani, Moacir; Taddei, Maria Helena T.

2002-01-01

The physico-chemical availability of radioactive elements ( 210 Pb, 226 Ra, 228 Ra, Th and U) in Brazilian phosphogypsum was investigated in a large scale leaching experiment carried out in lysimeters, using phosphogypsum samples (approximately 1.2 tons) from two phosphoric acid industries. Lysimeters were built using cylindrical concrete containers with 0.9 m inner diameter and 2 m depth. The bottom of the lysimeter was filled with a 10 cm layer of gravel covered with geomembrane sheet. Under this layer a pipe was designed to drain the percolated water. Three lysimeters were filled with phosphogypsum from each industry and a mixture of both. As percolated water comes exclusively from the rain, sample was collected daily when available. Samples were then pooled weekly, carefully prepared and submitted to radiochemical analysis. Radiochemical characterization of phosphogypsum and percolated water was performed by radiochemical separation followed by gross alpha and beta counting ( 226 Ra, 228 Ra and 210 Pb) and UV-Vis spectrophotometry with Arsenazo III (U and Th). This experiment was carried out from 12/01/1999 to 01/22/2001, with a precipitation of 2,732 mm. It was observed that approximately 40% (534 L) of the rain fall percolated through the lysimeter 1. The analysis of 22 samples of percolated water from lysimeter 1 showed mean radionuclides activities of 70±30 mBqL -1 , 70±50 mBqL -1 , 100±60 mBqL -1 and 110±55 mBqL -1 for U, 226 Ra, 228 Ra and 210 Pb, respectively. Thorium activities were below detection limit. (author)

IL-1RA gene-transfected bone marrow-derived mesenchymal stem cells in APA microcapsules could alleviate rheumatoid arthritis.

Science.gov (United States)

Hu, Jianhua; Li, Hongjian; Chi, Guanhao; Yang, Zhao; Zhao, Yi; Liu, Wei; Zhang, Chao

2015-01-01

In order to investigate the encapsulation of interleukin 1 receptor antagonist (IL-RA) gene-modified mesenchymal stem cells (MSCs) in alginate-poly-L-lysine (APA) microcapsules for the persistent delivery of interleukin 1 receptor antagonist (IL-RA) to treat Rheumatoid arthritis (RA). We transfect mesenchymal stem cells with IL-RA gene, and quantify the IL-RA proteins released from the encapsulated cells followed by microencapsulation of recombinant mesenchymal stem cells, and thus observe the permeability of APA microcapsules and evaluate clinical effects after induction and treatment of collagen-induced arthritis (CIA). The concentration of IL-RA in the supernatant was determined by IL-RA ELISA kit by run in technical triplicates using samples from three separate mice. Encapsulated IL-RA gene-transfected cells were capable of constitutive delivery of IL-RA proteins for at least 30 days. Moreover, the APA microcapsules could inhibit the permeation of fluorescein isothiocyanate-conjuncted immunoglobulin G. Also, it has been found that the APA microcapsules can significantly attenuate collagen induced arthritis after delivering of APA microcapsules to rats. Our results demonstrated that the nonautologous IL-RA gene-transfected stem cells are of potential utility for RA therapy.

Effectiveness and safety of tofacitinib in rheumatoid arthritis: a cohort study.

Science.gov (United States)

Machado, Marina Amaral de Ávila; Moura, Cristiano Soares de; Guerra, Steve Ferreira; Curtis, Jeffrey R; Abrahamowicz, Michal; Bernatsky, Sasha

2018-03-23

Tofacitinib is the first oral Janus kinase inhibitor approved for the treatment of rheumatoid arthritis (RA). We compared the effectiveness and safety of tofacitinib, disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor inhibitors (TNFi), and non-TNF biologics in patients with RA previously treated with methotrexate. We used MarketScan® databases (2011-2014) to study methotrexate-exposed patients with RA who were newly prescribed tofacitinib, DMARDs other than methotrexate, and biologics. The date of first prescription was defined as the cohort entry. The therapy was considered effective if all of the following criteria from a claims-based algorithm were achieved at the first year of follow-up: high adherence, no biologic or tofacitinib switch or addition, no DMARD switch or addition, no increase in dose or frequency of index drug, no more than one glucocorticoid joint injection, and no new/increased oral glucocorticoid dose. The safety outcome was serious infections requiring hospitalization. Non-TNF biologics comprised the reference group. We included 21,832 patients with RA, including 0.8% treated with tofacitinib, 24.7% treated with other DMARDs, 61.2% who had started therapy with TNFi, and 13.3% treated with non-TNF biologics. The rates of therapy effectiveness were 15.4% for tofacitinib, 11.1% for DMARDs, 18.6% for TNFi, and 19.8% for non-TNF biologics. In adjusted analyses, tofacitinib and non-TNF biologics appeared to have similar effectiveness rates, whereas DMARD initiators were less effective than non-TNF biologics. We could not clearly establish if tofacitinib was associated with a higher rate of serious infections. In patients with RA previously treated with methotrexate, our comparisons of tofacitinib with non-TNF biologics, though not definitive, did not demonstrate differences with respect to hospitalized infections or effectiveness.

Assessment of 226Ra, 228Ra and 40K contents in the Egyptian bottled natural water

International Nuclear Information System (INIS)

El-Afifi, E.M.; Hilal, M.A.; Khalifa, S.M.; Aly, H.F.

2004-01-01

The activity concentrations of 2 26Ra, 2 28Ra and 4 0 and k in different brands of the bottled egyptian natural water of different origins obtained from four regions, have been analyzed nondestructively by gamma- ray spectrometry. The study covers nine brands of natural water commonly used mainly for drinking in egypt. The results showed, concentrations up to 184, 156 and 1700 mBq I - 1 for 2 26Ra, 2 28Ra and 4 0K, respectively, in one brand of the natural water from water from Siwa oasis. Whereas, lower activity concentrations of 2 26Ra and 2 28Ra were found in one brand of these natural waters from El sadat region. The activity concentration of 4 0K was found to be in the background range in the brands from El sadat, kafr El arbein and beilbeis regions. The committed effective doses reached 1.9 x 10 - 2 m Sy Y - 1 for ingestion of 2 26Ra and 2 28Ra for one liter per day, respectively, which are lower than the standard permissible limit by the WHO and IAEA. However, it is recommended to moderate drinking of bottled natural water to avoid the accumulation effect of radioactive nuclides especially radium

26 CFR 301.6103(k)(9)-1 - Disclosure of returns and return information relating to payment of tax by credit card and debit...

Science.gov (United States)

2010-04-01

... relating to payment of tax by credit card and debit card. 301.6103(k)(9)-1 Section 301.6103(k)(9)-1... Disclosure of returns and return information relating to payment of tax by credit card and debit card... processing credit card and debit card transactions to effectuate payment of tax as authorized by § 301.6311-2...

Argentina: Disposal aspects of RA-1 research reactor decommissioning waste

Energy Technology Data Exchange (ETDEWEB)

Harriague, S; Barberis, C; Cinat, E; Grizutti, C; Scolari, H [Comision Nacional de Energia Atomica, Buenos Aires (Argentina)

2007-12-15

The objective of the project is to analyze disposal aspects of waste from total dismantling of Argentinean research reactors, starting with the oldest one, 48 years old RA-1. In order to estimate decommissioning waste, data was collected from files, area monitoring, measurements, sampling to measure activity and composition, operational history and tracing of operational incidents. Measurements were complemented with neutron activation calculations. Decommissioning waste for RA-1 is estimated to be 71.5 metric tons, most of it concrete (57 tons), the rest being steels, lead and reflector graphite (4.8 tons). Due to their low specific activities, no disposal problems are foreseen in the case of metals and concrete. Disposal of aluminium, steel, lead and concrete is analyzed. On the contrary, as the country has no experience in managing graphite radioactive waste, work was concentrated on that material. Stored (Wigner) energy may exist in RA-1 graphite reflectors irradiated at room temperature. Evaluation of stored energy by calorimetric methods is proposed, and its annealing by inductive heating; HEPA filters should be used to deal with gaseous activity emissions, mainly Cl-36 and C-14. Galvanic corrosion, dust explosion, ignition and oxidation can be addressed and should not become disposal problems. Care must be taken with graphite dust generation and disposal, due to wetting and flotation problems. Lessons learned from the project are presented, and the benefits of sharing international experience are stressed. (author)

[Cytokines and malaria. A study of TNF-alpha, IL1-beta, IL6 and IL2R in 28 patients].

Science.gov (United States)

Nicolas, P; Hovette, P; Merouze, F; Touze, J E; Martet, G

1994-01-01

Authors have studied TNF alpha, IL1 bêta, IL6 and RIL2s in 28 malaria illness patients. Increased levels of TNF, IL1 bêta and RIL2s in serum, are observed on admission to hospital. These cytokine levels are decreased, eight days later, after patients are treated. In discussion, TNF levels as a prognosis component is evocated.

Determination of 226Ra and 228Ra in gypsum

International Nuclear Information System (INIS)

Godoy, J.M.

1989-01-01

The content of 226 Ra and 228 Ra in different samples of phosphogypsum and three samples of gypsite were determined by gamma spectroscopy. For 226 Ra the 295, 352 and 609 KeV lines and for 228 Ra the 911 and 969 KeV lines were used. The specific activities values ranged from 0.36 to 22.8 pCi/g for 226 Ra and 0.90 to 10.3 pCi/g for 228 Ra. The contribution of a sypsum roof-covering to the 222 Rn concentration in a room was estimated, based on the highest value reported. (author) [pt

RENEWAL OF SWISS LEGITIMATION CARDS

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Division des Ressources Humaines; Human Resources Division; Tel. 79494-74683

2000-01-01

Members of the personnel, holders of SWISS LEGITIMATION CARDS due to expire during the year 2000, need to change them. Those concerned should bring : a recent passport photo (with NAME and first name on the back) the expired (or due to expire) card and a recto-verso photocopy on A4 size paper (for certified authentication)to: Bureau des cartes, Bât 33.1-009/1-011. Members of personnel will be notified by HR Division as soon as the new cards are available. Be careful: if you are in possession of expired cards (Swiss or French), or if you present non-certified copies, the Organization will not take any responsibility in case of difficulties with the customs authorities or the police.

RENEWAL OF SWISS LEGITIMATION CARDS

CERN Multimedia

Human Resources Division; Human Resources Division; Tel. 79494-74683

2000-01-01

Members of the personnel, holders of SWISS LEGITIMATION CARDS due to expire during the year 2000, need to change them. Those concerned should bring: ­ a recent passport photo (with NAME and first name on the back) ­ the expired (or due to expire) card and a recto-verso photocopy on A4 size paper (for certified authentication) to: Bureau des cartes, Bât 33.1-009/1-011 Members of the personnel will be notified by HR Division as soon as the new cards are available. Be careful: if you are in possession of expired cards (Swiss or French), or if you present non-certified copies, the Organization will not take any responsability in case of difficulties with the customs authorities or the police.

RENEWAL OF SWISS LEGITIMATION CARDS

CERN Multimedia

Division des Ressources Humaines; Human Resources Division; Tel. 79494-74683

2000-01-01

Members of the personnel, holders of SWISS LEGITIMATION CARDS due to expire during the year 2000, need to change them. Those concerned should bring : - a recent passport photo (with NAME and first name on the back) - the expired (or due to expire) card and a recto-verso photocopy on A4 size paper (for certified authentication) to: Bureau des cartes, bât 33.1-009/1-011. HR Division will notify members of personnel as soon as the new cards are available. Be careful: if you are in possession of expired cards (Swiss or French), or if you present non-certified copies, the Organization will not take any responsibility in case of difficulties with the customs authorities or the police.

Laminated dosimetric card

International Nuclear Information System (INIS)

Cox, F.M.; Chamberlain, J.D.; Shrader, E.F.; Shoffner, B.M.; Szalanczy, A.

