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Sample records for refractaria con infliximab

  1. [Neurological symptoms following infusion of infliximab].

    PubMed

    Bebe, Anna C K M; Harboe, Kirstine Moll; Nøjgaard, Camilla

    2012-10-01

    Infliximab is indicated for treatment of plaque psoriasis when traditional systemic therapy is inadequate or inappropriate. The treatment is efficient but also carries a risk of serious adverse drug events. We describe a case of neurological symptoms following the first infusion of infliximab in a patient treated for plaque psoriasis. The patient fully recovered after sensation of the therapy. We believe the symptoms could be related to infliximab and stress the importance of thorough information of patients treated with tumour necrosis factor-α-inhibitors, also about the risk of serious adverse events.

  2. 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

  3. Management of ankylosing spondylitis with infliximab

    PubMed Central

    Toussirot, Éric; Bertolini, Ewa; Wendling, Daniel

    2009-01-01

    Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and progressive loss of functional capacity with limited therapeutic options. Regular physical exercises together with the use of nonsteroidal antiinflammatory drugs are the two recognized treatment options in AS. Infliximab is a chimeric anti-tumor necrosis factor-α monoclonal antibody that has been demonstrated to be highly effective in the treatment of AS, providing clinical amelioration at both axial and peripheral skeleton. Infliximab also improves quality of life, function, biological parameters (acute phase reactants) and inflammatory lesions of the spine as detected by magnetic resonance imaging. It is given at a 5 mg/kg dosage, as an infusion at weeks 0, 2, 6, and every 6 to 8 weeks after. Open-label and placebo-controlled trials have well demonstrated its high level of efficacy, with an improvement of the disease activity of at least 50% in 60%–80% of patients. In a large placebo-controlled trial, Assessment in Ankylosing Spondylitis Response Criteria (ASAS20) responders were observed in 61.2% of patients receiving infliximab compared to 19.2% of patients under placebo. Long-term efficacy is maintained when infliximab is administered every 6–8 weeks. Consensus international guidelines for the initiation and the use of this expensive treatment are available. Some questions remain, including the long-term safety, in particular the risk of lymphoma, and the potential influence of infliximab on radiological progression which is not currently demonstrated. Despite these concerns, infliximab has revolutionized the management of AS and represents a considerable therapeutic advancement in this disabling disease.

  4. Low Dose Infliximab for Prevention of Postoperative Recurrence of Crohn’s Disease: Long Term Follow-Up and Impact of Infliximab Trough Levels and Antibodies to Infliximab

    PubMed Central

    Sorrentino, Dario; Marino, Marco; Dassopoulos, Themistocles; Zarifi, Dimitra; Del Bianco, Tiziana

    2015-01-01

    Objective In patients with postoperative recurrence of Crohn’s disease endoscopic and clinical remission can be maintained for up to 1 year with low infliximab doses (3 mg/Kg). However, in theory low-dose infliximab treated patients could develop subtherapeutic trough levels, infiximab antibodies, and might loose response to therapy. To verify this hypothesis infliximab pharmacokinetics and clinical/endoscopic response were checked in a group of patients treated in the long term with low infliximab doses. Design Infliximab antibodies, infliximab levels, highly-sensitive CRP and fecal calprotectin were measured during the 8-week interval in 5 consecutive patients in clinical (Crohn’s Disease Activity Index < 150) and endoscopic (Rutgeerts scores 0–1) remission after one year of therapy with infliximab 3 mg/Kg. For comparison with reported standards, infliximab pharmacokinetics and inflammatory parameters were also tested in 6 Crohn’s disease patients who did not undergo surgery and who were in clinical remission while on infliximab 5 mg/Kg. Patients on low infliximab dose also underwent colonoscopy after 18 additional months of therapy. Results Highly sensitive CRP and fecal calprotectin increased in all patients during the 8-week interval. Infliximab trough levels were lower in patients treated with the low dose compared to controls (mean±SE: 2.0±0.3 vs 4.75±0.83 μg/mL respectively p<0.05). Infliximab antibodies were present in two of the subjects treated with low infliximab dose and in none of the controls. However, in low dose-treated patients after 18 additional months of therapy endoscopy continued to show mucosal remission and none of them developed clinical recurrence or side effects. Conclusions Patients treated with low infliximab doses had lower trough levels compared to patients treated with 5 mg/Kg and some developed antibodies to infliximab. However, low infliximab doses sustained clinical and endoscopic remission for a total of 30 months of

  5. Infliximab in psoriasis and psoriatic arthritis.

    PubMed

    Papoutsaki, Marina; Osório, Filipa; Morais, Paulo; Torres, Tiago; Magina, Sofia; Chimenti, Sergio; Costanzo, Antonio

    2013-01-01

    Psoriasis is a chronic inflammatory disorder of the skin and joints. Although rarely life threatening, psoriasis can significantly impair quality of life (QOL) and cause considerable physical and psychological distress. Between 6 and 42% of patients with psoriasis develop psoriatic arthritis, which is characterized by stiffness, pain, swelling and tenderness of the joints. Nail psoriasis is highly prevalent in both plaque-type psoriasis and psoriatic arthritis and is found in approximately 50% of patients with psoriasis and in 80% of patients with psoriatic arthritis. Infliximab, a chimeric human-murine monoclonal antibody directed against tumour necrosis factor α, is approved in the USA and EU for the treatment of plaque psoriasis and psoriatic arthritis at a recommended dosage of 5 mg/kg administered by intravenous infusion at 0,2 and 6 weeks, then every 8 weeks thereafter. The EXPRESS and EXPRESS II trials demonstrated that infliximab is efficacious as induction and maintenance therapy in the treatment of moderate to severe plaque psoriasis and also improved health-related QOL. Infliximab is also efficacious in the treatment of psoriatic arthritis, as shown in the IMPACT and IMPACT II studies. Infliximab is generally well tolerated, with a similar adverse event profile in both psoriasis and psoriatic arthritis. The use of infliximab in three case reports is presented. The patients are similar to those normally seen by clinicians, and include a male patient with plaque psoriasis and a history of severe psoriatic arthritis who was corticosteroid dependent and in whom other systemic treatments were not effective or were not able to be used. This patient showed a rapid response to infliximab with no skin lesions or arthritis after 7 weeks' treatment. Infliximab was also safe and effective in the treatment of a female patient with plaque and nail psoriasis and a history of psoriatic arthritis. Importantly, this case report supports the efficacy of infliximab in

  6. Guidelines for treatment with infliximab for Crohn's disease.

    PubMed

    Hommes, D W; Oldenburg, B; van Bodegraven, A A; van Hogezand, R A; de Jong, D J; Romberg-Camps, M J L; van der Woude, J; Dijkstra, G

    2006-01-01

    Infliximab is an accepted induction and maintenance treatment for patients with Crohn's disease. The effectiveness of infliximab has been demonstrated for both active luminal disease and for enterocutaneous fistulisation. In addition, infliximab can be administered for extraintestinal symptoms of Crohn's disease, such as pyoderma gangrenosum, uveitis and arthropathy. Maintenance treatment with infliximab is effective and is regarded as safe as long as the necessary safety measures are heeded. Infusion reactions occur in 3 to 17% of the patients and are associated with the formation of antibodies to infliximab. A reduction in infusion reactions is possible by the concurrent administration of steroids and the use of immunosuppressants (azathioprine, 6-mercaptopurine, methotrexate). Furthermore, immunosuppressants increase the duration of the response to infliximab. For these reasons, the concomitant use of immunosuppressants with infliximab is recommended. Infections and most specifically tuberculosis need to be ruled out before infliximab is administered. Up to now, there are no indications for a connection between an increased risk for malignancies and treatment with infliximab. PMID:16929083

  7. 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

  8. Dramatic Response of Nail Psoriasis to Infliximab

    PubMed Central

    Safa, Gilles; Darrieux, Laure

    2011-01-01

    Nail psoriasis, affecting up to 50% of psoriatic patients, is an important cause of serious psychological and physical distress. Traditional treatments for nail psoriasis, which include topical or intralesional corticosteroids, topical vitamin D analogues, photochemotherapy, oral retinoids, methotrexate, and cyclosporin, can be time-consuming, painful, or limited by significant toxicities. Biological agents may have the potential to revolutionize the management of patients with disabling nail psoriasis. We present another case of disabling nail psoriasis that responded dramatically to infliximab. PMID:21629846

  9. 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

  10. 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

  11. Infliximab-induced scleredema in a patient with rheumatoid arthritis.

    PubMed

    Ranganathan, Prabha

    2005-12-01

    A 52-year-old patient with rheumatoid arthritis (RA) developed scleredema-like skin induration after treatment with the tumor necrosis factor alpha (TNFalpha) blocking agent, infliximab. Skin induration occurred within a few weeks of initiation of infliximab, resolved with discontinuation of the drug, and recurred with rechallenge with the drug, implicating infliximab as the offending agent. Laboratory evaluation revealed a high titer of human antichimeric antibodies (HACA). The skin induration improved within a few weeks of discontinuation of infliximab and did not recur with the use of etanercept. Scleredema has been reported in association with bacterial and viral infections, diabetes mellitus, and monoclonal gammopathies. Infliximab use should be added to the list of potential associations with scleredema. This effect appears possibly specific to infliximab and may be related to the development of HACA because it did not occur with the use of etanercept in this patient. In addition, there appears to be a complex relationship between TNFalpha and tumor growth factor beta (TGF-beta), a cytokine which promotes collagen synthesis and deposition. TNFalpha blockade with infliximab may affect TNFalpha-TGF-beta interactions and may be implicated in the development of scleredema in this case. PMID:16371802

  12. Respiratory failure due to infliximab induced interstitial lung disease.

    PubMed

    Kakavas, Sotiris; Balis, Evangelos; Lazarou, Vasiliki; Kouvela, Marousa; Tatsis, Georgios

    2013-01-01

    Although poorly understood, interstitial lung disease has been reported as a possible complication of tumor necrosis factor alpha inhibitors. We report a case of interstitial lung disease in a 64-year-old man with psoriasis 3 weeks after the initiation of infliximab treatment. The patient had received two fortnightly infusions of infliximab following a short course of methotrexate. Thoracic computed tomography showed bilateral ground glass and interstitial infiltrates, while the results of microbiology and immunologic workup were negative. Likewise, bronchoalveolar lavage detected neither typical nor atypical pathogens. Infliximab-induced interstitial lung injury was suspected and corticosteroid therapy was administered which resulted in rapid clinical and radiological improvement. This is one of the few reported cases of interstitial lung disease due to infliximab in the psoriasis population. The patient had no pre-existing lung pathology, while his previous exposure to methotrexate was minimal and was not temporally associated with the induction of interstitial lung disease.

  13. A case of infliximab-induced psoriasis.

    PubMed

    Richetta, A; Mattozzi, C; Carlomagno, V; Maiani, E; Carboni, V; Giancristoforo, S; D'Epiro, S; Bruni, F; Calvieri, S

    2008-11-15

    Anti-tumor necrosis factor (anti-TNF-alpha) are a group of new drugs able to inhibit the action of this cytokine. Although systemic side effects have been well described, cutaneous adverse reactions have not yet been clearly elucidated. The authors report a case of a 29-year-old man affected by Crohn disease and ankylosing spondylitis who developed psoriatic lesions after IV infusion of infliximab 5 mg/Kg. The patient underwent cyclosporine treatment after interruption of biological therapy, and had complete resolution of cutaneous lesions. The reason for this phenomenon is not clear, Obviously more studies are necessary to define more clearly this paradoxical reaction. In addition, dermatologists must be informed about this potential cutaneous adverse event.

