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Sample records for refractaria con infliximab

  1. Infliximab and insulin resistance.

    PubMed

    Ursini, Francesco; Naty, Saverio; Grembiale, Rosa Daniela

    2010-06-01

    Insulin resistance is the most important pathophysiologic feature of obesity, type 2 diabetes mellitus and prediabetic states. TNF-alpha, a proinflammatory cytokine, plays a pivotal role in the pathogenesis of inflammation-associated insulin resistance during the course of rheumatic diseases. Therapies aimed at neutralizing TNF-alpha, such as the monoclonal antibody infliximab, represent a novel approach for the treatment of rheumatic diseases and allow to obtain significant results in terms of control of the inflammatory process. In this article we reviewed the scientific evidence published in the literature about a potential role of TNF-alpha blockade in improving insulin resistance in non-diabetic rheumatic patients.

  2. Serum infliximab concentrations in psoriatic patients treated with infliximab: a systematic review.

    PubMed

    Dannepond, Carole; Maruani, Annabel; Machet, Laurent; Ternant, David; Paintaud, Gilles; Samimi, Mahtab

    2015-04-01

    The efficacy of infliximab is influenced by individual variability in its pharmacokinetics and pharmacodynamics. Serum infliximab concentrations could therefore be related to the efficacy and tolerance of infliximab, and assist adjustment of treatment. The aim of this systematic review was to assess the value of measuring serum infliximab concentrations in psoriatic patients. A bibliographic search was performed on MEDLINE, CENTRAL, EMBASE, LILACS for original studies on serum infliximab concentrations in psoriatic patients treated with infliximab. Ten articles were included, representing evaluation of serum infliximab concentrations in 733 patients. Predictive value of higher serum infliximab concentrations on long-term response maintenance was suggested in 3 studies. There was no information regarding the value of such measurements for adjustment of infliximab dosage. Trough serum infliximab concentrations that are at least detectable (>0.1 mg/L) at steady state (week 22) seem to be associated with maintaining a clinical response in the long term.

  3. Infliximab Biosimilar (CT-P13; Infliximab-dyyb): A Review in Autoimmune Inflammatory Diseases.

    PubMed

    Blair, Hannah A; Deeks, Emma D

    2016-10-01

    Infliximab biosimilar (CT-P13/infliximab-dyyb; Remsima(®), Inflectra(®)) is approved in several countries for use in all indications for which reference infliximab (Remicade(®)) is approved, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis, psoriasis, Crohn's disease, and ulcerative colitis. Clinical data contributing to the EU approval of infliximab biosimilar were obtained from two pivotal double-blind clinical trials in patients with AS (PLANETAS) or RA (PLANETRA). Infliximab biosimilar demonstrated equivalence to reference infliximab in terms of its pharmacokinetic profile in patients with AS, patients with RA, and in healthy volunteers, and in terms of its efficacy in patients with RA. Clinical response rates in patients with RA or AS were maintained over the longer term (up to 102 weeks). In addition, the efficacy of infliximab biosimilar in patients with RA or Crohn's disease and ulcerative colitis [i.e. inflammatory bowel disease (IBD)] has been demonstrated in the real-world setting. Infliximab biosimilar was generally well tolerated, with a tolerability profile similar to that of reference infliximab. Switching from reference infliximab to infliximab biosimilar had no detrimental effect on efficacy, safety, or immunogenicity compared with continuous infliximab biosimilar therapy, according to the extensions of PLANETAS and PLANETRA, and real-world data in IBD. Current evidence therefore suggests that infliximab biosimilar is a useful alternative to reference infliximab in patients with autoimmune inflammatory diseases.

  4. Parkinsonism as a side effect of infliximab.

    PubMed

    Henriksen, Jakob Nørgaard; Eriksson, Bengt Oluf Mikael

    2016-05-05

    We present a case of a 64-year-old man with Crohn's disease who developed parkinsonism after starting treatment with infliximab (Remicade). The patient had a 30-year history of Crohn's disease with previous surgical procedures and treatment with methotrexate. Treatment was augmented with infliximab, and 3 days after the first dose of 400 mg, a resting tremor began in the left leg. Over 4 months, symptoms progressed and now involved the right leg as well as both hands. There was no clinical effect of infliximab treatment, and the treatment was withdrawn 4 months later. The patient then experienced gradual, but continual, improvement of the resting tremor after withdrawal of infliximab. To the best of our knowledge, this is the first case report describing a patient developing parkinsonism after starting treatment with infliximab, with symptoms remitting on discontinuation.

  5. Response to infliximab in SAPHO syndrome

    PubMed Central

    Fruehauf, Julia; Cierny-Modrè, Brigitte; Caelen, Laila El-Shabrawi; Schwarz, Thomas; Weinke, Roland; Aberer, Elisabeth

    2009-01-01

    Infliximab has become increasingly important in the treatment of SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome. There is, however, little experience with this biological agent, and treatment protocols usually follow the regimens for spondylarthropathies. We report a patient with a highly unusual and severe clinical presentation of SAPHO syndrome including widespread bone and skin disease, and collagenous colitis. Infliximab treatment (5 mg/kg) given at weeks 0, 2 and 6 and every 8 weeks thereafter, induced rapid remission of the osteoarticular symptoms, although the skin lesions improved only partially, and after 10 months continuous therapy with infliximab a bone scan even uncovered new active bone lesions. Collagenous colitis is unresponsive to tumour necrosis factor α (TNFα) blocking agents. This moderate response to infliximab may indicate that a more aggressive treatment protocol is mandatory. We further believe that remission of osteoarticular complaints should be routinely confirmed by scintigraphic findings to verify treatment response. PMID:21686446

  6. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn's disease

    PubMed Central

    Vande Casteele, Niels; Khanna, Reena; Levesque, Barrett G; Stitt, Larry; Zou, G Y; Singh, Sharat; Lockton, Steve; Hauenstein, Scott; Ohrmund, Linda; Greenberg, Gordon R; Rutgeerts, Paul J; Gils, Ann; Sandborn, William J; Vermeire, Séverine; Feagan, Brian G

    2015-01-01

    Objective Although low infliximab trough concentrations and antibodies to infliximab (ATI) are associated with poor outcomes in patients with Crohn's disease (CD), the clinical relevance of ATI in patients with adequate infliximab concentrations is uncertain. We evaluated this question using an assay sensitive for identification of ATI in the presence of infliximab. Design In an observational study, 1487 trough serum samples from 483 patients with CD who participated in four clinical studies of maintenance infliximab therapy were analysed using a fluid phase mobility shift assay. Infliximab and ATI concentrations most discriminant for remission, defined as a C-reactive protein concentration of ≤5 mg/L, were determined by receiver operating characteristic curves. A multivariable regression model evaluated these factors as independent predictors of remission. Results Based upon analysis of 1487 samples, 77.1% of patients had detectable and 22.9% had undetectable infliximab concentrations, of which 9.5% and 71.8%, respectively, were positive for ATI. An infliximab concentration of >2.79 μg/mL (area under the curve (AUC)=0.681; 95% CI 0.632 to 0.731) and ATI concentration of <3.15 U/mL (AUC=0.632; 95% CI 0.589 to 0.676) were associated with remission. Multivariable analysis showed that concentrations of both infliximab trough (OR 1.8; 95% CI 1.3 to 2.5; p<0.001) and ATI (OR 0.57; 95% CI 0.39 to 0.81; p=0.002) were independent predictors of remission. Conclusions The development of ATI increases the probability of active disease even at low concentrations and in the presence of a therapeutic concentration of drug during infliximab maintenance therapy. Evaluation of strategies to prevent ATI formation, including therapeutic drug monitoring with selective infliximab dose intensification, is needed. PMID:25336114

  7. Listeria infections associated with infliximab: case reports.

    PubMed

    Kesteman, Thomas; Yombi, Jean-Cyr; Gigi, Jacques; Durez, Patrick

    2007-12-01

    Infliximab is a human-murine chimeric monoclonal antibody directed against tumor necrosis factor alpha (TNFalpha). Infliximab and other TNF blockers are used to treat inflammatory diseases such as rheumatoid arthritis (RA). TNF blockers are suspected to play a key role in some infections. We report here two cases of Listeria monocytogenes sepsis associated with infliximab treatment for RA. The first patient developed a terminal ileitis and a bacteraemia after three doses of infliximab; the second RA patient presented a bacteraemia associated with a prosthetic joint arthritis of the left hip, both related to Listeria. Those two cases occurred in a population of 518 patients treated with TNF blockers in our hospitals since the year 2000. Those events are of particular interest because of the severity of the infection, because the treatment differs from other infections, and because that, in the rheumatology unit, septic arthritis can mimic RA symptoms. They enhance the likelihood for this drug to increase the risk for infections with germs like Listeria.

  8. Infliximab-Related Infusion Reactions: Systematic Review

    PubMed Central

    Ron, Yulia; Kivity, Shmuel; Ben-Horin, Shomron; Israeli, Eran; Fraser, Gerald M.; Dotan, Iris; Chowers, Yehuda; Confino-Cohen, Ronit; Weiss, Batia

    2015-01-01

    Objective: Administration of infliximab is associated with a well-recognised risk of infusion reactions. Lack of a mechanism-based rationale for their prevention, and absence of adequate and well-controlled studies, has led to the use of diverse empirical administration protocols. The aim of this study is to perform a systematic review of the evidence behind the strategies for preventing infusion reactions to infliximab, and for controlling the reactions once they occur. Methods: We conducted extensive search of electronic databases of MEDLINE [PubMed] for reports that communicate various aspects of infusion reactions to infliximab in IBD patients. Results: We examined full texts of 105 potentially eligible articles. No randomised controlled trials that pre-defined infusion reaction as a primary outcome were found. Three RCTs evaluated infusion reactions as a secondary outcome; another four RCTs included infusion reactions in the safety evaluation analysis; and 62 additional studies focused on various aspects of mechanism/s, risk, primary and secondary preventive measures, and management algorithms. Seven studies were added by a manual search of reference lists of the relevant articles. A total of 76 original studies were included in quantitative analysis of the existing strategies. Conclusions: There is still paucity of systematic and controlled data on the risk, prevention, and management of infusion reactions to infliximab. We present working algorithms based on systematic and extensive review of the available data. More randomised controlled trials are needed in order to investigate the efficacy of the proposed preventive and management algorithms. PMID:26092578

  9. Herpes zoster in Crohn's disease during treatment with infliximab.

    PubMed

    Wang, Xiaobing; Zhao, Junzhang; Zhu, Siying; Xia, Bing

    2014-02-01

    Infliximab is widely used in both inducing and maintaining remission of patients with Crohn's disease (CD). The efficacy of infliximab has been undoubtedly proven; however, various opportunistic infections have emerged. Herpes virus infections (being a type of opportunistic infection) in CD patients treated with infliximab alone with no other concomitant medications are, however, rare and have not aroused enough attention. Gastroenterologists have limited knowledge of the immunization status of patients with CD, and rarely do they take an adequate immunization history before immunosuppressive therapy. Here we report two herpes zoster (HZ) events in CD patients while using infliximab alone: in the first case, HZ occurred during the patient's 12th infusion for maintance therapy, and in the second case, HZ occurred during the patient's first course of infliximab after surgery for therapy of inducing remission. We hope to increase the gastroenterologists' awareness of this potential infection in CD patients during treatment with infliximab.

  10. A study investigating the association of dermatological and infusion reactions to infliximab and infliximab trough levels

    PubMed Central

    Huang, Vivian Wai-Mei; Dhami, Neil; Fedorak, Darryl; Prosser, Connie; Shalapay, Carol; Kroeker, Karen Ivy; Halloran, Brendan Phillip; Dieleman, Levinus Albert; Fedorak, Richard Neil

    2015-01-01

    BACKGROUND: Although infliximab is an effective therapy for inflammatory bowel disease (IBD), it is associated with dermatological events and infusion reactions. It is not known whether a relationship between these adverse events (AEs) and infliximab trough levels (ITLs) exists. OBJECTIVES: To report the prevalence of infliximab-associated AEs in IBD patients receiving stable maintenance infliximab therapy, and to correlate ITLs with dermatological and infusion reactions to infliximab. METHODS: Adult IBD patients receiving stable maintenance infliximab therapy were recruited from the University of Alberta Infusion Clinic (Edmonton, Alberta). ITLs were measured in blood samples collected before infusion, and the patients’ records were reviewed for dermatological and infusion reactions to infliximab. RESULTS: One-quarter (18 of 71 [25.4%]) of patients experienced dermatological or infusion reactions to infliximab: nine (12.7%) dermatological events and nine (12.7%) infusion reactions. The median ITL was similar among patients with and without these AEs (7.2 μg/mL [interquartile range (IQR) 2.0 μg/mL to 13.3 μg/mL] versus 6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.648). The median ITL of patients who experienced infusion reactions (2.0 μg/mL [IQR 0.1 μg/mL to 5.7 μg/mL]) was lower than that of patients who experienced no such AEs (6.6 μg/mL [IQR 3.2 μg/mL to 12.7 μg/mL]; P=0.008]) and lower than that of patients who experienced dermatological AEs (13.3 μg/mL [IQR 8.8 μg/mL to 17.4 μg/mL]; P<0.001). CONCLUSION: One-quarter of IBD outpatients receiving stable maintenance infliximab therapy experienced dermatological and infusion reactions. Low ITLs were correlated with infusion reactions, and normal or high ITLs with dermatological events. PMID:25706572

  11. Effectiveness of infliximab after adalimumab failure in Crohn's disease

    PubMed Central

    Chaparro, María; Andreu, Montserrat; Barreiro-de Acosta, Manuel; García-Planella, Esther; Ricart, Elena; Domènech, Eugeni; Esteve, María; Merino, Olga; Nos, Pilar; Peñalva, Mireia; Gisbert, Javier P

    2012-01-01

    AIM: To evaluate the effectiveness of infliximab as a second-line therapy in Crohn’s disease patients after adalimumab failure. METHODS: A historical cohort study in a community-based gastroenterology practice evaluated Crohn’s disease patients treated with infliximab (induction plus maintenance) after adalimumab failure. Patients were identified using a large Spanish database (ENEIDA). RESULTS: We included 15 Crohn’s disease patients who received infliximab after adalimumab failure. Five patients discontinued adalimumab due to loss of response, 3 due to adverse events and 7 due to partial response. After infliximab therapy was started, all patients who had interrupted adalimumab due to loss of efficacy regained response. All patients who discontinued adalimumab due to adverse events responded to infliximab and maintained this response; one of these patients had an uneventful course on infliximab, but 2 developed adverse events. None of the 7 patients who interrupted adalimumab due to partial response reached remission with infliximab. CONCLUSION: Switching from adalimumab to infliximab may be useful in patients who develop adverse effects or loss of response, however, the benefit of infliximab in primary nonresponders was not established. PMID:23066316

  12. Erythema Multiforme Major Following Treatment with Infliximab

    PubMed Central

    Edwards, Dean; Boritz, Eli; Cowen, Edward W.; Brown, Ronald S.

    2012-01-01

    Background The growth in the use of anti-TNF-α agents for treatment of inflammatory conditions has led to increased recognition of the side effects associated with this class of drugs. Case Description We report a case of a patient who developed erythema multiforme (EM) major with characteristic oral and cutaneous lesions following treatment with the anti-TNF-α medication infliximab therapy for Crohn’s Disease (CD). Clinical Implications To our knowledge, this is the first reported case of infliximab-induced EM secondary to the treatment of CD. It is important for dental clinicians evaluating patients using anti-TNF-α agents to be aware of this possible complication. PMID:23036796

  13. The psoriatic patient profile for infliximab.

    PubMed

    Gisondi, P; Malara, G; Ardigò, M

    2011-12-01

    Psoriasis is a chronic inflammatory skin disease affecting 2-3% of the population worldwide. Psoriasis results from a complex and dynamic interplay between genetic and environmental factors that trigger an excessive inflammatory response in the skin which is driven by several mediators including TNF-alpha. The common form of the disease, termed 'chronic plaque psoriasis' is characterized by erythematous scaly plaques, typically on elbows, knees, scalp and buttocks. Psoriasis does not only affect the skin but also the nails and sometimes it is associated to a form of negative spondyloarthropathy, named the psoriatic arthritis (PsA), which could affect joints, tendons and/or the bone. Moreover, psoriasis is also frequently associated to metabolic comorbidities including obesity, dyslipidemia, diabetes and non alcoholic fatty liver disease. Consequently, psoriasis causes a high degree of morbidity and impairment of quality of life. There is no definite cure for psoriasis although there are treatments which could induce its remission. During the past decade, new very selective biological therapies for the management of psoriasis have been licensed. Biological drugs include TNF-alpha inhibitors (etanercept, infliximab and adalimumab) and ustekinumab which is an anti-IL 2/23 monoclonal antibody. Infliximab is very effective in the treatment of psoriasis either with nail involvement and/or PsA. Considering the characteristics of this drug, we propose a specific profile of the patient candidate to infliximab treatment. In particular, the main patient characteristics which drive the physician in selecting infliximab include the presence of a severe chronic plaque psoriasis, particularly if it is associated to a severe nail involvement and/or PsA, the urgency of psoriasis clearing, poor compliance of the patient for self-medication and the prospective of a long term continuous treatment.

  14. Pediatric Gastrointestinal Sarcoidosis: Successful Treatment with Infliximab

    PubMed Central

    Alawdah, Laila; Nahari, Ahmad; Alshahrani, Dayel; Fagih, Musa; Ghazi, Shahid; Al-Hussaini, Abdulrahman

    2016-01-01

    Gastrointestinal sarcoidosis is a rare disease with very limited data in children. Here we report the first pediatric case of successful treatment with infliximab. The first case was an 8-year-old Saudi girl who presented with fever, weight loss, and abdominal pain that was followed in a few months with hematemesis and development of hepatosplenomegaly. The second case was a 9-year-old Sudanese boy who manifested with vomiting, epigastric pain, and weight loss. On upper endoscopy, both cases demonstrated severe erosive nodular gastric mucosa. Gastric and esophageal biopsies had shown noncaseating granulomatous inflammation. The first case had histopathological evidence of granulomatous hepatitis, and both cases demonstrated lung nodularity on computed tomography chest. The boy had elevated angiotensin-converting enzyme level. Given the multisystem involvement with significant chest findings, tissue findings of granulomatous disease, and negative workup for other causes of granulomatous inflammation, both cases were diagnosed with active disseminated sarcoidosis, and treated with corticosteroids. The girl continued to be symptom-free for 4 years after tapering steroid therapy. The boy had relapses off steroids and the disease was brought into remission for 5 years off steroid therapy by infliximab. Pediatric GI sarcoidosis is a rare disease that exhibits heterogeneity in natural course. The chronic relapsing progressive form of the disease might benefit from infliximab therapy. PMID:27748327

  15. Infliximab-induced autoantibodies: a multicenter study.

    PubMed

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  16. Extensive preclinical evaluation of an infliximab biosimilar candidate.

    PubMed

    Velasco-Velázquez, M A; Salinas-Jazmín, N; Hisaki-Itaya, E; Cobos-Puc, L; Xolalpa, W; González, G; Tenorio-Calvo, A; Piña-Lara, N; Juárez-Bayardo, L C; Flores-Ortiz, L F; Medina-Rivero, E; Pérez, N O; Pérez-Tapia, S M

    2017-02-07

    Infliximab is therapeutic monoclonal antibody (mAb) against TNF-α employed in the treatment of immunoinflammatory diseases. The development of biosimilar mAbs is a global strategy to increase drug accessibility and reduce therapy-associated costs. Herein we compared key physicochemical characteristics and biological activities produced by infliximab and infliximab-Probiomed in order to identify functionally relevant differences between the mAbs. Binding of infliximab-Probiomed to TNF-α was specific and had kinetics comparable to that of the reference product. Both mAbs had highly similar neutralizing efficacy in HUVEC cell cultures stimulated with TNF-α. In vitro induction of CDC and ADCC were also similar between the evaluated products. In vivo comparability was assessed using a transgenic mouse model of arthritis that expresses human TNF-α in a 13-week multiple-administration study. Infliximab and infliximab-Probiomed showed comparable efficacy, safety, and pharmacokinetic profiles. Our results indicate that infliximab-Probiomed has highly similar activities to infliximab in preclinical models, warranting a clinical evaluation of its biosimilarity.

  17. Relationship between inflammation and infliximab pharmacokinetics in rheumatoid arthritis

    PubMed Central

    Ternant, David; Ducourau, Emilie; Perdriger, Aleth; Corondan, Anca; Le Goff, Benoît; Devauchelle-Pensec, Valérie; Solau-Gervais, Elisabeth; Watier, Hervé; Goupille, Philippe; Paintaud, Gilles; Mulleman, Denis

    2014-01-01

    Aims Infliximab, an anti-tumour necrosis factor-α monoclonal antibody, is indicated in rheumatoid arthritis (RA). Our objective was to evaluate the influence of the sources of infliximab pharmacokinetic variability in RA. Methods Eighty-four patients treated with infliximab for RA were included in a prospective noncomparative study. They were analysed between two consecutive infliximab infusions. Infliximab concentrations were measured before the infusion, 2 h, 1 and 4 weeks after the infusion and immediately before the next infusion. Infliximab concentrations were described using a two-compartment population pharmacokinetic model. Results The mean (interindividual standard deviation) estimated central volume of distribution was 2.3 l (36%) and systemic clearance was 0.019 l h−1 (37%). The central volume of distribution increased with bodyweight; it was doubled between 50 and 90 kg. Systemic clearance increased with pre-infusion C-reactive protein concentration by 20%, varying from 3 to 14 mg l−1, and was decreased by 30% when methotrexate was coadministered. Conclusions The influence of methotrexate and inflammation on infliximab clearance suggests that individual adjustment of infliximab doses according to disease activity may be useful in RA. PMID:24354889

  18. Serum sickness due to infliximab in a patient with psoriasis.

    PubMed

    Krishnan, Ravi S; Hsu, Sylvia

    2004-01-01

    Infliximab is a chimeric, murine-human, monoclonal antibody against tumor necrosis alpha which has shown great efficacy in the treatment of psoriasis. Serum sickness, which is an immune complex mediated syndrome consisting of a cutaneous eruption, fever, arthritis, edema, and lymphadenopathy, has been described in several patients receiving infliximab for the treatment of Crohn's disease. However, to our knowledge, this type of reaction has not been well described in a patient treated with infliximab for psoriasis. We describe a patient who developed serum sickness while receiving infliximab for psoriasis and discuss the pathogenesis, diagnosis, and treatment of serum sickness. We believe that with the increasing use of infliximab for psoriasis, more cases of serum sickness will occur. Therefore, awareness of this adverse effect is essential.

  19. Rapid Test for Infliximab Drug Concentration Allows Immediate Dose Adaptation

    PubMed Central

    Van Stappen, Thomas; Bollen, Lize; Vande Casteele, Niels; Papamichael, Konstantinos; Van Assche, Gert; Ferrante, Marc; Vermeire, Séverine; Gils, Ann

    2016-01-01

    OBJECTIVES: Therapeutic drug monitoring of infliximab improves treatment outcomes, but available assays to monitor infliximab lack speed to implement treatment algorithms immediately. Our aim is to validate a rapid, lateral flow-based assay (LFA) for quantitative determination of infliximab and to assess thresholds associated with mucosal healing in patients with ulcerative colitis. METHODS: Samples (n=190) from 29 anti-tumor necrosis factor naive patients with ulcerative colitis starting infliximab induction therapy between June 2010 and February 2012 were prospectively collected. All patients had a Mayo endoscopic sub-score ≥2 at baseline. Mucosal healing (MH), defined as a Mayo endoscopic sub-score ≤1, was evaluated at week 10–14. Infliximab trough concentrations (TC) were determined with a novel LFA, which was benchmarked with the RIDASCREEN infliximab Monitoring (ELISA). RESULTS: The LFA showed an excellent agreement with enzyme-linked immunosorbent assay (ELISA) for quantification of infliximab, as observed from Pearson and intraclass correlation coefficients of 0.95 and 0.95 during induction and 0.93 and 0.87 during maintenance therapy, respectively. In total, 45% of patients achieved MH. Using the LFA, week 14 TC ≥2.1 μg/ml (AUROC: 0.819, P=0.008) were associated with MH. After 2 years follow-up, 77% of patients with MH were still receiving infliximab therapy vs. 25% of patients without MH. CONCLUSIONS: We validated a LFA for quantification of infliximab and identified TC associated with MH. With a time-to-result of 20 min, individual sample analysis and user-friendliness, the LFA outplays ELISA as a rapid, accurate tool to monitor infliximab concentrations. PMID:27929524

  20. Inflammatory bowel disease of the lung: The role of infliximab?

    PubMed

    Hayek, Adam J; Pfanner, Timothy P; White, Heath D

    2015-01-01

    Pulmonary extra-intestinal manifestations (EIM) of inflammatory bowel disease are well described with a variable incidence. We present a case of Crohn's disease with pulmonary EIM including chronic bronchitis with non-resolving bilateral cavitary pulmonary nodules and mediastinal lymphadenopathy successfully treated with infliximab. Additionally, we present a case summary from a literature review on pulmonary EIM successfully treated with infliximab. Current treatment recommendations include an inhaled and/or systemic corticosteroid regimen which is largely based on case reports and expert opinion. We offer infliximab as an adjunctive therapy or alternative to corticosteroids for treatment of inflammatory bowel disease related pulmonary EIM.

  1. Infliximab and Dexamethasone Attenuate the Ductular Reaction in Mice

    PubMed Central

    Verhulst, Stefaan; Best, Jan; Syn, Wing-Kin; Reynaert, Hendrik; Hellemans, Karine H.; Canbay, Ali; Dolle, Laurent; van Grunsven, Leo A.

    2016-01-01

    Chronic hepatic injury is accompanied by a ductular response that is strongly correlated with disease severity and progression of fibrosis. To investigate whether anti-inflammatory drugs can modulate the ductular response, we treated mice suffering from a steatotic or cholestatic injury with anti-TNF-α antibodies (Infliximab) or glucocorticoids (Dexamethasone). We discovered that Dexamethasone and Infliximab can both modulate the adaptive remodeling of the biliary architecture that occurs upon liver injury and limit extracellular matrix deposition. Infliximab treatment, at least in these steatotic and cholestatic mouse models, is the safer approach since it does not increase liver injury, allows inflammation to take place but inhibits efficiently the ductular response and extracellular matrix deposition. Infliximab-based therapy could, thus, still be of importance in multiple chronic liver disorders that display a ductular response such as alcoholic liver disease or sclerosing cholangitis. PMID:27824131

  2. Pleural Tuberculosis following Infliximab Therapy for Ankylosing Spondylitis

    PubMed Central

    Krishnan, V. S. Gokul; Madhyastha, Sharath; Ramamoorthi, Kusugodlu; Acharya, Raviraj V.; Gopalaswamy, Vinaya

    2017-01-01

    We present a case of pleural tuberculosis (TB) in a patient on infliximab for ankylosing spondylitis. A 36-year-old male presented to our hospital with low back ache of inflammatory type along with multiple symmetric inflammatory type of joint pain. Further clinical examination, laboratory and radiological investigations were suggestive of ankylosing spondylitis. He was initially treated with nonsteroidal anti-inflammatory drugs but citing poor response it was decided to initiate biologic therapy using infliximab (antitumor necrosis factor-alpha). Mantoux test and chest radiograph were done before the therapy to rule out TB. Following three doses of infliximab, patient came with complaints of fever and cough for 1 week. On investigation, it was found to be a case of pulmonary TB. This shows the importance of close monitoring of patient for TB among patients on infliximab even though the screening test has come out to be negative.

  3. Vitiligo in a patient receiving infliximab for refractory ulcerative colitis.

    PubMed

    Ismail, Waleed A; Al-Enzy, Saleh A; Alsurayei, Saqer A; Ismail, Ali E

    2011-06-01

    Infliximab is a chimerical monoclonal antibody that inhibits pro-inflammatory activity of tumour-necrosis factor alpha (TNFα) and it is the primary biological agent used in the treatment of moderate-to-severe ulcerative colitis (UC). We report a case of vitiligo following infliximab administration in a patient with refractory UC. The case serves as a reminder of adverse cutaneous reactions induced by TNFα-antagonist therapy.

  4. Infliximab for the treatment of pouchitis

    PubMed Central

    Zippi, Maddalena; Cassieri, Claudio; Avallone, Eleonora Veronica; Pica, Roberta

    2013-01-01

    Pouchitis is not a rare complication that develops after an ileal-pouch anastomosis, performed after colectomy in patients refractory to treatment or with complicated ulcerative colitis. This condition may become chronic and unresponsive to medical therapies, including corticosteroids, antibiotics and probiotics. The advent of biological therapies (tumor necrosis factor-α inhibitors) has changed the course of these complications. In particular, in these cases, infliximab (IFX) may represent a safe and effective therapy in order to avoid the subsequent operation for a permanent ileostomy. This article reviews the therapeutic effects of one of the most widely used anti-tumor necrosis factor-α molecules, IFX, for the treatment of complicated pouchitis (refractory to conventional treatment and/or fistulizing). PMID:24303499

  5. Effectiveness of infliximab in refractory FDG PET-positive sarcoidosis.

    PubMed

    Vorselaars, Adriane D M; Crommelin, Heleen A; Deneer, Vera H M; Meek, Bob; Claessen, Anke M E; Keijsers, Ruth G M; van Moorsel, Coline H M; Grutters, Jan C

    2015-07-01

    Inconclusive evidence for the efficacy of infliximab in sarcoidosis hinders the global use of this potentially beneficial drug. To study infliximab efficacy in a clinical setting, we performed a prospective open-label trial in patients refractory to conventional treatment. Patients (n=56) received eight infusions of 5 mg·kg(-1) infliximab. Pulmonary function, disease activity measured by (18)F-fluorodeoxyglucose (FDG) by positron emission tomography (PET) and quality of life were part of the clinical work-up. Infliximab levels were measured before every infusion. After 26 weeks of infliximab treatment, mean improvement in forced vital capacity (FVC) was 6.6% predicted (p=0.0007), whereas in the 6 months before start of treatment, lung function decreased. Maximum standardised uptake value (SUVmax) of pulmonary parenchyma on (18)F-FDG PET decreased by 3.93 (p<0.0001). High SUVmax of pulmonary parenchyma at baseline predicted FVC improvement (R=0.62, p=0.0004). An overall beneficial response was seen in 79% of patients and a partial response was seen in 17% of patients. No correlation between infliximab trough level (mean 18.0 µg·mL(-1)) and initial response was found. In conclusion, infliximab causes significant improvement in FVC in refractory (18)F-FDG PET positive sarcoidosis. Especially in pulmonary disease, high (18)F-FDG PET SUVmax values at treatment initiation predict clinically relevant lung function improvement. These results suggest that inclusion of (18)F-FDG PET is useful in therapeutic decision-making in complex sarcoidosis.

  6. Long-term outcomes of refractory neurosarcoidosis treated with infliximab.

    PubMed

    Cohen Aubart, Fleur; Bouvry, Diane; Galanaud, Damien; Dehais, Caroline; Mathey, Guillaume; Psimaras, Dimitri; Haroche, Julien; Pottier, Corinne; Hie, Miguel; Mathian, Alexis; Devilliers, Hervé; Nunes, Hilario; Valeyre, Dominique; Amoura, Zahir

    2017-03-04

    Central nervous system localizations of sarcoidosis may be refractory to conventional treatment such as steroids and immunosuppressive drugs. Infliximab, a TNF-α antagonist chimeric antibody, has been shown to be effective for treatment of these localizations. The aim of this study was to evaluate the efficacy and safety, in particular the long-term outcomes, of the use of infliximab for the treatment of neurosarcoidosis. We retrospectively reviewed medical records of patients with neurosarcoidosis who had been treated with infliximab between 2009 and 2015. All patients had histologically proven non-caseating granulomas. Eighteen patients with histologically proven sarcoidosis were included in this study. All had neurological involvement consisting of meningeal (n = 16), cerebral (n = 10), spinal cord (n = 6), and/or optic nerve (n = 5) involvement. Sixteen patients had previously received at least one immunosuppressive drug in addition to corticosteroids, including cyclophosphamide in 11 patients. All patients received treatment with infliximab (3-7.5 mg/kg) associated with corticosteroids (n = 18), low-dose methotrexate (n = 15), azathioprine (n = 2), or mycophenolate (n = 1). Sixteen out of 18 patients improved clinically (initial median modified Rankin scale score of 3, final median score of 1; p < 0.0001). At 6 months after initiation of infliximab, six patients obtained complete remission (33%), ten attained partial remission (56%), and two had stable disease (11%). The median follow-up time was 20 months (range 6-93). Nine patients relapsed during follow-up (50%). Eight patients developed toxic side effects and seven of these side effects were infectious events. Infliximab is an efficacious treatment of refractory neurosarcoidosis. However, relapses frequently occurred during follow-up.

  7. A case of Crohn's disease that developed anti-infliximab and anti-adalimumab antibodies.

    PubMed

    Takahashi, Kenichiro; Fujimoto, Takehide; Shioya, Makoto; Nishida, Atsushi; Bamba, Shigeki; Inatomi, Osamu; Imaeda, Hirotsugu; Kitoh, Katsuyuki; Andoh, Akira

    2015-04-01

    There are few reports about the rapid appearance of anti-adalimumab antibodies in patients with Crohn's disease positive for anti-infliximab antibodies. We report the case of a 29-year-old female patient with a diagnosis of Crohn's disease who revealed a loss of response to infliximab due to high levels of antibodies to infliximab, and did not respond to the subsequent therapy by adalimumab, with a rapid appearance of antibodies to adalimumab. As one of the possible mechanisms of non-response to adalimumab, immunologic reactivity of infliximab to adalimumab was suspected, since the patient's IgG that was obtained just before the induction of adalimumab reacted with infliximab and adalimumab. We should pay attention to the easy appearance of anti-adalimumab antibodies in association with reactivity of anti-infliximab antibodies to adalimumab in patients with high levels of anti-infliximab antibodies.

  8. Pneumocystis jiroveci (carinii) pneumonia after infliximab therapy: a review of 84 cases.

    PubMed

    Kaur, Nirmal; Mahl, Thomas C

    2007-06-01

    Anti-tumor necrosis factor-alpha therapy, infliximab, has become an established effective therapy for Crohn's disease and rheumatoid arthritis. However, infliximab has been associated with various opportunistic pathogens such as tuberculosis, histoplasmosis, listeriosis, aspergillosis, and Pneumocystis jiroveci (carinii) pneumonia. We reviewed the FDA Adverse Event Reporting System for cases of Pneumocystis associated with infliximab use from January 1998 through December 2003. The database revealed 84 cases of PCP following infliximab therapy. Concomitant immunosuppressive medications included methotrexate, prednisone, azathioprine, 6-mercaptopurine, and cyclosporine. Mean time between infliximab infusion and onset of symptoms of pneumonia, when reported, was 21 days (+/-18 days; n=40). Twenty-three of the 84 (27%) patients died. The use of infliximab is associated with PCP infection. Further, the mortality rate for Pneumocystis following the use of infliximab is significant. The potential for severe disease, mortality, and often subtle presentation of these infections warrant close follow-up and careful monitoring after therapy.

  9. The Effect of Infliximab on Intestinal Anastomosis Healing in Rats.

    PubMed

    Karaköse, Oktay; Eken, Hüseyin; Ulusoy, Ali Naki; Topgül, Hüseyin Koray; Bilgin, Mehmet; Yürüker, Saim Savaş; Gülbahar, Mustafa Yavuz

    Intestinal anastomosis healing is a complex physiological process in which many local and systemic factors play a role. One of the significant cytokines in this process is TNF-α. Infliximab is a chimeric monoclonal antibody which binds to TNF-α with high affinity. Although this agent is used in ulcerative colitis and Crohn's disease, intestinal surgery may be required in these patients. In this study it was aimed to determine whether or not there was any negative effect of preoperative single dose infliximab treatment on intestinal anastomosis healing. Two groups of 10 rats were formed. One of these groups was administered with a single dose of infliximab 8 mg/kg as a 20-minute intravenous infusion from the femoral vein. Four days after the infusion, a full layer incision was made to the colon and anastomosis was applied to all the rats. At 7 days after anastomosis, the subjects were sacrificed. The anastomosis segment was removed and the bursting pressure was measured. Tissue samples were taken from this segment for hydroxyproline concentration and histopathological examination. A blood sample was taken to measure TNF-α values. No statistically significant difference was determined between the groups in terms of bursting pressure, tissue hydroxyproline concentration or histopathological scoring. A single dose of 8 mg/kg infliximab administered 4 days preoperatively was not found to have any negative effect on intestinal anastomosis healing in rats.

  10. Crohn's-associated chronic recurrent multifocal osteomyelitis responsive to infliximab.

    PubMed

    Carpenter, Ellen; Jackson, Mary Anne; Friesen, Craig A; Scarbrough, Marc; Roberts, Charles C

    2004-04-01

    We report a case of chronic recurrent clavicular osteomyelitis in association with Crohn disease. Steroid therapy resulted in partial remission; however, intractable shoulder pain and an enlarging clavicular mass subsequently recurred. Infliximab therapy resulted in significant improvement in the degree of bone pain and resolution of the large sclerotic clavicular lesion.

  11. Infliximab as the First Retreatment in Patients with Kawasaki Disease Resistant to Initial Intravenous Immunoglobulin.

    PubMed

    Youn, Youngmin; Kim, Jisoo; Hong, Young Mi; Sohn, Sejung

    2016-04-01

    Forty-three patients with Kawasaki disease who were resistant to initial intravenous immunoglobulin (IVIG) were randomized to receive either a second dose of IVIG (n = 32) or an infliximab (n = 11). With IVIG retreatment 21 patients (65.6%) responded, and with infliximab 10 patients (90.9%) responded. The infliximab group had shorter duration of fever and fewer days of hospitalization. Coronary artery outcomes and adverse events were similar.

  12. Characteristics and outcomes of rheumatoid arthritis patients who started biosimilar infliximab.

    PubMed

    Sung, Yoon-Kyoung; Cho, Soo-Kyung; Kim, Dam; Won, Soyoung; Choi, Chan-Bum; Bang, So-Young; Hong, Seung-Jae; Kim, Hyoun Ah; Koh, Eun-Mi; Lee, Hye-Soon; Suh, Chang-Hee; Yoo, Dae-Hyun; Bae, Sang-Cheol

    2017-02-18

    To compare the characteristics of rheumatoid arthritis (RA) patients receiving either biosimilar or originator infliximab and to identify the effectiveness and safety of biosimilar infliximab in RA patients in real-world practice. RA patients who started either biosimilar or originator infliximab were selected using the prospective biologic disease-modifying anti-rheumatic drugs (DMARDs) registry: BIOlogics Pharmacoepidemiologic StudY (BIOPSY). Baseline characteristics of the two groups were compared, and short-term treatment outcomes, including DAS28-ESR and HAQ-DI scores, were compared after initiation of biosimilar or originator infliximab. The drug retention rates of the two groups were also compared. A total of 100 RA patients, 55 biosimilar, and 45 originator infliximab users were included in this analysis. Baseline characteristics of age, disease duration, and previous or current medications were similar in the two groups. Baseline DAS28-ESR was higher in the originator infliximab group (6.3 ± 1.1 vs. 5.8 ± 1.1, p = 0.02). The early DAS28-ESR remission rates observed 7.9 ± 1.8 months after starting biosimilar and originator infliximab were 15.0 and 25.0%, respectively (p = 0.47). The change in HAQ-DI did not differ between the two groups (0.4 ± 0.7 vs. 0.4 ± 0.8, p = 0.94). Patients treated with biosimilar infliximab in clinical practice had lower disease activity at the start of treatment than those receiving originator infliximab. Biosimilar infliximab was well-tolerated, safe, and of similar clinical effectiveness to originator infliximab. Larger number of patient and longer follow-up data will be needed to confirm the effectiveness and safety of biosimilar infliximab in clinical practice.

  13. Infliximab Modulates Cisplatin-Induced Hepatotoxicity in Rats

    PubMed Central

    Cüre, Medine Cumhur; Cüre, Erkan; Kalkan, Yıldıray; Kırbaş, Aynur; Tümkaya, Levent; Yılmaz, Arif; Türkyılmaz, Ayşegül Küçükali; Şehitoğlu, İbrahim; Yüce, Süleyman

    2016-01-01

    Background: Cisplatin (Cis) is one of the most commonly used antineoplastic drugs. It is used as chemotherapy for many solid organ malignancies such as brain, neck, male and female urogenital, vesical and pulmonary cancers. Infliximab blocks tumor necrosis factor alpha (TNF-α). Several studies have reported that infliximab ameliorates cell damage by reducing cytokine levels. Aims: We aimed to investigate whether infliximab has a preventive effect against cisplatin-induced hepatotoxicity and whether it has a synergistic effect when combined with Cis. Study Design: Animal experimentation. Methods: Male Wistar albino rats were divided in three groups as follows: Cis group, infliximab + Cis (CIN) group and the control group. Each group comprised 10 animals. Animals in the Cis group received an intraperitoneal single-dose injection of Cis (7 mg/kg). In the CIN group, a single dose of infliximab (7 mg/kg) was administered 72 h prior to the Cis injection. After 72 h, a single dose of Cis (7 mg/kg) was administered. All rats were sacrificed five days after Cis injection. Results: TNF-α levels in the Cis group were significantly higher (345.5±40.0 pg/mg protein) than those of the control (278.7±62.1 pg/mg protein, p=0.003) and CIN groups (239.0±64.2 pg/mg protein, p=0.013). The Cis group was found to have high carbonic anhydrase (CA)-II and low carbamoyl phosphate synthetase-1 (CPS-1) levels. Aspartate transaminase (AST) and alanine transaminase (ALT) levels were lower in the CIN group as compared to the Cis group. Total histological damage was greater in the Cis group as compared to the control and CIN groups. Conclusion: Cis may lead to liver damage by increasing cytokine levels. It may increase oxidative stress-induced tissue damage by increasing carbonic anhydrase II (CA-II) enzyme levels and decreasing CPS-1 enzyme levels. Infliximab decreases Cis-induced hepatic damage by blocking TNF-α and it may also protect against liver damage by regulating CPS-1 and CA

  14. Concomitant alopecia areata and hypertrichosis after infliximab therapy: rara avis.

    PubMed

    Akarsu, Selim; Tok, Fatih; Tekin, Levent

    2013-01-01

    We present a 37 year-old man with HLA-B27 positive ankylosing spondylitis for the last 3 years. Interestingly, he developed both alopecia areata and hypertrichosis simultaneously following infliximab treatment. Reporting this interesting patient of ours -to our best notice for the first time in the literature- we call attention of clinicians to the contradistinctive effects of anti-TNF-α agents on hair growth cycle.

  15. New-onset vitiligo during long-term, stable infliximab treatment of pityriasis rubra pilaris.

    PubMed

    Mattox, Adam R; Chappell, Jeaneen A; Hurley, M Yadira

    2013-02-01

    Incidents of new-onset vitiligo attributed to infliximab therapy for rheumatoid arthritis and ulcerative colitis have been reported. Reported cases share a common theme in that symptoms manifested in close proximity to the initiation or significant dose increase of the medication. This case describes the presentation of infliximab-induced vitiligo in a patient using it for long-term treatment of stable pityriasis rubra pilaris. The patient was initiated and titrated to a stable dose of infliximab totaling 27 months' duration. He was able to achieve near-complete resolution of symptoms before developing depigmented patches consistent with vitiligo. Infliximab was discontinued. Tacrolimus 0.1% ointment and narrow-band ultraviolet B light successfully repigmented the patches. The association of discontinuing infliximab and resolution of vitiligo suggests infliximab had a role in this case. Though the mechanism of involvement is undetermined, infliximab may have induced an autoimmune process by paradoxically activating lymphocytes. Alternatively, infliximab antibodies may have led to the process by disrupting the normal balance of cytokines.

  16. A rare case of supraventricular tachycardia induced by Infliximab: a case report

    PubMed Central

    2009-01-01

    Background Infliximab, a chimeric monoclonal immunoglobulin antibody to tumor necrosis factor-α, has been established as a safe and effective treatment of rheumatoid arthritis, active and fistulising crohn's disease. Infliximab is generally well tolerated drug. The commonly reported cardiac side effects of Infliximab include exacerbation of congestive heart failure, hypotension and syncope. Symptomatic disorders of cardiac rhythm have been reported only rarely in few case reports and to the best of our knowledge, no tachyarrhythmia has been reported in past. Case report We report the case of a supraventricular tachycardia that occurred within three hours of Infliximab infusion in a patient with rheumatoid arthritis. Conclusion It is interesting to note that prior infusions in this patient did not precipitate similar consequences, thus, emphasising the importance of careful monitoring of patients on Infliximab therapy for possible reactions, even if prior exposures have been uneventful. PMID:19946518

  17. Experience with biosimilar infliximab (CT-P13) in paediatric patients with inflammatory bowel diseases.

    PubMed

    Sieczkowska, Joanna; Jarzębicka, Dorota; Meglicka, Monika; Oracz, Grzegorz; Kierkus, Jaroslaw

    2016-09-01

    Infliximab was the first monoclonal antibody used in the treatment of inflammatory bowel disease (IBD). Over several years, this antitumour necrosis factor (TNF) treatment proved its efficacy in both induction and maintenance therapy. In many cases this biological treatment stopped the progression of the disease, probably also decreasing morbidity and hospitalization rates, and improving patients' comfort. When the patent on infliximab started to expire, the first biosimilar of a monoclonal antibody was introduced onto the pharmacological market. Biosimilar infliximab was studied in rheumatology and proved a high similarity to the reference drug. Based on extrapolation, biosimilars were approved to treat adult and paediatric IBD patients. Biosimilar infliximab, mainly because of its lower cost, has started to be in common use in Europe. The first studies have shown a similar efficacy and safety profile in comparison with reference drug. Biosimilar infliximab is raising hopes for improving the availability of this effective treatment.

  18. Primary tuberculous peritonitis during infliximab therapy for Crohn's disease.

    PubMed

    Bonse-Geuking, Ulrich; Kraus, Michael

    2012-07-01

    A 64 year old male patient suffering from Crohn's disease received infliximab therapy for a period of 5 months prior to presentation to our hospital. Due to the symptoms fever, ascites, and diffuse abdominal tenderness on palpation of unknown origin, a CT scan of the abdomen was performed and led to the suspected diagnosis of a peritoneal carcinomatosis. QuantiFERON™ test revealed a tuberculosis infection and molecular analyses of a peritoneal specimen obtained by laparoscopy clearly identified Mycobacterium tuberculosis DNA. Quadruple tuberculostatic therapy was initiated and the patient's condition continuously improved thereafter.

  19. Development of Eosinophilic Fasciitis during Infliximab Therapy for Psoriatic Arthritis

    PubMed Central

    Hariman, Richard; Patel, Payal; Strouse, Jennifer; Collins, Michael P.; Rosenthal, Ann

    2016-01-01

    Eosinophilic fasciitis (EF) is a rare disorder involving chronic inflammation of the fascia and connective tissue surrounding muscles, nerves, and blood vessels. While its pathogenesis is not entirely understood, this disorder is thought to be autoimmune or allergic in nature. We present here a case of a 59-year-old male who developed peripheral eosinophilia and subsequent eosinophilic fasciitis during treatment with infliximab. To our knowledge, eosinophilic fasciitis has not been previously described in patients during treatment with an inhibitor of tumor necrosis factor α. PMID:27293946

  20. Real-Life Efficacy, Immunogenicity and Safety of Biosimilar Infliximab.

    PubMed

    Vegh, Zsuzsanna; Kurti, Zsuzsanna; Lakatos, Peter L

    2017-01-01

    Recently, the use of biosimilar infliximab (IFX) in the treatment of inflammatory bowel diseases has become widespread in some European and non-European countries. Data on the efficacy, safety and immunogenicity from real-life cohorts are accumulating. The first reports showed similar outcomes in the induction and maintenance of remission, mucosal healing, safety and immunogenicity profile to the originator IFX. In the present review, we aimed to summarize the existing knowledge on the efficacy, safety and immunogenicity profile of biosimilar IFX reported from real-life cohorts.

  1. Power Doppler ultrasonography in the evaluation of infliximab treatment for sacroiliitis in patients with ankylosing spondylitis.

    PubMed

    Jiang, Yeqing; Chen, Ling; Zhu, Jiaan; Xue, Qin; Wang, Niansong; Huang, Yunxia; Liu, Fang; Hu, Yizhou; Hu, Bing

    2013-08-01

    The aim of this study was to evaluate the feasibility of using power Doppler ultrasound (PDUS) to detect changes in the sacroiliac joint regions after infliximab (an anti-TNF-α blocker) treatment in active axial ankylosing spondylitis (AS) patients. A total of 110 sacroiliac joints in 55 patients with active AS were detected by PDUS before and after the infliximab treatment. The color flow signals inside the sacroiliac joints were observed, and the resistance index (RI) was measured. The clinical condition of the AS patients was improved compared with their condition before the infliximab treatment. Before the treatment, color flow signals were observed in 103 joints, and the mean RI value was 0.56 ± 0.06. Three months after the first infliximab treatment, color flow signals were observed in 50 joints, and the mean RI value was 0.87 ± 0.11. There were more blood flow signals in the sacroiliac joints before the infliximab treatment in patients with active AS (p < 0.01), and the mean RI value was higher after the infliximab treatment (p < 0.01). The blood flow signals in the sacroiliac joints became weaker or even disappeared and the RI values increased in patients with active sacroiliitis after infliximab treatment. This result shows that PDUS can be used in the follow-up of patients with axial AS.

  2. The role of infliximab on paracetamol-induced hepatotoxicity in rats.

    PubMed

    Ferah, Irmak; Halici, Zekai; Bayir, Yasin; Demirci, Elif; Unal, Bunyami; Cadirci, Elif

    2013-06-01

    Paracetamol has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Infliximab is tumor necrosis factor alpha (TNF-α) inhibitor agent, which has been developed as a therapeutic agent for TNF-α-mediated disease. It acts by binding and neutralizing TNF. The aim of our study was to evaluate the hepatoprotective activity of infliximab on paracetamol-induced hepatotoxicity and to understand the relationship between the TNF-α and paracetamol-induced liver injury. Fifty-six rats were divided into eight groups as each composed of seven rats: (1) intact, (2) 7 mg/kg infliximab, (3) 140 mg/kg NAC, (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 3 mg/kg infliximab, (7) 2 g/kg paracetamol + 5 mg/kg infliximab and (8) 2 g/kg paracetamol + 7 mg/kg infliximab groups. Liver function tests including lipid peroxidation levels were analyzed and histopathological changes of liver were also observed. There were statistically significant increases in the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), levels of TNF-α and malondialdehyde (MDA) and decreases in the activity of superoxide dismutase (SOD) and level of glutathione (GSH) in the group treated with paracetamol. Infliximab administration dramatically reduced serum ALT, AST and TNF-α level. Also, it restored GSH, SOD and decreased MDA levels in liver. Liver histopathological examination showed that infliximab administration antagonized paracetamol-induced liver pathological damage. The results of present study suggest that infliximab has significant hepatoprotective activity on paracetamol-induced hepatotoxicity.

  3. Inflammatory bowel disease of the lung: The role of infliximab?☆

    PubMed Central

    Hayek, Adam J.; Pfanner, Timothy P.; White, Heath D.

    2015-01-01

    Pulmonary extra-intestinal manifestations (EIM) of inflammatory bowel disease are well described with a variable incidence. We present a case of Crohn's disease with pulmonary EIM including chronic bronchitis with non-resolving bilateral cavitary pulmonary nodules and mediastinal lymphadenopathy successfully treated with infliximab. Additionally, we present a case summary from a literature review on pulmonary EIM successfully treated with infliximab. Current treatment recommendations include an inhaled and/or systemic corticosteroid regimen which is largely based on case reports and expert opinion. We offer infliximab as an adjunctive therapy or alternative to corticosteroids for treatment of inflammatory bowel disease related pulmonary EIM. PMID:26236612

  4. Adherence to Infliximab Treatment in a Pediatric Inflammatory Bowel Disease Cohort.

    PubMed

    Vitale, David S; Greenley, Rachel N; Lerner, Diana G; Mavis, Alisha M; Werlin, Steven L

    2015-10-01

    The aims of the study were to describe infliximab adherence in a pediatric inflammatory bowel disease cohort, to identify demographic and disease factors associated with adherence, and to examine differences in acute care use among adherent and nonadherent patients. Charts of patients who received infliximab at the Children's Hospital of Wisconsin (CHW) between October 2010 and October 2012 were retrospectively reviewed. A total of 151 patients met the inclusion criteria; 91.4% of the patients were adherent. Nonadherent patients had more emergency room visits and hospitalizations than adherent patients. The study is the first to show high adherence rates to infliximab in a pediatric cohort.

  5. Linear IgA Bullous Dermatosis Secondary to Infliximab Therapy in a Patient with Ulcerative Colitis.

    PubMed

    Hoffmann, Jochen; Hadaschik, Eva; Enk, Alexander; Stremmel, Wolfgang; Gauss, Annika

    2015-01-01

    Linear IgA bullous disease (LABD) is a rare vesiculobullous autoimmune skin disorder whose etiology and pathogenesis are not completely understood. Its occurrence has been related to malignancies, inflammatory diseases and several drugs. This report describes a 49-year-old Caucasian male with a 14-year history of ulcerative colitis who received infliximab to treat the refractory course of his bowel disease. During induction therapy with infliximab, he developed LABD. Treatment with infliximab was discontinued, and the skin lesions were successfully treated with oral steroids and dapsone. Considering the close chronological relation between administration of the tumor necrosis factor-α inhibitor and onset of the skin disease, we hypothesize that this is the first reported case of infliximab-induced LABD. Similar to psoriasis, it may represent a 'paradoxical' autoimmune reaction triggered by anti-tumor necrosis factor-α therapy.

  6. Acne fulminans with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome treated with infliximab.

    PubMed

    Iqbal, Marvi; Kolodney, Michael S

    2005-05-01

    Acne fulminans is a syndrome of sudden onset hemorrhagic and ulcerative acne involving the back, chest, and face combined with systemic symptoms. It can be the dermatologic manifestation of the synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome. Current therapy for acne fulminans consists of wound care, topical and systemic corticosteroids, isotretinoin, and nonsteroidal anti-inflammatory drugs (NSAIDs). Infliximab, a recently developed monoclonal antibody against tumor necrosis factor-alfa, has shown efficacy in the treatment of psoriatic arthritis and ankylosing spondylitis both of which share clinical similarities to the SAPHO syndrome. We report the case of a patient with the SAPHO syndrome and acne fulminans who was treated with infliximab. Ten months after initiating therapy with infliximab, the area of the patient's ulcerative lesions was reduced by 70%. Infliximab might be considered as a treatment option for patients with acne fulminans unresponsive to conventional therapies.

  7. Appropriate infliximab infusion dosage and monitoring: results of a panel meeting of rheumatologists, dermatologists and gastroenterologists

    PubMed Central

    de Vries, Hilbert S; van Oijen, Martijn G H; Driessen, Rieke J B; de Jong, Elke M G J; Creemers, Marjonne C W; Kievit, Wietske; de Jong, Dirk J

    2011-01-01

    AIMS Infliximab, an anti-TNF biologic agent, is currently indicated and reimbursed for rheumatoid arthritis, ankylosing spondylitis, Crohn's disease (both adult and paediatric), ulcerative colitis, psoriatic arthritis and plaque psoriasis. Development of national and international guidelines for rheumatology, gastroenterology and dermatology, was mostly based on clinical studies and expert opinion. The aim of this study was to compare available guidelines and local protocols for rheumatology, dermatology and gastroenterology, regarding dosage of infliximab, synergy of infliximab with concomitant medication and monitoring of vital signs during infliximab administration, for achieving optimal care. METHODS Current international, national and local guidelines on the use of infliximab were reviewed and compared, differences and shortcomings were identified, and optimal treatment schedules discussed during a meeting (July 2008) of clinical experts and researchers from three departments of a Dutch university hospital. RESULTS Recommended dosages of infliximab are not equal for different indications. Loss of response to infliximab is a common problem encountered within the three medical specialties, but indications for adjustments in treatment schedules are lacking in all of the guidelines. Monitoring of vital signs (blood pressure, pulse, temperature) during infusion with infliximab is common practice and recommended by some guidelines. Routine measurement of vital signs is not of any value in predicting or recognizing acute infusion reactions, in our experience, and this is confirmed by literature on inflammatory bowel disease. CONCLUSION Different indications encompass different dosing schedules. National and internal guidelines do not provide advice regarding loss of response. Routine measurement of vital signs during infusion is not valuable in detecting acute infusion reactions and should only be performed in case of an acute infusion reaction. These topics need to

  8. Spinal epidural abscess associated with infliximab treatment for psoriatic arthritis. Case report.

    PubMed

    Smith, Adam P; Musacchio, Michael J; O'Toole, John E

    2008-09-01

    Tumor necrosis factor-alpha inhibitors are used to treat numerous chronic inflammatory and rheumatological diseases, such as Crohn disease, rheumatoid arthritis, and psoriatic arthritis. Because the mechanism of these inhibitors is to decrease the body's inflammatory response, the primary complication of treatment is infection. The authors present the first case of a spinal epidural abscess in a patient receiving long-term infliximab therapy for severe psoriatic arthritis. Infliximab and its side-effect profile are discussed, along with other associated complications.

  9. Neutrophil-to-Lymphocyte Ratio for Predicting Loss of Response to Infliximab in Ulcerative Colitis

    PubMed Central

    Nishida, Yu; Yamagami, Hirokazu; Yukawa, Tomomi; Otani, Koji; Nagami, Yasuaki; Tanaka, Fumio; Taira, Koichi; Kamata, Noriko; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Kenji; Watanabe, Toshio; Tominaga, Kazunari; Fujiwara, Yasuhiro

    2017-01-01

    Objectives Neutrophil-to-lymphocyte ratio (NLR) has been used to determine the outcome in malignancies and coronary heart disease. Some reports considered the value of NLR as a predictor of response to infliximab in patients with Crohn’s disease or rheumatoid arthritis; however, no similar studies have been reported for ulcerative colitis (UC). This study aimed to evaluate the clinical significance of the baseline NLR in patients with UC treated by infliximab. Materials and Methods Patients with moderate-to-severe active UC who received the first infliximab infusion in our hospital between 2010 and 2015, who showed clinical response during the induction period, were retrospectively evaluated for long-term outcomes and risk factors for loss of response (LOR) during infliximab maintenance therapy. Baseline inflammatory markers including NLR were measured within one week before the initiation of infliximab. Results Fifty-nine patients with moderate-to-severe active UC started treatment with infliximab and 37 patients (62.7%) experienced clinical response after induction therapy. Fourteen of 37 patients on maintenance therapy lost the response during follow-up. Baseline NLR of patients with LOR was significantly higher than in patients with sustained response. The NLR cut-off value of 4.488 was predictive of LOR, using receiver operating characteristic analysis (sensitivity: 78.6%, specificity: 78.3%). A univariate analysis revealed a significant relationship between relapse-free survival and the NLR (P = 0.018). Multivariate analysis indicated the NLR as an independent prognostic factor for LOR (hazard ratio = 3.86, 95% confidence interval: 1.20–12.4, P = 0.023). Conclusions Baseline NLR is a useful prognostic marker in patients with moderate-to-severe active UC treated with infliximab, and may contribute to appropriate use of infliximab. PMID:28076386

  10. Perioperative infliximab application ameliorates acute rejection associated inflammation after intestinal transplantation.

    PubMed

    Pech, T; Finger, T; Fujishiro, J; Praktiknjo, M; Ohsawa, I; Abu-Elmagd, K; Limmer, A; Hirner, A; Kalff, J C; Schaefer, N

    2010-11-01

    As we have shown in the past, acute rejection-related TNF-α upregulation in resident macrophages in the tunica muscularis after small bowel transplantation (SBTx) results in local amplification of inflammation, decisively contributing to graft dysmotility. Therefore, the aim of this study is to investigate the effectiveness of the chimeric-monoclonal-anti-TNF-α antibody infliximab as perioperative single shot treatment addressing inflammatory processes during acute rejection early after transplantation. Orthotopic, isogenic and allogenic SBTx was performed in rats (BN-Lewis/BN-BN) with infliximab treatment. Vehicle and IV-immunoglobulin-treated animals served as controls. Animals were sacrificed after 24 and 168 h. Leukocyte infiltration was investigated in muscularis whole mounts by immunohistochemistry, mediator mRNA expression by Real-Time-RT-PCR, apoptosis by TUNEL and smooth muscle contractility in a standard organ bath. Both, infliximab and Sandoglobulin® revealed antiinflammatory effects. Infliximab resulted in significantly less leukocyte infiltration compared to allogenic controls and IV-immunoglobulin, which was accompanied by lower gene expression of MCP-1 (24 h), IFN-γ (168 h) and infiltration of CD8-positive cells. Smooth muscle contractility improved significantly after 24 h compared to all controls in infliximab treated animals accompanied by lower iNOS expression. Perioperative treatment with infliximab is a possible pharmaceutical approach to overcome graft dysmotility early after SBTx.

  11. [Legionella pneumonia after infliximab in a patient with rheumatoid arthritis].

    PubMed

    Giassi, Karina de Souza; Furlanetto, Vilson; Fialho, Sonia; Gomes Ribeiro, Giovana; Pereira, Ivânio Alves

    2014-01-01

    The antagonists of tumour necrosis factor (anti-TNF) have been successfully used in several chronic inflammatory diseases such as Rheumatoid Arthritis (RA), but some studies have observed the development of infections by intracellular pathogens in patients using anti-TNF. We report a case of a female patient with previous diagnosis of RA for 16 years that used several disease-modifying anti-rheumatic drugs (DMARDs) that resulted in treatment failure, and then was treated with infliximab. After fifteen days of the second dose, the patient developed ventilatory-dependent chest pain, dry cough and dyspnea. She was hospitalized, and the diagnosis of pneumonia by Legionella pneumophila was confirmed by the presence of Legionella antigen in an urine test. TNF is an inflammatory cytokine that also acts inhibiting the bacterial growth of intracellular pathogens, and its inhibition seems to increase susceptibility to these infections in some patients.

  12. Infliximab therapy increases the frequency of circulating CD16(+) monocytes and modifies macrophage cytokine response to bacterial infection.

    PubMed

    Nazareth, N; Magro, F; Silva, J; Duro, M; Gracio, D; Coelho, R; Appelberg, R; Macedo, G; Sarmento, A

    2014-09-01

    Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points. To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16(+) and CD16(-) monocytes and the frequency of TNF(+) cells among CD16(+) and CD16(-) monocyte-derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria. An infliximab-dependent increase in the frequency of circulating CD16(+) monocytes (particularly the CD14(++) CD16(+) subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD16(+) monocytes were higher TNF producers and CD16(+) macrophages from infliximab-treated CD patients showed increased frequency of TNF(+) cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16(+) circulating monocytes, particularly of the CD14(++) CD16(+) subset. Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages.

  13. Sarcoidosis associated with infliximab therapy in ulcerative colitis

    PubMed Central

    Gîlcă, Georgiana-Emmanuela; Diaconescu, Smaranda; Bălan, Gheorghe Gh.; Timofte, Oana; Ştefănescu, Gabriela

    2017-01-01

    Abstract Rationale: Although immunomodulatory therapy has been clearly stated as an important landmark in treatment of ulcerative colitis, significantly improving the quality of life for patients with inflammatory bowel disease, there are several aspects to be considered regarding the possible side-effects of anti-TNF alpha agents. In spite of a good safety profile, biologic TNF antagonists may induce paradoxical inflammation, which can manifest as sarcoid-like granulomatosis, consisting of noncaseating granulomas in the affected organs. Patient concerns: We report the case of a 30-year-old male patient, with no personal or familial history of lung disease, with a personal history of ulcerative colitis (UC), under clinical remission following infliximab therapy in maintenance dose, who was admitted for treatment administration, but also for dyspnea, nocturnal sweating, and nonproductive cough. Diagnoses: Based on clinical manifestations, biological landmarks excluding various infections, CT scan, fibrobronchoscopy with bronchoalveolar lavage for culture and immunohistochemical examination, followed by mediastinoscopy with sampling of paratracheal lymph node, which underwent histopathological examination, the patient was diagnosed with drug- induced stage II pulmonary sarcoidosis. Interventions: Since the patient had developed severe allergic reaction after being administered Infliximab at admission, the biological treatment was immediately discontinued. Following the diagnosis of pulmonary sarcoidosis, corticotherapy was initiated. Patient outcomes: After corticotherapy was initiated, the patient had a favorable outcome at 3 months reevaluation, both regarding the course of ulcerative colitis and sarcoidosis. Lessons: Patients under biological therapy using anti-TNF alpha agents must be carefully monitored, in order to early identify potential paradoxical inflammation (such as sarcoidosis) as a side-effect. The drug-related pulmonary disease tends to improve upon

  14. Effect of infliximab against cisplatin-induced nephrotoxicity

    PubMed Central

    Cure, Erkan; Kirbas, Aynur; Tumkaya, Levent; Cure, Medine C.; Şahin, Osman Z.; Kalkan, Yildiray; Yuce, Suleyman; Altuner, Durdu

    2014-01-01

    Objectives: To investigate whether infliximab (Ib), an inhibitor of tumor necrosis factor alpha (TNF-α), prevents cisplatin (Cis)-induced nephrotoxicity. Methods: The study was performed in the Department of Internal Medicine, Recep Tayyip Erdogan University, Rize, Turkey, between November 2012 and May 2013. Thirty male Wistar albino rats were divided into 3 groups, a control group, a Cis group, and a Cis+Ib group. The animals of the Cis group were injected with a single dose (7 mg/kg) of Cis intraperitoneally. The animals of the Cis+Ib group were injected with a single dose (7 mg/kg) of Ib 72 hours prior to Cis injection. Results: The TNF-α, interleukin-1 beta (IL-1β), nitric oxide (NO) and adenosine deaminase (ADA) levels of the Cis group were higher than both the control group TNF-α (p<0.001), IL-1a (p<0.001), NO (p<0.001) and ADA (p<0.001), and the Cis+Ib group TNF-α (p<0.001), IL-1β (p<0.001), NO (p<0.001), and ADA (p=0.003). Histopathological examination revealed extensive damage in the Cis group, while the damage in the Cis+Ib group was lower. While the carbonic anhydrase II (CA-II) level of the Cis group was lower than both groups, it was similar in the Cis+Ib and the control groups. Conclusion: Infliximab acts against Cis-induced nephrotoxicity by a strong inhibition of TNF-α. Additionally, the combination of these 2 drugs does not obviously change the level of CA-II. PMID:25228176

  15. Cardiac Tamponade as a Presenting Manifestation of Infliximab-Induced Lupus in Patient Treated for Crohn’s Disease

    PubMed Central

    Kulairi, Zain; Kam, Michael

    2017-01-01

    Crohn’s disease is characterized by inflammation of the mucosal lining of the gastrointestinal tract. Infliximab is a tumor necrosis factor-α inhibitor that has been associated with increased remission and decreased disease flare-ups. Biological agents such as infliximab have been associated with adverse events. We present a rare case of cardiac tamponade caused by infliximab treatment for Crohn’s disease in a 30-year-old female. She was treated with emergent pericardial window and drainage of pericardial fluid. Infliximab was discontinued, and serositis was treated with steroids. The patient was later successfully rechallenged with vedolizumab. PMID:28138445

  16. Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn’s disease

    PubMed Central

    Oh, Eun Hye; Ko, Dae-Hyun; Seo, Hyungil; Chang, Kiju; Kim, Gwang-Un; Song, Eun Mi; Seo, Myeongsook; Lee, Ho-Su; Hwang, Sung Wook; Yang, Dong-Hoon; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun; Park, Sang Hyoung

    2017-01-01

    AIM To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries. METHODS IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice. PMID:28293096

  17. Primary treatment of incomplete Kawasaki disease with infliximab and methylprednisolone in a patient with a contraindication to intravenous immune globulin.

    PubMed

    Shirley, Debbie-Ann; Stephens, Ina

    2010-10-01

    Incomplete Kawasaki disease was diagnosed in a 3-year-old boy. Because intravenous immune globulin infusion was not tolerated, he was treated with infliximab and methylprednisolone. Coronary aneurysms were not visualized on initial or follow-up echocardiograms. To our knowledge, this is the first report to document the use of infliximab and methylprednisolone as first line therapy for Kawasaki disease.

  18. Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product

    PubMed Central

    Abdalla, Abuelmagd; Byrne, Niamh; Conway, Richard; Walsh, Thomas; Mannion, Geraldine; Hanly, Michael; O’Sullivan, Miriam; Curran, Ann Maria; Carey, John J

    2017-01-01

    Purpose To evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center. Patients and methods In April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval. Results Around 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9), mean disease duration 14.79 years (9.7), median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3) months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively). There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7%) patients discontinued the biosimilar infliximab. Conclusion Our patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost. PMID:28331376

  19. The immunogenicity of biosimilar infliximab: can we extrapolate the data across indications?

    PubMed

    Ben-Horin, Shomron; Heap, Graham A; Ahmad, Tariq; Kim, HoUng; Kwon, TaekSang; Chowers, Yehuda

    2015-01-01

    Biopharmaceuticals or 'biologics' have revolutionized the treatment of many diseases. However, some patients generate an immune response to such drugs, potentially limiting clinical efficacy and safety. Infliximab (Remicade(®)) is a monoclonal antibody used to treat several immune-mediated inflammatory disorders. A biosimilar of infliximab, CT-P13 (Remsima(®), Inflectra(®)), has recently been approved in Europe for all indications in which infliximab is approved. Approval of CT-P13 was based in part on extrapolation of clinical trial data from two indications (rheumatoid arthritis and ankylosing spondylitis) to all other indications, including inflammatory bowel disease. This review discusses the validity of extrapolating immunogenicity data across indications - a process adopted by the EMA as part of their biosimilar approval process - with a focus on CT-P13.

  20. Dramatic improvement of pyoderma gangrenosum with infliximab in a patient with PAPA syndrome.

    PubMed

    Stichweh, Dorothee S; Punaro, Marilynn; Pascual, Virginia

    2005-01-01

    Infliximab, a chimeric antitumor necrosis factor alpha monoclonal antibody (anti-TNF alpha), has been recently shown to have a beneficial effect on pyoderma gangrenosum associated with inflammatory bowel disease. Patients with the syndromic triad of pyogenic sterile arthritis, pyoderma gangrenosum, and acne, an autoinflammatory process caused by mutations in the CD2 binding protein-1 (CD2BP1) gene, can have severe pyoderma gangrenosum. We describe a 14-year-old patient with this syndrome who was unresponsive to multiple therapies. A dramatic improvement in his pyoderma gangrenosum was observed after one infusion of infliximab, and a second infusion led to its resolution. Our observation extends the therapeutic use of infliximab to this component of PAPA syndrome.

  1. Disseminated nocardiosis in a patient on infliximab and methylprednisolone for treatment-resistant Sweet's syndrome.

    PubMed

    Drone, Elizabeth R; McCrory, Allison L; Lane, Natalie; Fiala, Katherine

    2014-07-01

    A 62-year-old white man with a 10-year history of treatment-refractory Sweet's syndrome was admitted to the hospital with the onset of purpuric lesions. Methylprednisolone and infliximab were administered. Our patient developed disseminated Nocardia infection and eventually succumbed. Opportunistic infections such as Nocardia have been associated with infliximab and other tumour necrosis factor (TNF)-α inhibitors. The astute clinician should be aware of the risk of rare opportunistic infections, particularly in patients on TNF-α inhibitors and systemic corticosteroids.

  2. Fungal arthritis of the wrist caused by Candida parapsilosis during infliximab therapy for rheumatoid arthritis.

    PubMed

    Miyamoto, Hideaki; Miura, Toshiki; Morita, Euan; Morizaki, Yutaka; Uehara, Kosuke; Ohe, Takashi; Tanaka, Sakae

    2012-11-01

    A 60-year-old woman with rheumatoid arthritis, who had been treated with infliximab, presented with uncontrollable wrist arthritis. Fungal arthritis caused by Candida parapsilosis was confirmed by examining her aspirated joint fluid. Her infliximab therapy was interrupted, and antifungal therapy with fluconazole was started. After the fungal infection had been ameliorated, surgical debridement and arthrodesis of the wrist joint were conducted, and her symptoms completely resolved. Although fungal arthritis is rare, it should be considered as a differential diagnosis of exacerbated monoarthritis in patients treated with biological agents.

  3. Successful infliximab therapy in a patient with comorbid spondyloarthritis, primary biliary cirrhosis and generalized morphea.

    PubMed

    Resorlu, Hatice; Kılıc, Sevilay; Isık, Selda; Gokmen, Ferhat

    2017-02-23

    The patient in this report was diagnosed simultaneously with primary biliary cirrhosis (PBC), spondyloarthritis, and generalized morphea and was started on infliximab therapy. In addition to an improvement in clinical symptoms with this therapy, an improvement was also observed in laboratory parameters such as cholestatic enzymes, C-reactive protein, and erythrocyte sedimentation rate. Infliximab was well tolerated in this 56-year-old patient. However, further studies must be performed in order to clarify the therapeutic role of TNF-α blockers in, PBC and generalized morphea.

  4. Effectiveness of infliximab in the treatment of perianal fistulas in ulcerative colitis: report of two cases.

    PubMed

    de la Piscina, Patricia Ramírez; Duca, Ileana; Estrada, Silvia; Spicakova, Katerina; Calderón, Rosario; Urtasun, Leire; Marra-López, Carlos; Salvador, Marta; Delgado, Elvira; Campos, Francisco García

    2013-01-01

    Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiopathogenesis and increasing incidence in recent years. Perianal complications of ulcerative colitis are rare and seem to be associated with higher extent of inflammation and a more severe course of the disease. The cases of two male patients with severe corticoid-dependent ulcerative colitis of protracted clinical course who developed perianal fistulas and abscesses successfully treated with infliximab are reported. Treatment with infliximab was followed by perianal fistula closure with marked improvement in the quality of life over 2-year follow-up period.

  5. Effectiveness of infliximab in the treatment of perianal fistulas in ulcerative colitis: report of two cases

    PubMed Central

    de la Piscina, Patricia Ramírez; Duca, Ileana; Estrada, Silvia; Spicakova, Katerina; Calderón, Rosario; Urtasun, Leire; Marra-López, Carlos; Salvador, Marta; Delgado, Elvira; Campos, Francisco García

    2013-01-01

    Ulcerative colitis is a chronic inflammatory bowel disease of unknown etiopathogenesis and increasing incidence in recent years. Perianal complications of ulcerative colitis are rare and seem to be associated with higher extent of inflammation and a more severe course of the disease. The cases of two male patients with severe corticoid-dependent ulcerative colitis of protracted clinical course who developed perianal fistulas and abscesses successfully treated with infliximab are reported. Treatment with infliximab was followed by perianal fistula closure with marked improvement in the quality of life over 2-year follow-up period. PMID:24714219

  6. Colectomy rates in patients with ulcerative colitis following treatment with infliximab or ciclosporin: a systematic literature review.