1975-01-01

A laminated card with one or more apertures, each adapted to peripherally seal an encapsulated dosimeter, is formed by bonding a foraminous, code-adaptable, rigid sheet of low-Z material with a codedly transparent sheet of low-Z material in light-transmitting registry with particular code-holes of the rigid sheet. The laminated card may be coded to identify the person carrying it, and/or the location or circumstances related to its exposure to radiation. This card is particularly adapted for use in an instrument capable of evaluating a multiplicity of cards, substantially continuously. The coded identification from the card may be displayed by an appropriate machine, and if desired an evaluation may be recorded because of a ''parity checking'' system incorporated in each card, which permits ''auto-correction.'' Alternatively, where means for effecting the correction automatically are available, the operation of the machine may be interrupted to permit visual examination of a rejected card. The card of this invention is also coded for identifying the type of card with respect to its specific function, and whether or not a card is correctly positioned at any predetermined location during its sequential progress through the instrument in which it is evaluated. Dosimeters are evaluated and the card identified in one pass through the instrument. (auth)

Determination of natural radionuclides, U, Th-232, Ra-226, Ra-228, Pb-210 and K-40 in sediments from CananÉIa-Iguape System, Brazil

International Nuclear Information System (INIS)

Jesus, Gleyka J.D.; Chiozzini, Vitor G.; Saueia, Cátia H.R.; Nisti, Marcelo B.; Braga, Elisabete S.; Fávaro, Deborah I.T.; Universidade de São Paulo

2017-01-01

The Cananéia-Iguape estuarine-lagoon complex, located in the south of São Paulo State, Brazil, is a protected area recognized by UNESCO as part of the Biosphere Reserve, due to its importance as a natural ecosystem. However, along the years, the mining activities in the region affected the river basin, to such an extent that contamination was observed for As, Cu, Pb and Zn. Since the mining activities can also enhance the levels of natural radioactivity in the sediments, this study aimed to determine the activity concentration of the natural radionuclides (K-40, U, Ra-226, Pb-210, Th-232 and Ra-228) in 34 bottom sediments samples collected in the Cananéia-Iguape system. The samples were measured by gamma spectrometry, using a HPGe for the determination of K-40, Ra-226, Pb-210 and Ra-228. The concentration of U and Th-232 was determined by instrumental neutron activation analysis. The activity concentration of K-40 varied from 119 ± 17 to 522 ± 74 Bq kg"-"1; U-238 varied from 0.31 ± 0.05 to 5.8 ± 0.3 mg kg"-"1; Ra-226 varied from 3.7 ± 0.3 to 43.3 ± 1.5 Bq kg"-"1; Pb-210 varied from 5.8 ± 2.6 to 118 ± 12 Bq kg"-"1; Th-232 varied from 0.67 ± 0.02 to 16.6 ± 0.4 mg kg"-"1 and Ra-228 varied from 3.5 ± 0.6 to 64.9 ± 2.4 Bq kg"-"1. These results were compared with literature values for the region, indicating that they are the background of the region and no contamination was observed from NORM (Naturally Occurring Radioactive Material) industries. (author)

Determination of natural radionuclides, U, Th-232, Ra-226, Ra-228, Pb-210 and K-40 in sediments from CananÉIa-Iguape System, Brazil

Energy Technology Data Exchange (ETDEWEB)

Jesus, Gleyka J.D.; Chiozzini, Vitor G.; Saueia, Cátia H.R.; Nisti, Marcelo B.; Braga, Elisabete S.; Fávaro, Deborah I.T., E-mail: gjdjesus@ipen.br, E-mail: chsaueia@ipen.br, E-mail: mbnisti@ipen.br, E-mail: defavaro@ipen.br, E-mail: vitor.chio@usp.br, E-mail: edsbraga@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil); Universidade de São Paulo (USP), SP (Brazil). Instituto Oceanográfico

2017-07-01

The Cananéia-Iguape estuarine-lagoon complex, located in the south of São Paulo State, Brazil, is a protected area recognized by UNESCO as part of the Biosphere Reserve, due to its importance as a natural ecosystem. However, along the years, the mining activities in the region affected the river basin, to such an extent that contamination was observed for As, Cu, Pb and Zn. Since the mining activities can also enhance the levels of natural radioactivity in the sediments, this study aimed to determine the activity concentration of the natural radionuclides (K-40, U, Ra-226, Pb-210, Th-232 and Ra-228) in 34 bottom sediments samples collected in the Cananéia-Iguape system. The samples were measured by gamma spectrometry, using a HPGe for the determination of K-40, Ra-226, Pb-210 and Ra-228. The concentration of U and Th-232 was determined by instrumental neutron activation analysis. The activity concentration of K-40 varied from 119 ± 17 to 522 ± 74 Bq kg{sup -1}; U-238 varied from 0.31 ± 0.05 to 5.8 ± 0.3 mg kg{sup -1}; Ra-226 varied from 3.7 ± 0.3 to 43.3 ± 1.5 Bq kg{sup -1}; Pb-210 varied from 5.8 ± 2.6 to 118 ± 12 Bq kg{sup -1}; Th-232 varied from 0.67 ± 0.02 to 16.6 ± 0.4 mg kg{sup -1} and Ra-228 varied from 3.5 ± 0.6 to 64.9 ± 2.4 Bq kg{sup -1}. These results were compared with literature values for the region, indicating that they are the background of the region and no contamination was observed from NORM (Naturally Occurring Radioactive Material) industries. (author)

TNF-α-308 polymorphism and risk of digestive system cancers: a meta-analysis.

Science.gov (United States)

Guo, Xu-Feng; Wang, Jun; Yu, Shi-Jie; Song, Jia; Ji, Meng-Yao; Cao, Zhuo; Zhang, Ji-Xiang; Wang, Jing; Dong, Wei-Guo

2013-12-28

To evaluate the association between the tumour necrosis factor alpha-308 (TNF-α-308) gene polymorphism and the risk of digestive system cancers. All eligible case-control studies published up to December 2012 were identified by searching PubMed, Web of Science, Embase and China National Knowledge Internet without language restrictions. The risk of digestive system cancers associated with the TNF-α-308 polymorphism was estimated for each study using odds ratio (OR) together with its 95%CI, respectively. Cochrane Collaboration RevMan 5.1 was used to perform the analysis. A χ²-test-based Q statistic test and an I² test were performed to assess the between-study heterogeneity. When the Q test was significant (P 50%, the random effects model was used, otherwise the fixed effects model was used. Fifty-eight studies from fifty-five publications with a total of 9986 cancer patients and 15511 healthy controls were included. Overall, a significant association was found between the TNF-α-308 polymorphism and the risk of digestive system cancers [dominant model: OR = 1.23, 95%CI: 1.09-1.39, (G/A) vs (G/G): OR = 1.15, 95%CI: 1.02-1.28, (A/A) vs (G/G): OR = 1.44, 95%CI: 1.19-1.73, recessive model: OR = 1.38, 95%CI: 1.15-1.66]. Furthermore, when the analysis was stratified by ethnicity, similar results were observed in both the Asian and Caucasian populations, except for the dominant model and heterozygote comparisons in the Asian population [dominant model: OR = 1.24, 95%CI: 0.99-1.56, (G/A) vs (G/G): OR = 1.09, 95%CI: 0.96-1.24]. When the cancer type subgroups were examined, similar results were detected in gastric and hepatocellular carcinomas; however, no significant association was observed among other digestive system cancers. The TNF-α-308 gene polymorphism may be significantly associated with the risk of gastric and hepatocellular carcinomas, but not colorectal, pancreatic, or oesophageal cancer, in the Asian population.

[Influence of ET-1 and ETA receptor blocker (BQ123) on the level of TNF-α in the brain rat].

Science.gov (United States)

Gorąca, Anna; Skibska, Beata

2016-06-01

Endothelin 1 (ET-1) in addition to the vasoconstriction, also has mitogenic, proinflammatory and proagregation activities. The mediators of inflammatory responses are cytokines, including special role attributed to tumor necrosis factor (TNF-α). The aim of this study was to evaluate the effect of ET-1 and its receptor blocker (BQ123) on the level of TNF-α in the brain rat. Experiments were performed on four groups of Wistar-Kyoto rats. Animals were divided into four groups of 8 rats. Group I - control was administered into the tail vein solution of 0.9 % NaCl. Group II - saline followed by ET-1 (3 μg/kg b.w.). Group III - saline followed by BQ123 (1 mg/kg b.w.). Group IV (BQ123/ET-1) - BQ123 (1 mg/kg b.w.) administered 30 min before ET-1 (3 μg/kg b.w.). Administration of ET-1 at doses of 3 μg/kg b.w. resulted in a statistically significant increase in TNF-α concentrations in brain homogenates compared to the control group (pET(A) receptor blocker - BQ123 (1mg/kg b.w.) 30 min before administration of ET-1 significantly decreased in TNF-α concentrations in brain homogenates (p ET-1 is significantly increased in TNF-α levels in brain homogenates, while BQ123 given 30 min before administration of ET-1 caused a significant decrease in TNF-α levels, suggesting that its anti-inflammatory activity. © 2016 MEDPRESS.

Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

Science.gov (United States)

Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

2017-10-01

Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

RA reactor operation and maintenance in 1996, Part 1

International Nuclear Information System (INIS)

Sotic, O.; Cupac, S.; Sulem, B.; Zivotic, Z.; Mikic, N.; Tanaskovic, M.

1996-01-01

During the previous period RA reactor was not operated because the Committee of Serbian ministry for health and social care has cancelled the operation licence in August 1984. The reason was the non existing emergency cooling system and lack of appropriate filters in the special ventilation system. The planned major tasks were fulfilled: building of the new emergency cooling system, reconstruction of the existing ventilation system, and renewal of the reactor power supply system. The existing RA reactor instrumentation was dismantled. Renewal of the reactor instrumentation was started but but it is behind the schedule because the delivery of components from USSR was stopped for political reasons. Since the RA reactor is shutdown since 1984, it is high time for decision making of its future status. Possible solutions for the future status of the RA reactor discussed in this report are: renewal of reactor components for the reactor restart, conservation of the reactor (temporary shutdown) or permanent reactor shutdown. Control and maintenance of the reactor instrumentation and devices was done regularly but dependent on the availability of the spare parts and financial means. Training of the existing personnel and was done regularly, but the new staff has no practical training since the reactor is not operated. Lack of financial support influenced strongly the status of RA reactor [sr

Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia.

Science.gov (United States)

Molanouri Shamsi, M; Chekachak, S; Soudi, S; Quinn, L S; Ranjbar, K; Chenari, J; Yazdi, M H; Mahdavi, M

2017-02-01

Cancer cachexia is characterized by inflammation, loss of skeletal muscle and adipose tissue mass, and functional impairment. Oxidative stress and inflammation are believed to regulate pathways controlling skeletal muscle wasting. The aim of this study was to determine the effects of aerobic interval training and the purported antioxidant treatment, selenium nanoparticle supplementation, on expression of IL-15 and inflammatory cytokines in 4T1 breast cancer-bearing mice with cachexia. Selenium nanoparticle supplementation accelerated cachexia symptoms in tumor-bearing mice, while exercise training prevented muscle wasting in tumor-bearing mice. Also, aerobic interval training enhanced the anti-inflammatory indices IL-10/TNF-α ratio and IL-15 expression in skeletal muscle in tumor-bearing mice. However, combining exercise training and antioxidant supplementation prevented cachexia and muscle wasting and additionally decreased tumor volume in 4T1 breast cancer mice. These finding suggested that combining exercise training and antioxidant supplementation could be a strategy for managing tumor volume and preventing cachexia in breast cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

RA Research reactor, Annual report 1988; Istrazivacki nuklearni reaktor RA - Izvestaj za 1988. godinu

Energy Technology Data Exchange (ETDEWEB)

Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1988-12-15

Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1989. godinu, koji finansira republicka zajednica za nauku SR Srbije po ugovoru br. 3705/1 sastoji se iz dva dela. Prvi deo obuhvata pogon i odrzavanje nuklearnog reaktora RA, sto predstavlja obavezu Odeljenja za reaktorski inzenjering u sastavu OOUR Instituta za multidisciplinarna istrazivanja i inzenjering RA. Drugi deo obuhvata poslove zastite od zracenja na reaktoru RA, sto predstavlja obavezu OOUR Instituta za zastitu od zracenja 'Zastita'. Naucno vece Instituta za multidisciplinarna istrazivanja i inzenjering RA ocenilo je da sadrzina ovog izvestaja odgovara izvrsenim poslovima na reaktoru RA u 1989. godini. Pozitivno se ocenjuje obim i kvalitet izvrsenih radova kako u pogledu odrzavanja i rekonstrukcije reaktora, tako i u pogledu poslova zastite od zracenja izvrsenih kod njega.

Towards the development of tumor necrosis factor (TNF) sensitizers: making TNF work against cancer.

Science.gov (United States)

Mocellin, Simone; Pilati, Pierluigi; Nitti, Donato

2007-01-01

Although TNF antitumor activity has been demonstrated in many preclinical models and in non-comparative clinical trials, no evidence exists that TNF-based treatments increase patient survival. Moreover, due to systemic toxicity, TNF can only be administered through sophisticated locoregional drug-delivery systems in patients with some types of organ-confined solid tumors; as a corollary, the impossibility to administer TNF through the systemic route does not allow to test the effectiveness of this cytokine in other clinical settings for the treatment of a broader spectrum of tumor types. A challenge many researchers are tackling is to dissect the cascade of molecular events underlying tumor sensitivity to TNF so to fully explore the anticancer potential of this molecule. The rationale for the development of strategies aimed at sensitizing malignant cells to TNF is to exploit tumor-specific molecular derangements to modulate TNF biological activities and ultimately maximize its tumor-selective cytotoxicity. This would not only enhance the anticancer activity of current TNF-based locoregional regimens, but would also open the avenue to the systemic administration of this cytokine and thus to a much wider clinical experimentation of TNF in the oncology field. In this review we first summarize the molecular biology of TNF and its cancer-related properties; then, the available findings regarding some among the most promising and best characterized TNF sensitizers are overviewed.

Operators retraining in RA-1

International Nuclear Information System (INIS)

Pereira, R; Daoud, A

2012-01-01

The nuclear activity in Argentina has its foundational milestone in the creation of the Comision Nacional de EnergIa Atomica in 1950. Achievements since then, linked to the area of nuclear reactors and nuclear fuel materials, fuel cycle facilities and the applications of nuclear technology in medicine, industry, agriculture, food preservation, environmental studies and many others, have relied on personnel trained in this specific technology in both professional and technical level. This training has been done in most cases in the exclusive scope of CNEA. Eventually CNEA has been linked with the University to ensure that personnel training concerned to work done in the nuclear field had guarantees of formality and excellence. The creation of the Instituto de Tecnologia Nuclear Dan Beninson that, under an agreement with the Universidad Nacional de General San Martin, has set up an enabling environment for the training of professionals and university technicians to serve with the multiple and growing use of this technology. On the other hand the Institute has been issuing, along with its careers, specialized courses that, in some cases, have been requested by CNEA's nuclear installations and companies related to the nuclear sector. In particular, the Specialization in Nuclear Reactors and its Fuel Cycle (ERCC) and the Courses of Introduction to Nuclear Technology-Complementary training for Installations Personnel Class I (CI-CC), this last, recognized by the ARN as a requirement for applying to the individual licensing examination, providing work experience in the RA-1 reactor among which we can find commissioning, control rods calibration by various methods and calculations of reactivity. With this practical framework developed in the RA-1 and the academic support provided by the Instituto de Tecnologia Nuclear Dan Beninson it was developed a training program for nuclear reactors operators. Let us stress that this research reactor has been forming generations

RIP1 regulates TNF-α-mediated lymphangiogenesis and lymphatic metastasis in gallbladder cancer by modulating the NF-κB-VEGF-C pathway.