  14. Comparison of infliximab drug measurement across three commercially available ELISA kits.

    PubMed

    Lee, Monique Wei Meng; Connor, Susan; Ng, Watson; Toong, Catherine Mei-Ling

    2016-10-01

    The monitoring of infliximab drug levels aids in the management of several autoimmune diseases, notably inflammatory bowel disease. Several commercial kits are now available and approved by the Therapeutic Goods Administration (TGA) for the measurement of infliximab levels, but there have been limited verification or comparison studies to date. Finding an assay that most accurately measures infliximab is essential for optimal drug titration and patient management. We performed this study to compare the performance of the Grifols Promonitor, Theradiag Lisatracker and R-Biopharm Ridascreen enzyme linked immunosorbent assay (ELISA) kits. Preparations of serum containing known concentrations of infliximab were assayed using each kit, including in the presence of interference from anti-infliximab antibodies, autoantibodies and other biological agents. The Lisatracker kit provided the most accurate determination of infliximab drug levels, however it yielded false positive results at low concentrations of infliximab. The average coefficients of variation (CVs) for the kits were 8% for Lisatracker, 5% for Ridascreen and 11% for Grifols. Infliximab measurements across all kits were affected by interference from antibodies to infliximab (ATI). This study identified the Lisatracker kit as the most accurate in quantifying infliximab levels, although it was limited by false positive results at low concentrations of infliximab as well as interference from ATI. This has important implications for the monitoring and management of patients receiving infliximab therapy. PMID:27567230

  15. A lupus-like syndrome associated with infliximab therapy.

    PubMed

    Klapman, Jason B; Ene-Stroescu, Daniel; Becker, Michael A; Hanauer, Stephen B

    2003-05-01

    Infliximab, a chimeric monoclonal antibody targeting tumor necrosis factor alpha (TNF-alpha), is efficacious in the treatment of rheumatoid arthritis and Crohn's disease. We report in detail an unusual adverse reaction to infliximab therapy, a drug-induced lupus-like clinical syndrome. A 45-year-old woman with steroid-dependent Crohn's colitis, successfully managed with maintenance infliximab infusions and methotrexate, developed a lupus-like syndrome eight months after her initial infusion. This was characterized by inflammatory arthritis and an urticarial and papulosquamous rash and was accompanied by high titers of antinuclear, double-stranded DNA, glomerular-binding, and histone antibodies and by reduced levels of the C4 component of complement. After discontinuance of infliximab infusions and treatment of symptoms with intermittent courses of prednisone, the patient's arthritis progressively improved, with accompanying decrements in autoantibody titers. One year later, she has minimal joint discomfort and no rash or gastrointestinal symptoms despite also discontinuing prednisone and methotrexate. Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation.

  16. Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis.

    PubMed

    Lyseng-Williamson, Katherine A; Foster, Rachel H

    2004-01-01

    Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2

  17. Infliximab in the treatment of Crohn’s disease

    PubMed Central

    Poggioli, Gilberto; Laureti, Silvio; Campieri, Massimo; Pierangeli, Filippo; Gionchetti, Paolo; Ugolini, Federica; Gentilini, Lorenzo; Bazzi, Piero; Rizzello, Fernando; Coscia, Maurizio

    2007-01-01

    The recent introduction of infliximab, a chimeric monoclonal antibody against tumor necrosis factor-α, has greatly modified the treatment of Crohn’s disease (CD). Data from the literature show encouraging results after intravenous infusion both for closure of intestinal or perianal fistulas and for induction and maintenance of remission in patients with moderate to severe intestinal disease unresponsive to other treatments. However, some contraindications such as fibrostenosing CD and sepsis have been identified. In addition, the data on long-term outcomes and safety is still limited. Our initial experience showed that in selected cases local injection of infliximab is effective in the treatment of complex perianal disease offering the possibility of using such treatment even in small bowel obstructing disease with minimal systemic effects. This paper analyzes the state of the use of both intravenous and local injection of infliximab in patients with CD. PMID:18360638

  18. Infliximab: a pharmacoeconomic review of its use in rheumatoid arthritis.

    PubMed

    Lyseng-Williamson, Katherine A; Foster, Rachel H

    2004-01-01

    Infliximab (Remicade), a biological disease-modifying antirheumatic drug (DMARD), binds to and inhibits the activity of tumour necrosis factor-alpha, which is thought to play an important role in the pathophysiology of rheumatoid arthritis. Intravenous infliximab plus methotrexate is recommended in patients with rheumatoid arthritis who have not achieved satisfactory disease control with adequate courses of other DMARDs. Pharmacoeconomic analyses have been based on efficacy data from the pivotal placebo-controlled Anti-Tumour Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy (ATTRACT) trial in patients with active, refractory rheumatoid arthritis. Infliximab every 8 weeks plus methotrexate demonstrated rapid and sustainable improvements in clinical response, delayed radiographic progression, and/or improved functional status and health-related QOL compared with placebo plus methotrexate at weeks 30, 54 and 102. In cost-utility analyses of infliximab plus methotrexate conducted from a healthcare payer and/or societal perspective in the US, Europe, Portugal, Sweden and the UK, infliximab 3 mg/kg every 8 weeks plus methotrexate was associated with acceptable (<$US50,000 per discounted QALY gained) cost-utility ratios relative to methotrexate alone in patients with active, refractory rheumatoid arthritis. When only direct costs were considered, the lifetime incremental cost per discounted QALY gained with infliximab plus methotrexate relative to methotrexate alone was $US30,500-38,700 (year of costing 1998 or not reported; treatment duration 54 or 102 weeks or lifelong) in the US and Europe analyses, and euro39 500 (year of costing not reported; lifelong treatment) in the Portuguese analysis. The cost-utility ratios were more favourable when lost productivity costs or the additional benefit of infliximab on radiographic stabilisation were considered. In the Swedish and UK analyses with a 10-year time horizon, infliximab plus methotrexate for 1 or 2

  19. Retrospective analysis of children with uveitis treated with infliximab.

    PubMed

    Tugal-Tutkun, Ilknur; Ayranci, Ozen; Kasapcopur, Ozgür; Kir, Nur

    2008-12-01

    Tumor necrosis factor-alpha (TNF-alpha) antagonists have been successfully used in refractory cases of pediatric uveitis.(1-7) We report our experience with the monoclonal anti-TNF-alpha antibody infliximab in the treatment of uveitis in 20 children. Twenty children with noninfectious uveitis were treated with infliximab as an initial line of immunomodulatory therapy (4 children) or for uncontrolled intraocular inflammation despite aggressive immunosuppressive therapy (16 children). Intraocular inflammation was controlled in the short term in all children; resistance developed in 4 children after long-term therapy. PMID:18930672

  20. 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

  1. Cat scratch disease during infliximab therapy: a case report and literature review.

    PubMed

    Zhou, Yi; Yin, Geng; Tan, Chunyu; Liu, Yi

    2015-05-01

    Cat scratch disease may occur during etanercept therapy, but there has been no report on infliximab-associated cat scratch disease. We report a case of a 23-year-old woman who developed right inguinal lymph node enlargement following a cat scratch. The patient had received infliximab therapy for spondyloarthropathy. She was successfully managed by discontinuing infliximab and by treatment with moxifloxacin and amikacin.

  2. Treatment of complex perianal fistulas in Crohn disease: infliximab, surgery or combined approach

    PubMed Central

    Sciaudone, Guido; Di Stazio, Crescenzo; Limongelli, Paolo; Guadagni, Ilaria; Pellino, Gianluca; Riegler, Gabriele; Coscione, Paolo; Selvaggi, Francesco

    2010-01-01

    Background The aim of this study was to compare the outcomes of the management of perianal fistulas in Crohn disease between infliximab, surgery or a combination of surgery and infliximab. Methods We prospectively subdivided 35 consecutive patients with Crohn disease with complex perianal fistulas into 3 groups: 11 patients received infliximab (5 mg/kg intravenously at 0, 2 and 6 wk; group A), 10 underwent surgery (group B) and 14 received a combination of surgery and postoperative infliximab (group C). We evaluated the rate and time of healing of perianal fistulas, the rate of recurrences and time to relapse at a median follow-up of 18.8 (standard deviation [SD] 10.8, range 8–38) months. Results The time to healing of fistulas was significantly shorter among patients who received surgery and infliximab than among those who received surgery alone (p < 0.05) and was close to statistically shorter among those who received both treatments than among those who received infliximab alone (p = 0.06). Patients who received surgery and infliximab had a significantly longer mean time to relapse (p < 0.05) than those who received infliximab (mean 2.6 [SD 0.7] mo) or surgery alone (mean 3.6 [SD 0.5] mo). Conclusion We found better outcomes among patients who received a combination of surgery and infliximab therapy. These patients experienced a short time to healing of fistulas and significantly longer mean time to relapse of complex fistulas. PMID:20858373

  3. 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.

  4. 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. PMID:23377397

  5. 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. PMID:27582886

  6. 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

  7. Chronic Inflammatory Demyelinating Polyneuropathy Following Anti-TNF-α Therapy With Infliximab for Crohn's Disease

    PubMed Central

    Concepcion, Orestes; Schlachterman, Alexander; Glover, Sarah; Forsmark, Christopher Y.

    2016-01-01

    We present a 29-year-old male with Crohn's disease who developed chronic inflammatory demyelinating polyneuropathy (CIDP) related to infliximab therapy. He developed lower extremity weakness and dysesthesia 3 weeks after a fourth infliximab dose. Laboratory examination revealed an elevated cerebrospinal fluid protein without pleocytosis. The patient initially responded to plasmapheresis therapy with marked symptomatic improvement, but relapsed and was refractory to subsequent treatments with plasmaphereisis, intravenous immunoglobulin, and glucocorticoids. While a causal relationship between infliximab and CIDP cannot be proven, clinicians should monitor Crohn's disease patients who are receiving TNF-α antagonists for neurologic symptoms suggestive of demyelinating disease. PMID:27144200

  8. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide.

    PubMed

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab's role in localized scleroderma.

  9. Ramsay Hunt Syndrome in a Patient with Rheumatoid Arthritis after Treatment with Infliximab

    PubMed Central

    Nagayama, Yoshio; Matsushiro, Naoki; Nampei, Akihide; Hashimoto, Hideo; Shi, Kenrin

    2014-01-01

    A 39-year-old female patient with rheumatoid arthritis developed Ramsay Hunt syndrome after infliximab treatment. This condition is caused by the reactivation of varicella zoster virus infection in the geniculate ganglion of facial nerve in the host's immunosuppression. She was treated immediately with valaciclovir and hydrocortisone, and the complete recovery was achieved at 6 months after the onset. This is the first report of Ramsay Hunt syndrome as an adverse effect of infliximab in rheumatoid arthritis. PMID:24660085

  10. Infliximab is a plausible alternative for neurologic complications of Behçet disease

    PubMed Central

    Zeydan, Burcu; Uygunoglu, Ugur; Saip, Sabahattin; Demirci, Onat N.; Seyahi, Emire; Ugurlu, Serdal; Hamuryudan, Vedat; Siva, Aksel

    2016-01-01

    Objective: We evaluated the effectiveness of infliximab in patients with neuro-Behçet syndrome for whom other immunosuppressive medications had failed. Methods: Patients whose common immunosuppressive medications fail in recurrent neuro-Behçet syndrome need an alternative. We report our experience with the tumor necrosis factor α blocker infliximab for long-term treatment of neuro-Behçet syndrome. We recruited patients within a multidisciplinary referral practice of Behçet disease and prospectively followed everyone with a neurologic symptom(s). Patients (n = 16) with ≥2 neurologic bouts (excluding purely progressive disease) while on another immunosuppressive treatment were switched to and successfully sustained on infliximab (5 mg/kg in weeks 0, 2, and 6, then once every 8 weeks; minimum follow-up duration ≥12 months). Infliximab was stopped within 2 months after initiation in one patient because of pulmonary and CNS tuberculosis. Results: Patients had stepwise worsening due to relapses in the Expanded Disability Status Scale modified for neuro-Behçet syndrome before switching to infliximab (median score of 5.0, range 2.0–7.0; median neuro-Behçet syndrome duration 29.1 months, range 5.0–180.7). Median duration of preinfliximab immunosuppressive medication use was 20.0 months (range 3.0–180.7). In all 15 patients, during infliximab treatment (median score 4.0, range 2.0–7.0; median duration 39.0 months, range 16.0–104.9 months), neurologic relapses were completely aborted and there was no further disability accumulation. Conclusion: We observed a significant beneficial effect of infliximab in neuro-Behçet syndrome. Classification of evidence: This study provides Class IV evidence that for patients with neuro-Behçet syndrome whose other immunosuppressive medications failed, infliximab prevents further relapses and stabilizes disability. PMID:27458602