    PubMed

    Thorne, Kymberley; Alrubaiy, Laith; Akbari, Ashley; Samuel, David G; Morrison-Rees, Sian; Roberts, Stephen E

    2016-04-01

    This review aimed to compile all available published data on colectomy rates following treatment using infliximab or ciclosporin in adult ulcerative colitis patients and to analyse colectomy rates, timing to colectomy and postcolectomy mortality for each treatment. We systematically reviewed the literature after 1990 reporting colectomy rates in ulcerative colitis patients treated with infliximab or ciclosporin, excluding articles on paediatric patients, patients with indeterminate colitis or Crohn's disease and bowel surgery not related to ulcerative colitis. We presented weighted mean colectomy rates and mortality rates. Cox's regression was used to assess time to colectomy adjusting for colitis severity, patient age and sex. We tabulated 78 studies reporting on ciclosporin and/or infliximab and colectomy rates or postcolectomy mortality rates. Not all studies reported data in a standardized manner. Infliximab had a significantly lower colectomy rate than ciclosporin at 36 months when analysing all studies, studies directly comparing infliximab and ciclosporin and studies using severe colitis patients, but not at 3, 12 or 24 months. Severity and age were key indicators in the likelihood of undergoing colectomy after treatment. Postcolectomy mortality rates were less than 1.5% for both drugs. This review indicates that long-term colectomy rates following infliximab are significantly lower than ciclosporin in the longer term, and that postcolectomy mortality following infliximab and ciclosporin is very low. However, many key data items were missing from research articles, reducing our ability to establish with more confidence the actual impact of these two drugs on colectomy rates and postcolectomy mortality rates.

  7. Neuropathie périphérique sous Infliximab: étude d’une observation

    PubMed Central

    Zinebi, Ali; Akhouad, Youssef; Rkiouak, Adil; Reggad, Ahmed; Kasmy, Zohour; Boudlal, Mostafa; Rabhi, Monsef; Ennibi, Khalid; Chaari, Jilali

    2016-01-01

    Les traitements Anti TNF alpha sont de prescription de plus en plus large. Des événements secondaires multiples ont été rapportés ses dernières années, en particulier les neuropathies périphériques. Nous rapportons un cas de neuropathie axonale survenant trois mois après le début d’un traitement par Infliximab. Il s’agit d’une patiente âgée de 60 ans, suivie pour réctocolite hémorragique résistant au traitement et ayant nécessité un traitement par Infliximab. Trois mois après, la patiente présente un tableau de neuropathie axonale sensitive. Le bilan étiologique restait négatif et la réduction des doses s’est accompagnée d’une amélioration de la symptomatologie. Le délai entre l’instauration du traitement à base d’Infliximab et l’apparition des manifestations cliniques de même que l’amélioration après réduction des doses plaident en faveur de la responsabilité de l’Infliximab dans la survenue de la neuropathie sensitive. La prise en charge n’est pas standardisée et doit être discuté au cas par cas. PMID:28154626

  8. Recurrent longitudinal extensive transverse myelitis in a neuro-Behçet syndrome treated with infliximab

    PubMed Central

    Uygunoğlu, Uğur; Pasha, Maarya; Saip, Sabahattin; Siva, Aksel

    2015-01-01

    Background Spinal cord involvement is not common, but can be seen in neuro-Behçet's syndrome (NBS). The major site of involvement is the cervical spinal cord with the myelitis-like inflammatory lesions continuing more than two segments, and extending to the brainstem. Case A 30-year-old male patient who has been followed with a diagnosis of Behçet's syndrome admitted to our neurology department clinically and radiologically suggestive of recurrent and extensive longitudinal myelitis. His anti-aquaporine antibody was negative. Because of insufficient effect of azathioprine, cyclophosphamide, and corticosteroids, infliximab was started. His clinical and radiological status is stationary for 3 years under infliximab treatment. Discussion Myelitis such as that occurring in our patient may have a similar presentation like neuromyelitis optica (NMO), which should therefore be included in differential diagnosis. Myelitis observed in both NMO and NBS shows spinal cord lesions longer than three or more vertebrae. Anti-aquaporine antibody must be evaluated in all patients presenting with longitudinal myelitis. Anti-tumor necrosis factor agent infliximab might be an alternative treatment in severe form of NBS such as myelitis. Conclusion In our case, successful treatment of recurrent and extensive longitudinal transverse myelitis in NBS with infliximab was demonstrated. PMID:24673549

  9. Visceral leishmaniasis with cutaneous symptoms in a patient treated with infliximab followed by fatal consequences.

    PubMed

    Juzlova, Katerina; Votrubova, Jana; Kacerovska, Denisa; Lukas, Milan; Bortlik, Martin; Rohacova, Hana; Nohynkova, Eva; Vojackova, Nadezda; Fialova, Jorga; Hercogova, Jana

    2014-01-01

    Leishmaniasis is an infectious disease caused by parasitic flagellates of the genus Leishmania. The authors present a case of 44-year-old man with Crohn's disease treated successfully with infliximab. This case report shows rare visceral leishmaniasis with cutaneous symptoms in an immunocompromised patient. Skin manifestations may occur before or after the visceral infection and they are often diverse.

  10. Severe Acute Respiratory Distress Syndrome during Infliximab Therapy in a Patient with Crohn Disease

    PubMed Central

    Schoehl, Johanna; Mechie, Nicolae-Catalin; Schwoerer, Harald; Moerer, Onnen; Quintel, Michael; Buck, Cordula; Ellenrieder, Volker; Neesse, Albrecht; Amanzada, Ahmad

    2016-01-01

    The occurrence of a noninfectious interstitial lung disease is a rare but life-threatening side effect of infliximab, an antitumor necrosis factor alpha antibody. The following case report of a patient with Crohn disease shows an extremely dramatic progression to a severe acute respiratory distress syndrome. PMID:27920644

  11. Transferability of antibody pairs from ELISA to fiber optic surface plasmon resonance for infliximab detection

    NASA Astrophysics Data System (ADS)

    Van Stappen, Thomas; Lu, Jiadi; Bloemen, Maarten; Geukens, Nick; Spasic, Dragana; Delport, Filip; Verbiest, Thierry; Lammertyn, Jeroen; Gils, Ann

    2015-03-01

    Tumor necrosis factor (TNF)-alpha is a pleiotropic cytokine up-regulated in inflammatory bowel disease, rheumatoid arthritis and psoriasis. The introduction of anti-TNF drugs such as infliximab has revolutionized the treatment of these diseases. Recently, therapeutic drug monitoring (TDM) of infliximab has been introduced in clinical decision making to increase cost-efficiency. Nowadays, TDM is performed using radio-immunoassays, homogeneous mobility shift assays or ELISA. Unfortunately, these assays do not allow for in situ treatment optimization, because of the required sample transportation to centralized laboratories and the subsequent assay execution time. In this perspective, we evaluated the potential of fiber optic-surface plasmon resonance (FO-SPR). To achieve this goal, a panel of 55 monoclonal anti-infliximab antibodies (MA-IFX) was developed and characterized in-house, leading to the identification of nine different clusters. Based on this high diversity, 22 antibody pairs were selected and tested for their reactivity towards IFX, using one MA-IFX as capture and one MA-IFX for detection, in a sandwich type ELISA and FO-SPR. This study showed that the reactivity towards IFX of each antibody pair in ELISA is highly similar to its reactivity on FO-SPR, indicating that antibody pairs are easily transferable between both platforms. Given the fact that FO-SPR shows the potential for miniaturization and fast assay time, it can be considered a highly promising platform for on-site infliximab monitoring.

  12. Topical infliximab for the suppression of wound healing following experimental glaucoma filtration surgery

    PubMed Central

    Turgut, Burak; Eren, Kenan; Akın, Mehmet Mustafa; Demir, Tamer; Kobat, Sabiha

    2014-01-01

    Background The purpose of this work was to look into the effects of infliximab on wound healing in experimental glaucoma filtration surgery and to compare the antifibrotic effects of this agent to that of mitomycin-C (MMC). Methods Twenty-eight male New Zealand White rabbits were randomly assigned to four groups, each including seven rabbits: control group, sham group, MMC group, and infliximab group. The rabbits in the control group were not operated on and did not receive any treatment. The rabbits in the sham group underwent trabeculectomy and had one drop of saline instilled four times a day for 14 days. The rabbits in the MMC treatment group underwent trabeculectomy, and a sponge soaked in 0.4 mg/mL MMC was applied intraoperatively to the scleral surgical site for three minutes. The rabbits in the infliximab treatment group underwent trabeculectomy and one drop of 10 mg/mL infliximab was instilled four times a day for 14 days after surgery. On day 14 of the experiment, the operated and control eyes were enucleated and histologically and immunohistochemically analyzed. Results The mean fibroblast and mononuclear cell (MNC) numbers and the mean immunostaining intensities of transforming growth factor-β (TGF-β), fibroblast growth factor-β (FGF-β), and platelet-derived growth factor (PDGF) in the sham group were higher than those of the control group (P<0.01). The mean fibroblast and MNC numbers and the mean immunostaining intensities of TGF-β, FGF-β, and PDGF in the MMC and infliximab groups were statistically significantly lower than those of the sham group (P<0.01). The mean fibroblast and MNC numbers and the mean TGF-β, FGF-β, and PDGF immunostaining intensities of the MMC and infliximab groups were similar (P>0.05). Conclusion Our study suggests that topical infliximab effectively suppresses the subconjunctival wound healing response after experimental glaucoma filtration surgery, reducing the MNC and fibroblast numbers and immunostaining intensities

  13. Budget impact analysis of biosimilar infliximab (CT-P13) for the treatment of rheumatoid arthritis in six Central and Eastern European countries.

    PubMed

    Brodszky, Valentin; Baji, Petra; Balogh, Orsolya; Péntek, Márta

    2014-05-01

    The first biosimilar monoclonal antibody (infliximab, CT-P13) was registered by the European Medicines Agency in 2013 for the treatment of several inflammatory conditions including rheumatoid arthritis (RA). Biosimilar infliximab is first being marketed in the Central and Eastern European countries. This paper presents the estimated budget impact of the introduction of biosimilar infliximab in RA over a 3-year time period in six selected countries, namely Bulgaria, the Czech Republic, Hungary, Poland, Romania and Slovakia. A prevalence-based model was constructed for budget impact analysis. Two scenarios were compared to the reference scenario (RSc) where no biosimilar infliximab is available: biosimilar scenario 1 (BSc1), where interchanging the originator infliximab with biosimilar infliximab is disallowed, and only patients who start new biological therapy are allowed to use biosimilar infliximab; as well as biosimilar scenario 2 (BSc2), where interchanging the originator infliximab with biosimilar infliximab is allowed, and 80% of patients treated with originator infliximab are interchanged to biosimilar infliximab. Compared to the RSc, the net savings are estimated to be €15.3 or €20.8 M in BSc1 and BSc2, respectively, over the 3 years. If budget savings were spent on reimbursement of additional biosimilar infliximab treatment, approximately 1,200 or 1,800 more patients could be treated in the six countries within 3 years in the two biosimilar scenarios, respectively. The actual saving is most sensitive to the assumption of the acquisition cost of the biosimilar drug and to the initial number of patients treated with biological therapy. The study focused on one indication (RA) and demonstrated that the introduction of biosimilar infliximab can lead to substantial budget savings in health care budgets. Further savings are expected for other indications where biosimilar medicines are implemented.

  14. Infliximab partially alleviates the bite force reduction in a mouse model of temporomandibular joint pain.

    PubMed

    Kim, Sang-Hyon; Son, Chang-Nam; Lee, Hyo-Jung; Cho, Ho-Chan; Jung, Sung-Won; Hur, Ji An; Baek, Won-Ki; Jung, Hye Ra; Hong, Ji Hee

    2015-05-01

    Temporomandibular joint (TMJ) disorder is clinically important because of its prevalence, chronicity, and therapy-refractoriness of the pain. In this study, we investigated the effect of infliximab in a mouse model of TMJ pain using a specially-engineered transducer for evaluating the changes in bite force (BF). The mice were randomly divided into three groups (7 mice per group): the control group, the complete Freund's adjuvant (CFA) group, and the infliximab group. BF was measured at day 0 (baseline BF). After measuring the baseline BF, CFA or incomplete Freund's adjuvant was injected into both TMJs and then the changes in BF were measured at days 1, 3, 5, 7, 9, and 13 after the TMJ injection. For measuring the BF, we used a custom-built BF transducer. Control, CFA, and infliximab groups showed similar baseline BF at day 0. From day 1, a significant reduction in BF was observed in the CFA group, and this reduction in BF was statistically significant compared to that in the control group (P < 0.05). This reduction in BF was maintained until day 7, and BF started to recover gradually from day 9. In the infliximab group also, the reduction in BF was observed on day 1, and this reduction was maintained until day 7. However, the degree of reduction in BF was less remarkable compared to that in the CFA group. The reduction in BF caused by injection of CFA into the TMJ could be partially alleviated by the injection of anti-tumor necrosis factor alpha, infliximab.

  15. Predictive Factors of Clinical Response of Infliximab Therapy in Active Nonradiographic Axial Spondyloarthritis Patients

    PubMed Central

    Lin, Zhiming; Liao, Zetao; Huang, Jianlin; Ai, Maixing; Pan, Yunfeng; Wu, Henglian; Lu, Jun; Cao, Shuangyan; Li, Li; Wei, Qiujing; Tang, Deshen; Wei, Yanlin; Li, Tianwang; Wu, Yuqiong; Xu, Manlong; Li, Qiuxia; Jin, Ou; Yu, Buyun; Gu, Jieruo

    2015-01-01

    Objectives. To evaluate the efficiency and the predictive factors of clinical response of infliximab in active nonradiographic axial spondyloarthritis patients. Methods. Active nonradiographic patients fulfilling ESSG criteria for SpA but not fulfilling modified New York criteria were included. All patients received infliximab treatment for 24 weeks. The primary endpoint was ASAS20 response at weeks 12 and 24. The abilities of baseline parameters and response at week 2 to predict ASAS20 response at weeks 12 and 24 were assessed using ROC curve and logistic regression analysis, respectively. Results. Of 70 axial SpA patients included, the proportions of patients achieving an ASAS20 response at weeks 2, 6, 12, and 24 were 85.7%, 88.6%, 87.1%, and 84.3%, respectively. Baseline MRI sacroiliitis score (AUC = 0.791; P = 0.005), CRP (AUC = 0.75; P = 0.017), and ASDAS (AUC = 0.778, P = 0.007) significantly predicted ASAS20 response at week 12. However, only ASDAS (AUC = 0.696, P = 0.040) significantly predicted ASAS20 response at week 24. Achievement of ASAS20 response after the first infliximab infusion was a significant predictor of subsequent ASAS20 response at weeks 12 and 24 (wald χ2 = 6.87, P = 0.009, and wald χ2 = 5.171, P = 0.023). Conclusions. Infliximab shows efficiency in active nonradiographic axial spondyloarthritis patients. ASDAS score and first-dose response could help predicting clinical efficacy of infliximab therapy in these patients. PMID:26273654

  16. The effect of infliximab on antiviral antibody profiles in patients with rheumatoid arthritis.

    PubMed

    Kaufman, Ilana; Moscovici, Yolanda Braun; Abudi, Yair; Sofer, Denit; Mendelson, Ella; Balbir-Gurman, Alexandra; Caspi, Dan; Elkayam, Ori

    2010-01-01

    The duration of humoral immunity in patients treated with immunosuppressive drugs is poorly defined. The objective of the study was to investigate the effect of infliximab on the levels of antiviral antibodies against poliomyelitis, rubella and measles in rheumatoid arthritis (RA) patients. Fifty-two consecutive RA patients being treated with 3 mg/kg infliximab were prospectively studied. The antiviral antibody profiles for measles, rubella and three serotypes of poliomyelitis were tested on the day of the first infusion of infliximab and 6 months later. The study group comprised 36 women and 16 men (mean age 54 years, range 33-81) with a mean disease duration of 15 +/- 9 years. Forty-two (81%) patients were being treated with methotrexate and 22 (42%) were receiving prednisone. All patients had baseline protective levels of antibodies against measles and the three strains of polio, while 48 (92%) patients had protective antibodies against rubella. No significant change in the levels of antiviral antibodies was observed after 6 months of treatment with infliximab: from 3.67 at baseline to 3.87 IU/ml for measles, 169.50-197.0 IU/ml for rubella. No change was noticed for the geometric mean concentrations of antibodies against strains of poliomyelitis: 366-478 IU/ml for the Mahoney polio strain, 906-845 IU/ml for the MEF strain and 175-196 IU/ml for the Sauket strain. Patients with longstanding RA conserve long-term immunity to common viruses despite the use of immunosuppressive drugs. Levels of antiviral antibodies against measles, rubella and polio remain stable under treatment with infliximab.

  17. The Production of a Stable Infliximab Powder: The Evaluation of Spray and Freeze-Drying for Production

    PubMed Central

    Kanojia, Gaurav; Have, Rimko ten; Bakker, Arjen; Wagner, Koen; Frijlink, Henderik W.; Kersten, Gideon F. A.; Amorij, Jean-Pierre

    2016-01-01

    In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn’s disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding. After thermal treatment, the dried formulations showed some chemical modification of the IgG in the dextran-sucrose formulation, probably due to Maillard reaction products. This study indicates that, with the appropriate formulation, both spray-drying and freeze-drying may be useful for (bulk) powder production of Infliximab. PMID:27706175

  18. Ashkenazi Jewish origin protects against formation of antibodies to infliximab and therapy failure.

    PubMed

    Ungar, Bella; Haj-Natour, Ola; Kopylov, Uri; Yavzori, Miri; Fudim, Ella; Picard, Orit; Loebstein, Ronen; Lahat, Adi; Maor, Yaakov; Avidan, Benjamin; Lang, Alon; Weiss, Batia; Chowers, Yehuda; Eliakim, Rami; Ben-Horin, Shomron

    2015-05-01

    Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity.To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes.One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17-0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13-0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15-0.65, P = 0.002; OR 0.42 95% CI 0.18-0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07-16.1, p = 0.04, OR 4.45 95% CI 1.2-16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14-0.96, p = 0.04). P = 0.04, respectively), whereas episodic/interrupted therapy was

  19. Ashkenazi Jewish Origin Protects Against Formation of Antibodies to Infliximab and Therapy Failure

    PubMed Central

    Ungar, Bella; Haj-Natour, Ola; Kopylov, Uri; Yavzori, Miri; Fudim, Ella; Picard, Orit; Loebstein, Ronen; Lahat, Adi; Maor, Yaakov; Avidan, Benjamin; Lang, Alon; Weiss, Batia; Chowers, Yehuda; Eliakim, Rami; Ben-Horin, Shomron

    2015-01-01

    Abstract Infliximab is an anti-tumor necrosis factor (TNF) used for treatment of inflammatory bowel disease (IBD) as well as rheumatoid arthritis, psoriasis, and other inflammatory conditions. Antibodies to infliximab (ATI) develop in approximately 45% of infliximab-treated IBD patients and are correlated with loss of clinical response. Scarce data exist as to factors which predict infliximab immunogenicity. To investigate factors that may predict formation of antibodies to infliximab (ATI) and infliximab therapy failure an observational study of consecutive IBD patients treated with infliximab between 2009 and 2013 was performed. Trough levels of ATI were measured. Patients were monitored for disease activity using clinical activity indexes and were classified according to ATI formation and clinical response. All clinical and demographic parameters were analyzed for association with the designated outcomes. One hundred fifty-nine patients were included and 1505 sera were tested. On multivariate analysis, Jewish Ashkenazi ethnicity was protective against both development of ATI (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.17–0.7, P = 0.005) and treatment failure (OR 0.29, 95% CI 0.13–0.66, P = 0.003). Concomitant immunomodulator therapy was also negatively associated with immunogenicity and infliximab therapy failure (OR 0.31, 95% CI 0.15–0.65, P = 0.002; OR 0.42 95% CI 0.18−0.99, p = 0.04, respectively), whereas episodic therapy was positively associated with both outcomes (OR 4.2 95% CI 1.07−16.1, p = 0.04, OR 4.45 95% CI 1.2−16.6, p = 0.026 respectively). All other variables, including IBD type, gender, weight, age, smoking status and disease duration, were not predictive of ATI formation or clinical failure. However, among Crohn's disease patients, a non-stricturing non-penetrating phenotype was protective against ATI formation (OR 0.4, 95% CI 0.14−0.96, p = 0.04). P = 0.04, respectively), whereas episodic

  20. Chronic Granulomatous Disease Mimicking Colonic Crohn’s Disease Successfully Treated with Infliximab

    PubMed Central

    Coelho, Rosa; Maia, Tiago; Sarmento, António; Magro, Fernando; Macedo, Guilherme

    2017-01-01

    Chronic granulomatous disease (CGD) is a genetically induced disease caused by mutations in one of the components of the NADPH-oxidase in phagocytes, characterized by life-threatening bacterial and fungal infections and granuloma formation. Treatment includes prevention of infectious complications and immunomodulation. However, a standard strategy is not yet defined. The authors report an X-linked CGD female carrier who presented during adulthood with diarrhea and colorectal ulcers, with high impairment of quality of life. Induction with infliximab 5 mg/kg (weeks 0, 2, and 6) with infectious prophylaxis was initiated. She continued infliximab 5 mg/kg every 8 weeks with complete symptomatic response at 15 months. PMID:28377934

  1. Pharmacokinetics of Infliximab and Reduction of Treatment for Inflammatory Bowel Diseases.

    PubMed

    Williet, Nicolas; Paul, Stephane; Peyrin-Biroulet, Laurent; Roblin, Xavier

    2016-04-01

    Local or national policy, patients' preferences, safety and/or economic concerns, or reimbursement issues may dictate stopping drug in inflammatory bowel diseases (IBD) patients. Sustained deep remission is an important predictor of a better outcome after anti-tumor necrosis (TNF) factor therapy discontinuation, including infliximab (IFX) in IBD patients, but this is not sufficient to prevent future relapse in these patients. In IBD patients under combotherapy, trough level of infliximab (TRI) could be helpful to choose stopping one of the two drugs. In patients on IFX monotherapy, TRI could help to decide reduction of drug dosing, particularly in IBD patients with supratherapeutic trough levels. Incidental findings of undetectable TRI in patients with deep remission may identify a subset of patients who may be considered for IFX cessation. Controlled trials further assessing this issue are eagerly awaited. Pending these trials, clear international recommendations for discontinuing anti-TNF therapy are needed.

  2. Segmental vitiligo after infliximab use for rheumatoid arthritis - A case report*

    PubMed Central

    Carvalho, Clarissa Luiza Dalla Bernardina; Ortigosa, Luciena Cegatto Martins

    2014-01-01

    The tumor necrosis factor alpha is a cytokine related to immune and inflammatory processes by acting on different parts of the body. It is secreted by several cell types including macrophages, lymphocytes, monocytes, neutrophils, dendritic cells, among others. Infliximab is a chimeric monoclonal antibody that specifically binds to soluble and transmembrane tumor necrosis factor alpha form blocking its action. In rheumatoid arthritis it is used because the cytokines that cause inflammation in this disease are regulated by tumor necrosis factor alpha and IL-1. We report the case of a 46-year-old patient with rheumatoid arthritis who developed segmental vitiligo after two months using infliximab. The event aims to alert to the existence of this adverse effect that can be induced with the use of this medication. PMID:24626663

  3. Weber-Christian disease with ileocolonic involvement successfully treated with infliximab

    PubMed Central

    Miranda-Bautista, José; Fernández-Simón, Alejandro; Pérez-Sánchez, Isabel; Menchén, Luis

    2015-01-01

    Weber-Christian disease (WCD) is an inflammatory disease whose main histological feature is lobular panniculitis of adipose tissue. The location of panniculitis determines the clinical presentation, being the subcutaneous adipose tissue the most frequent one, followed by liver, spleen, bone marrow and mesenteric adipose tissue. Systemic corticosteroids are first line treatment, but other options should be considered if systemic symptoms are observed or in case of refractory clinical situation. We report herein a case with WCD showing orbital, mesenteric and ileocolonic involvement, which required surgical treatment and also developed postoperative recurrence. Symptoms were resolved by administration of thalidomide and, afterwards, infliximab. To our knowledge, this is the first report of Weber-Christian disease with luminal ileocolonic involvement, treated with infliximab. PMID:25954116

  4. Combining infliximab, anti-MAP and hyperbaric oxygen therapy for resistant fistulizing Crohn's disease

    PubMed Central

    Agrawal, Gaurav; Borody, Thomas; Turner, Robert; Leis, Sharyn; Campbell, Jordana

    2015-01-01

    Background: Fistulizing Crohn's disease (CD) presents a therapeutic challenge as fistulae are notoriously difficult to heal. Mycobacterium avium ss paratuberculosis (MAP) treatment in CD is gaining attention. Aim: We evaluated healing of CD fistula(e) using a novel combination therapy. Study: Nine consecutive patients who failed to heal fistulae on conventional treatment including anti-TNF, were treated with at least three doses of infliximab, 18–30 courses of hyperbaric oxygen therapy and anti-MAP antibiotics comprising rifabutin, clarithromycin and clofazimine. Results: All patients achieved complete healing of fistulae by 6–28 weeks and follow-up for mean 18 months. Conclusion: Combining infliximab, hyperbaric oxygen therapy and anti-MAP, seems to enable healing of recalcitrant fistulae and although a small case series, all nine patients achieved complete healing. PMID:28031926

  5. New-onset psoriatic palmoplantaris pustulosis following infliximab therapy: a class effect?

    PubMed

    Roux, Christian Hubert; Brocq, Olivier; Leccia, Nathalie; Giacchero, Damien; Breuil, Veronique; Albert, Christine; Lacour, Jean; Perrin, Christophe; Euller-Ziegler, Lianna; Euler-Ziegler, Liana

    2007-02-01

    Reports of induction or exacerbation of psoriatic palmoplantaris pustulosis (PPPP) after anti-tumor necrosis factor-alpha (TNF-alpha) treatment are few. We describe 2 new cases of PPPP induced by infliximab. In 1999, a total of 442 patients in our department received anti-TNF-alpha treatment for a variety of chronic rheumatic conditions and were regularly followed. Medical records for 166 given infliximab were retrospectively reviewed for disease [rheumatoid arthritis (RA), spondylarthropathies (SpA) including psoriatic arthritis], disease duration, clinical characteristics, skin side-effects, and use of other potentially relevant medications. PPPP was observed in 2 patients treated with infliximab for symmetrical rheumatoid factor-positive RA; the patients had no personal or family history of psoriasis. In both cases, pustulosis appeared after several months of infliximab administration. There was no clinical, biological, or radiological evidence to support a diagnosis of psoriatic SpA. Both patients fulfilled ACR criteria for RA, and there was no reason to suspect previously unidentified psoriasis. Comorbid RA and psoriasis are unusual, and our patients exhibited a clear link between anti-TNF-alpha administration and cutaneous lesions, suggesting a direct effect in both cases. The 28 published cases of PPPP induced by anti-TNF-alpha treatment report lesions that tend towards pustulosis and palmoplantar localization. The mechanisms involved remain elusive. Disappearance of lesions in our second patient when switched to a soluble receptor suggests a molecule-specific side effect, while the literature describing variable reaction to switching anti-TNF agents, and/or their discontinuation and reintroduction, indicates otherwise. Given the rarity of this side effect, its elucidation will require systematic study.

  6. Use of infliximab and other biologics in Behçet disease.

    PubMed

    Li, J; Fernando, S; Herkes, G

    2014-01-01

    Behçet disease is a multisystem vasculitis characterised by recurrent oral ulceration in conjunction with other manifestations. Neurological involvement or neuro-Behçet disease is not common, but typically affects young men at its onset between the ages of 20 and 40 with significant long-term morbidity and mortality. There is substantial case literature to support the use of tumour necrosis factor antagonists, notably infliximab, in the treatment of neuro-Behçet disease.

  7. Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

    PubMed Central

    Foster, Erina N.; Nguyen, Khanh K.; Sheikh, Rafiq A.; Prindiville, Thomas P.

    2005-01-01

    The association of Crohn's disease (CD) and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions. PMID:16050146

  8. Infliximab-Associated Psoriasiform Dermatitis: Case Report and Review of a Seemingly Paradoxical Inflammatory Response

    PubMed Central

    Cohen, Philip R

    2016-01-01

    Background: Tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab, adalimumab, and certolizumab pegol are effective agents in the treatment of inflammatory bowel disease. Some individuals undergoing anti-TNF-α therapy for Crohn’s disease or ulcerative colitis develop psoriasiform lesions. This is a paradoxical finding, as classical psoriasis is known to respond to these agents. Purpose: The clinical features of anti-TNF-α-induced psoriatic dermatitis are described. Method: A 60-year-old man with Crohn’s disease treated with infliximab, who developed anti-TNF-α-induced psoriasiform dermatitis, is described. Results: The man developed erythematous skin lesions in the bilateral axillae two years after beginning infliximab treatment for Crohn’s disease. Biopsy revealed psoriasiform dermatitis, consistent with a diagnosis of anti-TNF-α-induced psoriasiform dermatitis. He was treated with clobetasol 0.05% ointment twice daily for two weeks and had significant improvement. Subsequently, he used the corticosteroid ointment two days per week and calcipotriene 0.005% ointment twice daily for five days per week to achieve and maintain clear skin. Conclusions: Anti-TNF-α-induced psoriasiform dermatitis is an infrequent complication of infliximab therapy. However, the condition may require discontinuation of the anti-TNF-α agent. Anti-TNF-α-induced psoriasiform dermatitis should be considered in the differential diagnosis when evaluating a new erythematous skin condition in an individual with a history of inflammatory bowel disease who is being treated with a TNF-α inhibitor. PMID:27738572

  9. Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid syndrome: Role of reduced oxidative stress.

    PubMed

    Benhamou, Ygal; Miranda, Sébastien; Armengol, Guillaume; Harouki, Najah; Drouot, Laurent; Zahr, Noel; Thuillez, Christian; Boyer, Olivier; Levesque, Hervé; Joannides, Robinson; Richard, Vincent

    2015-08-01

    Antiphospholipid syndrome (APS), induces endothelial dysfunction, oxidative stress and systemic inflammation that may be mediated by TNFα. Thus, we investigated the possible protective effect of the anti-TNFα antibody infliximab (5μg/g) on endothelial function in a mouse APS model (induced by injection of purified human anti-β2GP1-IgG). Seven days after anti-β2GPI-IgG injection, we observed an increase in plasma sVCAM-1 and sE-selectin levels and in aortic mRNA expression of VCAM-1 and E-selectin. This was associated with a decreased endothelium-dependent relaxation of isolated mesenteric arteries to acetylcholine, together with decreased mesenteric eNOS mRNA expression and increased eNOS uncoupling, accompanied by increased iNOS and gp91phox mRNA and increased left ventricular GSH/GSSH ratio. Infliximab significantly improved the NO-mediated relaxing responses to acetylcholine, and induced a decrease in iNOS and gp91phox mRNA expression. The õpro-adhesive and pro-coagulant phenotypes induced by the anti-β2GP1-IgG were also reversed. This study provides the first evidence that TNFα antagonism improves endothelial dysfunction in APS and suggests that endothelial dysfunction is mediated by TNFα and oxidative stress. Therefore, infliximab may be of special relevance in clinical practice.

  10. The urinary excretion of pyridinoline and deoxypyridinoline during rheumatoid arthritis therapy with infliximab.

    PubMed

    Ostanek, Lidia; Pawlik, Andrzej; Brzosko, Iwona; Brzosko, Marek; Sterna, Rozalia; Droździk, Marek; Gawrońska-Szklarz, Barbara

    2004-06-01

    Rheumatoid arthritis is a systemic disease that causes inflammation and joint destruction. As a result of pathological destruction in bone and cartilage, crosslinks in collagen are resorbed more rapidly. This causes a rise in circulating collagen crosslink levels and their urinary excretion. In RA, apart from the crosslink resorption at the site of inflamed joints, there may be increased resorption due to general bone loss associated with disease activity. The aim of this study was to evaluate the influence of therapy with infliximab on urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPYR) as a markers of collagen degradation and its correlation with clinical and biochemical parameters of disease activity. Seventeen patients with active rheumatoid arthritis treated with infliximab were recruited into the study. The therapy resulted in the reduction in the symptoms of RA and urinary excretion of PYD and DPYR. The urinary excretion of PYD correlated with a number of swollen joints, morning stiffness, CRP and ESR. The urinary excretion of DPYR correlated during infliximab therapy with the number of swollen and tender joints and morning stiffness. The measurement of urinary excretion of PYR and DPYR may give insight into bone metabolism and help us to better understand the actual changes in bone and cartilage caused by RA and its treatment.

  11. Infliximab Combined with Enteral Nutrition for Managing Crohn's Disease Complicated with Intestinal Fistulas

    PubMed Central

    Wu, Xiao-Li; Tao, Li-Ping; Wu, Jian-Sheng; Chen, Xiang-Rong

    2016-01-01

    Aim. This study was performed to evaluate the additional enteral nutrition (EN) in the efficacy of infliximab (IFX) compared with the conventional therapy in managing Crohn's disease (CD) complicated with intestinal fistulas. Methods. A total of 42 CD with intestinal fistulas were randomly divided into infliximab treatment group (n = 20) and conventional therapy group (n = 22). We evaluated the laboratory indexes, Crohn's disease activity index (CDAI), Crohn's disease simplified endoscopic score (SES-CD), and healing of fistula in the two groups before treatment, at 14 weeks, and at 30 weeks, respectively. Results. In the IFX treatment group, the CDAI score, the SES-CD, erythrocyte sedimentation rate, and C-reactive protein levels were significantly decreased during treatment compared with those before treatment. The body mass index and albumin levels were increased in both groups. Moreover, in the IFX treatment group, fistula healing was found in 8 at the 14th week and 18 at the 30th week, respectively, which was greater than that in the conventional therapy group. Conclusion. Our study suggested that infliximab combined with EN is an effective treatment for CD patients complicated with intestinal fistulas. PMID:27738427

  12. Comparison of two ELISA versions for infliximab serum levels in patients diagnosed with ankylosing spondylitis.

    PubMed

    Hernández-Flórez, Diana; Valor, Lara; de la Torre, Inmaculada; Nieto, Juan Carlos; Martínez-Estupiñán, Lina; González, Carlos; López-Longo, Francisco Javier; Monteagudo, Indalecio; Garrido, Jesús; Naredo, Esperanza; Carreño, Luis

    2015-06-01

    There are various immunosorbent assays which can be used to determine infliximab (IFX) levels. Results vary between assays complicating reliability in everyday clinical practice. The aim of this study was to determine whether quantitative or qualitative assay data prove more accurate in the assessment of infliximab levels in AS patients. We analyzed 40 serum samples, taken prior to infusion, from AS patients who had been undergoing IFX therapy as a first-line of biological treatment for more than a year. IFX levels and IFX-anti-drug antibodies (ADA) were measured using two different ELISA assays [Promonitor IFX R1 and R2 (version 1), Promonitor IFX and anti-IFX (version 2) (Progenika Biopharma, Spain)] strictly following the manufacturer's guidelines. Cohen's unweighted kappa and the intraclass correlation coefficient determined qualitative and quantitative agreement for serum levels in version 1 and version 2. Bland-Altman plots were drawn to compare both assays. The comparison of data measuring IFX levels for version 1 and version 2 resulted in questionable quantitative agreement (ICC 0.659; 95% CI 0.317-0.830) and moderate qualitative agreement (κ 0.607; 95% CI 0.387-0.879) owing to systematically higher values in version 2 than version 1. Version 2 consistently detected higher levels of infliximab, particularly when analyzed in a quantitative context. Further research is needed to synchronize cutoff levels between essays and diseases so therapeutic drug ranges can be established.

  13. Accelerated Infliximab Infusion: Safety, Factors Predicting Adverse Events, Patients’ Satisfaction and Cost Analysis. A Cohort Study in IBD Patients

    PubMed Central

    Mazzuoli, S.; Tricarico, D.; Demma, F.; Furneri, G.; Guglielmi, F. W.

    2016-01-01

    Background Standard Infliximab infusion consists of a 2-hour intravenous administration. Recently, Infliximab shortened infusion has been included in the Infliximab label as possible maintenance regimen for patients tolerating Infliximab induction therapy. Aim To verify if accelerated 1-hour Infliximab infusions are as safe as standard administrations, in patients with Inflammatory Bowel Disease. Methods Seventy-four patients treated between September 2008 and November 2014 were evaluated. Patients were eligible for 1-hour infusion if they had no history of infusion reactions during the previous 2-hour infusions. Results Twenty-three patients received 2-hour infusions, 16 patients received 1-hour infusions, 35 patients received 2-hour infusions followed by 1-hour infusions. A total of 1,123 Infliximab infusions were administered. The proportion of patients experiencing infusion reaction was: 4% over the 1-hour infusions and 9% over the 2-hour (P = 0.318). Adverse reaction/infusion rate was 0.55% over the 1-hour infusions and 0.66% over the 2-hour (P = 0.835). In the logistic model, accelerated infusion was the only statistically significant predictor of infusion reaction risk reduction (-90%; P = 0.024). Mean satisfaction was 8/10 (±0.84) with 1-hour regimen and 6/10 (±0.56) with 2-hour infusions (P = 0.000). The mean total cost was reduced by 47% with the 1-hour regimen (133.54€ and 250.86€ for 1-hour and 2-hour infusions, respectively). Conclusions Accelerated Infliximab infusion does not increase the acute infusion reaction incidence. In patients with inflammatory bowel disease, the 1-hour regimen should be preferred to 2-hour protocol also due to positive effects on indirect costs and patient’s satisfaction. PMID:27851772

  14. The Efficacy of Infliximab Monotherapy versus Infliximab-Azathioprine Sequential Treatment in Crohn's Disease: Experience from a Tertiary Medical Center in China

    PubMed Central

    Wang, Zhengting; Fan, Rong; Zhang, Maochen; Lin, Yun; Hong, Liwen; Zhou, Xiaolin; Hu, Shurong; Cheng, Mengmeng

    2016-01-01

    Objective. To evaluate the efficacy of infliximab (IFX) monotherapy versus infliximab-azathioprine sequential treatment in Crohn's disease (CD) patients. Methods. Patients newly diagnosed with CD using IFX as induction therapy were enrolled. After 6 times of IFX infusions, they were divided into IFX monotherapy group and IFX-AZA sequential therapy group. Clinical remission rates were assessed at weeks 57, 84, 111, and 138 while endoscopic remission rates were assessed at weeks 84 and 138 to evaluate the efficacy of these two groups. Results. A total of seventy-nine patients had accomplished 138-week follow-up. At weeks 84 and 138, the deep remission rate (18/22 and 17/22) of IFX monotherapy group was significantly higher compared to IFX-AZA sequential therapy group (26/57 and 21/57) (P = 0.004 and 0.001, resp.). Similar findings were found in complete endoscopic remission rate. The clinical remission rates of IFX monotherapy group were similar to that of IFX-AZA sequential therapy group (P > 0.05). At weeks 84 and 138, the endoscopic remission rate and the endoscopic improvement rate between these two groups displayed no significant difference (P > 0.05). Conclusion. IFX monotherapy provides higher deep remission rate compared with IFX-AZA sequential therapy in two-year maintenance therapy. For patients who could not receive prolonged IFX therapy, IFX-AZA sequential therapy is acceptable, though long-term efficacy remains to be seen. PMID:27896276

  15. Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

    PubMed Central

    Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

    2016-01-01

    Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and

  16. CARD15 gene overexpression reduces effect of etanercept, infliximab, and adalimumab on cytokine secretion from PMA activated U937 cells.

    PubMed

    Teimourian, Shahram; Masoudzadeh, Nooshin

    2015-09-05

    Crohn's disease (CD), a subcategory of inflammatory bowel disease, is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can take place in any region along the alimentary tract. The most important gene involved in the etiology of CD is NOD2/CARD15 located on chromosome 16. It has been shown that CARD15 is overexpressed in monocytes of CD patients. The common treatment for the disease is anti-TNF-alpha drugs, the most hopeful of which are probably infliximab and etanercept. Infliximab rapidly reduces signs and symptoms of active Crohn's disease. In contrast, etanercept shows no such effect. In the present study, we evaluated the effects of the CARD15 gene overexpression in monocytic cell line U937 in the production of anti-inflammatory cytokine, IL-10, and proinflammatory cytokine, Il-1 beta, produced after incubation with infliximab, adalimumab, and etanercept separately. Our results show that infliximab and adalimumab significantly decreased IL-10 and IL-1beta secretion levels. However, etanercept inhibition of secretion was less compared with infliximab or adalimumab. In all three cases, suppression of cytokine production is reduced by CARD15 overexpression.

  17. Detection of anti-infliximab antibodies is impacted by antibody titer, infliximab level and IgG4 antibodies: a systematic comparison of three different assays

    PubMed Central

    Afonso, Joana; Lopes, Susana; Gonçalves, Raquel; Caldeira, Paulo; Lago, Paula; Tavares de Sousa, Helena; Ramos, Jaime; Gonçalves, Ana Rita; Ministro, Paula; Rosa, Isadora; Vieira, Ana Isabel; Coelho, Rosa; Tavares, Patrícia; Soares, João; Sousa, Ana Lúcia; Carvalho, Diana; Sousa, Paula; da Silva, João Pereira; Meira, Tânia; Silva Ferreira, Filipa; Dias, Cláudia Camila; Chowers, Yehuda; Ben-Horin, Shomron; Magro, Fernando

    2016-01-01

    Background: There is scant information on the accuracy of different assays used to measure anti-infliximab antibodies (ADAs), especially in the presence of detectable infliximab (IFX). We thus aimed to evaluate and compare three different assays for the detection of IFX and ADAs and to clarify the impact of the presence of circulating IFX on the accuracy of the ADA assays. Methods: Blood samples from 79 ulcerative colitis (UC) patients treated with infliximab were assessed for IFX levels and ADAs using three different assays: an in-house assay and two commercial kits, Immundiagnostik and Theradiag. Sera samples with ADAs and undetectable levels of IFX were spiked with exogenous IFX and analyzed for ADAs. Results: The three assays showed 81–96% agreement for the measured IFX level. However, the in-house assay and Immundiagnostik assays detected ADAs in 34 out of 79 samples, whereas Theradiag only detected ADAs in 24 samples. Samples negative for ADAs with Theradiag, but ADA-positive in both the in-house and Immundiagnostik assays, were positive for IFX or IgG4 ADAs. In spiking experiments, a low concentration of exogenous IFX (5 µg/ml) hampered ADA detection with Theradiag in sera samples with ADA levels of between 3 and 10 µg/ml. In the Immundiagnostik assay detection interference was only observed at concentrations of exogenous IFX higher than 30 µg/ml. However, in samples with high levels of ADAs (>25 µg/ml) interference was only observed at IFX concentrations higher than 100 µg/ml in all three assays. Binary (IFX/ADA) stratification of the results showed that IFX+/ADA- and IFX-/ADAs+ were less influenced by the assay results than the double-positive (IFX+/ADAs+) and double-negative (IFX-/ADAs-) combination. Conclusions: All three methodologies are equally suitable for measuring IFX levels. However, erroneous therapeutic decisions may occur when patients show double-negative (IFX-/ADAs-) or double-positive (IFX+/ADAs+) status, since agreement between

  18. Efficacy and Safety of Infliximab Therapy and Predictors of Response in Korean Patients with Crohn's Disease: A Nationwide, Multicenter Study

    PubMed Central

    Choi, Chang Hwan; Song, In Do; Kim, Young-Ho; Koo, Ja Seol; Kim, You Sun; Kim, Joo Sung; Kim, Nayoung; Kim, Eun Soo; Kim, Jae Hak; Kim, Ji Won; Kim, Tae Oh; Kim, Hyun Soo; Kim, Hyo Jong; Park, Young Sook; Park, Dong Il; Park, Soo Jung; Song, Hyun Joo; Shin, Sung Jae; Yang, Suk-Kyun; Ye, Byong Duk; Lee, Kang-Moon; Lee, Bo In; Lee, Sun-Young; Lee, Chang Kyun; Im, Jong Pil; Jang, Byung Ik; Jeon, Tae Joo; Cho, Yu Kyung; Chang, Sae Kyung; Jeon, Seong Ran; Jung, Sung-Ae; Jeen, Yoon Tae; Cha, Jae Myung; Han, Dong Soo

    2016-01-01

    Purpose Infliximab is currently used for the treatment of active Crohn's disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD. Materials and Methods A total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated. Results In patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis. Conclusion Infliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events. PMID:27593865

  19. Systematic review and meta-analysis of third-line salvage therapy with infliximab or cyclosporine in severe ulcerative colitis

    PubMed Central

    Feuerstein, Joseph D.; Akbari, Mona; Tapper, Elliot B.; Cheifetz, Adam S.

    2016-01-01

    Background In patients with ulcerative colitis who fail corticosteroids and are treated with rescue therapy (e.g. infliximab or cyclosporine) but fail to respond, salvage therapy with infliximab or cyclosporine can be considered. We sought to assess the efficacy and safety of this third-line salvage therapy. Methods We performed a meta-analysis of trials published in PubMed up to January 2015 relating to the use of third-line salvage therapy following failure of intravenous corticosteroids and infliximab or cyclosporine. Pooled outcome rates for each salvage strategy and pooled odds ratio comparing the two strategies were calculated using the random effects model. Heterogeneity was assessed by the Q and I2 statistics. Results The search strategy yielded 40 articles of which 4 were eligible for inclusion. Four articles assessed patients who were treated with infliximab after failure of cyclosporine and 2 articles assessed the use of cyclosporine after failure of infliximab. There were 138 patients using infliximab as a third-line salvage therapy and 30 patients using cyclosporine. When comparing these two strategies, there was no significant difference in clinical response (RR 1.03, 95%CI 0.7-1.46 P=0.87), clinical remission (RR 0.69, 95%CI 0.30-1.57 P=0.37), or colectomy at 12 months (RR 1.14, 95%CI 0.79-1.67 P=0.48). Similarly, there was no significant difference in total (RR 1.91, 95% CI0.38-9.64 p=0.43) or serious adverse events (RR 1.18, 95%CI 0.34-4.07 P=0.80). Conclusion While third-line salvage therapy may be efficacious in achieving short-term clinical response/remission, there remains a significant risk of colectomy and adverse events. PMID:27366036

  20. Clinical role, optimal timing and frequency of serum infliximab and anti-infliximab antibody level measurements in patients with inflammatory bowel disease

    PubMed Central

    Bor, Renáta; Farkas, Klaudia; Fábián, Anna; Bálint, Anita; Milassin, Ágnes; Rutka, Mariann; Matuz, Mária; Nagy, Ferenc; Szepes, Zoltán; Molnár, Tamás

    2017-01-01

    Background Serum infliximab (IFX) and antibody-to-infliximab (ATI) levels are objective parameters, that may have a great role in the therapeutic decisions during maintenance biological therapy. Research design and methods 48 inflammatory bowel disease patients receiving maintenance IFX therapy were prospectively enrolled and divided into adequate (complete remission N = 20) and inadequate responder (partial response, loss of response, dose escalation; N = 28) groups. Blood samples were collected just before (trough level, TL) and two (W2aTL) and six weeks (W6aTL) after the administration of IFX. Results Single measurement of ATI titer was insufficient for predicting therapeutic response due to transient expression of ATI, however, using the three points’ measurements, significant difference has been detected between the adequate and inadequate responder group (5.0% vs 35.7%; p = 0.016). The mean value of TL was significantly higher in the adequate responder group (3.11±1.64 vs.1.19±1.11; p<0.001) without further difference on the second and sixth week. Sensitivity and specificity for predicting the therapeutic response were 85.0% and 71.4% based on the cut-off value of TL 2.0 μg/ml. Conclusion Simultaneous measurement of serum IFX level prior to administration of regular IFX infusion and ATI titers significantly increase the diagnostic accuracy for the therapeutic decision in patients uncertainly responding to the therapy. The measurement of W2aTL and W6aTL levels did not result in further improvement in the prediction of therapeutic response. PMID:28362851

  1. Real-world cost-effectiveness of infliximab, etanercept and adalimumab in rheumatoid arthritis patients: results of the CREATE registry.

    PubMed

    Cárdenas, M; de la Fuente, S; Font, P; Castro-Villegas, M C; Romero-Gómez, M; Ruiz-Vílchez, D; Calvo-Gutiérez, J; Escudero-Contreras, A; Casado, M A; Del Prado, J R; Collantes-Estévez, E

    2016-02-01

    Biological drugs have proven efficacy and effectiveness in treatment of rheumatoid arthritis (RA), although none has been shown to be superior. Few studies have evaluated the cost-effectiveness of biological drugs in real-life clinical conditions. The objective of this study was to compare the cost-effectiveness of infliximab, etanercept and adalimumab in achieving clinical remission (DAS28 < 2.6) when used as initial biological therapy. Patients were diagnosed with RA who began treatment with infliximab, etanercept or adalimumab in the Reina Sofia Hospital (Cordoba, Spain) between January 1, 2007, and December 31, 2012. Effectiveness was measured as the percentage of patients who achieved clinical remission after 2 years. The cost analysis considered the use of direct health resources (perspective of the healthcare system). Cost-effectiveness was calculated by dividing the total mean cost of each treatment by the percentage of patients who achieved remission. One hundred and thirty patients were included: 55 with infliximab, 44 with adalimumab and 31 with etanercept. After 2 years, 45.2 % of patients with adalimumab achieved clinical remission, versus 29.1 % with infliximab (p = 0.133) and 22.7 % with etanercept (p = 0.040), with no differences between etanercept and infliximab (p = 0.475). The average total cost at 2 years was €29,858, €25,329 and €23,309 for adalimumab, infliximab and etanercept, respectively, while the mean cost (95 %CI) to achieve remission was €66,057 (48,038–84,076), €87,040 (78,496–95,584) and €102,683 (94,559–110,807), respectively. Adalimumab was more efficient than etanercept (p < 0.001) and infliximab (p = 0.026), with no differences between etanercept and infliximab (p = 0.086). Adalimumab was the most cost-effective treatment in achieving clinical remission in real-life clinical conditions in RA patients during the study period.

  2. Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye

    PubMed Central

    Zhou, Chengxin; Robert, Marie-Claude; Kapoulea, Vassiliki; Lei, Fengyang; Stagner, Anna M.; Jakobiec, Frederick A.; Dohlman, Claes H.; Paschalis, Eleftherios I.

    2017-01-01

    Purpose Tumor necrosis factor (TNF)-α is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-α inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-α inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-α antibodies using a polymer-based drug delivery system (DDS). Methods The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 μg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-α DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. Results After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-α expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. Conclusions This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation. PMID:28114570

  3. Tubulointerstitial Nephritis as the Initial Presentation of Crohn’s Disease and Successful Treatment with Infliximab

    PubMed Central

    Caza, Tiffany; Huang, Dongmei; Beg, Mirza B.

    2017-01-01

    Tubulointerstitial nephritis (TIN) is not commonly associated in aminosalicylate-naïve patients with Crohn’s disease (CD). Our case describes the initial presentation, diagnosis, and management of an adolescent presenting with TIN and underlying CD. Our case emphasizes that CD should be considered in the differential diagnosis of interstitial nephritis as not only a medication-related effect, but also as an extraintestinal manifestation of CD. We also describe successful management of undiagnosed recurring and symptomatic CD-related TIN with infliximab. PMID:28286790

  4. A case of granulomatosis with polyangiitis and pyoderma gangrenosum successfully treated with infliximab and rituximab.

    PubMed

    Donmez, Salim; Pamuk, Omer N; Gedik, Mustafa; A K, Recep; Bulut, Gulay

    2014-05-01

    Here, we present a young male patient who was admitted with alveolar hemorrhage, arthritis and cutaneous lesions, who later developed bilateral orbital involvement and pyoderma gangrenosum (PG). He also had pathergy test positivity. The patient was refractory to conventional immunosuppressive therapy. Therefore, multiple devastating PG lesions and disease activity in granulomatosis with polyangiitis (GPA) were controlled with infliximab. Later, rituximab was used with success to prevent recurrence of symptoms. The relationship of PG with various autoimmune diseases is known; however, PG in GPA has been only rarely reported. Biologic agents might prove to be effective in GPA and PG patients who are refractory to standard immunosuppressive therapy.

  5. Pyoderma gangrenosum outside the context of inflammatory bowel disease treated successfully with infliximab.

    PubMed

    Swale, V J; Saha, M; Kapur, N; Hoffbrand, A V; Rustin, M H A

    2005-03-01

    A 63-year-old man with chronic lymphocytic leukaemia developed pyoderma gangrenosum following minor trauma to the leg. He required intensive inpatient management with a multitude of treatments including larval therapy, surgical debridement, ciclosporin, methotrexate, thalidomide, pulsed intravenous methylprednisolone and high-dose intravenous immunoglobulin, clofazamine and high dose oral corticosteroids, none of which were helpful. Treatment complications included steroid-induced diabetes, Cushing's syndrome and perforated peptic ulcer. The pyoderma remained refractory to treatment and continued to extend until he received intravenous infliximab 5 mg/kg at weeks 0, 2 and 6.

  6. Lewis-Sumner syndrome associated with infliximab therapy in rheumatoid arthritis.

    PubMed

    Hooper, Davyd R; Tarnopolsky, Mark A; Baker, Steven K

    2008-10-01

    We report 2 cases of Lewis-Sumner syndrome (LSS) diagnosed in patients suffering from rheumatoid arthritis undergoing treatment with the antitumor necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab. While experiencing clinical improvement in their arthritic symptoms, both patients experienced sensory deficits and weakness in multiple nerve distributions. They had electrodiagnostic evidence of motor conduction block and subsequent improvement with intravenous immunoglobulin (IVIg). We describe the details of the cases and review the literature on immune-mediated neuropathies associated with anti-TNF-alpha therapy.

  7. Use of adalimumab in patients with juvenile idiopathic arthritis refractory to etanercept and/or infliximab.

    PubMed

    Katsicas, María M; Russo, Ricardo A G

    2009-08-01

    To analyse the effectiveness and safety of adalimumab in a group of patients with juvenile idiopathic arthritis (JIA) who had failed treatment with etanercept and/or infliximab in a single paediatric rheumatology clinic. Patients with JIA with active polyarthritis refractory to metotrexate (MTX) (> or =20 mg/m2/week) for at least 3 months and to etanercept (up to 1 mg/kg twice weekly) and/or infliximab (up to 10 mg/kg every 4 weeks) for at least 6 months were included. All patients received adalimumab 24 mg/m2/week concomitantly with MTX 7.5-10 mg/week. Evaluation of efficacy included improvement as defined by the ACR paediatric 30 criteria, 50% and 70% improvement and remission. Six patients were included. Three patients met improvement criteria; 50% and 70% improvement occurred in two children. Improvement was sustained for 12, 24 and 36 months, respectively. Remission occurred in one patient. Adalimumab was discontinued due to lack of efficacy in three patients. No side effects were observed. Adalimumab appears to be effective and safe in patients with JIA refractory to other anti-TNF agents. Further controlled studies are needed in order to assess efficacy of adalimumab in children with refractory JIA.

  8. Atypical Cutaneous Blastomycosis in a Child With Juvenile Idiopathic Arthritis on Infliximab.

    PubMed

    Smith, Robert J; Boos, Markus D; Burnham, Jon M; McKay, Eileen M; Kim, Jason; Jen, Melinda

    2015-11-01

    Blastomyces dermatitidis is a dimorphic fungus endemic to much of North America, particularly the soils of the midwestern and southeastern United States. Human infection typically occurs through inhalation of airborne conidia, which can be followed occasionally by dissemination to the skin, bone, genitourinary system, and central nervous system. A hallmark of the pathogen is that it can cause disease in both immunocompetent and immunosuppressed populations. Blastomycosis is rare in pediatric patients, with cutaneous manifestations occurring even less frequently. Here, we report the case of a 9-year-old boy on iatrogenic immunosuppression with infliximab and methotrexate for juvenile idiopathic arthritis who presented with a nonhealing, indurated plaque of his right ear with significant superficial yellow crusting in the absence of constitutional symptoms. After failing a prolonged course of topical and oral antibiotic therapy, biopsy and tissue culture revealed Blastomyces dermatitidis infection. The area cleared after treatment with oral fluconazole and withdrawal of infliximab. To our knowledge, this is the first report of a pediatric patient developing an infection with B dermatitidis after initiation of therapy with a tumor necrosis factor-α inhibitor. This case also highlights an unusual morphology of cutaneous blastomycosis in an iatrogenically immunosuppressed child.

  9. Etanercept, infliximab, and leflunomide in established rheumatoid arthritis: clinical experience using a structured follow up programme in southern Sweden

    PubMed Central

    Geborek, P; Crnkic, M; Petersson, I; Saxne, T

    2002-01-01

    Objective: To explore the feasibility of prospectively monitoring treatment efficacy and tolerability of infliximab, etanercept, and leflunomide over a two year period in patients with established rheumatoid arthritis (RA) in clinical practice using a structured protocol. Methods: All patients with RA at seven centres in southern Sweden, for whom at least two disease modifying antirheumatic drugs, including methotrexate, had failed or not been tolerated, who started treatment with either infliximab, etanercept, or leflunomide were included. They were evaluated at predefined times using a standardised protocol including items required for evaluating response to the American College of Rheumatology (ACR) or EULAR criteria. All adverse events were recorded using World Health Organisation terminology. Concomitant treatment and survival while receiving a drug were recorded. Results: During the study 166 patients were treated with etanercept, 135 with infliximab, and 103 with leflunomide. Treatment response as determined by the ACR and EULAR response criteria was similar for the tumour necrosis factor (TNF) blockers. The TNF blockers performed significantly better than leflunomide both as determined by the response criteria and by survival on drug analysis. Thus 79% and 75% continued to receive etanercept or infliximab compared with 22% of patients who started leflunomide after 20 months. The spectrum of side effects did not differ from those previously reported in the clinical trials. The initial two year experience of a protocol for postmarketing surveillance of etanercept, infliximab, and leflunomide shows that a structured protocol with central data handling can be used in clinical practice for documenting the performance of newly introduced drugs. Conclusions: Efficacy data for the TNF blockers comply with results in clinical trials, whereas leflunomide appeared to perform worse than in clinical trials. Prolonged monitoring is required to identify possible rare side

  10. Effects of systemic Thalidomide and intracerebroventricular Etanercept and Infliximab administration in a Streptozotocin induced dementia model in rats.

    PubMed

    Kübra Elçioğlu, H; Kabasakal, Levent; Tufan, Fatih; Elçioğlu, Ömer H; Solakoglu, Seyhun; Kotil, Tugba; Karan, Mehmet Akif

    2015-03-01

    Tumor necrosis factor-alpha (TNF-α) upregulation enhances amyloid β (Aβ) induced neurotoxicity in Alzheimer's disease (AD). Intracerebroventricular streptozotocin (STZ) administration causes pathological changes and cognitive deficits similar to those seen in AD by causing impairment of brain glucose and energy metabolism. Recent reports indicate a protective role of Thalidomide, Etanercept, and Infliximab, all of which have anti-TNF-α activity, against cognitive and neuropathological changes in experimental and clinical studies. We aimed to investigate the protective effects of Thalidomide, Etanercept, and Infliximab in a rat model of intracerebroventricular STZ-induced dementia. Sprague-Dawley rats (250-300g) were separated to sham (n=6) and STZ (n=24) groups. The STZ group was divided into four groups (STZ, STZ-thalidomide, STZ-etanercept, and STZ-infliximab). Morris's water maze (MWM) and passive avoidance (PA) tests were performed. At the end of the third week, brain tissues were obtained. Histopathological analysis, immunohistochemistry, and electron microscopic examinations were done. The improvement performance of the STZ group was significantly reduced in the MWM test (p<0.001). Compared with the STZ, STZ-thalidomide, STZ-etanercept, and STZ-infliximab groups had significantly better performance (p<0.001, <0.05 and <0.05, respectively) in the MWM test. STZ administration caused a significant decrease in the mean escape latency in PA reflex (p<0.001). Thalidomide, Etanercept, and Infliximab were associated with better PA reflexes compared to the STZ group (p<0.001 for all). Morphological and immunohistochemical results showed increased neurodegenerative changes compared to sham group. Our findings are in line with the findings reported in the literature and encourage further studies with TNF-α antagonists, in particular Thalidomide.

  11. A scientific update on biosimilar infliximab (CT-P13) in rheumatic diseases.

    PubMed

    Taylor, Peter

    2015-01-01

    The development of biologic drugs has undoubtedly enhanced the spectrum of treatments available for immune-mediated inflammatory rheumatic diseases such as rheumatoid arthritis. However, despite their clear clinical benifits, use of biologics is often hindered by their high costs. The manufacture and subsequent approval of more cost-effective 'biosimilar' versions of these drugs may address this issue and improve patient access. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab (Remicade(®)), has shown comparable efficacy, safety and pharmacokinetics to its originator drug in clinical studies. The articles in this supplement present a scientific update on the development and use of biosimilars in rheumatic disorders, with specific focus on CT-P13. The information discussed highlights the predicted positive clinical and economic impact of biosimilars on the management of rheumatic diseases.

  12. Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab.

    PubMed

    Duca, Ileana; Ramírez de la Piscina, Patricia; Estrada, Silvia; Calderón, Rosario; Spicakova, Katerina; Urtasun, Leire; Marra-López, Carlos; Zabaleta, Salvador; Bengoa, Raquel; Marcaide, María Asunción; García-Campos, Francisco

    2013-01-28

    Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis. Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective. We describe a patient with long-standing ulcerative colitis, which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis (biochemical stage II/IV) in the course of his pancolitis. Treatment with infliximab (5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprine-related hepatic toxicity. At present, after two years of follow-up, the patient is asymptomatic with normal liver tests and complete resumption of daily life activities. This case draws attention to the usefulness of anti-tumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease.

  13. Emergence of antinuclear antibodies in psoriatic patients treated with infliximab: personal experience and literature review.

    PubMed

    Chimenti, Maria Sole; Spinelli, Francesca Romana; Giunta, Alessandro; Martinelli, Francesco; Saraceno, Rosita; Conti, Fabrizio; Perricone, Roberto; Valesini, Guido

    2014-11-01

    Psoriasis is a chronic inflammatory skin disease affecting up to 2.5% of the population, with joint involvement in approximately 30% of patients. Given the role of tumor necrosis factor (TNF) in the pathogenesis of psoriasis, anti-TNF therapies have been developed; several studies have demonstrated the efficacy of infliximab (IFX) as induction and maintenance therapy in the treatment of moderate to severe plaque psoriasis. The development of antinuclear antibodies (ANA) in anti-TNF-treated patients has been frequently reported. The aim of this study was to investigate the incidence of ANA and anti-double stranded DNA (anti-dsDNA) antibodies in psoriatic patients receiving IFX. Incidence of new ANA and anti-ds-DNA was 16.2% and 8.1% respectively. No case of anti-TNF induced Lupus was observed during the follow-up.

  14. Scientific rationale behind the development and approval of biosimilar infliximab (CT-P13) in Europe.

    PubMed

    Müller-Ladner, Ulf; Hong, SeungSuh; Oh, Choongseob; Taylor, Peter

    2015-01-01

    Biosimilars are drugs developed to be highly similar to their originator biologic (or 'reference medicinal product') with no clinically meaningful differences in purity, efficacy or safety. Production of biologics and biosimilars is highly complex and sensitive, with any change in manufacturing process having a potential impact on efficacy and safety. This review provides an overview of the manufacturing process for these drugs and considers the implications of any process changes. The scientific rationale underlying the regulatory comparability exercise for process-changed reference medicinal products and biosimilars is also discussed, as is the issue of 'switchability' from a reference medicinal product to its biosimilar. CT-P13 (Remsima(®), Inflectra(®)), a biosimilar of infliximab, is used as a case study to discuss these issues.

  15. Anti‐inflammatory effects of infliximab in mice are independent of tumour necrosis factor α neutralization

    PubMed Central

    Assas, B. M.; Levison, S. E.; Little, M.; England, H.; Battrick, L.; Bagnall, J.; McLaughlin, J. T.; Paszek, P.; Else, K. J.

    2016-01-01

    Summary Infliximab (IFX) has been used repeatedly in mouse preclinical models with associated claims that anti‐inflammatory effects are due to inhibition of mouse tumour necrosis factor (TNF)‐α. However, the mechanism of action in mice remains unclear. In this study, the binding specificity of IFX for mouse TNF‐α was investigated ex vivo using enzyme‐linked immunosorbent assay (ELISA), flow cytometry and Western blot. Infliximab (IFX) did not bind directly to soluble or membrane‐bound mouse TNF‐α nor did it have any effect on TNF‐α‐induced nuclear factor kappa B (NF‐κB) stimulation in mouse fibroblasts. The efficacy of IFX treatment was then investigated in vivo using a TNF‐α‐independent Trichuris muris‐induced infection model of chronic colitis. Infection provoked severe transmural colonic inflammation by day 35 post‐infection. Colonic pathology, macrophage phenotype and cell death were determined. As predicted from the in‐vitro data, in‐vivo treatment of T. muris‐infected mice with IFX had no effect on clinical outcome, nor did it affect macrophage cell phenotype or number. IFX enhanced apoptosis of colonic immune cells significantly, likely to be driven by a direct effect of the humanized antibody itself. We have demonstrated that although IFX does not bind directly to TNF‐α, observed anti‐inflammatory effects in other mouse models may be through host cell apoptosis. We suggest that more careful consideration of xenogeneic responses should be made when utilizing IFX in preclinical models. PMID:27669117

  16. Changes in Body Mass Index and Lipid Profile in Psoriatic Patients After Treatment With Standard Protocol of Infliximab.

    PubMed

    Ehsani, Amir Houshang; Mortazavi, Hossein; Balighi, Kamran; Hosseini, Mahboubeh Sadat; Azizpour, Arghavan; Hejazi, Seyyedeh Pardis; Goodarzi, Azadeh; Darvari, Seyyedeh Bahareh

    2016-09-01

    Psoriasis is a chronic and inflammatory dermatologic disease. Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial. Regarding frequent use of infliximab in psoriasis, and the hypothesis that anti TNF-α treatment may increase Body Mass Index (BMI) and alter lipid profile in these patients, the aim of this study was to assess changes in BMI and Lipid Profile and level of leptin in Psoriatic Patients under Treatment of Standard Protocol of Infliximab in a 24 week period. This study was accomplished as a before-after study. Twenty-seven psoriatic patients were included, and standard infliximab therapy was applied. All patients underwent 3 times of blood collection and in each session; LDL, HDL, Total Cholesterol, Triglycerides, Leptin, and PASI score were measured at the start of the study and at the 12th and 24th week of follow-up. Twenty-five patients consisted of 18 (72%) male and 7 (28%) female subjects were evaluated. The mean age of the patients was 36.91±13.31 years. PASI score demonstrated significant decrease after 24 weeks; however, BMI and HDL and leptin showed a significant increase during treatment. Significant negative correlation was seen between Leptin and PASI score changes (r=0.331, P=0.042). HDL and BMI had the most correlations with leptin (positive correlation) and PASI score (negative correlation). Results demonstrated a dramatic decrease in PASI, increase in BMI and HDL and increased in leptin; somewhat correlated to each other. These results suggest that patients taking infliximab should take more care of their weight and lipid profile, while on treatment.

  17. Repeated infusions of infliximab, a chimeric anti-TNFα monoclonal antibody, in patients with active spondyloarthropathy: one year follow up

    PubMed Central

    Kruithof, E; Van den Bosch, F; Baeten, D; Herssens, A; De Keyser, F; Mielants, H; Veys, E

    2002-01-01

    Background: In a pilot study, the anti-tumour necrosis factor α monoclonal antibody, infliximab, induced a rapid and significant improvement in global, peripheral, and axial disease manifestations of patients with active spondyloarthropathy. Objective: To determine whether repeated infusions of infliximab would effectively and safely maintain the observed effect. Methods: Safety and efficacy of a maintenance regimen (5 mg/kg infliximab every 14 weeks) was evaluated using the measurements reported in the pilot study. Of the 21 patients, 19 completed the one year follow up for efficacy; two patients changed to another dosing regimen after week 12 owing to partial lack of efficacy. However, they are still being followed up for safety analysis. Results: After each re-treatment a sustained significant decrease of all disease manifestations was observed. Before re-treatment, symptoms recurred in 3/19 (16%) at week 20, in 13/19 (68%) at week 34, and in 15/19 (79%) at week 48. No withdrawals due to adverse events occurred. Twelve minor infectious episodes were observed. Twelve patients (57%) developed antinuclear antibodies; in four of them (19%) anti-dsDNA antibodies were detected. However, no lupus-like symptoms occurred. Conclusion: In this open study of infliximab in patients with active spondyloarthropathy, the significant improvement of all disease manifestations was maintained over a one year follow up period without major adverse events. Although recurrence of symptoms was noted in a rising number of patients before each re-treatment, no loss of efficacy was observed after re-treatment. PMID:11830424

  18. Infliximab therapy balances regulatory T cells, tumour necrosis factor receptor 2 (TNFR2) expression and soluble TNFR2 in sarcoidosis.

    PubMed

    Verwoerd, A; Hijdra, D; Vorselaars, A D M; Crommelin, H A; van Moorsel, C H M; Grutters, J C; Claessen, A M E

    2016-08-01

    Sarcoidosis is a systemic granulomatous disease of unknown aetiology that most commonly affects the lungs. Although elevated levels of regulatory T cells (Tregs ) have been reported, the extent to which they play a role in sarcoidosis pathogenesis remains unclear. Tumour necrosis factor (TNF) is thought to be one of the driving forces behind granuloma formation, illustrated by the efficacy of infliximab in severe sarcoidosis. Tregs express TNF receptor 2 (TNFR2) highly. Here, we examined the influence of infliximab therapy on Tregs and (soluble) TNFR2 levels in sarcoidosis, and correlated these with response to therapy. We observed that relative frequencies of Tregs were significantly higher in patients (n = 54) compared to healthy controls (n = 26; median 6·73 versus 4·36%; P < 0·001) and decreased following therapy (4·95; P < 0·001). Baseline TNFR2 expression on Tregs was increased significantly in patients versus controls (99·4 versus 96·2%; P = 0·031), and also in responders to therapy versus non-responders (99·6 versus 97·3%; P = 0·012). Furthermore, baseline soluble TNFR2 (sTNFR2) was higher in responders than in non-responders (mean 174 versus 107 pg/ml; P = 0·015). After treatment, responders showed a significant reduction in sTNFR2 levels in peripheral blood (-44·7 pg/ml; P < 0·001), in contrast to non-responders (+3·59 pg/ml). Our results demonstrated that Treg frequencies and TNFR2 expression on Tregs are increased in sarcoidosis, followed by a decline during infliximab therapy, suggesting a pathophysiological role of this T cell subset. Interestingly, sTNFR2 levels at baseline differed significantly between responders and non-responders, making it a potential marker in predicting which patients might benefit from infliximab.

  19. The use of adalimumab, etanercept, golimumab and infliximab in rheumatic pathologies: variation between label dosage and real-world use.

    PubMed

    Martinez-Cutillas, Julio; Alerany-Pardo, Carme; Borrás-Blasco, Joaquín; Broto-Sumalla, Antonio; Burgos-SanJosé, Amparo; Climent-Bolta, Consuelo; Escudero-Vilaplana, Vicente; Fernández-Fuente, María Anunciación; Ferrit-Martin, Mónica; Gómez-Germá, Pilar; Martínez-Sesmero, José Manuel; Mayorga-Pérez, Jesús; Menchén-Viso, Belén; Merino-Alonso, Javier; Polache-Vengud, Josefa; Sánchez-Guerrero, Amelia

    2015-01-01

    Rheumatoid arthritis (AR), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) are autoimmune systemic diseases characterized by inflammation, pain and joint degeneration. The objective of this study is to evaluate, under the actual conditions of use, dosing patterns of adalimumab, etanercept, golimumab and infliximab in these pathologies, and compare them with the label regimens recommended, as well as evaluating the financial implications of these regimen modifications. The study population included all adult patients diagnosed with RA, PSA or AS who had been treated with adalimumab, etanercept, golimumab and infliximab for at least 6 months between 1 January 2011 and 31 December 2013. The main variable of this study was to assess the dose dispensed for drugs administered subcutaneously and the dose prepared/administered for drugs administered intravenously, and the annual costs of the treatment. A total of 5,428 episodes were included. The mean weekly dose was lower than the standard dose in the three pathologies studied in the patients treated with adalimumab and etanercept (84.3% vs 81.2% for RA, 85.0% vs 78.0% for PSA and 87.8% vs 81.6% for AS). The drugs with highest dose optimization in RA are etanercept (46.3%) followed by adalimumab (46%); however, the highest percentage of patients with major dose optimization corresponds to etanercept (11.6%). Both in the PA and the AS group, we also observed that etanercept is the drug more optimized, corresponding to 53.9 and 43% of patients, respectively. By contrast, 48.5% of patients with RA treated with infliximab required dose intensification; however, infliximab dose intensification in PSA and AS is not so pronounced. The practice of optimization of dose regimens in patients with rheumatic diseases under treatment with anti-TNFα is spreading among professionals, resulting in annual cost reduction in the treatment of rheumatic arthropathies. However, long term follow-up will be necessary to assess the

  20. Tnf-α inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy.

    PubMed

    Saritemur, Murat; Un, Harun; Cadirci, Elif; Karakus, Emre; Akpinar, Erol; Halici, Zekai; Ugan, Rustem Anil; Karaman, Adem; Atmaca, Hasan Tarik

    2015-03-01

    Contrast medium-induced nephropathy (CIN) remains as a problem with high incidence and mortality rates. The aim of this study is to examine the roles of infliximab (INF) in the glycerol (GLY) and CIN model in rats. The rats were separated into five groups (n=8): Healthy, GLY, GLY+CM, GLY+CM+INF 5mg/kg intraperitoneally (i.p.), and GLY+CM+INF 7 mg/kg (i.p.). Antioxidant levels in the therapy groups were observed to be quite similar to those in the healthy group. In this study, while the kidney TNF-α, IL-1β, TGF-1β and Caspase 3 gene expressions' levels increased in the nephrotoxic groups, these levels were found to have decreased in the treatment groups. Moreover, histopathologic examination showed that hyaline, haemorrhagic casts and necrosis were increased in nephrotoxicity group, whereas they decreased in the therapy group. Furthermore, TNF-α and NF-κB expression were decreased with infliximab administrated groups similar to control group. In conclusion, we suggest that infliximab have protective roles on CIN.

  1. Good response to infliximab in a patient with deep vein thrombosis associated with Behçet disease.

    PubMed

    Yoshida, Shuzo; Takeuchi, Tohru; Yoshikawa, Ayaka; Ozaki, Takuro; Fujiki, Yohei; Hata, Kenichiro; Makino, Shigeki; Hanafusa, Toshiaki

    2012-09-01

    Vascular involvement is a lethal complication in Behçet disease. It is often refractory to conventional therapy such as steroids and immunosuppressants in addition to anticoagulants. We describe here successful treatment with the anti-tumor necrosis factor-alpha (anti-TNF-α) antibody, infliximab, in a patient with Behçet disease presenting with deep vein thrombosis. A 60-year-old man with Behçet disease complained of edema and pain in the lower extremities. Computed tomography revealed a thrombosis extending from the popliteal vein to the inferior vena cava at the level of the renal vein and which recurred despite combination therapy of steroid and immunosuppressants such as cyclosporine, azathioprine, and methotrexate. The patient was then administered infliximab (5 mg/kg) in weeks 0 and 2 and every 4 weeks thereafter. Clinical and laboratory findings improved after the infliximab therapy. Computed tomography of the abdomen and lower extremities showed a reduction of the thrombosis. No severe adverse events occurred during the clinical course. Although further studies are needed to confirm the efficacy and safety of its use, anti-TNF-α antibody may be worth considering as treatment for refractory venous thrombosis in patients with Behçet disease.