Science.gov (United States)

Li, Cheng-Zong; Jiang, Xiao-Jie; Lin, Bin; Hong, Hai-Jie; Zhu, Si-Yuan; Jiang, Lei; Wang, Xiao-Qian; Tang, Nan-Hong; She, Fei-Fei; Chen, Yan-Ling

2018-01-01

Tumor necrosis factor alpha (TNF-α) enhances lymphangiogenesis in gallbladder carcinoma (GBC) via activation of nuclear factor (NF-κB)-dependent vascular endothelial growth factor-C (VEGF-C). Receptor-interacting protein 1 (RIP1) is a multifunctional protein in the TNF-α signaling pathway and is highly expressed in GBC. However, whether RIP1 participates in the signaling pathway of TNF-α-mediated VEGF-C expression that enhances lymphangiogenesis in GBC remains unclear. The RIP1 protein levels in the GBC-SD and NOZ cells upon stimulation with increasing concentrations of TNF-α as indicated was examined using Western blot. Lentiviral RIP1 shRNA and siIκBα were constructed and transduced respectively them into NOZ and GBC-SD cells, and then PcDNA3.1-RIP1 vectors was transduced into siRIP1 cell lines to reverse RIP1 expression. The protein expression of RIP1, inhibitor of NF-κB alpha (IκBα), p-IκBα, TAK1, NF-κB essential modulator were examined through immunoblotting or immunoprecipitation. Moreover, VEGF-C mRNA levels were measured by quantitative real-time polymerase chain reaction, VEGF-C protein levels were measured by immunoblotting and enzyme-linked immunosorbent assay, and VEGF-C promoter and NF-κB activities were quantified using a dual luciferase reporter assay. The association of NF-κB with the VEGF-C promoter was analysed by chromatin immunoprecipitation assay. A three-dimensional coculture method and orthotopic transplantation nude mice model were used to evaluate lymphatic tube-forming and metastasis ability in GBC cells. The expression of RIP1 protein, TNF-α protein and lymphatic vessels in human GBC tissues was examined by immunohistochemistry, and the dependence between RIP1 protein with TNF-α protein and lymphatic vessel density was analysed. TNF-α dose- and time-dependently increased RIP1 protein expression in the GBC-SD and NOZ cells of GBC, and the strongest effect was observed with a concentration of 50 ng/ml. RIP1 is fundamental

TNF and TNF Receptor Superfamily Members in HIV infection: New Cellular Targets for Therapy?

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Amit Kumar

2013-01-01

Full Text Available Tumor necrosis factor (TNF and TNF receptors (TNFR superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.

RA research reactor, Part 1, Operation and maintenance of the RA nuclear reactor for 1985

International Nuclear Information System (INIS)

Sotic, O.; Martinc, R.; Cupac, S.; Sulem, B.; Badrljica, R.; Majstorovic, D.; Sanovic, V.

1985-01-01

According to the plan, RA reactor was to be in operation in mid September 1985. But, since the building of the emergency cooling system, nor the reconstruction of the existing special ventilation system were not finished until the end of August reactor was not operated during 1985. During the previous four years reactor operation was limited by the temporary operating license issued by the Committee of Serbian ministry for health and social care, which was cancelled in August 1984. The reason was the non existing emergency cooling system and lack of appropriate filters in the special ventilation system. This temporary license has limited the reactor power to 2 MW from 1981-1984. Control and maintenance of the reactor instrumentation and tools was done regularly but dependent on the availability of the spare parts. In order to enable future reliable operation of the RA reactor, according to new licensing regulations, during 1984, three major tasks have started: building of the new emergency system, reconstruction of the existing ventilation system, and renewal of the reactor instrumentation. IAEA has approved the amount of 1,300,000 US dollars for the renewal of the instrumentation [sr

Genetic polymorphisms of RANTES, IL1-A, MCP-1 and TNF-A genes in patients with prostate cancer

International Nuclear Information System (INIS)

Sáenz-López, Pablo; Carretero, Rafael; Cózar, José Manuel; Romero, José Maria; Canton, Julia; Vilchez, José Ramón; Tallada, Miguel; Garrido, Federico; Ruiz-Cabello, Francisco

2008-01-01

Inflammation has been implicated as an etiological factor in several human cancers, including prostate cancer. Allelic variants of the genes involved in inflammatory pathways are logical candidates as genetic determinants of prostate cancer risk. The purpose of this study was to investigate whether single nucleotide polymorphisms of genes that lead to increased levels of pro-inflammatory cytokines and chemokines are associated with an increased prostate cancer risk. A case-control study design was used to test the association between prostate cancer risk and the polymorphisms TNF-A-308 A/G (rs 1800629), RANTES-403 G/A (rs 2107538), IL1-A-889 C/T (rs 1800587) and MCP-1 2518 G/A (rs 1024611) in 296 patients diagnosed with prostate cancer and in 311 healthy controls from the same area. Diagnosis of prostate cancer was significantly associated with TNF-A GA + AA genotype (OR, 1.61; 95% CI, 1.09–2.64) and RANTES GA + AA genotype (OR, 1.44; 95% CI, 1.09–2.38). A alleles in TNF-A and RANTES influenced prostate cancer susceptibility and acted independently of each other in these subjects. No epistatic effect was found for the combination of different polymorphisms studied. Finally, no overall association was found between prostate cancer risk and IL1-A or MCP-1 polymorphisms. Our results and previously published findings on genes associated with innate immunity support the hypothesis that polymorphisms in proinflammatory genes may be important in prostate cancer development

RENEWAL OF SWISS LEGITIMATION CARDS

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HR Division

2001-01-01

Members of the personnel and their families, holders of SWISS LEGITIMATION CARDS due to expire during the year 2001, need to change them. Those concerned should bring : a recent passport photo (with NAME and first name on the back) the expired (or due to expire) card and a recto-verso photocopy on A4 size paper (for certified authentication) to Bureau des cartes, building 33/1-009/1-015. Members of the personnel will be notified by the Social and Statutary Conditions Group, HR Division as soon as the new cards are available. Be careful: If you are in possession of expired cards (Swiss or French), or if you present non-certified copies, the Organization will not take any responsibility in case of difficulties with the customs authorities or the police.

Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy.

Science.gov (United States)

Wright, Helen L; Bucknall, Roger C; Moots, Robert J; Edwards, Steven W

2012-03-01

Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition. SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis. RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05). Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.

糖尿病视网膜病变患者外周血 IL-1β和 TNF-α的检测及临床意义%Expression and clinical significance of serum IL-1βand TNF-αin patients with diabetic retinopathy

Institute of Scientific and Technical Information of China (English)

韩青

2016-01-01

Objective To investigate the correlation and significance of serum IL-1β and TNF-α to type 2 diabetic retinopathy(DR).Methods Three groups of type 2 diabetic retinopathy patients:no diabetic retinopathy group (control group)50 cases,pure retinopathy group (NPDR group)41 cases,proliferative retinopathy group (PDR group)37 cases and 50 healthy controls (healthy group)were recruited.The serum IL-1βand TNF-αwere compared among 4 groups. Results The serum IL-1βand TNF-αin PDR group[(39.36±6.60)pg/ml and (86.38±11.05)pg/ml,respectively] were significantly higher than those in NPDR group [(27.48±5.05)pg/ml and (63.29±7.55)pg/ml,respectively,P<0.01].The serum IL-1βand TNF-αin NPDR group were significantly higher than those in control group [(12.63± 2.54)pg/ml and (39.97±11.61)pg/ml,respectively,P <0.01].The serum IL-1β and TNF-α in control group were significantly higher than those in healthy group [(7.41 ±0.85)pg/ml and (17.72 ± 6.39)pg/ml,respectively,P <0.01].There was a positive correlation of serum IL-1βto TNF-α(r=0.795,P <0.01).Serum IL-1βand TNF-αlevels positively correlated with body mass index and course of disease(r = 0.325,0.635,P < 0.01;r = 0.384,0.586,P <0.01).Conclusion The levels of serum IL-1βand TNF-αare increased in type 2 diabetic retinopathy,and can increase with the severity of disease.Combined detection of IL-1β and TNF-α can help estimate the severity and prognosis of type 2 diabetic retinopathy.%目的：比较不同糖尿病视网膜病变分期患者及健康对照者外周血 IL-1β和 TNF-α的含量，并探讨其与糖尿病视网膜病变之间的关系。方法选取2013年9月至2015年9月于我院就诊的2型糖尿病患者，其中无视网膜病变组（对照组）50例、非增殖性视网膜病变组（NPDR 组）41例，增殖性视网膜病变患者（PDR 组）37例，并选择50例健康对照，用 ELISA 法检测四组患者血清中 IL-1β和 TNF-α的含量，并进行相关性分析。结果PDR �

Improved experimental limit on the EDM of 225Ra

Science.gov (United States)

Bishof, Michael; Bailey, Kevin; Dietrich, Matthew R.; Greene, John P.; Holt, Roy J.; Kalita, Mukut R.; Korsch, Wolfgang; Lemke, Nathan D.; Lu, Zheng-Tian; Mueller, Peter; O'Connor, Tom P.; Parker, Richard H.; Rabga, Tenzin; Singh, Jaideep T.

2015-10-01

Searches for permanent electric dipole moments (EDMs) in fundamental and composite particles are sensitive probes of beyond-standard-model symmetry violation that could explain the dominance of matter over anti-matter. The 225Ra (t1/2 = 15d, I = 1/2) atom is a particularly attractive system to use for an EDM measurement because its large nuclear octupole deformation, closely spaced ground-state parity doublet, and large atomic mass make 225Ra uniquely sensitive to symmetry-violating interactions in the nuclear medium. We have developed an experiment to measure the EDM of 225Ra and demonstrated the first ``proof-of-principle'' measurement, giving a 95% confidence upper limit of 5E-22 e-cm. After implementing a vacuum upgrade, we have observed nuclear spin coherence after 20 s of free evolution - a factor of ten improvement over our earlier results - and have lowered the 225Ra EDM limit by over an order of magnitude. Upcoming experimental upgrades have the potential to further improve our EDM sensitivity by many orders of magnitude, allowing us to test symmetry violation at an unprecedented level. This work is supported by U.S. DOE, Office of Science, Office of Nuclear Physics, under Contract DE-AC02-06CH11357.

Data of evolutionary structure change: 1ONAD-2D3RA [Confc[Archive

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Full Text Available 1ONAD-2D3RA 1ONA 2D3R D A ADTIVAVELDTYPNTDIGDPSYPHIGIDIKSVRSKKTAK...WNMQNGKVGTAHIIYNSVDKRLSAVVSYPNADSATVSYDVDLDNVLPEWVRVGLSASTGLYKETNTILSWSFTSKLKT------NALHFMFNQFSKDQKDLILQGDAT...ID>1ONA D 1ONAD TRVSSNGSPQG <

RA reactor operation in 1991, Part 1; Deo 1 - Pogon i odrzavanje nuklearnog reaktora RA u 1991. godini

Energy Technology Data Exchange (ETDEWEB)

Sotic, O; Cupac, S; Sulem, B; Zivotic, Z; Majstorovic, D; Sanovic, V [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1992-01-01

During the previous period RA reactor was not operated because the Committee of Serbian ministry for health and social care has cancelled the operation licence in August 1984. The reason was the non existing emergency cooling system and lack of appropriate filters in the special ventilation system. Control and maintenance of the reactor instrumentation and tools was done regularly but dependent on the availability of the spare parts. In order to enable future reliable operation of the RA reactor, according to new licensing regulations, during 1991, three major tasks were fulfilled: building of the new emergency cooling system, reconstruction of the existing ventilation system, and renewal of the reactor power supply system. Renewal of the reactor instrumentation was started but but it is behind the schedule in 1991 because the delivery of components from USSR is late. Production of this instruments is financed by the IAEA according to the contract signed in December 1988 with Russian Atomenergoexport. According to this contract, it has been planned that the RA reactor instrumentation should be delivered to the Vinca Institute by the end of 1990. Since then any delivery of components to Yugoslavia was stopped because of the temporary embargo imposed by the IAEA for political reasons. In 1991 most of the existing RA reactor instrumentation was dismantled, only the part needed for basic measurements when reactor is not operated, was maintained. Training of the existing personnel was done regularly, but lack of financial support prevented employment of new workers that would be needed for operation in shifts and regular maintenance. [Serbo-Croat] U proteklom periodu reaktor RA nije bio u pogonu zato sto je 30. jula Republicki komitet za zdravlje i socijalnu politiku republike Srbije, zabranio njegov rad zbog toga sto reaktor ne poseduje sistem za udesno hladjenje i ne poseduje odgovarajuce filtere u sistemu specijalne ventilacije. Kako bi se ubuduce mogao obezbediti