  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. A systematic review on the efficacy and safety of Infliximab in patients with psoriasis

    PubMed Central

    Wang, Jin; Zhan, Qingxia; Zhang, Litao

    2016-01-01

    ABSTRACT Objective: To assess the efficacy and safety of infliximab for the treatment of psoriasis in a meta-analysis framework. Methods: Data were extracted by searching the EMBASE (1974–2014), PubMed(1966–2014) and the Cochrane library2013.4th databases. Only randomized and placebo-controlled studies were selected in this study. Results: Statistically significant differences in efficacy were found for the infliximab (3 or 5 mg/kg) group compared with the control group which received placebo in the treatment of psoriasis vulgaris [OR 13.55, 95%CI (11.14,16.48)]or[OR85.45, 95%CI (39.13,186.58)]. There were also significant differences in efficacy between the infliximab (5 mg/kg) group and the placebo control group during treatment of psoriasis arthritis (PsA) [OR8.36, 95%CI (5.63, 12.40)]. A controlled trial used infliximab (5 mg/kg) in the treatment of palmoplantar psoriasis. This study showed that the effective rate of the infliximab group was 33.3% (4/12) when compared to the placebo control group, which was 8.3% (1/12). Conclusion: Infliximab is significantly associated with symptom relief, skin lesion improvement, and an increase in the quality of life of psoriasis patients. The most common drug-induced adverse events were pain, hepatic dysfunction, and infusion reaction. PMID:26528924

  13. Infliximab: the evidence for its place in therapy in ulcerative colitis

    PubMed Central

    Van Assche, Gert; Vermeire, Séverine; Rutgeerts, Paul

    2007-01-01

    Introduction: Refractory ulcerative colitis has a high, unmet medical need for avoiding steroid dependency and avoiding colectomy. Controlled trials with biologic agents have recently been reported. Aims: We aimed to review the current evidence supporting the use of the monoclonal antitumor necrosis factor antibody, infliximab, in active ulcerative colitis and determine its current place in therapy. Evidence review: Although faced with initial conflicting data particularly in steroid-refractory patients, two large, placebo-controlled trials have shown that intravenous infliximab induces and maintains clinical improvement in a clinically significant proportion of patients when used with scheduled re-treatment. Infliximab also spares steroids and induces endoscopic remission in moderately ill patients. In fulminant colitis unresponsive to intravenous steroids, one placebo-controlled trial indicates that infliximab is able to prevent colectomy in this patient population. Evidence for cost effectiveness and avoidance of colectomy long term are still lacking. Place in therapy: Infliximab 5 mg/kg induction at 0, 2, and 6 weeks, and every 8 weeks thereafter should be considered in patients with moderately to severely active ulcerative colitis failing medical therapy. Steroid-dependent and steroid-refractory patients also qualify for infliximab therapy. PMID:21221182

  14. Predictors of infusion reactions during infliximab treatment in patients with arthritis

    PubMed Central

    Kapetanovic, Meliha C; Larsson, Lotta; Truedsson, Lennart; Sturfelt, Gunnar; Saxne, Tore; Geborek, Pierre

    2006-01-01

    In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999–2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions. PMID:16869978

  15. Predictors of infusion reactions during infliximab treatment in patients with arthritis.

    PubMed

    Kapetanovic, Meliha C; Larsson, Lotta; Truedsson, Lennart; Sturfelt, Gunnar; Saxne, Tore; Geborek, Pierre

    2006-01-01

    In the present study we evaluated the impact of baseline antinuclear antibody (ANA) status and use of methotrexate on development of infliximab-related infusion reactions in patients with rheumatoid arthritis (RA) or spondylarthropathies (SpAs), including psoriatic arthritis. All patients with RA (n = 213) or SpA (n = 76) treated with infliximab during the period 1999-2005 at the Department of Rheumatology in Lund, Sweden were included. ANAs were present in 28% and 25% of RA and SpA patients, respectively. Because of differences in baseline characteristics, we used a binary logistic regression model to calculate odds ratios (ORs), adjusting for age, sex and prednisolone dosage. Altogether 21% of patients with RA and 13% of patients with SpA developed infusion reactions (P = 0.126). The OR for development of infusion reactions in RA patients with baseline ANA positivity alone was 2.1. Infliximab without methotrexate and infliximab as monotherapy were associated with ORs of 3.1 and 3.6, respectively. Combining infliximab without methotrexate and ANA positivity yielded an OR for infusion reaction of 4.6. Lower age at disease onset and longer disease duration were associated with infusion reactions (P = 0.012 and P = 0.036, respectively), but age, sex, C-reactive protein, erythrocyte sedimentation rate, Health Assessment Questionnaire and Disease Activity Score-28 at baseline were not. No predictors of infusions reactions were identified in SpA patients. RA patients treated with infliximab without methotrexate, and who are positive at baseline for ANAs are at increased risk for developing infliximab-related infusion reactions.

  16. Effect of Systemic Infliximab Therapy in Patients with Sjögren’s Syndrome

    PubMed Central

    Betül Türkoğlu, Elif; Tuna, Serpil; Alan, Sevil; İhsan Arman, Mehmet; Tuna, Yaşar; Ünal, Mustafa

    2015-01-01

    Objectives: To investigate the effect of systemic infliximab therapy on tear function tests and the ocular surface in patients with Sjögren’s syndrome secondary to various autoimmune diseases. Ma­te­ri­als and Met­hods: This prospective study included 22 eyes of 22 patients with Sjögren’s syndrome who began treatment with systemic infliximab. Tear film break-up time (TBUT), anesthetized Schirmer’s 1 test, fluorescein staining test, and Ocular Surface Disease Index (OSDI) scores were recorded before treatment and in the 3rd and 6th months of treatment. Re­sults: In the 3rd month of infliximab therapy, no significant changes were observed in Schirmer’s values, TBUT, fluorescein staining, or OSDI scores (p=0.260, p=0.357, p=0.190 and p=0.07, respectively). In the 6th month of infliximab therapy, no significant changes were observed in TBUT, fluorescein staining, Schirmer’s value or OSDI scores (p=0.510, p=0.320, p=0.220 and p=0.344, respectively). Conclusion: Infliximab therapy, which is commonly used in systemic autoimmune diseases such as rheumatoid arthritis, Crohn’s disease, ulcerative colitis, and ankylosing spondylitis, did not show a positive effect on ocular surface and tear function tests. PMID:27800220

  17. Infliximab treatment in a case of rheumatoid scleromalacia perforans.

    PubMed

    Herrera-Esparza, R; Avalos-Díaz, E

    2009-01-01

    Ocular rheumatoid disease manifests as hyperemia of the conjunctiva and episclera, and in severe cases, episcleritis can result in nodular sclerotic and scleromalacia perforans. A clinical case of scleromalacia perforans in a 56-year-old woman with 20 years of seropositive rheumatoid arthritis of functional class IV is presented here. During that period, she received exclusively non-steroidal anti-inflammatory drugs (NSAIDs). She developed acute episcleritis of the left ocular globe, which rapidly progressed to scleromalacia perforans. Since the left eye became perforated, it was surgically enucleated, and the patient was maintained with steroidal therapy. Nevertheless, two months later she developed new-onset episcleritis of the right eye followed by scleromalacia. She was first evaluated by a rheumatologist and treated with 200 mg/dose of infliximab, which was administered monthly for the following four months. The biological treatment was accompanied by methotrexate and prednisone. With this therapy, the ocular lesion dramatically improved, and complete remission of rheumatoid arthritis and scleritis was archived four months later. In conclusion, tumour necrosis factor (TNF) blockers are effective therapeutic agents in ocular complications of rheumatoid arthritis.

  18. Treatment of erosive osteoarthritis of the hands by intra-articular infliximab injections: a pilot study.

    PubMed

    Fioravanti, Antonella; Fabbroni, Marta; Cerase, Alfonso; Galeazzi, Mauro

    2009-06-01

    Our pilot study aimed to investigate the efficacy and tolerability of intra-articular (i.a.) injections of infliximab as a therapy for erosive osteoarthritis of the hands. Ten women with bilateral involvement of the hands and typical erosive osteoarthritis radiographic findings were enrolled and followed for 12 months. All the patients were refractory to conventional drugs. Treatment consisted in monthly i.a. injections of 0.2 ml of infliximab (0.1 mg/ml) in each affected proximal and distal interphalangeal joint of the most involved hand, identified on the basis of clinical and radiological examinations. The other hand was treated with physiological saline (control). The patients did not know which hand was receiving infliximab. Clinical response was evaluated at enrollment, after 6 and 12 months. Posteroanterior radiographs of both hands were obtained at baseline and 12 months later. At 6 months all the patients experienced relief from spontaneous pain and pain on lateral pressure in the hand treated with infliximab and these findings became statistically significant after 1 year. No important modifications were recognized in the hand treated with physiological saline. The anatomical lesion progression system radiological score indicated a reduction, even if not statistically significant, in the hand treated with infliximab and a tendency to slow worsening in the hand treated with physiological saline at 12-month follow-up. No local or systemic adverse reactions were recorded. Our study shows the symptomatic effect and a possible disease modifying action of i.a. infliximab in erosive osteoarthritis of the hands.

  19. Safety and cost of infliximab for the treatment of Belgian pediatric patients with Crohn's disease.

    PubMed

    De Greef, E; Hoffman, I; D'Haens, G; Van Biervliet, S; Smets, F; Scaillon, M; Dewit, O; Peeters, H; Paquot, I; Alliet, P; Arts, W; Hauser, B; Vermeire, S; Van Gossum, A; Rahier, J F; Etienne, I; Louis, E; Coche, J C; Mahachie John, J; Van Steen, K; Veereman, G

    2012-12-01

    Biologicals have become an important component in the treatment of Crohn's disease in children. Their increased and long term use raises safety concerns. We describe safety and cost of infliximab in Belgian pediatric Crohn's disease patients. All patients on infliximab as part of the present or past treatment for Crohn's Disease until January 1st 2011 were selected from an existing database. Information on disease phenotype, medication and adverse events were extracted. Adverse events occurred in 25.9% of patients exposed to infliximab of which 29.6% were severe. In total 31.7% of patients stopped infliximab therapy. The main reasons for discontinuation were adverse events in 45.4% and loss of response in 30.3%. No malignancies or lethal complications occurred over this 241 patient year observation period. Immunomodulators were concomitant medication in 75% of patients and were discontinued subsequently in 38.4% of them. The cost of infliximab infusions per treated patient per year in the Belgian health care setting is approximately 9 474 euro, including only medication and hospital related costs. Even though infliximab is relatively safe in pediatric CD on the short term, close follow-up and an increased awareness of the possible adverse reactions is highly recommended. Adverse reactions appeared in 25.9% of all patients and were the main reason for discontinuation. Treatment cost has to be balanced against efficacy and modifications in disease course. In the Belgian health care system, the medication is available to all patients with moderate to severe CD. PMID:23402086

  20. 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.