  2. Infliximab reverses steatosis and improves insulin signal transduction in liver of rats fed a high-fat diet.

    PubMed

    Barbuio, Raquel; Milanski, Marciane; Bertolo, Manoel B; Saad, Mário J; Velloso, Lício A

    2007-09-01

    Non-alcoholic fatty liver disease, induced by nutritional factors, is one of the leading causes of hepatic dysfunction in the modern world. The activation of proinflammatory signaling in the liver, which is induced by systemic and locally produced cytokines, and the development of hepatic insulin resistance are two important factors associated with the progression from steatosis to steatohepatitis, a pre-cirrhotic condition. The objective of the present study was to evaluate the effect of inhibition of tumour necrosis factor (TNF)-alpha , using the monoclonal antibody infliximab, on the expression of cytokines, induction of steatosis and fibrosis, and insulin signal transduction in the liver of Wistar rats fed a high-fat diet. Ten days of treatment with infliximab significantly reduced the expression of the proinflammatory markers, TNF-alpha , IL-6, IL-1beta , and SOCS-3, in the liver of rats fed a high-fat diet. This was accompanied by reduced fat deposition and fibrosis and by improved insulin signal transduction through insulin receptor (IR)/IR substrate/Akt/FOXO1 and JAK2/STAT3 pathways. In conclusion, short-term inhibition of TNF-alpha with infliximab reduces inflammation and steatosis/fibrosis, while improving insulin signal transduction in an animal model treated with a high-fat diet.

  3. Infliximab, Infliximab-dyyb Injection

    MedlinePlus

    ... injection may cause serious allergic reactions during an infusion and for 2 hours afterward. A doctor or ... the following symptoms during or shortly after your infusion: hives; rash; itching; swelling of the face, eyes, ...

  4. Effect of infliximab on mRNA expression profiles in synovial tissue of rheumatoid arthritis patients

    PubMed Central

    Lindberg, Johan; af Klint, Erik; Catrina, Anca Irinel; Nilsson, Peter; Klareskog, Lars; Ulfgren, Ann-Kristin; Lundeberg, Joakim

    2006-01-01

    We examined the gene expression profiles in arthroscopic biopsies retrieved from 10 rheumatoid arthritis patients before and after anti-TNF treatment with infliximab to investigate whether such profiles can be used to predict responses to the therapy, and to study effects of the therapy on the profiles. Responses to treatment were assessed using European League Against Rheumatism response criteria. Three patients were found to be good responders, five patients to be moderate responders and two patients to be nonresponders. The TNF-α status of the biopsies from each of the patients before treatment was also investigated immunohistochemically, and it was detected in biopsies from four of the patients, including all three of the good responders. The gene expression data demonstrate that all patients had unique gene expression signatures, with low intrapatient variability between biopsies. The data also revealed significant differences between the good responding and nonresponding patients (279 differentially expressed genes were detected, with a false discovery rate < 0.025). Among the identified genes we found that MMP-3 was significantly upregulated in good responders (log2 fold change, 2.95) compared with nonresponders, providing further support for the potential of MMP-3 as a marker for good responses to therapy. An even more extensive list of 685 significantly differentially expressed genes was found between patients in whom TNF-α was found and nonresponders, indicating that TNF-α could be an important biomarker for successful infliximab treatment. Significant differences were also observed between biopsies taken before and after anti-TNF treatment, including 115 differentially expressed genes in the good responding group. Interestingly, the effect was even stronger in the group in which TNF-α was immunohistochemically detected before therapy. Here, 1,058 genes were differentially expressed, including many that were novel in this context (for example, CXCL3

  5. Validation of a sample pretreatment protocol to convert a drug-sensitive into a drug-tolerant anti-infliximab antibody immunoassay.

    PubMed

    Van Stappen, Thomas; Brouwers, Els; Vermeire, Séverine; Gils, Ann

    2017-02-01

    A meta-analysis revealed that up to 51% of patients treated with infliximab develop anti-drug Abs (ADA) which are associated with loss of response. Detection of ADA is strongly influenced by assay technique since drug-sensitive ADA assays are not able to detect ADA in the presence of drug and therefore underestimate ADA development. In addition, the lack of a calibrator antibody that can be used in a drug-sensitive and drug-tolerant assay hampers an adequate comparison among different assays. Here we present a sample pretreatment protocol to convert the bridging assay, originally developed as a drug-sensitive assay, into a drug-tolerant assay, allowing use of the same assay and calibrator antibody MA-IFX10F9. Using the sample pretreatment protocol, the bridging assay detects antibodies towards infliximab in samples containing up to 5-fold infliximab over anti-infliximab. Analysis of consecutive serum samples from infliximab treated patients revealed that the drug-tolerant assay detects ADA development up to 40 weeks earlier compared to the drug-sensitive assay. In conclusion, the sample pretreatment protocol can be implemented in various assay formats and allows determination of ADA in the presence of drug, providing the possibility for early treatment optimization. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Steroid-refractory ulcerative colitis and associated primary sclerosing cholangitis treated with infliximab

    PubMed Central

    Duca, Ileana; Ramírez de la Piscina, Patricia; Estrada, Silvia; Calderón, Rosario; Spicakova, Katerina; Urtasun, Leire; Marra-López, Carlos; Zabaleta, Salvador; Bengoa, Raquel; Marcaide, María Asunción; García-Campos, Francisco

    2013-01-01

    Primary sclerosing cholangitis is an infrequent extraintestinal manifestation of ulcerative colitis. Damage to bile ducts is irreversible and medical therapies to prevent progression of the disease are usually ineffective. We describe a patient with long-standing ulcerative colitis, which was refractory to corticosteroid therapy who developed primary sclerosing cholangitis (biochemical stage II/IV) in the course of his pancolitis. Treatment with infliximab (5 mg/kg as an induction dose followed by maintenance doses every two months) was indicated because of steroid-dependent disease associated to primary sclerosing cholangitis as well as sacroiliitis and uveitis and previous episode of severe azathioprine-related hepatic toxicity. At present, after two years of follow-up, the patient is asymptomatic with normal liver tests and complete resumption of daily life activities. This case draws attention to the usefulness of anti-tumor necrosis factor-alpha therapy for the management of primary sclerosing cholangitis as extraintestinal manifestation of inflammatory bowel disease. PMID:23382642

  7. Infliximab as a treatment option for patients with rheumatoid arthritis and primary biliary cirrhosis.

    PubMed

    Dimopoulou, Despoina; Dimitroulas, Theodoros; Akriviadis, Evangelos; Garyfallos, Alexandros

    2015-11-01

    Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease which commonly requires treatment with biologic agents targeting various inflammatory pathways. Tumor necrosis factor alpha is a proinflammatory cytokine which plays a pivotal role not only in the pathogenesis of RA but also in other autoimmune diseases such as primary biliary cirrhosis. The co-existence of more than one autoimmune disorder in the same individual is very challenging in the daily practice as therapy strategies applicable to one disease setting may cause clinical and/or biochemical relapse of the other clinical entity. As a result, treatment options able to control different diseases are highly desirable among rheumatologists and other specialties. In that respect, we present a case of a 61-year-old female patient with RA and concomitant primary biliary cirrhosis with poor clinical response to conventional disease-modifying drugs for RA. The introduction of tumor necrosis factor alpha antagonist infliximab led to significant clinical improvement of RA and to stabilization of liver function. In this case review study, we discuss aspects of pathophysiology of primary biliary cirrhosis associated with tumor necrosis alpha and we review the available data of similar published cases.

  8. Infliximab/Plasmapheresis in vanishing bile duct syndrome secondary to toxic epidermal necrolysis.

    PubMed

    White, Jason C; Appleman, Stephanie

    2014-10-01

    Vanishing bile duct syndrome (VBDS) is a rare disorder characterized by loss of interlobular bile ducts and progressive worsening cholestasis. The acute presentation of this disease is typically associated with a drug hypersensitivity and Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN). The mainstay of treatment has been ursodeoxycholic acid with mixed results from immunosuppressive regimens. Anti-tumor necrosis factor-α and plasmapheresis have been speculated to be of potential benefit. It is hoped that early identification and intervention in VBDS secondary to Stevens-Johnson syndrome/TEN with continued reporting will lead to better regimens and outcomes. Our case report details the first reported use of infliximab and plasmapheresis, in addition to steroids, in a patient with VBDS secondary to TEN, as well as a literature review that supports a mechanism for why these modalities could be effective treatments. Unfortunately, our patient died, and the use of these therapies had an unclear benefit on his liver and skin disease. We hope that additional work can be published to confirm or refute their utility in the treatment of these diseases.

  9. The protective effect of infliximab against carbon tetrachloride-induced acute lung injury

    PubMed Central

    Kurt, Aysel; Tumkaya, Levent; Yuce, Suleyman; Turut, Hasan; Cure, Medine Cumhur; Sehitoglu, Ibrahim; Kalkan, Yildiray; Pusuroglu, Gokhan; Cure, Erkan

    2016-01-01

    Objective(s): Carbon tetrachloride (CCl4) causes pulmonary toxicity. Infliximab (Ib) is a potent inhibitor of tumor necrosis factor-alpha (TNF-α). We aimed to investigate whether Ib has a protective effect on CCl4 induced lung injury. Materials and Methods: Rats were divided into control, CCl4, and CCl4+Ib groups. A single dose of 2 ml/kg CCI4 was administered to CCI4 group and a single dose of 7 mg/kg Ib was given to CCl4+Ib group 24 hr before applying CCI4. Results: TNF-α, malondialdehyde (MDA), nitric oxide (NO) and caspase-3 levels of the CCl4 group were markedly higher than both the control and CCl4+Ib groups. The CCI4+Ib group had lower histopathological injury than the CCl4 group. Conclusion: Ib as a strong TNF-α blocker decreases the production of proinflammatory cytokines, MDA, and oxidative stress leading to a protective effect against CCl4 induced lung tissue injury. PMID:27482351

  10. Methotrexate Reduced TNF Bioactivity in Rheumatoid Arthritis Patients Treated with Infliximab

    PubMed Central

    Rinaudo-Gaujous, Mélanie; Thomas, Thierry

    2017-01-01

    Objectives. To evaluate methotrexate effect on tumor necrosis factor (TNF) alpha bioactivity during infliximab (IFX) therapy in rheumatoid arthritis (RA) patients and to correlate TNF bioactivity with antibody towards IFX (ATI) development and RA clinical response. Materials and Methods. Thirty-nine active women RA patients despite conventional synthetic disease modifying antirheumatic drugs (csDMARDs) requiring IFX therapy were enrolled, and clinical data and blood samples were recorded at baseline (W0) and at 6 weeks (W6), W22, and W54 of IFX treatment. TNF bioactivity as well as IFX trough and ATI concentrations were assessed on blood samples. Results. TNF bioactivity decreased from W0 to W54 with a large range from W22 at the time of ATI detection. From W22, TNF bioactivity was lower in presence of methotrexate as csDMARD compared to other csDMARDs. IFX trough concentration increased from W0 to W54 with a large range from W22, similarly to TNF bioactivity. Methotrexate therapy prevented ATI presence at W22 and reduced TNF bioactivity compared to other csDMARDs (p = 0.002). Conclusion. This suggests that methotrexate plays a key role in TNF bioactivity and against ATI development. PMID:28352145

  11. Fulminant Hepatic Failure in a Patient with Crohn's Disease on Infliximab Possibly Related to Reactivation of Herpes Simplex Virus 2 Infection

    PubMed Central

    Worobetz, Lawrence

    2016-01-01

    HSV hepatitis is a rare but often fatal cause of liver failure which tends to affect immunocompromised individuals. Early treatment with Acyclovir has been shown to reduce mortality in HSV hepatitis making recognition of the condition critically important. Here, we present a case of HSV hepatitis in a young woman with Crohn's disease on Prednisone, Azathioprine, and Infliximab. We discuss the clinical presentation of HSV hepatitis as well as the possible causes of hepatitis in a patient on these medications. This case helps demonstrate the importance of early clinical suspicion for HSV in undifferentiated fulminate liver failure. It is also the first reported case of HSV hepatitis in a patient on Infliximab, raising the possibility of HSV reactivation in patients on Infliximab. PMID:27818806

  12. Determination of ANA specificity using multiplexed fluorescent microsphere immunoassay in patients with ANA positivity at high titres after infliximab treatment: preliminary results.

    PubMed

    Caramaschi, Paola; Ruzzenente, Orazio; Pieropan, Sara; Volpe, Alessandro; Carletto, Antonio; Bambara, Lisa Maria; Biasi, Domenico

    2007-05-01

    To evaluate ANA specificity using the fully automated multiplexed fluorescent microsphere immunoassay in patients affected either by rheumatoid arthritis or ankylosing spondylitis who developed strong positivity for ANA as assessed by indirect immunofluorescent method on HEp-2 cells during infliximab treatment. Three men affected by ankylosing spondylitis and 12 women affected by rheumatoid arthritis who developed ANA positivity at high titres during infliximab treatment underwent the identification of ANA specificity by multiplexed fluorescent microsphere immunoassay; moreover anti-DNA and anti-ENA antibodies were tested by indirect immunofluorescence and ELISA method, respectively. In 4 out of 15 cases, the determination of ANA reactivity by multiplexed fluorescent microsphere immunoassay was also performed on the serum collected before infliximab administration. One patient affected by rheumatoid arthritis showed multiple ANA reactivities against SS-A, SS-B, RNP, Sm, Jo-1 and histones; one patient affected by ankylosing spondylitis resulted positive for the same autoantibodies, except for anti-Sm antibody. Moreover, two patients, one with rheumatoid arthritis and one with ankylosing spondylitis, showed single antibody specificity to SS-B and RNP, respectively. The remaining 11 cases did not show any positivity. Instead, all the patients resulted negative for anti-ENA antibodies by the ELISA method. In the four cases tested for ANA specificity by multiplexed fluorescent microsphere immunoassay before and after infliximab administration no difference was found. The search for anti-DNA antibody always resulted negative by both the traditional immunofluorescent assay and the novel technique. The use of multiplexed fluorescent microsphere immunoassay in patients treated with infliximab with ANA positivity at high titres allowed to find some ANA specificities which were not revealed by ELISA method. Nevertheless, the majority of patients resulted negative in spite of

  13. Retrospective study evaluating dose standards for infliximab in patients with rheumatoid arthritis at Hospital Israelita Albert Einstein, São Paulo, Brazil.

    PubMed

    Scheinberg, Morton; Goldenberg, José; Feldman, Daniel P; Nóbrega, João Luiz

    2008-08-01

    We determined, in our surrounding environment, the proportion of patients being treated with infliximab who required a therapeutic scheme escalation (an infliximab dose increase surpassing the level of 3 mg/kg every 8 weeks and/or a decrease on the current between infusions' interval). This was a study of the retrospective analysis of data from the 41 rheumatoid arthritis (RA) patients receiving an infliximab therapy at the Albert Einstein Israelita Hospital, from January 2001 up to December 2005. A questionnaire was applied to these patients, assessing their clinical and laboratory data, adverse events, and individual information regarding the infliximab administration. Therapeutic dose information was available in 68% (28/41) of the RA patients, with 46% of these (13/28) receiving a dose increase, and 30% (8/27) experiencing a shortening of the between infusions' interval. The average final infliximab dose (4.21 mg/kg) was significantly greater than their average initial dose (3.29 mg/kg). The average time intervals between the initial and final infusions, though shortened, were not significantly different. A proportion of 73% (30/41) of these patients demonstrated improvement in at least one of the assessed clinical parameters, and 50% of these patients (15/30) experienced a dose increase, while 20% (6/30) experienced shortening of the between treatments' interval. A total of 20% (8/41) of the original patients experienced adverse events. Although infliximab is effective in the control of RA, dose adjustment and/or shortening of the between treatments' interval is frequently required.

  14. Infliximab reduces CD147, MMP-3, and MMP-9 expression in peripheral blood monocytes in patients with active rheumatoid arthritis.

    PubMed

    Huang, Jianlin; Xie, Baozhao; Li, Qiuxia; Xie, Xujing; Zhu, Shangling; Wang, Mingxia; Peng, Weixiang; Gu, Jieruo

    2013-01-05

    Recent studies have reported elevated expression levels in active rheumatoid arthritis patients of the cluster of differentiation (CD) 147 on CD14(+) peripheral blood monocytes and as a result, CD147 may be a target for the development of a novel rheumatoid arthritis therapy. This report describes the inhibitory effects of infliximab on CD147 and metalloproteinases (MMP)-3 and MMP-9 overexpression in peripheral blood monocytes obtained from patients with active rheumatoid arthritis. Thirty patients with active rheumatoid arthritis that were refractory to methotrexate therapy were randomized at a 4:1 ratio into groups A and B, respectively. Group A received three to four infusions of infliximab (3mg/kg) and group B participants received four infusions of placebo. Both groups were also treated with a stable background dose of methotrexate. The CD147 expression levels on CD14(+) peripheral blood monocytes of rheumatoid arthritis patients was detected by flow cytometry. The expression of CD147, MMP-3, and, MMP-9 mRNA in peripheral blood mononuclear cells was assayed by real-time quantitative PCR, and the expression of MMP-3 and MMP-9 in serum was measured by a multiplexed microsphere-based flow assay. Results showed that the expression of CD147 and MMP-9 mRNA in group A decreased compared to group B. Expression of CD147 on CD14(+) monocytes was reduced (P<0.05), and serum MMP-3 and -9 levels in group A were decreased by week 18. These data suggested that infliximab could inhibit CD147 expression on CD14(+) monocytes as well as reduce the levels of MMP-3 and MMP-9 in peripheral blood monocytes.

  15. Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT)

    PubMed Central

    Seagrove, Anne C; Alam, M Fasihul; Alrubaiy, Laith; Cheung, Wai-Yee; Clement, Clare; Cohen, David; Grey, Michelle; Hilton, Mike; Hutchings, Hayley; Morgan, Jayne; Rapport, Frances; Roberts, Stephen E; Russell, Daphne; Russell, Ian; Thomas, Linzi; Thorne, Kymberley; Watkins, Alan; Williams, John G

    2014-01-01

    Introduction Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC. Methods and analysis Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants’ scores, analysed by Cox regression. Secondary outcome measures include: the CCQ—an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures—EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants’ views on therapies for acute severe UC and healthcare professionals’ views on the two drugs and their administration. Ethics and dissemination The Research Ethics Committee

  16. Switching to biosimilar infliximab (CT-P13): Evidence of clinical safety, effectiveness and impact on public health.

    PubMed

    Braun, Jürgen; Kudrin, Alex

    2016-07-01

    CT-P13, the biosimilar of infliximab, has been recently approved in the EU, Australia, Canada, Japan and many other countries. Thus, it was the first biosimilar approved in the field of rheumatology, dermatology and gastroenterology. Since there has been debate about the issue of switching from RMP to the biosimilar and some national societies have expressed concerns, this review was written with the following objectives: The review concludes that whilst prudent switching practices should be employed, growing safety experience accumulated thus far with CT-P13 and other biosimilars is favorable and does not raise any specific concerns.

  17. Physicochemical and biological characterization of SB2, a biosimilar of Remicade® (infliximab)

    PubMed Central

    Hong, Juyong; Lee, Yuhwa; Lee, Changsoo; Eo, Suhyeon; Kim, Soyeon; Park, Seungkyu; Seo, Donghyuck; Lee, Youngji; Yeon, Soojeong; Bou-Assaf, George; Sosic, Zoran; Zhang, Wei

    2017-01-01

    ABSTRACT A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor–α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy. PMID:28005456

  18. Serum-Infliximab Trough Levels in 45 Children with Inflammatory Bowel Disease on  Maintenance Treatment

    PubMed Central

    Rolandsdotter, Helena; Marits, Per; Sundin, Ulf; Wikström, Ann-Charlotte; Fagerberg, Ulrika L.; Finkel, Yigael; Eberhardson, Michael

    2017-01-01

    The role of trough serum infliximab (s-IFX) and antibodies toward IFX (ATI) during maintenance treatment remains unclear in children. The aim of the present study was to investigate trough s-IFX and ATI to identify any correlation with inflammatory activity and clinical response in a pediatric inflammatory bowel disease (IBD) cohort. We investigated the s-IFX trough levels in pediatric IBD patients (n = 45) on maintenance IFX treatment. Ninety-three blood samples were collected and demographics, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and albumin were recorded. The mean s-IFX trough level was 5.2 µg/mL. The mean trough s-IFX level was significantly higher in the samples taken during remission (7.2 µg/mL) compared to active disease (4.5 µg/mL, p < 0.05). The trough s-IFX levels correlated with ESR, CRP, and albumin. S-IFX was undetectable in eight of the patients, all with positive ATI and active disease. Surprisingly, clinical and biochemical remission was observed at only 26 of the 93 visits. The correlation between dose variations and changes in trough s-IFX was not evident. In line with studies in adults, the s-IFX trough levels correlated with response to infliximab. PMID:28272355

  19. Increased viability but decreased culturability of Mycobacterium avium subsp. paratuberculosis in macrophages from inflammatory bowel disease patients under Infliximab treatment.

    PubMed

    Nazareth, Nair; Magro, Fernando; Appelberg, Rui; Silva, Jani; Gracio, Daniela; Coelho, Rosa; Cabral, José Miguel; Abreu, Candida; Macedo, Guilherme; Bull, Tim J; Sarmento, Amélia

    2015-12-01

    Mycobacterium avium subsp. paratuberculosis (MAP) has long been implicated as a triggering agent in Crohn's disease (CD). In this study, we investigated the growth/persistence of both M. avium subsp. hominissuis (MAH) and MAP, in macrophages from healthy controls (HC), CD and ulcerative colitis patients. For viability assessment, both CFU counts and a pre16SrRNA RNA/DNA ratio assay (for MAP) were used. Phagolysosome fusion was evaluated by immunofluorescence, through analysis of LAMP-1 colocalization with MAP. IBD macrophages were more permissive to MAP survival than HC macrophages (a finding not evident with MAH), but did not support MAP active growth. The lower MAP CFU counts in macrophage cultures associated with Infliximab treatment were not due to increased killing, but possibly to elevation in the proportion of intracellular dormant non-culturable MAP forms, as MAP showed higher viability in those macrophages. Increased MAP viability was not related to lack of phagolysosome maturation. The predominant induction of MAP dormant forms by Infliximab treatment may explain the lack of MAP reactivation during anti-TNF therapy of CD but does not exclude the possibility of MAP recrudescence after termination of therapy.

  20. Bioanalysis of bevacizumab and infliximab by high-temperature reversed-phase liquid chromatography with fluorescence detection after immunoaffinity magnetic purification.

    PubMed

    Todoroki, Kenichiro; Nakano, Tatsuki; Eda, Yasuhiro; Ohyama, Kaname; Hayashi, Hideki; Tsuji, Daiki; Min, Jun Zhe; Inoue, Koichi; Iwamoto, Naoki; Kawakami, Atsushi; Ueki, Yukitaka; Itoh, Kunihiko; Toyo'oka, Toshimasa

    2016-04-15

    This study presents two simple and rapid methods for the quantification of therapeutic mAbs based on LC. Two mAbs (bevacizumab and infliximab) in plasma samples were purified using magnetic beads immobilized with a commercially-available idiotype antibody for each mAb. Purified mAbs were separated with HT-RPLC and detected with their native fluorescence. Using immunoaffinity beads, each mAb was selectively purified and detected as a single peak in the chromatogram. The HT-RPLC achieved good separation for the mAbs with sharp peaks within 20 min. The calibration curves of the two mAbs ranged from 1 to 20 μg mL(-1) (bevacizumab) and 1-10 μg mL(-1) (infliximab), and they had strong correlation coefficients (r(2) > 0.998). The LOD of bevacizumab and infliximab was 0.07 and 0.15 μg mL(-1), and the LLOQ of bevacizumab and infliximab was 0.12 and 0.25 μg mL(-1), respectively. Thus, the sensitivities were sufficient for clinical analysis. Immunoaffinity purification with HT-RPLC produced a selective and accurate bioanalysis without an LC-MS/MS instrument. Both methods could become general-purpose analytical methods and complement the results obtained with conventional LBA.

  1. Use of biofluorescence imaging to compare the distribution of certolizumab pegol, adalimumab, and infliximab in the inflamed paws of mice with collagen-induced arthritis.

    PubMed

    Palframan, Roger; Airey, Michael; Moore, Adrian; Vugler, Alex; Nesbitt, Andrew

    2009-08-31

    Exposure to a drug at the site of inflammation may be an important consideration for the effective treatment of inflammatory disorders such as rheumatoid arthritis (RA). The purpose of this in vivo study was to identify a methodology to enable effective quantification of antibody-type reagents in normal and inflamed tissue by investigating the distribution of the tumor necrosis factor-alpha (TNF-alpha) inhibitors, certolizumab pegol, adalimumab, and infliximab, in healthy and inflamed murine tissue using a novel non-invasive biofluorescence method. Certolizumab pegol, adalimumab, and infliximab were labeled with the low molecular weight dye alexa680. The agents were administered intravenously at a dose of 2mg/kg in naïve DBA/1 mice and in DBA/1 mice with ongoing collagen-induced arthritis. Concentrations of the TNF inhibitors in the hind paws were measured using a Xenogen IVIS200 biofluorescence imager at multiple time points up to 26h post-administration. In 2 independent experiments, the distribution of certolizumab pegol was compared with that of adalimumab and infliximab. Certolizumab pegol, adalimumab, and infliximab all distributed more effectively into inflamed tissue than non-inflamed tissue in this animal model of arthritis. However, the ratio of penetration of certolizumab pegol into inflamed arthritic paws compared with normal tissue was greater than that observed with adalimumab and infliximab. Furthermore, the duration of exposure in the inflamed versus normal tissue was more prolonged for certolizumab pegol than for both adalimumab and infliximab, and the accumulation of certolizumab pegol in diseased tissue was more responsive to the severity of inflammation when compared with adalimumab and infliximab. It is probable that these features of certolizumab pegol are conferred on the molecule by PEGylation. It is important to assess exposure to drug at the site of inflammation, because distinct structural features of certain agents may affect efficacy

  2. A randomised, double-blind, phase III study comparing SB2, an infliximab biosimilar, to the infliximab reference product Remicade in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy

    PubMed Central

    Choe, Jung-Yoon; Prodanovic, Nenad; Niebrzydowski, Jaroslaw; Staykov, Ivan; Dokoupilova, Eva; Baranauskaite, Asta; Yatsyshyn, Roman; Mekic, Mevludin; Porawska, Wieskawa; Ciferska, Hana; Jedrychowicz-Rosiak, Krystyna; Zielinska, Agnieszka; Choi, Jasmine; Rho, Young Hee; Smolen, Josef S

    2017-01-01

    Objectives To compare the efficacy, safety, immunogenicity and pharmacokinetics (PK) of SB2 to the infliximab reference product (INF) in patients with moderate to severe rheumatoid arthritis (RA) despite methotrexate therapy. Methods This is a phase III, randomised, double-blind, multinational, multicentre parallel group study. Patients with moderate to severe RA despite methotrexate therapy were randomised in a 1:1 ratio to receive either SB2 or INF of 3 mg/kg. The primary end point was the American College of Rheumatology 20% (ACR20) response at week 30. Inclusion of the 95% CI of the ACR20 response difference within a ±15% margin was required for equivalence. Results 584 subjects were randomised into SB2 (N=291; 290 analysed) or INF (N=293). The ACR20 response at week 30 in the per-protocol set was 64.1% in SB2 versus 66.0% in INF. The adjusted rate difference was −1.88% (95% CI −10.26% to 6.51%), which was within the predefined equivalence margin. Other efficacy outcomes such as ACR50/70, disease activity score measured by 28 joints and European League against Rheumatism response were similar between SB2 and INF. The incidence of treatment-emergent adverse events was comparable (57.6% in SB2 vs 58.0% in INF) as well as the incidence of antidrug antibodies (ADA) to infliximab up to week 30 (55.1% in SB2 vs 49.7% in INF). The PK profile was similar between SB2 and INF. Efficacy, safety and PK by ADA subgroup were comparable between SB2 and INF. Conclusions SB2 was equivalent to INF in terms of ACR20 response at week 30. SB2 was well tolerated with a comparable safety profile, immunogenicity and PK to INF. Trial registration number NCT01936181. PMID:26318384

  3. [Reactions to infliximab infusions in dermatologic patients: consensus statement and treatment protocol. Working Group of the Grupo Español de Psoriasis de la Academia Española de Dermatología y Venereología ].

    PubMed

    Puig Sanz, Lluís; Sáez, E; Lozano, M J; Bordas, X; Carrascosa, J M; Gallardo, F; Luelmo, J; Sánchez-Regaña, M; Alsina, M; García-Patos, V

    2009-03-01

    Infliximab is a chimeric monoclonal antibody that binds to and blocks tumor necrosis factor alpha and is the most effective biologic agent approved for the treatment of moderate-to-severe psoriasis. It is administered by intravenous infusion, usually in day hospitals on an outpatient basis. The main problem with the administration of infliximab is the possibility of infusion reactions, which may be immediate or delayed; these reactions are related to the immunogenicity of this monoclonal antibody, leading to the production of anti-infliximab antibodies. Infusion reactions to infliximab are not usually anaphylactic (ie, they are not mediated by immunoglobulin E), and re-exposure of the patient using specific protocols to prevent and treat these reactions is therefore possible. The extensive experience in the use of infliximab for the treatment of rheumatic conditions and chronic inflammatory bowel disease has made it possible to develop infusion reaction management protocols; these can be applied to dermatologic patients, who constitute a growing proportion of patients treated with intravenous biological agents. The aim of this review is to draw up a consensus protocol for the treatment of infusion reactions in dermatologic patients treated with infliximab.

  4. The scientific and regulatory rationale for indication extrapolation: a case study based on the infliximab biosimilar CT-P13.

    PubMed

    Reinisch, Walter; Louis, Edouard; Danese, Silvio

    2015-01-01

    Extrapolation of clinical data from other indications is an important concept in the development of biosimilars. This process depends on strict comparability exercises to establish similarity to the reference medicinal product. However, the extrapolation paradigm has prompted a fierce scientific debate. CT-P13 (Remsima(®), Inflectra(®)), an infliximab biosimilar, is a TNF antagonist used to treat immune-mediated inflammatory diseases. On the basis of totality of similarity data, the EMA approved CT-P13 for all indications held by its reference medicinal product (Remicade(®)) including inflammatory bowel disease. This article reviews the mechanisms of action of TNF antagonists in immune-mediated inflammatory diseases and illustrates the comparable profiles of CT-P13 and reference medicinal product on which the extrapolation of indications including inflammatory bowel disease is based.

  5. Biologic Treatment Registry Across Canada (BioTRAC): a multicentre, prospective, observational study of patients treated with infliximab for ankylosing spondylitis

    PubMed Central

    Rahman, Proton; Choquette, Denis; Bensen, William G; Khraishi, Majed; Chow, Andrew; Zummer, Michel; Shaikh, Saeed; Sheriff, Maqbool; Dixit, Sanjay; Sholter, Dalton; Psaradellis, Eliofotisti; Sampalis, John S; Letourneau, Vincent; Lehman, Allen J; Nantel, François; Rampakakis, Emmanouil; Otawa, Susan; Shawi, May

    2016-01-01

    Objectives To describe the profile of patients with ankylosing spondylitis (AS) treated with infliximab in Canadian routine care and to assess the effectiveness and safety of infliximab in real world. Setting 46 primary care rheumatology practices across Canada. Participants 303 biological-naïve patients with AS or patients previously treated with a biological for <6 months and who were eligible for infliximab treatment as per routine care within the Biologic Treatment Registry Across Canada (BioTRAC). Intervention Not applicable (non-interventional study). Primary and secondary outcomes Effectiveness was assessed with changes in disease parameters (AS Disease Activity Score (ASDAS), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI), Health Assessment Questionnaire Disease Index (HAQ-DI), physician global assessment of disease activity (MDGA), patient global disease activity (PtGA), back pain, C-reactive protein, erythrocyte sedimentation rate (ESR), morning stiffness). Safety was assessed with the incidence of adverse events (AEs). Results Of the 303 patients included, 44.6% were enrolled in 2005–2007 and 55.4% in 2008–2013. Patients enrolled in 2005–2007 had significantly higher MDGA and ESR at baseline while all other disease parameters examined were numerically higher with the exception of PtGA. Treatment with infliximab significantly (p<0.001) improved all disease parameters over time in both groups. At 6 months, 56% and 31% of patients achieved clinically important (change≥1.1) and major (change≥2.0) improvement in ASDAS, respectively; at 48 months, these proportions increased to 75% and 50%, respectively. Among patients unemployed due to disability at baseline, 12.1% returned to work (mean Kaplan-Meier (KM)-based time=38.8 months). The estimated retention rate at 12 and 24 months was 78.3% and 60.1%, respectively. The profile and incidence of AEs were comparable to data previously reported for tumour necrosis

  6. A 10-Year, Single Tertiary Care Center Experience on the Durability of Infliximab in Pediatric Inflammatory Bowel Disease

    PubMed Central

    Vahabnezhad, Elaheh; Rabizadeh, Shervin; Dubinsky, Marla C.

    2017-01-01

    Background Despite increasing use of infliximab (IFX) in children with Crohn’s disease (CD) and ulcerative colitis (UC), long-term durability and safety of IFX beyond 1 year is limited in pediatric inflammatory bowel disease. Methods We performed a 10-year single-center retrospective cohort study of 188 patients initiating IFX at <21 years of age with 1-year minimum follow-up. Data were retrieved from medical records. IFX outcomes were defined as sustained remission in the absence of dose modification (sustained durable remission), recaptured response, and treatment failure. Adverse events, anti-infliximab antibodies (ATI), and role of concomitant low-dose oral methotrexate (<10 mg/wk) on IFX durability were analyzed. Univariate associations and survival analysis were performed. Results As of the last follow-up, 39% of patients with CD and 29% of patients with UC achieved sustained durable remission and another 60% recaptured and maintained response. For CD, 88% remained on IFX at 1 year, 80% at 2 years, and 82% at 5 years. In UC, 70% avoided colectomy at 1 year. Of IFX failures, 25% with CD and 11% with UC developed ATI. The most common adverse event causing cessation of therapy was infusion reactions. Treatment limiting recurrent infections occurred in <1%, and 1 patient developed lymphoproliferative disease. Low-dose methotrexate did not influence any IFX outcomes. Conclusions IFX is safe and effective for long-term maintenance therapy in pediatric patients with inflammatory bowel disease. IFX dose intensification can optimize durability and overcome loss of response. Loss of response is likely affected by development of ATI. Higher doses of oral methotrexate may be needed to optimize IFX. PMID:24552827

  7. Identification of Pathway-Specific Serum Biomarkers of Response to Glucocorticoid and Infliximab Treatment in Children with Inflammatory Bowel Disease

    PubMed Central

    Heier, Christopher R; Fiorillo, Alyson A; Chaisson, Ellen; Gordish-Dressman, Heather; Hathout, Yetrib; Damsker, Jesse M; Hoffman, Eric P; Conklin, Laurie S

    2016-01-01

    Objective: Serum biomarkers may serve to predict early response to therapy, identify relapse, and facilitate drug development in inflammatory bowel disease (IBD). Biomarkers are particularly important in children, in whom achieving early remission and minimizing procedures are especially beneficial. Methods: We profiled protein and micro RNA (miRNA) in serum from patients pre- and post-therapy, to identify molecular markers of pharmacodynamic effect. Serum was obtained from children with IBD before and after treatment with either corticosteroids (prednisone; n=12) or anti-tumor necrosis factor-α biologic (infliximab; n=7). Over 1,100 serum proteins were assayed using aptamer-based SOMAscan proteomics, and 22 miRNAs analyzed by quantitative real time PCR. Concordance of longitudinal changes between the groups was used to identify markers responsive to treatment. Bioinformatic analysis was used to build insight into mechanisms of changes in response to treatment. Results: We identified 18 proteins and three miRNAs responsive to both prednisone and infliximab. Eight markers that decreased are associated with inflammation and have gene promoters regulated by nuclear factor (NF)-κB. Several that increased are associated with resolving inflammation and tissue damage. We also identified six markers that appear to be steroid-specific, three of which have glucocorticoid receptor binding elements in their promoter region. Conclusions: Serum markers regulated by the inflammatory transcription factor NF-κB are potential candidates for pharmacodynamic biomarkers that, if correlated with later outcomes like endoscopic or histologic healing, could be used to monitor treatment, optimize dosing, and enhance drug development. The pharmacodynamic biomarkers identified here hold potential to improve both clinical care and drug development. Further studies are warranted to investigate these markers as early predictors of response, or possibly surrogate outcomes. PMID:27628422

  8. Selective TNF-α targeting with infliximab attenuates impaired oxygen metabolism and contractile function induced by an acute exposure to air particulate matter.

    PubMed

    Marchini, Timoteo; D'Annunzio, Verónica; Paz, Mariela L; Cáceres, Lourdes; Garcés, Mariana; Perez, Virginia; Tasat, Deborah; Vanasco, Virginia; Magnani, Natalia; Gonzalez Maglio, Daniel; Gelpi, Ricardo J; Alvarez, Silvia; Evelson, Pablo

    2015-11-15

    Inflammation plays a central role in the onset and progression of cardiovascular diseases associated with the exposure to air pollution particulate matter (PM). The aim of this work was to analyze the cardioprotective effect of selective TNF-α targeting with a blocking anti-TNF-α antibody (infliximab) in an in vivo mice model of acute exposure to residual oil fly ash (ROFA). Female Swiss mice received an intraperitoneal injection of infliximab (10 mg/kg body wt) or saline solution, and were intranasally instilled with a ROFA suspension (1 mg/kg body wt). Control animals were instilled with saline solution and handled in parallel. After 3 h, heart O2 consumption was assessed by high-resolution respirometry in left ventricle tissue cubes and isolated mitochondria, and ventricular contractile reserve and lusitropic reserve were evaluated according to the Langendorff technique. ROFA instillation induced a significant decrease in tissue O2 consumption and active mitochondrial respiration by 32 and 31%, respectively, compared with the control group. While ventricular contractile state and isovolumic relaxation were not altered in ROFA-exposed mice, impaired contractile reserve and lusitropic reserve were observed in this group. Infliximab pretreatment significantly attenuated the decrease in heart O2 consumption and prevented the decrease in ventricular contractile and lusitropic reserve in ROFA-exposed mice. Moreover, infliximab-pretreated ROFA-exposed mice showed conserved left ventricular developed pressure and cardiac O2 consumption in response to a β-adrenergic stimulus with isoproterenol. These results provides direct evidence linking systemic inflammation and altered cardiac function following an acute exposure to PM and contribute to the understanding of PM-associated cardiovascular morbidity and mortality.

  9. [Sleep disorders and quality of life in refractory partial epilepsy: results of the SLEEP study].

    PubMed

    García-Morales, Irene; Gil-Nagel, Antonio; de Rosendo, Jesús; Torres-Falcón, Alberto

    2014-02-16

    Introduccion. Las alteraciones del sueño son frecuentes en pacientes con epilepsia y se correlacionan con una peor calidad de vida. Objetivos. Evaluar la prevalencia de las alteraciones del sueño en pacientes con epilepsia focal refractaria y no refractaria y explorar la influencia de estas alteraciones en la calidad de vida de los pacientes. Pacientes y metodos. Estudio epidemiologico, controlado, transversal, realizado en 150 consultas ambulatorias de neurologia. Se reclutaron pacientes que habian sido tratados con dos farmacos antiepilepticos desde el inicio de la enfermedad (18-55 años). Resultados. Se incluyeron 237 pacientes con epilepsia focal no refractaria y 264 pacientes con epilepsia focal refractaria. El 22% del grupo con epilepsia no refractaria y el 45% del grupo con epilepsia refractaria (p < 0,0001) padecian alguna altera­cion del sueño. Los pacientes con epilepsia refractaria tenian peor calidad de vida (p < 0,001) medida con el cuestionario de calidad de vida QOLIE-10. Se observo una correlacion positiva y significativa entre la calidad de vida y la calidad del sue­ño, tanto en el insomnio cronico (r = 0,65; p < 0,0001) como en la somnolencia excesiva diurna (r = 0,43; p < 0,0001). Conclusion. Las alteraciones del sueño son mas frecuentes en la epilepsia refractaria que en la no refractaria, y afectan a la calidad de vida de los pacientes.

  10. Efficacy, tolerability and safety of switching from etanercept to infliximab for the treatment of moderate-to-severe psoriasis: A multicenter, open-label trial (TANGO).

    PubMed

    Ayala, Fabio; Lambert, Julien

    2015-01-01

    Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.

  11. Circulating T cells to infliximab are detectable mainly in treated patients developing anti‐drug antibodies and hypersensitivity reactions

    PubMed Central

    Vultaggio, A.; Petroni, G.; Pratesi, S.; Nencini, F.; Cammelli, D.; Milla, M.; Prignano, F.; Annese, V.; Romagnani, S.; Matucci, A.

    2016-01-01

    Summary Antibodies recognizing infliximab (IFX) may develop in a proportion of treated patients, leading to loss of response or hypersensitivity reactions (HRs). T cell response to IFX has been poorly investigated. This paper was addressed to detect IFX‐specific T cells in treated patients with inflammatory diseases developing, or not, anti‐drug antibodies (ADA) and to correlate the presence of specific T cells with the clinical outcomes of the treatment. A co‐culture system of IFX‐loaded dendritic cells and purified autologous CD4+ T cells was used to detect memory T cells in 32 ADA+ and 39 ADA– IFX‐treated patients and control groups. The cytokine profile of IFX‐specific T cells was also studied in culture supernatants. IFX‐specific cell proliferation was detected mainly in cells from ADA+ patients, irrespective of their different diseases. HR patients displayed higher T cell proliferation than non‐responder and tolerant patients. A mixed [interferon (IFN)‐γ, interleukin (IL)‐13, IL‐10] cytokine profile was shown in cells from ADA+ patients, while IL‐10 was the most frequently detected cytokine in the supernatants of cultures from ADA‐ patients. Immunoglobulin (Ig)E+ADA+ patients with previous HRs exhibited a more pronounced type 2 profile than IgE–ADA+ patients. This work provides evidence that IFX‐specific circulating T cells are detectable mainly in ADA+ patients with HRs, regardless of their disease. The IFX‐induced cytokine pattern partially correlates with the ADA isotype. PMID:27569750

  12. Progress in biosimilar monoclonal antibody development: the infliximab biosimilar CT-P13 in the treatment of rheumatic diseases.

    PubMed

    Braun, Jürgen; Kudrin, Alex

    2015-01-01

    Biosimilars are biologic medical products whose active drug substance is made by a living organism or derived from it. The term is used to describe a subsequent version of an innovator biopharmaceutical product aiming at approval following patent expiry on the reference product. Biosimilars of monoclonal need to demonstrate similar but not identical quality of nonclinical and clinical attributes. Not all data of the originator product need to be recapitulated, as large numbers of patient-years of exposure data are already available. Thus, biosimilar development is largely based on the safety profiles of the originator product. The evaluation of biosimilarity includes immunogenicity attributed risks. CT-P13 (Remsima™/Inflectra™, Celltrion/Hospira), a biosimilar of the innovator drug infliximab (INF), was the first approved complex biosimilar monoclonal antibody in the EU, within the framework of WHO, EMA and US FDA biosimilar guidelines. CT-P13 has shown analytical and nonclinical features highly similar to INF including pharmacokinetics, efficacy, safety and immunogenicity profiles in ankylosing spondylitis and rheumatoid arthritis. The objective of this article is to highlight the recent biosimilar development and to review the results from the studies PLANETRA and PLANETAS, which have supported the approval of CT-P13 for several indications.

  13. Evaluation of bone mineral density, bone metabolism, osteoprotegerin and receptor activator of the NFκB ligand serum levels during treatment with infliximab in patients with rheumatoid arthritis

    PubMed Central

    Vis, M; Havaardsholm, E A; Haugeberg, G; Uhlig, T; Voskuyl, A E; van de Stadt, R J; Dijkmans, B A C; Woolf, A D; Kvien, T K; Lems, W F

    2006-01-01

    Objectives To examine whether treatment with anti‐tumour necrosis factor (TNF) α prevents loss of bone mineral density (BMD) at the spine and hip (generalised) and in the hands (local) of patients with rheumatoid arthritis, and to study the changes in markers of bone metabolism, including receptor activator of the NFκB ligand (RANKL) and osteoprotegerin (OPG), during anti‐TNF treatment. Patients and methods 102 patients with active rheumatoid arthritis, who were treated with infliximab during 1 year, were included in this open cohort study. The BMD of the spine and hip (dual x ray absorptiometry ) and hands dual x ray radiogrammetry was measured before the start of treatment and after 1 year. Changes in osteocalcin formation, β‐isomerised carboxy terminal telopeptide of type 1 collagen (β‐CTx, resorption), RANKL and OPG were determined at 0, 14, 30 and 46 weeks. Results The BMD of the spine and hip was unchanged during treatment with infliximab, whereas BMD of the hand decreased significantly by 0.8% (p<0.01). The BMD of the hip in patients with a good European League Against Rheumatism response showed a favourable change compared with patients not achieving such a response. Serum β‐CTx and RANKL were both considerably decreased compared with baseline at all time points. The decrease in β‐CTx was associated with the decrease in Disease Activity Score of 28 joints and C reactive protein during the 0–14 weeks interval. Conclusion In patients with rheumatoid arthritis treated with infliximab, spine and hip bone loss is arrested, whereas metacarpal cortical hand bone loss is not stopped. The outcome of the study also supports a relationship between clinical response, in terms of reduced inflammatory activity, and changes in bone loss of the spine, hip and hands. PMID:16606653

  14. Efficacy and safety of CT-P13 (biosimilar infliximab) in patients with rheumatoid arthritis: comparison between switching from reference infliximab to CT-P13 and continuing CT-P13 in the PLANETRA extension study

    PubMed Central

    Yoo, Dae Hyun; Prodanovic, Nenad; Jaworski, Janusz; Miranda, Pedro; Ramiterre, Edgar; Lanzon, Allan; Baranauskaite, Asta; Wiland, Piotr; Abud-Mendoza, Carlos; Oparanov, Boycho; Smiyan, Svitlana; Kim, HoUng; Lee, Sang Joon; Kim, SuYeon; Park, Won

    2017-01-01

    Objectives To assess the efficacy and safety of switching from the infliximab reference product (RP; Remicade) to its biosimilar CT-P13 (Remsima, Inflectra) or continuing CT-P13 in patients with rheumatoid arthritis (RA) for an additional six infusions. Methods This open-label extension study recruited patients with RA who had completed the 54-week, randomised, parallel-group study comparing CT-P13 with RP (PLANETRA; NCT01217086). CT-P13 (3 mg/kg) was administered intravenously every 8 weeks from weeks 62 to 102. All patients received concomitant methotrexate. Endpoints included American College of Rheumatology 20% (ACR20) response, ACR50, ACR70, immunogenicity and safety. Data were analysed for patients who received CT-P13 for 102 weeks (maintenance group) and for those who received RP for 54 weeks and then switched to CT-P13 (switch group). Results Overall, 302 of 455 patients who completed the PLANETRA study enrolled into the extension. Of these, 158 had received CT-P13 (maintenance group) and 144 RP (switch group). Response rates at week 102 for maintenance versus switch groups, respectively, were 71.7% vs 71.8% for ACR20, 48.0% vs 51.4% for ACR50 and 24.3% vs 26.1% for ACR70. The proportion of patients with antidrug antibodies was comparable between groups (week 102: 40.3% vs 44.8%, respectively). Treatment-emergent adverse events occurred in similar proportions of patients in the two groups during the extension study (53.5% and 53.8%, respectively). Conclusions Comparable efficacy and tolerability were observed in patients who switched from RP to its biosimilar CT-P13 for an additional year and in those who had long-term CT-P13 treatment for 2 years. Trial registration number NCT01571219; Results. PMID:27130908

  15. Acute promyelocytic leukaemia (APL) in a patient with Crohn's disease and exposure to infliximab: a rare clinical presentation and review of the literature.

    PubMed

    Mohammad, Farhan; Vivekanandarajah, Abhirami; Haddad, Housam; Shutty, Christopher M; Hurford, Matthew T; Dai, Qun

    2014-05-19

    With the introduction of potent immunosuppressive and chemotherapeutic medications for various diseases, there is an increased incidence of therapy-related myeloid neoplasms. They are the result of mutational rearrangement and historically, have a grave prognosis compared with de novo myeloid neoplasms. We did a short review on various types of myeloid leukaemias reported after therapy with antitumour necrosis factor and also report, to the best of our knowledge, one among the very few cases of therapy-related acute promyelocytic leukaemia in a patient on infliximab therapy for refractory Crohn's disease. The patient responded well to the traditional treatment and is in complete remission for more than 5 years.

  16. Immunoassay for Detection of Infliximab in Whole Blood Using a Fiber-Optic Surface Plasmon Resonance Biosensor.

    PubMed

    Lu, Jiadi; Spasic, Dragana; Delport, Filip; Van Stappen, Thomas; Detrez, Iris; Daems, Devin; Vermeire, Séverine; Gils, Ann; Lammertyn, Jeroen

    2017-03-21

    Monitoring the concentration of a therapeutic drug antibody, infliximab (IFX), is recommended for enhancing its efficacy in patients with inflammatory bowel disease (IBD). However, IFX concentrations are currently determined in patients' serum/plasma, which requires sample preparation from blood, hence hampering the turnaround time. In this paper, we present a short immunoassay (10 min) using a fiber-optic surface plasmon resonance (FO-SPR) biosensor for detection of IFX spiked in 100-fold diluted serum, plasma, and whole blood. The calculated limits of detection (LOD) based on calibration curves were 1.42, 1.00, and 1.34 ng/mL, respectively, which coincides with expected IFX concentrations in diluted samples from IBD patients. A linear correlation was established among different matrixes, indicating that the matrix effect was insignificant. The established point-of-care (POC) FO-SPR bioassay was also used to measure IFX in 100-fold diluted extracts of dried blood spots (DBS), and LOD achieved was below 2 ng/mL. Although DBS might be ideal for POC, this is the first report of using an SPR biosensor for measuring DBS samples. Finally, the POC FO-SPR immunoassay was validated by using matching serum and plasma samples from five IBD patients. A Pearson correlation of 0.968 was obtained between serum and plasma samples. IFX concentrations determined with FO-SPR were compared to a clinically validated enzyme-linked immunosorbent assay (ELISA), resulting in excellent Pearson correlation and intraclass correlation coefficient, both being 0.99 for serum and plasma samples. In conclusion, this paper demonstrates that our FO-SPR biosensor can be used as a true POC diagnostic tool for determining IFX concentrations in a variety of matrixes.

  17. Clinical monitoring: infliximab biosimilar CT-P13 in the treatment of Crohn’s disease and ulcerative colitis

    PubMed Central

    Keil, Radan; Wasserbauer, Martin; Zádorová, Zdena; Hajer, Jan; Drastich, Pavel; Wohl, Pavel; Beneš, Marek; Bojková, Martina; Svoboda, Pavel; Konečný, Michal; Falt, Přemysl; Vaňásek, Tomáš; Pešta, Martin; Pešek, František; Bouchner, Luděk; Koželuhová, Jana; Novotný, Aleš; Bartůsková, Lucie; Špičák, Julius

    2016-01-01

    Abstract Objective: The infliximab biosimilar CT-P13 (Remsima®, Inflectra®) was approved in Europe for the treatment of inflammatory bowel disease (IBD) based on extrapolation of data from patients with rheumatic disease. Because there are limited published reports on clinical outcomes for IBD patients treated with CT-P13, we monitored responses to induction treatment with this biosimilar in patients with Crohn’s disease (CD) or ulcerative colitis (UC) in centres across the Czech Republic. Material and methods: Fifty-two patients with CD (n = 30) or UC (n = 22) were treated with 5 mg/kg CT-P13 for up to 14 weeks. Effectiveness of therapy was evaluated with the Crohn’s Disease Activity Index (CDAI) or the Mayo Scoring System (MSS) in patients with CD or UC, respectively, before and after 14 weeks. Additional goals were to evaluate weight changes, serum C-reactive protein (CRP) levels, and complications/adverse events. Results: In patients with CD, remission (CDAI <150) was achieved in 50.0% of cases, and partial response (≥70-point decrease in CDAI score from baseline) in the remaining 50.0%. In patients with UC, remission (total score on partial Mayo index ≤2 points) was achieved in 40.9% of cases, partial response (≥2-point decrease in partial Mayo score from baseline) in 54.5%, and no response in 4.5%. There were statistically significant improvements in CDAI, MSS and CRP serum levels after 14 weeks of therapy, and body weight increased. Four adverse events were identified (n = 1 each): lower-extremity phlebothrombosis, herpes labialis, pneumonia and allergic reaction. Conclusions: This prospective observational study provides evidence of the effectiveness of CT-P13 in IBD. PMID:27002981

  18. Top-down Infliximab Study in Kids with Crohn's disease (TISKids): an international multicentre randomised controlled trial

    PubMed Central

    Cozijnsen, M A; van Pieterson, M; Samsom, J N; Escher, J C; de Ridder, L

    2016-01-01

    Introduction Crohn's disease (CD) is a chronic inflammatory disease predominantly affecting the gastrointestinal tract. CD usually requires lifelong medication and is accompanied by severe complications, such as fistulae and strictures, resulting in surgery. Infliximab (IFX) is very effective for treating paediatric patients with CD, but is currently only registered for therapy refractory patients—the so-called step-up strategy. We hypothesise that using IFX first-line, that is, top-down, will give more mucosal healing, fewer relapses, less complications, need for surgery and hospitalisation. Methods and analysis This international multicentre open-label randomised controlled trial includes children, aged 3–17 years, with new-onset, untreated CD with moderate-to-severe disease activity (weighted Paediatric Crohn's Disease Activity Index (wPCDAI)>40). Eligible patients will be randomised to top-down or step-up treatment. Top-down treatment consists of 5 IFX infusions combined with azathioprine (AZA). After these 5 infusions, patients will continue AZA. Patients randomised to step-up will receive standard induction treatment, either oral prednisolone or exclusive enteral nutrition, combined with AZA as maintenance treatment. The primary outcome is clinical remission (wPCDAI<12.5) at 52 weeks without need for additional CD-related therapy or surgery. Total follow-up is 5 years. Secondary outcomes include clinical disease activity, mucosal healing by endoscopy (at week 10 and optionally week 52), faecal calprotectin, growth, quality of life, medication use and adverse events. Ethics and dissemination Conducted according to the Declaration of Helsinki and Good Clinical Practice. Medical-ethical approval will be obtained for each site. Trial registration number NCT02517684; Pre-results. PMID:28090335

  19. Pharmacokinetic Dashboard-Recommended Dosing Is Different than Standard of Care Dosing in Infliximab-Treated Pediatric IBD Patients.

    PubMed

    Dubinsky, Marla C; Phan, Becky L; Singh, Namita; Rabizadeh, Shervin; Mould, Diane R

    2017-01-01

    Standard of care (SOC; combination of 5-10 mg/kg and an interval every 6-8 weeks) dosing of infliximab (IFX) is associated with significant loss of response. Dashboards using covariates that influence IFX pharmacokinetics (PK) may be a more precise way of optimizing anti-TNF dosing. We tested a prototype dashboard to compare forecasted dosing regimens with actual administered regimens and SOC. Fifty IBD patients completing IFX induction were monitored during maintenance (weeks 14-54). Clinical and laboratory data were collected at each infusion; serum was analyzed for IFX concentrations and anti-drug antibodies (ADA) at weeks 14 and 54 (Prometheus Labs, San Diego). Dosing was blinded to PK data. Dashboard-based assessments were conducted on de-identified clinical, laboratory, and PK data. Bayesian algorithms were used to forecast individualized troughs and determine optimal dosing to maintain target trough concentrations (3 μg/mL). Dashboard forecasted dosing post-week 14 was compared to actual administered dose and frequency and SOC. Using week 14 clinical data only, the dashboard recommended either a dose or an interval change (<0.5 mg/kg or <1 week difference) in 43/50 patients; only 44% recommended to have SOC dosing. When IFX14 concentration and ADA status were added to clinical data, dose and/or interval changes based on actual dosing were recommended in 48/50 (96%) patients; SOC dosing was recommended in only 11/50 (22%). Dashboard recommended SOC IFX dosing in a minority of patients. Dashboards will be an important tool to individualize IFX dosing to improve treatment durability.

  20. Resection of a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment: a case report

    PubMed Central

    2013-01-01

    Introduction A liver abscess in Crohn’s disease is a rare but important entity that is associated with a poor prognosis and high mortality when treatment is delayed. We report a case of successful liver segmentectomy for a methicillin-resistant Staphylococcus aureus liver abscess in a patient with Crohn’s disease under infliximab treatment. Case presentation A 31-year-old Japanese man, who had been treated with infliximab infusions for Crohn’s disease, was referred to our hospital presenting with an abrupt onset of high fever and an elevated white blood cell count and serum C-reactive protein level. Computed tomography revealed a liver abscess occupying segment 8. The limited effect of percutaneous transhepatic abscess drainage and antibiotics led us to perform radical resection of the abscess. The patient recovered quickly after surgery and the postoperative course was uneventful. Conclusion The present case suggests that surgical removal of an abscess should be considered for patients under immunosuppression or refractory to conventional treatment. PMID:23374532

  1. Successful Treatment of Small Intestinal Bleeding in a Crohn's Patient with Noncirrhotic Portal Hypertension by Transjugular Portosystemic Shunt Placement and Infliximab Treatment.

    PubMed

    Heimgartner, Benjamin; Dawson, Heather; De Gottardi, Andrea; Wiest, Reiner; Niess, Jan Hendrik

    2016-01-01

    Small intestinal bleeding in Crohn's disease patients with noncirrhotic portal hypertension and partial portal and superior mesenteric vein thrombosis is a life-threatening event. Here, a case is reported in which treatment with azathioprine may have resulted in nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis. The 56-year-old patient with Crohn's disease developed nodular regenerative hyperplasia under treatment with azathioprine. He was admitted with severe bleeding. Gastroscopy showed small esophageal varices without bleeding stigmata. Blood was detected in the terminal ileum. CT scan revealed a partial portal vein thrombosis with extension to the superior mesenteric vein, thickening of the jejunal wall and splenomegaly. Because intestinal bleeding could not be controlled by conservative treatment, the thrombus was aspirated and a transjugular intrahepatic portosystemic shunt (TIPS) was placed. Switching the immunosuppressive medication to infliximab controlled Crohn's disease activity. Bleeding was stopped, hemoglobin normalized, and thrombocytopenia and bowel movements improved. In summary, small intestinal bleeding in a Crohn's patient with nodular regenerative hyperplasia, portal hypertension and portal vein thrombosis can be efficiently treated by TIPS. TIPS placement together with infliximab treatment led to the improvement of the blood panel and remission in this patient.

  2. Immunogenicity and Lupus-Like Autoantibody Production Can Be Linked to Each Other along With Type I Interferon Production in Patients with Rheumatoid Arthritis Treated With Infliximab: A Retrospective Study of a Single Center Cohort

    PubMed Central

    Ishikawa, Yuki; Fujii, Takao; Ishikawa, Seiko Kondo; Yukawa, Naoichiro; Hashimoto, Motomu; Furu, Moritoshi; Ito, Hiromu; Ohmura, Koichiro; Mimori, Tsuneyo

    2016-01-01

    Besides anti-drug antibodies, anti-nuclear antibodies and anti-DNA antibodies are often induced in patients with rheumatoid arthritis treated with tumor necrosis factor inhibitors. We examined the association between immunogenicity, autoantibody production, and serum cytokine profiles in patients with rheumatoid arthritis treated with infliximab. Japanese patients with rheumatoid arthritis (n = 57) were retrospectively examined. Serum trough levels of infliximab, anti-drug antibody, anti-nuclear antibody, and anti-DNA (Farr), anti-single-stranded DNA and anti-double-stranded DNA antibodies were measured. Interleukin-6, interferon-γ, interferon-α, and B-cell activating factor levels were also measured in the same sera. Then, we validated the association between anti-drug antibody and these serum markers along with clinical response to infliximab. Anti-drug antibodies developed in twenty-one patients (36.8%), whose serum trough levels of infliximab were significantly lower than those in anti-drug antibody-negative patients (0.09 ± 0.03 vs. 2.48 ± 0.326 μg/mL, p < 0.0001). There were no significant differences in clinical backgrounds between the two groups. The anti-drug antibody-positive patients were more likely to develop anti-nuclear antibody titers of ≥ ×160 compared to the negative patients (14 to 57% vs. 17 to 33%). In addition, anti-DNA antibodies (Farr) (from 1.5 ± 0.4 to 35 ± 17 IU/mL, p = 0.0001), especially IgM-anti-double stranded DNA antibody (from 5.1 ± 0.7 to 41 ± 8.9 IU/mL, p < 0.0001), and IgG-anti-single stranded DNA antibody (from 13 ± 1.1 to 35 ± 13, p = 0.0145) were significantly increased in anti-drug antibody-positive but not in negative patients. Moreover, the anti-drug antibody-positive, but not the negative patients, showed significant increased levels of interferon-α (from 248.7 ± 102.3 to 466.8 ± 135.1 pg/mL, p = 0.0353) and B-cell activating factor (from 1073 ± 75.1 to 1387 ± 136.5 pg/mL, p = 0.0208) following

  3. Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.

    PubMed

    Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi

    2016-07-01

    A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma.

  4. Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats.

    PubMed

    Altintas, Nejat; Erboga, Mustafa; Aktas, Cevat; Bilir, Bulent; Aydin, Murat; Sengul, Aysun; Ates, Zehra; Topcu, Birol; Gurel, Ahmet

    2016-02-01

    We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate

  5. ConSCRIPT

    PubMed Central

    Mottarella, Scott E.; Rosa, Mario; Bangura, Abdul; Bernstein, Herbert J.; Craig, Paul A.

    2011-01-01

    The aim of the Structural Biology Extensible Visualization Scripting Language (SBEVSL) project is to allow users who are experts in one scripting language to use that language in a second molecular visualization environment without requiring the user to learn a new scripting language. ConSCRIPT, the first SBEVSL release, is a plug-in for PyMOL that accepts RasMol scripting commands either as premade scripts or as line-by-line entries from PyMOL's own command line. The plug-in is available for download at http://sourceforge.net/projects/sbevsl/files in the ConSCRIPT folder. PMID:21567873

  6. Acute promyelocytic leukaemia (APL) in a patient with Crohn's disease and exposure to infliximab: a rare clinical presentation and review of the literature

    PubMed Central

    Mohammad, Farhan; Vivekanandarajah, Abhirami; Haddad, Housam; Shutty, Christopher M; Hurford, Matthew T; Dai, Qun

    2014-01-01

    With the introduction of potent immunosuppressive and chemotherapeutic medications for various diseases, there is an increased incidence of therapy-related myeloid neoplasms. They are the result of mutational rearrangement and historically, have a grave prognosis compared with de novo myeloid neoplasms. We did a short review on various types of myeloid leukaemias reported after therapy with antitumour necrosis factor and also report, to the best of our knowledge, one among the very few cases of therapy-related acute promyelocytic leukaemia in a patient on infliximab therapy for refractory Crohn's disease. The patient responded well to the traditional treatment and is in complete remission for more than 5 years. PMID:24842356

  7. LIMBIC ENCEPHALITIS ASSOCIATED WITH RELAPSING POLYCHONDRITIS RESPONDED TO INFLIXIMAB AND MAINTAINED ITS CONDITION WITHOUT RECURRENCE AFTER DISCONTINUATION: A CASE REPORT AND REVIEW OF THE LITERATURE

    PubMed Central

    KONDO, TAKESHI; FUKUTA, MAMIKO; TAKEMOTO, AYUMU; TAKAMI, YUICHIRO; SATO, MOTOKI; TAKAHASHI, NORIYUKI; SUZUKI, TOMIO; SATO, JUICHI; ATSUTA, NAOKI; SOBUE, GEN; TAKAHASHI, YUKITOSHI; BAN, NOBUTARO

    2014-01-01

    ABSTRACT Central nervous system (CNS) manifestations are rare complications of relapsing polychondritis (RP). The majority of patients respond well to glucocorticoid therapy, but need to maintain it. Some patients are refractory to initial glucocorticoid therapy and to additional immunosuppressants, and end up with an outcome worse than at therapy initiation. The standardized therapeutic protocol for this condition has not been established. The effects of anti-tumor necrosis factor (TNF) -α agents have been reported recently. We experienced a patient with RP and limbic encephalitis who was refractory to initial high-dose glucocorticoid, but subsequently responded to infliximab and did not show deterioration of signs and symptoms after stopping therapy. We report this case together with a systematic literature review. This is the first case report of RP with CNS manifestations successfully treated by an anti-TNF-α agent without recurrence after discontinuation. PMID:25741046

  8. Circulating Cytokines and Cytokine Receptors in Infliximab Treatment Failure Due to TNF-α Independent Crohn Disease.

    PubMed

    Steenholdt, Casper; Coskun, Mehmet; Buhl, Sine; Bendtzen, Klaus; Ainsworth, Mark A; Brynskov, Jørn; Nielsen, Ole H

    2016-04-01

    The inflammatory response at infliximab (IFX) treatment failure due to tumor necrosis factor (TNF)-α-independent Crohn disease activity is unknown. This is an exploratory, hypothesis-generating study based on samples collected in a clinical trial among patients failing conventional IFX dosages and treated with an intensified IFX regimen for 12 weeks. Patients with clinical response at week 12, as defined by a reduction of Crohn disease activity index by ≥70, were considered to suffer from nonimmune pharmacokinetic (PK) treatment failure (n = 18), and nonresponders had a presumed pharmacodynamic (PD) failure due to non-TNF-driven disease (n = 8). Patients failing IFX due to functional anti-IFX antibodies (n = 2) were excluded. The study population also comprised a group of 12 patients in long-term remission on IFX. A functional cell-based reporter gene assay was applied to measure IFX and anti-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 protein 1. The IFX levels were similar between patients with IFX failure caused by nonimmune PK or PD at treatment failure (median 1.4 vs 2.4 μg/mL; P = 0.52), during treatment intensification (8.1 vs 5.6; P = 0.85), and after 12 weeks (8.8 vs 7.7; P = 0.93), congruent with nonresponders failing IFX due to predominantly TNF-α-independent signaling pathways in their disease. Cytokine and cytokine receptor levels were comparable between patients with nonimmune PK failure and PD failure at time of manifestation of IFX failure, but with higher IL-6 and sTNF-R2 levels among IFX treatment failures as compared with patients in remission (IL-6 median 3.6 vs <3.1 pg/mL; P = 0.03; sTNF-R2 3207 vs 2547 pg/mL; P = 0.01). IL-6 and sTNF-R2

  9. The Con Test

    ERIC Educational Resources Information Center

    Fletcher, Michael

    2009-01-01

    In this article, the author describes the format of the Con Test, an Australian television game show which followed the same general rules and game play as the UK show PokerFace. At the end of each round a contestant needs to decide whether or not he or she should fold. A contestant needs to know how likely it is that he or she is in last place.…

  10. Nam Con Son Basin

    SciTech Connect

    Tin, N.T.; Ty, N.D.; Hung, L.T.

    1994-07-01

    The Nam Con Son basin is the largest oil and gas bearing basin in Vietnam, and has a number of producing fields. The history of studies in the basin can be divided into four periods: Pre-1975, 1976-1980, 1981-1989, and 1990-present. A number of oil companies have carried out geological and geophysical studies and conducted drilling activities in the basin. These include ONGC, Enterprise Oil, BP, Shell, Petro-Canada, IPL, Lasmo, etc. Pre-Tertiary formations comprise quartz diorites, granodiorites, and metamorphic rocks of Mesozoic age. Cenozoic rocks include those of the Cau Formation (Oligocene and older), Dua Formation (lower Miocene), Thong-Mang Cau Formation (middle Miocene), Nam Con Son Formation (upper Miocene) and Bien Dong Formation (Pliocene-Quaternary). The basement is composed of pre-Cenozoic formations. Three fault systems are evident in the basin: north-south fault system, northeast-southwest fault system, and east-west fault system. Four tectonic zones can also be distinguished: western differentiated zone, northern differentiated zone, Dua-Natuna high zone, and eastern trough zone.

  11. Infliximab therapy increases body fat mass in early rheumatoid arthritis independently of changes in disease activity and levels of leptin and adiponectin: a randomised study over 21 months

    PubMed Central

    2010-01-01

    Introduction Rheumatoid arthritis (RA) is associated with changes in body composition and bone mineral density (BMD). The purpose of the present study was to evaluate whether anti-TNF treatment in early RA has an impact on body composition and BMD besides that which could be achieved by intensive disease-modifying anti-rheumatic drug (DMARD) combination therapy. Methods Forty patients with early RA who failed treatment with methotrexate up to 20 mg/week for 3 months were randomised to addition of sulphasalazine and hydroxychloroquine (treatment A) or addition of infliximab (treatment B). At 3, 12 and 24 months, body composition and BMD were assessed by total-body dual-energy X-ray absorptiometry. At the same time points, leptin, adiponectin, apolipoproteins, insulin-like growth factor-1 (IGF-1) and markers of bone remodelling were analysed. Compliance to treatment was considered in the analyses. Data were analysed with a mixed, linear model. Results Patients treated with anti-TNF had a significant increase in fat mass at 2 years, 3.8 (1.6 to 5.9) kg, in contrast to patients in treatment A, 0.4 (-1.5 to 2.2) kg (P = 0.040), despite similar reduction in disease activity. Both treatment strategies prevented loss of muscle mass and bone. Leptin concentrations increased significantly in both groups at 2 years and adiponectin increased significantly at 2 years in treatment A and at 1 year in treatment B. There were no significant changes in apolipoproteins or IGF-1. The markers of bone resorption decreased at 12 months in both treatment groups with no significant difference between the treatment groups. Conclusions Infliximab therapy increased body fat mass, an effect that was not achieved with the combination of DMARDs, despite a similar reduction in disease activity, and thus seemed to be drug specific. The increase of fat mass was not associated with an exacerbated atherogenic lipid profile. Leptin and adiponectin concentrations increased in both treatment groups. The

  12. The anti-TNF-α antibody infliximab inhibits the expression of fat-transporter-protein FAT/CD36 in a selective hepatic-radiation mouse model.

    PubMed

    Martius, Gesa; Cameron, Silke; Rave-Fränk, Margret; Hess, Clemens F; Wolff, Hendrik A; Malik, Ihtzaz A

    2015-03-02

    Previously, we reported a radiation-induced inflammation triggering fat-accumulation through fatty-acid-translocase/cluster of differentiation protein 36 (FAT/CD36) in rat liver. Furthermore, inhibition of radiation-induced FAT/CD36-expression by anti-tumor necrosis factor-α (anti-TNF-α) (infliximab) was shown in vitro. The current study investigates fat-accumulation in a mouse-model of single-dose liver-irradiation (25-Gray) and the effect of anti-TNF-α-therapy on FAT/CD36 gene-expression. Mice livers were selectively irradiated in vivo in presence or absence of infliximab. Serum- and hepatic-triglycerides, mRNA, and protein were analyzed by colorimetric assays, RT-PCR, Immunofluorescence and Western-Blot, respectively. Sudan-staining was used demonstrating fat-accumulation in tissue. In mice livers, early (1-3 h) induction of TNF-α-expression, a pro-inflammatory cytokine, was observed. It was followed by elevated hepatic-triglyceride level (6-12 h), compared to sham-irradiated controls. In contrast, serum-triglyceride level was decreased at these time points. Similar to triglyceride level in mice livers, Sudan staining of liver cryosections showed a quick (6-12 h) increase of fat-droplets after irradiation. Furthermore, expression of fat-transporter-protein FAT/CD36 was increased at protein level caused by radiation or TNF-α. TNF-α-blockage by anti-TNF-α showed an early inhibition of radiation-induced FAT/CD36 expression in mice livers. Immunohistochemistry showed basolateral and cytoplasmic expression of FAT/CD36 in hepatocytes. Moreover, co-localization of FAT/CD36 was detected with α-smooth muscle actin (α-SMA+) cells and F4/80+ macrophages. In summary, hepatic-radiation triggers fat-accumulation in mice livers, involving acute-phase-processes. Accordingly, anti-TNF-α-therapy prevented early radiation-induced expression of FAT/CD36 in vivo.

  13. Quantification of active infliximab in human serum with liquid chromatography-tandem mass spectrometry using a tumor necrosis factor alpha -based pre-analytical sample purification and a stable isotopic labeled infliximab bio-similar as internal standard: A target-based, sensitive and cost-effective method.

    PubMed

    El Amrani, Mohsin; van den Broek, Marcel P H; Göbel, Camiel; van Maarseveen, Erik M

    2016-07-08

    The therapeutic monoclonal antibody Infliximab (IFX) is a widely used drug for the treatment of several inflammatory autoimmune diseases. However, approximately 10% of patients develop anti-infliximab antibodies (ATIs) rendering the treatment ineffective. Early detection of underexposure to unbound IFX would result in a timely switch of therapy which could aid in the treatment of this disease. Streptavidin coated 96 well plates were used to capture biotinylated-tumor necrosis factor -alpha (b-TNF-α), which in turn was used to selectively extract the active form of IFX in human serum. After elution, IFX was digested using trypsin and one signature peptide was selected for subsequent analysis on liquid chromatography-tandem mass spectrometry (LC-MS/MS). The internal standard used was a stable isotopic labeled IFX bio-similar. The assay was successfully validated according to European Medicines Agency (EMA) guidelines and was found to be linear in a range of 0.5-20μg/mL (r(2)=0.994). Lower limit of quantification for the assay (<20% CV) was 0.5μg/mL, requiring only 2μL of sample. Cross-validation against enzyme-linked immunosorbent assay (ELISA) resulted in a high correlation between methods (r(2)=0.95 with a ρc=0.83) and the accuracy was in line with previously published results. In conclusion, a sensitive, robust and cost-effective method was developed for the bio-analysis of IFX with LC-MS/MS by means of a target-based pre-analytical sample purification. Moreover, low volume and costs of consumables per sample promote its feasibility in (pre)clinical studies and in therapeutic drug monitoring. This method should be considered as first choice due to its accuracy and multiple degree of selectivity.

  14. Infliximab Dose Reduction Sustains the Clinical Treatment Effect in Active HLAB27 Positive Ankylosing Spondylitis: A Two-Year Pilot Study

    PubMed Central

    Mörck, Boel; Bremell, Tomas; Forsblad-d'Elia, Helena

    2013-01-01

    The rationale of the study was to evaluate the efficacy of infliximab (IFX) treatment in patients with ankylosing spondylitis (AS) and to determine whether IFX dose reduction and interval extension sustains the treatment effect. Nineteen patients were included and treated with IFX 5 mg/kg every 6 weeks for 56 weeks. All patients concomitantly received MTX with median dose 7.5 mg/weekly. During the second year, the IFX dose was reduced to 3 mg/kg every 8 weeks. Eighteen patients completed the 1-year and 15 patients the 2-year trial. The ≥50% improvement at week 16 from baseline of BASDAI was achieved in 16/19 (84%) patients. Significant reductions in BASDAI, BASFI, and BASMI scores, decrease in ESR and CRP, and improvement in SF-36 were observed at weeks 16 and 56. The MRI-defined inflammatory changes in the sacroiliac joints disappeared in 10/15 patients (67%) already at 16 weeks. IFX treatment effect was sustained throughout the second year after IFX dose reduction and interval extension. We conclude that IFX treatment is effective in well-established active AS and a dose reduction sustains the treatment effect. These observations are of clinical importance and open the opportunity to reduce the drug costs. This trial is registered with ClinicalTrials.gov NCT01850121. PMID:24089587

  15. The Utility of Infliximab Therapeutic Drug Monitoring among Patients with Inflammatory Bowel Disease and Concerns for Loss of Response: A Retrospective Analysis of a Real-World Experience

    PubMed Central

    Shuster, Constantin; DeMarco, Mari L.; Rosenfeld, Gregory

    2016-01-01

    Background. Infliximab (IFX) therapeutic drug monitoring (TDM) allows for objective decision making in patients with inflammatory bowel disease (IBD) and loss of response. Questions remain about whether IFX TDM improves outcomes. Methods. Patients with IBD who had IFX TDM due to concerns for loss of response were considered for inclusion. Serum IFX trough concentration and anti-drug antibody (ADA) concentrations were measured. Patients were grouped by TDM results: group 1, low IFX/high ADA; group 2, low IFX/low ADA; group 3, therapeutic IFX. Changes in management were analyzed according to groupings; remission rates were assessed at 6 months. Results. 71 patients were included of whom 37% underwent an appropriate change in therapy. Groups 1 (67%) and 2 (83%) had high adherence compared to only 9% in group 3. At 6 months, 57% had achieved remission. More patients who underwent an appropriate change in therapy achieved remission, though this did not reach statistical significance (69% versus 49%; P = 0.098). Conclusions. A trend towards increased remission rates was associated with appropriate changes in management following TDM results. Many patients with therapeutic IFX concentrations did not undergo an appropriate change in management, potentially reflecting a lack of available out-of-class options at the time of TDM or due to uncertainty of the meaning of the reported therapeutic range. PMID:27957480

  16. A multi-centered randomized trial of the treatment of pemphigus vulgaris patients with infliximab and prednisone compared to prednisone alone

    PubMed Central

    Hall, R.P.; Fairley, J.; Woodley, D.; Werth, V.P.; Hannah, D.; Streilein, R.D.; McKillip, J.; Okawa, J.; Rose, M.; Keyes-Elstein, L.L.; Pinckney, A.; Overington, A.; Wedgwood, J.; Ding, L.; Welch, B.