Fasting induces IL-1 resistance and free fatty acid-mediated up-regulation of IL-1R2 and IL-1RA

Directory of Open Access Journals (Sweden)

jenifer j joesting

2014-07-01

Full Text Available Objective: Weight loss is a near societal obsession and many diet programs use significant calorie restriction (CR including fasting/short term starvation to generate rapid effects. Fasting is also a well-recognized cause of immunosuppression especially within the innate immune system. In this study, we sought to determine if the IL-1 arm of the neuroimmune system was down-regulated by a 24 hr fast and how fasting might generate this effect. Design: Mice were allowed ad libitum access to food or had food withheld for 24 hrs. Expression of the endogenous IL-1 antagonists IL-1 receptor type 2 (IL-1R2 and IL-1 receptor antagonist (IL-1RA were determined as were sickness behaviors before and after IL-1 administration.Results: Fasting markedly increased gene expression of IL-1R2 (83-fold in adipose tissue, 9.5-fold in liver and IL-1RA (68-fold in liver. Fasted mice were protected from IL-1-induced weight loss, hypoglycemia, loss of locomotor and social anxiety. These protections were coupled to a large positive interaction of fasting and IL-1 on IL-1R2 gene expression in adipose tissue and liver (2.6-fold and 1.6-fold, respectively. Fasting not only increased IL-1RA and IL-1R2 protein 2.5-fold and 3.2-fold, respectively, in liver; but also increased IL-1R2 1.8-fold in adipose tissue. Fasting, in turn, triggered a 2.4-fold increase in plasma free-fatty acids (FFAs and a 2.1-fold increase in plasma corticosterone. Inhibition, of glucocorticoid action with mifepristone did not impact fasting-dependent IL-1R2 or IL-1RA gene expression. Administration of the FFA, palmitate, to mice increased liver IL-1R2 and IL-1RA gene expression by 14-fold and 11-fold, respectively. Conclusion: These findings indicate that fasting augments expression of endogenous IL-1 antagonists inducing IL-1 resistance. Fasting-induced increases in plasma FFAs appears to be a signal that drives immunosuppression during fasting/short term starvation.

Crucial factors of the inflammatory microenvironment (IL-1β/TNF-α/TIMP-1) promote the maintenance of the malignant hemopoietic clone of myelofibrosis: an in vitro study.

Science.gov (United States)

Sollazzo, Daria; Forte, Dorian; Polverelli, Nicola; Romano, Marco; Perricone, Margherita; Rossi, Lara; Ottaviani, Emanuela; Luatti, Simona; Martinelli, Giovanni; Vianelli, Nicola; Cavo, Michele; Palandri, Francesca; Catani, Lucia

2016-07-12

Along with molecular abnormalities (mutations in JAK2, Calreticulin (CALR) and MPL genes), chronic inflammation is the major hallmark of Myelofibrosis (MF). Here, we investigated the in vitro effects of crucial factors of the inflammatory microenvironment (Interleukin (IL)-1β, Tumor Necrosis Factor (TNF)-α, Tissue Inhibitor of Metalloproteinases (TIMP)-1 and ATP) on the functional behaviour of MF-derived circulating CD34+ cells.We found that, regardless mutation status, IL-1β or TNF-α increases the survival of MF-derived CD34+ cells. In addition, along with stimulation of cell cycle progression to the S-phase, IL-1β or TNF-α ± TIMP-1 significantly stimulate(s) the in vitro clonogenic ability of CD34+ cells from JAK2V617 mutated patients. Whereas in the JAK2V617F mutated group, the addition of IL-1β or TNF-α + TIMP-1 decreased the erythroid compartment of the CALR mutated patients. Megakaryocyte progenitors were stimulated by IL-1β (JAK2V617F mutated patients only) and inhibited by TNF-α. IL-1β + TNF-α + C-X-C motif chemokine 12 (CXCL12) ± TIMP-1 highly stimulates the in vitro migration of MF-derived CD34+ cells. Interestingly, after migration toward IL-1β + TNF-α + CXCL12 ± TIMP-1, CD34+ cells from JAK2V617F mutated patients show increased clonogenic ability.Here we demonstrate that the interplay of these inflammatory factors promotes and selects the circulating MF-derived CD34+ cells with higher proliferative activity, clonogenic potential and migration ability. Targeting these micro-environmental interactions may be a clinically relevant approach.

Clinical Significance and Expression of PAF and TNF-alpha in Seminal Plasma of Leukocytospermic Patients

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Chaodong Liu

2012-01-01

Full Text Available Objective. Discuss the changes and roles of PAF in the reproductive tract infection by observing the expression of platelet activating factor (PAF and tumor necrosis factor α (TNF-α in seminal plasma of patients with leukocytospermia. Methods. The seminal plasma was obtained from 22 cases of leukocytospermia and 15 cases of normal males; the peroxidase dyeing method was adopted for seminal plasma white blood count; the ELISA was adopted to test PAF and TNF-α concentration in seminal plasma. Result. PAF concentration ( ng/mL of leukocytospermia group was significantly lower than the normal group ( ng/mL, while TNF-α ( ng/mL was significantly higher than that of normal group ( ng/mL. There was negative correlation between PAF and TNF-α , (, ; the same situation existed in PAF and WBC (, ; but TNF-α was positively correlated to WBC (, . Conclusion. (1 Low expression of PAF and high expression of TNF-α in leukocytospermia affect the sperm motility, which is one of the reasons that leads to infertility. (2 Lower expression of PAF has its particularity during the reproductive tract infection.

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G.C., Anup

2013-01-01

Author: Anup G.C. Year: 2013 Subject of thesis: Credit Card Security Number of pages: 36+2 Credit Card is a widely used electronic chip for easy transactions. The main purpose of the report was to show the security measures of transaction by credit cards. The purpose was to give information about credit cards and how they were introduced. The thesis reportcontained the types of card theft with examples and sited the various protocols used for online ...

Microglial TNF and IL-1 as early disease-modifiers in Alzheimer's-like disease in mice

DEFF Research Database (Denmark)

Ilkjær, Laura; Babcock, Alicia; Finsen, Bente

2015-01-01

In Alzheimer's disease (AD) signs of microglial activation is evident already in prodromal and early AD. This and other evidence suggest that neuroinflammation contributes to the progression of the early disease development in AD. Microglial cells have the capacity to produce cytokines such as TNF...... in the APPswe/PS1DE9 mouse model of AD. In these mice, cortical As plaque load shows a sigmoidal trajectory with age, as it does in AD. At 12 months of age, when As pathology is welldeveloped, TNF and IL-1s are produced in significantly higher proportions of microglia in the APPswe/PS1DE9 mice, than in wildtype...

Determination of long-lived natural Ra isotopes, 226Ra, in mineral and spring waters from Caxambu (MG) and Aguas de Lindoia (SP) spas

International Nuclear Information System (INIS)

Negrao, Sergio Garcia

2012-01-01

The aim of this work was to study the long-lived Ra isotopes, 226 Ra and 228 Ra, natural distribution in mineral and spring waters from Caxambu (MG) and Aguas de Lindoia (SP) water parks. In Caxambu mineral waters it was observed 228 Ra activity concentrations slightly higher than those of 226 Ra. The elevated content of carbonates and bicarbonates of these waters can result in an increased solubility of the both Ra isotopes and may play an important role for the fate of 228 Ra and its equilibrium distribution between solid and liquid phases. In Caxambu Thermal Spa, arithmetic mean activities ranged from 83 mBq L -1 to 3599 mBq L -1 and from 60 mBq L -1 to 4481 mBq L -1 for 226 Ra and 228 Ra, respectively. The highest 226 Ra activity was found in Venancio Spring, while the maximum 228 Ra activity value was determined in Ernestina Guedes. 228 Ra/ 226 Ra activity ratios varied from 0.079 (Conde D'Eau and Princesa Isabel Spring) to 4.2 (Mairink II Spring). In Aguas de Lindoia, arithmetic mean activities ranged from 4.6 mBq L -1 to 41 mBq L -1 and from 30 mBq L -1 to 54 mBq L -1 for 226 Ra and 228 Ra, respectively. The maximum 226 Ra activity concentration was found in the bottled mineral water Sao Jorge, while the higher 228 Ra activity concentration was determined in Santa Filomena Spring (public station 2). 228 Ra/ 226 Ra activity ratios varied from 1.2 (bottled mineral water Sao Jorge) to 9.1 (bottled mineral water Jatoba 1). This work also performed the dose assessment due to the ingestion of 226 Ra and 228 Ra in Caxambu and Aguas de Lindoia mineral and spring waters. The committed effective doses were estimated by using a conservative dosimetric model and taking into account the results over a lifetime (70 years) following intake of both long-lived Ra isotopes. The results from this radiological evaluation showed that the guidance committed effective dose level of 0.1 mSv y-1 recommended by World Health Organization was exceeded in almost all samples studied in

Expression of an insulin/interleukin-1 receptor antagonist hybrid gene in insulin-producing cell lines (HIT-T15 and NIT-1) confers resistance against interleukin-1-induced nitric oxide production.

Science.gov (United States)

Welsh, N; Bendtzen, K; Welsh, M

1995-01-01

A hybrid gene consisting of the insulin gene enhancer/promoter region, the signal sequence, the insulin B- and C-chains, and the human interleukin-1 receptor antagonist (IL-1ra) gene was constructed. This hybrid gene was transfected together with the pSV2-neo construct into the insulin-producing cell lines HIT-T15 and NIT-1. One of the geneticin-selected clones, HITra2, expressed a 1.4-kb mRNA, which hybridized both to insulin and IL-1ra-cDNA in Northern blot analysis. Three proteins, with the mol wt 23, 17, and 14 kD, were immunoprecipitated with anti-IL-1ra antibodies from [35S]methionine-labeled HITra2 cells. Both at a low and at a high glucose concentration, 4-5 ng of IL-1ra/10(6) cells (ELISA) was released from these cells. On the other hand, a high glucose concentration evoked a three-fold increase in the release of insulin, suggesting that IL-1ra was released constitutively. Measured by nitrite production, transfected HIT, and NIT-1 cells exhibited a more than 10-fold decrease in IL-1 beta sensitivity. Since the conditioned culture media from the HITra2 cells exhibited an anti-IL-1 beta activity of only 0.5 U/ml, and mixed culture of HITra2 cells and isolated rat islets prevented IL-1 beta induced inhibition of insulin release, it is likely that IL-1ra acts locally at the cell surface. It is concluded that expression of a hybrid insulin/IL-1ra gene confers resistance to IL-1 and that this technique may be used to elucidate the role of IL-1 in autoimmune disorders such as insulin-dependent diabetes mellitus. Images PMID:7706480

Azadirachtin Interacts with the Tumor Necrosis Factor (TNF) Binding Domain of Its Receptors and Inhibits TNF-induced Biological Responses*

Science.gov (United States)

Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A.; Manna, Sunil K.

2010-01-01

The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor κB (NF-κB) and also expression of NF-κB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-κB (IκBα) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IκBα kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-κB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy. PMID:20018848

Azadirachtin interacts with the tumor necrosis factor (TNF) binding domain of its receptors and inhibits TNF-induced biological responses.

Science.gov (United States)

Thoh, Maikho; Kumar, Pankaj; Nagarajaram, Hampathalu A; Manna, Sunil K

2010-02-19

The role of azadirachtin, an active component of a medicinal plant Neem (Azadirachta indica), on TNF-induced cell signaling in human cell lines was investigated. Azadirachtin blocks TNF-induced activation of nuclear factor kappaB (NF-kappaB) and also expression of NF-kappaB-dependent genes such as adhesion molecules and cyclooxygenase 2. Azadirachtin inhibits the inhibitory subunit of NF-kappaB (IkappaB alpha) phosphorylation and thereby its degradation and RelA (p65) nuclear translocation. It blocks IkappaB alpha kinase (IKK) activity ex vivo, but not in vitro. Surprisingly, azadirachtin blocks NF-kappaB DNA binding activity in transfected cells with TNF receptor-associated factor (TRAF)2, TNF receptor-associated death domain (TRADD), IKK, or p65, but not with TNFR, suggesting its effect is at the TNFR level. Azadirachtin blocks binding of TNF, but not IL-1, IL-4, IL-8, or TNF-related apoptosis-inducing ligand (TRAIL) with its respective receptors. Anti-TNFR antibody or TNF protects azadirachtin-mediated down-regulation of TNFRs. Further, in silico data suggest that azadirachtin strongly binds in the TNF binding site of TNFR. Overall, our data suggest that azadirachtin modulates cell surface TNFRs thereby decreasing TNF-induced biological responses. Thus, azadirachtin exerts an anti-inflammatory response by a novel pathway, which may be beneficial for anti-inflammatory therapy.

Clinical significance of measurement of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis

International Nuclear Information System (INIS)

Wang Tongwu

2009-01-01

Objective: To explore the significance of changes of serum IL-8, IL-1β and TNF-α levels after treatment in patients with periodontitis. Methods: Serum IL-8, IL-1β and TNF-α(with RIA) levels were determined in 36 patients with periodontitis both before and after treatment as well as in 35 controls. Results: Before treatment, serum IL-8, IL-1β and TNF-α levels were significantly higher in the patients than those in controls (P 0.05). Conclusion: Detection of serum IL-8, IL-1β and TNF-α levels might reflect the progress of disease in patients with periodontitis and might be of important clinical value. (authors)

The TOTEM T1 read out card motherboard

OpenAIRE

Minutoli, S; Lo Vetere, M; Robutti, E

2010-01-01

This article describes the Read Out Card (ROC) motherboard, which is the main component of the T1 forward telescope front-end electronic system. The ROC main objectives are to acquire tracking data and trigger information from the detector. It performs data conversion from electrical to optical format and transfers the data streams to the next level of the system and it implements Slow Control modules which are able to receive, decode and distribute the LHC machine low jitter clock and fast c...