  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. PMID:25165648

  2. A Case Report of Successful Treatment of Recalcitrant Childhood Localized Scleroderma with Infliximab and Leflunomide

    PubMed Central

    Ferguson, Ian D; Weiser, Peter; Torok, Kathryn S

    2015-01-01

    Herein we report successful treatment of an adolescent Caucasian female with severe progressive localized scleroderma (mixed subtype, including generalized morphea and linear scleroderma of the trunk/limb) using infliximab and leflunomide. The patient demonstrated improvement after the first 9 months of therapy based on her clinical examination, objective measures, and patient and parent global assessments. Infliximab is a potential treatment option for pediatric localized scleroderma patients who have progression of disease or who are unable to tolerate the side effect profile of more standard systemic therapy. Larger longitudinal studies or case series are needed to confirm and further investigate infliximab’s role in localized scleroderma. PMID:26161155

  3. Serum protein profile of Crohn's disease treated with infliximab.

    PubMed

    Gazouli, Maria; Anagnostopoulos, Athanasios K; Papadopoulou, Aggeliki; Vaiopoulou, Anna; Papamichael, Konstantinos; Mantzaris, Gerassimos; Theodoropoulos, George E; Anagnou, Nicholas P; Tsangaris, George Th

    2013-11-01

    The infliximab (IFX) has dramatically improved the treatment of Crohn's disease (CD). However, the need for predictive factors, indicative of patients' response to IFX, has yet to be met. In the current study, proteomics technologies were employed in order to monitor for differences in protein expression in a cohort of patients following IFX administration, aiming at identifying a panel of candidate protein biomarkers of CD, symptomatic of response to treatment. We enrolled 18 patients, who either had achieved clinical and serological remission (Rm, n=6), or response (Rs, n=6) and/or were PNRs (n=6), to IFX. Serum samples were subjected to two-dimensional Gel Electrophoresis. Following evaluation of densitometrical data, protein spots exhibiting differential expression among the groups, were further characterized by MALDI-TOF-MS. Identified proteins where evaluated by immunoblot analysis while functional network association was carried out to asses significance. Proteins apolipoprotein A-I (APOA1), apolipoprotein E (APOE), complement C4-B (CO4B), plasminogen (PLMN), serotransferrin (TRFE), beta-2-glycoprotein 1 (APOH), and clusterin (CLUS) were found to be up-regulated in the PNR and Rs groups whereas their levels displayed no changes in the Rm group when compared to baseline samples. Additionally, leucine-rich alpha-2-glycoprotein (A2GL), vitamin D-binding protein (VTDB), alpha-1B-glycoprotein (A1BG) and complement C1r subcomponent (C1R) were significantly increased in the serum of the Rm group. Through the incorporation of proteomics technologies, novel serum marker-molecules demonstrating high sensitivity and specificity are introduced, hence offering an innovative approach regarding the evaluation of CD patients' response to IFX therapy.

  4. Postinduction serum infliximab trough level and decrease of C-reactive protein level are associated with durable sustained response to infliximab: a retrospective analysis of the ACCENT I trial

    PubMed Central

    Cornillie, Freddy; Hanauer, Stephen B; Diamond, Robert H; Wang, Jianping; Tang, Kezhen L; Xu, Zhenhua; Rutgeerts, Paul; Vermeire, Séverine

    2014-01-01

    Background Serum infliximab trough levels correlate with efficacy; dose escalation is often beneficial in patients with Crohn's disease who stop responding to infliximab treatment. Objective To carry out a post hoc analysis of A Crohn's Disease Clinical Trial Evaluating Infliximab in a New Long-term Treatment Regimen I (ACCENT I) to evaluate the association between serum infliximab trough levels and C-reactive protein (CRP) after 14 weeks of induction treatment with durable sustained long-term response (Crohn's Disease Activity Index decrease ≥70 points and reduction ≥25% from baseline). Design ACCENT I was a multicentre, randomised, placebo-controlled study. Week 14 trough levels and CRP percentage decrease from baseline to week 14 were compared between patients with and without durable sustained response through week 54. Sensitivity and specificity were determined to predict durable sustained response. Receiver operating characteristic (ROC) curves identified optimal cut-off points; logistic regression determined ORs. Results After induction with 5 mg/kg infliximab, 25% (37/147) and 33% (47/144) of patients sustained week 14 response to infliximab 5 or 10 mg/kg, respectively, administered every 8 weeks without dose escalation, through week 54. Median week 14 trough levels of patients with and without durable sustained response to infliximab 5 mg/kg were 4.0 and 1.9 μg/mL, respectively (p=0.0331). Optimal predictors of durable sustained response to maintenance infliximab 5 mg/kg were week 14 trough level ≥3.5 µg/mL and ≥60% CRP decrease (ORs (95% CI), 3.5 (1.1 to 11.4) and 7.3 (1.4 to 36.7)), respectively, in patients with raised baseline CRP (>8.0 mg/L); area under the ROC curve was 0.75 for both predictors. A ≥3.5 µg/mL week 14 infliximab serum level did not predict durable sustained response to 10 mg/kg maintenance infliximab. Conclusions Patients with durable sustained response to maintenance infliximab 5 mg/kg had higher

  5. Long-term efficiency of infliximab in patients with ankylosing spondylitis: real life data confirm the potential for dose reduction

    PubMed Central

    Heldmann, F; van den Bosch, F; Burmester, G; Gaston, H; van der Horst-Bruinsma, I E; Krause, A; Schmidt, R; Schneider, M; Sieper, J; Andermann, B; van Tubergen, A; Witt, M; Braun, J

    2016-01-01

    Objective To analyse the treatment outcome of patients with ankylosing spondylitis (AS) in the European AS infliximab cohort (EASIC) study after a total period of 8 years with specific focus on dosage and the duration of intervals between infliximab infusions. Methods EASIC included patients with AS who had received infliximab for 2 years as part of the ASSERT trial. After that period, rheumatologists were free to change the dose or the intervals of infliximab. Clinical data were status at baseline, end of ASSERT and for a total of 8 years of follow-up. Results Of the initially 71 patients with AS from EASIC, 55 patients (77.5%) had completed the 8th year of anti-tumour necrosis factor (TNF) treatment. Of those, 48 patients (87.3%) still continued on infliximab. The mean infusion interval increased slightly from 6 to 7.1±1.5 weeks, while 45.8% patients had increased the intervals up to a maximum of 12 weeks. The mean infliximab dose remained stable over time, with a minimum of 3.1 mg/kg and a maximum of 6.4 mg/kg. In patients receiving <5 mg/kg infliximab, the mean infusion interval increased to 7.0±1.2 weeks. In total, the mean cumulative dose per patient and per year decreased from 3566.30 to 2973.60 mg. Conclusions We could observe that over a follow-up of 8 years of treatment with infliximab, >85% patients still remained on the same treatment, without any major safety events. Furthermore, both the infusion intervals and also the mean infliximab dose were modestly reduced in ≥70% of the patients without the loss of clinical efficiency. PMID:27493791

  6. Risk of tuberculosis during infliximab therapy for inflammatory bowel disease, rheumatoid arthritis, and spondyloarthropathy: A meta-analysis

    PubMed Central

    Wang, Qiang; Wen, Zhenzhen; Cao, Qian

    2016-01-01

    Infliximab is a promising drug with good outcomes demonstrated for diseases such as inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and spondyloarthropathy (SpA). However, treatment with this drug may increase the risk of tuberculosis infection. The aim of the present study was to investigate infliximab-associated tuberculosis infection. Literature searches in PubMed, MEDLINE and EMBASE databases were performed. Randomized controlled trials with >95% of the patients >18 years-old were included. Meta-analysis was performed to investigate the incidence of tuberculosis infection after infliximab infusion. A total of 24 RCTs were included in the present meta-analysis. In total, 21 (0.51%) tuberculosis infections were detected among 4,111 patients administered infliximab therapy, compared with 0 (0%) among 2,229 patients assigned to the placebo group. Pooled odds ratio (OR) of developing tuberculosis infection was significantly higher with infliximab therapy than with placebo [2.86; 95% confidence interval (CI), 1.09–7.52]. The OR of tuberculosis infection was 3.93 (95% CI, 0.91–16.91) in RA, 2.46 (95% CI, 0.38–15.92) in SpA and 1.66 (95% CI, 0.26–10.57) in IBD. Rates of tuberculosis infection with infliximab therapy in RA, SpA and IBD were 0.70, 0.22 and 0.52%, respectively. Compared with placebo, infliximab therapy may increase the risk of developing tuberculosis. However, the ORs for the risk of infliximab-associated tuberculosis were not demonstrated to be significant in IBD, RA and SpA; therefore, these findings should be interpreted with caution. The risk of developing tuberculosis demonstrates the importance of the prevention and management of tuberculosis infection with infliximab therapy. PMID:27588089

  7. Remission of Cap Polyposis Maintained for More Than Three Years after Infliximab Treatment

    PubMed Central

    Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Chun, Hoon Jai; Um, Soon Ho; Kim, Chang Duck; Ryu, Ho Sang

    2009-01-01

    Cap polyposis is a rare disorder with characteristic endoscopic and histological features; its etiology is still unknown, and no specific treatment has been established. We report a case of cap polyposis that improved remarkably after infliximab infusion and had no recurrence for 3 years. PMID:20431770

  8. 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.

  9. Noninfectious interstitial lung disease during infliximab therapy: case report and literature review.

    PubMed

    Caccaro, Roberta; Savarino, Edoardo; D'Incà, Renata; Sturniolo, Giacomo Carlo

    2013-08-28

    Pulmonary abnormalities are not frequently encountered in patients with inflammatory bowel diseases. However, lung toxicity can be induced by conventional medications used to maintain remission, and similar evidence is also emerging for biologics. We present the case of a young woman affected by colonic Crohn's disease who was treated with oral mesalamine and became steroid-dependent and refractory to azathioprine and adalimumab. She was referred to our clinic with a severe relapse and was treated with infliximab, an anti-tumor necrosis factor α (TNF-α) antibody, to induce remission. After an initial benefit, with decreases in bowel movements, rectal bleeding and C-reactive protein levels, she experienced shortness of breath after the 5(th) infusion. Noninfectious interstitial lung disease was diagnosed. Both mesalamine and infliximab were discontinued, and steroids were introduced with slow but progressive improvement of symptoms, radiology and functional tests. This represents a rare case of interstitial lung disease associated with infliximab therapy and the effect of drug withdrawal on these lung alterations. Given the increasing use of anti-TNF-α therapies and the increasing reports of pulmonary abnormalities in patients with inflammatory bowel diseases, this case underlines the importance of a careful evaluation of respiratory symptoms in patients undergoing infliximab therapy.

  10. Mucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment

    PubMed Central

    Lemaire, Katleen; Quintens, Roel; Van Lommel, Leentje; Van Steen, Kristel; Leemans, Peter; Cleynen, Isabelle; Van Assche, Gert; Vermeire, Séverine; Geboes, Karel; Schuit, Frans; Rutgeerts, Paul

    2009-01-01

    Background Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD. Methodology/Principal Findings Mucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4–6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage. Conclusions/Significance Our study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms. PMID:19956723

  11. Psoriasis induced by infliximab in a Saudi patient with ankylosing spondylitis.

    PubMed

    Alabed, Iehab B; Qushmaq, Khalid A; Khan, Muhammad A

    2010-09-01

    Although the therapeutic uses of tumor necrosis factor alpha antagonists have added a highly effective treatment of ankylosing spondylitis and associated spondyloarthropathies, they are associated with many untoward effects. We describe a Saudi patient with ankylosing spondylitis who developed severe psoriatic lesions in treatment with infliximab. He had no personal, or family history of psoriasis, and no other triggering factors known to induce psoriasis.