    2014-01-01

    Background Pemphigus vulgaris (PV) is a blistering disease in which TNF-α has a role in the pathogenesis. Objectives The objective was to evaluate the safety of infliximab (IFX) with prednisone compared to prednisone alone in the treatment of PV. In addition, treatment response was assessed and mechanistic studies were performed. Methods PV subjects who had ongoing disease activity while maintained on prednisone were randomized to receive either IFX or placebo in addition to prednisone. Response status and IgG anti-DSG1 and DSG3 antibodies were assessed at 18 and 26 weeks. . Results 10 subjects were randomized to each group. There were no safety signals during the course of the study. At week 18, 1 subject in each group had responded. At week 26, 3 IFX treated subjects vs. none in the placebo group had responded (p =0 .21). At weeks 18 and 26, the median IgG anti-DSG1 and anti-DSG3 levels were lower in the IFX treated-patients (IgG anti DSG-1: week 18 p =0.035, week 26 p = 0.022; IgG anti-DSG3; week 18 p=0.035, week 26 p = 0.05)). Limitations This study is limited by the relative small sample size. Conclusions There was no significant difference between study arms in the proportion of subjects with treatment-related Adverse Events > Grade 3. IFX therapy was not shown to be effective for the treatment of patients with PV in this randomized, placebo-controlled trial, although IFX treatment may be associated with a decrease in anti-DSG1 and DSG3 antibodies. PMID:25123295

  17. Validation of an automated method for compounding monoclonal antibody patient doses: case studies of Avastin (bevacizumab), Remicade (infliximab) and Herceptin (trastuzumab).

    PubMed

    Peters, Bas J M; Capelle, Martinus A H; Arvinte, Tudor; van de Garde, Ewoudt M W

    2013-01-01

    Automation robots have recently come to the market as an alternative for manual compounding of drugs for intravenous administration. Our aim was to assess whether robotic compounding can be performed with monoclonal antibodies (mAbs) without influencing the aggregation state of the proteins. Three frequently used mAbs were studied: infliximab (Remicade, Janssen Biotech) and trastuzumab (Herceptin, Roche) in lyophilised form, and bevacizumab (Avastin, Roche) as a liquid formulation stored at 2°C to 8°C. The effects of different procedures to prepare the patient doses on antibody aggregation were evaluated. Remicade and Herceptin were reconstituted both manually and by a robotic arm (i.v.STATION, Health Robotics). Additionally, the influence of vigorous shaking during reconstitution was investigated. The effects of rapid aspiration and dispensing on antibody aggregation were investigated for all three mAbs. Aggregation state was assessed by UV-Vis absorbance, 90° light scatter, fluorescence spectroscopy, Nile red fluorescence microscopy, and field flow fractionation without cross and focus flow. Robotic reconstituted samples showed similar findings compared with manual reconstitution if performed exactly according to the summary of product characteristics (SPC). Vials that were vigorously shaken showed a significant increase in aggregates. Similarly, rapid aspiration/dispense cycles resulted in a strong increase in the number and sizes of aggregates for all three mAbs; this result was observed after just one rapid aspiration/dispense cycle. Our study showed that robotic compounding of mAbs is feasible if the robot is exactly programmed according to the SPC, indicating that robotic compounding can be used to achieve reproducible high-quality compounding for delicate formulations.

  18. One-month stability study of a biosimilar of infliximab (Remsima(®)) after dilution and storage at 4°C and 25°C.

    PubMed

    Vieillard, V; Astier, A; Sauzay, C; Paul, M

    2017-01-01

    There is currently only one monoclonal antibody for which there is a biosimilar: infliximab, which was released onto the French market in 2015. The SPC for the biosimilar (Remsima(®)) are superimposable on those of the original, including 24-hour stability at both 4 and 25°C. The aim of our study was to determine the stability of this biosimilar during one month at 4 and 25°C. Three different batches at two concentrations (0.7mg/mL or 1.6mg/mL) were used. Physicochemical stability was evaluated by the following methods: turbidity, UV spectrometry, DLS, ion chromatography (CEX), gel exclusion chromatography (SEC), and light microscopy. The analyses were performed in triplicate. All methods used have been demonstrated to be valid for measuring antibody stability. There were no signs of physicochemical instability after seven days (on D7) of storage at 4 or 25°C. From D15, we observed slight changes by ion (percentage distribution of the different isoforms) and gel exclusion chromatography (percentage distribution of different polymers, i.e. dimers, oligomers). However, the areas under the curves were unchanged, and the proportions of polymers remained lower than 0.5%. Tertiary structure analysis also showed a change from D15. All observed changes are consistent with progressive oligomerization by hydrophobic interactions. In conclusion, the reconstituted biosimilar is stable for seven days at 4 and 25°C. Gradual oligomerization is observed from D15 but appears to be less than 0.5%, suggesting instability, albeit very limited, in the longer term; the practical consequences of this remain to be evaluated.

  19. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study.

    PubMed

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-06-01

    Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy.IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint).The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3 intestinal BD

  20. Safety of Ferric Carboxymaltose Immediately after Infliximab Administration, in a Single Session, in Inflammatory Bowel Disease Patients with Iron Deficiency: A Pilot Study

    PubMed Central

    Cortes, Xavier; Borrás-Blasco, Joaquín; Molés, Jose Ramón; Boscá, Maia; Cortés, Ernesto

    2015-01-01

    Aim To obtain preliminary safety and efficacy data on intravenous (IV) administration of infliximab (IFX) and ferric carboxymaltose (FCM) to inflammatory bowel disease (IBD) patients in a single treatment session. Methods A two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12) received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33) received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA) or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs) during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM) and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed. Results All 45 patients (35 Crohn´s disease, 10 ulcerative colitis) received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving. Conclusion Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single

  1. Use of corticosteroids in patients with rheumatoid arthritis treated with infliximab: treatment implications based on a real-world Canadian population

    PubMed Central

    Haraoui, Boulos; Jovaisas, Algis; Bensen, William G; Faraawi, Rafat; Kelsall, John; Dixit, Sanjay; Rodrigues, Jude; Sheriff, Maqbool; Rampakakis, Emmanouil; Sampalis, John S; Lehman, Allen J; Otawa, Susan; Nantel, Francois; Shawi, May

    2015-01-01

    Objective To describe the rate of concomitant oral corticosteroid use at antitumour necrosis factor (TNF) initiation and at disease remission, and to assess its effect on incidence of infection and sustainability of remission among patients with rheumatoid arthritis (RA) treated with infliximab in Canadian routine care. Methods Biological naïve patients with RA followed in the Biologic Treatment Registry Across Canada (BioTRAC) were included. The time-dependent association between corticosteroid dose (no use, ≤5 mg/day, >5 mg/day) and the incidence of first infection, while considering possible confounders, remission sustainability and the incidence of subsequent infections were assessed with Cox regression. Results 838 patients were included; mean (SD) baseline age and disease duration were 55.6 (13.5) and 10.5 (9.8) years, respectively. After a mean (SD) of 51.3 (43.6) months, the total incidence of adverse events (AEs) and infections were 110.2 and 19.6 per 100 person-years (PY), respectively. In multivariate analysis, the HR (95% CI) for acquiring an infection was 2.48 (1.24 to 4.98) with >5 mg/day of corticosteroids versus no corticosteroids. Similarly, ≤5 mg/day of corticosteroids was associated with increased hazard for infection (2.12 (0.97 to 4.66)). Despite DAS28 (disease activity score 28) or Clinical Disease Activity Index (CDAI) remission, corticosteroids were continued in 16.4% and 16.7% of cases, respectively. Continued corticosteroid treatment was not associated with sustainability of remission (HRDAS28 (95% CI) 1.40 (0.95 to 2.06); HRCDAI 1.19 (0.75 to 1.88)), however, it had a significant impact on development of infection (HRDAS28 (95% CI) 1.78 (1.00 to 3.19); HRCDAI 2.38 (1.14 to 4.99)). Conclusions Oral corticosteroid treatment was associated with increased risk of development of infection without impacting sustainability of remission. These results support the notion that corticosteroids should be used concomitantly with anti

  2. Infliximab therapy for intestinal, neurological, and vascular involvement in Behcet disease: Efficacy, safety, and pharmacokinetics in a multicenter, prospective, open-label, single-arm phase 3 study

    PubMed Central

    Hibi, Toshifumi; Hirohata, Shunsei; Kikuchi, Hirotoshi; Tateishi, Ukihide; Sato, Noriko; Ozaki, Kunihiko; Kondo, Kazuoki; Ishigatsubo, Yoshiaki

    2016-01-01

    Abstract Behçet disease (BD) is a multisystem disease associated with a poor prognosis in cases of gastrointestinal, neurological, or vascular involvement. We conducted a multicenter, prospective, open-label, single-arm phase 3 study to determine the efficacy, safety, and pharmacokinetics of infliximab (IFX) in BD patients with these serious complications who had displayed poor response or intolerance to conventional therapy. IFX at 5 mg/kg was administered to 18 patients (11 intestinal BD, 3 neurological BD [NBD], and 4 vascular BD [VBD]) at weeks 0, 2, and 6 and every 8 weeks thereafter until week 46. In patients who showed inadequate responses to IFX after week 30, the dose was increased to 10 mg/kg. We then calculated the percentage of complete responders according to the predefined criteria depending on the symptoms and results of examinations (ileocolonoscopy, brain magnetic resonance imaging, computed tomography angiography, positron emission tomography, cerebrospinal fluid, or serum inflammatory markers), exploring the percentage of complete responders at week 30 (primary endpoint). The percentage of complete responders was 61% (11/18) at both weeks 14 and 30 and remained the same until week 54. Intestinal BD patients showed improvement in clinical symptoms along with decrease in C-reactive protein (CRP) levels after week 2. Consistently, scarring or healing of the principal ulcers was found in more than 80% of these patients after week 14. NBD patients showed improvement in clinical symptoms, imaging findings, and cerebrospinal fluid examinations. VBD patients showed improvement in clinical symptoms after week 2 with reductions in CRP levels and erythrocyte sedimentation rate. Imaging findings showed reversal of inflammatory changes in 3 of the 4 VBD patients. Irrespective of the type of BD, all patients achieved improvement in quality of life, leading to the dose reduction or withdrawal of steroids. IFX dose was increased to 10 mg/kg in 3

  3. Infliximab is the new kid on the block in Kawasaki disease: a single-centre study over 8 years from North India.

    PubMed

    Singh, Surjit; Sharma, Dhrubajyoti; Suri, Deepti; Gupta, Anju; Rawat, Amit; Rohit, Manoj Kumar

    2016-01-01

    This was a single-centre study to evaluate the usefulness of tumour necrosis factor-α (TNF-α) blocker, infliximab (IFX), for treatment of Kawasaki disease (KD) in children in Northern Indian. The study was carried out in the Paediatric Allergy-Immunology Unit, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh. The study period was January 2007 to March 2015. Review of records of 23 children with KD who had received IFX was carried out. Median age at presentation was 2 years (range 2 months to 12 years). Indications for using IFX were intravenous immunoglobulin (IVIg) resistance (12/23 patients); severe KD especially when coronary artery abnormalities (CAAs) had developed in spite of IVIg (9/23 patients); retinal vasculitis in association with KD (1 patient) and economic reasons (1 patient). Twenty one (21/23) patients had received IVIg (2 g/kg) as first line therapy. A dose of IFX was 5-7 mg/kg given intravenously. Screening tests for tuberculosis (chest xray, Tuberculin test, QuantiFERON-TB Gold test) were not carried out prior to IFX infusion in any patient. Duration of follow-up was 0-20 months in 13 patients; 21-40 months in 5 patients and >40 months in 6 patients. Mean follow-up was 28.78±25.49 months, range 1-84 months. Eleven of 12 patients (11/12) who had IVIg resistance showed prompt resolution with IFX. Nineteen patients (19/23) in the cohort had CAAs. Of these, 12 showed improvement over mean follow-up of 28.78±25.49 months (range 1-84 months) and 4 showed normalisation. No adverse reactions were noted during infusion of IFX. On follow-up, none of these patients has developed tuberculosis or any other significant infection over a cummulative follow-up of 662 months. IFX can be considered as a useful adjunct in treatment of children with KD.

  4. Safety, efficacy and immunogenicity of switching from innovator to biosimilar infliximab in patients with spondyloarthritis: a 6-month real-life observational study.

    PubMed

    Benucci, Maurizio; Gobbi, Francesca Li; Bandinelli, Francesca; Damiani, Arianna; Infantino, Maria; Grossi, Valentina; Manfredi, Mariangela; Parisi, Simone; Fusaro, Enrico; Batticciotto, Alberto; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola; Meacci, Francesca

    2016-07-23

    Biosimilar infliximab (INX) was recently approved by the European Medicine Agency for the treatment of rheumatoid arthritis, ankylosing spondylitis (AS), Crohn's disease, ulcerative colitis, psoriatic arthritis (PsA), and psoriasis on the grounds that its pharmacokinetics, safety, and efficacy were comparable to those of innovator INX. The aim of this study was to investigate the real-life efficacy, safety, and immunogenicity of switching from innovator to biosimilar INX in patients with spondyloarthritis (SpA). Forty-one patients attending three Italian rheumatology centres with a previous diagnosis of SpA and clinically inactive or moderate disease activity (ASDAS-CRP < 2.1; 22 with AS, five with enteropathic arthritis, 10 with PsA, and four with undifferentiated SpA), who had been treated for more than 6 months with innovator INX in accordance with the ASAS/EULAR guidelines, were switched to biosimilar INX for pharmaco-economic reasons (Tuscany Law No. 450 of 7 April 2015) and followed up for 6 months. A record was kept of their BASDAI, BASFI, ASDAS-CRP, DAS28-CRP (in the presence of peripheral disease), MASES, VAS pain scores, the duration of morning stiffness, and adverse events (AEs). At the time of the switch, the patients had a median age of 50.9 years (range 23-80), a median disease duration of 124.5 months (range 14-372), and a median duration of treatment with innovator INX of 73.7 months (range 6-144). After 6 months of biosimilar INX therapy, there were no statistical differences in their median BASDAI (2.73 ± 1.5 vs. 2.6 ± 1.3, p = .27), BASFI (2.34 ± 1.3 vs. 2.17 ± 1.2, p = 0.051), ASDAS-CRP (1.35 ± 0.3 vs. 1.28 ± 0.2, p = 0.24), DAS28-CRP (2.66 ± 0.67 vs. 2.67 ± 0.35, p = 0.92), MASES (0.35 ± 0.7 vs. 0.17 ± 0.4, p = 0.08), or VAS pain scores (18 ± 14.7 vs. 16.7 ± 11.3, p = 0.55), whereas the median duration of morning stiffness had significantly decreased (7.2 ± 6.9 vs. 5.8 ± 6, p = 0

  5. Efficacy and safety of switching from reference infliximab to CT-P13 compared with maintenance of CT-P13 in ankylosing spondylitis: 102-week data from the PLANETAS extension study

    PubMed Central

    Park, Won; Yoo, Dae Hyun; Miranda, Pedro; Brzosko, Marek; Wiland, Piotr; Gutierrez-Ureña, Sergio; Mikazane, Helena; Lee, Yeon-Ah; Smiyan, Svitlana; Lim, Mie-Jin; Kadinov, Vladimir; Abud-Mendoza, Carlos; Kim, HoUng; Lee, Sang Joon; Bae, YunJu; Kim, SuYeon; Braun, Jürgen

    2017-01-01

    Objectives To investigate the efficacy and safety of switching from infliximab reference product (RP) to its biosimilar or maintaining biosimilar treatment in patients with ankylosing spondylitis (AS). Methods This open-label extension study recruited patients with AS who completed a 54-week, randomised controlled study comparing CT-P13 with RP (PLANETAS). CT-P13 (5 mg/kg) was administered intravenously every 8 weeks from week 62 to week 102. Efficacy end points included the proportion of patients achieving Assessment of SpondyloArthritis international Society (ASAS)20. Antidrug antibodies (ADAs) were measured using an electrochemiluminescent method. Data were analysed for patients treated with CT-P13 in the main PLANETAS study and the extension (maintenance group) and those who were switched to CT-P13 during the extension study (switch group). Results Overall, 174 (82.9%) of 210 patients who completed the first 54 weeks of PLANETAS and agreed to participate in the extension were enrolled. Among these, 88 were maintained on CT-P13 and 86 were switched to CT-P13 from RP. In these maintenance and switch groups, respectively, ASAS20 response rates at week 102 were 80.7% and 76.9%. ASAS40 and ASAS partial remission were also similar between groups. ADA positivity rates were comparable (week 102: 23.3% vs 27.4%). Adverse events led to treatment discontinuation during the extension study in 3 (3.3%) and 4 (4.8%) patients, respectively. Conclusions This is the first study to show that switching from RP to its biosimilar CT-P13 is possible without negative effects on safety or efficacy in patients with AS. In the maintenance group, CT-P13 was effective and well tolerated over 2 years of treatment. Trial registration number NCT01571206; Results. PMID:27117698

  6. Mincle Signaling Promotes Con A Hepatitis.

    PubMed

    Greco, Stephanie H; Torres-Hernandez, Alejandro; Kalabin, Aleksandr; Whiteman, Clint; Rokosh, Rae; Ravirala, Sushma; Ochi, Atsuo; Gutierrez, Johana; Salyana, Muhammad Atif; Mani, Vishnu R; Nagaraj, Savitha V; Deutsch, Michael; Seifert, Lena; Daley, Donnele; Barilla, Rocky; Hundeyin, Mautin; Nikifrov, Yuriy; Tejada, Karla; Gelb, Bruce E; Katz, Steven C; Miller, George

    2016-10-01

    Con A hepatitis is regarded as a T cell-mediated model of acute liver injury. Mincle is a C-type lectin receptor that is critical in the immune response to mycobacteria and fungi but does not have a well-defined role in preclinical models of non-pathogen-mediated inflammation. Because Mincle can ligate the cell death ligand SAP130, we postulated that Mincle signaling drives intrahepatic inflammation and liver injury in Con A hepatitis. Acute liver injury was assessed in the murine Con A hepatitis model using C57BL/6, Mincle(-/-), and Dectin-1(-/-) mice. The role of C/EBPβ and hypoxia-inducible factor-1α (HIF-1α) signaling was assessed using selective inhibitors. We found that Mincle was highly expressed in hepatic innate inflammatory cells and endothelial cells in both mice and humans. Furthermore, sterile Mincle ligands and Mincle signaling intermediates were increased in the murine liver in Con A hepatitis. Most significantly, Mincle deletion or blockade protected against Con A hepatitis, whereas Mincle ligation exacerbated disease. Bone marrow chimeric and adoptive transfer experiments suggested that Mincle signaling in infiltrating myeloid cells dictates disease phenotype. Conversely, signaling via other C-type lectin receptors did not alter disease course. Mechanistically, we found that Mincle blockade decreased the NF-κβ-related signaling intermediates C/EBPβ and HIF-1α, both of which are necessary in macrophage-mediated inflammatory responses. Accordingly, Mincle deletion lowered production of nitrites in Con A hepatitis and inhibition of both C/EBPβ and HIF-1α reduced the severity of liver disease. Our work implicates a novel innate immune driver of Con A hepatitis and, more broadly, suggests a potential role for Mincle in diseases governed by sterile inflammation.

  7. Galaxias australes con núcleo doble

    NASA Astrophysics Data System (ADS)

    Gimeno, G.; Díaz, R.; Carranza, G.

    Se estudia una muestra de galaxias australes con núcleo doble a partir de una búsqueda extensiva en la literatura. Se analizan las características morfológicas, fotométricas y espectroscópicas de la muestra. Para algunas galaxias se han realizado observaciones con el espectrógrafo multifunción (EMF) de la Estación Astrofísica de Bosque Alegre a partir de las cuales se determinaron parámetros cinemáticos.

  8. InterCon Travel Health: Case B

    ERIC Educational Resources Information Center

    Truman, Gregory E.; Pachamanova, Dessislava A.; Goldstein, Michael A.

    2010-01-01

    InterCon provides services to health insurers of foreign tourists who travel to the United States and Canada. Management wants to implement a new information system that will deal with several operational problems, but it is having difficulty securing the capital resources to fund the system's development. After an initial failure, the chief…

  9. Ependimoma myxopapilar sacro gigante con osteolisis

    PubMed Central

    Ajler, Pablo; Landriel, Federico; Goldschmidt, Ezequiel; Campero, Álvaro; Yampolsky, Claudio

    2014-01-01

    Objetivo: la presentación de un caso de una paciente con un ependimoma sacro con extensa infiltración y destrucción ósea local. Descripción del caso: una mujer de 53 años acudió a la consulta por dolor lumbosacro y alteraciones sensitivas perineales y esfinterianas. La imágenes por Resonancia Magnética (IRM) y la Tomografía Axial Computada (TAC) mostraron una lesión expansiva gigante a nivel S2-S4 con extensa osteólisis e invasión de tejidos adyacentes. Se realizó una exéresis tumoral completa con mejoría del estatus funcional. La anatomía patológica informó ependimoma mixopapilar. Discusión: la extensión de la resección quirúrgica es el mejor predictor de buen pronóstico. El tratamiento radiante se reserva como opción adyuvante para las resecciones incompletas y recidiva tumoral. La quimioterapia sólo debería utilizarse en casos en que la cirugía y la radioterapia estén contraindicadas. Conclusión: Los ependimomas mixopapilares sacros con destrucción ósea y presentación intra y extradural son muy infrecuentes y deben ser tenidos en cuenta entre los diagnósticos diferenciales preoperatorios. Su resección total, siempre que sea posible, es la mejor alternativa terapéutica. PMID:25165615

  10. Somatic cell nuclear transfer: pros and cons.

    PubMed

    Sumer, Huseyin; Liu, Jun; Tat, Pollyanna; Heffernan, Corey; Jones, Karen L; Verma, Paul J

    2009-01-01

    Even though the technique of mammalian SCNT is just over a decade old it has already resulted in numerous significant advances. Despite the recent advances in the reprogramming field, SCNT remains the bench-mark for the generation of both genetically unmodified autologous pluripotent stem cells for transplantation and for the production of cloned animals. In this review we will discuss the pros and cons of SCNT, drawing comparisons with other reprogramming methods.

  11. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  12. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  13. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  14. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  15. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  16. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  17. 9 CFR 319.301 - Chili con carne with beans.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne with beans. 319.301 Section 319.301 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Dehydrated Meat Food Products § 319.301 Chili con carne with beans. Chili con carne with beans shall...

  18. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  19. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  20. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Chili con carne. 319.300 Section 319.300 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Products § 319.300 Chili con carne. “Chili con carne” shall contain not less than 40 percent of...

  1. Finemet versus ferrite -- Pros and cons

    SciTech Connect

    K.Y. Ng and Z.B. Qian

    1999-05-19

    There is a new magnetic alloy called Finemet which has very constant {mu}'{sub p}Qf up to {approximately} 2 kG and is very stable at high magnet flux density and temperature. It may be a good can-didate for high-gradient rf cavities. However, it has a rather low quality factor and is therefore very lossy. We compare the pros and cons of Finemet versus the common ferrite, when used in low-energy accelerating cavities, insertion for space-charge compensation, and barrier cavities.

  2. Energy Star program benefits Con Edison

    SciTech Connect

    1995-05-01

    Impressed with savings in energy costs achieved after upgrading the lighting and air conditioning systems at its Manhattan headquarters, Home Box Office (HBO) wanted to do more, James Flock, vice president for computer and office systems, contacted Con Edison Co. of New York in March 1991 to determine what the company could do to save money by reducing energy consumed by personal computers. Arthur Kressner, Con Edison Research and Development manager contacted industry organizations and manufacturers for advice, but was told only to shut off computers at night and on weekends. Kressner arranged a series of meetings with IBM and the Electric Power Research Institute (EPRI) to discuss the issue, then approached the U.S. Environmental Protection Agency (EPA), which was designing a program to promote the introduction and use of energy-efficient office equipment. In 1992, the EPA announced the Energy Star program for PCs, enabling manufacturers to display the Energy Star logo on machines meeting program criteria, including the ability to enter a sleep mode in which neither the computer nor monitor consume more than 30 W or electricity. Industry experts estimate national energy consumption by office equipment could double by the year 2000, but Energy Star equipment is expected to improve efficiency and help maintain electric loads.

  3. Cervical disc arthroplasty: Pros and cons

    PubMed Central

    Moatz, Bradley; Tortolani, P. Justin

    2012-01-01

    Background: Cervical disc arthroplasty has emerged as a promising potential alternative to anterior cervical discectomy and fusion (ACDF) in appropriately selected patients. Despite a history of excellent outcomes after ACDF, the question as to whether a fusion leads to adjacent segment degeneration remains unanswered. Numerous US investigational device exemption trials comparing cervical arthroplasty to fusion have been conducted to answer this question. Methods: This study reviews the current research regarding cervical athroplasty, and emphasizes both the pros and cons of arthroplasty as compared with ACDF. Results: Early clinical outcomes show that cervical arthroplasty is as effective as the standard ACDF. However, this new technology is also associated with an expanding list of novel complications. Conclusion: Although there is no definitive evidence that cervical disc replacement reduces the incidence of adjacent segment degeneration, it does show other advantages; for example, faster return to work, and reduced need for postoperative bracing. PMID:22905327

  4. Pros and cons of the proteomics.

    PubMed

    Gupta, Ashish; Kumar, Ashutosh

    2014-01-01

    The number of proteins produced by the 30,000-40,000 genes of the human genome is estimated to be three or four orders of magnitude higher. Proteomics is a rapidly developing science. In principle, two main areas in the field of proteomics have been developed, each of them having its pros and cons. These fields are profiling and functional proteomics. The aim of the proteomic profiling is to describe and index the whole set of proteins of a biological sample, which could be an organism, an organ, or a cell, or parts there of like individual's tissue or organelles. In our understanding, both types of proteomics (profiling and functional) are valuable tools complementing other biological methodologies.

  5. Pros and cons of phage therapy

    PubMed Central

    Loc-Carrillo, Catherine

    2011-01-01

    Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this commentary is to discuss many of those issues in a single location. In terms of “Pros,” for example, phages can be bactericidal, can increase in number over the course of treatment, tend to only minimally disrupt normal flora, are equally effective against antibiotic-sensitive and antibiotic-resistant bacteria, often are easily discovered, seem to be capable of disrupting bacterial biofilms, and can have low inherent toxicities. In addition to these assets, we consider aspects of phage therapy that can contribute to its safety, economics, or convenience, but in ways that are perhaps less essential to the phage potential to combat bacteria. For example, autonomous phage transfer between animals during veterinary application could provide convenience or economic advantages by decreasing the need for repeated phage application, but is not necessarily crucial to therapeutic success. We also consider possible disadvantages to phage use as antibacterial agents. These “Cons,” however, tend to be relatively minor. PMID:22334867

  6. Pro/con a precessional geodynamo

    NASA Astrophysics Data System (ADS)

    Vanyo, J.

    2003-04-01

    The modest amount of research that exists on the ability, or lack of ability, of mantle precession to power a geodynamo developed mostly during the last half of the 1900s. Papers by Roberts and Stewartson (1965) and by Busse (1968) studied precession generally without a pro/con conclusion. Malkus in the late 1960s attempted to advance a positive role for precession through experiments and analysis. His experiments have survived criticism, but his analyses were discounted, especially by Rochester, Jacobs, Smylie, and Chong (1975) and by Loper (1975). Rochester, et al. critiqued existing analyses of precession, including those of Malkus, but did not reach a strong position either pro or con a precessional geodynamo. Loper argued emphatically that precession was not capable of powering the geodynamo. Explicit analyses that either critique or support Loper’s arguments have yet to appear in the literature. During the 1970s, Vanyo and associates studied energy dissipation during precession of satellite liquid fuels and its effect on satellite attitude stability. Engineers and scientists in every country that has launched satellites completed similar research. Some is published in the aerospace literature, more is available in company and government reports. Beginning in 1981, Vanyo and associates applied this knowledge to the very similar problem of energy dissipation and flow patterns in precessing mechanical models scaled geometrically and dynamically to the Earth’s liquid core. Energy experiments indicate massive amounts of mechanical energy are dissipated at the CMB, and flow experiments show complex motions within the boundary layer and axial flows with helicity throughout the interior. Analysis of Earth core precession also advanced, especially in several papers by Kerswell and by Tilgner in the late 1990s. Detail numerical models have yet to appear. Although progress in understanding the role of precession in Earth core motions has advanced, there remains a

  7. Trazando la materia oscura con cúmulos globulares

    NASA Astrophysics Data System (ADS)

    Forte, J. C.

    Se describe la estrategia adoptada para mapear la distribución de materia oscura y bariónica en galaxias elípticas cuyos cúmulos globulares están siendo observados con los telescopios VLT y Gemini. Se ejemplifican los resultados con los datos obtenidos en el cúmulo de Fornax.

  8. Games Con Men Play: The Semiosis of Deceptive Interaction.

    ERIC Educational Resources Information Center

    Hankiss, Agnes

    1980-01-01

    Analyzes some of the most frequent deceptive interactions as rendered through case histories of male con artists and their victims taken from police records. Discusses the recurrent elements in both the con-games strategies and victims' way of interpreting those strategies. (JMF)

  9. Breath Analysis Science at PittCon 2012, Orlando, Florida

    EPA Science Inventory

    Breath analysis science was featured in three organized sessions at this year’s Pittsburgh Conference and Exposition, or ‘PittCon 2012’ (http://www.pittcon.org/). As described in previous meeting reports, PittCon is one of the largest international conferences for analytical chem...

  10. RoboCon: A general purpose telerobotic control center

    SciTech Connect

    Draper, J.V.; Noakes, M.W.; Schempf, H.; Blair, L.M.

    1997-02-01

    This report describes human factors issues involved in the design of RoboCon, a multi-purpose control center for use in US Department of Energy remote handling applications. RoboCon is intended to be a flexible, modular control center capable of supporting a wide variety of robotic devices.

  11. [Cement augmentation of pedicle screws : Pros and cons].

    PubMed

    Schnake, K J; Blattert, T R; Liljenqvist, U

    2016-09-01

    Cement augmentation of pedicle screws biomechanically increases screw purchase in the bone. However, clinical complications may occur. The pros and cons of the technique are discussed from different clinical perspectives.

  12. Planificación Neuroquirúrgica con Software Osirix

    PubMed Central

    Jaimovich, Sebastián Gastón; Guevara, Martin; Pampin, Sergio; Jaimovich, Roberto; Gardella, Javier Luis

    2014-01-01

    Introducción: La individualidad anatómica es clave para reducir el trauma quirúrgico y obtener un mejor resultado. Actualmente, el avance en las neuroimágenes ha permitido objetivar esa individualidad anatómica, permitiendo planificar la intervención quirúrgica. Con este objetivo, presentamos nuestra experiencia con el software Osirix. Descripción de la técnica: Se presentan 3 casos ejemplificadores de 40 realizados. Caso 1: Paciente con meningioma de la convexidad parasagital izquierda en área premotora; Caso 2: Paciente con macroadenoma hipofisario, operada previamente por vía transeptoesfenoidal en otra institución con una resección parcial; Caso 3: Paciente con lesiones en pedúnculo cerebeloso medio bilateral. Se realizó la planificación prequirúrgica con el software OsiriX, fusionando y reconstruyendo en 3D las imágenes de TC e IRM, para analizar relaciones anatómicas, medir distancias, coordenadas y trayectorias, entre otras funciones. Discusión: El software OsiriX de acceso libre y gratuito permite al cirujano, mediante la fusión y reconstrucción en 3D de imágenes, analizar la anatomía individual del paciente y planificar de forma rápida, simple, segura y económica cirugías de alta complejidad. En el Caso 1 se pudo analizar las relaciones del tumor con las estructuras adyacentes para minimizar el abordaje. En el Caso 2 permitió comprender la anatomía post-operatoria previa del paciente, para determinar la trayectoria del abordaje transnasal endoscópico y la necesidad de ampliar su exposición, logrando la resección tumoral completa. En el Caso 3 permitió obtener las coordenadas estereotáxicas y trayectoria de una lesión sin representación tomográfica. Conclusión: En casos de no contar con costosos sistemas de neuronavegación o estereotáxia el software OsiriX es una alternativa a la hora de planificar la cirugía, con el objetivo de disminuir el trauma y la morbilidad operatoria. PMID:25165617

  13. [I costi farmacologici della terapia di conversione con farmaci biologici nel carcinoma del colon-retto con metastasi epatiche].

    PubMed

    Giuliani, Jacopo; Bonetti, Andrea

    2016-08-01

    Riassunto. Lo scopo di questo studio è quello di valutare i costi dei farmaci (con particolare riferimento alle terapie con farmaci biologici) utilizzati nella terapia di conversione in una popolazione non selezionata di pazienti affetti da carcinoma del colon-retto in stadio avanzato, al fine di ottenere una resezione epatica R0. In questa rassegna sono stati selezionati i report completi e gli aggiornamenti di tutti gli studi clinici randomizzati (di fase II e fase III) che confrontassero almeno 2 regimi di terapia con farmaci biologici in prima linea in pazienti affetti da carcinoma del colon-retto in stadio avanzato di malattia. I costi dei farmaci sono stati ricavati dalla nostra Farmacia Ospedaliera e sono espressi in euro (€). Il nostro studio inizia con la valutazione di 683 abstract. 48 tria sono stati considerati adeguati per una successiva analisi. Una valutazione più approfondita ha portato all'esclusione di 37 trial, lasciando alla valutazione finale 11 studi clinici randomizzati (3 trial di fase II, per un totale di 522 pazienti, e 8 studi di fase III, per un totale di 7191 pazienti). I costi dei farmaci utilizzati nella terapia di conversione aumentano con la sostituzione del 5-fluorouracile con la capecitabina e, in misura maggiore, con l'introduzione degli agenti biologici. In questo lavoro sono presentati due punti chiave. Primo, i costi degli agenti farmacologici utilizzati nei regimi di prima linea a base di agenti biologici più comunemente utilizzati nel trattamento del carcinoma del colon-retto in stadio avanzato sono molto variabili. Secondo, i dati di efficacia dei regimi pubblicati, in termini di tassi di resezione, dipendono dalla selezione dei pazienti, dalle caratteristiche del tumore e dal tipo di schema di terapia.

  14. Detail of conning tower atop the submarine. Note the wire ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of conning tower atop the submarine. Note the wire rope wrapped around the base of the tower, which may have been used in an attempt to pull the submarine offshore. - Sub Marine Explorer, Located along the beach of Isla San Telmo, Pearl Islands, Isla San Telmo, Former Panama Canal Zone, CZ

  15. Utilice en forma segura los productos con cebo para roedores

    EPA Pesticide Factsheets

    Si se usan de manera inadecuada, los productos con veneno para ratas y ratones podrían hacerle daño a usted, a sus hijos o a sus mascotas. Siempre que use pesticidas lea la etiqueta del producto y siga todas las indicaciones.

  16. Canceling Some d-CON Mouse and Rat Control Products

    EPA Pesticide Factsheets

    EPA has reached agreement with the manufacturer, to cancel 12 d-CON products that do not meet our testing protocols that better protect children, pets and non-target wildlife from accidental exposure to the pesticide. These products will be phased out.

  17. Three dimensional boundary layers on submarine conning towers and rudders

    NASA Astrophysics Data System (ADS)

    Gleyzes, C.

    1988-01-01

    Solutions for the definition of grids adapted to the calculation of three-dimensional boundary layers on submarine conning towers and on submarine rudders and fins are described. The particular geometry of such bodies (oblique shaped hull, curved fins) required special adaptations. The grids were verified on examples from a test basin.

  18. Providers debate pros and cons of pneumonia vaccination at discharge.

    PubMed

    2001-02-01

    When to vaccinate against pneumonia? Does it makes sense when patients are in the hospital? Or should patients wait for the first post-op visit with the PCP? Office-based and hospital-based physicians weigh the pros and cons of each.

  19. International Field Reversible Thermal Connector (RevCon) Challenge

    DTIC Science & Technology

    2016-07-01

    of Figures Figure Page Figure 1: Comparison Temperature History of T3 from each Thermal Connector........................ 6...OHP Thermal Connector Delivered by MissStateU .................................................. 54 Figure 49: Comparison Temperature History of T1...88 Figure A2: Schematic of Temperature Monitoring and Vibration Detection Setup for RevCon IV

  20. Teaching after Retirement: The Pros and the Cons

    ERIC Educational Resources Information Center

    Sommer, Robert

    2014-01-01

    Having enjoyed teaching during my active career, I continued to teach summer school following retirement. Self-observed sensory and cognitive impairments, although not mentioned by students in their evaluations, induced me to consider the pros and cons of continuing to teach. My hope is that this list of benefits and problems will be of assistance…

  1. Inclusion: The Pros and Cons--A Critical Review

    ERIC Educational Resources Information Center

    Savich, Carl

    2008-01-01

    The purpose of this paper was to review, analyze, and critique the pros and cons, the advantages and disadvantages, of inclusion. The methodology consisted in analyzing and comparing research findings on the benefits and costs of inclusion. Federal legislation and regulations on inclusion were examined, analyzed, and discussed. The results showed…

  2. LunGradCon: The Lunar Graduate Conference

    NASA Astrophysics Data System (ADS)

    Dove, A.; Poppe, A.; Neish, C.; Fagan, A.; Fuqua, H.; Kramer, G. Y.; Horanyi, M.

    2011-12-01

    Members of the Colorado Center for Lunar Dust and Atmospheric Studies (CCLDAS) initiated the Lunar Graduate Conference (LunGradCon), modeled after the highly successful Astrobiology Graduate Conference (AbGradCon). The purpose of this conference is to enhance the professional development of graduate students and early postdoctoral researchers by providing an opportunity to present and discuss scientific research in an environment of their peers. For the first two years, LunGradCon has been held as a one-day conference in conjunction with the NASA Lunar Science Institue's (NLSI) Lunar Science Forum at the NASA Ames Research Center. Activities include an invited overview talk on each of the NASA Lunar Science Institute's three main research areas (OF the Moon, ON the Moon, and FROM the Moon), submitted oral presentations from graduate students and postdoctoral researchers, and networking opportunities with established member of the lunar science community and the NLSI. In each of the first two years of LunGradCon, there have been 20-25 attendees, with about 15 of those presenting submitted talks. Each speaker received feedback forms from the other participants in order to improve on their presentation techniques. Participants also provided feedback on the conference as a whole in order to evaluate the content and provide suggestions for improvement in following years. Overall, the feedback has been extremely positive. This talk will summarize the achievements of past LunGradCons and plans for expansion of the conference to ensure a long-term positive impact on the early careers of future lunar, planetary and space science researchers.

  3. [Autism spectrum disorder and epilepsy: the role of ketogenic diet].

    PubMed

    Garcia-Penas, J J

    2016-01-01

    Introduccion. Un 5-40% de los pacientes autistas desarrolla epilepsia. Aunque generalmente se controlan bien con medicacion, hasta un 20-30% de estas epilepsias son refractarias al tratamiento farmacologico. En esta poblacion, la dieta cetogenica (DC) puede ser una terapia alternativa altamente eficaz y debe considerarse seriamente. Objetivo. Revisar el papel de la DC en el tratamiento de la epilepsia infantil refractaria y en los pacientes que asocian autismo y epilepsia. Desarrollo. La DC es un tratamiento eficaz y bien tolerado para las epilepsias infantiles refractarias, incluyendo los pacientes que asocian autismo y epilepsia. Es fundamental caracterizar de forma precisa el sindrome epileptico para conocer cuales son los mejores candidatos para tratar con DC. Por otra parte, el efecto positivo de la DC sobre las alteraciones del metabolismo oxidativo mitocondrial y la evidencia experimental obtenida con DC en animales autistas sugieren que pueda ser una alternativa eficaz en los pacientes con autismo. Conclusiones. Basandose en la utilidad demostrada de la DC en el tratamiento de pacientes con epilepsia y autismo, esta terapia se ha usado en los ultimos años como una terapia alternativa para los pacientes autistas, aunque se desconoce cual es su eficacia real. Es necesario realizar un estudio aleatorizado y controlado para definir el perfil de eficacia y seguridad en esta poblacion.

  4. A complex photoreceptor system mediates the regulation by light of the conidiation genes con-10 and con-6 in Neurospora crassa.

    PubMed

    Olmedo, María; Ruger-Herreros, Carmen; Luque, Eva M; Corrochano, Luis M

    2010-04-01

    Genes con-10 and con-6 in Neurospora crassa are activated during conidiation or after illumination of vegetative mycelia. Light activation requires the white-collar complex (WCC), a transcription factor complex composed of the photoreceptor WC-1 and its partner WC-2. We have characterized the photoactivation of con-10 and con-6, and we have identified 300bp required for photoactivation in the con-10 promoter. A complex stimulus-response relationship for con-10 and con-6 photoactivation suggested the activity of a complex photoreceptor system. The WCC is the key element for con-10 activation by light, but we suggest that other photoreceptors, the cryptochrome CRY-1, the rhodopsin NOP-1, and the phytochrome PHY-2, modify the activity of the WCC for con-10 photoactivation, presumably through a repressor. In addition we show that the regulatory protein VE-1 is required for full photocarotenogenesis. We propose that these proteins may modulate the WCC in a gene-specific way.

  5. Apoyo a Estudios Geodinamicos con GPS en Guatemala

    NASA Astrophysics Data System (ADS)

    Robles, V. R.

    2013-05-01

    El Instituto Geografico Nacional de Guatemala implemento 17 estaciones GNSS en el año 2009, como un proyecto de credito mixto de donacion de equipamiento del Gobierno de Suiza, el cual, este equipamiento de estaciones CORS GNSS es un sistema de recepción y transmisión de datos crudos GPS RInex que utiliza la tecnologia Spider Web de Leica, asi mismo este sistema esta sirviendo para el espablecimiento de un marco geodesico nacional de coordenadas geodesicas oficiales, el cual se calculan u obtienen las velocidades en tiempos temporales programados de las 17 Estaciones CORS. La infraestructura del marco geodesico de Guatemala esta sirviendo de base para las aplicaciones de estudios geodinamicos como el monitoreo de del desplazamiento de las placas tectonicas por medio de un estudio que se inicio en el año de 1999, llamado medicion con GPS el sistema de Fallas de los rios Polochic Motagua de Guatemala, tambien para un estudio que se implemento para deformación de corteza terrestre local en un Volcan Activo de Guatemala llamado Pacaya. Para el estudio de medicion con GPS en el sistema de falla de los Rios del polochic Motagua se implementaron 16 puntos para medir con GPS de dos frecuencias en el año de 1999, el cual, tres puntos son estaciones geodesicas CORS IGS llamados GUAT, ELEN y HUEH, despues en el año de 2003 se hizo otra medicion en un total de 20 puntos, que permitió calcular las velocidades de desplazamieinto de los puntos en mención, usando como referencia el modelo NUVEL 1A de DeMets de la placa de Norteamerica. Este estudio fue en cooperación internacional por la universidad de Nice de Francia y el IGNde Francia. Para el estudio del monitoreo con GPS del volcan activo de Guatemala, se implementaron cuatro puntos al rededor del volcan, el cual, se realizan cuatro mediciones al año, que permiten determinar axialmente la distancias entre los puntos, y rebisar estadisticamente cual es el comportamiento de las distancias en funcion del tiempo, si

  6. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning.

    PubMed

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2015-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs.

  7. Molecular diagnostics: Molecular Med Tri-Con 2013.

    PubMed

    Klein, Roger D

    2013-07-01

    The 20th annual Molecular Med Tri-Con conference, sponsored by Cambridge Health Institute (MA, USA), consisted of over 250 presentations within five parallel 'channels': 'Diagnostics, Therapeutics, Clinical, Informatics and Cancer', along with five preliminary symposia, 15 short courses, a plenary keynote session entitled 'Personalized Oncology - Fulfilling the Promise for Today's Patients' and a keynote panel entitled, 'Emerging Technologies and Industry Perspectives'. Over 3000 individuals from academia, clinical laboratories and industry were in attendance. This article will focus on the Keynote Session of 'Molecular Diagnostics' track within the Diagnostics Channel.

  8. [National consensus on the ketogenic diet].

    PubMed

    Armeno, Marisa; Caraballo, Roberto; Vaccarezza, María; Alberti, M Julia; Ríos, Viviana; Galicchio, Santiago; de Grandis, Elizabeth S; Mestre, Graciela; Escobal, Nidia; Matarrese, Pablo; Viollaz, Rocío; Agostinho, Ariela; Díez, Cecilia; Cresta, Araceli; Cabrera, Analía; Blanco, Virginia; Ferrero, Hilario; Gambarini, Victoria; Sosa, Patricia; Bouquet, Cecilia; Caramuta, Luciana; Guisande, Silvina; Gamboni, Beatriz; Hassan, Amal; Pesce, Laura; Argumedo, Laura; Dlugoszewski, Corina; DeMartini, Martha G; Panico, Luis

    2014-09-01

    Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, mayormente de inicio durante la infancia. Un tercio de los pacientes evoluciona hacia una forma refractaria al tratamiento con farmacos antiepilepticos, lo que plantea al equipo de salud un desafio terapeutico. La dieta cetogenica (DC) es un tratamiento no farmacologico efectivo utilizado como un metodo alternativo para el tratamiento de la epilepsia refractaria. Objetivos. Es necesario establecer directrices para utilizar la DC adecuadamente y asi expandir su conocimiento y utilizacion en paises hispanoparlantes. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso para estandarizar el uso de la DC basandose en la bibliografia publicada y la experiencia clinica. El grupo esta formado por neuropediatras, medicos nutricionistas y licenciadas en nutricion de cinco provincias de Argentina pertenecientes a 10 centros que aplican la DC como tratamiento de la epilepsia refractaria. Desarrollo. Se exponen temas tales como la seleccion del paciente, el asesoramiento a la familia antes del tratamiento, las interacciones de la DC con la medicacion anticonvulsionante, los suplementos, el control de efectos adversos y la retirada de dicha dieta. Conclusiones. La DC es un tratamiento util para los pacientes pediatricos con epilepsia intratable. Es fundamental la educacion y colaboracion del paciente y la familia. El tratamiento debe llevarlo a cabo un equipo interdisciplinar experimentado, siguiendo un protocolo. La formacion de un grupo nacional interdisciplinar, y la publicacion de este consenso, ofrece la posibilidad de orientar a nuevos centros en su implantacion.

  9. Cannabinoids and cancer: pros and cons of an antitumour strategy

    PubMed Central

    Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

    2006-01-01

    In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called ‘endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy. PMID:16501583

  10. Endoscopic scoring systems for inflammatory bowel disease: pros and cons.

    PubMed

    Tontini, Gian Eugenio; Bisschops, Raf; Neumann, Helmut

    2014-07-01

    Endoscopy plays a pivotal role for diagnosis and assessment of disease activity and extent in patients with inflammatory bowel diseases. International guidelines recommend the use of endoscopic scoring systems for evaluation of the prognosis and efficacy of medical treatments. Ideal scoring systems are easy to use, reproducible, reliable, responsive to changes, and validated in different clinical settings in order to guide therapeutic strategies. However, currently available endoscopic scoring systems often appear as complex for routine endoscopy and suffer from insufficient interobserver agreement and lack of formal validation which often limit their use in clinical trials. Here, we describe the role of endoscopic scoring systems in inflammatory bowel diseases focusing on pros and cons in the era of advanced endoscopic imaging and mucosal healing.

  11. Caffe con Troll: Shallow Ideas to Speed Up Deep Learning

    PubMed Central

    Hadjis, Stefan; Abuzaid, Firas; Zhang, Ce; Ré, Christopher

    2016-01-01

    We present Caffe con Troll (CcT), a fully compatible end-to-end version of the popular framework Caffe with rebuilt internals. We built CcT to examine the performance characteristics of training and deploying general-purpose convolutional neural networks across different hardware architectures. We find that, by employing standard batching optimizations for CPU training, we achieve a 4.5× throughput improvement over Caffe on popular networks like CaffeNet. Moreover, with these improvements, the end-to-end training time for CNNs is directly proportional to the FLOPS delivered by the CPU, which enables us to efficiently train hybrid CPU-GPU systems for CNNs. PMID:27314106

  12. Gradient Optimization for Analytic conTrols - GOAT

    NASA Astrophysics Data System (ADS)

    Assémat, Elie; Machnes, Shai; Tannor, David; Wilhelm-Mauch, Frank

    Quantum optimal control becomes a necessary step in a number of studies in the quantum realm. Recent experimental advances showed that superconducting qubits can be controlled with an impressive accuracy. However, most of the standard optimal control algorithms are not designed to manage such high accuracy. To tackle this issue, a novel quantum optimal control algorithm have been introduced: the Gradient Optimization for Analytic conTrols (GOAT). It avoids the piecewise constant approximation of the control pulse used by standard algorithms. This allows an efficient implementation of very high accuracy optimization. It also includes a novel method to compute the gradient that provides many advantages, e.g. the absence of backpropagation or the natural route to optimize the robustness of the control pulses. This talk will present the GOAT algorithm and a few applications to transmons systems.

  13. Balancing Ethical Pros and Cons of Stem Cell Derived Gametes.

    PubMed

    Segers, Seppe; Mertes, Heidi; de Wert, Guido; Dondorp, Wybo; Pennings, Guido

    2017-01-13

    In this review we aim to provide an overview of the most important ethical pros and cons of stem cell derived gametes (SCD-gametes), as a contribution to the debate about reproductive tissue engineering. Derivation of gametes from stem cells holds promising applications both for research and for clinical use in assisted reproduction. We explore the ethical issues connected to gametes derived from embryonic stem cells (both patient specific and non-patient specific) as well as those related to gametes derived from induced pluripotent stem cells. The technology of SCD-gametes raises moral concerns of how reproductive autonomy relates to issues of embryo destruction, safety, access, and applications beyond clinical infertility.

  14. Cannabinoids and cancer: pros and cons of an antitumour strategy.

    PubMed

    Bifulco, Maurizio; Laezza, Chiara; Pisanti, Simona; Gazzerro, Patrizia

    2006-05-01

    In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called 'endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy.

  15. [Modern tribology in total hip arthroplasty: pros and cons].

    PubMed

    Gómez-García, F

    2014-01-01

    The wear products and adverse reactions that occur on bearing surfaces represent one of the greatest challenges in prosthetic replacements, as the latter experience increasing demands due to the large number of young and older adult patients that have a long life expectancy and remarkable activity. The purpose of this review is to analyze the pros and cons of the new advances in the bearing components of the articular surfaces of current total hip arthroplasties. We also discuss the strategies used historically, their problems, results and the surgeon's role in prescribing the tribologic couple that best fits each patient's needs. We conclude with practical recommendations for the prescription and management of the latest articular couples for total hip arthroplasty.

  16. Pros and Cons of the Acceleration Scheme (NF-IDS)

    SciTech Connect

    Bogacz, Alex; Bogacz, Slawomir

    2008-07-01

    The overall goal of the acceleration systems: large acceptance acceleration to 25 GeV and beam shaping can be accomplished by various fixed field accelerators at different stages. They involve three superconducting linacs: a single pass linear Pre-accelerator followed by a pair of multi-pass Recirculating Linear Accelerators (RLA) and finally a nonâ scaling FFAG ring. The present baseline acceleration scenario has been optimized to take maximum advantage of appropriate acceleration scheme at a given stage. Pros and cons of various stages are discussed here in detail. The solenoid based Pre-accelerator offers very large acceptance and facilitates correction of energy gain across the bunch and significant longitudinal compression trough induced synchrotron motion. However, far off-crest acceleration reduces the effective acceleration gradient and adds complexity through the requirement of individual RF phase control for each cavity. Close proximity of strong solenoids and superc

  17. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J.; Do Van Luu; Lee, E.K.; Hong, S.S.

    1996-12-31

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  18. Neogene sequence stratigraphy, Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    McMillen, K.J. ); Do Van Luu; Lee, E.K.; Hong, S.S. )

    1996-01-01

    An integrated well log, biostratigraphic, and seismic stratigraphic study of Miocene to Recent deltaic sediments deposited in the Nam Con Son Basin offshore from southern Vietnam shows the influence of eustacy and tectonics on sequence development. Sediments consist of Oligocene non-marine rift-basin fill (Cau Formation), early to middle Miocene tide-dominated delta plain to delta front sediments (TB 1.5 to TB 2.5, Due and Thong Formations), and late Miocene to Recent marine shelf sediments (TB. 2.6 to TB 3.1 0, Mang Cau, Nam Con Son, and Bien Dong Formations). Eustacy controlled the timing of key surfaces and sand distribution in the tectonically-quiet early Miocene. Tectonic effects on middle to late Miocene sequence development consist of thick transgressive systems tracts due to basin-wide subsidence and transgression, sand distribution in the basin center, and carbonate sedimentation on isolated fault blocks within the basin. Third-order sequence boundaries (SB) are identified by spore peaks, sand stacking patterns, and channel incision. In the basin center, widespread shale beds with coal occur above sequence boundaries followed by transgressive sandstone units. These TST sandstones merge toward the basin margin where they lie on older HST sandstones. Maximum flooding surfaces (MFS) have abundant marine microfossils and mangrove pollen, a change in sand stacking pattern, and often a strong seismic reflection with downlap. Fourth-order genetic-type sequences are also interpreted. The MFS is the easiest marker to identify and correlate on well logs. Fourth-order SB occur within these genetic units but are harder to identify and correlate.

  19. Oxaliplatin and Infliximab Combination Synergizes in Inducing Colon Cancer Regression

    PubMed Central

    Li, Wenya; Xu, Jian; Zhao, Jian; Zhang, Rui

    2017-01-01

    Background Colon cancer is one of the most common malignant cancers and causes millions of deaths each year. There are still no effective treatments for colon cancer patients who are at advanced stage. Tumor necrosis factor-alpha (TNF-α) might be a good therapy target due to its widely-accepted roles in regulating multiple important biological processes, especially in promoting inflammation. Material/Methods We evaluated the expression of TNF-α in 108 human colon cancer tissue samples and 2 colon cancer cell lines (CT26 and HCT116), and analyzed its prognostic values. Further, we explored the roles and mechanism of anti-TNF-α treatment in combination with chemotherapy in vitro and in vivo. Results We found that TNF-α was highly expressed in colon cancer cell lines. The survival analysis and Cox regression analysis indicated that high TNF-α was an independent adverse prognosticator of colon cancer. In addition, anti-TNF-α treatment enhanced the effects of chemotherapy in the xenograft mouse model through inducing ADCC and CDC effects. Conclusions We conclude that TNF-α is an independent adverse prognosticator of colon cancer, and anti-TNF-α might benefit colon cancer patients. PMID:28190020

  20. Modulation of ConA-induced inflammatory ascites by histamine - short communication.

    PubMed

    Baintner, Károly

    2015-03-01

    The early phase of the ConA-induced inflammatory ascites was studied, with special reference to histamine. Concanavalin A (ConA), a cell-surface binding lectin was injected i.p. (25 mg/kg bw) to mice. After 1 h the animals were killed, the ascitic fluid collected and measured. Other agents were injected s.c., 10 min before the ConA-challenge. Exogenous histamine markedly inhibited the ConA-induced ascites. Release of endogenous vasoactive agents from the mast cells by Compound 48/80 had a similar, but slight effect. Cromolyn, a mast cell stabilizing agent, and chloropyramine, a histamine H1 receptor antagonist was ineffective. Although histamine increases endothelial permeability, it did not enhance the formation of ascitic fluid, on the contrary, it inhibited the ConA-induced ascites, presumably due to its known hypotonic effect. It is concluded that ConA-induced ascites is not mediated by mast cell histamine.

  1. Laparoscopy for inflammatory bowel disease: pros and cons.

    PubMed

    Sardinha, T C; Wexner, S D

    1998-04-01

    The role of laparoscopic surgery in the treatment of colorectal malignancies is still under investigation, although it can offer significant benefits to many patients with inflammatory bowel disease (IBD). The aim of this study was to assess the pros and cons of the laparoscopic management of IBD. Data were obtained from a review of the literature published since 1992, when the first report of laparoscopic surgery for IBD appeared in print. From 1992 to 1997 several series of laparoscopic colorectal surgery for the management of IBD have been reported. A close evaluation of these studies revealed that laparoscopy in patients with terminal ileal Crohn's disease or anal Crohn's disease in need of fecal diversion offers significant advantages compared to laparotomy, including decreased pain, length of hospitalization, and disability. An additional bonus is improved cosmesis and a reduction in symptomatic postoperative adhesions. These many benefits can be achieved without any increase in morbidity or expense. Conversely, the use of this technology for restorative proctocolectomy in patients with mucosal ulcerative colitis is associated with a longer operative time and an increased incidence of both intra- and postoperative complications compared to laparotomy. Laparoscopic colorectal surgery can thus be advantageous for treatment of terminal ileal Crohn's disease but cannot be routinely justified for the treatment of mucosal ulcerative colitis.

  2. Pros and cons of circumcision: an evidence-based overview.

    PubMed

    Friedman, B; Khoury, J; Petersiel, N; Yahalomi, T; Paul, M; Neuberger, A

    2016-09-01

    Based on three large randomized controlled trials (RCTs) conducted in Africa, it can clearly be stated that circumcision lowers the risk of infection with the human immunodeficiency virus (HIV) and some sexually transmitted infections (STIs) among males in settings of high HIV and STI endemicity. Similar effects on STI risk may exist for females, although this may result from an indirect effect of decreasing risk of infection among male partners. It is unknown whether circumcision prevents HIV acquisition in men who have sex with men (MSM), although there might be a protective effect for men who engage mainly in insertive anal intercourse. When the effects of adult circumcision on sexual function and satisfaction of men are examined, high-quality evidence strongly supports lack of harm. Whether circumcision alters sexual satisfaction of female partners is not known as fewer and smaller studies reported conflicting results. Circumcision rarely causes serious complications if practiced by trained practitioners, in a sterile setting, and with a proper follow-up. These conclusions are limited by the lack of high-quality data from areas outside of Africa. RCTs have not been conducted to assess the effects of circumcising infants or MSM. Circumcision has well-proven benefits for people residing in areas with high prevalence of STIs, including HIV, and is not unethical for those who choose to be circumcised or have their children circumcised on religious, social, or cultural grounds. For many others, a definite pro or con recommendation, based on a risk-benefit ratio, cannot be made.

  3. Pros, Cons, and Alternatives to Weight Based Cost Estimating

    NASA Technical Reports Server (NTRS)

    Joyner, Claude R.; Lauriem, Jonathan R.; Levack, Daniel H.; Zapata, Edgar

    2011-01-01

    Many cost estimating tools use weight as a major parameter in projecting the cost. This is often combined with modifying factors such as complexity, technical maturity of design, environment of operation, etc. to increase the fidelity of the estimate. For a set of conceptual designs, all meeting the same requirements, increased weight can be a major driver in increased cost. However, once a design is fixed, increased weight generally decreases cost, while decreased weight generally increases cost - and the relationship is not linear. Alternative approaches to estimating cost without using weight (except perhaps for materials costs) have been attempted to try to produce a tool usable throughout the design process - from concept studies through development. This paper will address the pros and cons of using weight based models for cost estimating, using liquid rocket engines as the example. It will then examine approaches that minimize the impct of weight based cost estimating. The Rocket Engine- Cost Model (RECM) is an attribute based model developed internally by Pratt & Whitney Rocketdyne for NASA. RECM will be presented primarily to show a successful method to use design and programmatic parameters instead of weight to estimate both design and development costs and production costs. An operations model developed by KSC, the Launch and Landing Effects Ground Operations model (LLEGO), will also be discussed.

  4. [Vagus nerve stimulation in patients with migraine].

    PubMed

    Mosqueira, Antonio J; López-Manzanares, Lydia; Canneti, Beatrice; Barroso, Alejandro; García-Navarrete, Eduardo; Valdivia, Antonio; Vivancos, José

    2013-07-16

    Introduccion. La estimulacion del nervio vago (ENV) esta aprobada para el tratamiento de la epilepsia refractaria cuando no es posible cirugia resectiva, con una eficacia bien establecida. Series publicadas sugieren un efecto beneficioso de la ENV en la migraña. Objetivos. Determinar el grado de mejoria de la cefalea en pacientes migrañosos a los que se les habia implantado una ENV para tratamiento de la epilepsia refractaria y evaluar que variables se asocian a mayor posibilidad de exito con esta medida. Pacientes y metodos. Estudio observacional y retrospectivo desde el 1 de enero de 1999 hasta el 31 de diciembre de 2010. Se contacto telefonicamente con los pacientes con ENV para epilepsia refractaria, seleccionando a aquellos que cumplian los criterios de la Sociedad Internacional de Cefaleas para la migraña. Se recogieron edad, genero, año de implantacion, edad de inicio de la epilepsia y la migraña, mejoria de crisis y de migraña, presencia de aura migrañosa y coexistencia de sindrome ansiosodepresivo. Se contacto con 94 pacientes con ENV y se selecciono a 13 pacientes migrañosos. Resultados. Tras la implantacion de la ENV, se observo una disminucion de al menos el 50% de los episodios de migraña en nueve pacientes (69%) (p = 0,004), asi como una disminucion del numero de episodios de migraña en aquellos pacientes que tambien habian reducido sus crisis epilepticas (p = 0,012). No se observaron asociaciones estadisticamente significativas en cuanto al sexo, edad, tiempo de evolucion, existencia de aura migrañosa o coexistencia de sindrome ansiosodepresivo. Conclusiones. La ENV podria resultar beneficiosa en pacientes con migraña, especialmente en casos de dificil control. Debido al tipo estudio, hay que tomar estas conclusiones con precaucion. Seran necesarios estudios clinicos prospectivos antes de llevarse a la practica clinica habitual.

  5. Meeting Report: Breath Biomarkers Networking Sessions at PittCon 2010, Orlando, Florida

    EPA Science Inventory

    The Pittsburgh Conference and Exposition, or "PittCon" (www.pittcon.org/), is one of the largest international conferences for analytical chemistry and instrumentation typically attracting about 25,000 attendees and 1,000 commercial exhibitors. PittCon began in 1950 as a small sp...

  6. Synergistic hemolysins of coagulase-negative staphylococci (CoNS).

    PubMed

    Różalska, Małgorzata; Derczyńska, Anna; Maszewska, Agnieszka

    2015-01-01

    A total of 104 coagulase negative staphylococci, belonging to S. capitis, S. hominis, S. haemolyticus and S. warneri, originating from the collection of the Department of Pharmaceutical Microbiology (ZMF), Medical University of Lodz, Poland, were tested for their synergistic hemolytic activity. 83% of strains produced δ-hemolysin, however, the percentage of positive strains of S. haemolyticus, S. warneri, S. capitis and S. hominis was different - 98%, 78%, 75% and 68%, respectively. Highly pure hemolysins were obtained from culture supernatants by protein precipitation with ammonium sulphate (0-70% of saturation) and extraction by using a mixture of organic solvents. The purity and molecular mass of hemolysins was determined by TRIS/Tricine PAGE. All CoNS hemolysins were small peptides with a molar mass of about 3.5 kDa; they possessed cytotoxic activity against the line of human foreskin fibroblasts ATCC Hs27 and lysed red cells from different mammalian species, however, the highest activity was observed when guinea pig, dog and human red blood cells were used. The cytotoxic effect on fibroblasts occurred within 30 minutes. The S. cohnii ssp. urealyticus strain was used as a control. The antimicrobial activity was examined using hemolysins of S. capitis, S. hominis, S. cohnii ssp. cohnii and S. cohnii ssp. urealyticus. Hemolysins of the two S. cohnii subspecies did not demonstrate antimicrobial activity. Cytolysins of S. capitis and S. hominis had a very narrow spectrum of action; out of 37 examined strains, the growth of only Micrococcus luteus, Corynebacterium diphtheriae and Pasteurella multocida was inhibited.

  7. Surgical animal models of neuropathic pain: Pros and Cons.

    PubMed

    Challa, Siva Reddy

    2015-03-01

    One of the biggest challenges for discovering more efficacious drugs for the control of neuropathic pain has been the diversity of chronic pain states in humans. It is now acceptable that different mechanisms contribute to normal physiologic pain, pain arising from tissue damage and pain arising from injury to the nervous system. To study pain transmission, spot novel pain targets and characterize the potential analgesic profile of new chemical entities, numerous experimental animal pain models have been developed that attempt to simulate the many human pain conditions. Among the neuropathic pain models, surgical models have paramount importance in the induction of pain states. Many surgical animal models exist, like the chronic constriction injury (CCI) to the sciatic nerve, partial sciatic nerve ligation (pSNL), spinal nerve ligation (SNL), spared nerve injury (SNI), brachial plexus avulsion (BPA), sciatic nerve transaction (SNT) and sciatic nerve trisection. Most of these models induce responses similar to those found in causalgia, a syndrome of sustained burning pain often seen in the distal extremity after partial peripheral nerve injury in humans. Researchers most commonly use these surgical models in both rats and mice during drug discovery to screen new chemical entities for efficacy in the area of neuropathic pain. However, there is scant literature that provides a comparative discussion of all these surgical models. Each surgical model has its own benefits and limitations. It is very difficult for a researcher to choose a suitable surgical animal model to suit their experimental set-up. Therefore, particular attention has been given in this review to comparatively provide the pros and cons of each model of surgically induced neuropathic pain.

  8. Self-Exfoliated Guanidinium-Based Ionic Covalent Organic Nanosheets (iCONs).

    PubMed

    Mitra, Shouvik; Kandambeth, Sharath; Biswal, Bishnu P; Khayum M, Abdul; Choudhury, Chandan K; Mehta, Mihir; Kaur, Gagandeep; Banerjee, Subhrashis; Prabhune, Asmita; Verma, Sandeep; Roy, Sudip; Kharul, Ulhas K; Banerjee, Rahul

    2016-03-02

    Covalent organic nanosheets (CONs) have emerged as functional two-dimensional materials for versatile applications. Although π-π stacking between layers, hydrolytic instability, possible restacking prevents their exfoliation on to few thin layered CONs from crystalline porous polymers. We anticipated rational designing of a structure by intrinsic ionic linker could be the solution to produce self-exfoliated CONs without external stimuli. In an attempt to address this issue, we have synthesized three self-exfoliated guanidinium halide based ionic covalent organic nanosheets (iCONs) with antimicrobial property. Self-exfoliation phenomenon has been supported by molecular dynamics (MD) simulation as well. Intrinsic ionic guanidinium unit plays the pivotal role for both self-exfoliation and antibacterial property against both Gram-positive and Gram-negative bacteria. Using such iCONs, we have devised a mixed matrix membrane which could be useful for antimicrobial coatings with plausible medical benefits.

  9. [The use of the ketogenic diet as treatment for refractory epilepsy in the paediatric age].

    PubMed

    Pablos-Sánchez, Tamara; Oliveros-Leal, Liliana; Núñez-Enamorado, Noemí; Camacho-Salas, Ana; Moreno-Villares, José Manuel; Simón-De las Heras, Rogelio

    2014-01-16

    Introduccion. El 23-25% de los niños epilepticos son refractarios a farmacos antiepilepticos. El interes por la dieta cetogenica como tratamiento en estos pacientes no candidatos a otras opciones terapeuticas ha resurgido ultimamente. Objetivo. Valorar la eficacia y seguridad del tratamiento con dieta cetogenica en un importante numero de pacientes pediatricos con epilepsia refractaria en nuestro centro y determinar si los resultados obtenidos corroboran otros de publicacion reciente. Pacientes y metodos. Se revisaron retrospectivamente las historias clinicas de 41 niños con epilepsia refractaria que fueron tratados con dieta cetogenica entre 1998 y 2011, la mayoria con dieta tipo Radcliffe II. La mediana de edad al inicio de la dieta fue de 3,92 años. Resultados. A los seis meses del inicio de la dieta se redujeron las crisis en al menos un 50% en un 36,84% de la muestra (el 10,53% de los niños alcanzo mas de un 90% de reduccion y un 5,26% quedo sin crisis). Aproximadamente un 50% por grupo de edad en los mas pequeños respondio de manera positiva. Un 58,54% de los pacientes presento algun efecto secundario, tolerable y transitorio, principalmente elevacion de los niveles de colesterol y estreñimiento, sin observarse variacion en los parametros antropometricos. Conclusiones. La dieta cetogenica supone una buena alternativa terapeutica en los casos de epilepsia refractaria en la edad pediatrica, con mayor probabilidad de beneficio cuanto menor sea la edad del niño al inicio de la dieta. En general, es bien tolerada. Son de gran importancia en estos pacientes las revisiones periodicas con control nutricional.

  10. Antibiotic susceptibility of coagulase-negative staphylococci (CoNS): emergence of teicoplanin-non-susceptible CoNS strains with inducible resistance to vancomycin.

    PubMed

    Ma, Xiao Xue; Wang, En Hua; Liu, Yong; Luo, En Jie

    2011-11-01

    Coagulase-negative staphylococci (CoNS) have become increasingly recognized as important agents of nosocomial infection. One of the characteristics of CoNS is their resistance to multiple antimicrobial agents commonly used for the treatment of staphylococcal infections. CoNS strains (n = 745) isolated from a university teaching hospital in China between 2004 and 2009 were tested for antibiotic resistance. The antibiotics were placed into three categories based on resistance levels of the CoNS strains to these antibiotics: high resistance (resistance rate >70 %), including penicillin G, oxacillin and erythromycin; medium resistance (resistance rate between 30 and 70 %), including tetracycline, clindamycin, ciprofloxacin, trimethoprim/sulfamethoxazole and chloramphenicol; and low resistance (resistance rate <30 %), including rifampicin, ceftizoxime and gentamicin. We also found that the prevalence of strains non-susceptible to teicoplanin increased from 4.5 to 6.7 % between 2008 and 2009. A one-step vancomycin agar selection experiment and subsequent population analysis revealed potentially vancomycin-resistant subpopulations that have been selected from the teicoplanin-non-susceptible strains. Vigilant surveillance of nosocomial isolates of CoNS is needed to determine their resistance to glycopeptides.

  11. Analyses of muscular dystrophy and Con A deficiency traits in testcross progeny of chickens.

    PubMed

    Kline, K; Sanders, B G

    1984-01-01

    Hereditary muscular dystrophic chickens of the Storrs strain possess two genetic disorders, muscular dystrophy (MD) and a deficient concanavalin A (Con A), a T-cell mitogen, mediated splenic lymphocyte blastogenic response. A possible amelioration of the MD phenotype in MD chickens expressing normal Con A was postulated on the basis of progeny segregating for these two traits in F2 genetic analyses. To test this possibility, testcross progeny were examined for segregation of MD and Con A deficiency traits, and for the degree of muscle destruction and Con A deficiency. The data show both traits to be inherited independently as autosomal recessive traits, and do not support any phenotypic modifications occurring in chickens expressing MD with normal Con A. In the testcross progeny, the Con A deficiency disorder is equally deficient in normal and MD progeny, and the degree of muscle destruction as measured by serum creatine phosphokinase levels is equally great in MD chickens with or without the Con A deficiency trait. The reduced numbers of MD chickens in the testcross progeny can be accounted for by chance and probably reflect losses during in ovo development.

  12. Targeted Drug Delivery in Covalent Organic Nanosheets (CONs) via Sequential Postsynthetic Modification.

    PubMed

    Mitra, Shouvik; Sasmal, Himadri Sekhar; Kundu, Tanay; Kandambeth, Sharath; Illath, Kavya; Díaz Díaz, David; Banerjee, Rahul

    2017-03-29

    Covalent organic nanosheets (CONs) have emerged as a new class of functional two-dimensional (2D) porous organic polymeric materials with a high accessible surface, diverse functionality, and chemical stability. They could become versatile candidates for targeted drug delivery. Despite their many advantages, there are limitations to their use for target specific drug delivery. We anticipated that these drawbacks could be overturned by judicious postsynthetic modification steps to use CONs for targeted drug delivery. The postsynthetic modification would not only produce the desired functionality, it would also help to exfoliate to CONs as well. In order to meet this requirement, we have developed a facile, salt-mediated synthesis of covalent organic frameworks (COFs) in the presence of p-toluenesulfonic acid (PTSA). The COFs were subjected to sequential postsynthetic modifications to yield functionalized targeted CONs for targeted delivery of 5-fluorouracil to breast cancer cells. This postsynthetic modification resulted in simultaneous chemical delamination and functionalization to targeted CONs. Targeted CONs showed sustained release of the drug to the cancer cells through receptor-mediated endocytosis, which led to cancer cell death via apoptosis. Considering the easy and facile COF synthesis, functionality based postsynthetic modifications, and chemical delamination to CONs for potential advantageous targeted drug delivery, this process can have a significant impact in biomedical applications.

  13. Abundancias químicas de estrellas de Mercurio-Manganeso obtenidas con espectros EBASIM

    NASA Astrophysics Data System (ADS)

    Pintado, O. I.; Adelman, S. J.

    Se determinan las abundancias químicas de estrellas de HgMn usando espectros obtenidos con EBASIM en CASLEO en un rango de longitud de onda comprendido entre los 400 y 890 nm. Los valores iniciales de temperatura efectiva y gravedad superficial se calculan con la fotometría uvbyβ. Las abundancias se calculan usando WIDTH9 y SYNTHE. Los resultados se comparan análisis realizados por los autores usando espectros obtenidos con el espectrógrado REOSC del CASLEO, el espectrógrafo echelle del Telescopio Anglo-Australiano y el espectrógrafo Coudé del Dominion Astrophysical Observatory.

  14. [Predictive factors of the response to treatment with onabotulinumtoxinA in refractory migraine].