Association between TNF-α and IL-1β genotypes vs Helicobacter pylori infection in Indonesia

Science.gov (United States)

Zhao, Yang; Wang, Jing-Wen; Tanaka, Tsutomu; Hosono, Akihiro; Ando, Ryosuke; Tokudome, Shinkan; Soeripto; Triningsih, FX Ediati; Triono, Tegu; Sumoharjo, Suwignyo; Achwan, EY Wenny Astuti; Gunawan, Stephanus; Li, Yu-Min

2013-01-01

AIM: To investigate the correlation between the Helicobacter pylori (H. pylori) infection and host genetic background of healthy populations in Indonesia. METHODS: In March 2007, epidemiological studies were undertaken on the general population of a city in Indonesia (Mataram, Lombok). The participants included 107 men and 187 women, whose ages ranged from 6 to 74 years old, with an average age of 34.0 (± 14.4) (± SD). The H. pylori of subject by UBT method determination, and through the polymerase chain reaction with confronting two-pair primers (PCR-CTPP) method parsing the single nucleotide polymorphism of interleukin (IL)-8, IL-4, IL-1β, CD14, tumor necrosis factor (TNF-α) and tyrosine-protein phosphates non-receptor type 11 (PTPN11) genotypes. The experimental data were analyzed by the statistical software SAS. RESULTS: The H. pylori infection rates in the healthy Indonesian population studied were 8.4% for men and 12.8% for women; no obvious differences were noted for H. pylori infection rates by sex or age. TC genotypes of IL-4, TC and CC genotypes of TNF-α, and GA genotypes of PTPN11, were higher in frequency. Both CC and TC genotype of TNF-α T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of (OR = 1.99; 95%CI: 0.67-5.89) and (OR = 1.66; 95%CI: 0.73-3.76), respectively. C allele of IL-1β T-31C gene locus was at a higher risk (OR = 1.11; 95%CI: 0.70-1.73) of H. pylori infection, but no statistical significance was found in our study. CONCLUSION: We reveal that the association between the TNF-α and IL-1β genotypes may be the susceptibility of H. pylori in the studied population. PMID:24379597

A pilot study on temporal changes in IL-1β and TNF-α serum levels after spinal cord injury: the serum level of TNF-α in acute SCI patients as a possible marker for neurological remission.

Science.gov (United States)

Biglari, B; Swing, T; Child, C; Büchler, A; Westhauser, F; Bruckner, T; Ferbert, T; Jürgen Gerner, H; Moghaddam, A

2015-07-01

Serum levels of interleukin-1β (IL-1β) and tumour necrosis factor-α (TNF-α) were measured over a 12-week period in 23 patients with spinal cord injury (SCI) with and without neurological improvement. To determine the course of IL-1β and TNF-α in patients with SCI and observe a possible relationship between improvements in neurological functioning and cytokine levels. All patients were treated at the BG Trauma Centre, Ludwigshafen, Germany. All lab work was done at the University Hospital, Heidelberg. Spinal cord injury was classified according to the American Spinal Injury Association (ASIA) impairment scale (AIS) in 23 patients. TNF-α and IL-1β levels were measured upon arrival at the hospital, after 4 h, 9 h and 12 h, on days 1 and 3 and at the end of weeks 1, 2, 4, 8 and 12. Temporal changes in TNF-α and IL-1β in SCI patients were seen. Patients with AIS improvement (Group 1) had significantly lower TNF-α levels at 9 h compared with patients without AIS improvement (Group 2; PSCI. Our data show differences in measured cytokines over a 12-week period for SCI patients with and without neurological improvement.

RA reactor operation and maintenance in 1989, Part 1

International Nuclear Information System (INIS)

Sotic, O.; Martinc, R.; Cupac, S.; Sulem, B.; Zivotic, Z.; Majstorovic, D.; Sanovic, V.

1989-01-01

During the previous period RA reactor was not operated because the Committee of Serbian ministry for health and social care has cancelled the operation licence in July 1984. The reason was the non existing emergency cooling system and lack of appropriate filters in the special ventilation system. The following major tasks were fulfilled: building of the new emergency cooling system, reconstruction of the existing ventilation system, and renewal of the power supply system. Project concerned with renewal of RA reactor complete instrumentation was started at the end of 1988. Contract was signed between the IAEA and Soviet Atomenergoexport for supplying the new instrumentation for the RA reactor. Project concerned with increase of the storage space and the efficiency of handling the spent fuel elements has started in 1988. In 1989, device for water purification designed by the reactor staff started operation and spent fuel handling equipment is being mounted. Training of the existing personnel and was done regularly, but the new staff has no practical training since the reactor is not operated. Lack of financial support influenced strongly the status of RA reactor [sr

TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1) Virus Infection in the Mexican Population

Science.gov (United States)

García-Ramírez, Román Alejandro; Ramírez-Venegas, Alejandra; Quintana-Carrillo, Roger; Camarena, Ángel Eduardo; Falfán-Valencia, Ramcés; Mejía-Aranguré, Juan Manuel

2015-01-01

Background Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1) virus infections. Most patients infected with the influenza A (H1N1) pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α). We propose that single-nucleotide polymorphisms (SNPs) in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1) pdm09 virus infection. Methods 145 patients with influenza A (H1N1) (pA/H1N1), 133 patients with influenza-like illness (ILI), and 360 asymptomatic healthy contacts (AHCs) were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8) using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4) were measured on a Luminex 100. Results The IL6 rs1818879 (GA) heterozygous genotype was associated with severe influenza A (H1N1) virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05–11.56), and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively). Genetic susceptibility was determined (pA/H1N1 vs. AHC): the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9), and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89). Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007). Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001) and IL-6 (p  =  0.007) levels. Conclusions The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were

TNF, IL6, and IL1B Polymorphisms Are Associated with Severe Influenza A (H1N1 Virus Infection in the Mexican Population.

Directory of Open Access Journals (Sweden)

Román Alejandro García-Ramírez

Full Text Available Hypercytokinemia is the main immunopathological mechanism contributing to a more severe clinical course in influenza A (H1N1 virus infections. Most patients infected with the influenza A (H1N1 pdm09 virus had increased systemic levels of pro-inflammatory cytokines; including interleukin IL-6, IL-8, and tumor necrosis factor-alpha (TNF-α. We propose that single-nucleotide polymorphisms (SNPs in the promoter regions of pro-inflammatory genes are associated with the severity of influenza A (H1N1 pdm09 virus infection.145 patients with influenza A (H1N1 (pA/H1N1, 133 patients with influenza-like illness (ILI, and 360 asymptomatic healthy contacts (AHCs were included. Eleven SNPs were genotyped in six genes (TNF, LT, IL1B, IL6, CCL1, and IL8 using real-time PCR; the ancestral genotype was used for comparison. Genotypes were correlated with 27 clinical severity variables. Ten cytokines (GM-CSF, TNF-α, IL-2, IL-1β, IL-6, IL-8, IFN-γ, IL-10, IL-5, and IL-4 were measured on a Luminex 100.The IL6 rs1818879 (GA heterozygous genotype was associated with severe influenza A (H1N1 virus infection (odds ratio [OR] = 5.94, 95% confidence interval [CI] 3.05-11.56, and two IL1B SNPs, rs16944 AG and rs3136558 TC, were associated with a decreased risk of infection (OR = 0.52 and OR = 0.51, respectively. Genetic susceptibility was determined (pA/H1N1 vs. AHC: the LTA rs909253 TC heterozygous genotype conferred greater risk (OR = 1.9, and a similar association was observed with the IL1B rs3136558 CC genotype (OR = 1.89. Additionally, severely ill patients were compared with moderately ill patients. The TNF-238 GA genotype was associated with an increased risk of disease severity (OR = 16.06, p = 0.007. Compared with ILIs, patients with severe pA/H1N1 infections exhibited increased serum IL-5 (p <0.001 and IL-6 (p  =  0.007 levels.The TNF gene was associated with disease severity, whereas IL1B and IL6 SNPs were associated with influenza A (H1N1 virus

Inventory of 226Ra, 228Ra and 210Pb in marine sediments cores of Southwest Atlantic Ocean

International Nuclear Information System (INIS)

Costa, Alice M.R.; Oliveira, Joselene de; Figueira, Rubens C.L.; Mahiques, Michel M.; Sousa, Silvia H.M.

2015-01-01

210 Pb (22.3 y) is a radioactive isotope successfully applied as tracer of sediment dating of the last 100-150 years. The application of 226 Ra and 228 Ra as paleoceanographic tracers (half-lives of 1,600 y and 5.7 y, respectively) also gives some information of ocean's role in past climate change. In this work, it was analyzed 2 sediment cores collect at Southwest Atlantic Ocean. The sediments samples were freeze-dried and acid digested in microwave. It was carried out a radiochemical separation of 226 Ra, 228 Ra and 210 Pb and performed a gross alpha and gross beta measurement of both precipitates Ba(Ra)SO 4 and PbCrO 4 in a low background gas-flow proportional counter. Activity concentrations of 226 Ra ranged from 45 Bq kg -1 to 70 Bq kg -1 in NAP-62 and from 57 Bq kg -1 to 82 Bq kg -1 in NAP-63 samples. The concentration of 228 Ra varied between 37 Bq kg -1 and 150 Bq kg -1 in NAP-62 and between 23 Bq kg -1 and 111 Bq kg -1 in NAP-63 samples. The concentration of total 210 Pb ranged from 126 Bq kg -1 to 256 Bq kg -1 in NAP-62 and from 63 Bq kg -1 to 945 Bq kg -1 in NAP-63 samples. Results of 210 Pb uns varied from 68 Bq kg -1 to 192 Bq kg -1 for NAP-62, while varied from <4.9 Bq kg -1 to 870 Bq kg -1 in NAP-63 profile. Increased values of 210 Pb uns were found on the top of both NAP-62 and NAP- 63 sediment profile. (author)

A new determination method of 226Ra, 224Ra, and 228Th in water

International Nuclear Information System (INIS)

Horiuchi, Kimiko; Murakami, Yukio.

1981-01-01

A new method for the determination of 226 Ra, 224 Ra and 228 Th in water samples is described. It consists of extraction of 222 Rn and 220 Rn into a scintillator-toluene solution in equilibrium with 226 Ra and 224 Ra and the application of integral counting techniques with a liquid scintillation counter. One liter water sample, weakly acidified with hydrochloric acid, is transferred to a glass bottle, and vigorously bubbled with a stream of nitrogen to expel any radon or thoron in the water sample. Twenty five ml of the scintillator-toluene solution is added to the bottle (time is recorded). The bottle is stoppered with a Teflon stopper and kept at an upside-down position for a given period of time (usually 4 -- 16 days) to allow radon and thoron in partial equilibrium with their parent nuclides. Then, the sample system is vigorously shaken for 2 m and the organic layer is gently transferred to a counting vial through a specially devised transferring tube which is connected to the bottle. The initial counting time is set at 4 h after the separation of organic layer. The measurements are repeated 3 times each immediately and after 106 h from the initial counting time. From these results, the integral counting rates of radon and thoron at the initial counting time are easily obtained. The activities of 226 Ra, 224 Ra and 228 Th in the water sample are calculated from these integral counting rates by the proposed formulas. Some data on the 226 Ra and 224 Ra contents of mineral springs are presented. The lowest detection limits for 226 Ra and 224 Ra were 1.10 x 10 -12 and 1.47 x 10 -9 Ci, respectively. The present method is rapid, easy and accurate and eliminates a time-consuming sealing of the sample in Curie bottle and tedious procedure to transfer the sample gas through a vacuum system to the detector. (author)

Inhibition of HIF-1α decreases expression of pro-inflammatory IL-6 and TNF-α in diabetic retinopathy.

Science.gov (United States)

Gao, Xiuhua; Li, Yonghua; Wang, Hongxia; Li, Chuanbao; Ding, Jianguang

2017-12-01

Recent studies demonstrate that pro-inflammatory cytokines (PICs, i.e. IL-1β, IL-6 and TNF-α) in retinal tissues are likely involved in the development of diabetic retinopathy (DR). In this report, we particularly examined contributions of hypoxia inducible factor subtype 1α (HIF-1α) to the expression of PICs and their receptors in diabetic retina. Streptozotocin (STZ) was systemically injected to induce hyperglycaemia in rats. ELISA and Western blot analysis were employed to determine the levels of HIF-1α and PICs as well as PIC receptors in retinal tissues of control rats and STZ rats. The levels of retinal HIF-1α were significantly increased in STZ rats 4-10 weeks after induction of hyperglycaemia as compared with control animals. With increasing HIF-1α retinal PICs including IL-1β, IL-6 and TNF-α, their respective receptors, namely IL-1R, IL-6R and TNFR1, were also elevated in STZ rats. Moreover, inhibition of HIF-1α by injection of 2-methoxyestradiol (2-MET) significantly decreased the amplified expression IL-6, TNF-α, IL-6R and TNFR1 in diabetic retina, but did not modify IL-1β pathway. In addition, we examined protein expression of Caspase-3 indicating cell apoptosis in the retina of STZ rats after infusing 2-MET, demonstrating that 2-MET attenuated an increase in Caspase-3 evoked by STZ. Hypoxia inducible factor subtype 1α (HIF-1α) activated in diabetic retina is likely to play a role in regulating pathophysiological process via IL-6 and TNF-α mechanism. This has pharmacological implications to target specific HIF-1α, IL-6 and TNF-α signalling pathway for dysfunction and vulnerability related to DR. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection

Directory of Open Access Journals (Sweden)

Ulrike Schleicher

2016-05-01

Full Text Available Neutralization or deletion of tumor necrosis factor (TNF causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1 expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO synthase (NOS2 was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.