  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. Apolipoprotein A-I and platelet factor 4 are biomarkers for infliximab response in rheumatoid arthritis

    PubMed Central

    Trocmé, Candice; Marotte, Hubert; Baillet, Athan; Pallot-Prades, Béatrice; Garin, Jérome; Grange, Laurent; Miossec, Pierre; Tebib, Jacques; Berger, François; Nissen, Michael J.; Juvin, Robert; Morel, Françoise; Gaudin, Philippe

    2009-01-01

    Objectives The use of biologics such as infliximab has dramatically improved the treatment of rheumatoid arthritis (RA). However, factors predictive of therapeutic response need to be identified. A proteomic study was performed prior to infliximab therapy to identify a panel of candidate protein biomarkers of RA predictive of treatment response. Methods Plasma profiles of 60 RA patients (28 non-responders ACR 20 negative and 32 responders ACR 70 positive to infliximab) were studied by SELDI-TOF-MS technology on two types of arrays, an anion exchange array (SAX2) and a nickel affinity array (IMAC3-Ni). Biomarker characterization was carried out using classical biochemical methods (purification by ammonium sulfate precipitation or metal affinity chromatography) and identification by MALDI-TOF analysis. Results Two distinct protein profiles were observed on both arrays and several proteins were differentially expressed in both patient populations. Five proteins at 3.86, 7.77, 7.97, 8.14 and 74.07 kDa were overexpressed in the non-responder group, whereas one at 28 kDa was increased in the responder population (sensitivity > 56%, specificity > 77.5%). Moreover combination of several biomarkers improved both the sensitivity and specificity of the detection of patient response to over 97%. The 28 kDa protein was characterized as apolipoprotein A-I and the 7.77 kDa biomarker was identified as platelet factor 4. Conclusions We characterized six plasma biomarkers, enabling the detection of patient response to infliximab with high sensitivity and specificity. Apolipoprotein A-1 was predictive of a good response to infliximab, whereas platelet factor 4 was associated with non-responders. PMID:18664547

  14. Effects of infliximab on bacterial translocation in experimental acute necrotizing pancreatitis

    PubMed Central

    Aydin, Sezai; Isik, A. Turan; Unal, Bulent; Comert, Bilgin; Ozyurt, Mustafa; Deveci, Salih; Ozgur, Gokhan; Cengiz, Omer; Tasci, Ilker; Mas, M. Refik

    2012-01-01

    Background & objectives: Translocation of bacteria from the gut is an important factor in the development of septic complications and mortality in acute pancreatitis (AP). The present study was designed to assess the effects of infliximab treatment on bacterial translocation (BT) in experimental acute necrotizing pancreatitis. Methods: Male Sprague-Dawley rats (n=45) were allocated into three groups. AP was induced in group II (positive control, n=15) and group III (Infliximab; n=15) by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (Sham; n=15) received normal saline infusion into the common biliopancreatic duct as placebo. Groups I and II were treated by normal saline and group III was treated with infliximab intraperitoneally on 6, 30 and 54 h after induction of pancreatitis. All surviving animals were killed 60 h after the induction of pancreatitis, and specimens were collected for amylase measurement as well as histopathologic and microbiologic examinations. Results: Oedema, acinar cell necrosis, inflammatory infiltration, haemorrhage, fat necrosis and perivascular inflammation in group III rats were decreased with infliximab treatment when compared with group II (P<0.001). BT to mesentery lymph node in groups I, II and III were 20, 100 and 46 per cent, respectively. BT to peritoneum and pancreas in group III was lower than group II (P<0.05). Interpretation & conclusions: Infliximab administration resulted in beneficial effects on BT and histopathologic changes in the experimental necrotizing pancreatitis. Whether anti-TNF therapy has a role in prevention of complications of ANP needs to be established. PMID:22771595

  15. 74-week follow-up of safety of infliximab in patients with refractory rheumatoid arthritis

    PubMed Central

    2010-01-01

    Introduction The objective was to describe the prevalence, types, and predictors of adverse events (AEs) in rheumatoid arthritis (RA) patients treated with infliximab and methotrexate in a daily clinical setting. Methods This was a prospective, multi-center, open-label, 74-week observational study in patients with active RA despite treatment with methotrexate and at least one other disease-modifying anti-rheumatic drug. Patients were treated with 3 mg/kg infliximab at weeks 0, 2, and 6 and then every 8 weeks. At weeks 0, 6, 26, 50, and 74, patients answered a health assessment questionnaire, a swollen joint count was made, and adverse events (AEs) occurring during the previous period were registered. Results Five hundred and seventy-five patients were treated with infliximab, of which 346 were still on infliximab at the study end, 158 discontinued treatment, and 71 were lost to follow-up. Reasons for discontinuation included safety (n = 74), elective reasons (n = 43), and inefficacy (n = 41). Infusion reactions (n = 33) and infections (n = 20) were the most common AEs causing discontinuation and the most common AEs overall. There were four cases of tuberculosis, all of which occurred in patients negative at screening. Total AEs, serious AEs, and infusion reactions as well as discontinuations for AEs were most frequent during the first 26 weeks. Higher age was a predictor of serious adverse events (SAEs), infection, and discontinuation due to an SAE, but odds ratios were close to one. Conclusions AEs and discontinuations due to AEs occur most frequently during the first half year of infliximab treatment in refractory RA patients. The main reasons for discontinuing treatment are infections and infusion reactions. Tuberculosis and other infections remain an important concern in these patients. PMID:20569501

  16. 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.

  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. Regulation of peripheral classical and non-classical monocytes on infliximab treatment in patients with rheumatoid arthritis and ankylosing spondylitis

    PubMed Central

    Aeberli, Daniel; Kamgang, Richard; Balani, Deepak; Hofstetter, Willy; Villiger, Peter M; Seitz, Michael

    2016-01-01

    Objective To investigate the regulatory effect of tumour necrosis factor (TNF) blockade with infliximab on the distribution of peripheral blood monocyte subpopulations in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Methods Purified CD11b+CD14+ monocytes from 5 patients with RA and 5 AS were analysed ex vivo before and after infliximab treatment by flow cytometry for CD16, CD163, CD11b, C-C chemokine receptor type 2 (CCR2) and CXC chemokine receptor 4 (CXCR4) at baseline and at days 2, 14, 84 and 168 after the first infliximab administration. Serum levels of the stromal cell-derived factor (SDF)-1 and monocyte chemotactic peptide (MCP)-1 at different time points were measured in either patient group before and on infliximab treatment. Results Anti-TNF treatment with infliximab led to a significant increase of circulating CD11b+ non-classical and a concomitantly decrease of CD11b+ classical monocytes, to a decline in SDF-1 levels and reduced expression of CCR2 and CXCR4 on non-classical monocyte subpopulation. Conclusions Our study shows, that TNFα blockade by infliximab resulted in a dichotomy of the regulation of classical and non-classical monocytes that might have substantial impact on inhibition of osteoclastogenesis and of subsequent juxta-articular bone destruction and systemic bone loss in RA and AS. PMID:26819749

  19. Infliximab in patients with psoriasis and other inflammatory diseases: evaluation of adverse events in the treatment of 168 patients*

    PubMed Central

    Antonio, João Roberto; Sanmiguel, Jessica; Cagnon, Giovana Viotto; Augusto, Marília Silveira Faeda; de Godoy, Moacir Fernandes; Pozetti, Eurides Maria Oliveira

    2016-01-01

    Background Psoriasis is immune-mediated chronic inflammatory disease with preference for skin and joints. The skin involvement occurs by hyperproliferation and abnormal differentiation of keratinocytes. It is associated with comorbidities, mainly related to the clinical manifestations of the metabolic syndrome. Increased TNF-alpha expression (TNF-α) is related to its pathophysiology. Infliximab is an intravenous drug that acts neutralizing the biological activity of TNF-α and prevents the binding of the molecule to the target cell receptor, inhibiting cell proliferation of psoriasis and other diseases mediated by TNF-α. A lot of infusion reactions have been described in the literature. Objective To evaluate the adverse effects of intravenous treatment with infliximab, analyzing patients with psoriasis compared to those with other chronic inflammatory diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis). Method Analysis of medical records and adverse events of 168 patients undergoing infliximab infusion for psoriasis and chronic inflammatory diseases treatment. Results 168 patients who have used infliximab were evaluated, 24 had psoriasis and 144 had chronic inflammatory diseases. Only 2 (8.3%) patients with psoriasis showed adverse events requiring treatment discontinuation, and just 6 (4.2%) female patients with chronic inflammatory diseases experienced adverse events. Conclusion Infliximab is a safe drug, with a low percentage of adverse events and there were more adverse events in women with chronic inflammatory diseases and in patients who received more infliximab infusions. PMID:27438197

  20. 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

  1. 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

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

    PubMed

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

    2015-05-01

    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

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

    PubMed

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

    2015-05-01

    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.

  4. Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

    PubMed

    Rüddel, J; Schleenvoigt, B T; Schüler, E; Schmidt, C; Pletz, M W; Stallmach, A

    2016-09-01

    We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature.

  5. Yellow fever vaccination during treatment with infliximab in a patient with ulcerative colitis: A case report.

    PubMed

    Rüddel, J; Schleenvoigt, B T; Schüler, E; Schmidt, C; Pletz, M W; Stallmach, A

    2016-09-01

    We report the case of a 59-year-old patient who accidentally underwent live vaccination against yellow fever during continuous treatment with the TNF-α-antibody (AB) infliximab for ulcerative colitis. The clinical course showed fever of short duration and elevation of liver enzymes without further clinical complications. Yellow fever viremia was not detectable and protective antibodies were developed. A primary vaccination against yellow fever under infliximab has not been reported in the literature before, although vaccination is an important topic in IBD. Live vaccinations, like Stamaril(®) against yellow fever, are contraindicated during TNF-α-AB treatment. Treatment regimens containing TNF-α-AB are of growing importance, not only in gastroenterology, but also in rheumatology and dermatology. We discuss this topic by presenting our case and reviewing the current literature. PMID:27612222

  6. Long-term outcome of infliximab combined with surgery for perianal fistulizing Crohn's disease

    PubMed Central

    Yang, Bo-Lin; Chen, Yu-Gen; Gu, Yun-Fei; Chen, Hong-Jin; Sun, Gui-Dong; Zhu, Ping; Shao, Wan-Jin

    2015-01-01

    AIM: To evaluate the efficacy and long-term outcome of infliximab combined with surgery to treat perianal fistulizing Crohn’s disease (CD). METHODS: The work was performed as a prospective study. All patients received infliximab combined with surgery to treat perianal fistulizing CD, which was followed by an immunosuppressive agent as maintenance therapy. RESULTS: A total of 28 patients with perianal fistulizing CD were included. At week 30, 89.3% (25/28) of the patients were clinically cured with an average healing time of 31.4 d. The CD activity index decreased to 70.07 ± 77.54 from 205.47 ± 111.13 (P < 0.01) after infliximab treatment. The perianal CD activity index was decreased to 0.93 ± 2.08 from 8.54 ± 4.89 (P < 0.01). C-reactive protein, erythrocyte sedimentation rate, platelets, and neutrophils all decreased significantly compared with the pretreatment levels (P < 0.01). Magnetic resonance imaging results for 16 patients after therapy showed that one patient had a persistent presacral-rectal fistula and another still had a cavity without clinical symptoms at follow-up. After a median follow-up of 26.4 mo (range: 14-41 mo), 96.4% (27/28) of the patients had a clinical cure. CONCLUSION: Infliximab combined with surgery is effective and safe in the treatment of perianal fistulizing CD, and this treatment was associated with better long-term outcomes. PMID:25741157

  7. 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

  8. Adalimumab Treatment in Pediatric-Onset Crohn's Disease Patients after Infliximab Failure: A Single Center Study

    PubMed Central

    Song, Won Jae; Kang, Ben; Choi, So Yoon

    2016-01-01

    Purpose We aimed to investigate the efficacy and safety of adalimumab in pediatric-onset Crohn's disease patients who had failed treatment with infliximab. Methods In this retrospective study, patients included were those who had been diagnosed with Crohn's disease before 18 years old, and had received treatment with adalimumab after infliximab failure. The efficacy of adalimumab treatment was investigated at 1 month and 1 year, and adverse events that had occurred during treatment with adalimumab were explored. Results Ten patients were included in this study. The median duration from diagnosis to adalimumab treatment was 5.5 years (range: 2.4-7.9 years). At 1 month after adalimumab initiation, 80% (8/10) of patients showed clinical response, and 40% (4/10) achieved clinical remission. At 1 year, 71% (5/7) of patients showed clinical response, and 43% (3/7) were under clinical remission. Among the total included patients, 5 patients (50%) showed clinical response at 1 year. Primary non-response to adalimumab was observed in 2 patients (20%), and secondary failure to adalimumab was observed in 3 patients (30%) during 1 year treatment with adalimumab. No serious adverse event had occurred during adalimumab treatment. Conclusion Adalimumab was effective for 1 year without serious adverse events in half of pediatric-onset Crohn's disease patients who had failed treatment with infliximab. PMID:27437188

  9. 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.