    PubMed

    Pagola, Inmaculada; Esteve-Belloch, Patricia; Palma, José Alberto; Luquin, M Rosario; Riverol, Mario; Martinez-Vila, Eduardo; Irimia, Pablo

    2014-03-16

    Objetivo. Identificar las caracteristicas clinicas que predicen una respuesta favorable al tratamiento con onabotulinumtoxina A (OnabotA) en pacientes con migraña refractaria. Pacientes y metodos. Estudio retrospectivo de pacientes con migraña refractaria que recibieron al menos dos infiltraciones de OnabotA entre los años 2008 y 2012. Los pacientes fueron divididos en respondedores y no respondedores a OnabotA y se compararon entre ambos grupos, y de forma retrospectiva, una serie de caracteristicas clinicas consideradas predictoras de respuesta en estudios previos: localizacion unilateral de la cefalea, presencia de tension muscular pericraneal, tipo de dolor (implosivo, explosivo u ocular), tiempo de evolucion de la migraña (menor o mayor de 10 años) y abuso de medicacion analgesica. Resultados. Se incluyeron 39 pacientes (35 mujeres) con una edad media de 46 años. En 18 pacientes (46,2%) se observo una reduccion mayor del 50% en el numero de dias de cefalea/mes (pacientes respondedores). Al analizar las diferentes caracteristicas de la migraña, se observo que todas ellas fueron igualmente prevalentes en los pacientes respondedores y en los no respondedores (p > 0,05): localizacion unilateral (66,7% frente a 66,6%, respectivamente), dolor implosivo (27,8% frente a 38,1%), presencia de tension muscular pericraneal (33,3% frente a 38,1%), tiempo de evolucion de la migraña mayor de 10 años (77,8% frente a 69,2%) y presencia de abuso de medicacion analgesica (50% frente a 81%). Conclusion. En esta serie de pacientes no se ha identificado ningun rasgo clinico que permita predecir en pacientes con migraña refractaria una respuesta favorable al tratamiento con OnabotA.

  15. The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM)

    Cancer.gov

    The International Consortium for the Investigation of Renal Malignancies (I-ConFIRM) was formed to promote international, multidisciplinary collaborations to advance our understanding of the etiology and outcomes of kidney cancer.

  16. Characterization of the effector cells in Con A-induced cytotoxicity against HEp 2 tumour targets.

    PubMed

    Pócsik, E; González-Cabello, R; Benedek, K; Perl, A; Láng, I; Gergely, P

    1983-01-01

    Con A-induced cytotoxic activity of human lymphocyte subpopulations obtained by cell fractionation procedures was studied in a test system using human epipharynx carcinoma cells (HEp 2) as targets. Only T lymphocytes were cytotoxic, non-T cells exerted no cytotoxic activity, but enhanced the adherence of the tumour cells. Tnon-G lymphocytes (Fc-receptor negative T cells) were more active than TG cells (Fc-receptor-positive T cells) in mediating the Con A-induced cytotoxic reaction.

  17. SLUDGE PARTICLE SEPAPATION EFFICIENCIES DURING SETTLER TANK RETRIEVAL INTO SCS-CON-230

    SciTech Connect

    DEARING JI; EPSTEIN M; PLYS MG

    2009-07-16

    The purpose of this document is to release, into the Hanford Document Control System, FA1/0991, Sludge Particle Separation Efficiencies for the Rectangular SCS-CON-230 Container, by M. Epstein and M. G. Plys, Fauske & Associates, LLC, June 2009. The Sludge Treatment Project (STP) will retrieve sludge from the 105-K West Integrated Water Treatment System (IWTS) Settler Tanks and transfer it to container SCS-CON-230 using the Settler Tank Retrieval System (STRS). The sludge will enter the container through two distributors. The container will have a filtration system that is designed to minimize the overflow of sludge fines from the container to the basin. FAI/09-91 was performed to quantify the effect of the STRS on sludge distribution inside of and overflow out of SCS-CON-230. Selected results of the analysis and a system description are discussed. The principal result of the analysis is that the STRS filtration system reduces the overflow of sludge from SCS-CON-230 to the basin by roughly a factor of 10. Some turbidity can be expected in the center bay where the container is located. The exact amount of overflow and subsequent turbidity is dependent on the density of the sludge (which will vary with location in the Settler Tanks) and the thermal gradient between the SCS-CON-230 and the basin. Attachment A presents the full analytical results. These results are applicable specifically to SCS-CON-230 and the STRS filtration system's expected operating duty cycles.

  18. Pros and cons: prospective predictors of marijuana use on a college campus.

    PubMed

    Elliott, Jennifer C; Carey, Kate B

    2013-03-01

    Marijuana use on college campuses is prevalent and associated with high rates of abuse and dependence. The Marijuana Decisional Balance (MDB) scales measure perceived pros and cons toward marijuana use. Evidence supports reliability and concurrent validity of these scales, but the predictive validity has not yet been assessed. The current study evaluated the prospective predictive validity of pros and cons scales for marijuana use, as well as explored predictive validity for marijuana problem indicators. Secondary analyses included test-retest reliability and internal consistency, to provide additional evidence of psychometric properties. A total of 149 college students (57% recent marijuana users, 77% lifetime users) participated in a baseline survey, then completed a second survey one month later. All provided data on marijuana pros and cons, as well as use status in the past month. Users at each time point reported on use frequency, problems, and disorder symptoms. In the month between assessments, 55% of the students used marijuana. Both pros and cons subscales prospectively predicted use status in the subsequent month, but not use frequency. Pros prospectively predicted marijuana problems and dependence symptoms at follow-up, and remained a significant predictor of later dependence symptoms even after controlling for baseline dependence symptoms. In contrast, pros only marginally predicted abuse. Cons did not predict problems, abuse, or dependence symptoms. Pros and cons showed strong test-retest reliability (rs = 0.80-0.85) and internal consistency (alphas = 0.92-0.95). In a college sample, pros and cons of marijuana use demonstrated stability over one month, and prospectively predicted use. Pros may also have utility in predicting problems and dependence potential on college campuses.

  19. ConA-based glucose sensing using the long-lifetime azadioxatriangulenium fluorophore

    NASA Astrophysics Data System (ADS)

    Cummins, Brian; Simpson, Jonathan; Gryczynski, Zygmunt; Sørensen, Thomas Just; Laursen, Bo W.; Graham, Duncan; Birch, David; Coté, Gerard

    2014-02-01

    Fluorescent glucose sensing technologies have been identified as possible alternatives to current continuous glucose monitoring approaches. We have recently introduced a new, smart fluorescent ligand to overcome the traditional problems of ConA-based glucose sensors. For this assay to be translated into a continuous glucose monitoring device where both components are free in solution, the molecular weight of the smart fluorescent ligand must be increased. We have identified ovalbumin as a naturally-occurring glycoprotein that could serve as the core-component of a 2nd generation smart fluorescent ligand. It has a single asparagine residue that is capable of displaying an N-linked glycan and a similar isoelectric point to ConA. Thus, binding between ConA and ovalbumin can potentially be monovalent and sugar specific. This work is the preliminary implementation of fluorescently-labeled ovalbumin in the ConA-based assay. We conjugate the red-emitting, long-lifetime azadioxatriangulenium (ADOTA+) dye to ovalbumin, as ADOTA have many advantageous properties to track the equilibrium binding of the assay. The ADOTA-labeled ovalbumin is paired with Alexa Fluor 647-labeled ConA to create a Förster Resonance Energy Transfer (FRET) assay that is glucose dependent. The assay responds across the physiologically relevant glucose range (0-500 mg/dL) with increasing intensity from the ADOTA-ovalbumin, showing that the strategy may allow for the translation of the smart fluorescent ligand concept into a continuous glucose monitoring device.

  20. ConTour: Data-Driven Exploration of Multi-Relational Datasets for Drug Discovery.

    PubMed

    Partl, Christian; Lex, Alexander; Streit, Marc; Strobelt, Hendrik; Wassermann, Anne-Mai; Pfister, Hanspeter; Schmalstieg, Dieter

    2014-12-01

    Large scale data analysis is nowadays a crucial part of drug discovery. Biologists and chemists need to quickly explore and evaluate potentially effective yet safe compounds based on many datasets that are in relationship with each other. However, there is a lack of tools that support them in these processes. To remedy this, we developed ConTour, an interactive visual analytics technique that enables the exploration of these complex, multi-relational datasets. At its core ConTour lists all items of each dataset in a column. Relationships between the columns are revealed through interaction: selecting one or multiple items in one column highlights and re-sorts the items in other columns. Filters based on relationships enable drilling down into the large data space. To identify interesting items in the first place, ConTour employs advanced sorting strategies, including strategies based on connectivity strength and uniqueness, as well as sorting based on item attributes. ConTour also introduces interactive nesting of columns, a powerful method to show the related items of a child column for each item in the parent column. Within the columns, ConTour shows rich attribute data about the items as well as information about the connection strengths to other datasets. Finally, ConTour provides a number of detail views, which can show items from multiple datasets and their associated data at the same time. We demonstrate the utility of our system in case studies conducted with a team of chemical biologists, who investigate the effects of chemical compounds on cells and need to understand the underlying mechanisms.

  1. Soluciones analiticas AL problema de jets con velocidad de eyeccion variable EN EL tiempo.

    NASA Astrophysics Data System (ADS)

    Canto, J.; Raga, A. C.; D'Alessio, P.

    1998-11-01

    Se presenta un nuevo metodo que permite resolver de manera exacta y analitica las ecuaciones que describen un jet hipersonico con velocidad de eyeccion variable en el tiempo. El metodo se basa en consideraciones sencillas de conservacion de momento para las superficies de trabajo que se forman en el interior del jet. Como ejemplo, se presentan soluciones para jets con variacion sinusoidal en la velocidad de eyeccion, y tambien para el caso de un incremento lineal en el tiempo. Estas soluciones analiticas tienen una clara aplicacion en la interpretacion de las observaciones de jets asociados a objetos Herbig-Haro.

  2. Silence, Metaperformance, and Communication in Pedro Almodóvar's "Hable con ella"

    ERIC Educational Resources Information Center

    Fellie, Maria C.

    2016-01-01

    Many scenes in Pedro Almodóvar's "Hable con ella" (2002) include shots of metaperformances such as silent films, dances, television shows, concerts, and bullfights. Spectators often observe passive characters who are in turn observing. By presenting these performances within cinematic performance, Almodóvar highlights our role as viewers…

  3. Non Invasive Biomedical Analysis - Breath Networking Session at PittCon 2011, Atlanta, Georgia

    EPA Science Inventory

    This was the second year that our breath colleagues organized a networking session at the Pittsburgh Conference and Exposition or ''PittCon'' (http://www.pincon.org/).This time it was called "Non-invasive Biomedical Analysis" to broaden the scope a bit, but the primary focus rema...

  4. "Con todo mi corazón": Mentoring Latinas in Educational Leadership Doctoral Programs

    ERIC Educational Resources Information Center

    Rodríguez, Mariela A.

    2016-01-01

    Personal narrative essays were used to analyze the experiences of four Latina doctoral students who completed their first year in an educational leadership doctoral program in a Hispanic-Serving Institution (HSI) in the southwestern U.S. Four themes emerged from their "testimonios" 1) "Con todo el corazón"; 2) "Somos como…

  5. End-User Use of Data Base Query Language: Pros and Cons.

    ERIC Educational Resources Information Center

    Nicholes, Walter

    1988-01-01

    Man-machine interface, the concept of a computer "query," a review of database technology, and a description of the use of query languages at Brigham Young University are discussed. The pros and cons of end-user use of database query languages are explored. (Author/MLW)

  6. Impact of the ConRed program on different cyberbulling roles.

    PubMed

    Del Rey, Rosario; Casas, José A; Ortega, Rosario

    2016-01-01

    This article presents results from an evaluation of the ConRed cyberbullying intervention program. The program's impacts were separately determined for the different roles within cyberbullying that students can take, i.e., cyber-victims, cyber-bullies, cyber-bully/victims, and bystanders. The ConRed program is a theory-driven program designed to prevent cyberbullying and improve cyberbullying coping skills. It involves students, teachers, and families. During a 3-month period, external experts conducted eight training sessions with students, two with teachers and one with families. ConRed was evaluated through a quasi-experimental design, in which students from three secondary schools were separated into experimental and control groups. The sample comprised 875 students, aged between 11 and 19 years. More students (n = 586) were allocated to the experimental groups at the specific insistence of the management of all schools; the remainder (n = 289) formed the control. Repeated measures MANOVA showed that cyber victims, cyber aggressors and cyberbully/victims reduced their involvement in cyberbullying. Moreover, cyber-victims and bystanders adjusted their perceptions about their control of personal information on the Internet, and cyber aggressors and bystanders reduced their Internet dependence. The ConRed program had stronger effects on male participants, especially in heightening their affective empathy.

  7. Are You Ready to Go Digital?: The Pros and Cons of Electronic Portfolio Development

    ERIC Educational Resources Information Center

    Heath, Marilyn

    2005-01-01

    There is an increasing need for educators to have professional portfolios, which are considered to be authentic tools for evaluating the knowledge, skill, beliefs and attitudes of prospective educators. Electronic portfolios are gaining in popularity and their relative pros and cons are examined.

  8. Mandated Mental Health Insurance: A Complex Case of Pros and Cons. Human Resources Series.

    ERIC Educational Resources Information Center

    Paterson, Andrea

    1986-01-01

    The pros and cons of state laws mandating mental health insurance are discussed in this report. The history of a 1985 Supreme Court case which held that states could mandate mental health benefits introduces the report. In an overview of the issue, the long-standing argument between the insurance industry and the mental health establishment is…

  9. ConMap: Investigating New Computer-Based Approaches to Assessing Conceptual Knowledge Structure in Physics.

    ERIC Educational Resources Information Center

    Beatty, Ian D.

    There is a growing consensus among educational researchers that traditional problem-based assessments are not effective tools for diagnosing a student's knowledge state and for guiding pedagogical intervention, and that new tools grounded in the results of cognitive science research are needed. The ConMap ("Conceptual Mapping") project, described…

  10. The Con Edison Emergency Child Care Plan for Management Employees: Summary Plan Description.

    ERIC Educational Resources Information Center

    Consolidated Edison Co., Brooklyn, NY.

    This summary plan description offers guidelines for participation in a pilot program that provides short-term emergency care for children of Con Edison managers who are under 13 years old. The plan offers professional, in-home child care that can be used when usual arrangements have collapsed. The summary plan description addresses the following…

  11. A National Look at Postmodernism's Pros and Cons in Educational Leadership

    ERIC Educational Resources Information Center

    Townsell, Rhodena

    2007-01-01

    The purpose of this article is to take a look at the pros and cons of postmodernism. It is imperative for administrators to closely examine educational theories and practices prior to instituting changes. The ability to read and digest challenging material keeps one informed and prepared to lead effectively. This paper will list the pros and cons…

  12. Optimizing Electrospray Interfaces Using Slowly Diverging Conical Duct (ConDuct) Electrodes

    NASA Astrophysics Data System (ADS)

    Krutchinsky, Andrew N.; Padovan, Júlio C.; Cohen, Herbert; Chait, Brian T.

    2015-04-01

    We demonstrate that the efficiency of ion transmission from atmosphere to vacuum through stainless steel electrodes that contain slowly divergent conical duct (ConDuct) channels can be close to 100%. Here, we explore the properties of 2.5-cm-long electrodes with angles of divergence of 0°, 1°, 2°, 3°, 5°, 8°, 13°, and 21°, respectively. The ion transmission efficiency was observed to jump from 10-20% for the 0° (straight) channels to 90-95% for channels with an angle of divergence as small as 1°. Furthermore, the 2-3° ConDuct electrodes produced extraordinarily low divergence ion beams that propagated in a laser-like fashion over long distances in vacuum. To take advantage of these newly discovered properties, we constructed a novel atmosphere-to-vacuum ion interface utilizing a 2° ConDuct as an inlet electrode and compared its ion transmission efficiency with that of the interface used in the commercial (Thermo Fisher Scientific, San Jose, CA, USA) Velos Orbitrap and Q Exactive mass spectrometers. We observed that the ConDuct interface transmitted up to 17 times more ions than the commercial reference interface and also yielded improved signal-to-noise mass spectra of peptides. We infer from these results that the performance of many current atmosphere-to-vacuum interfaces utilizing metal capillaries can be substantially improved by replacing them with 1° or 2° metal ConDuct electrodes, which should preserve the convenience of supplying ion desolvation energy by heating the electrode while greatly increasing the efficiency of ion transmission into the mass spectrometer.

  13. Optimizing Electrospray Interfaces Using Slowly Diverging Conical Duct (ConDuct) Electrodes

    PubMed Central

    Krutchinsky, Andrew N.; Padovan, Júlio C.; Cohen, Herbert; Chait, Brian T.

    2015-01-01

    We demonstrate that the efficiency of ion transmission from atmosphere to vacuum through stainless steel electrodes that contain slowly divergent conical duct (ConDuct) channels can be close to 100%. Here, we explore the properties of 2.5 cm long electrodes with angles of divergence of 0°, 1°, 2°, 3°, 5°, 8°, 13°, and 21°, respectively. The ion transmission efficiency was observed to jump from 10–20% for the 0° (straight) channels to 90–95% for channels with an angle of divergence as small as 1°. Furthermore, the 2–3° ConDuct electrodes produced extraordinarily low divergence ion beams that propagated in a laser-like fashion over long distances in vacuum. To take advantage of these newly discovered properties, we constructed a novel atmosphere-to-vacuum ion interface utilizing a 2° ConDuct as an inlet electrode and compared its ion transmission efficiency with that of the interface used in the commercial (Thermo) Velos Orbitrap and Q Exactive mass spectrometers. We observed that the ConDuct interface transmitted up to 17 times more ions than the commercial reference interface and also yielded improved signal-to-noise mass spectra of peptides. We infer from these results that the performance of many current atmosphere-tovacuum interfaces utilizing metal capillaries can be substantially improved by replacing them with 1° or 2° metal ConDuct electrodes, which should preserve the convenience of supplying ion desolvation energy by heating the electrode while greatly increasing the efficiency of ion transmission into the mass spectrometer. PMID:25667060

  14. ConMap - a new spatial data mining framework for terrain based digital soil mapping

    NASA Astrophysics Data System (ADS)

    Behrens, T.; Schmidt, K.; Scholten, T.

    2009-04-01

    In this talk, we present a new digital terrain analysis framework for digital soil mapping based on spatial data mining, referred to as the contextual elevation mapping (ConMap). Aiming at integrating different scales, which can be important at landscape scale level due to interrelations of topo- and climofunctions, it comprises local surface function approximations in terms of standard local terrain attributes as well as the incorporation of geomorphic arrangements within larger neighborhoods. In contrast to common digital terrain analysis of deriving multiple terrain attributes, ConMap is based on elevation differences from the center pixel to each pixel in a local neighborhood. These differences are then used as predictors in machine learning approaches such as Random Forests. Thus, it is not necessary to choose a specific set of terrain attributes. Additionally, possibly unknown surface functions can be taken into account, as well as larger geomorphic settings. We applied and validated the framework by predicting topsoil silt content for an area of 1150 km2 in Rhineland-Palatinate and Hesse, Germany, based on 342 samples, a 20 m resolution DEM, and neighborhood sizes up to 12 km. Cross-validation R2 values increase from 0.15 for standard digital terrain analysis to 0.61 using ConMap. This effect is due to a spatial trend in the data. As ConMap is able to map this trend and as it is based on the pedological concept of integrating scales it can be seen as a new entry to spatial prediction approaches such as Kriging or Geographically Weighted Regression. We conclude that ConMap shows a great potential for future digital soil mapping studies.

  15. Air Traffic Management Technology Demonstration-1 Concept of Operations (ATD-1 ConOps)

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Johnson, William C.; Swenson, Harry; Robinson, John E.; Prevot, Thomas; Callantine, Todd; Scardina, John; Greene, Michael

    2012-01-01

    The operational goal of the ATD-1 ConOps is to enable aircraft, using their onboard FMS capabilities, to fly Optimized Profile Descents (OPDs) from cruise to the runway threshold at a high-density airport, at a high throughput rate, using primarily speed control to maintain in-trail separation and the arrival schedule. The three technologies in the ATD-1 ConOps achieve this by calculating a precise arrival schedule, using controller decision support tools to provide terminal controllers with speeds for aircraft to fly to meet times at a particular meter points, and onboard software providing flight crews with speeds for the aircraft to fly to achieve a particular spacing behind preceding aircraft.

  16. BeadCons: detection of nucleic acid sequences by flow cytometry.

    PubMed

    Horejsh, Douglas; Martini, Federico; Capobianchi, Maria Rosaria

    2005-11-01

    Molecular beacons are single-stranded nucleic acid structures with a terminal fluorophore and a distal, terminal quencher. These molecules are typically used in real-time PCR assays, but have also been conjugated with solid matrices. This unit describes protocols related to molecular beacon-conjugated beads (BeadCons), whose specific hybridization with complementary target sequences can be resolved by cytometry. Assay sensitivity is achieved through the concentration of fluorescence signal on discrete particles. By using molecular beacons with different fluorophores and microspheres of different sizes, it is possible to construct a fluid array system with each bead corresponding to a specific target nucleic acid. Methods are presented for the design, construction, and use of BeadCons for the specific, multiplexed detection of unlabeled nucleic acids in solution. The use of bead-based detection methods will likely lead to the design of new multiplex molecular diagnostic tools.

  17. NASA KSC/AFRL Reusable Booster System (RBS) Concept of Operations (ConOps)

    NASA Technical Reports Server (NTRS)

    Zeno, Dnany; Mosteller, Ted; McCleskey, Carey; Jhnson, Robert; Hopkins, Jason; Miller, Thomas

    2010-01-01

    This slide presentation reviews the study and findings of the study on the Concept of Operations (ConOps) for Reusable Booster System (RBS) centering on rapid turnaround and launch of a two-stage partially reusable payload delivery system (i.e., 8 hours between launches). The study was to develop rapid ground processing (aircraft like concepts) and identify areas for follow-on study, technology needs, and proof-of-concept demonstrations.

  18. The pros and cons of endovascular and open surgical treatments for patients with acute limb ischemia.

    PubMed

    Branco, B C; Montero-Baker, M F; Mills, J L

    2015-06-01

    The present review addresses the pros and cons of the current, wide variety of therapeutic options available for the treatment of acute limb ischemia (ALI). Despite five prospective randomized controlled trials comparing catheter directed thrombolysis and open surgical revascularization, no single treatment strategy can yet be considered optimal for patients with ALI. This report includes 20 years of published data to evaluate the efficacy and safety profile of thrombolytic agents and adjunctive endovascular techniques when compared to open surgical revascularization.

  19. Precisión de las velocidades radiales obtenidas con el REOSC

    NASA Astrophysics Data System (ADS)

    González, J. F.; Lapasset, E.

    Complementando una línea de trabajo iniciada con anterioridad discutimos la estabilidad del espectrógrafo REOSC de CASLEO en DC para la medición de velocidades radiales en base al análisis de observaciones realizadas en enero y abril de 1997. En esas oportunidades obtuvimos 26 espectros de estrellas patrones y 27 espectros de 3 estrellas usadas como estrellas de referencia en nuestro programa de cúmulos abiertos. Además tomamos 26 espectros de crepúsculo con el telescopio en posiciones cubriendo el rango H=-4,+4 y δ =-90,+30. Mediante correlaciones cruzadas derivamos la velocidad de 19 órdenes en cada uno de estos espectros. En base a un análisis estadístico de los datos obtenidos discutimos la contribución de los distintos factores que afectan a la dispersión de lectura observada. En particular, la flexión del instrumento no introduciría errores significativos cuando se observa con masas de aire menores que 2.0. La dispersión de los valores de velocidad medidos para espectros de alta relación S/N de una misma estrella resultó del orden de 0.5 km/s. La comparación con los valores de velocidad publicados por distintos autores para las estrellas patrones no permite distinguir ninguna diferencia sistemática apreciable de las velocidades de CASLEO, siendo la media cuadrática de los residuos del orden de 1.0 km/s.

  20. Simulaciones numéricas hidrodinámicas con formación estelar

    NASA Astrophysics Data System (ADS)

    Volpe, M. G.; Merchan, M.; García Lambas, D.

    Se realizan simulaciones numéricas cosmológicas utilizando el código HYDRA modificado para incluir formación estelar. A partir de éstas, se estiman diferentes parámetros observacionales como la relación Tully- Fisher, función de luminosidad y la tasa de formación estelar en función del redshift. Estos resultados son comparados con datos observacionales de diferentes autores.

  1. Extreme lateral lumbar interbody fusion: Do the cons outweigh the pros?

    PubMed Central

    Epstein, Nancy E.

    2016-01-01

    Background: Major factors prompted the development of minimally invasive (MIS) extreme lateral interbody fusion (XLIF; NuVasive Inc., San Diego, CA, USE) for the thoracic/lumbar spine. These include providing interbody stabilization and indirect neural decompression while avoiding major visceral/vessel injury as seen with anterior lumbar interbody fusion (ALIF), and to avert trauma to paraspinal muscles/facet joints found with transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), and posterior-lateral fusion techniques (PLF). Although anticipated pros of MIS XLIF included reduced blood loss, operative time, and length of stay (LOS), they also included, higher fusion, and lower infection rates. Unanticipated cons, however, included increased morbidity/mortality rates. Methods: We assessed the pros and cons (e.g., risks, complications, comparable value/superiority/inferiority, morbidity/mortality) of MIS XLIF vs. ALIF, TLIF, PLIF, and PLF. Results: Pros of XLIF included various biomechanical and technical surgical advantages, along with multiple cons vs. ALIF, TLIF, PLIF, and PLF. For example, XLIF correlated with a considerably higher frequency of major neurological deficits vs. other constructs; plexus injuries 13.28%, sensory deficits 0–75% (permanent in 62.5%), motor deficits 0.7–33.6%, and anterior thigh pain 12.5–25%. XLIF also disproportionately contributed to other major morbidity/mortality; sympathectomy, major vascular injuries (some life-ending others life-threatening), bowel perforations, and seromas. Furthermore, multiple studies documented no superiority, and the potential inferiority of XLIF vs. ALIF, TLIF, PLIF, and PLF. Conclusion: Reviewing the pros of XLIF (e.g. radiographic, technical, biomechanical) vs. the cons (inferiority, increased morbidity/mortality) vs. ALIF, TLIF, PLIF, and PLF, we question whether XLIF should remain part of the lumbar spinal surgical armamentarium. PMID:27843688

  2. Mound-ACT*DE*CON{sup SM} feasibility study. Phase 2: Final report

    SciTech Connect

    1994-12-01

    A portion of the abandoned Miami-Erie Canal paralleling the Greater Miami River receives the runoff and storm-water discharge from Mound Laboratory. In 1969, a low-level plutonium leak contaminated sediment as far away as 1.5 mi from the Mound site along the old canal system. An estimated one million cubic feet of sediment requires remediation. The technology being evaluated for the remediation of the low-level plutonium-238 contamination of the sediment involves two processes: washing the sediments with ACT*DE*CON{sup SM} solution to dissolve the contaminant, followed by extraction of the solution and processing with the MAG*SEP{sup SM} process to concentrate the contaminant and allow reuse of the ACT*DE*CON{sup SM} solution. The processes are being optimized for pilot-scale and field demonstration. Phase 2 of the project primarily involved identification at the laboratory scale of the optimal ACT*DE*CON{sup SM} formulation, identification of the ion-exchanger and MAG*SEP{sup SM} particles, verification of the plutonium mobility in the treated soil, and evaluation of other process parameters according to a series of tasks.

  3. ConA and UEA-I lectin histochemistry of parotid gland mucoepidermoid carcinoma.

    PubMed

    Sobral, Ana Paula V; Rego, Moacyr J B M; Cavalacanti, Carmelita L B; Carvalho, Luiz B; Beltrão, Eduardo I C

    2010-03-01

    Mucoepidermoid carcinoma (MEC) corresponds to 5-12% of all salivary gland tumours, and is classified as low, intermediate or high grade. Traditionally, immunohistochemistry was considered as the complementary tool for diagnosis of salivary gland neoplasia. Lectin histochemistry has also been increasingly used in recent years. In this work, lectins were used as histochemical markers for normal and transformed parotid glands. Biopsy specimens of 15 cases diagnosed as MEC (low, intermediate and high grade) of the parotid gland were trypsin- and methanol-H(2)O(2)-treated and incubated with horseradish peroxidase (HRP)-conjugated lectins, Concanavalin A (Con A-HRP) and Ulex europeus I (UEA-I-HRP). Con A stained the neoplasic cells of MEC (all grades). In high and intermediate cases, ductal cells were weakly stained by Con A. UEA-I weakly stained normal cells of the excretory duct and neoplasic cells in high grade. Neoplasic cells in intermediate grade were moderately stained and in low grade, the cell membrane was intensely stained with UEA-I. Stroma presented a direct relation between malignancy and staining intensity for UEA-I. The results indicated that lectin histochemistry distinguished the cell biology among histological grades of MEC.

  4. ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules.

    PubMed

    Ashkenazy, Haim; Abadi, Shiran; Martz, Eric; Chay, Ofer; Mayrose, Itay; Pupko, Tal; Ben-Tal, Nir

    2016-07-08

    The degree of evolutionary conservation of an amino acid in a protein or a nucleic acid in DNA/RNA reflects a balance between its natural tendency to mutate and the overall need to retain the structural integrity and function of the macromolecule. The ConSurf web server (http://consurf.tau.ac.il), established over 15 years ago, analyses the evolutionary pattern of the amino/nucleic acids of the macromolecule to reveal regions that are important for structure and/or function. Starting from a query sequence or structure, the server automatically collects homologues, infers their multiple sequence alignment and reconstructs a phylogenetic tree that reflects their evolutionary relations. These data are then used, within a probabilistic framework, to estimate the evolutionary rates of each sequence position. Here we introduce several new features into ConSurf, including automatic selection of the best evolutionary model used to infer the rates, the ability to homology-model query proteins, prediction of the secondary structure of query RNA molecules from sequence, the ability to view the biological assembly of a query (in addition to the single chain), mapping of the conservation grades onto 2D RNA models and an advanced view of the phylogenetic tree that enables interactively rerunning ConSurf with the taxa of a sub-tree.

  5. What are the pros and cons of electronically monitoring inhaler use in asthma? A multistakeholder perspective

    PubMed Central

    Howard, Sam; Lang, Alexandra; Sharples, Sarah; Shaw, Dominick

    2016-01-01

    Introduction Electronic monitoring devices (EMDs) are the optimal method for collecting objective data on inhaler use in asthma. Recent research has investigated the attitudes of patients with asthma towards these devices. However, no research to date has formally considered the opinions of stakeholders and decision-makers in asthma care. These individuals have important clinical requirements that need to be taken into account if EMDs are to be successfully provisioned, making collecting their opinions on the key barriers facing these devices a valuable process. Methods Three rounds of surveys in a Delphi format were used to assess the most important pros and cons of EMDs for asthma care in a sample of 31 stakeholders which included healthcare professionals and members of clinical commissioning groups. Results The respondents identified 29 pros and 32 cons. Pros that were rated as most important included new visual evidence to aid clinical discussions with a patient and an increase in patient involvement and motivation. The cons that were rated as most important included a need for more clinical evidence of the effectiveness of EMDs, as well as better clarity over who has responsibilities in managing, interpreting and discussing data with a patient. Conclusions The research provides a guide for EMD developers by highlighting where these devices may provide the most benefit as well as prioritising the key issues that need addressing if they are to be used effectively in everyday asthma care. PMID:27933181

  6. Nuevas observaciones de 3C10 con el VLA*: estudio de la expansión

    NASA Astrophysics Data System (ADS)

    Reynoso, E. M.; Moffett, D. A.:; Dubner, G. M.; Giacani, E. B.; Reynolds, S. P.; Goss, W. M.; Dickel, J.

    Se presentan nuevos resultados sobre la expansión del remanente de la supernova de Tycho a lo largo de un intervalo de 10.9 años, comparando nuevas observaciones tomadas con el VLA a 1375 y 1635 MHz durante 1994 y 1995, con observaciones previas realizadas entre 1983 y 1984 (Dickel y col. ~1991 AJ 101, 2151), usando las mismas configuraciones, anchos de banda, calibradores y tiempos de integración. El coeficiente de expansión se calcula para sectores radiales de 4o de ancho cada uno, ajustando la correlación cruzada de las derivadas de los perfiles promedio para cada época. A partir de la expansión medida, se estima el índice (parámetro de expansión) de la ley potencial R∝ tm como m≡ d ln R/d ln t . Este valor se compara con coeficientes teóricos para diferentes fases evolutivas de remanentes de supernova.

  7. Salud mental en desastres naturales: estrategias interventivas con adultos mayores en sectores rurales de Chile.

    PubMed

    Osorio-Parraguez, Paulina; Espinoza, Adriana

    2016-06-01

    En el presente artículo se da a conocer una estrategia de intervención llevada a cabo con adultos mayores en la comuna de Paredones, sexta región de Chile, con posterioridad al terremoto y tsunami del 27 de febrero 2010 en Chile, en el contexto de una investigación sobre fortalezas y vulnerabilidades desplegadas por este grupo etario, con posterioridad a un desastre natural. Se presenta una descripción del desarrollo metodológico de la intervención y de los sustentos teóricos y conceptuales en los que se basa. Como resultado de este proceso, se propone una estrategia que trabaje a través de la identificación de las propias experiencias y fortalezas de los sujetos. De tal forma se minimizan los efectos negativos de los determinantes sociales de la salud (como la edad y el lugar de residencia) en contexto de crisis; permitiendo a los adultos mayores fortalecer sus recursos individuales y colectivos, en pro de su bienestar psicosocial.

  8. Structure, stratigraphy and petroleum geology of the south east Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    Fraser, A.J.; Matthews, S.J.; Lowe, S.; Todd, S.P.; Simon, P. Peel, F.J. )

    1996-01-01

    Recent exploration of the south east Nam Con Son Basin, offshore Vietnam, by BP in alliance with Statoil has involved acquisition of new seismic and well data. These new data have allowed re-evaluation of the tectono-stratigraphic development and petroleum geology, and have provided additional constraints on the regional tectonic evolution. The offshore Vietnamese basins have evolved in response to the complex relative motions of Indochina, Peninsular Malaysia, Borneo and the South China Sea during the Cenozoic. On the regional scale these motions have been accommodated by strike-slip fault development, rifting and contraction. In the Nam Con Son Basin these motions have interacted in different ways from the Palaeogene to recent. Two rifting episodes are recognized; a Palaeogene phase dominated by E-W trending extensional faults, and a Miocene phase dominated by N-S to NE-SW trending faults. The structural evolution is complicated by a pulse of mild contraction during the Middle Miocene. The sedimentary fill of the basin evolves from continental fluvio-lacustrine in the Palaeogene through to fully marine following the second phase of rifting in the Miocene. This pulsed structural and stratigraphic evolution has resulted in basinwide deposition of source, reservoir and seal facies, and produced a variety of potential trapping styles. This paper describes the hydrocarbon habitat of the south east Nam Con Son Basin within the context of the regional tectono-stratigraphic model.

  9. Structure, stratigraphy and petroleum geology of the south east Nam Con Son Basin, offshore Vietnam

    SciTech Connect

    Fraser, A.J.; Matthews, S.J.; Lowe, S.; Todd, S.P.; Simon, P. Peel, F.J.

    1996-12-31

    Recent exploration of the south east Nam Con Son Basin, offshore Vietnam, by BP in alliance with Statoil has involved acquisition of new seismic and well data. These new data have allowed re-evaluation of the tectono-stratigraphic development and petroleum geology, and have provided additional constraints on the regional tectonic evolution. The offshore Vietnamese basins have evolved in response to the complex relative motions of Indochina, Peninsular Malaysia, Borneo and the South China Sea during the Cenozoic. On the regional scale these motions have been accommodated by strike-slip fault development, rifting and contraction. In the Nam Con Son Basin these motions have interacted in different ways from the Palaeogene to recent. Two rifting episodes are recognized; a Palaeogene phase dominated by E-W trending extensional faults, and a Miocene phase dominated by N-S to NE-SW trending faults. The structural evolution is complicated by a pulse of mild contraction during the Middle Miocene. The sedimentary fill of the basin evolves from continental fluvio-lacustrine in the Palaeogene through to fully marine following the second phase of rifting in the Miocene. This pulsed structural and stratigraphic evolution has resulted in basinwide deposition of source, reservoir and seal facies, and produced a variety of potential trapping styles. This paper describes the hydrocarbon habitat of the south east Nam Con Son Basin within the context of the regional tectono-stratigraphic model.

  10. The Transcription Factor Con7-1 Is a Master Regulator of Morphogenesis and Virulence in Fusarium oxysporum.

    PubMed

    Ruiz-Roldán, Carmen; Pareja-Jaime, Yolanda; González-Reyes, José Antonio; Roncero, M Isabel G

    2015-01-01

    Previous studies have demonstrated the essential role of morphogenetic regulation in Fusarium oxysporum pathogenesis, including processes such as cell-wall biogenesis, cell division, and differentiation of infection-like structures. We identified three F. oxysporum genes encoding predicted transcription factors showing significant identities to Magnaporthe oryzae Con7p, Con7-1, plus two identical copies of Con7-2. Targeted deletion of con7-1 produced nonpathogenic mutants with altered morphogenesis, including defects in cell wall structure, polar growth, hyphal branching, and conidiation. By contrast, simultaneous inactivation of both con7-2 copies caused no detectable defects in the resulting mutants. Comparative microarray-based gene expression analysis indicated that Con7-1 modulates the expression of a large number of genes involved in different biological functions, including host-pathogen interactions, morphogenesis and development, signal perception and transduction, transcriptional regulation, and primary and secondary metabolism. Taken together, our results point to Con7-1 as general regulator of morphogenesis and virulence in F. oxysporum.

  11. Wildland Fire Induced Heating of Dome 375 Perma-Con®

    SciTech Connect

    Flores, Eugene Michael

    2016-08-09

    AET-1 was tasked by ADEM with determining the temperature rise in the drum contents of drums stored in the Dome 375 Perma-Con® at TA-54 given a wildland fire. The wildland fire causes radiative and convective heating on the Perma-Con® exterior. The wildland fire time histories for the radiative and convective heating environment were provided to AET-1 by EES-16. If the calculated temperature rise results in a drum content temperature over 40 °C, then ADEM desires a design solution to ensure the peak temperature remains below 40 °C. An axi-symmetric FE simulation was completed to determine the peak temperature of the contents of a drum stored in the Dome 375 Perma-Con® during a wildland fire event. Three wildland fire time histories for the radiative and convective heat transfer were provided by EES-16 and were inputs for the FE simulation. The maximum drum content temperature reached was found to be 110 °C while using inputs from the SiteG_2ms_4ign_wind_from_west.xlsx time history input and not including the SWB in the model. Including the SWB in the results in a peak drum content temperature of 61 °C for the SiteG_2ms_4ign_wind_from_west.xlsx inputs. EES-16 decided that by using fuel mitigation efforts, such as mowing the grass and shrubs near the Perma-Con® they could reduce the shrub/grass fuel loading near the Perma-Con® from 1.46 kg/m2 to 0.146 kg/m2 and by using a less conservative fuel loading for the debris field inside the Dome 375 perimeter, reducing it from 0.58 kg/m2 to 0.058 kg/m2 in their model. They also greatly increased the resolution of their radiation model and increased the accuracy of their model’s required convergence value. Using this refined input the maximum drum content temperature was found to be 28 °C with no SWB present in the model. Additionally, this refined input model was modified to include worst case emissivity values for the concrete, drum and Perma-Con® interior, along with adding a

  12. Con_A-carbone nanotube conjugate with short wave near-infrared laser ablation for tumor therapy

    NASA Astrophysics Data System (ADS)

    Lei, Huan-Yao; Peng, Ching-An; Tang, Ming-Jer; Reindhart, Kit; Szu, Harold H.

    2009-04-01

    Using the characteristics of T cell mitogen called lectin protein from the jack-beam Canavalia ensiformis Concanavalin A (Con_A) with dual activities, cytotoxicity and immunomodulation, we have shown it has a therapeutic effect on hepatoma. Injection of Con_A can eradicate the established malign tumor, because Con_A can induce tumor cell autophagic, cell-programmed death, as well as activate the effector T cells. Combined, in this paper, with the absorption exceeding the Carbon NanoTube (CNT) band-gap (ɛbg=~1/CNT diameter) with an active short wave near-infrared (SWIR) (1.2~1.5 micron wavelengths), which happened to be translucent to the irradiation upon animal skin, similar to that used in hospital fingertip-clamped Pulse Oxymetry. Once the Con_ACNT is guided to hepatoma cells, it is bonded and internalized into the mitochondria (MC) compartment, the cellular energy factory. Con_A has the higher specificity for tumor cells useful for targeting because of the abnormal glycosylation on tumor cells. When CNT hitch hike with Con_A, they can t together like a laser-denotable chemical missile surgically targeting at the tumor cells precisely by Con_A-guidance. We switch on SWIR laser, when the Con_A-CNT conjugated complex has been bonded and internalized to MC of malign cells and already commenced cellular programmed death. Thus, it might appear to casual readers that we have initiated an overkill, chemical drugged autophage followed with physical laser ablation, but what if we can eradicate hepatoma totally if no blue print is left behind inadvertently in case of a partial failure. We conclude that using Con_A-CNT conjugated complex targeting specifically at malign tumor cells is a novel targeted-laser-radiation therapy for tumors in mice.

  13. Lectin-dependent cell-mediated cytotoxicity in an invertebrate model: Con A does not act as a bridge.

    PubMed Central

    Boswell, C A; Bayne, C J

    1986-01-01

    The plant lectin concanavalin A (Con A) has been used in an invertebrate model of lectin-dependent cell-mediated cytotoxicity (LDCC). Macrophage-like cells from the susceptible host snail Biomphalaria glabrata become cytotoxic effectors when they encounter sporocysts of the parasitic trematode Schistosoma mansoni that have been treated with Con A. The sugar alpha-methyl mannoside and rabbit anti-Con A antibodies fail to block this LDCC. Con A is effective only when the target, not the effector cell, has been exposed to it. These results constitute evidence against the molecular bridging hypothesis and support the notion that surface modulation of the target may be the stimulus that provokes cytotoxicity. Results from this invertebrate model are discussed in the context of murine T lymphocyte LDCC. PMID:3949370

  14. Segundo Catálogo Estelar del Hemisferio Sur con Astrolabio Fotoeléctrico PAII

    NASA Astrophysics Data System (ADS)

    Manrique, W. T.; Podestá, R. C.; Alonso, E.; Actis, E. V.; Pacheco, A. M.; Bustos, G.; Lizhi, L.; Zezhi, W.; Fanmiao, Z.; Hongqi, W.; Perdomo, R.

    Recordamos que entre el Observatorio Astronómico ``Félix Aguilar'', el Observatorio Astronómico de Beijing y el Observatorio Astronómico de La Plata, se ha convenido en desarrollar un Proyecto de Investigación conjunto, para la observación sistemática de estrellas en el Hemisferio Sur, con el objeto de la elaboración de un Catálogo Estelar Global utilizando un Astrolabio Fotoeléctrico PAII del Observatorio de Beijing, que ha sido usado con éxito en la República de China. En este trabajo se presenta el Segundo Catálogo Estelar del Hemisferio Sur, derivado de las observaciones realizadas con el PAII instalado en el OAFA, durante el períiodo Febrero de 1992 a Marzo de 1997. En este lapso se han observado mas de 400000 pasajes estelares, obteniéndose las correcciones Δ α y Δ δ de 5241 estrellas del FK4, FK5, FK5 Ext., SRS, CAMC y GC. Las precisiones medias son del orden de ± 3,2 ms en ascensión recta y ±0."057 en declinación. Rango de magnitudes : 2,0 a 11,5 Rango de declinaciones : -3o a -60o Epoca Media : 1994.9 Se analizan los residuos en función de la magnitud y tipo espectral, correcciones de grupo y frecuencia de distribución Δ α y Δ δ.

  15. A phase 2 trial of long-acting TransCon growth hormone in adult GH deficiency.

    PubMed

    Höybye, Charlotte; Pfeiffer, Andreas F H; Ferone, Diego; Christiansen, Jens Sandahl; Gilfoyle, David; Christoffersen, Eva Dam; Mortensen, Eva; Leff, Jonathan A; Beckert, Michael

    2017-04-01

    TransCon growth hormone is a sustained-release human growth hormone prodrug under development in which unmodified growth hormone is transiently linked to a carrier molecule. It is intended as an alternative to daily growth hormone in the treatment of growth hormone deficiency. This was a multi-center, randomized, open-label, active-controlled trial designed to compare the safety (including tolerability and immunogenicity), pharmacokinetics and pharmacodynamics of three doses of weekly TransCon GH to daily growth hormone (Omnitrope). Thirty-seven adult males and females diagnosed with adult growth hormone deficiency and stable on growth hormone replacement therapy for at least 3 months were, following a wash-out period, randomized (regardless of their pre-study dose) to one of three TransCon GH doses (0.02, 0.04 and 0.08 mg GH/kg/week) or Omnitrope 0.04 mg GH/kg/week (divided into 7 equal daily doses) for 4 weeks. Main outcomes evaluated were adverse events, immunogenicity and growth hormone and insulin-like growth factor 1 levels. TransCon GH was well tolerated; fatigue and headache were the most frequent drug-related adverse events and reported in all groups. No lipoatrophy or nodule formation was reported. No anti-growth hormone-binding antibodies were detected. TransCon GH demonstrated a linear, dose-dependent increase in growth hormone exposure without accumulation. Growth hormone maximum serum concentration and insulin-like growth factor 1 exposure were similar after TransCon GH or Omnitrope administered at comparable doses. The results suggest that long-acting TransCon GH has a profile similar to daily growth hormone but with a more convenient dosing regimen. These findings support further TransCon GH development.

  16. The pros and cons about the digital recording of Intangible Cultural Heritage and some strategies

    NASA Astrophysics Data System (ADS)

    Yang, H.

    2015-08-01

    Intangible Cultural Heritage (referred to as ICH), whose fundamental nature different from the tangible cultural heritage is "Intangible", and the related physical presence of the heritage is not the core content. Digital means have irreplaceable advantages in recording intangible and dynamic ICH resources, while it also needs flexible and rigorous recording means as a support, thus striving to maximize resources recording and protection. This article will focus on the pros and cons about the digital recording of ICH, and preliminarily discuss some strategies used in the process of recording.

  17. La interacción de estrellas WN con el medio circundante

    NASA Astrophysics Data System (ADS)

    Arnal, M.; Cappa, C.; Rizzo, J. R.; Cichovolski, S.

    Se presentan resultados preliminares de un estudio de la distribución del hidrógeno neutro en los alrededores de estrellas WR de la serie del nitrógeno. Los datos observacionales de la línea de 21 cm provienen de un relevamineto de baja resolución angular (36'), así como de observaciones de resolución angular intermedia (9') tomadas con el radiotelescopio de Effelsberg. Este análisis ha permitido detectar cavidades y envolturas de H I en expansión vinculadas a las estrellas que componen la muestra.

  18. On application of optimal control to SEIR normalized models: Pros and cons.

    PubMed

    de Pinho, Maria do Rosario; Nogueira, Filipa Nunes

    2017-02-01

    In this work we normalize a SEIR model that incorporates exponential natural birth and death, as well as disease-caused death. We use optimal control to control by vaccination the spread of a generic infectious disease described by a normalized model with L1 cost. We discuss the pros and cons of SEIR normalized models when compared with classical models when optimal control with L1 costs are considered. Our discussion highlights the role of the cost. Additionally, we partially validate our numerical solutions for our optimal control problem with normalized models using the Maximum Principle.

  19. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons.

    PubMed

    Westmark, Cara J

    2016-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition.

  20. Nano anti-cancer drugs: pros and cons and future perspectives.

    PubMed

    Ali, Imran

    2011-02-01

    For last one decade, scientists are working for developing nano anti-cancer drugs with claim of ideal ones due to their targeted chemotherapic nature. These drugs have many beneficial properties such as targeted drug delivery and gene therapy modalities with minimum side effects. This article describes pros and cons and future perspectives of nano anti-cancer drugs. Efforts have been made to address importance, special features, toxicities (general, blood identities, immune system and environmental) and future perspectives of nano anti-cancer drugs. It was concluded that nano anti-cancer drugs may be magic bullet drugs for cancer treatment leading to bright future of the whole world.

  1. Highlights from day three of the EuroSciCon 2015 Sports Science Summit

    PubMed Central

    Chawla, Amit; McGregor, Alison

    2015-01-01

    This EuroSciCon Sports Science Summit represented a significant gathering of leading professionals in the field of sports science. The conference was held on 13–15 January 2015 at the O2 arena, London, UK. The chairman on the third day was Mr Greg Robertson, a specialist trainee Orthopedic surgeon from Edinburgh. The conference attracted over 80 attendants from all over the world, with 32 presentations from invited speakers and peer-reviewed submissions. This meeting report provides a summary of the best abstracts from the conference. PMID:28031889

  2. Confrontando teorías físicas con la Cosmología

    NASA Astrophysics Data System (ADS)

    Vucetich, H.

    Hay numerosas teorías físicas que no pueden contrastarse con el experimento en laboratorio y eso las hace poco interesantes como descripción de la naturaleza. Sin embargo, algunas de estas teorías tienen consecuencias cosmológicas observables y se abre la posibilidad de contrastación a través de la observación. Se discuten las observaciones capaces de poner a prueba tales teorías y se examinan ejemplos de teorías limitadas por la observación.

  3. Soy-Based Therapeutic Baby Formulas: Testable Hypotheses Regarding the Pros and Cons

    PubMed Central

    Westmark, Cara J.

    2017-01-01

    Soy-based infant formulas have been consumed in the United States since 1909, and currently constitute a significant portion of the infant formula market. There are efforts underway to generate genetically modified soybeans that produce therapeutic agents of interest with the intent to deliver those agents in a soy-based infant formula platform. The threefold purpose of this review article is to first discuss the pros and cons of soy-based infant formulas, then present testable hypotheses to discern the suitability of a soy platform for drug delivery in babies, and finally start a discussion to inform public policy on this important area of infant nutrition. PMID:28149839

  4. The pros and cons of risk communication: A project manager`s guide

    SciTech Connect

    Perry, S.D.

    1995-12-31

    Communicating risk is in itself a risky, yet essential, part of any successful hazardous waste project`s community relations strategy. Essential, because no project requiring public involvement can achieve success without effective communication of technical data and associated risks. Risky, because the stakes are high, the public and media are often contentious, and their science and engineering are difficult to relate to non-technical audiences. Given that communicating project risks cannot be avoided, or are avoided at one`s own peril, project managers lacking mastery of communication skills can build winning strategies by heeding the following ``pros`` and ``cons`` of risk communication.

  5. Uso de Sustancias en Mujeres con Desventaja Social: Riesgo para el Contagio de VIH/SIDA

    PubMed Central

    Cianelli, R.; Ferrer, L; Bernales, M.; Miner, S.; Irarrázabal, L.; Molina, Y.

    2009-01-01

    Antecedentes La caracterización epidemiológica en Chile apunta a feminización, pauperización y heterosexualización de la epidemia del VIH, lo que implica un mayor riesgo para las mujeres en desventaja social. Si a esto se suma la utilización de sustancias, la vulnerabilidad de este grupo frente al VIH/SIDA aumenta. Objetivo Describir el uso de sustancias en mujeres con desventaja social e identificar factores de riesgo de contagio de VIH, asociados a este consumo. Material y Método 52 mujeres fueron entrevistadas como parte del proyecto “Testeando una intervención en prevención de VIH/SIDA en mujeres chilenas” GRANT # RO1 TW 006977. Se describen variables sociodemográficas y de consumo de sustancias a través de estadísticas descriptivas y se analiza la relación entre variables a través de pruebas de correlación. Resultados Los resultados indican un perfil sociodemográfico que sitúa a las mujeres en situación de vulnerabilidad frente al contagio de VIH/SIDA, con alto índice de uso de sustancias que acentúa el riesgo. Conclusiones Los hallazgos apuntan a la necesidad de considerar intervenciones que se enfoquen en la prevención de VIH en mujeres, abordando los riesgos asociados al consumo de sustancias. PMID:21197380

  6. RETOS EN LA INTERVENCIÓN CON ADOLESCENTES PUERTORRIQUEÑOS/AS QUE MANIFIESTAN COMPORTAMIENTO SUICIDA*

    PubMed Central

    Vélez, Yovanska Duarté; Dávila, Paloma Torres; Hernández, Samariz Laboy

    2015-01-01

    Presentamos un estudio de caso de una adolescente puertorriqueña con comportamiento suicida. Esta comenzó una Terapia Socio Cognitivo-Conductual para el Comportamiento Suicida (TSCC-CS) de tipo ambulatorio luego de una hospitalización por intento suicida. La TSCC-CS incorpora una perspectiva ecológica y de desarrollo a la terapia cognitivo-conductual. Inicialmente mostró baja autoestima y severos síntomas depresivos y de ansiedad. Al finalizar el tratamiento, manifestó un cambio significativo en su sintomatología clínica y evidenció una mejoría en sus destrezas de manejo. No presentó ideas suicidas durante meses previos, ni durante el seguimiento. El análisis de este caso permitió realizar cambios en el protocolo de tratamiento, particularmente en las sesiones de familia y de comunicación con el fin de aumentar la viabilidad del tratamiento. PMID:26702337

  7. Targeting of proConA to the plant vacuole depends on its nine amino-acid C-terminal propeptide.

    PubMed

    Saint-Jore-Dupas, Claude; Claude, Saint-Jore-Dupas; Gilbert, Marie-Agnès; Marie-Agnès, Gilbert; Ramis, Catalina; Catalina, Ramis; Paris, Nadine; Nadine, Paris; Kiefer-Meyer, Marie-Christine; Marie-Christine, Kiefer-Meyer; Neuhaus, Jean-Marc; Jean-Marc, Neuhaus; Faye, Loïc; Loïc, Faye; Gomord, Véronique; Véronique, Gomord

    2005-10-01

    Concanavalin A (ConA) is a well characterized and extensively used lectin accumulated in the protein bodies of jack bean cotyledons. ConA is synthesized as an inactive precursor proConA. The maturation of inactive proConA into biologically active ConA is a complex process including the removal of an internal glycopeptide and a C-terminal propeptide (CTPP), followed by a head-to-tail ligation of the two largest polypeptides. The cDNA encoding proConA was cloned and expressed in tobacco BY-2 cells. ProConA was slowly transported to the vacuole where its maturation into ConA was similar to that in jack bean cotyledons, apart from an incomplete final ligation. To investigate the role of the nine amino acid CTPP, a truncated form lacking the propeptide (proConADelta9) was expressed in BY-2 cells. In contrast to proConA, proConADelta9 was rapidly chased out of the endoplasmic reticulum (ER) and secreted into the culture medium. The CTPP was then fused to the C-terminal end of a secreted form of green fluorescent protein (secGFP). When expressed in tobacco BY-2 cells and leaf protoplasts, the chimaeric protein was located in the vacuole whereas secGFP was located in the culture medium and in the vacuole. Altogether, our results show we have isolated a new C-terminal vacuolar sorting determinant.

  8. Overcoming the aggregation problem: A new type of fluorescent ligand for ConA-based glucose sensing

    PubMed Central

    Cummins, Brian M.; Li, Mingchien; Locke, Andrea K.; Birch, David J.S.; Vigh, Gyula; Coté, Gerard L.

    2016-01-01

    Competitive binding assays based on the lectin Concanavalin A (ConA) have displayed significant potential to serve in continuous glucose monitoring applications. However, to date, this type of fluorescent, affinity-based assay has yet to show the stable, glucose predictive capabilities that are required for such an application. This instability has been associated with the extensive crosslinking between traditionally-used fluorescent ligands (presenting multiple low-affinity moieties) and ConA (presenting multiple binding sites) in free solution. The work herein introduces the design and synthesis of a new type of fluorescent ligand that can avoid this aggregation and allow the assay to be sensitive across the physiologically relevant glucose concentration range. This fluorescent ligand (APTS–MT) presents a single high-affinity trimannose moiety that is recognized by ConA’s full binding site and a fluorophore that can effectively track the ligand’s equilibrium binding via fluorescent anisotropy. This is confirmed by comparing its measured fluorescent lifetime to experimentally-determined rotational correlation lifetimes of the free and bound populations. Using an assay comprised of 200 nM APTS–MT and 1 μM ConA, the fluorescence anisotropy capably tracks the concentration of monosaccharides that are known to bind to ConA’s primary binding site, and the assay displays a MARD of 6.5% across physiologically relevant glucose concentrations. Ultimately, this rationally-designed fluorescent ligand can facilitate the realization of the full potential of ConA-based glucose sensing assays and provide the basis for a new set of competing ligands to be paired with ConA. PMID:25058939

  9. Overcoming the aggregation problem: a new type of fluorescent ligand for ConA-based glucose sensing.

    PubMed

    Cummins, Brian M; Li, Mingchien; Locke, Andrea K; Birch, David J S; Vigh, Gyula; Coté, Gerard L

    2015-01-15

    Competitive binding assays based on the lectin Concanavalin A (ConA) have displayed significant potential to serve in continuous glucose monitoring applications. However, to date, this type of fluorescent, affinity-based assay has yet to show the stable, glucose predictive capabilities that are required for such an application. This instability has been associated with the extensive crosslinking between traditionally-used fluorescent ligands (presenting multiple low-affinity moieties) and ConA (presenting multiple binding sites) in free solution. The work herein introduces the design and synthesis of a new type of fluorescent ligand that can avoid this aggregation and allow the assay to be sensitive across the physiologically relevant glucose concentration range. This fluorescent ligand (APTS-MT) presents a single high-affinity trimannose moiety that is recognized by ConA's full binding site and a fluorophore that can effectively track the ligand's equilibrium binding via fluorescent anisotropy. This is confirmed by comparing its measured fluorescent lifetime to experimentally-determined rotational correlation lifetimes of the free and bound populations. Using an assay comprised of 200 nM APTS-MT and 1 µM ConA, the fluorescence anisotropy capably tracks the concentration of monosaccharides that are known to bind to ConA's primary binding site, and the assay displays a MARD of 6.5% across physiologically relevant glucose concentrations. Ultimately, this rationally-designed fluorescent ligand can facilitate the realization of the full potential of ConA-based glucose sensing assays and provide the basis for a new set of competing ligands to be paired with ConA.

  10. [National consensus on the modified Atkins diet].

    PubMed

    Vaccarezza, María; Agustinho, Ariela; Alberti, M Julia; Argumedo, Laura; Armeno, Marisa; Blanco, Virginia; Bouquet, Cecilia; Cabrera, Analía; Caraballo, Roberto; Caramuta, Luciana; Cresta, Araceli; de Grandis, Elizabeth S; DeMartini, Martha G; Diez, Cecilia; Diz, Mariana; Dlugoszewski, Corina; Escobal, Nidia; Ferrero, Hilario; Galicchio, Santiago; Gambarini, Victoria; Gamboni, Beatriz; Gonzalez, Lara; Guisande, Silvina; Hassan, Amal; Matarrese, Pablo; Mestre, Graciela; Pesce, Laura; Rios, Viviana; Semprino, Marcos; Sosa, Patricia; Toma, Marisol; Viollaz, Rocío; Panico, Luis

    2016-04-16

    Introduccion. La epilepsia es una enfermedad cronica que afecta al 0,5-1% de la poblacion, y un tercio de los pacientes evoluciona hacia una forma refractaria a los farmacos antiepilepticos. Dentro de los tratamientos no farmacologicos disponibles, la dieta cetogenica Atkins modificada es un tratamiento efectivo utilizado desde 2003 como otra alternativa en niños y adultos con epilepsia refractaria. Desarrollo. El Comite Nacional de Dieta Cetogenica, dependiente de la Sociedad Argentina de Neurologia Infantil, elaboro este consenso sobre dieta Atkins modificada basandose en una revision de la bibliografia y en su experiencia clinica. Este consenso explica los distintos aspectos que hay que tener en cuenta sobre la dieta Atkins modificada, eleccion de pacientes, forma de implementacion, diversos controles y efectos adversos. A diferencia de la dieta cetogenica clasica, se inicia sin ayuno ni hospitalizacion, y no hay restriccion proteica, calorica o hidrica, por lo que mejora la palatabilidad y, consecuentemente, la tolerabilidad. Conclusiones. La dieta Atkins modificada es un tratamiento util para pacientes con epilepsia intratable. La publicacion de este consenso ofrece la posibilidad de orientar a nuevos centros en su implementacion.

  11. Contribution of the Kallikrein/Kinin System to the Mediation of ConA-Induced Inflammatory Ascites.

    PubMed

    Baintner, Károly

    2016-03-01

    Intraperitoneal administration of concanavalin A (ConA, 25 mg/kg b.w.), a cell-binding plant lectin was used for inducing inflammatory ascites, and potential inhibitors were tested in 1 h and 2.5 h experiments, i.e. still before the major influx of leucocytes. At the end of the experiment the peritoneal fluid was collected and measured. The ConA-induced ascites was significantly (p<0.01) and dose-dependently inhibited by icatibant (HOE-140), a synthetic polypeptide antagonist of bradykinin receptors. Aprotinin, a kallikrein inhibitor protein also had significant (p<0.01), but less marked inhibitory effect. L-NAME, an inhibitor of NO synthesis, and atropine methylnitrate, an anticholinergic compound, were ineffective. It is concluded, that the kallikrein/kinin system contributes to the mediation of the ConA-induced ascites by increasing subperitoneal vascular permeability, independent of the eventual vasodilation produced by NO. It is known, that membrane glycoproteins are aggregated by the tetravalent ConA and the resulting distortion of membrane structure may explain the activation of the labile prekallikrein. Complete inhibition of the ConA-induced ascites could not be achieved by aprotinin or icatibant, which indicates the involvement of additional mediators.

  12. Comparison of phenotypic methods in predicting methicillin resistance in coagulase-negative Staphylococcus (CoNS) from animals.

    PubMed

    Zhang, Yifan; Wang, Xiaogang; LeJeune, Jeffrey T; Zervos, Marcus; Bhargava, Kanika

    2011-02-01

    Phenotypic detection of methicillin resistance in coagulase-negative Staphylococcus (CoNS) of animal origin has been challenging due to the heterogeneous expression of mecA. To compare different phenotypic methods in predicting the mecA presence in CoNS, a total of 87 CoNS isolates from agricultural animals were analyzed in this study by agar dilution, disk diffusion, and broth microdilution. mecA was present in 81 CoNS isolates. Broth microdilution demonstrated the highest sensitivity of 100% in predicting the mecA presence, followed by 72.8% by agar dilution and 70.4% by disk diffusion. The results indicate that broth microdilution may be more suitable for predicting the presence of mecA in CoNS from animals than the other two methods, although staphylococcal species may also be a factor affecting the sensitivities of the methods as the top three staphylococcal species in this study were Staphylococcus lentus, Staphylococcus sciuri, and Staphylococcus xylosus (a total of 75 of 87).

  13. Multipotent (adult) and pluripotent stem cells for heart regeneration: what are the pros and cons?

    PubMed

    Liao, Song-Yan; Tse, Hung-Fat

    2013-12-24

    Heart failure after myocardial infarction is the leading cause of mortality and morbidity worldwide. Existing medical and interventional therapies can only reduce the loss of cardiomyocytes during myocardial infarction but are unable to replenish the permanent loss of cardiomyocytes after the insult, which contributes to progressive pathological left ventricular remodeling and progressive heart failure. As a result, cell-based therapies using multipotent (adult) stem cells and pluripotent stem cells (embryonic stem cells or induced pluripotent stem cells) have been explored as potential therapeutic approaches to restore cardiac function in heart failure. Nevertheless, the optimal cell type with the best therapeutic efficacy and safety for heart regeneration is still unknown. In this review, the potential pros and cons of different types of multipotent (adult) stem cells and pluripotent stem cells that have been investigated in preclinical and clinical studies are reviewed, and the future perspective of stem cell-based therapy for heart regeneration is discussed.

  14. From in vitro Experiments to in vivo and Clinical Studies; Pros and Cons.

    PubMed

    Saeidnia, Soodabeh; Manayi, Azadeh; Abdollahi, Mohammad

    2015-01-01

    Biomedical investigators use different methods including experimental animals, tissue, and cell cultures as well as computational simulations and clinical studies finding the ways to treat human diseases and disorders. All the mentioned procedures have their own advantages and disadvantages. For instance although animal models provide some drawbacks like difference in biokinetics parameters or extrapolation of results to human, they are more reliable than in vitro tests. The disadvantage of the in vitro procedures is that they are mostly performed on cancerous cell lines that have a substantially abnormal function. Furthermore, although in vitro models are fruitfully used in biological fields, finding an end point, the initial aim of chemical attack, and extrapolation of the effects to the human are some real weaknesses. Absence of biokinetics in in vitro methods may lead to a misinterpretation of the data. The present review has criticized the pros and cons of both methods, especially in the fields of pharmacology, toxicology, and medical sciences.

  15. What to consider when regulating electronic cigarettes: Pros, cons and unintended consequences.

    PubMed

    Caponnetto, Pasquale; Saitta, Daniela; Sweanor, David; Polosa, Riccardo

    2015-06-01

    Many public health experts, medical research societies, large health organizations and policy makers have expressed concerns about the increased popularity of electronic cigarettes and have pushed for more restrictive measures ranging from complete bans to tight regulations of these products either as medicines or as tobacco products. But these concerns have never been adequately qualified nor quantified. Without judicious assessment and thorough evaluation, regulations may have unintended consequences that can do more damage than good in public health terms. In this article, we will appraise the existing prominent regulatory frameworks for e-cigarettes, namely, general consumer product, medicinal product and tobacco product regulation, to highlight their pros and cons. Moreover, we provide concrete examples of the unintended consequences which may arise from inappropriate regulatory action.

  16. Pros and cons of healthcare information technology implementation: the pros win.

    PubMed

    Maffei, Roxana

    2006-01-01

    Countless studies and investigations have been performed siding either for or against the implementation of technology in the healthcare setting. This article presents both sides of this debate, with an obvious conclusion that the pros of this debate win. The practice of information technology in the medical domain lags behind its knowledge and discovery by at least 7 years. The key to closing this gap is to show, through various studies, how information technology systems provide decision support to users at the point in time when decisions are needed. What the reader will obtain from this article is that the pros for information technology implementation in healthcare settings weigh much more and have a greater effect than the cons.

  17. The new human papillomavirus (HPV) vaccine: pros and cons for pediatric and adolescent health.

    PubMed

    Thomas, Tami L

    2008-01-01

    The new human papillomavirus (HPV) vaccine is a research breakthrough for pediatric/adolescent health to prevent cervical cancer and related morbidity. The annual heath care cost for the treatment of cervical cancer and genital warts is estimated to be more than three billion dollars a year. The new HPV vaccine has incredible potential to improve reproductive health promotion, reduce health care costs, and close health care disparity gaps. However, issues both for and against the new HPV vaccine, including mandating vaccination, high cost of the vaccine, the short duration of protection offered, and the perceived promotion of sexual activity, cause confusion. Pediatric nurses, including those in advanced practice, benefit by understanding the pros and cons of these issues in advocating for their patients.

  18. [Funzioni esecutive metacognitive ed emozionali/motivazionali nel disturbo dello spettro dell'autismo e nel disturbo da deficit di attenzione con iperattività: risultati preliminari].

    PubMed

    Panerai, Simonetta; Tasca, Domenica; Ferri, Raffaele; Catania, Valentina; Genitori D'Arrigo, Valentina; Di Giorgio, Rosa; Zingale, Marinella; Trubia, Grazia; Torrisi, Anna; Elia, Maurizio

    2016-01-01

    RIASSUNTO. Scopo. I deficit delle funzioni esecutive (FE) sono frequentemente osservati nei disturbi dello spettro dell'autismo (ASD) e nel disturbo da deficit di attenzione con iperattività (ADHD). Lo scopo di questo studio è quello di valutare e confrontare le funzioni esecutive metacognitive ed emozionali/motivazionali di bambini con ASD e ADHD, sia fra di loro che con un gruppo di controllo. Metodi. Il campione è costituito da un totale di 58 soggetti, di cui 17 con ASD senza disabilità intellettiva, 18 con ADHD-manifestazione combinata e 23 con sviluppo tipico, abbinati per genere, età cronologica e livello intellettivo. Le valutazioni hanno riguardato alcune aree del funzionamento esecutivo, nello specifico pianificazione, flessibilità mentale, generatività e inibizione della risposta, che rappresentano sia le funzioni esecutive metacognitive sia quelle emozionali/motivazionali. Risultati. I risultati hanno rilevato un'ampia sovrapposizione delle disfunzioni esecutive nei due gruppi clinici con ASD e ADHD, e non sono stati indicativi della presenza di due profili realmente distinti del funzionamento esecutivo. Tuttavia, nell'ADHD è stato trovato un deficit più severo nell'inibizione della risposta prepotente (funzione emozionale/motivazionale). Conclusioni. I risultati del nostro studio sono parzialmente in accordo con quelli della letteratura. Ulteriori ricerche con gruppi più numerosi potranno chiarire più approfonditamente quali punti di forza e debolezza, nell'ampio spettro delle funzioni esecutive, differenzino fra loro le prestazioni di persone con ASD e ADHD.

  19. [Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review].

    PubMed

    Araya-Quintanilla, F; Celis-Rosati, A; Rodriguez-Leiva, C; Silva-Navarro, C; Silva-Pinto, Y; Toro-Jeria, B

    2016-05-16

    Introduccion. La epilepsia es una patologia cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogenica ha ganado prestigio como otra opcion de tratamiento en pacientes con epilepsia refractaria. Sujetos y metodos. Se realiza una sintesis de la evidencia a traves de una revision sistematica de ensayos clinicos aleatorizados que hayan comparado una dieta cetogenica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogenica en la disminucion de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de busqueda incluyo ensayos clinicos aleatorizados y ensayos clinicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis articulos que cumplian con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogenica en comparacion con la dieta de trigliceridos de cadena media es mas efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta gradual (2,5:1 y 3:1) es mas efectiva para disminuir las crisis epilepticas. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta Atkins es mas efectiva para disminuir la frecuencia de convulsiones en tres meses. La decision de aplicar este tipo de dietas tambien debe basarse en costes, preferencias y seguridad del tratamiento. Ademas, debe considerarse la probabilidad de que algunos estudios, por problemas de indizacion, hayan quedado fuera de la revision.

  20. DESAFÍOS ÉTICOS DE LA INVESTIGACIÓN CON ANIMALES, MANIPULACIÓN GENÉTICA

    PubMed Central

    Yunta, Eduardo Rodríguez

    2012-01-01

    En la investigación con animales existen cuestionamientos éticos tanto en el uso como modelos de enfermedades humanas y requisito previo para ensayos en humanos como en la introducción de modificaciones genéticas. Algunos de estos cuestionamientos son: no representar exactamente la condición humana como modelos, realizar pruebas de toxicidad con grave daño para los animales, alterar su naturaleza mediante modificaciones genéticas, riesgos de la introducción de organismos genéticamente modificados. El uso de animales en investigación para beneficio humano, impone al ser humano la responsabilidad moral de respetarlo, no haciéndoles sufrir innecesariamente, al estar trabajando con seres vivientes y sentientes. PMID:23338641

  1. Formación estelar en NGC 6357: viendo a través del polvo con Gemini

    NASA Astrophysics Data System (ADS)

    Bosch, G.; Morrell, N.; Barbá, R.

    Presentamos aquí los primeros resultados de fotometría JHKs obtenidos con Flamingos I en el telescopio Gemini Sur. El mosaico comprendido por tres posiciones adyacentes tomadas a lo largo de varios semestres nos permite caracterizar la población estelar en la zona que presenta una interacción más importante entre las estrellas masivas y la nube molecular que les dió origen. Los diagramas color-magnitud nos permiten identificar numerosas fuentes con exceso infrarrojo, la mayoría de ellas imposible de detectarse en el rango óptico debido a la fuerte absorción del polvo presente en la región. Es altamente probable que la mayoría de estas fuentes con exceso sean protoestrellas, aunque es necesario realizar espectroscopía infrarroja de las mismas para confirmar su naturaleza.

  2. La salud en personas con discapacidad intelectual en España: estudio europeo POMONA-II

    PubMed Central

    Martínez-Leal, Rafael; Salvador-Carulla, Luis; Gutiérrez-Colosía, Mencía Ruiz; Nadal, Margarida; Novell-Alsina, Ramón; Martorell, Almudena; González-Gordón, Rodrigo G.; Mérida-Gutiérrez, M. Reyes; Ángel, Silvia; Milagrosa-Tejonero, Luisa; Rodríguez, Alicia; García-Gutiérrez, Juan C.; Pérez-Vicente, Amado; García-Ibáñez, José; Aguilera-Inés, Francisco

    2011-01-01

    Introducción Estudios internacionales demuestran que existe un patrón diferenciado de salud y una disparidad en la atención sanitaria entre personas con discapacidad intelectual (DI) y población general. Objetivo Obtener datos sobre el estado de salud de las personas con DI y compararlos con datos de población general. Pacientes y métodos Se utilizó el conjunto de indicadores de salud P15 en una muestra de 111 sujetos con DI. Los datos de salud encontrados se compararon según el tipo de residencia de los sujetos y se utilizó la Encuesta Nacional de Salud 2006 para comparar estos datos con los de la población general. Resultados La muestra con DI presentó 25 veces más casos de epilepsia y el doble de obesidad. Un 20% presentó dolor bucal, y existió una alta presencia de problemas sensoriales, de movilidad y psicosis. Sin embargo, encontramos una baja presencia de patologías como la diabetes, la hipertensión, la osteoartritis y la osteoporosis. También presentaron una menor participación en programas de prevención y promoción de la salud, un mayor número de ingresos hospitalarios y un uso menor de los servicios de urgencia. Conclusiones El patrón de salud de las personas con DI difiere del de la población general, y éstas realizan un uso distinto de los servicios sanitarios. Es importante el desarrollo de programas de promoción de salud y de formación profesional específicamente diseñados para la atención de personas con DI, así como la implementación de encuestas de salud que incluyan datos sobre esta población. PMID:21948011

  3. Economic and Ethical Consequences of Natural Hazards in Alpine Valleys (EE-Con)

    NASA Astrophysics Data System (ADS)

    Ortner, Florian; Brantl, Dirk; Meyer, Lukas; Steininger, Karl; Sass, Oliver

    2015-04-01

    The Alps and their population are particularly vulnerable to geomorphological and hydrological hazards and this problem might be amplified by ongoing climate change. Natural disasters cause severe monetary damage which often leads to the difficult question whether it socially pays to protect settlements at high costs or whether alternatively settlement areas should better be abandoned. By investigations in the Johnsbachtal and the Kleinsölktal (Styria), the interdisciplinary project "Economic and Ethical Consequences of Natural Hazards in Alpine Valleys" (EE-Con), funded by the Austrian Academy of Sciences, seeks to answer the following questions: (1) Are natural hazards and associated damages in fact increasing, and is this due to meteorological triggers, to anthropogenic factors or to internal process dynamics? (2) What is the perception and knowledge of local people, how is risk and risk prevention communicated? (3) What is the respective cost ratio between protection infrastructure, soft measures of adaptation and other options (e.g. reduction of settlement area)? (4) What legitimate claims to compensation do people have, how far does societal responsibility go and where does individual responsibility start if parts of the settlement area had to be abandoned? These questions will be tackled in an interdisciplinary cooperation between geography, economics and normative theory (philosophy). EE-Con will follow broadly the path of risk analysis and risk assessment, focusing on the temporal dimension (past - present - future) with the aim to unravel the history of natural hazards in the areas and to analyse the economic values involved. In the following, natural hazard scenarios for the future (2050 and 2100) will be developed considering the economic consequences. Besides this, the project deals with local knowledge, risk perception and risk communication, which will be investigated via group interviews and stakeholder workshops and be integrated into a human

  4. Future of clip-on weapon sights: pros and cons from an applications perspective

    NASA Astrophysics Data System (ADS)

    Knight, C. Reed; Greenslade, Ken; Francisco, Glen

    2015-05-01

    US Domestic, International, allied Foreign National Warfighters and Para-Military First Responders (Police, SWAT, Special Operations, Law Enforcement, Government, Security and more) are put in harm's way all the time. To successfully complete their missions and return home safely are the primary goals of these professionals. Tactical product improvements that affect mission effectiveness and solider survivability are pivotal to understanding the past, present and future of Clip-On in-line weapon sights. Clip-On Weapon Sight (WS) technology was deemed an interim solution by the US Government for use until integrated and fused (day/night multi-sensor) Weapon Sights (WSs) were developed/fielded. Clip-On has now become the solution of choice by Users, Warriors, Soldiers and the US Government. SWaP-C (size, weight and power -cost) has been improved through progressive advances in Clip-On Image Intensified (I2), passive thermal, LL-CMOS and fused technology. Clip-On Weapon Sights are now no longer mounting position sensitive. Now they maintain aim point boresight, so they can be used for longer ranges with increased capabilities while utilizing the existing zeroed weapon and daysight optic. Active illuminated low-light level (both analog I2 and digital LL-CMOS) imaging is rightfully a real-world technology, proven to deliver daytime and low-light level identification confidence. Passive thermal imaging is also a real-world technology, proven to deliver daytime, nighttime and all-weather (including dirty battlefield) target detection confidence. Image processing detection algorithms with intelligent analytics provide documented promise to improve confidence by reducing Users, Warriors and Soldiers' work-loads and improving overall system engagement solution outcomes. In order to understand the future of Clip-On in-line weapon sights, addressing pros and cons, this paper starts with an overview of historical weapon sight applications, technologies and stakeholder decisions

  5. Self-efficacy, pros, and cons as variables associated with adjacent stages of change for regular exercise in Japanese college students.