Research nuclear reactor RA - Annual Report 1989; Istrazivacki nuklearni reaktor RA - Izvestaj za 1989. godinu

Energy Technology Data Exchange (ETDEWEB)

Sotic, O [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1989-12-15

Annual report concerning the project 'RA research nuclear reactor' for 1989, financed by the Serbian ministry of science is divided into two parts. First part is concerned with RA reactor operation and maintenance, which is the task of the Division for reactor engineering of the Institute for multidisciplinary studies and RA reactor engineering. Second part deals with radiation protection activities at the RA reactor which is the responsibility of the Institute for radiation protection. Scientific council of the Institute for multidisciplinary studies and RA reactor engineering has stated that this report describes adequately the activity and tasks fulfilled at the RA reactor in 1989. The scope and the quality of the work done were considered successful both concerning the maintenance and reconstruction, as well as radiation protection activities. [Serbo-Croat] Godisnji izvestaj po projektu 'Istrazivacki nuklearni reaktor RA' za 1989. godinu, koji finansira republicka zajednica za nauku SR Srbije po ugovoru br. 3705/1 sastoji se iz dva dela. Prvi deo obuhvata pogon i odrzavanje nuklearnog reaktora RA, sto predstavlja obavezu Odeljenja za reaktorski inzenjering u sastavu OOUR Instituta za multidisciplinarna istrazivanja i inzenjering RA. Drugi deo obuhvata poslove zastite od zracenja na reaktoru RA, sto predstavlja obavezu OOUR Instituta za zastitu od zracenja 'Zastita'. Naucno vece Instituta za multidisciplinarna istrazivanja i inzenjering RA ocenilo je da sadrzina ovog izvestaja odgovara izvrsenim poslovima na reaktoru RA u 1989. godini. Pozitivno se ocenjuje obim i kvalitet izvrsenih radova kako u pogledu odrzavanja i rekonstrukcije reaktora, tako i u pogledu poslova zastite od zracenja izvrsenih kod njega.

Inhibition of TNF-α and IL-1 by compounds from selected plants for ...

African Journals Online (AJOL)

Purpose: To investigate the inhibitory activities of herbal compounds from Curcuma longa, Sophora japonica and Camellia sinensis against tumor necrosis factor alpha (TNF-α) and interleukin-1 (IL-1) using in vivo and in silico tools. Methods: The extracts of the medicinal herbs (Curcuma longa, Sophora japonica and ...

The secrets of the green and white cards | Hagemeister | Southern ...

African Journals Online (AJOL)

Southern African Journal of HIV Medicine. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 15, No 1 (2014) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. The secrets of the green and white cards.

Reproduction of the RA reactor fuel element fabrication; Reprodukcija izrade gorivnog elementa za reaktor RA

Energy Technology Data Exchange (ETDEWEB)

Novakovic, M [Institute of Nuclear Sciences Boris Kidric, Vinca, Beograd (Serbia and Montenegro)

1961-12-15

This document includes the following nine reports: Final report on task 08/12 - testing the Ra reactor fuel element; design concept for fabrication of RA reactor fuel element; investigation of the microstructure of the Ra reactor fuel element; Final report on task 08/13 producing binary alloys with Al, Mo, Zr, Nb and B additions; fabrication of U-Al alloy; final report on tasks 08/14 and 08/16; final report on task 08/32 diffusion bond between the fuel and the cladding of the Ra reactor fuel element; Final report on task 08/33, fabrication of the RA reactor fuel element cladding; and final report on task 08/36, diffusion of solid state metals. Ovaj rad sadrzi devet priloga: 1. Zavrsni izvestaj o podzadatku 08/12, ispitivanje elementa goriva reaktora RA; 2. Koncepcija izrade gorivnog elementa reaktora RA; 3. Ispitivanje mikrostrukture gorivnog elementa reaktora RA; 4. Zavrsni izvestaj o podzadatku 08/13, dobijanje binarnih legura urana sa legirajucim komponentama Al, Mo, Zr, Nb i B; 5. Dobijanje legure U-Al; 6. Zavrsni izvestaj o podzadacima 08/14 i 08/16; 7. Zavrsni izvestaj o podzadatku 08/32, difuziona veza goriva i kosuljice gorivnog elementa reaktora RA; 8. Zavrsni izvestaj o podzadatku 08/33, izrada kosuljice gorivnog elementa reaktora RA; 9. Zavrsni izvestaj o podzadatku 08/36, difuzija kod metala u cvrstom stanju.

TNF-α and IL-1β Dependent Induction of CCL3 Expression by Nucleus Pulposus Cells Promotes Macrophage Migration through CCR1

Science.gov (United States)

Wang, Jianru; Tian, Ye; Phillips, Kate L.E.; Chiverton, Neil; Haddock, Gail; Bunning, Rowena A.; Cross, Alison K.; Shapiro, Irving M.; LeMaitre, Christine L.; Risbud, Makarand V.

2012-01-01

Objective To investigate TNF-α and IL-1β regulation of CCL3 expression in nucleus pulposus (NP) cells and in macrophage migration. Methods qRT-PCR and immunohistochemistry were used to measure CCL3 expression in NP cells. Transfections were used to determine the role of NF-κB, C/EBP-β and MAPK on cytokine mediated CCL3 promoter activity. Effect of NP-conditioned medium on macrophage migration was measured using a transwell system. Results An increase in CCL3 expression and promoter activity was observed in NP cells after TNF-α or IL-1β treatment. Treatment of cells with NF-κB and MAPK inhibitors abolished the effect of the cytokines on CCL3 expression. The inductive effect of p65 and C/EBP-β on CCL3 promoter was confirmed through gain- and loss-of-function studies. Noteworthy, co-transfection of p50 completely blocked cytokine and p65 dependent induction. In contrast, c-Rel and RelB had little effect on promoter activity. Lentiviral transduction with Sh-p65 and Sh-Ikkβ significantly decreased TNF-α dependent increase in CCL3 expression. Analysis of degenerate human NP tissues showed that CCL3, but not CCL4 expression correlated positively with the grade of tissue degeneration. Importantly, treatment of macrophages with conditioned medium of NP cells treated with TNF-α or IL-1β promoted their migration; pretreatment of macrophages with antagonist to CCR1, primary receptor for CCL3 and CCL4, blocked cytokine mediated migration. Conclusions By controlling the activation of MAPK, NF-κB and C/EBPβ signaling, TNF-α and IL-1β modulate the expression of CCL3 in NP cells. The CCL3-CCR1 axis may play an important role in promoting macrophage infiltration in degenerate, herniated discs. PMID:23233369

Neutron spectrometry in mixed fields: characterisation of the Ra-1- reactor workplace

International Nuclear Information System (INIS)

Gregori, B.; Carelli, J.; Cruzate, J.; Papadopulos, S.

2006-01-01

The characterisation of the neutron spectrum of a workplace is an essential dosimetric tool for improving the assessment of the personal equivalent dose of the workers. In addition, if the operational conditions of the facility are well defined, the set of field spectra obtained may be used as a reference for comparing the performance of different type of neutron detectors. Recently, using a neutron spectrometric system based on a set of moderated spheres with 3 He detector, the characterisation of the neutron spectra in workplaces of the Argentine Reactor No. 1 (R.A. -1) has been carried out. The spectrometric system consists of 12 spheres made of the high density polyethylene d mean δ =0.95 g cm 3 , with diameters between 3'' and 12'' and a proportional counter of 3 He, 4 atm of nominal pressure, Centronic trade mark, located in the centre of the spheres. The neutron response matrix was calculated using the M.C.N.P. -I.V.B. code and E.N.D.F./B-VI library in the energy range between thermal neutron and 100 MeV. The neutron spectrum was unfolded using the M.A.X.E.D. unfolding code. The validation of the spectrometric system was performed at Cea-Cadarache (France) with of 252 Cf, Am Be, and 252 Cf + D 2 O sources. Therefore, in this work, the spectral fluence of the field in the selected points of the facility (R.A.-1) has been presented and the ambient dose equivalent, H *(10), and the personal dose equivalent, Hp(10), have been derived from the neutron fluence, applying ICRP-74 recommended fluence to dose conversion factors. The quantities evaluated have uncertainties less than 15%, which is considered good enough for radiation protection requirements. (authors)

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

International Nuclear Information System (INIS)

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

2013-01-01

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

Plant cyclopeptide RA-V kills human breast cancer cells by inducing mitochondria-mediated apoptosis through blocking PDK1–AKT interaction

Energy Technology Data Exchange (ETDEWEB)

Fang, Xian-Ying; Chen, Wei [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Fan, Jun-Ting [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Song, Ran; Wang, Lu [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Gu, Yan-Hong [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing (China); Zeng, Guang-Zhi [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Shen, Yan; Wu, Xue-Feng [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Tan, Ning-Hua, E-mail: nhtan@mail.kib.ac.cn [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China); Sun, Yang, E-mail: yangsun@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing (China)

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.

Print a Bed Bug Card - (Single Cards)

Science.gov (United States)

Two sets of business-card-sized lists of tips for recognizing bed bugs and the signs of an infestation, including a photo of bed bugs to assist identification. One card is for general use around home or office, the other for travelers.

Automated measurement of 224Ra and 226Ra in water

International Nuclear Information System (INIS)

Dimova, N.; Burnett, W.C.; Horwitz, E.P.; Lane-Smith, D.

2007-01-01

We present a new simple approach for automated, non-destructive measurement of the alpha-emitting radium isotopes ( 223 Ra, 224 Ra, and 226 Ra) in water based on the emanation of their respective radon daughters ( 219 Rn, 220 Rn, and 222 Rn). The method combines the high adsorption uptake of MnO 2 Resin for radium (K d =2.4x10 4 ml/g) over a wide pH range with the simplicity of the activity registration using a commercial radon-in-air analyzer (RAD7, DURRIDGE Company, Inc). Radium is first adsorbed onto the MnO 2 Resin by passing a water sample through the resin packed in a gas-tight glass cartridge. The same cartridge is then connected to the radon analyzer via a simple tubing system to circulate air through the resin and a drying system. The efficiency of the proposed system is determined by running standards prepared in the same manner. Our results indicate that the efficiency for 226 Ra is >22% if both 218 Po and 214 Po counts are collected. This is comparable with typical efficiencies for alpha spectrometry but with much less sample preparation. We estimate that an MDA of 0.8 pCi/L for 226 Ra may be obtained with this new approach using a 1 L water sample and less than 4 h of counting

Measurements at the RA Reactor related to the VISA-2 project - Part 1, Start-up of the RA reactor and measurement of new RA reactor core parameters

International Nuclear Information System (INIS)

Markovic, H.

1962-07-01

The objective of the measurements was determining the neutron flux in the RA reactor core. Since the number of fuel channels is increased from 56 to 68 within the VISA-2 project, it was necessary to attain criticality of the RA reactor and measure the neutron flux properties. The 'program of RA reactor start-up' has been prepared separately and it is included in this report. Measurements were divided in two phases. First phase was measuring of the neutron flux after the criticality was achieved but at zero power. During phase two measurements were repeated at several power levels, at equilibrium xenon poisoning. This report includes experimental data of flux distributions and absolute values of the thermal and fast neutron flux in the RA reactor experimental channels and values of cadmium ratio for determining the neutron epithermal flux. Data related to calibration of regulatory rods for cold un poisoned core are included [sr

Mechanistic insights into the role of C-type lectin receptor/CARD9 signaling in human antifungal immunity

Directory of Open Access Journals (Sweden)

Rebecca A. Drummond

2016-04-01

Full Text Available Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs. CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS. In the last few years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2 and CARD9-binding partners (MALT1, BCL10 affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.

RA Reactor; Reaktor RA

Energy Technology Data Exchange (ETDEWEB)

NONE

1989-07-01

This chapter includes the following: General description of the RA reactor, organization of work, responsibilities of leadership and operators team, regulations concerning operation and behaviour in the reactor building, regulations for performing experiments, regulations and instructions for inserting samples into experimental channels. [Serbo-Croat] Ovo (prvo) poglavlje sadrzi sledece: Opis reaktora RA; semu organizacije rada i rukovodjenja; prava i duznosti direktora i rukovodioca pogona reaktora, propise o rezimu rada i kretanja u zgradi reaktora, propise o izvodjenju eksperimenata, propise o unosenju uzoraka u eksperimentalne kanale reaktora.