  10. 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

  11. Treatment of psoriasis: focus on clinic-based management with infliximab.

    PubMed

    de Eusebio, Esther; Armario-Hita, José Carlos; de Miquel, Víctor Alegre

    2014-02-01

    Psoriasis is a disabling chronic inflammatory condition of the skin and joints that typically requires long-term treatment. Recommended treatments for psoriasis include a wide range of topical and systemic options, from topical agents and targeted phototherapy for mild psoriasis to traditional systemic agents such as methotrexate, cyclosporine and acitretin for more serious disease. The introduction of targeted biological agents such as T-cell-modulating agents, tumor necrosis factor α (TNFα) antagonists and interleukin (IL)-12 and IL-23 inhibitors has provided new choices for the management of psoriasis and psoriatic arthritis that may offer better long-term efficacy and tolerability than traditional approaches. Most biological agents are administered by subcutaneous injection. Infliximab, a TNFα antagonist, is the only biological agent approved for psoriasis that is administered by intravenous infusion, in the setting of hospital-based or specialized infusion center-based clinics. Infliximab allows weight-based dosing and may offer more rapid disease control than other biological agents, with significant improvements seen as early as 1 week after treatment initiation. This article gives an overview of psoriasis management, focusing on clinic-based infusion therapy with infliximab.

  12. Transcriptional Signatures Related to Glucose and Lipid Metabolism Predict Treatment Response to the Tumor Necrosis Factor Antagonist Infliximab in Patients with Treatment-Resistant Depression

    PubMed Central

    Mehta, Divya; Raison, Charles L.; Woolwine, Bobbi J.; Haroon, Ebrahim; Binder, Elisabeth B.; Miller, Andrew H.; Felger, Jennifer C.

    2013-01-01

    The tumor necrosis factor (TNF) antagonist infliximab was recently found to reduce depressive symptoms in patients with increased baseline inflammation as reflected by a plasma C-reactive protein concentration >5mg/L. To further explore predictors and targets of response to infliximab, differential gene expression was examined in peripheral blood mononuclear cells from infliximab responders (n=13) versus non-responders (n=14) compared to placebo at baseline and 6hr, 24hr, and 2 weeks after the first infliximab infusion. Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2 fold, adjusted p≤0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis. Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time in infliximab responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6hr and 24hr after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. PMID:23624296

  13. 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

  14. 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

  15. Antiphospholipid antibodies during 6-month treatment with infliximab: A preliminary report

    PubMed Central

    Kolarz, Bogdan; Majdan, Maria; Darmochwał-Kolarz, Dorota A.; Dryglewska, Magdalena

    2014-01-01

    Background The introduction of tumor necrosis factor (TNF) antagonists (adalimumab, infliximab, and etanercept) was a major advance and was highly important and beneficial in most rheumatoid arthritis (RA) patients. The adverse effects of this treatment are infrequent, but include opportunistic intracellular infection (especially the reactivation of latent Mycobacterium tuberculosis); exacerbation of demyelinating disorders; and the production of various types of antibodies such as antinuclear antibodies (ANA) or double-stranded DNA autoantibodies (dsDNA) and antiphospholipid antibodies (aPL) such as anti-cardiolipin antibodies (aCL) and anti-B2GP-I antibodies (B2GP-I). The aim of the study was to determine the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Material/Methods We determined the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Results We observed a statistically important increase only in the group of B2GP-I IgM (p<0.05). There are contradictory results concerning the ability of infliximab to induce aPL, but most authors confirm this phenomenon. Conclusions Further investigations are needed to determine if the new aPL appears in patients with β2-GPI gene polymorphisms such as leucine-to-valine substitution at position 247, which can lead to a conformational changes in β2-GPI protein, leading to aPL synthesis. The role of aPL in pathogenesis of APS is still unclear, but we should remember the immunogenic aspect of TNF antagonist treatment. Therefore, we recommend early detection of aPL and observation of the patient, paying special attention to signs and symptoms of thromboembolism. PMID:25027437

  16. The role of endoscopic assessment in ulcerative colitis in the era of infliximab.

    PubMed

    Daperno, M; Sostegni, R; Pera, A; Rognone, D; Rigazio, C; Ercole, E; Crocellà, L; Lavagna, A; Rocca, R

    2008-07-01

    Endoscopic evaluation of mucosal appearance is important for the clinical management of ulcerative colitis patients, as it offers valuable prognostic tools and data useful to change the management and treatment strategies. In the field of severe ulcerative colitis, partial endoscopy and bioptic sampling allows to obtain additional and relevant prognostic information: if severe endoscopic lesions are present, response to standard treatment is less likely, and if CMV superinfection is detected, anti-viral treatment should be added to conventional treatments. When clinical remission is obtained with conventional treatments, distal colonoscopy may add valuable data: the occurrence of complete endoscopic healing is a major predictor of long-term remission with no clinical activity. Finally, biologic treatments, and mainly infliximab, were shown to induce remarkable and significant mucosal healing also in ulcerative colitis, and patients with complete endoscopic healing in response to infliximab were shown to be more likely to experience fewer clinical relapses during the follow-up. Therefore endoscopic evaluation has to be considered a major prognostic marker in ulcerative colitis. In this review data from the Literature supporting this role will be reviewed. PMID:18598992

  17. Peripheral blood derived gene panels predict response to infliximab in rheumatoid arthritis and Crohn's disease

    PubMed Central

    2013-01-01

    Background Biological therapies have been introduced for the treatment of chronic inflammatory diseases including rheumatoid arthritis (RA) and Crohn's disease (CD). The efficacy of biologics differs from patient to patient. Moreover these therapies are rather expensive, therefore treatment of primary non-responders should be avoided. Method We addressed this issue by combining gene expression profiling and biostatistical approaches. We performed peripheral blood global gene expression profiling in order to filter the genome for target genes in cohorts of 20 CD and 19 RA patients. Then RT-quantitative PCR validation was performed, followed by multivariate analyses of genes in independent cohorts of 20 CD and 15 RA patients, in order to identify sets ofinterrelated genes that can separate responders from non-responders to the humanized chimeric anti-TNFalpha antibody infliximab at baseline. Results Gene panels separating responders from non-responders were identified using leave-one-out cross-validation test, and a pool of genes that should be tested on larger cohorts was created in both conditions. Conclusions Our data show that peripheral blood gene expression profiles are suitable for determining gene panels with high discriminatory power to differentiate responders from non-responders in infliximab therapy at baseline in CD and RA, which could be cross-validated successfully. Biostatistical analysis of peripheral blood gene expression data leads to the identification of gene panels that can help predict responsiveness of therapy and support the clinical decision-making process. PMID:23809696

  18. Pharmacology and metabolism of infliximab biosimilars - A new treatment option in inflammatory bowel diseases.

    PubMed

    Włodarczyk, Marcin; Fichna, Jakub; Sobolewska-Włodarczyk, Aleksandra

    2016-08-01

    Biological therapy with monoclonal antibodies to tumor necrosis factor alpha (TNF-α) was shown in large clinical trials to be effective in inducing and maintaining clinical remission in patients with moderate to severe Crohn's disease (CD) and ulcerative colitis (UC). Infliximab, the first anti-TNF-α biologic drug, has significantly improved inflammatory bowel disease (IBD) treatment outcomes by preventing structural damage progression, thereby reducing complications and the need for surgery and hospitalization. The major concern associated with the use of biologics is their high cost. However, as these therapies lose patent protection, cheaper biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13. Position statements from several scientific societies and some experts in their reviews have expressed concerns to the concept of extrapolation without direct IBD clinical evidence, whereas European Medicines Agency (EMA) experts have supported extrapolation. In this review, we focus on the pharmacokinetics, pharmacodynamics properties and comparative effectiveness of anti-TNF-α biosimilars, related to their use in IBD. PMID:27162107

  19. Infliximab enhances the therapeutic effects of 5-fluorouracil resulting in tumor regression in colon cancer

    PubMed Central

    Liu, Fen; Ai, Feiyan; Tian, Li; Liu, Shaojun; Zhao, Lian; Wang, Xiaoyan

    2016-01-01

    Colon cancer (CC) is among the most common malignant diseases with a dismal survival. Tumor necrosis factor-alpha (TNF-α) has been identified as a therapeutic target in various cancers, and anti-TNF-α treatment has shown promising effects in different cancer models. However, if TNF-α can be targeted in CC, the therapeutic values of anti-TNF-α treatment in CC remain unknown. Our study indicated that TNF-α is highly expressed in CC cell lines and patient tumor samples. High expression of TNF-α is an independent adverse prognosticator of CC. Targeting the TNF-α by its antibody infliximab induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity and enhanced apoptosis leading to cell death. The combination of infliximab with 5-fluorouracil showed better responses in vitro and in vivo than 5-fluorouracil alone. In conclusion, this study identified TNF-α as a target of CC and anti-TNF-α treatment synergized with chemotherapy leading to a better outcome in preclinical models. PMID:27757041

  20. Development and validation of a homogeneous mobility shift assay for the measurement of infliximab and antibodies-to-infliximab levels in patient serum.

    PubMed

    Wang, Shui-Long; Ohrmund, Linda; Hauenstein, Scott; Salbato, Jared; Reddy, Rukmini; Monk, Patrick; Lockton, Steven; Ling, Nicholas; Singh, Sharat

    2012-08-31

    Antibody-based drugs such as infliximab (IFX) are effective for the treatment of inflammatory bowel disease (IBD) and other immune-mediated disorders. The development of antibodies against these drugs may result in unfavorable consequences, including the loss of drug efficacy, hypersensitivity reactions, and other adverse events. Therefore, accurate monitoring of serum drug and anti-drug antibody levels should be an important part of therapy for patients being treated with an antibody-based drug. Current methods for the assessment of anti-drug antibodies and drug levels, involving various bridging ELISA and radioimmunoassay techniques, are limited by their sensitivity, interference, and/or complexity. To overcome these limitations, we have developed a non-radiolabeled homogeneous mobility shift assay (HMSA) to measure the antibodies-to-infliximab (ATI) and IFX levels in serum samples. Full method validation was performed on both the ATI- and IFX-HMSA, and the clinical sample test results were also compared with those obtained from a bridging ELISA method to evaluate the difference in performance between the two assays. Validation of the ATI-HMSA revealed a lower limit of quantitation of 0.012 μg/mL in serum. The linear range of quantitation was 0.029-0.54 μg/mL. The intra- and inter-assay precision was less than 20% of coefficient of variation (CV), and the accuracy (% error) of the assay was less than 20%. In serum samples, ATI as low as 0.036 μg/mL can be measured, even in the presence of 60 μg/mL of IFX in the serum. Sera from 100 healthy subjects were tested to determine the cut point of the assay. ATI-positive samples that had been previously analyzed by using a bridging ELISA from 100 patients were also measured by the new method. There was a high correlation between the two methods for ATI levels (p<0.001). Significantly, the new method identified five false-positive samples from the bridging ELISA method. Validation of the mobility shift IFX assay also

  1. 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.