    PubMed

    Horiuchi, Satoshi; Tsuda, Akira; Kobayashi, Hisanori; Fallon, Elizabeth A; Sakano, Yuji

    2016-01-18

    This study examined self-efficacy (confidence to exercise), pros (exercise's advantages), and cons (exercise's disadvantages) as variables associated across the transtheoretical model's six stages of change in 403 Japanese college students. A series of logistic regression analyses were conducted. Results showed that higher pros and lower cons were associated with being in contemplation compared to precontemplation. Lower cons were associated with being in preparation compared to contemplation. Higher self-efficacy was associated with being in action compared to preparation as well as being in maintenance compared to action. Lower cons were associated with being in termination compared to maintenance.

  6. Air Traffic Management Technology Demonstration-1 Concept of Operations (ATD-1 ConOps), Version 3.0

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Johnson, William C.; Scardina, John; Shay, Richard F.

    2016-01-01

    This document describes the goals, benefits, technologies, and procedures of the Concept of Operations (ConOps) for the Air Traffic Management (ATM) Technology Demonstration #1 (ATD-1), and provides an update to the previous versions of the document [ref 1 and ref 2].

  7. iPathCons and iPathDB: an improved insect pathway construction tool and the database

    PubMed Central

    Zhang, Zan; Yin, Chuanlin; Liu, Ying; Jie, Wencai; Lei, Wenjie; Li, Fei

    2014-01-01

    Insects are one of the most successful animal groups on earth. Some insects, such as the silkworm and honeybee, are beneficial to humans, whereas others are notorious pests of crops. At present, the genomes of 38 insects have been sequenced and made publically available. In addition, the transcriptomes of dozens of insects have been sequenced. As gene data rapidly accumulate, constructing the pathway of molecular interactions becomes increasingly important for entomological research. Here, we developed an improved tool, iPathCons, for knowledge-based construction of pathways from the transcriptomes or the official gene sets of genomes. Considering the high evolution diversity in insects, iPathCons uses a voting system for Kyoto Encyclopedia of Genes and Genomes Orthology assignment. Both stand-alone software and a web server of iPathCons are provided. Using iPathCons, we constructed the pathways of molecular interactions of 52 insects, including 37 genome-sequenced and 15 transcriptome-sequenced ones. These pathways are available in the iPathDB, which provides searches, web server, data downloads, etc. This database will be highly useful for the insect research community. Database URL: http://ento.njau.edu.cn/ipath/ PMID:25388589

  8. Treatment of plutonium contaminated soil/sediment from the Mound site using the ACT*DE*CON{sup SM} process

    SciTech Connect

    Negri, M.C.; Swift, N.A.; North, J.P.

    1996-10-01

    The removal and/or treatment of contaminated soil is a major problem facing the US DOE. The EG&G Mound Applied Technologies site in Miamisburg, Ohio, has an estimated 1.5 million cubic feet of soils from past disposal and waste burial practices awaiting remediation from plutonium contamination. This amount includes sediment from the Miami-Erie Canal that was contaminated in 1969 following a pipe- rupture accident. Conventional soil washing techniques that use particle separation would generate too large a waste volume to be economically feasible. Therefore, innovative technologies are needed for the cleanup. The ACT*DE*CON process was developed by SELENTEC for washing soils to selectively dissolve and remove heavy metals and radionuclides. ACT*DE*CON chemically dissolves and removes heavy metals and radionuclides from soils and sediments into an aqueous medium. The ACT*DE*CON process uses oxidative carbonate/chelant chemistry to dissolve the contaminant from the sediment and hold the contaminant in solution. The objective of recent work was to document the proves conditions necessary to achieve the Mound-site and regulatory-cleanup goals using the ACT*DE*CON technology.

  9. Pro/Con debate: Is occupational asthma induced by isocyanates an immunoglobulin E-mediated disease?

    PubMed

    Wisnewski, A V; Jones, M

    2010-08-01

    Isocyanates, low-molecular weight chemicals essential to polyurethane production, are one of the most common causes of occupational asthma, yet the mechanisms by which exposure leads to disease remain unclear. While isocyanate asthma closely mirrors other Type I Immune Hypersensitivity (Allergic) disorders, one important characteristic of hypersensitivity ('allergen'-specific IgE) is reportedly absent in a large portion of affected individuals. This variation from common environmental asthma (which typically is induced by high-molecular weight allergens) is important for two reasons. (1) Allergen-specific IgE is an important mediator of many of the symptoms of bronchial hyper-reactivity in 'allergic asthma'. Lack of allergen-specific IgE in isocyanate hypersensitive individuals suggests differences in pathogenic mechanisms, with potentially unique targets for prevention and therapy. (2) Allergen-specific IgE forms the basis of the most commonly used diagnostic tests for hypersensitivity (skin prick and RAST). Without allergen-specific IgE, isocyanates may go unrecognized as the cause of asthma. In hypersensitive individuals, chronic exposure can lead to bronchial hyperreactivity that persists years after exposure ceases. Thus, the question of whether or not isocyanate asthma is an IgE-mediated disease, has important implications for disease screening/surveillance, diagnosis, treatment and prevention. The present Pro/Con Debate, addresses contemporary, controversial issues regarding IgE in isocyanate asthma.

  10. Structural and magnetic properties of N doped Fe_mCon superlattices: First principles calculations.

    NASA Astrophysics Data System (ADS)

    Kim, Miyoung; Freeman, A. J.

    2001-03-01

    Magnetic alloys and multilayers have been widely investigated because of their potential for magnetic device applications. In this, materials exhibiting high magnetization as well as good soft magnetic properties are desirable. We investigated the magnetic and structural properties of Fe_mCon superlattices with various compositions via first principles local density full potential linearized augmented plane wave (FLAPW) method^(1) calculations. For the 25% Co composition which showed the maximum magnetic moments, we inserted N atoms to make (Fe_3Co)_4N_2, in order to examine the possible magnetic enhancement by N, which has drawn much attention since the first report (in 1972) of a giant magnetic moment for the quasi-stable α-Fe_16N_2. The structural optimization was fully accomplished by total energy and atomic force calculations. Despite the lattice expansion due to the N insertion, the magnetic moment of (Fe_3Co)_4N2 was found to be reduced from the value of the Fe_3Co superlattice by the strong hybridization of N with Fe and Co. (1) E. Wimmer, H. Krakauer, M. Weinert and A. J. Freeman, Phys. Rev. B 24, 864 (1981).

  11. A new millimeter-wave observation of the weakly bound CO-N2 complex

    NASA Astrophysics Data System (ADS)

    Surin, L. A.; Potapov, A.; Müller, H. S. P.; Schlemmer, S.

    2015-01-01

    New millimeter-wave transitions of the CO-N2 van der Waals complex have been observed using the intracavity OROTRON jet spectrometer in the frequency range of 103-159 GHz. For the less abundant form, CO-paraN2, a total of 37 rotational transitions were assigned to three K = 0-0, 0-1, 2-1 subbands connecting the (jCO, jN2) = (1, 1) and (jCO, jN2) = (0, 1) internal rotor states. The upper K = 0 and K = 2 "stacks" of rotational levels were probed for the first time here by millimeter-wave spectroscopy following a recent infrared study by Rezaei et al. (2013). The observation of new subbands fixes with higher precision not only these upper K = 0 and K = 2 but also lower K = 1(f) levels, not linked with other stacks in earlier rotational studies. For the more abundant form, CO-orthoN2, five new P-branch rotational transitions of the K = 0-0 "CO bending" subband are reported, thus extending previous measurements. Nuclear quadrupole hyperfine structure due to the presence of two equivalent 14N nuclei was partly resolved and analyzed to give additional information about the angular orientation of the N2 molecule in the complex.

  12. Assessing ComSciCon 2013: A science communication workshop for STEM graduate students (Invited)

    NASA Astrophysics Data System (ADS)

    Kohler, S.; Ranjan, S.; Sanders, N.; Morey, S.

    2013-12-01

    We report on the efficacy of Communicating Science 2013, a science communication workshop for graduate students. Effective science communication is imperative for the sharing of scientific ideas, continued funding and support from policy makers, and education of the public. Science graduate students are a prime group to target for communication training, as they will be our future scientists, educators, and EPO professionals. To this end, Communicating Science 2013 (ComSciCon), a workshop organized by and for STEM graduate students, was held in June of this year. This workshop taught graduate students from around the nation to effectively communicate science to both their peers and the public. To learn about grad students' attitudes toward science communication and establish the workshop's efficacy, we surveyed the participants both before and after the workshop. This assessment probed topics such as communication preparation the participants have already received, how science communication is perceived in their home department, and what participants gained from the workshop. We report the results here.

  13. Nonalcoholic Fatty Liver Disease: Pros and Cons of Histologic Systems of Evaluation.

    PubMed

    Brunt, Elizabeth M

    2016-01-13

    The diagnostic phenotype of nonalcoholic fatty liver disease (NAFLD)--in particular, the most significant form in terms of prognosis, nonalcoholic steatohepatitis (NASH)--continues to rely on liver tissue evaluation, in spite of remarkable advances in non-invasive algorithms developed from serum-based tests and imaging-based or sonographically-based tests for fibrosis or liver stiffness. The most common tissue evaluation remains percutaneous liver biopsy; considerations given to the needle size and the location of the biopsy have the potential to yield the most representative tissue for evaluation. The pathologist's efforts are directed to not only global diagnosis, but also assessment of severity of injury. Just as in other forms of chronic liver disease, these assessments can be divided into necroinflammatory activity, and fibrosis with parenchymal remodeling, in order to separately analyze potentially reversible (grade) and non-reversible (stage) lesions. These concepts formed the bases for current methods of evaluating the lesions that collectively comprise the phenotypic spectra of NAFLD. Four extant methods have specific applications; there are pros and cons to each, and this forms the basis of the review.

  14. Pros and cons in endocrine practice: pre-surgical treatment with somatostatin analogues in acromegaly.

    PubMed

    Losa, Marco; Bollerslev, Jens

    2016-06-01

    The aim of this commentary is to balance the pros and cons for pre-surgical SSA treatment in a modern perspective ending up with a pragmatic recommendation for treatment based on the current evidence and expertise of the authors. Even though prospective and randomized studies in this particular area are hampered by obvious limitations, the interpretation of the four published trials has in general been in favor of pre-treatment with SSA, showing a better outcome following surgery. However, major drawbacks of these studies, such as non-optimal diagnostic criteria for cure, potential selection bias, and timing of the postoperative evaluation in SSA pre-treated patients, limit their overall interpretation. Three matched-controlled studies showed remarkably similar results with no apparent beneficial effect of SSA pre-treatment on surgical outcome. Both prospective, randomized studies and retrospective studies did not find any significant difference in the rate of endocrine and non-endocrine complications related to surgery, despite the beneficial clinical effects of SSA treatment in most acromegalic patients. The newly diagnosed patient with acromegaly should be carefully evaluated in the trans-disciplinary neuroendocrine team and treatment individualized accordingly. The issue of SSA pre-treatment to improve surgical outcome is yet to be settled and further methodologically sound studies are probably necessary to clarify this point.

  15. Synthesis of colloidal metal nanocrystals in droplet reactors: the pros and cons of interfacial adsorption.

    PubMed

    Zhang, Lei; Wang, Yi; Tong, Limin; Xia, Younan

    2014-07-09

    Droplet reactors have received considerable attention in recent years as an alternative route to the synthesis and potentially high-volume production of colloidal metal nanocrystals. Interfacial adsorption will immediately become an important issue to address when one seeks to translate a nanocrystal synthesis from batch reactors to droplet reactors due to the involvement of higher surface-to-volume ratios for the droplets and the fact that nanocrystals tend to be concentrated at the water-oil interface. Here we report a systematic study to compare the pros and cons of interfacial adsorption of metal nanocrystals during their synthesis in droplet reactors. On the one hand, interfacial adsorption can be used to generate nanocrystals with asymmetric shapes or structures, including one-sixth-truncated Ag octahedra and Au-Ag nanocups. On the other hand, interfacial adsorption has to be mitigated to obtain nanocrystals with uniform sizes and controlled shapes. We confirmed that Triton X-100, a nonionic surfactant, could effectively alleviate interfacial adsorption while imposing no impact on the capping agent typically needed for a shape-controlled synthesis. With the introduction of a proper surfactant, droplet reactors offer an attractive platform for the continuous production of colloidal metal nanocrystals.

  16. Ground and lowest-lying electronic states of CoN. A multiconfigurational study.

    PubMed

    Gobbo, João Paulo; Borin, Antonio Carlos

    2006-12-28

    The lowest-lying X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and B1II electronic states of CoN have been investigated at the ab initio MRCI and MS-CASPT2 levels, with extended atomic basis sets and inclusion of scalar relativistic effects. Among the singlet states, the A1Phi and B1II states have been described for the first time. Potential energy curves, excitation energies, spectroscopic constants, and bonding character for all states are reported. Comparison with other early transition-metal nitrides (ScN, TiN, VN, and CrN), isoelectronic (NiC) and isovalent (RhN and IrN) species has been made, besides analyzing the B1II <=> X1+ electronic transition in terms of Franck-Condon factors, Einstein coefficients, and radiative lifetimes. At both levels of theory, the following energetic order has been obtained: X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and B1II, with good agreement with experimental results. In contrast, previous DFT and MRCI calculations predicted the ground state to be the 5Delta state.

  17. Pros and cons of condom use among gay and bisexual men as explored via the Internet.

    PubMed

    Gullette, Donna L; Turner, Joan G

    2003-01-01

    The purpose of this study was to conduct a survey utilizing Internet technology related to gay and bisexual men's condom use behavior as an expression of safer sexual practices. A total of 241 self-identified gay and bisexual men responded to the questionnaire in a 3-month period of time. Confidentiality was assured by utilizing an electronic system whereby the respondents e-mail address was eliminated. The study was conceptually guided by the use of the Transtheoretical Model of Behavioral Change (TMC) and the pros and cons of condom of use were explored. Fifty-six percent of the participants reported that one advantage (pro) of using condoms with casual partners was that it would make them safer from disease. About half of the respondents (n = 119, 49%) reported a history of one or more sexually transmitted diseases. There were 14 variables found to be significantly associated with using a condom with primary and casual partners among gay and bisexual men. Essentially, findings from this study corresponded to results obtained by more traditional data collection methods. Therefore, the authors conclude that electronic data collection may well be an alternative means for collecting sensitive data such as those collected in this study.

  18. Pros and cons of the liposome platform in cancer drug targeting.

    PubMed

    Gabizon, Alberto A; Shmeeda, Hilary; Zalipsky, Samuel

    2006-01-01

    Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.

  19. Thromboprophylaxis in carriers of antiphospholipid antibodies (APL) without previous thrombosis: "Pros" and "Cons".

    PubMed

    Ceccarelli, Fulvia; Chighizola, Cecilia; Finazzi, Guido; Meroni, Pier Luigi; Valesini, Guido

    2012-06-01

    The presence of anti-phospholipid (aPL) is necessary but not sufficient to induce a thrombotic event. The "second hit" hypothesis suggested that an additional trigger may be needed to develop a vascular event in aPL carriers. In this article, pro and con of primary thromboprophylaxis in aPL carriers is deeply discussed, concluding that univocal data are not available, due to conflicting results of available clinical trials. However, in clinical practice the primary thromboprophylaxis is not indicated in all unselected asymptomatic aPL carriers, and the best strategy begin with the assessment of the peculiar risk profile of the subject. Thus, it is mandatory to eliminate modifiable prothrombotic risk factors (i.e. smoking, oral contraceptive), to treat the irreversible risk factors (i.e. hypertension, diabetes) and to introduce an aggressive prophylaxis with subcutaneous LMWH in high-risk situations (i.e. surgical procedures with prolonged immobilization). A different evaluation should be addressed to aPL carriers with a concomitant autoimmune disease that are considered as an additional pro-thrombotic risk factor. Similarly, concomitant positivity for more than one anti-phospholipid test confer a stronger risk of developing the thrombotic manifestations. Specific trials with larger cohorts of patients are needed to better clarify this issue.

  20. Pros and cons of BCG vaccination in countries with low incidence of tuberculosis.

    PubMed

    Tala, E O; Tala-Heikkilä, M M

    1994-07-01

    Preventive bacille Calmette-Guérin (BCG) vaccination, together with case finding and effective chemotherapy, has formed an integral part of the tuberculosis (TB) control program in most countries. In some low-incidence countries the balance of prevention has been more on the side of chemoprophylaxis than of BCG vaccination. The time clearly has come when the strategy of mass BCG vaccination no longer is indicated medically, nor is it cost-effective. The pros and cons of the programs need to be critically evaluated against the present epidemiological background, taking into account the facts that TB, the killer disease, is recovering strength, human immunodeficiency virus infection is on the increase, and multidrug-resistant TB has changed the outcome of this previously fully curable disease. Although no longer appropriate for mass programs, BCG vaccination still should be considered for the protection of selected risk groups in low-incidence countries. The overall efficacy may be of the order 50% to 80%, but the variation is great. Therefore, further research urgently is needed on the effectiveness of BCG as an intervention in local TB programs.

  1. Pros and cons of liver transplantation in human immunodeficiency virus infected recipients.

    PubMed

    Baccarani, Umberto; Righi, Elda; Adani, Gian Luigi; Lorenzin, Dario; Pasqualucci, Alberto; Bassetti, Matteo; Risaliti, Andrea

    2014-05-14

    Before the introduction of combined highly active antiretroviral therapy, a positive human immunodeficiency virus (HIV) serological status represented an absolute contraindication for solid organ transplant (SOT). The advent of highly effective combined antiretroviral therapy in 1996 largely contributed to the increased demand for SOT in HIV-positive individuals due to increased patients' life expectancy associated with the increasing prevalence of end-stage liver disease (ESLD). Nowadays, liver failure represents a frequent cause of mortality in the HIV-infected population mainly due to coinfection with hepatitis viruses sharing the same way of transmission. Thus, liver transplantation (LT) represents a reasonable approach in HIV patients with stable infection and ESLD. Available data presently supports with good evidence the practice of LT in the HIV-positive population. Thus, the issue is no longer "whether it is correct to transplant HIV-infected patients", but "who are the patients who can be safely transplanted" and "when is the best time to perform LT". Indeed, the benefits of LT in HIV-infected patients, especially in terms of mid- and long-term patient and graft survivals, are strictly related to the patients' selection and to the correct timing for transplantation, especially when hepatitis C virus coinfection is present. Aim of this article is to review the pros and cons of LT in the cohort of HIV infected recipients.

  2. Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

    PubMed Central

    Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

    2015-01-01

    Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

  3. [Long-term infliximab therapy for ulcerative colitis in real clinical practice].

    PubMed

    Knyazev, O V; Parfenov, A I; Kagramanova, A V; Ruchkina, I N; Shcherbakov, P L; Shakhpazyan, N K; Noskova, K K; Ivkina, T I; Khomeriki, S G

    Резюме Цель исследования. Ретроспективная оценка эффективности длительного лечения инфликсимабом (ИФЛ) больных с рефрактерными формами язвенного колита (ЯК). Материалы и методы. В исследование включили 48 больных с рефрактерными формами ЯК, получавших ИФЛ с 2008 по 2014 г. Стероидозависимый или стероидорефрактерный ЯК установлен у 40 (83,3%) пациентов, у 8 (16,7%) отмечена рефрактерность к терапии азатиоприном или 6-меркаптопурином. У 7 пациентов в биоптатах слизистой оболочки толстой кишки (СОТК) обнаружены ДНК цитомегаловируса. Противовирусную терапию получал 1 больной. Индукционная терапия ИФЛ заключалась в применении ИФЛ в дозе 5 мг/кг на 0, 2 и 6-й неделях, после чего продолжали поддерживающую терапию каждые 8 нед. Результаты. После проведения индукционного курса ИФЛ 3 (6,3%) больных не ответили на терапию и были исключены из исследования. Из 45 больных, ответивших на терапию, 25 (55,5%) до настоящего времени продолжают получать ИФЛ в дозах 5 мг/кг через каждые 8 нед и находятся в состоянии клинической ремиссии; 4 (8,8%) пациента получают интенсифицированную терапию ИФЛ. Изначально комбинированную терапию ИФЛ + иммуносупрессор получали 23 больных, монотерапию ИФЛ — 22. У 5 (11,1%) больных наблюдалось ускользание эффекта от проводимой терапии, что потребовало ее интенсификации. У 4 (8,8%) пациентов на фоне усиления терапии ИФЛ сохраняется ремиссия, в одном (2,2%) случае выполнена колэктомия. Вторичная потеря ответа на ИФЛ, непереносимость ИФЛ, развитие тяжелых инфекционных осложнений, не позволивших дальнейшее проведение поддерживающей терапии ИФЛ, сформировались у 11 (24,4%) пациентов, 5 (11,1%) прекратили терапию в связи с исключением из списка по дополнительному льготному обеспечению лекарственными средствами. Поддерживающая терапия ИФЛ оказалась успешной на протяжении 64 мес у 29 (64,4%) из 45 пациентов, на протяжении 64 мес при условии повышения ее интенсивности в случае необходимости. Заключение. Длительное применение ИФЛ при ЯК подтвердило его высокую эффективность в достижении клинического ответа, индукции клинической ремиссии, способности к заживлению СОТК и поддержании ремиссии.

  4. 40 CFR 180.1213 - Coniothyrium minitans strain CON/M/91-08; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Coniothyrium minitans strain CON/M/91... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1213 Coniothyrium minitans strain CON/M... tolerance is established for residues of the microbial pesticide Coniothyrium minitans strain...

  5. 40 CFR 180.1213 - Coniothyrium minitans strain CON/M/91-08; exemption from the requirement of a tolerance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Coniothyrium minitans strain CON/M/91... PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1213 Coniothyrium minitans strain CON/M... tolerance is established for residues of the microbial pesticide Coniothyrium minitans strain...

  6. (Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy

    PubMed Central

    Yong, Keir X.X.; Shakespeare, Timothy J.; Cash, Dave; Henley, Susie M.D.; Warren, Jason D.; Crutch, Sebastian J.

    2014-01-01

    Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease. PMID:24841985

  7. 40Ar/39Ar laserprobe study of the Day Nui Con Voi Metamorphic Complex, Vietnam

    NASA Astrophysics Data System (ADS)

    Wu, C.; Lo, C.; Yeh, M.; Chung, S.; Lee, T.

    2009-12-01

    The garnet bearing gneiss within the Day Nui Con Voi (DNCV) Metamorphic Complex along the Red River Shear Zone (RRSZ) in North Vietnam, recorded a long tectonothermal history since the Indosinian orogeny. In-situ 40Ar/39Ar laserprobe study of biotite inclusions within garnet porphyroblasts and matrix biotites, combining with microstructural and scanning electron microscopy (SEM) studies, deciphered the timing and duration of thermal events. Biotites from two matrix fabrics from different deformation events show approximately similar 40Ar/39Ar age ranges in 19-24Ma, depending grain size. These matrix biotite ages are best interpreted to record a rapid cooling event associating with the left-lateral shearing event of the RRSZ. Whereas, all biotite inclusions exhibit age zoning patterns with 40Ar/39Ar ages gradually increase from 17 Ma to more than 28 Ma according to their diffusion pathways. These age variations may have resultant from a combination effect of argon retention by garnet shielding, which provides a best recorder to the metamorphic event, and argon diffusion loss along the deformed cracks during the shearing event of the RRSZ. Diffusion modeling of these age zoning indicated that the total duration of argon diffusion loss may have lasted for nearly 9 Myr and argon diffusion may have occurred sometime around 24.5Ma. These results are generally in good agreement with previous interpretation, but provide better resolution of 40Ar/39Ar age data for deciphering the history of thermal event in the DNCV Metamorphic Complex and the left-lateral shearing event of the RRSZ in Vietnam, as well.

  8. Characterization Data Package for Containerized Sludge Samples Collected from Engineered Container SCS-CON-210

    SciTech Connect

    Fountain, Matthew S.; Fiskum, Sandra K.; Baldwin, David L.; Daniel, Richard C.; Bos, Stanley J.; Burns, Carolyn A.; Carlson, Clark D.; Coffey, Deborah S.; Delegard, Calvin H.; Edwards, Matthew K.; Greenwood, Lawrence R.; Neiner, Doinita; Oliver, Brian M.; Pool, Karl N.; Schmidt, Andrew J.; Shimskey, Rick W.; Sinkov, Sergey I.; Snow, Lanee A.; Soderquist, Chuck Z.; Thompson, Christopher J.; Trang-Le, Truc LT; Urie, Michael W.

    2013-09-10

    This data package contains the K Basin sludge characterization results obtained by Pacific Northwest National Laboratory during processing and analysis of four sludge core samples collected from Engineered Container SCS-CON-210 in 2010 as requested by CH2M Hill Plateau Remediation Company. Sample processing requirements, analytes of interest, detection limits, and quality control sample requirements are defined in the KBC-33786, Rev. 2. The core processing scope included reconstitution of a sludge core sample distributed among four to six 4-L polypropylene bottles into a single container. The reconstituted core sample was then mixed and subsampled to support a variety of characterization activities. Additional core sludge subsamples were combined to prepare a container composite. The container composite was fractionated by wet sieving through a 2,000 micron mesh and a 500-micron mesh sieve. Each sieve fraction was sampled to support a suite of analyses. The core composite analysis scope included density determination, radioisotope analysis, and metals analysis, including the Waste Isolation Pilot Plant Hazardous Waste Facility Permit metals (with the exception of mercury). The container composite analysis included most of the core composite analysis scope plus particle size distribution, particle density, rheology, and crystalline phase identification. A summary of the received samples, core sample reconstitution and subsampling activities, container composite preparation and subsampling activities, physical properties, and analytical results are presented. Supporting data and documentation are provided in the appendices. There were no cases of sample or data loss and all of the available samples and data are reported as required by the Quality Assurance Project Plan/Sampling and Analysis Plan.

  9. Perfiles de luminosidad en galaxias con núcleo tipo Seyfert 1

    NASA Astrophysics Data System (ADS)

    Boris, N.; Rodriguez-Ardilla, A. A.; Pastoriza, M. G.

    Presentamos imágenes CCD en los filtros BVI y Hα de una muestra de 10 galaxias Seyfert 1 y Narrow Line Seyfert 1. Recientes observaciones muestran que hay una diferencia significante en el índice espectral óptico entre NLS1s y Sy1 normales, siendo para las primeras del orden de 2. Otra característica importante es que la mayor parte de las NLS1s muestran tasas de FeII/Hβ mayores que las observadas en otras Sy1s. Desde el punto de vista fotométrico, estas galaxias no tienenningún tipo de estudio previo. Presentamos magnitudes totales, perfiles de luminosidad y mapas de color junto con un detallado análisis de la formación estelar en estos objetos. Encontramos que la descomposición en bulbo + disco representa adecuadamente los perfiles de luminosidad de las galaxias de la muestra. Sin embargo, en todos los casos es necesario que el disco tenga un agujero en su centro. El radio de este agujero va desde los 3 a los 9 kpc. Si bien no tenemos aún una explicación para este hecho, los agujeros parecen estar asociados a anillos circumnucleares de alto oscurecimiento E(B-V) ~1. Los perfiles presentan también un fuerte gradiente de color, siendo notablemente más azules hacia la región nuclear. Los objetos de la muestra cubren todo el rango de tipos morfológicos, no obstante, no encontramos regiones de formación estelar en las regiones exteriores de las galaxias. La formación estelar está confinada a la región nuclear y se data en alrededor de 5 x 107 años.

  10. (Con)text-specific effects of visual dysfunction on reading in posterior cortical atrophy.

    PubMed

    Yong, Keir X X; Shakespeare, Timothy J; Cash, Dave; Henley, Susie M D; Warren, Jason D; Crutch, Sebastian J

    2014-08-01

    Reading deficits are a common early feature of the degenerative syndrome posterior cortical atrophy (PCA) but are poorly understood even at the single word level. The current study evaluated the reading accuracy and speed of 26 PCA patients, 17 typical Alzheimer's disease (tAD) patients and 14 healthy controls on a corpus of 192 single words in which the following perceptual properties were manipulated systematically: inter-letter spacing, font size, length, font type, case and confusability. PCA reading was significantly less accurate and slower than tAD patients and controls, with performance significantly adversely affected by increased letter spacing, size, length and font (cursive < non-cursive), and characterised by visual errors (69% of all error responses). By contrast, tAD and control accuracy rates were at or near ceiling, letter spacing was the only perceptual factor to influence reading speed in the same direction as controls, and, in contrast to PCA patients, control reading was faster for larger font sizes. The inverse size effect in PCA (less accurate reading of large than small font size print) was associated with lower grey matter volume in the right superior parietal lobule. Reading accuracy was associated with impairments of early visual (especially crowding), visuoperceptual and visuospatial processes. However, these deficits were not causally related to a universal impairment of reading as some patients showed preserved reading for small, unspaced words despite grave visual deficits. Rather, the impact of specific types of visual dysfunction on reading was found to be (con)text specific, being particularly evident for large, spaced, lengthy words. These findings improve the characterisation of dyslexia in PCA, shed light on the causative and associative factors, and provide clear direction for the development of reading aids and strategies to maximise and sustain reading ability in the early stages of disease.

  11. "Pros and cons" of total hip arthroplasty with metaphyseal Proxima endoprosthesis.

    PubMed

    Wraźen, Waldemar; Golec, Edward B; Tomaszewski, Krzysztof A; Golec, Piotr; Jaworowski, Michał de Lubicz; Dudkiewicz, Zbigniew

    2015-01-01

    The authors present their own experience concerning total hip arthroplasty with the metaphyseal prosthesis Proxima. Proxima, a metaphyseal prosthesis, provides an innovative supplement to total hip arthroplasty. In this study, the authors present their own experience using Proxima in patients with hip osteoarthritis. This study was performed between 2008 to 2013 and comprised of 62 patients, of which 38 were male (61.3%) and 24 female (38.7%). All patients were operated on due to hip osteoarthritis using total hip arthroplasty with the metaphyseal prosthesis Proxima. The age of patients included into the study ranged from 23 years to 62 years with the mean age of 46 years. The authors paid close attention to the "pros and cons" of surgical techniques and assessed clinical and radiological results in both the short and long-term observation periods. The clinical evaluation was based on the Harris Hip Score and radiological assessment of fixation of the acetabular cup of the endoprosthesis was based on Pradhan's criteria. The endoprosthesis Proxima stem was positioned using the manufacturer's recommended method, evaluating the direction, scope and duration of the displacement in the marrow cavity of the proximal stump of the femur. According to the authors' analysis, the surgery gives good functional and radiological results both in the short- and long-term observation periods. The effectiveness depends on precise qualification for surgery, proper surgical techniques and specific anatomical conditions of the proximal femur stump. The most common reasons for primary and secondary dislocations of the metaphyseal endoprosthesis Proxima stem occur during the first three months post surgery. This is due to incorrect surgical techniques, which disregard the importance of specific anatomical conditions of the proximal femoral stump, which affects Proxima implantation, and cause deviations towards a varus or valgus orientation.

  12. Outreach Opportunities for Early Career Scientists at the Phoenix ComiCon

    NASA Astrophysics Data System (ADS)

    Horodyskyj, L.; Walker, S. I.; Forrester, J. H.

    2014-12-01

    The Phoenix ComiCon (PCC) is a rapidly growing annual four-day pop culture event, featuring guests, costuming, exhibits, and discussion panels for popular sci-fi, fantasy, horror, and anime franchises. In 2013, PCC began experimenting with science discussion panels. The popularity of the science programming resulted in an expansion of the track for 2014, which Horodyskyj was responsible for coordinating. Thirty hours of programming were scheduled, including 25 discussion panels, NASA's FameLab, and a Mars room. Panelists included industry specialists, established scientists, STEM outreach enthusiasts, and early career scientists. The majority of the panelists were early career scientists recruited from planetary sciences and biology departments at ASU and UA. Panel topics included cosmology, biotechnology, artificial intelligence, space exploration, astrobiology, and the cross-linkages of each with pop culture. Formats consisted of Q&A, presentations, and interactive game shows. Although most panels were aimed at the general audience, some panels were more specialized. PCC 2014 attracted 77,818 attendees. The science programming received rave reviews from the audience, the PCC management, and the panelists themselves. Many panel rooms were filled to capacity and required crowd control to limit attendance. We observed the formation of science "groupies" who sought out the science panels exclusively and requested more information on other science public events in the Phoenix area. We distributed surveys to several select sessions to evaluate audience reasons for attending the science panels and their opinion of the scientists they observed. We will present the results of these surveys. As the PCC continues to grow at an exponential rate, the science programming will continue to expand. We will discuss ideas for continued expansion of the PCC science programming both to serve the public and as a unique public outreach opportunity for early career scientists.

  13. Estereotipos Sexuales y su Relación con Conductas Sexuales Riesgosas1,2,3

    PubMed Central

    Pérez-Jiménez, David; Orengo-Aguayo, Rosaura E.

    2012-01-01

    Resumen Los estereotipos sexuales son creencias generalmente aceptadas y poco cuestionadas que podrían contribuir a cómo los hombres y las mujeres debemos expresar nuestra sexualidad. Los objetivos de este estudio eran identificar cuántos hombres y mujeres heterosexuales en Puerto Rico endosaban ciertos estereotipos acerca de la sexualidad masculina y femenina y explorar la relación entre el endoso de estos estereotipos sexuales y las actitudes hacia el condón masculino y su uso en relaciones sexuales vaginales Llevamos a cabo un estudio descriptivo-correlacional mediante el cual le administramos dos escalas, una sobre sexualidad masculina y otra sobre sexualidad femenina a un grupo de 429 personas heterosexuales. Encontramos que los hombres endosaron estereotipos sexuales masculinos y femeninos más que las mujeres y que estos tienden a tener una visión más conservadora respecto a la sexualidad femenina que la que tienen sobre su propia sexualidad. Las mujeres, por otra parte, tienden a ver su propia sexualidad y la sexualidad masculina en términos menos estereotipados y más equitativos. También encontramos que a mayor endoso de creencias tradicionales sobre la sexualidad masculina y femenina, peor la actitud hacia el uso del condón masculino. Sin embargo, el endosar estereotipos sexuales masculinos y/o femeninos no se relacionó con el uso del condón. Estos hallazgos contradicen la literatura que sugiere que estos estereotipos sexuales y de género resultan en conductas sexuales de alto riesgo, lo cual tiene implicaciones importantes para el desarrollo e implementación de programas de prevención. PMID:24575164

  14. Strain Rate into South American Plate by SIRGAS-CON Geodetic Observations

    NASA Astrophysics Data System (ADS)

    Marotta, G. S.; Franca, G. S.; Monico, J. G.; Fuck, R. A.

    2013-05-01

    In this study were investigated the surface strain rates computed from the direction variations and velocity values estimated from the coordinates of the continuous monitoring geodetic network called SIRGAS-CON. That investigation was done using points located in the South American plate. The determination of the strain rate was based on the Finite Element method using points defined by Delaunay triangulation (sub-networks). Each one of sub-networks was considered as an homogeneous solid body. Using these methods was possible to separate the strain from the plate movement. The results showed that there are differences of strain rate along the South American plate. From the results were suggest that near to the west board of the plate, the strain is more significant, as expected, because this region is near to one area where Nazca Plate subduct South American Plate. It was detected that the contraction region founded in this area coincides whit the region where occurs most of earthquakes of greater magnitude. Far from the board, there are some areas with anomalies of significant strain of extension and contraction that can be originated by differences of stress aligned with different geological composites. By the results, It may be concluded that large surface movements occur in regions with more heterogeneous geological structures and multiple event of rupture, that large earthquakes arising from large tectonic activity into South American Plate are concentrated in areas with contraction strain rates predominantly oriented towards northeast-southwest, that significant amounts of elastic strain can be accumulated over geological structures away from fault plate boundary and that the behavior of contractions and extensions are similar to that found by different researches involving geophysical studies. Dilation and principal components of strain rate

  15. Iliac crest autograft versus alternative constructs for anterior cervical spine surgery: Pros, cons, and costs

    PubMed Central

    Epstein, Nancy E.

    2012-01-01

    Background: Grafting choices available for performing anterior cervical diskectomy/fusion (ACDF) procedures have become a major concern for spinal surgeons, and their institutions. The “gold standard”, iliac crest autograft, may still be the best and least expensive grafting option; it deserves to be reassessed along with the pros, cons, and costs for alternative grafts/spacers. Methods: Although single or multilevel ACDF have utilized iliac crest autograft for decades, the implant industry now offers multiple alternative grafting and spacer devices; (allografts, cages, polyether-etherketone (PEEK) amongst others). While most studies have focused on fusion rates and clinical outcomes following ACDF, few have analyzed the “value-added” of these various constructs (e.g. safety/efficacy, risks/complications, costs). Results: The majority of studies document 95%-100% fusion rates when iliac crest autograft is utilized to perform single level ACDF (X-ray or CT confirmed at 6-12 postoperative months). Although many allograft studies similarly quote 90%-100% fusion rates (X-ray alone confirmed at 6-12 postoperative months), a recent “post hoc analysis of data from a prospective multicenter trial” (Riew KD et. al., CSRS Abstract Dec. 2011; unpublished) revealed a much higher delayed fusion rate using allografts at one year 55.7%, 2 years 87%, and four years 92%. Conclusion: Iliac crest autograft utilized for single or multilevel ACDF is associated with the highest fusion, lowest complication rates, and significantly lower costs compared with allograft, cages, PEEK, or other grafts. As spinal surgeons and institutions become more cost conscious, we will have to account for the “value added” of these increasingly expensive graft constructs. PMID:22905321

  16. Pros and cons of intraperitoneal chemotherapy in the treatment of epithelial ovarian cancer.

    PubMed

    Zeimet, Alain G; Reimer, Daniel; Radl, Alice C; Reinthaller, Alexander; Schauer, Christian; Petru, Edgar; Concin, Nicole; Braun, Stephan; Marth, Christian

    2009-07-01

    Development of the pros and cons of intraperitoneal (IP) chemotherapy in the treatment of epithelial ovarian cancer based on the most prominent data published on the evolution of IP chemotherapy and on experience with this therapeutic strategy in clinical routine. The literature published on IP chemotherapy in ovarian cancer between 1970 and 2008 was identified systematically by computer-based searches in MEDLINE and the Cochrane Library. Furthermore, a preliminary analysis of data recorded during an observational nationwide multicenter study of the Austrian AGO on IP-IV chemotherapy using the GOG-172 treatment regimen was performed. The literature review unequivocally revealed a significantly greater toxicity for IP than for intravenous (IV) cisplatin-based chemotherapy. However, according to a Cochrane meta-analysis, IP-IV administration of chemotherapy is associated with a 21.6% decrease in the risk for death. In agreement with earlier reports, the most frequently mentioned side-effects in the Austria-wide observational study were long-lasting neurotoxicity, abdominal pain, fatigue, gastrointestinal and metabolic toxicities, and catheter-related complications. Most of these toxicities were identified as mirroring the toxicity profile of high-dose IV cisplatin (>or=100 mg/m(2)). In some patients, the classic IP-IV regimen with cisplatin/paclitaxel was changed to an alternative schedule comprising carboplatin AUC 5 (d1) and weekly paclitaxel 60 mg/m(2) (d1, 8, 15) completely administered via the IP route. This treatment was better tolerated and quality of life was significantly less compromised. However, neutropenia and thrombocytopenia were the limiting side-effects of this IP regimen. In cases where optimal cytoreduction with residual disease

  17. [Etanercept on steroid-refractary acute graft-versus-host disease].

    PubMed

    González Munguía, Silvia; Pérez León, Moisés; Piñero González, Marta; Díaz Pestano, Marina Magnolia; Molero Gómez, Rafael; Luzardo Henríquez, Hugo Daniel

    2015-05-01

    Objetivo: Describir el uso y la efectividad de etanercept como terapia en la enfermedad de injerto contra huésped refractaria a corticoides tras el trasplante alogénico de progenitores hematopoyéticos. Método: Se seleccionaron los pacientes en los que se utilizó etanercept fuera de indicación para el tratamiento de la enfermedad de injerto contra huésped y se revisaron retrospectivamente sus historias clínicas para evaluar la respuesta al tratamiento. Resultados: De un total fueron cinco pacientes tratados cuatro presentaban enfermedad con afectación digestiva y otro con manifestación pulmonar y hepática. En el 80% de los casos se alcanzó alguna respuesta clínica: 60% respuesta parcial y 20% respuesta completa. En cuatro pacientes se utilizo etanecept 25mg dos veces por semana con duración variable, obteniendo una respuesta nula en uno (3 semanas), parcial en dos (4 y 8 semanas) y total en otro (8 semanas). Sólo en un caso se usó etanercept 50mg dos veces en semana durante 5 semanas con respuesta parcial. Conclusiones: Los resultados obtenidos de respuesta clínica son coherentes con los publicados previamente y vienen a incrementar la escasa bibliografía sobre la utilidad de etanercept en el tratamiento en la enfermedad de injerto contra huésped aguda y refractaria a corticoides. Dadas las limitaciones del diseño y el reducido número de pacientes, estudios controlados deberán evaluar en el futuro la eficacia y la seguridad de etanercept en estos pacientes.

  18. Single step purification of concanavalin A (Con A) and bio-sugar production from jack bean using glucosylated magnetic nano matrix.

    PubMed

    Kim, Ho Myeong; Cho, Eun Jin; Bae, Hyeun-Jong

    2016-08-01

    Jack bean (JB, Canavalia ensiformis) is the source of bio-based products, such as proteins and bio-sugars that contribute to modern molecular biology and biomedical research. In this study, the use of jack bean was evaluated as a source for concanavalin A (Con A) and bio-sugar production. A novel method for purifying Con A from JBs was successfully developed using a glucosylated magnetic nano matrix (GMNM) as a physical support, which facilitated easy separation and purification of Con A. In addition, the enzymatic conversion rate of 2% (w/v) Con A extracted residue to bio-sugar was 98.4%. Therefore, this new approach for the production of Con A and bio-sugar is potentially useful for obtaining bio-based products from jack bean.

  19. The ConNECT Framework: a model for advancing behavioral medicine science and practice to foster health equity.

    PubMed

    Alcaraz, Kassandra I; Sly, Jamilia; Ashing, Kimlin; Fleisher, Linda; Gil-Rivas, Virginia; Ford, Sabrina; Yi, Jean C; Lu, Qian; Meade, Cathy D; Menon, Usha; Gwede, Clement K

    2017-02-01

    Health disparities persist despite ongoing efforts. Given the United States' rapidly changing demography and socio-cultural diversity, a paradigm shift in behavioral medicine is needed to advance research and interventions focused on health equity. This paper introduces the ConNECT Framework as a model to link the sciences of behavioral medicine and health equity with the goal of achieving equitable health and outcomes in the twenty-first century. We first evaluate the state of health equity efforts in behavioral medicine science and identify key opportunities to advance the field. We then discuss and present actionable recommendations related to ConNECT's five broad and synergistic principles: (1) Integrating Context; (2) Fostering a Norm of Inclusion; (3) Ensuring Equitable Diffusion of Innovations; (4) Harnessing Communication Technology; and (5) Prioritizing Specialized Training. The framework holds significant promise for furthering health equity and ushering in a new and refreshing era of behavioral medicine science and practice.

  20. UniCon3D: de novo protein structure prediction using united-residue conformational search via stepwise, probabilistic sampling

    PubMed Central

    Bhattacharya, Debswapna; Cao, Renzhi; Cheng, Jianlin

    2016-01-01

    Motivation: Recent experimental studies have suggested that proteins fold via stepwise assembly of structural units named ‘foldons’ through the process of sequential stabilization. Alongside, latest developments on computational side based on probabilistic modeling have shown promising direction to perform de novo protein conformational sampling from continuous space. However, existing computational approaches for de novo protein structure prediction often randomly sample protein conformational space as opposed to experimentally suggested stepwise sampling. Results: Here, we develop a novel generative, probabilistic model that simultaneously captures local structural preferences of backbone and side chain conformational space of polypeptide chains in a united-residue representation and performs experimentally motivated conditional conformational sampling via stepwise synthesis and assembly of foldon units that minimizes a composite physics and knowledge-based energy function for de novo protein structure prediction. The proposed method, UniCon3D, has been found to (i) sample lower energy conformations with higher accuracy than traditional random sampling in a small benchmark of 6 proteins; (ii) perform comparably with the top five automated methods on 30 difficult target domains from the 11th Critical Assessment of Protein Structure Prediction (CASP) experiment and on 15 difficult target domains from the 10th CASP experiment; and (iii) outperform two state-of-the-art approaches and a baseline counterpart of UniCon3D that performs traditional random sampling for protein modeling aided by predicted residue-residue contacts on 45 targets from the 10th edition of CASP. Availability and Implementation: Source code, executable versions, manuals and example data of UniCon3D for Linux and OSX are freely available to non-commercial users at http://sysbio.rnet.missouri.edu/UniCon3D/. Contact: chengji@missouri.edu Supplementary information: Supplementary data are

  1. Induction of Antibodies Directed Against Branched Core O-Mannosyl Glycopeptides-Selectivity Complimentary to the ConA Lectin.

    PubMed

    Yu, Jin; Grant, Oliver C; Pett, Christian; Stahl, Sabine; Woods, Robert J; Westerlind, Ulrika

    2017-03-08

    Mammalian protein O-mannosylation, initiated by attachment of α-mannopyranose to Ser or Thr residues, comprise a group of post-translational modifications (PTMs) involved in muscle and brain development. Recent advances in glycoproteomics methodology and the "SimpleCell" strategy have enabled rapid identification of glycoproteins and specific glycosylation sites. Despite the enormous progress made, the biological impact of the mammalian O-mannosyl glycoproteome remains largely unknown to date. Tools are still needed to investigate the structure, role, and abundance of O-mannosyl glycans. Although O-mannosyl branching has been shown to be of relevance in integrin-dependent cell migration, and also plays a role in demyelinating diseases, such as multiple sclerosis, a broader understanding of the biological roles of branched O-mannosyl glycans is lacking in part due to the paucity of detection tools. In this work, a glycopeptide vaccine construct was synthesized and used to generate antibodies against branched O-mannosyl glycans. Glycopeptide microarray screening revealed high selectivity of the induced antibodies for branched glycan core structures presented on different peptide backbones, with no cross-reactivity observed with related linear glycans. For comparison, microarray screening of the mannose-binding lectin concanavalin A (ConA), which is commonly used in glycoproteomics workflows to enrich tryptic O-mannosyl peptides, showed that the ConA lectin did not recognize branched O-mannosyl glycans. The binding preference of ConA for short linear O-mannosyl glycans was rationalized in terms of molecular structure using crystallographic data augmented by molecular modeling. The contrast between the ConA binding specificity and that of the new antibodies indicates a novel role for the antibodies in studies of protein O-mannosylation.

  2. Violación del Principio de Equivalencia en Teorías con Dilatón de Cuerdas

    NASA Astrophysics Data System (ADS)

    Landau, S. J.; Sisterna, P. D.; Vucetich, H.

    Se estudian las violaciones al Principio de Equivalencia en Teorías con Dilatón de Cuerdas. En estos modelos, algunas de las constantes fundamentales dependen del espacio y del tiempo. Se muestra que los experimentos de caída libre no tienen aún precisión como para poner límites a los parámetros de la teoría.

  3. Con_A-CNT (Carbon Nanotube) Conjugate with Short Wave Near-Infrared (SWIR) Laser Ablation for Tumor Therapy

    DTIC Science & Technology

    2010-02-11

    originate from hematopoietic stem cells in bone marrow during childhood development for “adaptive immune system” in Thymus organ with a variety of “T...cells,” short for Thymus cells,: so-called helper, cytotoxic, memory, regulator, natural killer (NK), alpha-beta-gamma-delta receptor called T cells...cells [17-19]. We have reported Concanavalin A (Con A), a plant lectin isolated from Canavalia ensiformis (Jack bean) seeds, can agglutinate cells with

  4. Encefalitis por anticuerpos contra el receptor de NMDA: experiencia con seis pacientes pediátricos. Potencial eficacia del metotrexato

    PubMed Central

    Bravo-Oro, Antonio; Abud-Mendoza, Carlos; Quezada-Corona, Arturo; Dalmau, Josep; Campos-Guevara, Verónica

    2016-01-01

    Introducción La encefalitis por anticuerpos contra el receptor de N-metil-D-aspartato (NMDA) es una entidad cada vez más diagnosticada en edad pediátrica. A diferencia de los adultos, en muchos casos no se asocia a tumores y las manifestaciones iniciales en niños más frecuentes son crisis convulsivas y trastornos del movimiento, mientras que en los adultos predominan las alteraciones psiquiátricas. Casos clínicos Presentamos seis casos pediátricos confirmados con anticuerpos contra la subunidad NR1 del receptor de NMDA en suero y líquido cefalorraquídeo. Cinco de los casos comenzaron con crisis convulsivas como manifestación clínica inicial antes de desarrollar el cuadro clásico de esta entidad. En todos los casos se utilizaron esteroides como primera línea de tratamiento, con los que sólo se observó control de las manifestaciones en uno, por lo que el resto de los pacientes requirió inmunomoduladores de segunda línea. Todos los pacientes recibieron metotrexato como tratamiento inmunomodulador para evitar recaídas y la evolución fue a la mejoría en todos ellos. Conclusiones En nuestra serie de pacientes con encefalitis por anticuerpos contra el receptor de NMDA, ninguno se asoció a tumores. Todos los casos recibieron metotrexato por lo menos durante un año, no observamos eventos adversos clínicos ni por laboratorio, ni hubo secuelas neurológicas ni recaídas durante el tratamiento. Aunque es una serie pequeña y es deseable incrementar el número y tiempo de evolución, consideramos el metotrexato una excelente alternativa como tratamiento inmunomodulador para esta patología. PMID:24150952

  5. Nqrs Data for C10H12CoN2NaO8 (Subst. No. 1263)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H12CoN2NaO8 (Subst. No. 1263)

  6. Exploring the use of Generalized Indirect Covariance to reconstruct pure shift NMR spectra: Current Pros and Cons

    NASA Astrophysics Data System (ADS)

    Fredi, André; Nolis, Pau; Cobas, Carlos; Martin, Gary E.; Parella, Teodor

    2016-05-01

    The current Pros and Cons of a processing protocol to generate pure chemical shift NMR spectra using Generalized Indirect Covariance are presented and discussed. The transformation of any standard 2D homonuclear and heteronuclear spectrum to its pure shift counterpart by using a reference DIAG spectrum is described. Reconstructed pure shift NMR spectra of NOESY, HSQC, HSQC-TOCSY and HSQMBC experiments are reported for the target molecule strychnine.

  7. Exploring the use of Generalized Indirect Covariance to reconstruct pure shift NMR spectra: Current Pros and Cons.

    PubMed

    Fredi, André; Nolis, Pau; Cobas, Carlos; Martin, Gary E; Parella, Teodor

    2016-05-01

    The current Pros and Cons of a processing protocol to generate pure chemical shift NMR spectra using Generalized Indirect Covariance are presented and discussed. The transformation of any standard 2D homonuclear and heteronuclear spectrum to its pure shift counterpart by using a reference DIAG spectrum is described. Reconstructed pure shift NMR spectra of NOESY, HSQC, HSQC-TOCSY and HSQMBC experiments are reported for the target molecule strychnine.

  8. [Malattia di Marchiafava-Bignami con coinvolgimento della corteccia frontale e insorgenza tardiva di sintomi psichiatrici resistenti: un caso clinico].

    PubMed

    Gramaglia, Carla; Feggi, Alessandro; Vecchi, Camilla; Di Marco, Sarah; Venesia, Alessandra; Delicato, Claudia; Chieppa, Nunzia; De Marchi, Fabiola; Cantello, Roberto; Zeppegno, Patrizia

    2016-01-01

    RIASSUNTO. Scopo. Descrivere il management di un paziente con malattia di Marchiafava-Bignami (MBD) associata a lesioni frontali corticali, senza sintomi specifici al primo accesso in Pronto Soccorso, e insorgenza tardiva di sintomi psichiatrici atipici. Metodi. Descriviamo il caso di un paziente di 44 anni con storia di abuso cronico di alcol, a cui è stata diagnosticata la MBD. Risultati. La risonanza magnetica ha evidenziato lesioni nello splenio e corpo del corpo calloso e lesioni bilaterali della corteccia frontale. Il paziente ha sviluppato sintomi psichiatrici atipici a insorgenza tardiva, che sono risultati essere resistenti alle terapie farmacologiche impostate. Discussione. Il caso che descriviamo sembra supportare le attuali, ma ancora scarse evidenze che descrivono il coinvolgimento corticale nella MBD, suggerendone l'associazione con una prognosi peggiore. I sintomi psichiatrici possono risultare difficili da trattare a causa della resistenza alle terapie. Conclusione. Il coinvolgimento di psichiatri, radiologi e neurologi secondo un approccio di consultazione-liaison si è dimostrato di fondamentale importanza per la diagnosi e l'impostazione della terapia adeguata al paziente.

  9. ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites

    PubMed Central

    Lelieveld, Stefan H.; Schütte, Judith; Dijkstra, Maurits J.J.; Bawono, Punto; Kinston, Sarah J.; Göttgens, Berthold; Heringa, Jaap; Bonzanni, Nicola

    2016-01-01

    Eukaryotic gene expression is regulated by transcription factors (TFs) binding to promoter as well as distal enhancers. TFs recognize short, but specific binding sites (TFBSs) that are located within the promoter and enhancer regions. Functionally relevant TFBSs are often highly conserved during evolution leaving a strong phylogenetic signal. While multiple sequence alignment (MSA) is a potent tool to detect the phylogenetic signal, the current MSA implementations are optimized to align the maximum number of identical nucleotides. This approach might result in the omission of conserved motifs that contain interchangeable nucleotides such as the ETS motif (IUPAC code: GGAW). Here, we introduce ConBind, a novel method to enhance alignment of short motifs, even if their mutual sequence similarity is only partial. ConBind improves the identification of conserved TFBSs by improving the alignment accuracy of TFBS families within orthologous DNA sequences. Functional validation of the Gfi1b + 13 enhancer reveals that ConBind identifies additional functionally important ETS binding sites that were missed by all other tested alignment tools. In addition to the analysis of known regulatory regions, our web tool is useful for the analysis of TFBSs on so far unknown DNA regions identified through ChIP-sequencing. PMID:26721389

  10. Pros and cons of prostate cancer screening: associations with screening knowledge and attitudes among urban African American men.

    PubMed

    Davis, Stacy N; Diefenbach, Michael A; Valdimarsdottir, Heiddis; Chen, Tianle; Hall, Simon J; Thompson, Hayley S

    2010-03-01

    Discussion of the pros and cons of prostate cancer screening tests, rather than routine screening, is recommended to support informed screening decisions, particularly among African American men. This study explored physician explanation of pros and cons of the prostate-specific antigen (PSA) test and digital rectal exam (DRE) and its association with knowledge and screening attitudes. Two hundred-one African American men were asked if a physician had ever provided a comprehensive explanation of pros and cons of the PSA test and DRE. All men completed a 10-item prostate cancer knowledge scale and a subset completed a 26-item attitudes measure. Only 13% of the sample reported receiving a comprehensive explanation. Also, prostate cancer knowledge in the sample was low (mean = 43% correct). Multivariate analyses revealed that total prostate cancer knowledge was associated with men receiving a comprehensive explanation (p = .05), as well as past prostate cancer screening (p = .02) and younger age (p = .009). Although comprehensive explanation of prostate cancer screening was related to total prostate cancer knowledge, it was unrelated to a subset of items that may be central to fully informed screening decisions. Furthermore, comprehensive explanation of prostate cancer screening (p = .02), along with DRE recommendation (p = .009) and older age (p = .02), were related to fewer negative screening attitudes. Findings suggest that continued focus on patient education and physician communication is warranted.

  11. Cálculos ab initio con correlación electrónica

    NASA Astrophysics Data System (ADS)

    Merchán Bonete, M.

    Estamos entrando en una era donde la ortogonalidad entre las investigaciones de carácter experimental y de naturaleza teórica se irá difuminando progresivamente y la problemática a resolver quedará en escena como el único actor principal de la obra. Como premisa para una cooperación teórico-experimental de igual a igual, la metodología químico-cuántica utilizada debe ser capaz de ofrecer resultados de carácter predictivo. Sin duda, esta madurez en la metodología químico-cuántica ya la hemos alcanzado hace algunos años, tal y como muestra entre otras muchas, la labor que nuestro grupo ha realizado en el transcurso de la última década, dentro del campo de la Espectroscopía Teórica. Los estudios realizados comprenden una amplia gama de sistemas, variando tanto en tamaño como en complejidad, abordando problemáticas espectroscópicas consideradas tradicionalmente como especialmente controvertidas. Nuestra contribución científica más relevante reside en el carácter cuantitativo de las asignaciones espectroscópicas que hemos propuesto en base a resultados ab initio. Recordemos que en los años noventa los resultados ab initio solían presentar para las energías de excitación de sistemas de tamaño molecular moderado, como el benceno, errores de más de 1 eV. En comparación con el éxito relativo de los métodos semiempíricos, la frustración de la metodología ab initio quedaba todavía más patente. Los estudios que hemos presentado representan una comprensión profunda de los espectros electrónicos en sistemas orgánicos claves, mostrando el camino a seguir para obtener asignaciones espectroscópicas precisas (entre 0.1-0.2 eV). La naturaleza del método CASPT2 junto al diseño de estrategias computacionales nos ha permitido alcanzar el carácter cuantitativo con el que se caracterizan nuestras contribuciones[1,2]. Por todo ello, algunos de los trabajos publicados se consideran clásicos dentro del campo, pues en cierto modo definen el

  12. Stellate Cell Activation and Imbalanced Expression of TGF-β1/TGF-β3 in Acute Autoimmune Liver Lesions Induced by ConA in Mice

    PubMed Central

    Tu, Lei; Zhang, Jinping; Qian, Wei

    2017-01-01

    Objective. To study the pathogenic feature of liver injury, activation of hepatic stellate cells, and dynamic expression of TGF-β1/TGF-β3 to reveal their role in liver injury induced by ConA. Methods. Mice were randomly divided into control group and ConA treatment group. ConA (20 mg/kg) was injected through vena caudalis in ConA treatment group; the controls received the same volume of saline injection. After injection for 2 h, 8 h, 24 h, and 48 h, animals were terminated. Blood, liver, and spleen were harvested. Liver function and histopathology were studied. α-SMA, vimentin, TGF-β1, and TGF-β3 were detected. Results. After ConA injection, liver damage started to increase. Expression of α-SMA, vimentin, TGF-β1, and TGF-β3 was significantly enhanced; all above indicators reached peak at 8 h; but from 24 h after ConA injection, TGF-β3 expression began to decline, while the TGF-β1/TGF-β3 ratio at 48 h was significantly lower than control. Conclusion. (1) Autoimmune liver injury induced by ConA showed time-based features, in which the most serious liver lesions happened at 8 h after ConA injection. (2) Early activation of HSC and imbalance expression of TGF-β1 and TGF-β3 existed in ConA-induced acute autoimmune liver injury, which may be associated with liver dysfunction and the mechanisms of progression to fibrosis. PMID:28246592

  13. [Characteristics of patients with refractory epilepsy attended in a tertiary referral center in Costa Rica].

    PubMed

    Sanabria-Castro, A; Henriquez-Varela, F; Lara-Maier, S; Monge-Bonilla, C; Sittenfeld-Appel, M

    2016-07-16

    Introduccion. El 30% de los pacientes con epilepsia presenta convulsiones recurrentes, porcentaje que representa aproximadamente a 15 millones de personas en el mundo y constituye una poblacion escasamente descrita. Objetivo. Caracterizar sociodemografica y clinicamente la poblacion de pacientes diagnosticados con epilepsia refractaria en un hospital terciario de Costa Rica. Pacientes y metodos. Se analizan los registros medicos de los pacientes con epilepsia refractaria valorados en la unidad de epilepsia del Hospital San Juan de Dios de la Caja Costarricense del Seguro Social desde agosto de 2012 a octubre de 2014. Resultados. Se incluyen los expedientes clinicos de 91 pacientes. La edad media de inicio fue de 13,1 ± 11,1 años. Las crisis secundariamente generalizadas constituyen el tipo predominante (81,3%), la etiologia mas frecuente es la esclerosis mesial temporal (48,3%) y la mayoria de los pacientes presentaba examenes neurologicos normales y valoraciones neuro­psicologicas normales o bajas. Alrededor de la mitad (48,8%) de los pacientes habia sido medicada con un rango de 4-6 farmacos antiepilepticos, y los mas prescritos fueron lamotrigina, carbamacepina, acido valproico y fenitoina. Las principales recomendaciones en estos pacientes fueron: optimizacion de tratamiento, neurocirugia y reingreso. Se observan diferencias entre la edad de inicio y el sexo, la frecuencia de las crisis y el sexo, el tiempo de evolucion de la patologia y la cantidad de tratamientos fallidos, y el tiempo de evolucion de la enfermedad y la ocupacion. Conclusiones. Las caracteristicas sociodemograficas, el manejo de los pacientes, los farmacos antiepilepticos utilizados y las diferencias encontradas son similares a las descritas en otras latitudes.

  14. "Estudio tribologico de aceros para moldes. Aplicacion al moldeo por inyeccion de polibutilentereftalato reforzado con fibra de vidrio"

    NASA Astrophysics Data System (ADS)

    Martinez Mateo, Isidoro Jose

    fabricacion del molde, tienen una gran influencia sobre su comportamiento en servicio a lo largo de la vida util del molde. En la primera parte del presente estudio, a partir de ensayos punzon sobre disco, se ha determinado la relacion entre la resistencia al desgaste y la dureza de aceros para moldes obtenidos a partir de bloques de gran espesor, estudiando los principales mecanismos de desgaste que tienen lugar. A continuacion, con el fin de determinar el dano superficial que sufren los aceros para moldes en condiciones reales de inyeccion, se han estudiado distintos tipos de aceros utilizados comercialmente en moldes de inyeccion de polimeros y materiales compuestos, seleccionando las condiciones de operacion para determinar la variacion de la rugosidad superficial del acero en funcion del material inyectado, del numero de operaciones sucesivas de inyeccion y de la orientacion del flujo de inyeccion, mediante tecnicas de perfilometria optica y microscopia electronica de barrido. Ademas del dano superficial sufrido por el acero con el numero de piezas inyectadas, tambien se ha determinado la evolucion de la rugosidad superficial de los materiales inyectados, polibutilentereftalato (PBT) puro y materiales compuestos derivados de PBT por adicion de un 20 o un 50% en peso de fibra de vidrio. En el caso de las piezas inyectadas, se ha caracterizado su microestructura en funcion del flujo de inyeccion y de la densidad de fibra, se han determinado sus propiedades termicas y dinamico-mecanicas, asi como la variacion de la rugosidad superficial de las piezas inyectadas con el numero de operaciones de inyeccion y con la geometria de las distintas secciones de las piezas. Finalmente, se ha evaluado la resistencia a la abrasion de PBT reforzado con un 50% de fibra, en funcion del numero de piezas inyectadas y de la direccion de rayado con respecto a la orientacion del flujo de inyeccion.

  15. Nanoparticulas basadas en complejos de Fe(II) con transicion de espin: sintesis, caracterizacion y aplicaciones en electronica molecular

    NASA Astrophysics Data System (ADS)

    Monrabal Capilla, Maria

    Esta tesis doctoral esta organizada en 5 capitulos y esta destinada al estudio de sistemas de Fe (II) que presentan el fenomeno de la transicion de espin a escala nanometrica. El capitulo 1 contiene una introduccion general sobre materiales moleculares multifuncionales, destacando aquellos ejemplos mas importantes. Por otro lado, se explicara el fenomeno de la transicion de espin, tratando aspectos conceptuales, los antecedentes mas importantes y la situacion actual. En el capitulo 2 se describen los diferentes procesos existentes para la obtencion de diferentes tipos de nanoparticulas. Ademas, se presenta la sintesis y caracterizacion de nanoparticulas del polimero de coordinacion unidimensional [Fe(Htrz)2(trz)]BF4, obtenidas mediante el metodo de micelas inversas. Estas nanoparticulas, con una estrecha distribucion de tamanos centrada alrededor de los 11 nm, presentan una transicion de espin muy abrupta, con un ancho ciclo de histeresis termica de unos 40K. En el capitulo 3 se describe el proceso de modificacion del tamano de las nanoparticulas descritas en el capitulo anterior, llevado a cabo variando la proporcion de surfactante/H2O en el medio. Ademas, con el objetivo de modificar las propiedades magneticas de las nanoparticulas obtenidas en el capitulo 2, se lleva a cabo la sintesis de nanoparticulas de polimeros de la misma familia del [Fe(Htrz)2(trz)]BF4. En concreto se sintetizaron 3 nuevos tipos de nanoparticulas basadas en el polimero [Fe(Htrz)1-x(NH2trz)x](ClO4)2, siendo x = 0.05, 0.15 y 0.3, en cada caso. Estas nanoparticulas siguen presentando una estrecha distribucion de tamanos y una transicion de espin muy abrupta y con un ancho ciclo de histeresis. Ademas, se observa que este ciclo se desplaza a temperaturas mas proximas a la temperatura ambiente a medida que se aumenta el porcentaje de 4-amino-1, 2, 4- triazol en la muestra. Pero al mismo tiempo se produce una disminucion de la anchura de este ciclo. Por ultimo, en este capitulo se presenta la

  16. Análisis del espectro infrarrojo del polvo interestelar asociado con cúmulos globulares y de su evolución temporal

    NASA Astrophysics Data System (ADS)

    Pellizza, L. J.; Forte, J. C.; Carpintero, D.

    El trabajo que se presenta investiga la dinámica de las partículas de polvo interestelar eyectadas por estrellas gigantes rojas en un cúmulo globular utilizando simulaciones numéricas de su interacción con el campo gravitatorio y con la radiación electromagnética de las estrellas. Se pretende con ello determinar la distribución espacial de ese material como una función del tiempo en un sistema similar a NGC 104 (47 Tuc). A partir de la distribución espacial resultante se obtuvo el espectro infrarrojo integrado el cual sugiere que el máximo contraste con la radiación estelar ocurre en longitudes de onda cercanas a 300 μm y que decrece rápidamente hacia longitudes de onda menores, en las que suelen realizarse las observaciones.

  17. Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report

    PubMed Central

    Manchia, Mirko; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Aubry, Jean-Michel; Backlund, Lena; Banzato, Claudio EM.; Baune, Bernhard T.; Bellivier, Frank; Bengesser, Susanne; Biernacka, Joanna M.; Brichant-Petitjean, Clara; Bui, Elise; Calkin, Cynthia V.; Cheng, Andrew Tai Ann; Chillotti, Caterina; Cichon, Sven; Clark, Scott; Czerski, Piotr M.; Dantas, Clarissa; Zompo, Maria Del; DePaulo, J. Raymond; Detera-Wadleigh, Sevilla D.; Etain, Bruno; Falkai, Peter; Frisén, Louise; Frye, Mark A.; Fullerton, Jan; Gard, Sébastien; Garnham, Julie; Goes, Fernando S.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Heilbronner, Urs; Hoban, Rebecca; Hou, Liping; Jamain, Stéphane; Kahn, Jean-Pierre; Kassem, Layla; Kato, Tadafumi; Kelsoe, John R.; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kuo, Po-Hsiu; Kusumi, Ichiro; Laje, Gonzalo; Lavebratt, Catharina; Leboyer, Marion; Leckband, Susan G.; López Jaramillo, Carlos A.; Maj, Mario; Malafosse, Alain; Martinsson, Lina; Masui, Takuya; Mitchell, Philip B.; Mondimore, Frank; Monteleone, Palmiero; Nallet, Audrey; Neuner, Maria; Novák, Tomás; O’Donovan, Claire; Ösby, Urban; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Potash, James B.; Reich-Erkelenz, Daniela; Reif, Andreas; Reininghaus, Eva; Richardson, Sara; Rouleau, Guy A.; Rybakowski, Janusz K.; Schalling, Martin; Schofield, Peter R.; Schubert, Oliver K.; Schweizer, Barbara; Seemüller, Florian; Grigoroiu-Serbanescu, Maria; Severino, Giovanni; Seymour, Lisa R.; Slaney, Claire; Smoller, Jordan W.; Squassina, Alessio; Stamm, Thomas; Steele, Jo; Stopkova, Pavla; Tighe, Sarah K.; Tortorella, Alfonso; Turecki, Gustavo; Wray, Naomi R.; Wright, Adam; Zandi, Peter P.; Zilles, David; Bauer, Michael; Rietschel, Marcella; McMahon, Francis J.

    2013-01-01

    Objective The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the “Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder” scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (κ)] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (κ = 0.66 and κ = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (ICC1 = 0.71 and ICC2 = 0.75, respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study. PMID:23840348

  18. Sophocarpine Protects Mice from ConA-Induced Hepatitis via Inhibition of the IFN-Gamma/STAT1 Pathway

    PubMed Central

    Sang, Xiu-Xiu; Wang, Rui-Lin; Zhang, Cong-En; Liu, Shi-Jing; Shen, Hong-Hui; Guo, Yu-Ming; Zhang, Ya-Ming; Niu, Ming; Wang, Jia-Bo; Bai, Zhao-Fang; Xiao, Xiao-He

    2017-01-01

    Sophocarpine is the major pharmacologically active compound of the traditional Chinese herbal medicine Radix Sophorae Subprostratae which has been used in treating hepatitis for years in China. It has been demonstrated that Sophocarpine exerts an activity in immune modulation and significantly decreases the production of inflammatory cytokines. However, the protective effects of Sophocarpine in T cell-dependent immune hepatitis remained unknown. The aim of this study was to determine the protective effects and pharmacological mechanisms of Sophocarpine on Concanavalin A (ConA)-induced hepatitis, an experimental model of T cell-mediated liver injury. BALB/C mice were pretreated with Sophocarpine or Bicyclol for five consecutive days. Thirty minutes after the final administration, the mice were injected with 15 mg⋅kg-1 of ConA intravenously. The results indicated that pretreatment with Sophocarpine significantly ameliorated liver inflammation and injury as evidenced by both biochemical and histopathological observations. Moreover, in Sophocarpine-pretreated mice, liver messenger RNA expression levels of chemokines and adhesion molecules, such as macrophage inflammatory protein-1α, CXC chemokine ligand 10, and Intercellular adhesion molecule-1, were markedly reduced. Further studies revealed that Sophocarpine significantly downregulated the expression of T-bet via inhibition of signal transducers and activators of transcription1 (STAT1) activation and overexpression of suppressor of cytokine signaling1, inhibiting the activation of Th1 cells and the expression of Interferon-γ (IFN-γ). Altogether, these results suggest new opportunities to use Sophocarpine in the treatment of T cell-mediated liver disease. In summary, Sophocarpine could attenuate ConA-induced liver injury, and the protective effect of Sophocarpine was associated with its inhibition effect of pro-inflammatory cytokines, chemokines, and the IFN-γ/STAT1 signaling pathway. PMID:28377718

  19. The InterCon network: a program for education partnerships at the University of Texas-Houston Health Science Center.

    PubMed

    Castro, G A; Bouldin, P A; Farver, D W; Maugans, L A; Sanders, L C; Booker, J

    1999-04-01

    The University of Texas-Houston Health Science Center (UT-Houston) has created programs and activities to address the state's pressing needs in minority education. Through InterCon, a network of universities and K-12 schools, UT-Houston works with its partners to identify competitive candidates in the current pool of minority graduates with bachelor's degrees and to help them--along with their non-minority counterparts--progress in their education. Another objective is to expand the pool of minorities underrepresented in medicine who complete high school and go to college. In 1994 UT-Houston and Prairie View A&M University created a collaborative venture to provide new educational opportunities at UT-Houston for Prairie View's predominantly African American students. A three-track summer internship program--a result of that collaboration--has since been expanded to partnerships with other minority and majority universities throughout Texas. In 1998, for example, 108 undergraduate students from these universities (and 40 other universities nationwide) participated in research, professional, and administrative summer internships at UT-Houston. The InterCon network also has partnerships with K-12 schools. UT-Houston works with inner-city, suburban, and rural school districts to develop education models that can be transferred throughout the state. The partnerships deal with helping to teach basic academic skills and computer literacy, improve science-related instruction, meet demands for health promotion materials and information for school-initiated health and wellness programs, and develop distance-learning paradigms. UT-Houston views InterCon as a program helping Texas institutions to engage and adapt to the socioeconomic factors, demographic changes, and technology explosion that currently challenge public education.

  20. Influence of parameter values and variances and algorithm architecture in ConsExpo model on modeled exposures.

    PubMed

    Arnold, Susan F; Ramachandran, Gurumurthy

    2014-01-01

    This study evaluated the influence of parameter values and variances and model architecture on modeled exposures, and identified important data gaps that influence lack-of-knowledge-related uncertainty, using Consexpo 4.1 as an illustrative case study. Understanding the influential determinants in exposure estimates enables more informed and appropriate use of this model and the resulting exposure estimates. In exploring the influence of parameter placement in an algorithm and of the values and variances chosen to characterize the parameters within ConsExpo, "sensitive" and "important" parameters were identified: product amount, weight fraction, exposure duration, exposure time, and ventilation rate were deemed "important," or "always sensitive." With this awareness, exposure assessors can strategically focus on acquiring the most robust estimates for these parameters. ConsExpo relies predominantly on three algorithms to assess the default scenarios: inhalation vapors evaporation equation using the Langmuir mass transfer, the dermal instant application with diffusion through the skin, and the oral ingestion by direct uptake algorithm. These algorithms, which do not necessarily render health conservative estimates, account for 87, 89 and 59% of the inhalation, dermal and oral default scenario assessments,respectively, according them greater influence relative to the less frequently used algorithms. Default data provided in ConsExpo may be useful to initiate assessments, but are insufficient for determining exposure acceptability or setting policy, as parameters defined by highly uncertain values produce biased estimates that may not be health conservative. Furthermore, this lack-of-knowledge uncertainty makes the magnitude of this bias uncertain. Significant data gaps persist for product amount, exposure time, and exposure duration. These "important" parameters exert influence in requiring broad values and variances to account for their uncertainty. Prioritizing

  1. Antidepressant-like effect of Canavalia brasiliensis (ConBr) lectin in mice: evidence for the involvement of the glutamatergic system.