Card Product Use and Perception of Marketing Communication by Card Issuers among Students

Directory of Open Access Journals (Sweden)

Đurđana Ozretić Došen

2011-06-01

Full Text Available Student population is a very interesting and important segment of the market to the marketing practitioners involved in card business. The services and products offered by card issuers to students are created with a view to attracting the kind of users who will grow accustomed to a long-term, loyal use of a chosen card brand, i.e. beyond the point at which they complete their academic education. This paper describes the exploratory research on card products designed for the student population which was conducted in the Republic of Croatia. Student awareness of card products and their habits associated with card use were also examined. Additional areas of research were student attitudes and perceptions with regard to card products and to the appeal of the marketing communications which target this specific market segment. Results showed that the majority of students hold debit cards of the banks in which they have their current accounts. Students use cards actively, most of all for the purpose of withdrawing cash at automated teller machines (ATMs and least of all for Internet purchases. They assess card use as being simple, and card holders are also aware of the various benefits provided through it. However, the recall of advertisements for card products point to the conclusion that card issuers do not communicate with students in a manner which the latter would find appealing.

Behavior and distribution of 226Ra and 228Ra in the east coast of Peninsular Malaysia marine environment

International Nuclear Information System (INIS)

Nurrul Assyikeen Mohd Jaffary; Zal Uyun Wan Mahmood; Zaharudin Ahmad; Yii, Mei Wo; Kamarozaman Ishak

2010-01-01

The present distributions of 226 Ra, 228 Ra and activity ratios of 228 Ra/ 226 Ra covering the east coast of Peninsular Malaysia were studied. Sediment core samples were collected at 10 identified stations with the thickness of water column between 14 - 72 m depth during the cruise conducted in 2008. Activity concentrations of 226 Ra and 228 Ra in sediment cores of the studied area were in the range of 18.95 ±4.25 Bq/ kg to 46.48 ± 6.41 Bq/ kg dry wt. and 35.50 ± 7.50 Bq/ kg to 77.10 ±11.37 Bq/ kg dry wt., respectively. Meanwhile, the calculated activity ratios of 228 Ra/ 226 Ra were varied mostly 1.48 to 2.24. The finding showed that there has relationships between 226 Ra, 228 Ra and oceanographic parameters which are can be attributed for better understanding of its transport processes and behavior in the east coast of Peninsular Malaysia marine environment. (author)

1 GSPS digitizer based on the FPGA Mezzanine Card (FMC) standard with low-count pin connector.

CERN Document Server

Vasilyev, Mikhail

2015-01-01

Under the scope of a CERN summer student project, the schematic for ADC based on FMC mezzanine card with 1 GSPS sampling rate and 8 bit resolution was developed. The mezzanine is fully compatible with the standard: FPGA Mezzanine Card (FMC) [1]. A low-pin count connector was used to connect the mezzanine with the “carrier”. The carrier was an Open Hardware project: Simple PCIe FMC carrier (SPEC).

Turning a Private Label Bank Card into a Multi-function Campus ID Card.

Science.gov (United States)

James, Thomas G.; Norwood, Bill R.

1991-01-01

This article describes the development at Florida State University of the Seminole ACCESS card, which functions simultaneously as a bank automated teller machine card, a student identification card, and a debit card. Explained are the partnership between the university and the bank charge card center, funding system, technologies involved, and…

RA reactor operation and maintenance in 1992, Part 1

International Nuclear Information System (INIS)

Sotic, O.; Cupac, S.; Sulem, B.; Zivotic, Z.; Majstorovic, D.; Tanaskovic, M.

1992-01-01

During 1992 Ra reactor was not in operation. All the activities were fulfilled according to the previously adopted plan. Basic activities were concerned with revitalisation of the RA reactor and maintenance of reactor components. All the reactor personnel was busy with reconstruction and renewal of the existing reactor systems and building of the new systems, maintenance of the reactor devices. Part of the staff was trained for relevant tasks and maintenance of reactor systems [sr

PTEN differentially regulates expressions of ICAM-1 and VCAM-1 through PI3K/Akt/GSK-3β/GATA-6 signaling pathways in TNF-α-activated human endothelial cells.

Science.gov (United States)

Tsoyi, Konstantin; Jang, Hwa Jin; Nizamutdinova, Irina Tsoy; Park, Kyungok; Kim, Young Min; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Chang, Ki Churl

2010-11-01

Phosphotase and tensin homolog deleted on chromosome 10 (PTEN) is a potent negative regulator of PI3K/Akt pathway. Here, we tried to elucidate the role of PTEN in the regulation of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM)-1 and intracellular adhesion molecule (ICAM)-1, induced by TNF-α in human endothelial cells (ECs). Transfection with PTEN overexpressing vector resulted in the significant decrease in phosphorylation of Akt in TNF-α-treated ECs. PTEN strongly inhibited VCAM-1 but not ICAM-1, however this inhibitory effect was reversed by co-transfection with constitutively active-Akt (CA-Akt-HA) in TNF-α-stimulated ECs. Additionally, silencing of PTEN with specific siRNA showed significant increase of phosphor-Akt compared with TNF-α alone treated ECs. siPTEN significantly upregulated VCAM-1 but was indifferent to ICAM-1 in TNF-α-treated cells. Further, chromatin immunoprecipitation (ChIP) assay showed that PTEN targets GATA-6 but not IRF-1 binding to VCAM-1 promoter. In addition, GATA-6 is associated with glycogen synthesis kinase-3beta (GSK-3β) which is in turn regulated by PTEN-dependent Akt activity. Finally, PTEN significantly prevented monocyte adhesion to TNF-α-induced ECs probably through VCAM-1 regulation. It is concluded that PTEN selectively inhibits expression of VCAM-1 but not ICAM-1 through modulation of PI3K/Akt/GSK-3β/GATA-6 signaling cascade in TNF-α-treated ECs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

On the interpretation of the 14C fine structure observed in the 223Ra decay

International Nuclear Information System (INIS)

Hussonnois, M.; Le Du, J.F.; Brillard, L.

1989-01-01

The low hindrance factors observed in the 14 C decay of 223 Ra to the 209 Pb excited states at 779 and 1423 KeV are interpreted as a consequence of the similitude of the wave functions describing the uncoupled neutron in 223 Ra, Ω = 3/2 (3/2 [631] x3/2 [761], and in the two first excited states of 209 Pb, namely the 1i 11/2 and 1j 15/2 shell model orbits

The caspase-1 inhibitor CARD18 is specifically expressed during late differentiation of keratinocytes and its expression is lost in lichen planus.

Science.gov (United States)

Qin, Haihong; Jin, Jiang; Fischer, Heinz; Mildner, Michael; Gschwandtner, Maria; Mlitz, Veronika; Eckhart, Leopold; Tschachler, Erwin

2017-08-01

CARD18 contains a caspase recruitment domain (CARD) via which it binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro-inflammatory cytokine interleukin (IL)-1β. To determine the expression profile and the role of CARD18 during differentiation of keratinocytes and to compare the expression of CARD18 in normal skin and in inflammatory skin diseases. Human keratinocytes were induced to differentiate in monolayer and in 3D skin equivalent cultures. In some experiments, CARD18-specific siRNAs were used to knock down expression of CARD18. CARD18 mRNA levels were determined by quantitative real-time PCR, and CARD18 protein was detected by Western blot and immunofluorescence analyses. In situ expression was analyzed in skin biopsies obtained from healthy donors and patients with psoriasis and lichen planus. CARD18 mRNA was expressed in the epidermis at more than 100-fold higher levels than in any other human tissue. Within the epidermis, CARD18 was specifically expressed in the granular layer. In vitro CARD18 was strongly upregulated at both mRNA and protein levels in keratinocytes undergoing terminal differentiation. In skin equivalent cultures the expression of CARD18 was efficiently suppressed by siRNAs without impairing stratum corneum formation. Epidermal expression of CARD18 was increased after ultraviolet (UV)B irradiation of skin explants. In skin biopsies of patients with psoriasis no consistent regulation of CARD18 expression was observed, however, in lesional epidermis of patients with lichen planus, CARD18 expression was either greatly diminished or entirely absent whereas in non-lesional areas expression was comparable to normal skin. Our results identify CARD18 as a differentiation-associated keratinocyte protein that is altered in abundance by UV stress. Its downregulation in lichen planus indicates a potential role in inflammatory reactions of the epidermis in this disease. Copyright © 2017 Japanese Society for Investigative

RAPIDARC (RA) in the uterine cervical cancer; dosimetric gain vs 3D-Crt; RAPIDARC (RA) en el cancer de cervix uterino; ganancia dosimetrica vs 3D-CRT

Energy Technology Data Exchange (ETDEWEB)

Ramirez, J.; Garcia, B.; Quispe, K.; Gonzales, A.; Marquina, J., E-mail: jose.ramirez@aliada.com.pe [Clinica Aliada, Oncologia Integral, Av. Jose Galvez Barrenechea 1044, San Isidro, Lima (Peru)

2014-08-15

This work aims to quantitatively assess RAPIDARC (RA) treatments versus three dimensional-Conformal Radiation Therapy with field to field technique (3D-Crt-Fin F). 11 patients with cervical cancer treated at our institution radically or adjuvant clinical stages I-III B were evaluated. The prescribed dose was 50 Gy (2 Gy / Fr). The RA plans consisted of two isocentric complete arcs and conformational plans of 4 isocentric fields (previous, subsequent, right side and left side) with 3D-Crt-Fin F technique; both cases carried out ??in the Eclipse version 10 planner with calculation algorithm analytical anisotropic algorithm (AAA) and volumetric optimization software (for VMAT plans). Homogeneity indices (Hi), conformity indices (CI) Sigma indices (S-Index), monitor units (MU) and the time required for each treatment were compared. The mean age was 52 years (32-65) of the 11 patients 9 were clinical stages I-II B. The Hi varied from 0.052 for RA to 0.163 for 3D-Crt-Fin F (p = 0.009), and the CI between 1.005 and 1.35 (p = 0.26), the S-index from 1.2 to 3.7 (p = 0.001) and the H-index of 1.08 to 1.15 (p = 0.24). All dose limits in risk organs were met with a significant difference in the RA plans versus 3D-Crt-Fin F. In patients with cervical cancer the treatment plans quality with the indices aforementioned seems to be better with the RA technique, being observed a significant reduction of radiation to surrounding organs. (author)

8 CFR 1212.6 - Border crossing identification cards.

Science.gov (United States)

2010-01-01

... combined B-1/B-2 visitor visa and non-biometric border crossing identification card or (a similar stamp in... non-biometric border crossing identification card (or similar stamp in a passport), issued by the DOS... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Border crossing identification cards. 1212...

Evaluation of IL-1β, IL-1ra, and IL-10 levels and outcome of periodontal therapy in chronic periodontitis with familial Mediterranean fever.

Science.gov (United States)

Bostanci, Vildan; Toker, Hulya; Senel, Soner; Poyraz, Omer; Akpinar, Aysun; Görgün, Emine Pirim; Bakar, Olcay

2017-01-01

This study aimed to examine the IL-1β, IL-1ra, and IL-10 cytokine levels in gingival crevicular fluid (GCF) and serum of familial Mediterranean fever (FMF) and chronic periodontitis (CP) patients, and their response to nonsurgical periodontal therapy. A total of 50 patients, 15 FMF patients with generalized chronic periodontitis (FMF-CP), 15 systemically healthy patients with generalized chronic periodontitis (CP), ten systemically and periodontal healthy controls (HC), and ten periodontally healthy FMF patients (FMF-HC) were enrolled in the study. The cytokine levels in GCF and serum were determined by ELISA. Probing depth, clinical attachment level, and gingival and plaque indices in each participant were also measured. The GCF and clinical parameters at baseline and 6 weeks were recorded. The study indicated statistically significant healing of the clinical parameters in both FMF-CP and CP groups after periodontal treatment. GCF IL-1β levels at 6 weeks in FMF-CP group were significantly lower than the CP group (p  0.05). The results of our study suggested that there was a positive correlation between gingival inflammation and serum cytokine levels in FMF patients and also colchicine treatment showed protective effects on GCF cytokine levels in FMF-CP group. Following treatment, GCF IL-1β and GCF IL-1ra levels were decreased in FMF-CP group. GCF IL-10 levels were increased in FMF-CP group compared to other groups. Also, the serum cytokine levels associated with periodontal inflammation in FMF patients.

Seasonal variation of 228Ra/226Ra ratio in seaweed: implications for water circulation patterns in coastal areas of the Noto Peninsula, Japan

International Nuclear Information System (INIS)

Inoue, M.; Kofuji, H.; Yamamoto, M.; Komura, K.