  2. Infliximab has no apparent effect in the inner ear hearing function of patients with rheumatoid arthritis and ankylosing spondylitis.

    PubMed

    Toktas, H; Okur, E; Dundar, U; Dikici, A; Kahveci, O K

    2014-01-01

    Animal studies suggest that tumor necrosis factor (TNF) alpha blockers may pass to the inner ear in adequate concentration. In this prospective study, we aimed to evaluate the effect of infliximab on the inner ear hearing function in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA). The patients with high disease activity, who were planned to begin infliximab for therapy by physical medicine and rehabilitation department, were referred to ear-nose-throat clinic for consultation. After physical and otoscopic examination, audiological tests were performed. Air conduction thresholds between 250 and 8,000 Hz, bone conduction thresholds between 500 and 4,000 Hz, pure tone average, speech discrimination scores, distortion product otoacoustic emission (DPOAE) were used to evaluate the hearing function. The tests were repeated 2 and 6 months after the initiation of the drug "infliximab." A total of 44 ears of 22 patients (17 males and 5 females) were evaluated. Fifteen patients had a diagnosis of AS, and seven patients had RA. After initiation of infliximab therapy, statistically significant improvement was observed in disease activity scores [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for AS, Disease Activity Score 28 (DAS-28) for RA] after 2 and 6 months (p < 0.05). We did not find any statistically significant difference between the air conduction thresholds, bone conduction thresholds, pure tone average, speech discrimination scores, and measurements of DPOAE before the initiation of treatment and after 2 and 6 months (p > 0.05). Any problem about the balance, vertigo, or dizziness was not reported from the patients during the treatment period. As a result, our study showed that there was no notable change or deterioration in the hearing function of the patients with AS and RA who were treated with infliximab. Further studies with higher number of patients with AS and RA and also with different TNF alpha inhibitors are

  3. Autoantibody profile in rheumatoid arthritis during long-term infliximab treatment

    PubMed Central

    Bobbio-Pallavicini, Francesca; Alpini, Claudia; Caporali, Roberto; Avalle, Stefano; Bugatti, Serena; Montecucco, Carlomaurizio

    2004-01-01

    The aim of the present study was to investigate the effect of long-term infliximab treatment on various autoantibodies in patients with rheumatoid arthritis. Serum samples from 30 consecutive patients, who were prospectively followed during infliximab and methotrexate therapy for refractory rheumatoid arthritis, were tested at baseline and after 30, 54 and 78 weeks. At these points, median values of the Disease Activity Score were 6.38 (interquartile range 5.30–6.75), 3.69 (2.67–4.62), 2.9 (2.39–4.65) and 3.71 (2.62–5.06), respectively. Various autoantibodies were assessed by standard indirect immunofluorescence and/or ELISA. Initially, 50% of patients were positive for antinuclear antibodies, and this figure increased to 80% after 78 weeks (P = 0.029). A less marked, similar increase was found for IgG and IgM anticardiolipin antibody titre, whereas the frequency of anti-double-stranded DNA antibodies (by ELISA) exhibited a transient rise (up to 16.7%) at 54 weeks and dropped to 0% at 78 weeks. Antibodies to proteinase-3 and myeloperoxidase were not detected. The proportion of patients who were positive for rheumatoid factor (RF) was similar at baseline and at 78 weeks (87% and 80%, respectively). However, the median RF titre exhibited a progressive reduction from 128 IU/ml (interquartile range 47–290 IU/ml) to 53 IU/ml (18–106 IU/ml). Anti-cyclic citrullinated peptide (CCP) antibodies were found in 83% of patients before therapy; anti-CCP antibody titre significantly decreased at 30 weeks but returned to baseline thereafter. In conclusion, the presence of anti-double-stranded DNA antibodies is a transient phenomenon, despite a stable increase in antinuclear and anticardiolipin antibodies. Also, the evolution of RF titres and that of anti-CCP antibody titres differed during long-term infliximab therapy. PMID:15142273

  4. 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.

  5. Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate.

    PubMed

    Ekenberg, Christina; Friis-Møller, Nina; Ulstrup, Thomas; Aalykke, Claus

    2016-01-01

    We present a case of a 56-year-old woman with Crohn's disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated in patients treated with immunosuppressive drugs. Following vaccination, the patient fell ill with influenza-like illness. Elevated transaminase levels and YF viremia were detected. Despite being immunocompromised, the patient did not develop more severe adverse effects. Neutralising antibodies to YF virus were detected on day 14 following vaccination and remained protective at least 10 months after vaccination. Limited data is available on outcomes of YFV in patients receiving immunosuppressive therapy, including biologics, and we report this case as a reminder of vigilance of vaccine recommendations in this population.

  6. Inadvertent yellow fever vaccination of a patient with Crohn's disease treated with infliximab and methotrexate.

    PubMed

    Ekenberg, Christina; Friis-Møller, Nina; Ulstrup, Thomas; Aalykke, Claus

    2016-01-01

    We present a case of a 56-year-old woman with Crohn's disease, treated with methotrexate and infliximab, who inadvertently received yellow fever vaccination (YFV) prior to a journey to Tanzania. She was not previously vaccinated against YF. YFV contains live-attenuated virus, and is contraindicated in patients treated with immunosuppressive drugs. Following vaccination, the patient fell ill with influenza-like illness. Elevated transaminase levels and YF viremia were detected. Despite being immunocompromised, the patient did not develop more severe adverse effects. Neutralising antibodies to YF virus were detected on day 14 following vaccination and remained protective at least 10 months after vaccination. Limited data is available on outcomes of YFV in patients receiving immunosuppressive therapy, including biologics, and we report this case as a reminder of vigilance of vaccine recommendations in this population. PMID:27571912

  7. B-Cell Dysregulation in Crohn's Disease Is Partially Restored with Infliximab Therapy

    PubMed Central

    Timmermans, Wilhelmina M. C.; van Laar, Jan A. M.; van der Houwen, Tim B.; Kamphuis, Lieke S. J.; Bartol, Sophinus J. W.; Lam, King H.; Ouwendijk, Rob J.; Sparrow, Miles P.; Gibson, Peter R.; van Hagen, P. Martin

    2016-01-01

    Background B-cell depletion can improve a variety of chronic inflammatory diseases, but does not appear beneficial for patients with Crohn’s disease. Objective To elucidate the involvement of B cells in Crohn’s disease, we here performed an ‘in depth’ analysis of intestinal and blood B-cells in this chronic inflammatory disease. Methods Patients with Crohn’s disease were recruited to study B-cell infiltrates in intestinal biopsies (n = 5), serum immunoglobulin levels and the phenotype and molecular characteristics of blood B-cell subsets (n = 21). The effects of infliximab treatment were studied in 9 patients. Results Granulomatous tissue showed infiltrates of B lymphocytes rather than Ig-secreting plasma cells. Circulating transitional B cells and CD21low B cells were elevated. IgM memory B cells were reduced and natural effector cells showed decreased replication histories and somatic hypermutation (SHM) levels. In contrast, IgG and IgA memory B cells were normally present and their Ig gene transcripts carried increased SHM levels. The numbers of transitional and natural effector cells were normal in patients who responded clinically well to infliximab. Conclusions B cells in patients with Crohn’s disease showed signs of chronic stimulation with localization to granulomatous tissue and increased molecular maturation of IgA and IgG. Therapy with TNFα-blockers restored the defect in IgM memory B-cell generation and normalized transitional B-cell levels, making these subsets candidate markers for treatment monitoring. Together, these results suggest a chronic, aberrant B-cell response in patients with Crohn’s disease, which could be targeted with new therapeutics that specifically regulate B-cell function. PMID:27468085

  8. Herpetic Keratouveitis and Trabeculectomy Failure during Infliximab Therapy in a Patient with Behçet’s Disease

    PubMed Central

    Gür Güngör, Sirel; Asena, Leyla; Akman, Ahmet; Gökmen, Onur

    2016-01-01

    A 51-year-old man was diagnosed with Behçet’s disease in 2001. The patient was resistant to all immunosuppressive therapies. After 6 months of infliximab therapy, he presented to our clinic with pain and blurred vision in his right eye. The visual acuity was 20/200 and the intraocular pressure was 35 mmHg in the right eye. Biomicroscopic examination revealed corneal dendritic ulcers and 2+ cells in the anterior chamber in the right eye. The herpetic keratouveitis attack was controlled with antiviral therapy but the patient needed another glaucoma surgery. Trabeculectomy with mitomycin C was performed about halfway through an eight-week interval between two doses of infliximab. PMID:27800267

  9. Infliximab, Infliximab-dyyb Injection

    MedlinePlus

    ... doctor if you have ever been treated with phototherapy (a treatment for psoriasis that involves exposing the skin to ultraviolet light) and if you have or have ever had a disease that affects your nervous system, such as multiple sclerosis (MS; ...

  10. 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

  11. 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.

  12. Combined infliximab and methotrexate treatment improves the depressive state in rheumatoid arthritis patients more effectively than methotrexate alone

    PubMed Central

    Miwa, Yusuke; Nishimi, Airi; Nishimi, Shinichiro; Saito, Mayu; Tokunaga, Takahiro; Yanai, Ryo; Takahashi, Ryo; Wakabayashi, Kuninobu; Kasama, Tsuyoshi; Hosaka, Michio

    2014-01-01

    Objective Rheumatoid arthritis (RA) patients have a greater depressive tendency than normal subjects, and infliximab is known to provide quick therapeutic effects and to have high bioavailability for RA. We therefore investigated whether the depressive state of RA patients would be improved by infliximab. Material and Methods The Self-Rating Depression Scale (SDS) was used to evaluate 34 RA patients before and 14 or 30 weeks after inflixi mab treatment using the SDS and Disease Activity Score (DAS) 28. The SDS and DAS28 results before and after treatment were compared. Results We also included 42 cases treated with methotrexate as the control group. The SDS decreased in both groups, and the intraindividual vari ability was p<0.001, indicating that the drugs had significantly different effects on the SDS. The DAS tended to decrease in both groups, but the intraindividual variability was p=0.199, indicating no difference between the two drugs. Conclusion This study is a preliminary study, but the data suggest that infliximab may reduce RA disease activity and improve the depressive state.