    PubMed

    Rieger, Débora K; Costa, Ana Paula; Budni, Josiane; Moretti, Morgana; Barbosa, Sabrina Giovana Rocha; Nascimento, Kyria S; Teixeira, Edson H; Cavada, Benildo S; Rodrigues, Ana Lúcia S; Leal, Rodrigo B

    2014-07-01

    Lectins recognize and reversibly bind to carbohydrates attached to proteins and lipids modulating a variety of signaling pathways. We previously showed that ConBr, a lectin from Canavalia brasiliensis seeds, produced an antidepressant-like effect in mice by modulating the monoaminergic neurotransmitter systems. Moreover, ConBr blocked hippocampal neurotoxicity induced by quinolinic acid in vivo and by glutamate in vitro, suggesting a neuroprotective activity of ConBr via glutamatergic system modulation. Therefore, the present study was undertaken to investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like action displayed by ConBr in the forced swimming test (FST). With the aim of verifying the involvement of NMDA receptors in the antidepressant-like effect of ConBr (10 μg/site, i.c.v.), an intracerebroventricular (i.c.v.) pretreatment with either NMDA (0.1 pmol/site) or D-serine (30 μg/site) was carried out. The results show that both treatments blocked the effect of ConBr. Furthermore, the coadministration of subeffective doses of the NMDA receptor antagonist MK-801 (0.001 mg/kg, i.p.) or ketamine (0.1 mg/kg, i.p.; NMDA receptor antagonist) and ConBr (0.1 μg/site, i.c.v.) caused a synergistic reduction in immobility time. In order to verify the dependence of the L-arginine-NO-cGMP pathway, on the effect of ConBr in the FST, a pretreatment with the NO precursor, L-arginine (750 mg/kg, i.p.), or the PDE5 inhibitor, sildenafil (5 mg/kg, i.p.), was performed. Both drugs abolished the antidepressant-like action of ConBr. Finally, the administration of subeffective doses of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 30 pmol/site, i.c.v.) and ConBr (0.1 μg/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST. Taken together, the results suggest that the antidepressant-like effect of ConBr in the FST involves NMDA

  2. Hacia el consumo informado de tabaco en México: efecto de las advertencias con pictogramas en población fumadora

    PubMed Central

    Thrasher, James F; Pérez-Hernández, Rosaura; Arillo-Santillán, Edna; Barrientos-Gutiérrez, Inti

    2015-01-01

    Resumen Objetivo Evaluar el efecto de las advertencias sanitarias (AS) con pictogramas en las cajetillas de tabaco en adultos fumadores. Material y métodos Cohorte de fumadores con representatividad poblacional de siete ciudades mexi canas, antes (2010) y después (2011) de la implementación de AS con pictogramas (ASP). Para determinar el cambio en las variables sobre el impacto cognitivo y conductual de las advertencias, se estimaron modelos bivariados y ajustados de ecuaciones de estimación generalizada. En el Segundo levantamiento (2011), se estimaron modelos para determiner los factores que se asocian con el reporte de recordar cada advertencia que había entrado al mercado, además de los factores asociados con el autorreporte del impacto de cada advertencia vigente. Resultados Se observaron incrementos importantes de 2010 a 2011 en los conocimientos sobre los riesgos de fumar, los componentes tóxicos del tabaco y el número telefónico para recibir consejos sobre dejar de fumar. La recordación e impacto de las primeras advertencias con pictogramas parecen ser amplios y equitativos a través de la población fumadora. En comparación con 2010, un mayor nivel de ex fumadores entrevistados en 2011 reportaron que las advertencias habían influido mucho en dejar de fumar (RM=2.44, 95% IC 1.27–4.72). Conclusiones Las AS con pictogramas han logrado un impacto importante en el conocimiento y conducta, información relevante para la población y en tomadores de decisiones. PMID:22689162

  3. Pros and Cons of Using Arrays of Small Antennas Versus Large Single Dish Antennas for the Deep Space Network

    NASA Technical Reports Server (NTRS)

    Bagri, Durgadas S.

    2009-01-01

    This paper briefly describes pros and cons of using arrays of small antennas instead of large single dish antennas for spacecraft telemetry, command, and tracking (TT and C) - communications and navigation (C and N) - and science support that the Deep Space Network (DSN) normally provides. It considers functionality and performance aspects, mainly for TT and C, though it also considers science. It only briefly comments on the cost aspects that seem to favor arrays of small antennas over large single antennas, at least for receiving (downlinks).

  4. Cámara CCD Directa con el Telescopio de 2.15 m del CASLEO: algunos diagnósticos

    NASA Astrophysics Data System (ADS)

    Cellone, S. A.

    Se efectuaron algunas pruebas con la cámara CCD (+ Reductor Focal) instalada en el foco Cassegrain del Telescopio de 2.15 m del Complejo Astronómico El Leoncito (CASLEO). Las conclusiones más significativas son: Los tiempos de exposición efectivos difieren de los nominales en una fracción apreciable de segundo. En exposiciones de menos de 3 segundos, la iluminación no es pareja en todo el detector. En consecuencia, se recomiendan los pasos a seguir por los astrónomos tanto durante la observación como en la reducción de sus datos.

  5. A signal-on electrochemiluminescence biosensor for detecting Con A using phenoxy dextran-graphite-like carbon nitride as signal probe.

    PubMed

    Ou, Xin; Tan, Xingrong; Liu, Xiaofang; Lu, Qiyi; Chen, Shihong; Wei, Shaping

    2015-08-15

    A novel signal-on electrochemiluminescence (ECL) biosensor for detecting concanavalin A (Con A) was fabricated with phenoxy dextran-graphite-like carbon nitride (DexP-g-C3N4) as signal probe. In this construction strategy, the nanocomposites of three-dimensional graphene and gold nanoparticles (3D-GR-AuNPs) were used as matrix for high loading of glucose oxidase (GOx), which served as recognition element for bounding Con A. Con A further interacted with DexP-g-C3N4 through a specific carbohydrate-Con A interaction to achieve a sandwiched scheme. With the increase of Con A incubated onto the electrode, the ECL signal resulted from DexP-g-C3N4 would enhance, thus achieving a signal-on ECL biosensor for Con A detection. Due to the integration of the virtues of 3D-GR-AuNPs and the excellent ECL performance of DexP-g-C3N4, the prepared biosensor exhibits a wide linear response range from 0.05 ng/mL to 100 ng/mL and a low detection limit of 17 pg/mL (S/N=3).

  6. A Recovery-Oriented Care Approach: Weighing the Pros and Cons of a Newly Built Mental Health Facility.

    PubMed

    Ahern, Catherine Clark; Bieling, Peter; McKinnon, Margaret C; McNeely, Heather E; Langstaff, Karen

    2016-02-01

    The current study adopted a recovery-oriented care approach by emphasizing patients' perspectives and experiences regarding changes to a newly built mental health facility. The inpatient entrance, or "portal," intended to balance the aims of recovery-oriented care with minimizing risk. A mixed-methods study of the portal's pros and cons was conducted, according to four themes: (a) autonomy versus inconvenience; (b) safety and security versus stigma; (c) unit door versus portal operating costs; and (d) privacy versus community integration. Focus groups engaging with patients (N = 39) indicated that the design effectively supported recovery-oriented care. Patients did not find the portal to be stigmatizing or triggering and valued the safety and privacy it created, and visitors also generally had a positive experience. Survey responses (N = 101) from portal users were also positive about the new design. The study findings suggest that the pros outweighed the cons of the new design. [Journal of Psychosocial Nursing and Mental Health Services, 54(2), 39-48.].

  7. Actitudes Éticas de los estudiantes y egresados en carrera de medicina con metodologías activas

    PubMed Central

    Novaes, Maria Rita Carvalho Garbi; Novaes, Luiz Carlos Garcez; Guilhem, Dirce; Stepke, Fernando Lolas; Silveira, Carla Cristina Costa; Komatsu, Ricardo Shoiti; Trindade, Eliane Mendonça Vilar; Guiotti, Murilo Galvão

    2010-01-01

    El presente estudio tiene por objeto desarrollar un diagnostico de la inserción integrada de la ética en la carrera de medicina brasileña con una metodología de aprendizaje basada en problemas y describir las percepciones de actitudes éticas de los estudiantes y egresados. El diseño metodológico es un estudio de caso, descriptivo y documental, con abordaje cualitativo y cuantitativo. La muestra de esta investigación ha sido constituida por 120 estudiantes y 40 egresados de dos promociones del Curso de Medicina de la ESCS. Este proyecto fue aprobado por el Comité de Ética en Investigación - SES/DF. Los estudiantes y egresados de la ESCS demostraron un buen manejo en el abordaje de los conflictos éticos y respeto a los pacientes. Sin embargo, el análisis de sensibilidad ética mostró una fragilidad en las percepciones y aptitudes inapropiadas de los estudiantes de la carrera de medicina, identificada básicamente en los años iniciales, que necesitan más discusiones sistematizadas sobre los aspectos éticos y bioéticos integrados a las actividades prácticas para estimular y fortalecer la reflexión ética de los estudiantes. PMID:20981242

  8. Development of a novel DNA SynCon tetravalent dengue vaccine that elicits immune responses against four serotypes.

    PubMed

    Ramanathan, Mathura P; Kuo, Yuan-Chia; Selling, Bernard H; Li, Qianjun; Sardesai, Niranjan Y; Kim, J Joseph; Weiner, David B

    2009-10-30

    The increased transmission and geographic spread of dengue fever (DF) and its most severe presentations, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), make it one of the most important mosquito-borne viral disease of humans. Four distinct serotypes of dengue viruses are transmitted to humans through the bites of the mosquitoes. Currently there is no vaccine or antiviral drug against DV infections. Cross-protection between dengue virus serotypes is limited and antibody dependent enhancement (ADE) contributes significantly to the severity of the disease. The major challenge is to induce a broad durable immune response against all four serotypes of dengue virus simultaneously while avoiding the possible exacerbation of risk of developing the severe forms of disease through incomplete or modified responses. In order to address this worldwide concern, we present a synthetic consensus (SynCon) human codon optimized DNA vaccine that elicits immunity against all four dengue serotypes. We cloned consensus DIII domain of E protein from all serotypes and expressed them as a single open reading frame in a mammalian expression vector, called pDV-U-DIII (dengue-vaccine universal). In mice, this dengue-universal construct elicits significant level of anti-DIII antibody that neutralizes all four dengue subtypes and prevents cell death induced by dengue infection. This is the first SynCon DNA vaccine that provides tetravalent immunity against all four serotypes of dengue virus.

  9. Modelo de accesibilidad de conceptos matematicos aplicados en el curso de Astronomia Descriptiva para estudiantes con impedimentos visuales en la UPR

    NASA Astrophysics Data System (ADS)

    Isidro Villamizar, Gloria Maria

    Este estudio utiliza metodologia de investigacion cualitativa, con el proposito de describir, analizar y evaluar los procesos de diseno y desarrollo de un modelo de accesibilidad que consiste en estrategias de ensenanza de las matematicas para estudiantes con impedimentos visuales matriculados en el curso de Astronomia Descriptiva en la UPR. Se utilizaron las siguientes estrategias para recopilar la informacion, 1) reflexiones de la investigadora en el proceso de diseno y desarrollo de las lecciones adaptadas, que se registraron en un diario reflexivo. 2) entrevista semiestructurada luego de haber trabajado las lecciones de aprendizaje adaptadas con los participantes. 3) observaciones y notas de la investigadora del trabajo de los participantes. Para obtener la informacion de los participantes se obtuvo los permisos institucionales necesarios; se seleccionaron los participantes y se validaron los instrumentos; se realizo el desarrollo de las lecciones adaptadas con los participantes; y finalmente, se analizo la informacion obtenida. El diseno de las lecciones de aprendizaje adaptadas se hizo siguiendo las recomendaciones curriculares de los temas de matematicas aplicados en el curso de Astronomia Descriptiva realizado por la investigadora durante su semestre de internado. El testimonio de las voces de los participantes se obtuvo del proceso de desarrollo de las lecciones de aprendizaje adaptadas de temas seleccionados de conceptos matematicos requeridos en el curso de Astronomia Descriptiva y de la entrevista semiestructurada con los participantes, luego de haber trabajado las lecciones de aprendizaje. Para el desarrollo de las lecciones de aprendizaje, se utilizaron materiales tactiles adaptados, materiales tactiles disenados y materiales disponibles comercialmente. Los textos de las lecciones se imprimieron en tinta y en Braille. Se exhorta a disenar y desarrollar estrategias de ensenanza accesibles, considerando como recursos para evaluar su efectividad a

  10. Desarrollo de la Escala sobre el Estigma Relacionado con el VIH/SIDA para Profesionales de la Salud mediante el uso de métodos mixtos123

    PubMed Central

    Varas-Díaz, Nelson; Neilands, Torsten B.; Guilamo-Ramos, Vincent; Cintrón Bou, Francheska N.

    2009-01-01

    El estigma relacionado con el VIH/SIDA continúa siendo un obstáculo para la prevención primaria y secundaria del VIH. Las consecuencias para las personas que viven con la enfermedad han sido muy documentadas y continúan siendo una gran preocupación para las personas que proveen servicios de salud y para aquellas que investigan el tema. Estas consecuencias son preocupantes cuando el estigma emana de profesionales de la salud porque se puede limitar el acceso a los servicios. Uno de los principales obstáculos para la investigación del estigma relacionado con el VIH en Puerto Rico es la falta de instrumentos cuantitativos para evaluar las manifestaciones del estigma entre profesionales de la salud. El objetivo principal de este estudio fue desarrollar y probar las propiedades psicométricas de una escala sobre el estigma relacionado con el VIH/SIDA culturalmente apropiada para personas que proveen servicios de salud puertorriqueñas y desarrollar una versión corta de la escala que pudiera usarse en escenarios clínicos con tiempo limitado. El instrumento desarrollado estuvo basado en evidencia cualitativa recopilada entre profesionales y estudiantes de profesiones de la salud puertorriqueños/as (n=80) y administrado a una muestra de 421 profesionales de la salud en adiestramiento. La escala contenía 12 dimensiones del estigma relacionado con el VIH/SIDA. El análisis cuantitativo corroboró 11 de ellas, teniendo como resultado un instrumento con validez y confiabilidad satisfactoria. Estas dimensiones, a su vez, fueron subcomponentes de un factor de estigma general superior. PMID:20333258

  11. Presentación del estudio “Links” de hombres que tienes sexo con hombres en Buenos Aires, Argentina

    PubMed Central

    Carballo-Diéguez, Alex; Ávila, María M; Balán, Iván C.; Marone, Rubén; Pando, María A.; Barreda, Victoria

    2011-01-01

    Resumen Estudios previos en Buenos Aires reportaron altas prevalencias de HIV entre HSH, con valores que oscilan entre 9 y 14% durante casi 10 años de continuo testeo. El objetivo principal de este estudio fue la evaluación de factores relacionados al comportamiento de alto riesgo para transmisión del HIV entre HSH entre los que se incluyen el conocimiento y factores emocionales, socioculturales y ambientales. Por otro lado se realizó la estimación de prevalencia e incidencia de HIV utilizando RDS (Respondent Driven Sampling), así como la presencia de otras infecciones de transmisión sexual. Por último se evaluaron los hábitos de testeo para HIV indagando que factores facilitan o impiden su realización. El estudio constó de dos fases, en primer lugar una fase cualitativa y posteriormente una fase cuantitativa con una duración total de 4 años y medio. Durante la fase cualitativa se realizaron 44 entrevistas individuales en profundidad, 8 grupos focales y 10 observaciones etnográficas (hoteles, baños públicos (“teteras”), cines pornográficos, fiestas privadas, dark rooms y discotecas). Durante la fase cuantitativa del estudio se realizó el reclutamiento de 500 participantes que provinieron de la Ciudad Autónoma de Buenos Aires, así como del Gran Buenos Aires. El reclutamiento se comenzó con 16 participantes llamados semillas. Se realizó el diagnóstico de infección por HIV, hepatitis B y C (HBV y HCV), Treponema pallidum, Virus Papiloma Humano (HPV) y Chlamidias. La colaboración establecida entre los grupos de trabajo enfocados en áreas diversas posibilitó el abordaje conjunto de nuevas estrategias de investigación antes no exploradas en nuestro país. Los resultados más relevantes de esta investigación serán progresivamente publicados en sucesivos números de Actualizaciones en SIDA. PMID:25264397

  12. Presentación del estudio "Links" de hombres que tienes sexo con hombres en Buenos Aires, Argentina.

    PubMed

    Carballo-Diéguez, Alex; Avila, María M; Balán, Iván C; Marone, Rubén; Pando, María A; Barreda, Victoria

    2011-03-01

    Estudios previos en Buenos Aires reportaron altas prevalencias de HIV entre HSH, con valores que oscilan entre 9 y 14% durante casi 10 años de continuo testeo. El objetivo principal de este estudio fue la evaluación de factores relacionados al comportamiento de alto riesgo para transmisión del HIV entre HSH entre los que se incluyen el conocimiento y factores emocionales, socioculturales y ambientales. Por otro lado se realizó la estimación de prevalencia e incidencia de HIV utilizando RDS (Respondent Driven Sampling), así como la presencia de otras infecciones de transmisión sexual. Por último se evaluaron los hábitos de testeo para HIV indagando que factores facilitan o impiden su realización. El estudio constó de dos fases, en primer lugar una fase cualitativa y posteriormente una fase cuantitativa con una duración total de 4 años y medio. Durante la fase cualitativa se realizaron 44 entrevistas individuales en profundidad, 8 grupos focales y 10 observaciones etnográficas (hoteles, baños públicos ("teteras"), cines pornográficos, fiestas privadas, dark rooms y discotecas). Durante la fase cuantitativa del estudio se realizó el reclutamiento de 500 participantes que provinieron de la Ciudad Autónoma de Buenos Aires, así como del Gran Buenos Aires. El reclutamiento se comenzó con 16 participantes llamados semillas. Se realizó el diagnóstico de infección por HIV, hepatitis B y C (HBV y HCV), Treponema pallidum, Virus Papiloma Humano (HPV) y Chlamidias. La colaboración establecida entre los grupos de trabajo enfocados en áreas diversas posibilitó el abordaje conjunto de nuevas estrategias de investigación antes no exploradas en nuestro país. Los resultados más relevantes de esta investigación serán progresivamente publicados en sucesivos números de Actualizaciones en SIDA.

  13. Hepatic NK cell-mediated hypersensitivity to ConA-induced liver injury in mouse liver expressing hepatitis C virus polyprotein.

    PubMed

    Fu, Qiuxia; Yan, Shaoduo; Wang, Licui; Duan, Xiangguo; Wang, Lei; Wang, Yue; Wu, Tao; Wang, Xiaohui; An, Jie; Zhang, Yulong; Zhou, Qianqian; Zhan, Linsheng

    2016-08-04

    The role of hepatic NK cells in the pathogenesis of HCV-associated hepatic failure is incompletely understood. In this study, we investigated the effect of HCV on ConA-induced immunological hepatic injury and the influence of HCV on hepatic NK cell activation in the liver after ConA administration. An immunocompetent HCV mouse model that encodes the entire viral polyprotein in a liver-specific manner based on hydrodynamic injection and φC31o integrase was used to study the role of hepatic NK cells. Interestingly, the frequency of hepatic NK cells was reduced in HCV mice, whereas the levels of other intrahepatic lymphocytes remained unaltered. Next, we investigated whether the reduction in NK cells within HCV mouse livers might elicit an effect on immune-mediated liver injury. HCV mice were subjected to acute liver injury models upon ConA administration. We observed that HCV mice developed more severe ConA-induced immune-mediated hepatitis, which was dependent on the accumulated intrahepatic NK cells. Our results indicated that after the administration of ConA, NK cells not only mediated liver injury through the production of immunoregulatory cytokines (IFN-γ, TNF-α and perforin) with direct antiviral activity, but they also killed target cells directly through the TRAIL/DR5 and NKG2D/NKG2D ligand signaling pathway in HCV mice. Our findings suggest a critical role for NK cells in oversensitive liver injury during chronic HCV infection.

  14. A New Method for Re-Analyzing Evaluation Bias: Piecewise Growth Curve Modeling Reveals an Asymmetry in the Evaluation of Pro and Con Arguments.

    PubMed

    Jirschitzka, Jens; Kimmerle, Joachim; Cress, Ulrike

    2016-01-01

    In four studies we tested a new methodological approach to the investigation of evaluation bias. The usage of piecewise growth curve modeling allowed for investigation into the impact of people's attitudes on their persuasiveness ratings of pro- and con-arguments, measured over the whole range of the arguments' polarity from an extreme con to an extreme pro position. Moreover, this method provided the opportunity to test specific hypotheses about the course of the evaluation bias within certain polarity ranges. We conducted two field studies with users of an existing online information portal (Studies 1a and 2a) as participants, and two Internet laboratory studies with mostly student participants (Studies 1b and 2b). In each of these studies we presented pro- and con-arguments, either for the topic of MOOCs (massive open online courses, Studies 1a and 1b) or for the topic of M-learning (mobile learning, Studies 2a and 2b). Our results indicate that using piecewise growth curve models is more appropriate than simpler approaches. An important finding of our studies was an asymmetry of the evaluation bias toward pro- or con-arguments: the evaluation bias appeared over the whole polarity range of pro-arguments and increased with more and more extreme polarity. This clear-cut result pattern appeared only on the pro-argument side. For the con-arguments, in contrast, the evaluation bias did not feature such a systematic picture.

  15. Quercetin Protects Mice from ConA-Induced Hepatitis by Inhibiting HMGB1-TLR Expression and Down-Regulating the Nuclear Factor Kappa B Pathway.

    PubMed

    Li, Xi; Liu, Hong-chun; Yao, Qun-yan; Xu, Bei-li; Zhang, Shun-cai; Tu, Chuan-tao

    2016-02-01

    The dietary flavonoid quercetin has hepatoprotective effects. We analyzed the effects of quercetin on concanavalin A (ConA)-induced hepatitis in mice and its underlying molecular mechanisms of action. Mice were administered quercetin (50 mg/kg body weight, i.p.) or vehicle 30 min before intravenous administration of ConA. Quercetin pretreatment significantly reduced the ConA-induced elevations in plasma aminotransferase concentrations and liver necrosis, as well as reducing serum concentrations of the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interferon-γ, and interleukin-4. Quercetin pretreatment also reduced expression of high-mobility group box 1 protein (HMGB1) and toll-like receptor (TLR)-2 and TLR-4 messenger RNA (mRNA) and protein in liver tissues. Quercetin pretreatment significantly inhibited degradation of inhibitory kappa B alpha and modulated ConA-induced nuclear translocation in the liver of nuclear factor kappa B (NF-κB) p65. These results demonstrate that quercetin protects against ConA-mediated hepatitis in mice by attenuating the HMGB1-TLRs-NF-κB signaling pathway.

  16. A New Method for Re-Analyzing Evaluation Bias: Piecewise Growth Curve Modeling Reveals an Asymmetry in the Evaluation of Pro and Con Arguments

    PubMed Central

    Jirschitzka, Jens; Kimmerle, Joachim; Cress, Ulrike

    2016-01-01

    In four studies we tested a new methodological approach to the investigation of evaluation bias. The usage of piecewise growth curve modeling allowed for investigation into the impact of people’s attitudes on their persuasiveness ratings of pro- and con-arguments, measured over the whole range of the arguments’ polarity from an extreme con to an extreme pro position. Moreover, this method provided the opportunity to test specific hypotheses about the course of the evaluation bias within certain polarity ranges. We conducted two field studies with users of an existing online information portal (Studies 1a and 2a) as participants, and two Internet laboratory studies with mostly student participants (Studies 1b and 2b). In each of these studies we presented pro- and con-arguments, either for the topic of MOOCs (massive open online courses, Studies 1a and 1b) or for the topic of M-learning (mobile learning, Studies 2a and 2b). Our results indicate that using piecewise growth curve models is more appropriate than simpler approaches. An important finding of our studies was an asymmetry of the evaluation bias toward pro- or con-arguments: the evaluation bias appeared over the whole polarity range of pro-arguments and increased with more and more extreme polarity. This clear-cut result pattern appeared only on the pro-argument side. For the con-arguments, in contrast, the evaluation bias did not feature such a systematic picture. PMID:26840219

  17. Probabilidad de colisión de cometas periódicos con partículas interplanetarias

    NASA Astrophysics Data System (ADS)

    Gil Hutton, R.

    Se presentan resultados sobre la probabilidad de colisión de cometas de corto período con la población de partículas interplanetarias presentes en la región del cinturón de asteroides. Se encuentra que este proceso colisional afecta la evolución física de los cometas de manera no despreciable y puede ser el responsable de variaciones de brillo de tipo ``outburst". Se presentan resultados para algunos cometas en particular y se obtiene un límite inferior para el tamaño de los núcleos en función de la distribución de radios del cinturón de asteroides.

  18. In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies.

    PubMed

    Lipi, Farhana; Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N

    2016-12-01

    Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries.

  19. In vitro evolution of chemically-modified nucleic acid aptamers: Pros and cons, and comprehensive selection strategies

    PubMed Central

    Chen, Suxiang; Chakravarthy, Madhuri; Rakesh, Shilpa; Veedu, Rakesh N.

    2016-01-01

    ABSTRACT Nucleic acid aptamers are single-stranded DNA or RNA oligonucleotide sequences that bind to a specific target molecule with high affinity and specificity through their ability to adopt 3-dimensional structure in solution. Aptamers have huge potential as targeted therapeutics, diagnostics, delivery agents and as biosensors. However, aptamers composed of natural nucleotide monomers are quickly degraded in vivo and show poor pharmacodynamic properties. To overcome this, chemically-modified nucleic acid aptamers are developed by incorporating modified nucleotides after or during the selection process by Systematic Evolution of Ligands by EXponential enrichment (SELEX). This review will discuss the development of chemically-modified aptamers and provide the pros and cons, and new insights on in vitro aptamer selection strategies by using chemically-modified nucleic acid libraries. PMID:27715478

  20. ON EFFECT OF HAZARD MAP ON CONS CIOUSNESS OF FLOOD DISASTER PREVENSION OF RESIDENTS WHO EXPERIENCED FLOOD RECENTLY

    NASA Astrophysics Data System (ADS)

    Asai, Koji; Koga, Syota; Sakakibara, Hiroyuki

    In this paper, the effect of the flood hazard map distributed to the residents who experienced flood disasters recently and an effective method for improving consciousness of flood di saster prevention are discussed. The questionnaire surveys were conducted on the residents living in the middle basin of the Nishiki River, Iwakuni city, Yamaguchi Prefecture, before and after the distribution of the hazard map. It is found from this investigation that "knowledge", "att achment", and "crisis", are the main factors in the psychological process related to the flood prevention behavior. The effect of the distribution of the hazard map is judged from the probability of the flood prevention behavior. In addition, it is also found that "knowledge", "flood experiment of T0514", "crisis", "eff ectiveness", "load", and "easy reading of the hazard map", are keys to improve the cons ciousness of flood di saster prevention.

  1. Nitrogen oxides and carbon chain oxides formed after ion irradiation of CO:N2 ice mixtures

    NASA Astrophysics Data System (ADS)

    Sicilia, D.; Ioppolo, S.; Vindigni, T.; Baratta, G. A.; Palumbo, M. E.

    2012-07-01

    Context. High CO depletion as well as depletion of N-bearing species is observed in dense pre-stellar cores. It is generally accepted that depleted species freeze out onto dust grains to form icy mantles and that these ices suffer energetic processing due to cosmic ion irradiation and ion-induced UV photons. Aims: The aim of this work is to study the chemical and structural effects induced by ion irradiation on different CO:N2 mixtures at low temperature (16 K) to simulate the effects of cosmic ion irradiation of icy mantles. Methods: Different CO:N2 mixtures and pure CO and pure N2 were irradiated with 200 keV H+ at 16 K. Infrared transmittance spectra of the samples were obtained in situ before and after irradiation. The samples were warmed up and spectra were taken at different temperatures. The residues left over on the substrate at room temperature were analysed ex situ by micro Raman spectroscopy. Results: Several new absorption features are present in the infrared spectra after irradiation, indicating that new species are formed. The most abundant are nitrogen oxides (such as NO, NO2 and N2O), carbon chain oxides (such as C2O, C3O and C3O2), carbon chains (such as C3 and C6), O3 and N3. A refractory residue is also formed after ion irradiation and is clearly detected by Raman spectroscopy. Conclusions: We suggest that carbon chains and nitrogen oxides observed in the gas phase towards star-forming regions are formed in the solid phase after cosmic ion irradiation of icy grain mantles and are released into the gas phase after desorption of grain mantles. We expect that the Atacama Large Millimeter/submillimeter Array (ALMA), thanks to its high sensitivity and resolution, will increase the number of nitrogen oxides and carbon chain oxides detected towards star-forming regions.

  2. PubMed

    Fernandez-Gallego, V; Hernández Herrera, G; Moreno Arciniegas, A; Moreno Rolando, E

    2016-12-30

    Presentamos el caso de un paciente que sufrió una parada cardiorrespiratoria extrahospitalaria en helicóptero sanitario, refractaria a tratamiento médico y eléctrico convencional. El paciente recuperó la circulación espontánea tras 58 minutos en paro cardiaco y 31 descargas eléctricas, estando monitorizado en todo momento de la reanimación cardiopulmonar con capnografía (valores > 20 mm/Hg). A su llegada al hospital, se le realizó una angioplastia primaria, colocándosele un stent en la arteria coronaria derecha. El paciente fue dado de alta hospitalaria, sin secuelas neurológicas (categoría de función cerebral 1).

  3. Binding of NIR-conPK and NIR-6T to Astrocytomas and Microglial Cells: Evidence for a Protein Related to TSPO

    PubMed Central

    Sexton, Michelle; Woodruff, Grace; Cudaback, Eiron; Kreitzer, Faith R.; Xu, Cong; Lin, Yi Hsing; Möller, Thomas; Bai, Mingfeng; Manning, H. Charles; Bornhop, Darryl; Stella, Nephi

    2009-01-01

    PK 11195 and DAA1106 bind with high-affinity to the translocator protein (TSPO, formerly known as the peripheral benzodiazepine receptor). TSPO expression in glial cells increases in response to cytokines and pathological stimuli. Accordingly, [11C]-PK 11195 and [11C]-DAA1106 are recognized molecular imaging (MI) agents capable of monitoring changes in TSPO expression occurring in vivo and in response to various neuropathologies. Here we tested the pharmacological characteristics and TSPO-monitoring potential of two novel MI agents: NIR-conPK and NIR-6T. NIR-conPK is an analogue of PK 11195 conjugated to the near-infrared (NIR) emitting fluorophore: IRDye 800CW. NIR-6T is a DAA1106 analogue also conjugated to IRDye 800CW. We found that NIR-6T competed for [3H]-PK 11195 binding in astrocytoma cell homogenates with nanomolar affinity, but did not exhibit specific binding in intact astrocytoma cells in culture, indicating that NIR-6T is unlikely to constitute a useful MI agent for monitoring TSPO expression in intact cells. Conversely, we found that NIR-conPK did not compete for [3H]-PK 11195 binding in astrocytoma cell homogenate, but exhibited specific binding in intact astrocytoma cells in culture with nanomolar affinity, suggesting that NIR-conPK binds to a protein distinct, but related to, TSPO. Accordingly, treating intact astrocytoma cells and microglia in culture with cytokines led to significant changes in the amount of NIR-conPK specific binding without corresponding change in TSPO expression. Remarkably, the cytokine-induced changes in the protein targeted by NIR-conPK in intact microglia were selective, since IFN-γ (but not TNFα and TGFβ) increased the amount of NIR-conPK specific binding in these cells. Together these results suggest that NIR-conPK binds to a protein that is related to TSPO, and expressed by astrocytomas and microglia. Our results also suggest that the expression of this protein is increased by specific cytokines, and thus allows for

  4. Estudio de la influencia de la refrigeracion con aire de forma natural e inducida en el comportamiento de instalaciones fotovoltaicas

    NASA Astrophysics Data System (ADS)

    Mazon Hernandez, Rocio

    panels are analysed to compare and select the best configuration. The presented research provides a deep knowledge of how they work as well as information and results for an improvement in future designs of building integrated photovoltaic systems. Este estudio se centra en analizar la influencia negativa de la temperatura en la produccion electrica de paneles fotovoltaicos al estar emplazados sobre cubierta de acero, como sucede en naves industriales y sobre un invernadero. Se estudian diferentes configuraciones que permitan refrigerar los paneles, reduciendo su temperatura y mejorar su rendimiento. Para abordar este problema, se han construido dos instalaciones experimentales, fieles a plantas solares en funcionamiento. Una instalacion engloba dos paneles fotovoltaicos sobre estructura fija al suelo. Uno de los paneles esta integrado sobre una superficie paralela y metalica. Entre ambas superficies existe un espacio que posibilita circular aire, permitiendo refrigerar el panel por conveccion natural, o conveccion forzada impulsando el aire con un ventilador. El otro panel, libre por su cara posterior y se ha considerado de referencia. Se ha estudiado el comportamiento del panel integrado sobre cubierta para diferentes secciones de aire y velocidades inducidas, comparandolo con el panel de referencia. Se ha desarrollado un modelo experimental que nos permite determinar la temperatura del panel en funcion de las variables que influyen en su refrigeracion. Adicionalmente, se han analizado los datos de una planta solar en funcionamiento, con paneles de igual caracteristicas, obteniendo correlaciones entre la temperatura del panel y las variables electricas y comparandolos con las obtenidas en la instalacion experimental. La segunda instalacion experimental reproduce parte de una instalacion solar sobre un invernadero, formada por cuatro paneles fotovoltaicos colocados sobre el plastico del invernadero, existiendo un canal divergente entre ambas superficies. Se estudia la

  5. [Occipital nerve stimulation for refractory chronic migraine].

    PubMed

    Bermejo, Pedro E; Torres, Cristina V; Sola, Rafael G

    2015-06-01

    Introduccion. La estimulacion de nervios occipitales (ENO) es un tratamiento preventivo de la migraña cronica refractaria que esta adquiriendo una importancia creciente en los ultimos años. Objetivo. Evaluar el mecanismo de accion, estudios clinicos, tecnica de implantacion y criterios de inclusion de la ENO en el tratamiento preventivo de la migraña. Desarrollo. Se realiza una revision no sistematica de la bibliografia sobre los aspectos anteriormente expuestos en la ENO como tratamiento para la migraña cronica. Esta patologia afecta aproximadamente al 2% de la poblacion y da lugar a una importante disminucion de la calidad de vida e interferencia con las actividades laborales y sociales. La ENO es una terapia emergente y prometedora para el tratamiento de la migraña cronica que ha demostrado una disminucion superior al 50% en el dolor en la mayoria de los estudios abiertos y ensayos clinicos publicados. Aunque el mecanismo de accion es desconocido, parece existir una neuromodulacion de la informacion nociceptiva trigeminal en el nucleo caudal del trigemino explicada mediante la teoria de la puerta de entrada de Melzack y Wall. La ENO es un tratamiento seguro y bien tolerado, y los efectos secundarios son habitualmente locales, como desplazamiento de los electrodos o infecciones de la herida quirurgica, que habitualmente no requieren su retirada. Conclusiones. La ENO es un tratamiento eficaz, bien tolerado y seguro en la prevencion de la migraña cronica, y supone una opcion util para aquellos pacientes con migraña cronica refractaria a los tratamientos medicos convencionales.

  6. Inversor Resonante de Tres Elementos L-LC con Caracteristica Cortocircuitable para Aplicaciones de Calentamiento por Induccion

    NASA Astrophysics Data System (ADS)

    Espi Huerta, Jose Miguel

    Los generadores de calentamiento por induccion son puentes inversores con carga resonante, cuya mision es basicamente crear una corriente sinusoidal de gran amplitud sobre la "bobina de caldeo", que forma parte del tanque resonante. En el interior de esta bobina se introduce la pieza que se desea calentar. EI campo magnetico creado induce corrientes superficiales (corrientes de Foucault) sobre la pieza, que producen su calentamiento. Los tanques resonantes (tambien llamados osciladores) utilizados en la actualidad son el resonante serie y el resonante paralelo. Aunque ya desde hace algun tiempo se vienen construyendo generadores de alta potencia basados en estos dos osciladores, el exito nunca ha. sido completo en ninguno de los dos casos. Tal y como se explica en la introduccion de esta memoria, los puentes inversores utilizados deben operar sobre una carga inductiva (corriente retrasada) para evitar el fenomeno de la recuperacion inversa de sus diodos y la consiguiente ruptura de los transistores. De la restriccion topologica anterior se deduce que el generador paralelo debe conmutar a frecuencias inferiores a la resonancia, y el serie a frecuencias superiores. A esta restriccion topologica hay que unir otra que es exclusiva del calentamiento por induccion: La corriente por la bobina de caldeo debe ser sinusoidal. De no ser asi, resultaria imposible disponer toda la potencia de calentamiento sobre la pieza en el espesor requerido por la aplicacion. Como consecuencia, los inversores no pueden operar por debajo de la frecuencia de resonancia del oscilador, pues en ese caso se amplifican los armonicos de orden superior de la tension/corriente de entrada situados sobre la resonancia, con la consiguiente distorsion de la corriente de salida. La conjuncion de las dos restricciones anteriores obligan al inversor paralelo a funcionar a la frecuencia de resonancia del oscilador. Esto imposibilita un control por variacion de frecuencia, regulandose la potencia desde la

  7. [Refractory encephalitis because of seronegative celiac disease: a case report].

    PubMed

    Filippín, Federico A; Alfonso, Alejandra; López-Presas, Héctor

    2016-04-01

    Introduccion. La enfermedad celiaca es una enteropatia inducida por el gluten por mecanismos inmunes, que puede presentar afectacion sistemica y producir un amplio espectro de manifestaciones neurologicas, que van desde polineuropatia periferica, ataxia, epilepsia y migraña hasta encefalitis. El objetivo es informar de un caso de posible encefalitis refractaria por enfermedad celiaca. Caso clinico. Varon de 45 años con diagnostico histopatologico de enfermedad celiaca y anticuerpos anticeliaquia negativos que intercurre con encefalitis, manifestaciones del tronco encefalico y del sistema nervioso periferico, entre las que se incluyen deterioro cognitivo y convulsiones, diplopia y ataxia, y polirradiculopatia y polineuropatia, respectivamente; liquido cefalorraquideo inflamatorio y multiples lesiones corticosubcorticales supratentoriales y en el tronco encefalico con leve realce con contraste. Los deficits neurologicos progresan a pesar de una dieta libre de gluten y el tratamiento farmacologico inmunosupresor. Durante el curso de la enfermedad se estudian patologias con afectacion simultanea intestinal y del sistema nervioso, como sarcoidosis, lupus eritematoso sistemico, enfermedad de Sjogren, sindrome paraneoplasico, sida, enfermedad de Whipple y deficit de vitamina B12. Conclusion. La encefalitis es una manifestacion clinica infrecuente en la enfermedad celiaca, con pocos casos notificados a pesar de la alta prevalencia de la enfermedad. Los diagnosticos diferenciales son dificiles y exigen una alta sospecha diagnostica, por lo que es un reto terapeutico.

  8. Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a general hospital at São Paulo city, Brasil.

    PubMed

    d'Azevedo, P A; Secchi, C; Antunes, A L S; Sales, T; Silva, F M; Tranchesi, R; Pignatari, A C C

    2008-10-01

    In the last decades, coagulase-negative staphylococci (CoNS), especially Staphylococcus epidermidis have become an important cause of bloodstream infections. In addition, rates of methicillin-resistance among CoNS have increased substantially, leading to the use of glicopeptides for therapy. The objective of this study was to evaluate eleven consecutives clinically relevant cases of oxacillin-resistant CoNS bacteremia in a general hospital localized in São Paulo city, Brazil. Five different species were identified by different phenotypic methods, including S. epidermidis (5), S. haemolyticus (3), S. hominis (1), S. warneri (1) and S. cohnii subsp urealyticus (1). A variety of Pulsed Field Gel Electrophoresis profiles was observed by macrorestriction DNA analysis in S. epidermidis isolates, but two of three S. haemolyticus isolates presented the same profile. These data indicated the heterogeneity of the CoNS isolates, suggesting that horizontal dissemination of these microorganisms in the investigated hospital was not frequent. One S. epidermidis and one S. haemolyticus isolates were resistant to teicoplanin and susceptible to vancomycin. The selective pressure due to the use of teicoplanin in this hospital is relevant.

  9. Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package.

    PubMed

    Borbulevych, Oleg Y; Plumley, Joshua A; Martin, Roger I; Merz, Kenneth M; Westerhoff, Lance M

    2014-05-01

    Macromolecular crystallographic refinement relies on sometimes dubious stereochemical restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule and any covalently bound ligand(s). The ligand stereochemical restraint file (CIF) requires a priori understanding of the ligand geometry within the active site, and creation of the CIF is often an error-prone process owing to the great variety of potential ligand chemistry and structure. Stereochemical restraints have been replaced with more robust functionals through the integration of the linear-scaling, semiempirical quantum-mechanics (SE-QM) program DivCon with the PHENIX X-ray refinement engine. The PHENIX/DivCon package has been thoroughly validated on a population of 50 protein-ligand Protein Data Bank (PDB) structures with a range of resolutions and chemistry. The PDB structures used for the validation were originally refined utilizing various refinement packages and were published within the past five years. PHENIX/DivCon does not utilize CIF(s), link restraints and other parameters for refinement and hence it does not make as many a priori assumptions about the model. Across the entire population, the method results in reasonable ligand geometries and low ligand strains, even when the original refinement exhibited difficulties, indicating that PHENIX/DivCon is applicable to both single-structure and high-throughput crystallography.

  10. Studies on prevalence of biofilm associated genes and primary observation on sasX gene in clinical isolates of coagulase negative staphylococci (CoNS).

    PubMed

    Soumya, Kandammuriyil Radhakrishnan; Mathew, Shiji; Sugathan, Sheela; Mathew, Jyothis; Radhakrishnan, Edayileveettil Krishnankutty

    2016-04-01

    Coagulase negative staphylococci (CoNS) are nosocomial pathogens that cause indwelling medical device associated infections due to its biofilm forming potential and multiple antibiotic resistance. The current study focused on species identification, antibiotic resistance profile and molecular basis of biofilm formation and attachment of CoNS isolated from clinical samples. Along with this, molecular screening for mecA and newly identified surface colonization protein encoded by sasX gene was also conducted. S. epidermidis (n = 19, 47%) was identified as the most prevalent CoNS species and very interestingly two biofilm forming, mecA positive S. epidermidis isolates were found to carry all the biofilm associated genes screened in this study, which indicates its potential to form the strong biofilm. Another novel observation of the study is the detection of sasX gene in one biofilm positive S. epidermidis isolate. The study also identified one doxycycline resistant mecA positive, multidrug resistant S. haemolyticus isolate. In conclusion, the study signifies the existence of multiple biofilm related genes, multidrug resistance and the presence of sasX gene among clinical isolates of CoNS.

  11. Synthesis, growth, structural, spectral, thermal, chemical etching, linear and nonlinear optical and mechanical studies of an organic single crystal 4-chloro 4-nitrostilbene (CONS): A potential NLO material

    NASA Astrophysics Data System (ADS)

    Dinakaran, Paul M.; Kalainathan, S.

    2013-07-01

    4-Chloro 4-nitrostilbene (CONS) a new organic nonlinear optical material has been synthesized. Employing slow evaporation method, good optical quality single crystals (dimensions up to 6 × 2 × 3 mm3) have been grown using ethyl methyl ketone (EMK) as a solvent. The grown crystals have been subjected to various characterizations such as single crystal X-ray diffraction, powder XRD, Fourier Transform Infrared spectroscopy (FTIR), proton NMR, solid UV absorption, SHG studies. Single crystal X-ray diffraction reveals that the crystal system belongs to monoclinic with noncentrosymmetric space group P21. The UV-Vis absorption spectrum has been recorded and found that the cut off wavelength is 380 nm. Functional groups and the structure of the title compound have been confirmed by FTIR and 1H NMR spectroscopic analyses respectively. Molecular mass of the CONS confirmed by the high resolution mass spectral analysis .The thermal behavior of the grown crystal has been studied by TG/DTA analysis and it shows the melting point is at 188.66 °C. Dislocations and growth pattern present in the grown crystal revealed by the etching study. The mechanical strength of the CONS crystal has been studied by Vicker's hardness measurement. The SHG efficiency of the grown crystal has been determined by Kurtz and Perry powder test which revealed that the CONS crystal (327 mV) has 15 times greater efficiency than that of KDP (21.7 mV).

  12. Synthesis, growth, structural, spectral, thermal, chemical etching, linear and nonlinear optical and mechanical studies of an organic single crystal 4-chloro 4-nitrostilbene (CONS): a potential NLO material.

    PubMed

    Dinakaran, Paul M; Kalainathan, S

    2013-07-01

    4-Chloro 4-nitrostilbene (CONS) a new organic nonlinear optical material has been synthesized. Employing slow evaporation method, good optical quality single crystals (dimensions up to 6×2×3 mm(3)) have been grown using ethyl methyl ketone (EMK) as a solvent. The grown crystals have been subjected to various characterizations such as single crystal X-ray diffraction, powder XRD, Fourier Transform Infrared spectroscopy (FTIR), proton NMR, solid UV absorption, SHG studies. Single crystal X-ray diffraction reveals that the crystal system belongs to monoclinic with noncentrosymmetric space group P21. The UV-Vis absorption spectrum has been recorded and found that the cut off wavelength is 380 nm. Functional groups and the structure of the title compound have been confirmed by FTIR and (1)H NMR spectroscopic analyses respectively. Molecular mass of the CONS confirmed by the high resolution mass spectral analysis .The thermal behavior of the grown crystal has been studied by TG/DTA analysis and it shows the melting point is at 188.66 °C. Dislocations and growth pattern present in the grown crystal revealed by the etching study. The mechanical strength of the CONS crystal has been studied by Vicker's hardness measurement. The SHG efficiency of the grown crystal has been determined by Kurtz and Perry powder test which revealed that the CONS crystal (327 mV) has 15 times greater efficiency than that of KDP (21.7 mV).

  13. Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package

    PubMed Central

    Borbulevych, Oleg Y.; Plumley, Joshua A.; Martin, Roger I.; Merz, Kenneth M.; Westerhoff, Lance M.

    2014-01-01

    Macromolecular crystallographic refinement relies on sometimes dubious stereochemical restraints and rudimentary energy functionals to ensure the correct geometry of the model of the macromolecule and any covalently bound ligand(s). The ligand stereochemical restraint file (CIF) requires a priori understanding of the ligand geometry within the active site, and creation of the CIF is often an error-prone process owing to the great variety of potential ligand chemistry and structure. Stereochemical restraints have been replaced with more robust functionals through the integration of the linear-scaling, semiempirical quantum-mechanics (SE-QM) program DivCon with the PHENIX X-ray refinement engine. The PHENIX/DivCon package has been thoroughly validated on a population of 50 protein–ligand Protein Data Bank (PDB) structures with a range of resolutions and chemistry. The PDB structures used for the validation were originally refined utilizing various refinement packages and were published within the past five years. PHENIX/DivCon does not utilize CIF(s), link restraints and other parameters for refinement and hence it does not make as many a priori assumptions about the model. Across the entire population, the method results in reasonable ligand geometries and low ligand strains, even when the original refinement exhibited difficulties, indicating that PHENIX/DivCon is applicable to both single-structure and high-throughput crystallography. PMID:24816093

  14. Fragilidad y su asociación con mortalidad, hospitalizaciones y dependencia funcional en mexicanos de 60 años o más

    PubMed Central

    de León González, Enrique Díaz; Pérez, Héctor Eloy Tamez; Hermosillo, Hugo Gutiérrez; Rodríguez, Javier Armando Cedillo; Torres, Gabriela

    2016-01-01

    Fundamento y objetivo Determinar la asociación entre fragilidad y mortalidad, dependencia funcional, caídas y hospitalizaciones en el Estudio Nacional de Salud y Envejecimiento en México (ENASEM). Sujetos y métodos Estudio prospectivo poblacional en México en el que se seleccionaron sujetos de 60 años o más, que fueron evaluados en las variables de fragilidad durante la primera vuelta del estudio en el año 2001 y que incluyó: dificultad para levantarse de una silla después de haber estado sentado(a) durante largo tiempo, pérdida de peso de 5 kilogramos o más en los últimos dos años y falta de energía. Los sujetos fueron catalogados como robustos, prefrágiles y frágiles cuando tenían cero, una o dos de las características anteriores, respectivamente. La mortalidad, hospitalizaciones, caídas y dependencia funcional fueron evaluadas en la segunda vuelta del estudio en el año 2003. Se calculó el riesgo relativo para cada una de las complicaciones, así como análisis multivariado con regresión de Cox para el caso de mortalidad y regresión logística para el resto. Resultados Los estados de prefragilidad y fragilidad se asociaron independientemente con mortalidad, con índices de riesgo ajustados de 1,61 (intervalo de confianza del 95% [IC 95%] 1,01-2,55) y 1,94 (IC 95% 1,20-3,13), respectivamente. Sólo el estado de fragilidad se asoció independientemente con hospitalización y dependencia funcional, con una razón de momios ajustada de 1,53 (IC 95% 1,13-2,07) y 3,07 (IC 95% 1,76-5,34), respectivamente. No hubo asociación entre los estados de prefragilidad y fragilidad con caídas. Conclusión El estado de fragilidad se asocia independientemente con mortalidad, hospitalizaciones y disfuncionalidad en actividades básicas de la vida diaria en los siguientes dos años en población mexicana. PMID:21612803

  15. Aspergilosis cervical con diseminación al sistema nervioso central. Presentación de un caso y revisión de bibliografía

    PubMed Central

    Vergara, Guillermo Enrique; Roura, Natalia; del Castillo, Marcelo; Mora, Andrea; Alcorta, Santiago Condomi; Mormandi, Rubén; Cervio, Andrés; Salvat, Jorge

    2015-01-01

    Introducción: la Aspergilosis Invasiva (AI) del Sistema Nervioso Central (SNC) es infrecuente y ocurre generalmente en pacientes inmunocomprometidos. Puede presentarse con cuadros de meningitis, aneurismas micóticos, infartos o abscesos. Es una infección con pronóstico reservado y puede afectar el SNC de forma primaria o secundaria a partir de un foco que se disemina por vía hematógena. Presentamos el caso de un paciente con AI con invasión primaria a nivel óseo y diseminación posterior al cerebro. Caso clínico: Paciente masculino de 25 años con diagnóstico de leucemia linfática aguda en tratamiento quimioterápico que presentó neumonitis por metotrexate por lo que inicia tratamiento con corticoides. Posteriormente agregó cervicalgia y con el diagnóstico de osteomielitis cervical se realiza punción bajo tomografía computada (TC) sin aislarse gérmenes. Se colocó Halo Vest e inició tratamiento antibiótico empírico. Posteriormente presentó afasia de expresión secundaria a lesión frontal izquierda. Se realizó evacuación de absceso cerebral aislando A. fumigatus. El tratamiento antibiótico específico posterior permitió una buena respuesta clínica y radiológica. Conclusión: La presencia de lesiones en el SNC de pacientes inmunocomprometidos debe incluir a las micosis como diagnóstico diferencial. La evacuación quirúrgica permite llegar rápidamente al diagnóstico mejorando la respuesta posterior al tratamiento antibiótico. Para evaluar la respuesta terapéutica y posibles recaídas se debe realizar un seguimiento periódico clínico radiológico. Palabras clave: Aspergilosis cerebral; Aspergilosis cervical; Aspergilosis invasiva; Voriconazol. PMID:26600985

  16. Should a Preschool Child with Acute Episodic Wheeze be Treated with Oral Corticosteroids? A Pro/Con Debate.

    PubMed

    Beigelman, Avraham; Durrani, Sandy; Guilbert, Theresa W

    2016-01-01

    Traditionally, preschool-aged children with an acute wheezing episode have been treated with oral corticosteroids (OCSs) based on the efficacy of OCSs in older children and adolescents. However, this practice has been recently challenged based on the results of recent studies. The argument supporting the use of OCSs underscores the observation that many children with recurrent preschool wheezing develop atopic disease in early life which predicts both an increased risk to develop asthma in later life and response to OCS therapy. Further, review of the literature demonstrates heterogeneity of study designs, OCS dosage, interventions, study medication adherence, and settings and overall lack of predefined preschool wheezing phenotypes. The heterogeneity of these studies does not allow a definitive recommendation discouraging OCS use. Advocates against the use of OCSs in this population argue that most of studies investigating the efficacy of OCSs in acute episodic wheeze in preschool-aged children have not demonstrated beneficial effects. Moreover, repeated OCS bursts may be associated with adverse effects. Finally, both sides can agree that there is a significant need to conduct efficacy trials evaluating OCS treatment in preschool-aged children with recurrent wheezing targeted at phenotypes that would be expected to respond to OCSs. This article presents a summary of recent literature regarding the use of OCSs for acute episodic wheezing in preschool-aged children and a "pro" and "con" debate for such use.

  17. Air Traffic Management Technology Demonstration-1 Concept of Operations (ATD-1 ConOps), Version 2.0

    NASA Technical Reports Server (NTRS)

    Baxley, Brian T.; Johnson, William C.; Swenson, Harry N.; Robinson, John E.; Prevot, Tom; Callantine, Todd J.; Scardina, John; Greene, Michael

    2013-01-01

    This document is an update to the operations and procedures envisioned for NASA s Air Traffic Management (ATM) Technology Demonstration #1 (ATD-1). The ATD-1 Concept of Operations (ConOps) integrates three NASA technologies to achieve high throughput, fuel-efficient arrival operations into busy terminal airspace. They are Traffic Management Advisor with Terminal Metering (TMA-TM) for precise time-based schedules to the runway and points within the terminal area, Controller-Managed Spacing (CMS) decision support tools for terminal controllers to better manage aircraft delay using speed control, and Flight deck Interval Management (FIM) avionics and flight crew procedures to conduct airborne spacing operations. The ATD-1 concept provides de-conflicted and efficient operations of multiple arrival streams of aircraft, passing through multiple merge points, from top-of-descent (TOD) to the Final Approach Fix. These arrival streams are Optimized Profile Descents (OPDs) from en route altitude to the runway, using primarily speed control to maintain separation and schedule. The ATD-1 project is currently addressing the challenges of integrating the three technologies, and their implantation into an operational environment. The ATD-1 goals include increasing the throughput of high-density airports, reducing controller workload, increasing efficiency of arrival operations and the frequency of trajectory-based operations, and promoting aircraft ADS-B equipage.

  18. Con-forming bodies: the interplay of machines and bodies and the implications of agency in medical imaging.

    PubMed

    Wood, Lisa A

    2016-06-01

    Attending to the material discursive constructions of the patient body within cone beam computed tomography (CBCT) imaging in radiotherapy treatments, in this paper I describe how bodies and machines co-create images. Using an analytical framework inspired by Science and Technology Studies and Feminist Technoscience, I describe the interplay between machines and bodies and the implications of materialities and agency. I argue that patients' bodies play a part in producing scans within acceptable limits of machines as set out through organisational arrangements. In doing so I argue that bodies are fabricated into the order of work prescribed and embedded within and around the CBCT system, becoming, not only the subject of resulting images, but part of that image. The scan is not therefore a representation of a passive subject (a body) but co-produced by the work of practitioners and patients who actively control (and contort) and discipline their body according to protocols and instructions and the CBCT system. In this way I suggest they are 'con-forming' the CBCT image. A Virtual Abstract of this paper can be found at: https://youtu.be/qysCcBGuNSM.

  19. Evaluation of GO_CONS_GCF_2_TIM and GOCO01S Geopotential Models in Venezuela and Caribbean Region

    NASA Astrophysics Data System (ADS)

    Orihuela, N. D.; Garcia, A. D.; Tabare, T.; Scientific Team Of Venezuelan; Caribbean Crustal Study From Satellital Data

    2010-12-01

    This paper shows two maps of the magnitude of the surface gravity vector (MSGV) of Venezuela and Caribbean region at 1:500.000 scale in the geographic window between the 0-20 north latitude and 74-58 western longitude (Fig. 1 and Fig. 2), that were generated from GOCE gravity gradients data provided by the European Space Agency (ESA). The maps that are showed come from the combined global gravity field model GOCO01s [GOCO Consortium., 2010] and from the satellite-only global gravity field model GO_CONS_GCF_2_TIM [Pail et al., 2010], both of 224 degree. The DEMs used for the evaluation of the MSGV are: Etopo2v2 [NGDC., 2006] and Etopo1 [Amante and Eakins, 2009] respectively. The data processing was done using: Shm2func [ICGEM., 2007]; Goce User Toolbox [ESA., 2009]; Gravsoft package [Tscherning et al., 1992] and Oasis Montaj (Geosoft). This research shows a review of observed gravity in the main geological provinces of the Venezuela and Caribbean region geography, revealing gravitational features important of the geological structures that are in Venezuelan and Caribbean subsurface.

  20. Laboratory simulation of Kuiper belt object volatile ices under ionizing radiation: CO-N2 ices as a case study.

    PubMed

    Kim, Y S; Zhang, F; Kaiser, R I

    2011-09-21

    The exposure of icy Kuiper belt objects (KBOs) by ionizing radiation was simulated in this case of exposing carbon monoxide-nitrogen (CO-N(2)) ices by energetic electrons. The radiation-induced chemical processing was monitored on-line and in situ via FTIR spectroscopy and quadrupole mass spectrometry. Besides the array of carbon oxides being reproduced as in neat irradiated carbon monoxide (CO) ices studied previously, the radiation exposure at 10 K resulted in the formation of nitrogen-bearing species of isocyanato radical (OCN), linear (l-NCN), nitric oxide (NO), nitrogen dioxide (NO(2)), plus diazirinone (N(2)CO). The infrared assignments of these species were further confirmed by isotopic shifts. The temporal evolution of individual species was found to fit in first-order reaction schemes, prepping up the underlying non-equilibrium chemistry on the formation of OCN, l-NCN, and NO radicals in particular. Also unique to the binary KBO model ices and viable for the future remote detection is diazirinone (N(2)CO) at 1860 cm(-1) (2ν(5)) formed at lower radiation exposure.

  1. Document-level classification of CT pulmonary angiography reports based on an extension of the ConText algorithm.

    PubMed

    Chapman, Brian E; Lee, Sean; Kang, Hyunseok Peter; Chapman, Wendy W

    2011-10-01

    In this paper we describe an application called peFinder for document-level classification of CT pulmonary angiography reports. peFinder is based on a generalized version of the ConText algorithm, a simple text processing algorithm for identifying features in clinical report documents. peFinder was used to answer questions about the disease state (pulmonary emboli present or absent), the certainty state of the diagnosis (uncertainty present or absent), the temporal state of an identified pulmonary embolus (acute or chronic), and the technical quality state of the exam (diagnostic or not diagnostic). Gold standard answers for each question were determined from the consensus classifications of three human annotators. peFinder results were compared to naive Bayes' classifiers using unigrams and bigrams. The sensitivities (and positive predictive values) for peFinder were 0.98(0.83), 0.86(0.96), 0.94(0.93), and 0.60(0.90) for disease state, quality state, certainty state, and temporal state respectively, compared to 0.68(0.77), 0.67(0.87), 0.62(0.82), and 0.04(0.25) for the naive Bayes' classifier using unigrams, and 0.75(0.79), 0.52(0.69), 0.59(0.84), and 0.04(0.25) for the naive Bayes' classifier using bigrams.

  2. Circulating microRNA Biomarkers as Liquid Biopsy for Cancer Patients: Pros and Cons of Current Assays.

    PubMed

    Ono, Shigeshi; Lam, Stella; Nagahara, Makoto; Hoon, Dave S B

    2015-10-23

    An increasing number of studies have focused on circulating microRNAs (cmiRNA) in cancer patients' blood for their potential as minimally-invasive biomarkers. Studies have reported the utility of assessing specific miRNAs in blood as diagnostic/prognostic biomarkers; however, the methodologies are not validated or standardized across laboratories. Unfortunately, there is often minimum limited overlap in techniques between results reported even in similar type studies on the same cancer. This hampers interpretation and reliability of cmiRNA as potential cancer biomarkers. Blood collection and processing, cmiRNA extractions, quality and quantity control of assays, defined patient population assessment, reproducibility, and reference standards all affect the cmiRNA assay results. To date, there is no reported definitive method to assess cmiRNAs. Therefore, appropriate and reliable methodologies are highly necessary in order for cmiRNAs to be used in regulated clinical diagnostic laboratories. In this review, we summarize the developments made over the past decade towards cmiRNA detection and discuss the pros and cons of the assays.

  3. Status and Progress of a Fault Current Limiting Hts Cable to BE Installed in the con EDISON Grid

    NASA Astrophysics Data System (ADS)

    Maguire, J.; Folts, D.; Yuan, J.; Henderson, N.; Lindsay, D.; Knoll, D.; Rey, C.; Duckworth, R.; Gouge, M.; Wolff, Z.; Kurtz, S.

    2010-04-01

    In the last decade, significant advances in the performance of second generation (2G) high temperature superconducting wire have made it suitable for commercially viable applications such as electric power cables and fault current limiters. Currently, the U.S. Department of Homeland Security is co-funding the design, development and demonstration of an inherently fault current limiting HTS cable under the Hydra project with American Superconductor and Consolidated Edison. The cable will be approximately 300 m long and is being designed to carry 96 MVA at a distribution level voltage of 13.8 kV. The underground cable will be installed and energized in New York City. The project is led by American Superconductor teamed with Con Edison, Ultera (Southwire and nkt cables joint venture), and Air Liquide. This paper describes the general goals, design criteria, status and progress of the project. Fault current limiting has already been demonstrated in 3 m prototype cables, and test results on a 25 m three-phase cable will be presented. An overview of the concept of a fault current limiting cable and the system advantages of this unique type of cable will be described.

  4. Monitoring chemical reactions by low-field benchtop NMR at 45 MHz: pros and cons.

    PubMed

    Silva Elipe, Maria Victoria; Milburn, Robert R

    2016-06-01

    Monitoring chemical reactions is the key to controlling chemical processes where NMR can provide support. High-field NMR gives detailed structural information on chemical compounds and reactions; however, it is expensive and complex to operate. Conversely, low-field NMR instruments are simple and relatively inexpensive alternatives. While low-field NMR does not provide the detailed information as the high-field instruments as a result of their smaller chemical shift dispersion and the complex secondary coupling, it remains of practical value as a process analytical technology (PAT) tool and is complimentary to other established methods, such as ReactIR and Raman spectroscopy. We have tested a picoSpin-45 (currently under ThermoFisher Scientific) benchtop NMR instrument to monitor three types of reactions by 1D (1) H NMR: a Fischer esterification, a Suzuki cross-coupling, and the formation of an oxime. The Fischer esterification is a relatively simple reaction run at high concentration and served as proof of concept. The Suzuki coupling is an example of a more complex, commonly used reaction involving overlapping signals. Finally, the oxime formation involved a reaction in two phases that cannot be monitored by other PAT tools. Here, we discuss the pros and cons of monitoring these reactions at a low-field of 45 MHz by 1D (1) H NMR. Copyright © 2015 John Wiley & Sons, Ltd.

  5. The Use of Laser Microdissection in Forensic Sexual Assault Casework: Pros and Cons Compared to Standard Methods.

    PubMed

    Costa, Sergio; Correia-de-Sá, Paulo; Porto, Maria J; Cainé, Laura

    2017-01-30

    Sexual assault samples are among the most frequently analyzed in a forensic laboratory. These account for almost half of all samples processed routinely, and a large portion of these cases remain unsolved. These samples often pose problems to traditional analytic methods of identification because they consist most frequently of cell mixtures from at least two contributors: the victim (usually female) and the perpetrator (usually male). In this study, we propose the use of current preliminary testing for sperm detection in order to determine the chances of success when faced with samples which can be good candidates to undergo analysis with the laser microdissection technology. Also, we used laser microdissection technology to capture fluorescently stained cells of interest differentiated by gender. Collected materials were then used for DNA genotyping with commercially available amplification kits such as Minifiler, Identifiler Plus, NGM, and Y-Filer. Both the methodology and the quality of the results were evaluated to assess the pros and cons of laser microdissection compared with standard methods. Overall, the combination of fluorescent staining combined with the Minifiler amplification kit provided the best results for autosomal markers, whereas the Y-Filer kit returned the expected results regardless of the used method.

  6. Special funding schemes for innovative medical devices in French hospitals: the pros and cons of two different approaches.

    PubMed

    Martelli, Nicolas; van den Brink, Hélène

    2014-07-01

    Financing innovative medical devices is an important challenge for national health policy makers, and a crucial issue for hospitals. However, when innovative medical devices are launched on the European market there is generally little clinical evidence regarding both efficacy and safety, both because of the flaws in the European system for regulating such devices, and because they are at an early stage of development. To manage the uncertainty surrounding the reimbursement of innovation, several European countries have set up temporary funding schemes to generate evidence about the effectiveness of devices. This article explores two different French approaches to funding innovative in-hospital devices and collecting supplementary data: the coverage with evidence development (CED) scheme introduced under Article L. 165-1-1 of the French Social Security Code; and national programs for hospital-based research. We discuss pros and cons of both approaches in the light of CED policies in Germany and the UK. The CED policies for devices share common limitations. Thus, transparency of CED processes should be enhanced and decisions need to be made in a timely way. Finally, we think that closer collaboration between manufacturers, health authorities and hospitals is essential to make CED policies more operational.

  7. Virgin Caenorhabditis remanei females are attracted to a coital pheromone released by con-specific copulating males

    PubMed Central

    Markert, Mathew; García, Luis René

    2013-01-01

    The gonochoristic soil nematode Caenorhabditis remanei strictly requires copulation for species propagation. Males of this species are sexually promiscuous with females of other species; therefore, we asked in this study whether virgin C. remanei females display evidence of mate choice. We digitally recorded and measured the locomotor behaviors of one or more virgin females in the presence of a single male on a 5 mm diameter mating lawn. We observed that initially only the male modifies his locomotor trajectory to another animal on the mating lawn; the virgin females showed no locomotor bias toward the mate-searching male. However, once a male started to copulate, females in the vicinity altered their movement trajectories toward the copulating couple. Newly inseminated females are refractive to the coital signal, but partially regain their attraction to copulating males after 24 h. We found only copulating males with an intact gonad can attract females, and that the coital signal can be broadcasted at least 1.5 mm through the air. Unlike males, which are also attracted to hetero-specific females, virgin C. remanei females will only crawl toward a copulating con-specific male. We suggest that Caenorhabditis females use the coital signal as a pheromone to identify a vigorous male of their own species. PMID:24058874

  8. Balancing the pros and cons of GMOs: socio-scientific argumentation in pre-service teacher education

    NASA Astrophysics Data System (ADS)

    Cinici, Ayhan

    2016-07-01

    This study investigates the role of the discursive process in the act of scientific knowledge building. Specifically, it links scientific knowledge building to risk perception of Genetically Modified Organisms (GMOs). To this end, this study designed and implemented a three-stage argumentation programme giving pre-service teachers (PSTs) the opportunity to consider, discuss and construct shared decisions about GMOs. The study involved 101 third-year PSTs from two different classes, randomly divided into control and experimental groups. The study utilised both quantitative and qualitative methods. During the quantitative phase, researchers administered a pre- and post-intervention scale to measure both groups' risk perception of GMOs. During the qualitative phase, data were collected from the experimental group alone through individual and group reports and an open-ended questionnaire. T-test results showed a statistically significant difference between the experimental and control groups' risk perception of GMOs. Qualitative analysis also revealed differences, for example, in PSTs' weighing of the pros and cons of scientific research demonstrating positive results of GMOs. In addition, PSTs' acceptance of GMOs increased. Consequently, this study suggests that developing familiarity with scientific enterprise may play an effective role in adopting a scientific perspective as well as a more balanced risk perception of GMOs.

  9. Circulating microRNA Biomarkers as Liquid Biopsy for Cancer Patients: Pros and Cons of Current Assays

    PubMed Central

    Ono, Shigeshi; Lam, Stella; Nagahara, Makoto; Hoon, Dave S. B.

    2015-01-01

    An increasing number of studies have focused on circulating microRNAs (cmiRNA) in cancer patients’ blood for their potential as minimally-invasive biomarkers. Studies have reported the utility of assessing specific miRNAs in blood as diagnostic/prognostic biomarkers; however, the methodologies are not validated or standardized across laboratories. Unfortunately, there is often minimum limited overlap in techniques between results reported even in similar type studies on the same cancer. This hampers interpretation and reliability of cmiRNA as potential cancer biomarkers. Blood collection and processing, cmiRNA extractions, quality and quantity control of assays, defined patient population assessment, reproducibility, and reference standards all affect the cmiRNA assay results. To date, there is no reported definitive method to assess cmiRNAs. Therefore, appropriate and reliable methodologies are highly necessary in order for cmiRNAs to be used in regulated clinical diagnostic laboratories. In this review, we summarize the developments made over the past decade towards cmiRNA detection and discuss the pros and cons of the assays. PMID:26512704

  10. Conózcanos

    EPA Pesticide Factsheets

    Principal de la EPA: información sobre el Administrador o la Administradora, los altos directivos; ubicaciones y direcciones de las oficinas; presupuesto, la planificación y los resultados de rendimiento

  11. The Classics, Con Brio

    ERIC Educational Resources Information Center

    Hansen, James

    1978-01-01

    Sponsored by a consortium of 30 American universities, Rome's Intercollegiate Center for Classical Studies offers a year of study to American undergraduate classics majors. Instructors are also American and normally stay only a year; teaching assistants are always ex-students of the center. Extensive field trips are an important part of the…

  12. Neo-Conned University

    ERIC Educational Resources Information Center

    Jones, Andee

    2014-01-01

    Censorship, says Australian political theorist John Keane (1991), can "echo within us, take up residence within ourselves, spying on us, a private amanuensis who reminds us never to go too far... It makes us zip our lips, tremble and think twice" (p. 39). It can also make us sick. The author states that this is her argument here: that,…

  13. Fotodensitometro realizzato con microscopio.

    NASA Astrophysics Data System (ADS)

    di Giovanni, G.

    1989-02-01

    This work describes the chracteristics and use of a microphotometer suitable for the measure of photographic density of photos of stars. The optics is a normal microscope which projects the small photographic image of a star on the plate of a photodiode. This high sensitivity instrument is easy to build up.

  14. [Weighing pros and cons].

    PubMed

    de Wit, W

    1992-03-15

    An adequate, high-quality animal health service is indispensable to animal production in the Netherlands. Modern intensive animal husbandry, with its high density of animals, needs a considerable input of knowledge, vaccines and drugs. The consumer expects healthy and especially safe products. These two goals are in seeming contradiction. Moreover, veterinary help, the necessary use of drugs, the supervision and control of AID (Agricultural Inspection Services) and RVV (Inspection Service for Meat and Meat Products) add to the already substantial costs of modern animal husbandry. From the point of view of integral quality control, the question is what changes are necessary to achieve a more effective health service. Goals for the future include: reducing the structural dependence on drugs and additives; substantially reducing the number of active substances used; increasing consumer confidence in animal products.

  15. Concepciones Alternativas de "Fotosintesis" en estudiantes Universitarios del curso basico de Biologia y posibles correcciones con el Modelo Educativo MODEF

    NASA Astrophysics Data System (ADS)

    De Jesus Roman, Sandra

    Concepciones Alternativas de Fotosíntesis en estudiantes Universitariosdel curso básico de Biología y posibles correcciones con el Modelo Educativo MODEF El modelo educativo para la enseñanza de Fotosíntesis (MODEF) se implantó para trabajar el problema de las concepciones alternativas (CA) en un curso de Biología General. Se evaluaron los resultados en cuanto al logro del aprendizaje significativo. La pregunta central de la investigación fue: ¿Cómo aporta el modelo educativo en la didáctica y comprensión del tema de fotosíntesis? Se efectuó una investigación acción con una fase cuantitativa y una cualitativa. Para la fase cuantitativa se elaboró una prueba para determinar las concepciones alternativas, se validó y se sometió a los estudiantes que participaron en el estudio antes y después de ofrecer la unidad de metabolismo celular. Los participantes eran estudiantes de primer año de la Universidad de Puerto Rico en Bayamón (UPRB). Se llevó a cabo un análisis de consistencia interna de la prueba mediante el método Alfa de Cronbach. Se analizaron las contestaciones a cada pregunta mediante la prueba de Ji cuadrado de contingencia, se efectuó la prueba de t y el coeficiente r de Pearson. La fase cualitativa incluyó la observación participativa de la investigadora- profesora, las reflexiones de los estudiantes y la información de las entrevistas semi-estructuradas que se realizaron a tres estudiantes del curso. El análisis se llevó a cabo mediante el Modelo de Wolcott. Se trabajaron diez CA de las cuales siete fueron corregidas mediante el Modelo MODEF. Las actividades más importantes para el proceso de aprendizaje incluyeron el trabajo de investigación o búsqueda de información para hacer una presentación digital, la elaboración de tablas, los mapas de conceptos, el uso de visuales o videos y las analogías para explicar conceptos o procesos. En conclusión: se recomienda el uso del Modelo MODEF para la discusión del tema de

  16. Pros and Cons of Using the Informed Basis Set to Account for Hemodynamic Response Variability with Developmental Data.

    PubMed

    Cignetti, Fabien; Salvia, Emilie; Anton, Jean-Luc; Grosbras, Marie-Hélène; Assaiante, Christine

    2016-01-01

    Conventional analysis of functional magnetic resonance imaging (fMRI) data using the general linear model (GLM) employs a neural model convolved with a canonical hemodynamic response function (HRF) peaking 5 s after stimulation. Incorporation of a further basis function, namely the canonical HRF temporal derivative, accounts for delays in the hemodynamic response to neural activity. A population that may benefit from this flexible approach is children whose hemodynamic response is not yet mature. Here, we examined the effects of using the set based on the canonical HRF plus its temporal derivative on both first- and second-level GLM analyses, through simulations and using developmental data (an fMRI dataset on proprioceptive mapping in children and adults). Simulations of delayed fMRI first-level data emphasized the benefit of carrying forward to the second-level a derivative boost that combines derivative and nonderivative beta estimates. In the experimental data, second-level analysis using a paired t-test showed increased mean amplitude estimate (i.e., increased group contrast mean) in several brain regions related to proprioceptive processing when using the derivative boost compared to using only the nonderivative term. This was true especially in children. However, carrying forward to the second-level the individual derivative boosts had adverse consequences on random-effects analysis that implemented one-sample t-test, yielding increased between-subject variance, thus affecting group-level statistic. Boosted data also presented a lower level of smoothness that had implication for the detection of group average activation. Imposing soft constraints on the derivative boost by limiting the time-to-peak range of the modeled response within a specified range (i.e., 4-6 s) mitigated these issues. These findings support the notion that there are pros and cons to using the informed basis set with developmental data.