2005-01-01

To examine water circulation patterns of coastal water, 72 seaweed (Sargasso) samples and 27 coastal water samples were collected from coastal areas of the Noto Peninsula, Japan, during the period from December 1998 to June 2002. The 228 Ra and 226 Ra activities of those samples were measured by low-background γ-ray spectrometry. There was a wide range of activities of 228 Ra (0.5-2 Bq/kg-fresh) and 226 Ra (0.5-1.2 Bq/kg-fresh) in the Sargasso samples. The 228 Ra/ 226 Ra activity ratio of Sargasso samples exhibited seasonal variation with minimum values in June ( 228 Ra/ 226 Ra = ∼1) and maximum values in December (1.5-2.5), which was mainly governed by changes in 228 Ra activity. It is also notable that the seasonal variation of the 228 Ra/ 226 Ra ratio of Sargasso is in approximate agreement with that of the ambient coastal water. Sargasso samples appear to have retained the 228 Ra/ 226 Ra ratio of the ambient coastal waters, and the temporal variations in that ratio provide insight into seasonal changes in water circulation in the Noto Peninsula coastal area

TNF{alpha} and IL-1{beta} are mediated by both TLR4 and Nod1 pathways in the cultured HAPI cells stimulated by LPS

Energy Technology Data Exchange (ETDEWEB)

Zheng, Wenwen; Zheng, Xuexing [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Liu, Shue [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Ouyang, Hongsheng [College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province (China); Levitt, Roy C.; Candiotti, Keith A. [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States); Hao, Shuanglin, E-mail: shao@med.miami.edu [Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, FL 33136 (United States)

2012-04-20

Highlights: Black-Right-Pointing-Pointer LPS induces proinflammatory cytokine release in HAPI cells. Black-Right-Pointing-Pointer JNK pathway is dependent on TLR4 signaling to release cytokines. Black-Right-Pointing-Pointer NF-{kappa}B pathway is dependent on Nod1 signaling to release cytokines. -- Abstract: A growing body of evidence recently suggests that glial cell activation plays an important role in several neurodegenerative diseases and neuropathic pain. Microglia in the central nervous system express toll-like receptor 4 (TLR4) that is traditionally accepted as the primary receptor of lipopolysaccharide (LPS). LPS activates TLR4 signaling pathways to induce the production of proinflammatory molecules. In the present studies, we verified the LPS signaling pathways using cultured highly aggressively proliferating immortalized (HAPI) microglial cells. We found that HAPI cells treated with LPS upregulated the expression of TLR4, phospho-JNK (pJNK) and phospho-NF-{kappa}B (pNF-{kappa}B), TNF{alpha} and IL-1{beta}. Silencing TLR4 with siRNA reduced the expression of pJNK, TNF{alpha} and IL-1{beta}, but not pNF-{kappa}B in the cells. Inhibition of JNK with SP600125 (a JNK inhibitor) decreased the expression of TNF{alpha} and IL-1{beta}. Unexpectedly, we found that inhibition of Nod1 with ML130 significantly reduced the expression of pNF-{kappa}B. Inhibition of NF-{kappa}B also reduced the expression of TNF{alpha} and IL-1{beta}. Nod1 ligand, DAP induced the upregulation of pNF-{kappa}B which was blocked by Nod1 inhibitor. These data indicate that LPS-induced pJNK is TLR4-dependent, and that pNF-{kappa}B is Nod1-dependent in HAPI cells treated with LPS. Either TLR4-JNK or Nod1-NF-{kappa}B pathways is involved in the expression of TNF{alpha} and IL-1{beta}.

A Comparison of Fentanyl and Flurbiprofen Axetil on Serum VEGF-C, TNF-α, and IL-1ß Concentrations in Women Undergoing Surgery for Breast Cancer.

Science.gov (United States)

Wen, Yiyun; Wang, Mingde; Yang, Jinfeng; Wang, Yichun; Sun, Huiping; Zhao, Jianghong; Liu, Weizhen; Zhou, Zhengyu; Deng, Hongwu; Castillo-Pedraza, Catalina; Zhang, Yi; Candiotti, Keith A

2015-07-01

Vascular endothelial growth factor-C (VEGF-C), tumor necrosis factor-α (TNF-α), and interleukin-1ß(IL-1ß) have been shown to be associated with the recurrence and metastasis of breast cancer after surgery. This study tested the hypothesis that patients undergoing surgery for breast cancer, who received postoperative analgesia with flurbiprofen axetil combined with small doses of fentanyl (FA), exhibited reduced levels of VEGF-C, TNF-α, and IL-1ß compared with those patients receiving fentanyl alone (F). Forty-women with primary breast cancer undergoing a modified radical mastectomy were randomized to receive postoperative analgesia with flurbiprofen axetil combined with fentanyl or fentanyl alone. Venous blood was sampled before anesthesia, at the end of surgery, and at 48 hours after surgery, and the serum was analyzed. The primary endpoint was changes in the VEGF-C concentrations in serum. Group FA patients reported similar analgesic effects as group F patients at 2, 24, and 48 hours. At 48 hours, mean postoperative concentrations of VEGF-C in group F patients were higher than in group FA patients, 730.9 versus. 354.1 pg/mL (P = 0.003), respectively. The mean postoperative concentrations of TNF-α in group F patients were also higher compared with group FA patients 27.1 vs. 15.8 pg/mL (P = 0.005). Finally, the mean postoperative concentrations of IL-1ß in group F were also significantly higher than in group FA 497.5 vs. 197.7 pg/mL (P = 0.001). In patients undergoing a mastectomy, postoperative analgesia with flurbiprofen axetil, combined with fentanyl, were associated with decreases in serum concentrations of VEGF-C, TNF-α, and IL-1ß compared with patients receiving doses of only fentanyl. © 2014 World Institute of Pain.

226Ra, 228Ra and 40K in scales formed in boilers of industrial installations

International Nuclear Information System (INIS)

Poggi, Claudia M. Braga; Farias, Emerson Emiliano G. de; Hazin, Clovis A.; Gazineu, Maria Helena P.; Universidade Catolica de Pernambuco

2011-01-01

Many industrial processes involve the production of steam in boilers, which is sent through pipes to machines and other equipment used in different sectors of the installations. The water commonly used in these processes is groundwater, which generally has high concentrations of calcium and magnesium salts, that can co-precipitate with naturally occurring radioactive elements such as 226 Ra and 228 Ra creating radioactive scales, which are deposited in pipes, thus decreasing the efficiency of steam production. In addition, 40 K that is present in all soils and rocks with a concentration of about 0.012% of natural potassium can also be concentrated in these scales. No data was found in literature relating to radionuclides present in the scales formed on boilers in general. In this context, the purpose of this work was to determine concentrations of 226 Ra, 228 Ra and 40 K, in scales generated inside boilers from different industries in the cities of Caruaru, Paulista and Goiana, Pernambuco. Determination of the radionuclides concentration was performed by gamma spectrometry with an HPGe detector, calculating their specific activities. Activity concentrations of 226 Ra were in the range of -1 and 228 Ra activity concentrations varied from 1 . Activity concentrations of 40 K were in the range of -1 . All these activity concentrations were lower than the limits established by the Brazilian Nuclear Energy Commission of for this type of matrix. (author)

From patients with arthralgia, pre-RA and recently diagnosed RA: What is the current status of understanding RA pathogenesis?

NARCIS (Netherlands)

M. Molendijk (Marlieke); J.M.W. Hazes (Mieke); E.W. Lubberts (Erik)

2018-01-01

textabstractIt is believed that therapy for rheumatoid arthritis (RA) is the most effective and beneficial within a short time frame around RA diagnosis. This insight has caused a shift from research in patients with established RA to patients at risk of developing RA and recently diagnosed

Natural uranium and 226Ra in bottled potable waters of Argentina

International Nuclear Information System (INIS)

Bomben, Ana M.; Palacios, Miguel A.

2001-01-01

This paper presents the results obtained of the measurement of the natural uranium and 226 Ra concentrations carried out on 345 drinking water samples coming from different provinces of Argentina. The samples were collected from tap water systems and private wells. Six bottled mineral waters samples, selected from those most extensively consumed, were also analyzed. The natural uranium concentration was determined by a fluorimetric procedure and 226 Ra by the 222 Rn emanation technique and liquid scintillation counting. Values ranging from 0,03 to 50 μg L -1 of natural uranium and concentrations up to 22 mBq L -1 were found in the drinking water samples analyzed. Natural uranium concentrations from 0,04 to 3,8 μg L -1 and 226 Ra concentrations up to 2,4 mBq L -1 were measured in the bottled mineral waters samples. Based on the water intake rate and the measured concentrations of both radionuclides analyzed, an annual collective effective dose of 1,5 man Sv and an average committed effective dose of 0,5 μSv a -1 , were calculated for the City of Buenos Aires inhabitants. (author)

TNF Lectin-Like Domain Restores Epithelial Sodium Channel Function in Frameshift Mutants Associated with Pseudohypoaldosteronism Type 1B

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Anita Willam

2017-05-01

Full Text Available Previous in vitro studies have indicated that tumor necrosis factor (TNF activates amiloride-sensitive epithelial sodium channel (ENaC current through its lectin-like (TIP domain, since cyclic peptides mimicking the TIP domain (e.g., solnatide, showed ENaC-activating properties. In the current study, the effects of TNF and solnatide on individual ENaC subunits or ENaC carrying mutated glycosylation sites in the α-ENaC subunit were compared, revealing a similar mode of action for TNF and solnatide and corroborating the previous assumption that the lectin-like domain of TNF is the relevant molecular structure for ENaC activation. Accordingly, TNF enhanced ENaC current by increasing open probability of the glycosylated channel, position N511 in the α-ENaC subunit being identified as the most important glycosylation site. TNF significantly increased Na+ current through ENaC comprising only the pore forming subunits α or δ, was less active in ENaC comprising only β-subunits, and showed no effect on ENaC comprising γ-subunits. TNF did not increase the membrane abundance of ENaC subunits to the extent observed with solnatide. Since the α-subunit is believed to play a prominent role in the ENaC current activating effect of TNF and TIP, we investigated whether TNF and solnatide can enhance αβγ-ENaC current in α-ENaC loss-of-function frameshift mutants. The efficacy of solnatide has been already proven in pathological conditions involving ENaC in phase II clinical trials. The frameshift mutations αI68fs, αT169fs, αP197fs, αE272fs, αF435fs, αR438fs, αY447fs, αR448fs, αS452fs, and αT482fs have been reported to cause pseudohypoaldosteronism type 1B (PHA1B, a rare, life-threatening, salt-wasting disease, which hitherto has been treated only symptomatically. In a heterologous expression system, all frameshift mutants showed significantly reduced amiloride-sensitive whole-cell current compared to wild type αβγ-ENaC, whereas membrane

22 CFR 50.9 - Card of identity.

Science.gov (United States)

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Card of identity. 50.9 Section 50.9 Foreign... of United States Nationality of a Person Abroad § 50.9 Card of identity. When authorized by the Department, consular offices or designated nationality examiners may issue a card of identity for travel to...

Clinical significance of determination of changes of serum hs-CRP, sICAM-1 and TNF-α levels in patients with gestational diabetes mellitus

International Nuclear Information System (INIS)

Yu Qiuyue

2009-01-01

Objective: To study the relationship between changes of serum sensitive C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and development of the disease in patients with gestational diabetes mellitus(GDM). Methods: Serum levels of TNF-α and sICAM-1(with RIA) and hs-CRP(with immunoturbidimetry) were measured in 30 patients with GDM and 30 normal pregnant women as controls. Results: The serum hs-CRP, sICAM-1 and TNF-α contents in the patients with GDM were all significantly higher than those in normal pregnant women (all P<0.01).The serum hs-CRP levels were mutually positivety correlated with TNF-α and sICAM-1 levels (r=0.6097, 0.7213, all P<0.01). Conclusion: Determination of changes of serum hs-CRP, TNF-α and sICAM-1 levels in patients with gestational diabetes mellitus would be helpful for outcome prediction. (authors)

Determination of sup 226 Ra and sup 228 Ra in gypsum

Energy Technology Data Exchange (ETDEWEB)

Godoy, J M [Instituto de Radioprotecao e Dosimetria, Rio de Janeiro, RJ (Brazil)

1989-01-01

The content of {sup 226}Ra and {sup 228}Ra in different samples of phosphogypsum and three samples of gypsite were determined by gamma spectroscopy. For {sup 226}Ra the 295, 352 and 609 KeV lines and for {sup 228}Ra the 911 and 969 KeV lines were used. The specific activities values ranged from 0.36 to 22.8 pCi/g for {sup 226}Ra and 0.90 to 10.3 pCi/g for {sup 228}Ra. The contribution of a sypsum roof-covering to the {sup 222}Rn concentration in a room was estimated, based on the highest value reported. (author).

Bioavailability of radionuclides 226Ra, 228Ra and 210Pb present in the brazilian phosphate fertilizers and phosphogypsum

International Nuclear Information System (INIS)

Russo, Ana Carolina

2013-01-01

Phosphogypsum, also called gypsum, by-product of the phosphate fertilizer industry, can be used as soil conditioner since it provides improvements in the soil-plant system. However, this by-product concentrates radionuclides of the U and Th series, present in the phosphate rock used as raw material, which can impact the environment. In order to study the bioavailability of radionuclides, samples of phosphogypsum and phosphate fertilizers (monoammonium phosphate and triple superphosphate) were analyzed. The concentration of 226 Ra, 228 Ra and 210 Pb were determined by gamma spectrometry. The samples were leached with a mild EDTA solution and the radionuclides present in the final solution were determined by total alpha and beta counting on a gas flow proportional counter. The percentage of extraction varied from 1.6% to 1.7% for 210 Pb, from 0.5% to 1.4% for 226 Ra and from 0.1% to 1.0% for the 228 Ra in phosphogypsum samples. The low percentage of extraction obtained for the radionuclides can be partly explained by the low solubility of phosphogypsum, which ranged from 7.7% to 16%. For the monoammonium phosphate samples the percentage of extraction were less than 26% for 226 Ra, less than 10% for '2 28 Ra and less than 10% for 210 Pb. In spite of the high solubility of 77% of monoammonium phosphate in the EDTA solution, low concentrations of radionuclides were observed in the leached solution. For the triple superphosphate samples, the percentage of extraction was 2.3% for 226 Ra, 1.2% for 228 Ra and 11.3% for 210 Pb. In spite of the high solubility of 66% of triple superphosphate in the EDTA solution, low concentrations of radionuclides were observed in the leached solution. (author)

Anti-TNF-α biotherapies