  17. Pros and Cons of Using the Informed Basis Set to Account for Hemodynamic Response Variability with Developmental Data

    PubMed Central

    Cignetti, Fabien; Salvia, Emilie; Anton, Jean-Luc; Grosbras, Marie-Hélène; Assaiante, Christine

    2016-01-01

    Conventional analysis of functional magnetic resonance imaging (fMRI) data using the general linear model (GLM) employs a neural model convolved with a canonical hemodynamic response function (HRF) peaking 5 s after stimulation. Incorporation of a further basis function, namely the canonical HRF temporal derivative, accounts for delays in the hemodynamic response to neural activity. A population that may benefit from this flexible approach is children whose hemodynamic response is not yet mature. Here, we examined the effects of using the set based on the canonical HRF plus its temporal derivative on both first- and second-level GLM analyses, through simulations and using developmental data (an fMRI dataset on proprioceptive mapping in children and adults). Simulations of delayed fMRI first-level data emphasized the benefit of carrying forward to the second-level a derivative boost that combines derivative and nonderivative beta estimates. In the experimental data, second-level analysis using a paired t-test showed increased mean amplitude estimate (i.e., increased group contrast mean) in several brain regions related to proprioceptive processing when using the derivative boost compared to using only the nonderivative term. This was true especially in children. However, carrying forward to the second-level the individual derivative boosts had adverse consequences on random-effects analysis that implemented one-sample t-test, yielding increased between-subject variance, thus affecting group-level statistic. Boosted data also presented a lower level of smoothness that had implication for the detection of group average activation. Imposing soft constraints on the derivative boost by limiting the time-to-peak range of the modeled response within a specified range (i.e., 4–6 s) mitigated these issues. These findings support the notion that there are pros and cons to using the informed basis set with developmental data. PMID:27471441

  18. Acquired haemophilia A in a patient with chronic hepatitis C virus infection receiving treatment with pegylated interferon plus ribarivin: role of rituximab.

    PubMed

    Fernández de Palencia Espinosa, M Á; Arocas Casañ, V; Garrido Corro, B; de la Rubia Nieto, A

    2013-01-01

    Antecedentes: la hemofilia adquirida es un trastorno infrecuente causado por el desarrollo de inhibidores del factor de coagulación. Para eliminarlos, se requiere tratamiento con corticoides y fármacos citotóxicos. Métodos: describimos el caso del uso de rituximab en hemofilia adquirida refractaria al tratamiento convencional en un hombre de 63 años con infección crónica por el virus de la hepatitis C y que estaba recibiendo tratamiento con interferón pegilado a-2a y ribarivina. Resultados: tras 21 semanas de tratamiento antivírico, el paciente fue ingresado en el hospital por un gran hematoma en la musculatura abdominal. La concentración de factor VIII era nula y el título de inhibidor fue de 345 unidades Bethesda. Se administró tratamiento inmunosupresor oral con metilprednisolona y ciclofosfamida durante 1 mes, con escasa mejoría. Así pues, se sustituyó la ciclofosfamida por una dosis semanal de rituximab intravenoso. Dos meses después, la concentración de factor VIII se normalizó y el título de inhibidor era indetectable. Conclusión: Rituximab puede ser útil en el tratamiento de la hemofilia adquirida resistente al tratamiento estándar.

  19. Obtención de velocidades radiales de precisión con el espectrógrafo REOSC de CASLEO

    NASA Astrophysics Data System (ADS)

    González, J. F.; Lapasset, E.

    Con el fin de ser empleados como espectros de referencia, han sido obtenidos recientemente 80 espectrogramas de estrellas candidatas a patrones de velocidad radial de todos los tipos espectrales desde B0 a M5, con una dispersión aproximada de 7 Å/mm. Se estudia la influencia de distintos factores (flexión, refracción atmosférica, etc.) en la determinación de velocidades radiales. Se analizan diferentes técnicas de reducción y medición de velocidades, su aplicación a estrellas de diferentes tipos espectrales y velocidades de rotación y se discute la precisión obtenible en cada caso.

  20. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis.

    PubMed

    Li, Jingjing; Chen, Kan; Li, Sainan; Liu, Tong; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis.

  1. Assessing physician and patient acceptance of infliximab biosimilars in rheumatoid arthritis, ankylosing spondyloarthritis and psoriatic arthritis across Germany

    PubMed Central

    Waller, John; Sullivan, Emma; Piercy, James; Black, Christopher M; Kachroo, Sumesh

    2017-01-01

    Objectives We examined rheumatologists’ motivation for prescribing biosimilars, assessed their treatment preferences in relation to prescribing behavior and explored patient attitudes to biosimilars. Methods Data were taken from the Adelphi Real World Biosimilars Programme, a real-world, cross-sectional study undertaken with German rheumatologists and patients with rheumatoid arthritis, ankylosing spondyloarthritis or psoriatic arthritis in 2015–2016. Rheumatologists provided data on their prescribing behavior and attitudes toward biosimilars and invited the next eight eligible consecutive consulting patients to complete a questionnaire. Rheumatologists were split into “investigative”, “conservative” and “other” groups. Results Overall, 50 rheumatologists and 261 patients participated. Biosimilars accounted for <10% of all biologic therapy prescriptions, and >95% of rheumatologists would prescribe a biooriginator rather than biosimilar as the first- or second-line therapy if unrestricted. Patients showed some reluctance to accept biosimilars, and a small proportion of patients were unhappy when switched from a biooriginator to a biosimilar. Satisfaction with treatment was highest in patients who started treatment with a biooriginator prior to biosimilar availability. Patient concerns when starting treatment with a biooriginator or a biosimilar included not knowing enough about the drug (25%–41%), potential side effects (26%–32%) and potential long-term problems (19%–30%). Conclusion Study results demonstrate that there is some reluctance from patients to accept biosimilars and the need to educate patients who are unsure to allow them to be involved in decision making, highlighting the importance of patient and physician communication. There remains a need for further research into nonclinical switching and the long-term impact of prescribing biosimilars. PMID:28331299

  2. TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis

    PubMed Central

    Liu, Jing; Dong, Zheng; Zhu, Qi; He, Dongyi; Ma, Yanyun; Du, Aiping; He, Fan; Zhao, Dongbao; Xu, Xia; Zhang, Hui; jin, Li; Wang, Jiucun

    2016-01-01

    While previous studies have researched in association analyses between TNFα promoter polymorphisms and responses to TNF blockers in spondyloarthritis patients, their results were conflicting. Therefore, we aimed to determine whether TNFα promoter polymorphisms could predict response to TNF blockers and find the source of heterogeneity. Data were extracted and analyzed from published articles and combined with our unpublished data. We found that the greatest potential sources of heterogeneity in the results were gender ratio, disease type, continents, and TNF blockers. Then Stratification analysis showed that the TNFα −308 G allele and the −238 G allele predicted a good response to TNF blockers (OR = 2.64 [1.48–4.73]; 2.52 [1.46–4.37]). However, G alleles of TNFα −308 and −238 could predict the response to etanercept (OR = 4.02 [2.24–7.23]; 5.17 [2.29–11.67]) much more powerfully than the response to infiliximab/adalimumab (OR = 1.68 [1.02–2.78]; 1.28 [0.57–2.86]). TNFα −857 could not predict the response in either subgroup. Cumulative meta-analysis performed in ankylosing spondylitis patients presented the odds ratio decreased with stricter response criteria. In conclusion, TNFα −308 A/G and −238 A/G are more powerful to predict the response to Etanercept and it is dependent on the criteria of response. PMID:27578555

  3. Biosimilar infliximab for inflammatory bowel disease: from concepts to clinical practice. Case study illustrated with CT-P13.

    PubMed

    Schreiber, Stefan; Panés, Julian; Kwon, ByoungOh; Hong, SeungSuh; Peyrin-Biroulet, Laurent

    2015-01-01

    The introduction of biologic drugs represents the most significant advance in the management of immune-mediated inflammatory diseases for a decade. However, complex proteins are expensive to produce and manufacture. Biosimilar versions of established biologics are becoming available as another version of the reference medicinal product and are expected to provide substantial cost savings. However, because of their complexity, the approval of biosimilars requires strict controls to ensure that all therapeutically relevant characteristics are comparable to the reference medicinal product. This review summarizes the scientific principles and data requirements underpinning regulatory approval of biosimilars and the assumptions that enable extrapolation of data between indications. These important concepts are exemplified by CT-P13 (Remsima(®), Inflectra(®)), the first biosimilar monoclonal antibody approved in Europe.

  4. Feasibility of aseptic processing of a low-acid multiphase food product (salsa con queso) using a continuous flow microwave system.

    PubMed

    Kumar, P; Coronel, P; Simunovic, J; Sandeep, K P

    2007-04-01

    Aseptic processing of a low-acid multiphase food product using a continuous flow microwave heating system can combine the advantages of an aseptic process along with those of microwave heating. Dielectric properties of 2 different brands of 1 such product (salsa con queso) were measured under continuous flow conditions at a temperature range of 20 to 130 degrees C. At 915 MHz, the dielectric constant ranged from 58.7 at 20 degrees C to 41.3 at 130 degrees C with dielectric loss factor ranging from 41.0 at 20 degrees C to 145.5 at 130 degrees C. The loss tangent at 915 MHz ranged from 0.61 at 20 degrees C to 3.52 at 130 degrees C. The temperature profiles at the outlet during processing of salsa con queso in a 5-kW microwave unit showed a narrow temperature distribution between the center and the wall of the tube. The study showed the feasibility of aseptic processing of salsa con queso using a continuous flow microwave system.

  5. Distribución espacial de cúmulos y asociaciones estelares con diferentes edades en la Nube Mayor de Magallanes

    NASA Astrophysics Data System (ADS)

    Bica, E.; Clariá, J. J.; Dottori, H.; Santos, J. F. C.; Piatti, A. E.

    Sobre la base de observaciones realizadas en Cerro Tololo y el Casleo, se presenta un catálogo con fotometría UBV integrada de 504 cúmulos y 120 asociaciones estelares en la Nube Mayor de Magallanes. Se determinan edades en términos de los tipos SWB y se identifican 38 cúmulos tipo VII, muchos de los cuales pueden ser cúmulos globulares clásicos. El tamaño de las distribuciones espaciales crece uniformemente con la edad (tipo SWB), en tanto que existe una diferencia en el cociente axial entre los grupos más jóvenes y más viejos que 30 millones de años, lo que implica una orientación aproximadamente de frente para los primeros y una posición inclinada ~ 45o para el segundo grupo. Las asimetrías en las distribuciones espaciales, juntamente con la falta de coincidencia de los centroides de los diferentes grupos de edad, sugiere que el disco de la Nube Mayor de Magallanes fue severamente perturbado en el pasado.

  6. Guided ion beam studies of the reactions of Con+ (n=1-18) with N2: Cobalt cluster mononitride and dinitride bond energies

    NASA Astrophysics Data System (ADS)

    Liu, Fuyi; Li, Ming; Tan, Lin; Armentrout, P. B.

    2008-05-01

    The reactions of Con+ (n=1-18) with N2 are measured as a function of kinetic energy over a range of 0-15eV in a guided ion beam tandem mass spectrometer. A variety of Com+, ComN+, and ComN2+ (m⩽n) product ions are observed, all in endothermic processes, with collision-induced dissociation dominating the products for all clusters. Bond dissociation energies for both cobalt cluster nitrides and dinitrides are derived from threshold analysis of the energy dependence of the endothermic reactions using several different approaches. These values show only a mild dependence on cluster size over the range studied, although the Co13+-N bond energy is relatively weak. The bond energies of Con+-N for larger clusters suggest that a reasonable value for the desorption energy of atomic nitrogen from bulk phase cobalt is 6.3±0.2eV, which is somewhat lower than the only available value in the literature, an estimate based on the enthalpy of formation of bulk cobalt nitride. The trends in the cobalt nitride thermochemistry are also compared to previously determined metal-metal bond energies, D0(Con+-Co), and to D0(Fen+-N). Implications for catalytic ammonia production using cobalt versus iron are discussed.

  7. Conséquences des nouvelles formes de commande sur les matériaux de l'isolation statorique

    NASA Astrophysics Data System (ADS)

    Bellomo, J. P.; Lebey, Th.; Peltier, Fr.; Oraison, J. M.

    1997-05-01

    Use of inverter drive for rotating machines speed control leads to the application of new stress on stator insulation materials. The integrity of these materials under such stresses has therefore to be studied. Thanks to specially equipped motor, the different voltage shapes have been identified. Very short rise time fronts, large overvoltages and high oscillation frequencies are obtained. These voltages are then reproduced on laboratory samples (Polyethylene Terephtalate). The main result is the existence of trapped surface charges related both to the rise front value and to the existence of polar mechanisms in the material bulk. The consequences of this surface charge existence on the reliability of a real system are then discussed. L'utilisation de nouvelles formes de commande pour les machines à courant alternatif se traduit par l'apparition d'un nouveau type de contraintes sur les matériaux de l'isolation statorique. L'étude de leur comportement sous l'action de ce type de contraintes revêt un intérêt tout particulier pour la validation et la stabilité de ces systèmes dans le temps. Nous présentons, tout d'abord, ces différentes formes de tension identifiées à l'aide d'un moteur spécialement instrumenté. L'existence de fronts de tension très élevés, de surtensions importantes (jusqu'à 500V) et d'oscillations hautes fréquences (2MHz), est mise en évidence. La reproduction de ces contraintes en laboratoire sur des échantillons de polyesters (PolyÉthylène Térephthalate) permet alors de déterminer l'influence des formes de tension carrées sur les propriétés intrinsèques du matériau. Elle se traduit par l'existence d'une charge piégée en surface du diélectrique. Cette charge superficielle est associée, d'une part à l'existence de phénomènes de relaxation dans les matériaux étudiés et d'autre part à la valeur des fronts de tension appliqués. Pour finir, les conséquences possibles de l'existence de ces charges superficielles

  8. A methodological approach to comparing pros and cons of delocalizing villages: socio-economic and technical issues

    NASA Astrophysics Data System (ADS)

    Guadagno, Eleonora; Iovine, Giulio G. R.; Petrucci, Olga; Forciniti, Pinuccia R.

    2014-05-01

    Cavallerizzo have been analysed within the frame of a PhD thesis by one of the authors. The present study focuses on the Cavallerizzo case study to discuss a methodological approach useful to comparing pros and cons of delocalizing villages, aiming at properly considering socio-economic effects in addition to technical issues.

  9. Emerging and Legacy Contaminants in The Foodweb in The Lower Columbia River: USGS ConHab Project

    NASA Astrophysics Data System (ADS)

    Nilsen, E. B.; Alvarez, D.; Counihan, T.; Elias, E.; Gelfenbaum, G. R.; Hardiman, J.; Jenkins, J.; Mesa, M.; Morace, J.; Patino, R.; Torres, L.; Waite, I.; Zaugg, S.

    2012-12-01

    An interdisciplinary study, USGS Columbia River Contaminants and Habitat Characterization (ConHab) project, investigates transport pathways, chemical fate, and effects of polybrominated diphenyl ethers (PBDEs) and other endocrine disrupting chemicals (EDCs) in aquatic media and the foodweb in the lower Columbia River, Oregon and Washington. Polar organic chemical integrative samplers (POCIS) and semipermeable membrane devices (SPMDs) were co-deployed at each of 10 sites in 2008 to provide a measure of the dissolved concentrations of select PBDEs, chlorinated pesticides, and other EDCs. PBDE-47 was the most prevalent of the PBDEs detected. Numerous organochlorine pesticides, both banned and current-use, including hexachlorobenzene, pentachloroanisole, dichlorodiphenyltrichloroethane (DDT) and its degradates, chlorpyrifos, endosulfan, and the endosulfan degradation products, were measured at each site. EDCs commonly detected included a series of polycyclic aromatic hydrocarbons (PAHs), fragrances (galaxolide), pesticides (chlorpyrifos and atrazine), plasticizers (phthalates), and flame retardants (phosphates). The downstream sites tended to have the highest concentrations of contaminants in the lower Columbia River. In 2009 and 2010 passive samplers were deployed and resident largescale suckers (Catostomus macrocheilus) and surface bed sediments were collected at three of the original sites representing a gradient of exposure based on 2008 results. Brain, fillet, liver, stomach, and gonad tissues were analyzed. Chemical concentrations were highest in livers, followed by brain, stomach, gonad, and, lastly, fillet. Concentrations of halogenated compounds in tissue samples ranged from <1 to 400 ng g-1 wet tissue. PBDEs, organochlorine pesticides, DDT and its degradates, and polychlorinated biphenyls (PCBs) were detected at all sites in nearly all organs tested. PBDE congeners most frequently detected and at the highest concentrations were PBDE-47 > PBDE-100 > PBDE-154

  10. The pros and cons of ecological risk assessment based on data from different levels of biological organization.

    PubMed

    Rohr, Jason R; Salice, Christopher J; Nisbet, Roger M

    2016-10-01

    Ecological risk assessment (ERA) is the process used to evaluate the safety of manufactured chemicals to the environment. Here we review the pros and cons of ERA across levels of biological organization, including suborganismal (e.g., biomarkers), individual, population, community, ecosystem and landscapes levels. Our review revealed that level of biological organization is often related negatively with ease at assessing cause-effect relationships, ease of high-throughput screening of large numbers of chemicals (it is especially easier for suborganismal endpoints), and uncertainty of the ERA because low levels of biological organization tend to have a large distance between their measurement (what is quantified) and assessment endpoints (what is to be protected). In contrast, level of biological organization is often related positively with sensitivity to important negative and positive feedbacks and context dependencies within biological systems, and ease at capturing recovery from adverse contaminant effects. Some endpoints did not show obvious trends across levels of biological organization, such as the use of vertebrate animals in chemical testing and ease at screening large numbers of species, and other factors lacked sufficient data across levels of biological organization, such as repeatability, variability, cost per study and cost per species of effects assessment, the latter of which might be a more defensible way to compare costs of ERAs than cost per study. To compensate for weaknesses of ERA at any particular level of biological organization, we also review mathematical modeling approaches commonly used to extrapolate effects across levels of organization. Finally, we provide recommendations for next generation ERA, submitting that if there is an ideal level of biological organization to conduct ERA, it will only emerge if ERA is approached simultaneously from the bottom of biological organization up as well as from the top down, all while employing

  11. Relación Entre el Tamaño Condilar y la Asimetría Facial Transversal en Individuos con Hiperplasia Condilar

    PubMed Central

    Olate, Sergio; Cantín, Mario; Alister, Juan Pablo; Uribe, Francisca; Navarro, Pablo; Olate, Gabriela; de Moraes, Márcio

    2016-01-01

    La asimetría facial es una patología de compromiso funcional y estético que puede estar generado por hiperplasia condilar; el objetivo de esta investigación es determinar la influencia del tamaño condilar en la asimetría facial. Doce sujetos fueron estudiados mediante el análisis de tomografía computadorizada cone beam; todos los pacientes presentaron cintigrama óseo que determino la presencia de hiperplasia condilar activa; el análisis se realizo en un software del sistema de captura modelo Pax Zenith, marca Vatech (Korea 2011), utilizando 90 kV y 120 mA; se obtuvo mediciones de la distancia antero-posterior, superior-inferior y medio-lateral de la cabeza del cóndilo, relacionándose con la posición del cóndilo con la línea mediana facial y la posición de puntos faciales entre incisivos centrales superior e inferior así como con el mentón. Los resultados mostraron un promedio de desvío de mentón de 6,5 mm considerando un cóndilo hiperplásico con un tamaño de 2,7 mm mas que los cóndilos normales. El desvío de incisivo central inferior determinó que por cada 1 mm de desvío dentario existe 2,2 mm de desvío de mentón. El cóndilo hiperplásico fue de mayor tamaño y se posiciono casi 2 mm mas hacia lateral que los cóndilos no hiperplásicos. Es posible concluir que el cóndilo hiperplásico presenta clara influencia en la asimetría facial transversa y es posible estimar una relación de tamaño condilar con grado de asimetría facial. PMID:28066127

  12. Flight Deck Surface Trajectory-based Operations (STBO): Results of Piloted Simulations and Implications for Concepts of Operation (ConOps)

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Hooey, Becky L.; Bakowski, Deborah L.

    2013-01-01

    The results offour piloted medium-fidelity simulations investigating flight deck surface trajectory-based operations (STBO) will be reviewed. In these flight deck STBO simulations, commercial transport pilots were given taxi clearances with time and/or speed components and required to taxi to the departing runway or an intermediate traffic intersection. Under a variety of concept of operations (ConOps) and flight deck information conditions, pilots' ability to taxi in compliance with the required time of arrival (RTA) at the designated airport location was measured. ConOps and flight deck information conditions explored included: Availability of taxi clearance speed and elapsed time information; Intermediate RTAs at intermediate time constraint points (e.g., intersection traffic flow points); STBO taxi clearances via ATC voice speed commands or datal ink; and, Availability of flight deck display algorithms to reduce STBO RTA error. Flight Deck Implications. Pilot RTA conformance for STBO clearances, in the form of ATC taxi clearances with associated speed requirements, was found to be relatively poor, unless the pilot is required to follow a precise speed and acceleration/deceleration profile. However, following such a precise speed profile results in inordinate head-down tracking of current ground speed, leading to potentially unsafe operations. Mitigating these results, and providing good taxi RTA performance without the associated safety issues, is a flight deck avionics or electronic flight bag (EFB) solution. Such a solution enables pilots to meet the taxi route RTA without moment-by-moment tracking of ground speed. An avionics or EFB "error-nulling" algorithm allows the pilot to view the STBO information when the pilot determines it is necessary and when workload alloys, thus enabling the pilot to spread his/her attention appropriately and strategically on aircraft separation airport navigation, and the many other flight deck tasks concurrently required

  13. Estudio fotométrico y espectroscópico de dos cúmulos abiertos jóvenes del disco con apariencia globular

    NASA Astrophysics Data System (ADS)

    Piatti, A. E.; Clariá, J. J.; Bica, E.

    Se presentan y discuten resultados obtenidos en el CASLEO y en el Observatorio de Las Campanas de dos cúmulos abiertos compactos con apariencia globular: Westerlund1 (BH197), ubicado en dirección hacia el centro galáctico, y Westerlund2. A partir de espectroscopía CCD integrada de ambos e imágenes CCD en las bandas VI obtenidas para el primero de ellos, se derivan sus parámetros fundamentales y se examinan sus apariencias estructurales. Se encuentra que Westerlund1 es un cúmulo joven (7 ± 3 millones de años), ubicado sobre el plano galáctico a 1.0 ± 0.4 kpc del sol, en una región caracterizada por una absorción excepcionalmente elevada (Av~=13.0 mag), en tanto que Westerlund2 es también un cúmulo joven (4-6 millones de años) ubicado sobre el plano, en una región afectada por una absorción menor (Av~=5.7 mag). Desde el punto de vista estructural, Westerlund 1 se presenta como uno de los pocos cúmulos abiertos jóvenes de la Galaxia con apariencia tipicamente globular, en contraste con los cúmulos azules de las Nubes de Magallanes en los cuales la apariencia globular constituye un fenómeno común. Westerlund2, aunque menos rico en estrellas, puede también ser incluído dentro de esta interesante clase de objetos.

  14. ConBr, A Lectin Purified from the Seeds of Canavalia brasiliensis, Protects Against Ischemia in Organotypic Culture of Rat Hippocampus: Potential Implication of Voltage-Gated Calcium Channels.

    PubMed

    Rieger, D K; Navarro, E; Buendia, I; Parada, E; González-Lafuente, L; Leon, R; Costa, A P; Heinrich, I A; Nascimento, K S; Cavada, B S; Lopez, M G; Egea, J; Leal, R B

    2017-02-01

    Lectins are proteins that bind cellular glycans and can modulate various neuronal functions. We have evaluated the neuroprotective effect of ConBr, a lectin purified from the seeds of Canavalia brasiliensis in a model of rat organotypic hippocampal cultures (OHCs) exposed to oxygen and glucose deprivation (OGD). OGD for 15 min followed by 24 h re-oxygenation significantly increased cell death, caused mitochondrial depolarization and increased reactive oxygen species (ROS) in CA1 region of OHCs. ConBr (0.1 μg/mL) added during the re-oxygenation period counteracted cell death, mitochondrial depolarization and overproduction of ROS induced by OGD. Moreover, ConBr restored the levels of Akt and ERK1 phosphorylation that were reduced by OGD. Modulation of intracellular Ca(2+) by ConBr was evaluated in isolated hippocampal neurons loaded with the fluorescent calcium dye Fluo-4/AM. ConBr (0.1 and 1 µg/mL) reduced by 25-30 % the Ca(2+) increment induced by 70 mM K(+). A sub effective concentration of ConBr (0.01 µg/mL) together with a sub effective concentration of the L-type calcium channel antagonist nifedipine (0.3 µM) conferred a synergic neuroprotective effect in OHCs subjected to OGD. In conclusion, ConBr provides OHCs neuroprotection against OGD. The mechanism was not fully addressed but it may involve modulation of L-type voltage-gated Ca(2+) channels by ConBr.

  15. Engaging Community With Promotores de Salud to Support Infant Nutrition and Breastfeeding Among Latinas Residing in Los Angeles County: Salud con Hyland's.

    PubMed

    Rios-Ellis, Britt; Nguyen-Rodriguez, Selena T; Espinoza, Lilia; Galvez, Gino; Garcia-Vega, Melawhy

    2015-01-01

    The Salud con Hyland's Project: Comienzo Saludable, Familia Sana [Health With Hyland's Project: Healthy Start, Healthy Family],was developed to provide education and support to Latina mothers regarding healthy infant feeding practices and maternal health. The promotora-delivered intervention was comprised of two charlas (educational sessions) and a supplemental, culturally and linguistically relevant infant feeding and care rolling calendar. Results indicate that the intervention increased intention to breastfeed exclusively, as well as to delay infant initiation of solids by 5 to 6 months. Qualitative feedback identified barriers to maternal and child health education as well as highlighted several benefits of the intervention.

  16. [Modello di Management (Mo.Ma) del paziente affetto da schizofrenia: controllo della crisi, mantenimento, prevenzione delle ricadute e recovery con gli antipsicotici LAI].

    PubMed

    Brugnoli, Roberto; Rapinesi, Chiara; Kotzalidis, Georgios D; Marcellusi, Andrea; Mennini, Francesco S; De Filippis, Sergio; Carrus, Dario; Ballerini, Andrea; Francomano, Antonio; Ducci, Giuseppe; Del Casale, Antonio; Girardi, Paolo

    2016-01-01

    RIASSUNTO. La schizofrenia colpisce circa l'1% della popolazione e rappresenta un grave disturbo mentale con un notevole impatto anche sul funzionamento sociale, lavorativo e sulle attività della vita quotidiana. Le persone con schizofrenia hanno un tasso di mortalità superiore di 2-2,5 rispetto a quello della popolazione generale. La non aderenza ai farmaci antipsicotici è uno dei più importanti fattori di rischio per le ricadute e le ospedalizzazioni, sia nei pazienti con disturbo cronico sia al primo episodio, e conseguentemente contribuisce all'aumento dei costi sanitari. Gli antipsicotici atipici LAI possono migliorare l'aderenza al trattamento contribuendo a diminuire i tassi di ricaduta nei pazienti affetti da schizofrenia fin dall'esordio. Gli obiettivi primari nella gestione dei pazienti schizofrenici sono diretti, non solo alla riduzione dei sintomi nel breve termine, ma anche al mantenimento fisico e della funzionalità mentale, migliorando la qualità della vita e promuovendo il recupero del paziente. Scopo. Proporre un modello integrato, basato sulle evidenze, che fornisca un algoritmo efficace per il recupero del paziente schizofrenico e indagare l'efficacia e la sicurezza degli antipsicotici LAI nel trattamento, nel mantenimento, nella prevenzione delle ricadute e nella recovery dei pazienti affetti da schizofrenia. Metodi. Dopo un'accurata analisi di letteratura abbiamo identificato, raccolto e analizzato gli elementi qualificanti per un'ottimale gestione del paziente schizofrenico, definendo un modello di gestione e selezione delle alternative terapeutiche. Conclusioni. Il modello di gestione della schizofrenia proposto potrebbe consentire un migliore recupero funzionale del paziente grazie alla scelta di iniziare il percorso terapeutico, fin dalle prime fasi del disturbo soprattutto se in giovane età e al primo episodio, con un farmaco atipico LAI. All'interno dei farmaci antipsicotici atipici la formulazione LAI rappresenta una scelta

  17. FACTORES SOCIO-ESTRUCTURALES Y EL ESTIGMA HACIA EL VIH/SIDA: EXPERIENCIAS DE PUERTORRIQUEÑOS/AS CON VIH/SIDA AL ACCEDER SERVICIOS DE SALUD

    PubMed Central

    RIVERA-DIAZ, MARINILDA; VARAS-DIAZ, NELSON; REYES-ESTRADA, MARCOS; SURO, BEATRIZ; CORIANO, DORALIS

    2013-01-01

    RESUMEN El estigma relacionado al VIH/SIDA continúa afectando la prestación de servicios de salud y el bienestar físico y mental de las personas con VIH/SIDA (PVS). Recientemente la literatura científica ha señalado la importancia de comprender las manifestaciones de estigma más allá de las interacciones individuales. Por tal razón, investigaciones recientes en y fuera de Puerto Rico enfatizan la importancia de entender cómo factores socio-estructurales (FSE) influyen en los procesos de estigmatización social. Con el propósito de examinar los FSE que influyen en las manifestaciones de estigma relacionado al VIH/SIDA, realizamos y analizamos nueve grupos focales compuestos por hombres y mujeres en tratamiento para el VIH/SIDA que habían tenido experiencias estigmatizantes. Los participantes identificaron FSE relacionados a las manifestaciones de estigma, tales como el uso de viviendas especializadas, descentralización de los servicios de salud y el desarrollo de protocolos administrativos excluyentes en los servicios de salud. Los resultados demuestran la importancia de considerar los FSE en el desarrollo e implementación de intervenciones dirigidas a la población. PMID:24639599

  18. Potential pros and cons of external healthcare performance evaluation systems: real-life perspectives on Iranian hospital evaluation and accreditation program

    PubMed Central

    Jaafaripooyan, Ebrahim

    2014-01-01

    Background: Performance evaluation is essential to quality improvement in healthcare. The current study has identified the potential pros and cons of external healthcare evaluation programs, utilizing them subsequently to look into the merits of a similar case in a developing country. Methods: A mixed method study employing both qualitative and quantitative data collection and analysis techniques was adopted to achieve the study end. Subject Matter Experts (SMEs) and professionals were approached for two-stage process of data collection. Results: Potential advantages included greater attractiveness of high accreditation rank healthcare organizations to their customers/purchasers and boosted morale of their personnel. Downsides, as such, comprised the programs’ over-reliance on value judgment of surveyors, routinization and incurring undue cost on the organizations. In addition, the improved, standardized care processes as well as the judgmental nature of program survey were associated, as pros and cons, to the program investigated by the professionals. Conclusion: Besides rendering a tentative assessment of Iranian hospital evaluation program, the study provides those running external performance evaluations with a lens to scrutinize the virtues of their own evaluation systems through identifying the potential advantages and drawbacks of such programs. Moreover, the approach followed could be utilized for performance assessment of similar evaluation programs. PMID:25279381

  19. Pretreatment with Fucoidan from Fucus vesiculosus Protected against ConA-Induced Acute Liver Injury by Inhibiting Both Intrinsic and Extrinsic Apoptosis

    PubMed Central

    Li, Jingjing; Chen, Kan; Li, Sainan; Liu, Tong; Wang, Fan; Xia, Yujing; Lu, Jie; Zhou, Yingqun; Guo, Chuanyong

    2016-01-01

    This study aimed to explore the effects of fucoidan from Fucus vesiculosus on concanavalin A (ConA)-induced acute liver injury in mice. Pretreatment with fucoidan protected liver function indicated by ALT, AST and histopathological changes by suppressing inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). In addition, intrinsic and extrinsic apoptosis mediated by Bax, Bid, Bcl-2, Bcl-xL and Caspase 3, 8, and 9 were inhibited by fucoidan and the action was associated with the TRADD/TRAF2 and JAK2/STAT1 signal pathways. Our results demonstrated that fucoidan from Fucus vesiculosus alleviated ConA-induced acute liver injury via the inhibition of intrinsic and extrinsic apoptosis mediated by the TRADD/TRAF2 and JAK2/STAT1 pathways which were activated by TNF-α and IFN-γ. These findings could provide a potential powerful therapy for T cell-related hepatitis. PMID:27035150

  20. On the role of localized surface plasmon resonance in UV-Vis light irradiated Au/TiO₂ photocatalysis systems: pros and cons.

    PubMed

    Lin, Zhongjin; Wang, Xiaohong; Liu, Jun; Tian, Zunyi; Dai, Loucheng; He, Beibei; Han, Chao; Wu, Yigui; Zeng, Zhigang; Hu, Zhiyu

    2015-03-07

    The role of localized surface plasmon resonance (LSPR) in UV-Vis light irradiated Au/TiO2 photocatalysis systems has been investigated, and it is demonstrated experimentally for the first time that both pros and cons of LSPR exist simultaneously for this photocatalytic reaction. We have proved that when operating under mixed UV and green light irradiation, the LSPR injected hot electrons (from the Au nanoparticles to TiO2 under green light irradiation) may surmount the Schottky barrier (SB) formed between the Au nanoparticles and TiO2, and flow back into the TiO2. As a result, these electrons may compensate for and even surpass those transferred from TiO2 to the Au nanoparticles, thus accelerating the recombination of UV excited electron-hole pairs in TiO2. This is the negative effect of LSPR. On the other hand, more hot electrons existing on the surface of the Au nanoparticles due to LSPR would favor the photocatalytic reaction, which accompanied by the negative effect dominates the overall photocatalytic performance. The presented results reveal the multi-faceted essence of LSPR in Au/TiO2 structures, and is instructive for the application of metal-semiconductor composites in photocatalysis. Moreover, it is confirmed that the extent to which the above pros and cons of LSPR dominate the overall photocatalytic reaction depends on the intensity ratio of visible to UV light.

  1. The International Consortium on Lithium Genetics (ConLiGen): An Initiative by the NIMH and IGSLI to Study the Genetic Basis of Response to Lithium Treatment

    PubMed Central

    Schulze, Thomas G.; Alda, Martin; Adli, Mazda; Akula, Nirmala; Ardau, Raffaella; Bui, Elise T.; Chillotti, Caterina; Cichon, Sven; Czerski, Piotr; Del Zompo, Maria; Detera-Wadleigh, Sevilla D.; Grof, Paul; Gruber, Oliver; Hashimoto, Ryota; Hauser, Joanna; Hoban, Rebecca; Iwata, Nakao; Kassem, Layla; Kato, Tadafumi; Kittel-Schneider, Sarah; Kliwicki, Sebastian; Kelsoe, John R.; Kusumi, Ichiro; Laje, Gonzalo; Leckband, Susan G.; Manchia, Mirko; MacQueen, Glenda; Masui, Takuya; Ozaki, Norio; Perlis, Roy H.; Pfennig, Andrea; Piccardi, Paola; Richardson, Sara; Rouleau, Guy; Reif, Andreas; Rybakowski, Janusz K.; Sasse, Johanna; Schumacher, Johannes; Severino, Giovanni; Smoller, Jordan W.; Squassina, Alessio; Turecki, Gustavo; Young, L. Trevor; Yoshikawa, Takeo; Bauer, Michael; McMahon, Francis J.

    2010-01-01

    For more than half a decade, lithium has been successfully used to treat bipolar disorder. Worldwide, it is considered the first-line mood stabilizer. Apart from its proven antimanic and prophylactic effects, considerable evidence also suggests an antisuicidal effect in affective disorders. Lithium is also effectively used to augment antidepressant drugs in the treatment of refractory major depressive episodes and prevent relapses in recurrent unipolar depression. In contrast to many psychiatric drugs, lithium has outlasted various pharmacotherapeutic ‘fashions’, and remains an indispensable element in contemporary psychopharmacology. Nevertheless, data from pharmacogenetic studies of lithium are comparatively sparse, and these studies are generally characterized by small sample sizes and varying definitions of response. Here, we present an international effort to elucidate the genetic underpinnings of lithium response in bipolar disorder. Following an initiative by the International Group for the Study of Lithium-Treated Patients (www.IGSLI.org) and the Unit on the Genetic Basis of Mood and Anxiety Disorders at the National Institute of Mental Health, lithium researchers from around the world have formed the Consortium on Lithium Genetics (www.ConLiGen.org) to establish the largest sample to date for genome-wide studies of lithium response in bipolar disorder, currently comprising more than 1,200 patients characterized for response to lithium treatment. A stringent phenotype definition of response is one of the hallmarks of this collaboration. ConLiGen invites all lithium researchers to join its efforts. PMID:20453537

  2. Medición de placas astrométricas obtenidas con el telescopio Astrográfico de La Plata

    NASA Astrophysics Data System (ADS)

    di Sisto, R. P.; Orellana, R.

    El Observatorio de La Plata cuenta con un gran número de placas de asteroides y cometas obtenidas con el telescopio astrográfico, que cubren gran parte del cielo del hemisferio sur. En 1996 se recopilaron y clasificaron 2187 placas (Beca para estudiantes de la AAA 1996) de las cuales 2031 corresponden a asteroides. Los datos de cada placa se volcaron en una base de datos creada para facilitar su manejo y preservar la información. A partir de este trabajo se revisaron los MPC electrónicos y se identificaron aquellas placas de asteroides pertenecientes a nuestra base de datos cuyos resultados no fueron publicados en los mismos. De un total de 400 placas que no aparecían publicadas sobresalía un paquete constituído por 40 placas obtenidas en 1977. Estas últimas fueron reducidas utilizando las posiciones y movimientos propios de las estrellas de referencia obtenidas del catálogo SAO 2000 dadas para el sistema FK5. Las posiciones calculadas fueron enviadas y publicadas en los Minor Planet Circulars (MPC).

  3. Con A-binding protein Zn-α2-glycoprotein on human sperm membrane is related to acrosome reaction and sperm fertility.

    PubMed

    Liu, Y; Qu, F; Cao, X; Chen, G; Guo, Q; Ying, X; Guo, W; Lu, L; Ding, Z

    2012-04-01

    Fertilization, the recognition and fusion between spermatozoa and oocyte, involves various molecules on the spermatozoa and oocyte membranes. Concanavalin A (ConA)-binding proteins may be one of the molecules involved in mammal spermatozoa fertilization; however, their structure and function remain largely unknown. Here, we initially identified a ConA-binding protein, Zn-α2-glycoprotein (ZAG), involved in regulating the acrosome reaction (AR) of human spermatozoa. ZAG is localized on the pre-equatorial region covering the acrosome, neck and tail (some parts of middle piece and principal piece respectively) regions of the acrosome intact human spermatozoa, and disappears in the acrosomal region of the acrosome-reacted spermatozoa. Polyclonal antibodies against human recombinant ZAG significantly reduced the AR and sperm capability binding to human zona pellucida or penetration into zona-free hamster oocytes. Furthermore, assessment of the signaling pathways regulated by ZAG revealed that ZAG affects sperm AR through both the cAMP/PKA and PKC pathways. These results indicate that ZAG, which is present on the human sperm membrane, plays a critical role in the AR and subsequently, may be involved in sperm fertility.

  4. Food for thought: a pilot study of the pros and cons of changing eating patterns within cognitive-behavioural therapy for the eating disorders.

    PubMed

    Waller, Glenn; Evans, Jane; Pugh, Matthew

    2013-09-01

    Evidence-based cognitive-behavioural therapy (CBT) for the eating disorders has an early focus on behavioural changes around food intake. However, patients' anxiety around such change might account for why they often seem unmotivated in treatment. In order to determine the impact of changing intake, this pilot study of patients with bulimic disorders (N = 19) or anorexia nervosa (N = 9) used a mixed quantitative and qualitative design to retrospectively examine their perspectives of the short- and long-term pros and cons of such change. As expected, change was seen negatively in the short-term (with particularly high numbers reporting anxiety), but there were few reports of long-term negative outcomes. In contrast, there were both short- and long-term benefits of changing eating. The patients described what was helpful in making changes and what they had learned as a result. In both cases, their descriptions mapped closely onto the content and process of evidence-based CBT for the eating disorders. Although there is a need for more extensive research, these findings suggest that patients (and therapists) might benefit from being aware of the contrast between the short- and the long-term pros and cons of changing eating within CBT for the eating disorders.

  5. Fuentes de variabilidad en el diagnóstico de gastritis atrófica multifocal asociada con la infección por Helicobacter pylori1

    PubMed Central

    Bravo, Luis Eduardo; Bravo, Juan Carlos; Realpe, José Luis; Zarama, Guillermo; Piazuelo, MarÍa Blanca; Correa, Pelayo

    2014-01-01

    RESUMEN Introducción El mapeo de las diferentes regiones del estómago y el número de fragmentos de mucosa gástrica disponibles para evaluación histopatológica son fuentes importantes de variación en el momento de clasificar y hacer la gradación de la gastritis crónica. Objetivos Estimar la sensibilidad del número de fragmentos de mucosa gástrica necesarios para establecer los diagnósticos de gastritis atrófica con metaplasia intestinal (MI), displasia y estado de infección por Helicobacter pylori. Además evaluar la variabilidad intra-observador en la clasificación de estas lesiones precursoras del cáncer gástrico. Materiales y métodos En una cohorte de 6 años de seguimiento se evaluaron 1,958 procedimientos de endoscopia realizados por dos gastroenterólogos. En cada procedimiento y de cada participante se obtuvieron 5 biopsias de mucosa gástrica que representaban antro, incisura angularis y cuerpo. Un único patólogo hizo la interpretación histológica de las 5 biopsias y proporcionó un diagnóstico definitivo global que se utilizó como patrón de referencia. Cada fragmento de mucosa gástrica examinado condujo a un diagnóstico individual para cada biopsia que se comparó con el patrón de referencia. La variabilidad intra-observador se evaluó en 127 personas que corresponden a una muestra aleatoria de 20% del total de endoscopias hechas a los 72 meses de seguimiento. Resultados La sensibilidad del diagnóstico de MI y displasia gástrica aumentó de manera significativa con el número de fragmentos de mucosa gástrica evaluados El sitio anatómico de mayor sensibilidad para el diagnóstico de MI y displasia fue la incisura angularis. Para descubrir H. pylori se logró alta sensibilidad con el estudio de un solo fragmento de mucosa gástrica (95.9%) y fue independiente del sitio de obtención de la biopsia. El acuerdo intra-observador para el diagnóstico de gastritis crónica fue 86.1% con valor kappa de 0.79 IC 95% (0.76-0.85). Las

  6. Errores sistemáticos del Catálogo Fundamental FK5, deducidos de las observaciones con Astrolabio Fotoeléctrico PAII, en el Hemisferio Sur

    NASA Astrophysics Data System (ADS)

    Manrique, W. T.; Podestá, R. C.; Alonso, E.; Actis, E. V.; Pacheco, A. M.; Bustos, G.; Lizhi, L.; Zezhi, W.; Fanmiao, Z.; Hongqi, W.; Perdomo, R.; González, A.; Gómez, G.

    Se dan los resultados obtenidos de los Errores Sistemáticos del Catálogo Fundamental FK5, Δ α δ, Δ α α, Δ δ α y Δ δ δ, derivados de las observaciones estelares con el Astrolabio Fotoeléctrico PAII del Observatorio de Beijing instalado en el Observatorio Astronómico ``Félix Aguilar'' de San Juan, de acuerdo al Proyecto de Colaboración entre los observatorios de San Juan, Beijing y La Plata. Se han usado los residuos seleccionados de 11000 estrellas aproximadamente, derivados de más de 400000 pasajes estelares en 1550 días, desde Febrero de 1992 a Marzo de 1997. La precisión media de los residuos es de 0,"043.

  7. Dinámica y frecuencias características de una protuberancia solar observada con los instrumentos SUMER y CDS/SOHO

    NASA Astrophysics Data System (ADS)

    Rovira, M.; Costa, A.; Bocchialini, K.

    La estructura de la protuberancia estudiada puede dividirse en cuatro regiones. A partir del análisis de las imágenes del CDS y los espectros del SUMER utilizando técnicas de multiresolución con Wavelets se obtuvieron las frecuencias y velocidades relativas de cada una de las regiones. Se observan frecuencias características del orden de los 5 min y otras de largo período. Se obtuvo una fuerte anticorrelación entre las intensidades y las velocidades Doppler. La presencia de las oscilaciones de 5 min en todas las regiones sugieren el acoplamiento entre la estructura cromosférica y la protuberancia.

  8. Experience in managing a large-scale rescreening of Papanicolaou smears and the pros and cons of measuring proficiency with visual and written examinations.

    PubMed

    Rube, I F

    1989-01-01

    Experiences in a large-scale interlaboratory rescreening of Papanicolaou smears are detailed, and the pros and cons of measuring proficiency in cytology are discussed. Despite the additional work of the rescreening project and some psychological and technical problems, it proved to be a useful measure of the laboratory's performance as a whole. One problem to be avoided in future similar studies is the creation of too many diagnostic categories. Individual testing and certification have been shown to be accurate predictors of proficiency. For cytology, such tests require a strong visual component to test interpretation and judgment skills, such as by the use of glass slides or photomicrographs. The potential of interactive videodisc technology for facilitating cytopathologic teaching and assessment is discussed.

  9. Broadening, shifting, and line asymmetries in the 2<--0 band of CO and CO-N2: Experimental results and theoretical calculations

    NASA Astrophysics Data System (ADS)

    Predoi-Cross, Adriana; Bouanich, J. P.; Benner, D. Chris; May, A. D.; Drummond, J. R.

    2000-07-01

    We have measured the room temperature, widths, pressure shifts, and line asymmetry coefficients for many transitions of the first overtone band of CO and CO perturbed by N2. The broadening coefficients were obtained with an accuracy of about 1%. The pure CO profiles have been fitted by a Voigt profile while the CO-N2 spectral profiles have been fitted with a Lorentz and an empirical line shape model (HCv) that blends together a hard collision model and a speed-dependent Lorentz profile. In addition to the Voigt, Lorentz, and HCv models, we have added a dispersion profile to account for weak line mixing. The line broadening and shift coefficients are compared to semiclassical calculations employing a variety of intermolecular interactions. The line asymmetry results are compared to line mixing calculations based on the energy corrected sudden (ECS) model. The results indicate that effects other than line mixing also contribute to the measured line asymmetry.

  10. Pros and Cons of Physical/Empirical SAR Altimetry Retracking in Seasonally Ice-Covered Waters in Preparation for Sentinel-3

    NASA Astrophysics Data System (ADS)

    Jain, Maulik; Andersen, Ole Baltazar; Stenseng, Lars

    2015-12-01

    An investigation is performed into the retrieval of sea surface heights in the Arctic Ocean to evaluate the determination of seasonal sea level in the Arctic Ocean from satellite altimetry. Physical retrackers assume a uniform probability density function for the wave height within the footprint which is frequently compromised in the Arctic Ocean due to the presence of seasonal sea ice and the period of initial freezing of the ocean. Preliminary investigations highlight the pros of the empirical retrackers for seasonal sea ice covered regions as it does not assume anything about physical properties and the pros of a physical retracker for either permanent near fully ice covered or open ocean. Comparison with tide gauge data is performed in this study to highlight the pros and cons of physical and empirical retracking in the Arctic Ocean.

  11. Conversation with Lara about the Earth and Land. (Spanish Title: Conversando con Lara sobre la Tierra y la Teirra.) Conversando com Lara sobre a Terra e a Terra

    NASA Astrophysics Data System (ADS)

    da Conceição Barbosa-Lima, Maria

    2010-12-01

    The present article is the analysis of a conversation between the author and Lara, a four-yearold- girl, enrolled in nursery school, while she makes a drawing of the Earth. It took place outside school environment and without any other person around to avoid interference during the interview. According to Ferreira & Silva (2004), a researcher can only comprehend a child's drawing, or form, by listening to him/her while he/she is creating it. Lara presented the traditional flat drawing, picturing the sky parallel to the ground, as reported by Nardi & Carvalho (1996). However, when asked to draw the World - term used by Butterworth et al. (2002), in order to avoid unnecessary confusion - she represented it by a circle, with herself on the surface. Her drawings led to the conclusion that such girl does not know yet the World in which she lives is the Earth, and probably because of that, within her age and consequent maturity, she accurately differentiates the concepts of land and Earth. El presente artículo analiza una entrevista libre, mientras una niña de 4 años y 4 meses, matriculada en el pregrado, dibuja la Tierra. Esta entrevista se realizó fuera del ambiente escolar y sin otra persona alrededor que pudiera interferir. De acuerdo con Ferreira Silva (2004), para quien investiga es posible conocer realmente lo que un niño o una niña pone en el papel a través de grafismos y/o dibujos si se lo escucha durante el proceso de creación de la escritura con imágenes. La niña, en este caso, representa la Tierra con el tradicional dibujo plano y el "cielo" paralelo al suelo, conforme analizaron Nardi & Carvalho (1996). Pero, cuando se Le solicita dibujar el "Mundo" - palabra empleada en un trabajo de Butterworth et al. (2002), con intención de no provocar "confusiones" innecesarias a sus sujetos de investigación- lo representa de forma circular, poniéndose sobre su superficie. Sus dibujos llevan a concluir que esta niña aún no tiene conocimiento que el mundo

  12. Linking innovative measurement technologies (ConMon and Dataflow© systems) for high-resolution temporal and spatial dissolved oxygen criteria assessment.

    PubMed

    O'Leary, C A; Perry, E; Bayard, A; Wainger, L; Boynton, W R

    2015-10-01

    One consequence of nutrient-induced eutrophication in shallow estuarine waters is the occurrence of hypoxia and anoxia that has serious impacts on biota, habitats, and biogeochemical cycles of important elements. Because of the important role of dissolved oxygen (DO) on these ecosystem features, a variety of DO criteria have been established as indicators of system condition. However, DO dynamics are complex and vary on time scales ranging from diel to decadal and spatial scales from meters to multiple kilometers. Because of these complexities, determining DO criteria attainment or failure remains difficult. We propose a method for linking two common measurement technologies for shallow water DO criteria assessment using a Chesapeake Bay tributary as a test case. Dataflow© is a spatially intensive (30-60-m collection intervals) system used to map surface water conditions at the whole estuary scale, and ConMon is a high-frequency (15-min collection intervals) fixed station approach. The former technology is effective with spatial descriptions but poor regarding temporal resolution, while the latter provides excellent temporal but very limited spatial resolution. Our methodology for combining the strengths of these measurement technologies involved a sequence of steps. First, a statistical model of surface water DO dynamics, based on temporally intense ConMon data, was developed. The results of this model were used to calculate daily DO minimum concentrations. Second, this model was then inserted into Dataflow©-generated spatial maps of DO conditions and used to adjust measured DO concentrations to daily minimum concentrations. This information was used to assess DO criteria compliance at the full tributary scale. Model results indicated that it is vital to consider the short-term time scale DO criteria across both space and time concurrently. Large fluctuations in DO occurred within a 24-h time period, and DO dynamics varied across the length and width of the

  13. Detailed magnetic studies on Co(N3)2(4-acetylpyridine)2: a weak-ferromagnet with a very big canting angle.

    PubMed

    Wang, Xin-Yi; Wang, Zhe-Ming; Gao, Song

    2008-07-07

    The magnetic properties of Co(N 3) 2(4acpy) 2 have been thoroughly reexamined on both powder and well-oriented single crystal samples. This azido-bridged cobalt compound of (4, 4) layer shows a weak-ferromagnetic state below T C = 11.2 K. The magnetic axes were determined to be along the crystallographic a*, b, and c axes for the monoclinic space group P2 1/c. The easy axis lies along the b-axis, the canting is along the a*-axis, and the hard axis is along the c-axis. Strong anisotropy due to the oriented moments in the ordered state and/or the single-ion anisotropy of Co (2+) exists in the whole temperature range from 2 to 300 K. Below T C, very big spontaneous magnetization was observed and was attributed to the very big canting angle (15 degrees at 2 K). A possible spin configuration was then proposed to explain the experimental results. The origin of the big spin canting was discussed, and a weak-ferromagnetic approach toward molecular magnets with big spontaneous magnetization was proposed accordingly.

  14. A novel mammalian myosin I from rat with an SH3 domain localizes to Con A-inducible, F-actin-rich structures at cell-cell contacts

    PubMed Central

    1995-01-01

    In an effort to determine diversity and function of mammalian myosin I molecules, we report here the cloning and characterization of myr 3 (third unconventional myosin from rat), a novel mammalian myosin I from rat tissues that is related to myosin I molecules from protozoa. Like the protozoan myosin I molecules, myr 3 consists of a myosin head domain, a single light chain binding motif, and a tail region that includes a COOH-terminal SH3 domain. However, myr 3 lacks the regulatory phosphorylation site present in the head domain of protozoan myosin I molecules. Evidence was obtained that the COOH terminus of the tail domain is involved in regulating F-actin binding activity of the NH2-terminal head domain. The light chain of myr 3 was identified as the Ca(2+)-binding protein calmodulin. Northern blot and immunoblot analyses revealed that myr 3 is expressed in many tissues and cell lines. Immunofluorescence studies with anti-myr 3 antibodies in NRK cells demonstrated that myr 3 is localized in the cytoplasm and in elongated structures at regions of cell-cell contact. These elongated structures contained F-actin and alpha-actinin but were devoid of vinculin. Incubation of NRK cells with Con A stimulated the formation of myr 3-containing structures along cell-cell contacts. These results suggest for myr 3 a function mediated by cell-cell contact. PMID:7730414

  15. Surface and volume non-invasive methods for the structural monitoring of the bass-relief 'Madonna con Bambino' (Gorizia, Northern Italy).

    PubMed

    Alberghina, Maria Francesca; Macchia, Andrea; Capizzi, Patrizia; Schiavone, Salvatore; Ruffolo, Silvestro Antonio; Comite, Valeria; Barberio, Marianna; La Russa, Mauro Francesco

    2016-11-23

    Structural analysis of marble statues, carried out by non-invasive and in situ methods, is crucial to define the state of conservation of the artworks and to identify the deterioration phenomena that can affect them. In this work, we combined in situ non-destructive techniques, ultrasonic tomography (US), ultraviolet-induced visible fluorescence (UV-IF) and X-ray fluorescence (XRF) to study the bass-relief 'Madonna con Bambino' (Gorizia, Italy). The US revealed the presence of some metallic pivots, associated with areas of high sound velocity; moreover, a more degraded area has been identified in the lower part of the bass-relief. The acquired UV-IF image confirmed the presence of surface degradation, allowing a preliminary evaluation of the extension of a fracture, from surface to bulk. In addition, the different materials (both original and/or integrations) that compose the studied surface have been identified. The XRF has contributed to define the nature of the inorganic materials applied during undocumented previous restoration works on the surface as filler for lacunae.

  16. Obtención de perfiles teóricos de elementos metálicos con velocidades macroscópicas

    NASA Astrophysics Data System (ADS)

    Cirigliano, D.; Costa, A.; Rovira, M.

    El propósito de este trabajo es poder establecer -a partir de la modelización de perfiles de distintas especies- patrones de comparación observacional que permitan caracterizar los fenómenos físicos que están presentes en las estructuras que se observan. Para ello se resuelven las ecuaciones de equilibrio de ionización para un determinado átomo y una atmósfera de parámetros determinados. A partir de ello se definen las poblaciones para los distintos grados de ionización. Considerando distintas configuraciones e intensidades de flujos de masa se deducen la función fuente, el espesor óptico y se calculan los perfiles de las distintas líneas. Se obtuvieron perfiles teóricos de líneas del CII, CIV y del OIV para flujos entrante, saliente y pasante. La forma del perfil, las intensidades relativas entre los distintos flujos y el corrimiento Doppler da cuenta de una caracterización teórica a partir de la cual se comparará con observaciones.

  17. Distribución espacial de órbitas con diferentes grados de caoticidad en modelos autoconsistentes de satélites galácticos

    NASA Astrophysics Data System (ADS)

    Muzzio, J. C.; Mosquera, M.

    En trabajos anteriores (Carpintero et al., Cel. Mech. Dynam. Astron. 85, 247, 2003), mostramos que las órbitas caóticas son muy importantes en los satélites galácticos. Sin embargo, los únicos modelos autoconsistentes de los que se disponía para ellos eran los de Heggie-Ramamani, cuya función de distribución depende sólo de la energía por lo que no mostraban diferencias entre las distribuciones de sus órbitas regulares y caóticas. Ahora, mediante una aproximación cuadrupolar, hemos logrado construir modelos autoconsistentes de satélites galácticos con distribuciones de velocidades anisotrópicas (lo que indica que sus funciones de distribución no dependen sólo de la energía) y hemos logrado revelar las diferencias entre las estructuras espaciales de las órbitas de distinta caoticidad.

  18. Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

    PubMed

    Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

    2002-06-01

    The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

  19. Separation and quantitation of hepatoma-associated gamma-glutamyltransferase by affinity chromatography with Affi-Gel blue and Con A-Sepharose.

    PubMed

    Izumi, M; Taketa, K

    1983-01-01

    Isozymes of serum gamma-glutamyltransferase (GGT) in patients with hepatocellular carcinoma (HCC) and other liver diseases were separated into two groups by double-affinity column chromatography with Affi-Gel blue and Con A-Sepharose, one recovered in the unbound fraction and the other in the bound fraction. Upon electrophoresis with polyacrylamide gradient gel slabs, the unbound fraction gave a GGTI1 band and a faint II1 band and the bound fraction gave a GGT I band and faint bands of GGT I", II' and X, when the original serum contained hepatoma-associated GGT (I1, I" and II') and high-molecular-weight lipid-protein complex, GGT(X). GGT I was present in all cases as a common isozyme. Other lipoprotein-associated GGT isozymes, III-IX, were removed by passing through Affi-Gel blue. GGT activities of unbound fraction in patients with HCC were generally higher than those in patients with non-HCC liver diseases, although the difference was not significant. When the percent of GGT activity of unbound (unbound + bound) was taken, 54% of patients with HCC had a ratio greater than 22%, whereas none of the healthy subjects or patients with other liver diseases gave values greater than this. The present technique may prove to be a useful clinical test for the diagnosis of HCC.

  20. [Reversible neuropsychological deterioration associated to zonisamide in a paediatric patient with tuberous sclerosis].

    PubMed

    Fournier-Del Castillo, M Concepción; Melero-Llorente, Javier; Blanco-Beregana, Miriam; Robles-Bermejo, Fernando; Budke, Marcelo; Garcia-Fernandez, Marta; Garcia-Penas, Juan José; Perez-Jimenez, M Ángeles

    2015-01-16

    Objetivo. Documentar el deterioro cognitivo reversible asociado a altas dosis de zonisamida, utilizando indices de cambio fiable para controlar los efectos de practica derivados de evaluaciones neuropsicologicas repetidas. Caso clinico. Niño de 11 años con complejo esclerosis tuberosa y epilepsia refractaria del lobulo frontal izquierdo, evaluado en el contexto de un programa de cirugia de la epilepsia pediatrica. La zona epileptogena se relaciono con un tuber epileptogeno localizado en el giro frontal inferior del hemisferio izquierdo. Los efectos de altas dosis de zonisamida mimetizaron una afectacion de la corteza elocuente en la zona epileptogena y un impacto de las crisis no controladas en el funcionamiento cognitivo asociado al hemisferio dominante para el lenguaje. La retirada del farmaco mejoro significativamente, mas alla de los efectos de practica, el cociente intelectual total, el indice intelectual de comprension verbal y habilidades cognitivas especificas sustentadas en el lenguaje. Conclusiones. La diferenciacion entre los efectos cognitivos de los farmacos y la existencia de un deficit funcional por afectacion de la corteza elocuente en el area epileptogena puede ser crucial para la toma de decisiones en cirugia de la epilepsia.

  1. FloCon 2006 Proceedings

    DTIC Science & Technology

    2006-10-01

    SNORT: KICKASS_PORN DRAGON: PORN HARDCORE SOURCEDEST SOURCE SOURCE SOURCE DEST DEST DEST DEST Stepping stone 51.251.22.183 Username password Sept...While packet counts do only show a minor increase in distance before and af- ter the Blaster outbreak, the other three metrics indicate a more drastic...consists of approximately 40 user assigned hosts, although the actual number of hosts is subject to minor fluctuations over time. Approximately an

  2. FloCon 2011 Proceedings

    DTIC Science & Technology

    2011-01-01

    0. 08 0. 10 Nonzero Mobility Score P ro ba bi lit y 1e−09 1e−07 1e−05 0.001 0.1 10 1000 1e+05 Graph |I | |H| %a` RN RE G 667033 172283 1.00 3.87 4.56...COT 10127Q010 12:36 COT 100 80 -:::. 60 ~ -40 .c (’Ill .c 0 20 ... Q. 0 m. t echnologies High quality anomalies can be found without...l , , Tvoes ’ :0 ~ ~ , : : : , , , Date co cor m. t echnologies Customer Example 3: Malware Outbreak • R•pon R•suln m ~· AIIdr

  3. Crossing the Rubric-Con

    ERIC Educational Resources Information Center

    Bailey, James R.

    2014-01-01

    This essay engages the prospect and peril of employing rubrics in America. It discusses how institutional independence affects the enterprise, and addresses whether rubrics will be received as salvation or subservience by educational agents. It asks how rubrics can benefit stakeholders while examining their unintended consequences. It concludes by…

  4. FloCon 2004 Proceedings

    DTIC Science & Technology

    2004-07-01

    dataset gives us a large enough record of traffic to test hypotheses in network security. Ø Given this, we select and evaluate various security...they detect a spoof Further Work Ø Exploiting our DoS attack traffic records further • We know how the network ...DoS and Internet worms, syslog/SSH • DNS performance and anomalies • Visualization • P2P traffic detection and modelling 2 University California

  5. FloCon 2005 Proceedings

    DTIC Science & Technology

    2005-09-01

    c, e5 = b which we will write as e1:5 = aabcb for convenience. Possible state sequences that match this sequence of ob- served events could be AABCB...applicability. The application programmer sim- ply connects the input event streams and then focuses on writing process models. Models can be...Pharming • Writing to media • paper • drives • etc Increased outbound data Normal activity Scanning Infection Data Access Low Likelihood of Malicious

  6. [Utility of recruitment maneuvers (con)].

    PubMed

    Ochagavia, A; Blanch, L; Lopez-Aguilar, J

    2009-04-01

    A reduction in both total lung volume and in lung parenchyma useful for gas exchange has been observed in ARDS patients. Applying an appropriate ventilatory pattern that includes PEEP can open up collapsed areas of the lung to aeration, thus ensuring a more homogeneous distribution of air in the lung. However, the heterogeneous patterns observed in patients with ARDS vary widely in their response to ventilation with PEEP. Recruitment maneuvers (RM) have been proposed as an adjuvant treatment to mechanical ventilation to re-expand collapsed lung tissue in ARDS. Nevertheless, it is unclear whether RM are useful when patients are ventilated with high PEEP or when they have fibrosis, stiff chest wall, or hypovolemia, among other conditions. Likewise, decisions about RM must take into account not only their short- and long-term efficacy and reversibility, but also possible adverse effects derived from the high pressures reached during RM, including barotrauma, hemodynamic alterations, reduced systolic volume and aortic flow, and difficulties in venous return, as well as the possibility of bacterial translocation to the bloodstream or other organs. This article review the effects of RM as adjuvant treatment to mechanical ventilation in ARDS patients and discuss its efficacy and potential benefits as well as the different interactions that RM can have with the diverse conditions that can be associated to ARDS.

  7. Videoimaging: the pros and cons.

    PubMed

    Sarver, D M

    1993-01-01

    I have tried to make some thoughtful points based on a fair amount of experience in the use of videoimaging, both in research and clinical application. The technical development of computerized videoimaging has progressed greatly in the past several years, in response to the profession's interest in it. While many orthodontists have become interested in this technology because of its potential in communication and marketing, I feel its greatest potential lies in the area of diagnosis and treatment planning. The use of integrated and facial images has allowed me to visualize the face (primarily in profile, although the frontal view can be useful when evaluated and manipulated properly) and recognize particular aspects and patterns of treatment options I had not recognized before (Figures 4-6). Obviously, a great deal of research must be done in the future before we can completely integrate this technology into our treatment of patients. These studies are just beginning. I feel confident that computerized videoimaging will help expand our vision as we strive to deliver the best care possible; nevertheless, we must evaluate this technology rationally and define its strengths and weaknesses just as clearly as we have for our cephalometric tools.

  8. Cabergoline treatment in acromegaly: cons.

    PubMed

    Kasuki, Leandro; Vieira Neto, Leonardo; Gadelha, Mônica R

    2014-06-01

    Many options are available for the treatment of acromegaly, including surgery, radiotherapy, and medical treatment. Cabergoline (CAB), a dopamine agonist with high affinity for dopamine receptor type 2, has been used both in monotherapy and in conjunction with somatostatin analogs (SSAs). Although it is administered orally and has a relatively lower-cost in comparison with SSAs, few studies have demonstrated its usefulness, there is a lack of randomized-controlled trials and other drugs (SSAs and pegvisomant) with more data in the literature are available; these issues are the main drawbacks of adopting CAB for the treatment of acromegaly.

  9. FloCon 2008 Proceedings

    DTIC Science & Technology

    2008-01-01

    anomalous traffic of the node ÷ total anomalous traffic – Make parent nodes by merging child node information. prefix/length coverage/collateral...A T A U P L O A D F L O W S E N S O R 5. DATA DOWNLOAD FLOW SENSOR 1. RECON SNORT: KICKASS_PORN DRAGON: PORN HARDCORE SOURCEDEST SOURCE SOURCE...traffic • Make parent nodes by merging child node information. prefix/length coverage/collateral 0.0.0.0/0 100/100 depth=0 non divided 0.0.0.0/1 50/30

  10. Entrenamiento con el traje espacial

    NASA Video Gallery

    Después de 10 paseos espaciales, el astronauta de la NASA Michael López- Alegría sabe bastante de trajes espaciales. En este video, López Alegría comparte su experiencia acerca del uso y el entrena...

  11. Coagulase-negative staphylococci (CoNS) isolated from ready-to-eat food of animal origin--phenotypic and genotypic antibiotic resistance.

    PubMed

    Chajęcka-Wierzchowska, Wioleta; Zadernowska, Anna; Nalepa, Beata; Sierpińska, Magda; Łaniewska-Trokenheim, Łucja

    2015-04-01

    The aim of this work was to study the pheno- and genotypical antimicrobial resistance profile of coagulase negative staphylococci (CoNS) isolated from 146 ready-to-eat food of animal origin (cheeses, cured meats, sausages, smoked fishes). 58 strains were isolated, they were classified as Staphylococcus xylosus (n = 29), Staphylococcus epidermidis (n = 16); Staphylococcus lentus (n = 7); Staphylococcus saprophyticus (n = 4); Staphylococcus hyicus (n = 1) and Staphylococcus simulans (n = 1) by phenotypic and genotypic methods. Isolates were tested for resistance to erythromycin, clindamycin, gentamicin, cefoxitin, norfloxacin, ciprofloxacin, tetracycline, tigecycline, rifampicin, nitrofurantoin, linezolid, trimetoprim, sulphamethoxazole/trimethoprim, chloramphenicol, quinupristin/dalfopristin by the disk diffusion method. PCR was used for the detection of antibiotic resistance genes encoding: methicillin resistance--mecA; macrolide resistance--erm(A), erm(B), erm(C), mrs(A/B); efflux proteins tet(K) and tet(L) and ribosomal protection proteins tet(M). For all the tet(M)-positive isolates the presence of conjugative transposons of the Tn916-Tn1545 family was determined. Most of the isolates were resistant to cefoxitin (41.3%) followed by clindamycin (36.2%), tigecycline (24.1%), rifampicin (17.2%) and erythromycin (13.8%). 32.2% staphylococcal isolates were multidrug resistant (MDR). All methicillin resistant staphylococci harboured mecA gene. Isolates, phenotypic resistant to tetracycline, harboured at least one tetracycline resistance determinant on which tet(M) was most frequent. All of the isolates positive for tet(M) genes were positive for the Tn916-Tn1545 -like integrase family gene. In the erythromycin-resistant isolates, the macrolide resistance genes erm(C) or msr(A/B) were present. Although coagulase-negative staphylococci are not classical food poisoning bacteria, its presence in food could be of public health significance due to the possible spread of

  12. Application of the New Propulsion Theory to the Design of Propellers. Comparison with the Lifting Line Theory (Aplicacion de la Nueva Teoria de la Impulsion al Diseno de Propulsores. Comparacion con la Teoria de las Lineas Sustentadoras),

    DTIC Science & Technology

    1983-11-07

    Results and Improvement Thereon," Ingenieria Naval, May 1978. 11. Perez Gomez, G., "Fundamentos teoricos de los modernos procedimientos de proyecto de...TRANSLATED BY: 9198 SOJRCE: INGENIERIA NAVAL, JULY 1983, PP. 267-278; SPANISH DTICSELECTE DEC 9 I983 ~D MWS TRANSLATION No 72D DATE 7 NOVEMBER 1903 [-M...Impulsion al Diseno de Propulsores. Comparacion con la Teoria de las Lineas Sustentadoras.; Ingenieria Naval, July 1983; pp. 267-278] *Department of Ship

  13. HPLC-ESI-MS and MS/MS structural characterization of multifucosylated N-glycoforms of the basic proline-rich protein IB-8a CON1+ in human saliva.

    PubMed

    Cabras, Tiziana; Boi, Roberto; Pisano, Elisabetta; Iavarone, Federica; Fanali, Chiara; Nemolato, Sonia; Faa, Gavino; Castagnola, Massimo; Messana, Irene

    2012-05-01

    This study describes the characterization of the glycan moieties and the peptide backbone of six glycoforms of IB-8a CON1(+), a basic proline-rich protein present in human saliva. MS analyses on the intact glycoproteins before and after N-deglycosylation with PNGase F and high-resolution MS/MS sequencing by LTQ Orbitrap XL of peptides and glycopeptides from tryptic digests allowed the structural characterization of the glycan moieties and the polypeptide backbone, as well as to establish the glycosylation site at the asparagine residue at 98th position. Five of the glycoforms carry a biantennary N-linked glycan fucosylated in the innermost N-acetylglucosamine of the core and showing from zero to four additional fucoses in the antennal region. The sixth glycoform carries a monoantennary monofucosylated oligosaccharide. The glycoform cluster was detected on 28 of 71 adult saliva specimens. Level of fucosylation showed interindividual variability with the major relative abundance for the trifucosylated glycoform. Nonglycosylated IB-8a CON1(+) and the variant IB-8a CON1(-), lacking of the glycosylation site, have been also detected in human saliva.

  14. Structural evolution of the Day Nui Con Voi metamorphic complex: Implications on the development of the Red River Shear Zone, Northern Vietnam

    NASA Astrophysics Data System (ADS)

    Yeh, Meng-Wan; Lee, Tung-Yi; Lo, Ching-Hua; Chung, Sun-Lin; Lan, Ching-Ying; Anh, Tran Tuan

    2008-12-01

    The Day Nui Con Voi (DNCV) metamorphic complex in North Vietnam is the southernmost high-grade metamorphic zone along the NW-SE trending Red River Shear Zone (RRSZ) in Indochina. The RRSZ was considered as a classical large-scale continental strike-slip fault that had played a significant role in the continental extrusion of Southeast Asia since the collision of India and Eurasia. Earlier ideas determined the RRSZ as a steep shear zone that penetrated the entire lithosphere. Both metamorphism and structures within rocks along the DNCV metamorphic complex have been previously thought to be formed syn-tectonically by left-lateral shearing of the RRSZ during the Oligocene-Miocene continental escape tectonics. However, our meso- and microstructural re-examination of this region shows that these metamorphic rocks were formed during earlier tectonic episodes unrelated to strike-slip shearing. High angle to near orthogonal overprinting fabrics indicated that this region recorded three episodes of ductile deformation followed by brittle faulting events with different intensity spanning from the Triassic to the Tertiary. D 1 is preserved as NW-SE striking upright folds under garnet grade regional metamorphism during the Triassic Indosinian orogeny as South China block amalgamated with the Indochina block. The large-scale horizontal D 2 folds with a dominant top to N-NW bottom to S-SW sense of shear, and sub-horizontal fold axial planes suggest that the DNCV metamorphic complex remained at midcrustal depths since the Indosinian orogeny. The youngest ductile deformation event, D 3, refolded D 2 recumbent folds into a dome, and uplifted the DNCV as lower-temperature fabrics, S 3, indicated. Steep mylonite zones with left-lateral kinematic indicators and brittle faulting were developed on both limbs of the dome along the steep Song Hong and Song Chay faults during left-lateral movement of the RRSZ. Our new spatial, temporal and kinematic correlations of metamorphic fabrics

  15. Total and subtypes of dietary fat intake and risk of type 2 diabetes mellitus in the Prevención con Dieta Mediterránea (PREDIMED) study.

    PubMed

    Guasch-Ferré, Marta; Becerra-Tomás, Nerea; Ruiz-Canela, Miguel; Corella, Dolores; Schröder, Helmut; Estruch, Ramon; Ros, Emilio; Arós, Fernando; Gómez-Gracia, Enrique; Fiol, Miquel; Serra-Majem, Lluís; Lapetra, José; Basora, Josep; Martín-Calvo, Nerea; Portoles, Olga; Fitó, Montserrat; Hu, Frank B; Forga, Lluís; Salas-Salvadó, Jordi

    2017-03-01

    Background: The associations between dietary fat and cardiovascular disease have been evaluated in several studies, but less is known about their influence on the risk of diabetes.Objective: We examined the associations between total fat, subtypes of dietary fat, and food sources rich in saturated fatty acids and the incidence of type 2 diabetes (T2D).Design: A prospective cohort analysis of 3349 individuals who were free of diabetes at baseline but were at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study was conducted. Detailed dietary information was assessed at baseline and yearly during the follow-up using a food frequency questionnaire. Multivariable Cox proportional hazards models were used to estimate T2D HRs and 95% CIs according to baseline and yearly updated fat intake.Results: We documented 266 incident cases during 4.3 y of follow-up. Baseline saturated and animal fat intake was not associated with the risk of T2D. After multivariable adjustment, participants in the highest quartile of updated intake of saturated and animal fat had a higher risk of diabetes than the lowest quartile (HR: 2.19; 95% CI: 1.28, 3.73; and P-trend = 0.01 compared with HR: 2.00; 95% CI: 1.29, 3.09; and P-trend < 0.01, respectively). In both the Mediterranean diet and control groups, participants in the highest quartile of updated animal fat intake had an ∼2-fold higher risk of T2D than their counterparts in the lowest quartile. The consumption of 1 serving of butter and cheese was associated with a higher risk of diabetes, whereas whole-fat yogurt intake was associated with a lower risk.Conclusions: In a Mediterranean trial focused on dietary fat interventions, baseline intake of saturated and animal fat was not associated with T2D incidence, but the yearly updated intake of saturated and animal fat was associated with a higher risk of T2D. Cheese and butter intake was associated with a higher risk of T2D, whereas whole-fat yogurt intake

  16. Study on the Strategies for the Soil and Water Resource Con-servation of Slopeland in Taiwan in Response to the Extreme Climate

    NASA Astrophysics Data System (ADS)

    Huang, Wen-Cheng

    2014-05-01

    Global climate change results in extreme weather, especially ex-treme precipitation in Taiwan. Though the total amount of precipi-tation remains unchanged, the frequency of rainfall return period increases which affects slopeland and causes sediment disaster. In Taiwan, slopeland occupies about 73% of national territory. Under harsh environmental stress, soil and water conservation of slope-land becomes more important. In response to the trends of global-ization impacts of climate change, long term strategic planning be-comes more necessary. This study reviewed international practices and decision making process about soil and water conservation of slopeland; and conducted the compilation and analysis of water and soil conservation related research projects in Taiwan within the past five years. It is necessary for Taiwan to design timely adaptive strategies about conducting the all-inclusive conservation of na-tional territory, management and business operation of watershed based on the existing regulation with the effects of extreme weather induced by climate change and the changes of social-economic en-vironments. In order to realize the policy vision of "Under the premise of multiple uses, operating the sustainable business and management of the water and soil resources in the watershed through territorial planning in response to the climate and so-cial-economic environment change". This study concluded the future tasks for soil and water con-servation: 1.Design and timely amend strategies for soil and wand water conservation in response to extreme weather. 2. Strengthen the planning and operating of the land management and integrated conservation of the water and soil resources of key watershed. 3. Manage and operate the prevention of debris flow disaster and large-scale landslide. 4. Formulate polices, rel