  13. Metabolic profiling of human CD4+ cells following treatment with methotrexate and anti-TNF-α infliximab

    PubMed Central

    Chimenti, Maria Sole; Tucci, Paola; Candi, Eleonora; Perricone, Roberto; Melino, Gerry; Willis, Anne E

    2013-01-01

    The autoimmune process in rheumatoid arthritis depends on activation of immune cells, which utilize intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. CD4+ T cells comprise a large proportion of the inflammatory cells that invade the synovial tissue and may therefore be a cell type of pathogenic importance. Both methotrexate and infliximab are effective in the treatment of inflammatory arthritis; however, the biological effects triggered by these treatments and the biochemical mechanisms underlining the cell response are still not fully understood. Thus, in this study the global metabolic changes associated with methotrexate or infliximab treatment of isolated human CD4+ T cells were examined using gas chromatography/mass spectrometry or liquid chromatography/mass spectrometry. In total 148 metabolites involved in selective pathways were found to be significantly altered. Overall, the changes observed are likely to reflect the effort of CD4+ cells to increase the production of cellular reducing power to offset the cellular stress exerted by treatment. Importantly, analysis of the global metabolic changes associated with MTX or infliximab treatment of isolated human CD4+ T cells suggested that the toxicity associated with these agents is minimal when used at clinically relevant concentrations. PMID:23974102

  14. Open‐label, pilot protocol of patients with rheumatoid arthritis who switch to infliximab after an incomplete response to etanercept: the opposite study

    PubMed Central

    Furst, Daniel E; Gaylis, Norman; Bray, Vance; Olech, Ewa; Yocum, David; Ritter, Jeffrey; Weisman, Michael; Wallace, Daniel J; Crues, John; Khanna, Dinesh; Eckel, Gregory; Yeilding, Newman; Callegari, Peter; Visvanathan, Sudha; Rojas, Jeannie; Hegedus, Ronald; George, Laura; Mamun, Khalid; Gilmer, Keith; Troum, Orrin

    2007-01-01

    Objective To incorporate a new trial design to examine clinical response, cytokine expression and joint imaging in patients with rheumatoid arthritis (RA) switching from etanercept to infliximab treatment. Methods A randomised, open‐label, clinical trial of 28 patients with an inadequate response to etanercept was conducted. Eligible patients received background methotrexate and were randomised 1:1 to discontinue etanercept and receive infliximab 3 mg/kg at weeks 0, 2, 6, 14 and 22, or to continue etanercept 25 mg twice weekly. Data were analysed for clinical response, serum biomarker levels, radiographic progression, MRI and adverse events. Results At week 16, 62% of infliximab‐treated patients achieved American College of Rheumatology 20% criteria for improvement in RA (ACR20) responses compared with 29% of etanercept‐treated patients. A 30.8% decrease from baseline in Disease Activity Score 28 was observed in patients receiving infliximab, compared with a 16.0% decrease in patients receiving etanercept. ACR20 and American College of Rheumatology 50% criteria for improvement in RA responses correlated at least minimally with intracellular adhesion molecule‐1 and interleukin 8 in patients receiving infliximab. 38% of patients who were switched to infliximab showed reductions in Health Assessment Questionnaire scores (>0.4), compared with 0% of patients receiving etanercept. MRI analyses were inconclusive. Both drugs were well tolerated; 54% of infliximab‐treated patients and 50% of etanercept‐treated patients reported adverse events. Conclusions In this exploratory, open‐label trial (with single‐blind evaluator), patients were randomised to continue with etanercept or switch to infliximab. The small sample size of this hypothesis‐generating study was underpowered to show statistical differences between groups. There was a numerical trend favouring patients who switched to infliximab, therefore warranting further study with a more rigorous

  15. Infliximab ameliorating depression-like behavior through inhibiting the activation of the IDO-HAAO pathway mediated by tumor necrosis factor-α in a rat model.

    PubMed

    Fu, Xiao-Yan; Li, Hai-Yan; Jiang, Qing-Song; Cui, Ting; Jiang, Xin-Hui; Zhou, Qi-Xin; Qiu, Hong-Mei

    2016-09-01

    In recent years, some studies have suggested that the activation of inflammatory system plays a role in the occurrence of depression. Tumor necrosis factor-α (TNF-α), as one of the preinflammatory cytokines, has been reported to be involved in the occurrence of various diseases including depression. Infliximab, an antagonist of TNF-α, is usually used to treat some autoimmune diseases such as Crohn's disease and can perhaps be used to treat other diseases. In this study, the antidepressant effect and a possible mechanism of infliximab were investigated by studying the depression-like behavior and expression of TNF-α, indoleamine 2, 3-dioxygenase (IDO), and 3-hydroxyl amino acid oxygenase (HAAO) from the cortex and hippocampus in rat exposed to chronic unpredicted stress. Forty male Sprague-Dawley rats were divided into a control group (CG), an infliximab-treated control group, a model group (MG), and an infliximab-treated model group (IFXM). Infliximab (5 mg/kg once week) was administered to the infliximab-treated control group and IFXM rats by an intraperitoneal injection, whereas an equivalent volume of vehicle was administered to CG and MG rats. Rat behaviors and the expression of TNF-α, IDO, and HAAO in the cortex and hippocampus were determined. It was found that a significant relief in depression-like behaviors was observed with a downregulation of TNF-α, IDO, and HAAO expression in the IFXM rats compared with MG rats. The results show the antidepressant effect of infliximab and suggest that its mechanism is partly related to inhibition of IDO-HAAO pathway activation mediated by TNF-α in rat brain.

  16. Acute and long-term effect of infliximab on humoral and echocardiographic parameters in patients with chronic inflammatory diseases.

    PubMed

    Tomáš, L'ubomír; Lazúrová, Ivica; Pundová, Lýdia; Oetterová, Mária; Zakuciová, Mária; Petrášová, Darina; Studenčan, Martin

    2013-01-01

    Tumor necrosis factor alpha (TNF-alpha) plays an important role in the pathogenesis of chronic inflammatory diseases, i.e., rheumatoid arthritis (RA), ankylosing spondylitis (AS), Crohn's disease (CD), and ulcerative colitis (UC). Anti-TNF-alpha strategies are successfully used in their treatment. However, their effect on heart function is still uncertain. The objectives of the study were to examine the acute and long-term effect of infliximab on the heart morphology and function in patients with chronic inflammatory disorders. Thirty-one patients (21 men and 10 women) were included. Ten percent of them were diagnosed with RA, 22.5 % with AS, 22.5 % with CD, and 45 % with UC, respectively. N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) was measured before and immediately after infliximab administration at the beginning of the study and in the sixth and 12th months. Echocardiography was performed at baseline and in the sixth and 12th months. There was a significant increase in NT-proBNP after the first infliximab infusion (88.40 ± 14.09 vs. 95.24 ± 14.28 pg/ml, p = 0.0046) and similar response was detected after each infusion in the sixth and 12th months. Plasma NT-proBNP slightly but not significantly decreased (88.40 ± 14.09 vs. 81.74 ± 23.14 pg/ml, p = 0.583, and 88.40 ± 14.09 vs. 56.83 ± 17.77 pg/ml, p = 0.0576, in the sixth and 12th months, respectively). There were no significant changes in echocardiographic structural and functional parameters of the left ventricle during follow-up. Plasma NT-proBNP mildly but significantly increases immediately after infliximab infusion. However, long-term infliximab administration does not deteriorate both cardiac morphology and function. PMID:23010850

  17. 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

  18. A Case of Severe Panuveitis Associated with Psoriasis Vulgaris Successfully Treated with Infliximab

    PubMed Central

    Sakurai, Yuri; Namba, Kenichi; Mizuuchi, Kazuomi; Nomura, Toshihumi; Ishida, Susumu

    2016-01-01

    Purpose Uveitis associated with psoriasis vulgaris is usually seen as an anterior segment inflammation, and it is very rare that the inflammation extends to the posterior segment. We herein report a case of severe panuveitis associated with psoriasis vulgaris presenting as retinal neovascularization, leading to vitreous hemorrhages that were successfully treated with infliximab (IFX). Case Report A 27-year-old male with psoriasis vulgaris was referred to our hospital due to prolonged severe uveitis OU. He showed a severe anterior chamber inflammation with fibrin formation and total posterior iris synechia OU. With topical corticosteroid treatment, these conditions were relieved for a short time; however, the intraocular inflammation was exacerbated with vitreous hemorrhages caused by retinal neovascularization OS. After the administration of IFX therapy, the intraocular inflammation and retinal neovascularization was resolved, and so far, no severe recurrences have been seen for 3 years with the therapy. Conclusion When we see patients with severe panuveitis associated with psoriasis extending to the posterior segment, IFX treatment may be a good therapeutic option. PMID:27239187

  19. Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

    PubMed Central

    Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

    2015-01-01

    This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

  20. 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.

  1. Clinical experience with infliximab biosimilar Remsima (CT-P13) in inflammatory bowel disease patients.

    PubMed

    Jahnsen, Jørgen

    2016-05-01

    Many reference biological therapies have now reached or are near to patent expiry, and therefore a number of biosimilars have been or will be developed. The term biosimilar can be defined as a biotherapeutic product that is similar in efficacy, safety and quality to the licensed reference product. Biosimilars may lead to a reduced price and significant cost savings for the health community and hopefully more patients globally will have easier access to biological therapy when indicated. CT-P13, which is a TNF-alfa inhibitor, is the first monoclonal antibody biosimilar being used in clinical practice. The drug is approved for all indications as an innovator product although clinical efficacy has only been demonstrated in rheumatic diseases. Until now the number of patients with inflammatory bowel disease (IBD) treated with CT-P13 is confined, but experience is continuously growing. Based on current data, CT-P13 seems to be efficacious and generally well tolerated in IBD especially in patients who are naïve to biological therapy. Knowledge with regard to interchangeability between CT-P13 and the originator infliximab is however, still rather sparse and more data are desired. Immunogenicity and long-term safety related to CT-P13 are other areas of great importance and good and reliable postmarketing pharmacovigilance is therefore required in the coming years. PMID:27134662

  2. 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.

  3. 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.

  4. Cost-effectiveness of adalimumab, infliximab or vedolizumab as first-line biological therapy in moderate-to-severe ulcerative colitis

    PubMed Central

    Yokomizo, Lauren; Limketkai, Berkeley; Park, K T

    2016-01-01

    Background There are no head-to-head randomised controlled trials (RCTs) comparing the effectiveness of biologics in ulcerative colitis (UC). We aimed to assess the cost-effectiveness of adalimumab, infliximab and vedolizumab as first-line agents to induce clinical remission and mucosal healing (MH) in UC. Methods We constructed a decision tree based on a payer's perspective in the USA to estimate the first year costs of adalimumab, infliximab or vedolizumab to achieve clinical remission and MH in patients with moderate-to-severe UC. Transition probabilities were derived from ACT, ULTRA and GEMINI RCT data. Costs were derived from Medicare reimbursement rates and wholesale drug prices. Results Assuming a biological-naïve cohort, infliximab 5 mg/kg every 8 weeks was more cost-effective ($99 171 per MH achieved) than adalimumab 40 mg every other week ($316 378 per MH achieved) and vedolizumab every 8 weeks ($301 969 per MH achieved) at 1 year. Non-drug administration cost of infliximab exceeding $1974 per infusion would make adalimumab more cost-effective. First-line UC therapy with vedolizumab would be cost-effective if the drug acquisition price was <$2537 for each 300 mg administration during the 1-year time horizon. Conclusions If non-drug costs of infliximab administration are not excessive (<$2000), infliximab is the most cost-effective first-line biologic for moderate-to-severe UC. Exceeding this threshold infusion-related cost would make adalimumab the more cost-effective therapy. Considering its drug costs in the USA, vedolizumab appears to be appropriately used as a second-line biologic after antitumour necrosis factor failure. PMID:27195130

  5. Independent Candidate Serum Protein Biomarkers of Response to Adalimumab and to Infliximab in Rheumatoid Arthritis: An Exploratory Study

    PubMed Central

    Ortea, Ignacio; Roschitzki, Bernd; López-Rodríguez, Rosario; Tomero, Eva G.; Ovalles, Juan G.; López-Longo, Javier; de la Torre, Inmaculada; González-Alvaro, Isidoro; Gómez-Reino, Juan J.; González, Antonio

    2016-01-01

    Response to treatment of rheumatoid arthritis shows large inter-individual variability. This heterogeneity is observed with all the anti-rheumatic drugs, including the commonly used TNF inhibitors. It seems that drug-specific and target-specific factors lead individual patients to respond or not to a given drug, although this point has been challenged. The search of biomarkers distinguishing responders from non-responders has included shotgun proteomics of serum, as a previous study of response to infliximab, an anti-TNF antibody. Here, we have used the same study design and technology to search biomarkers of response to a different anti-TNF antibody, adalimumab, and we have compared the results obtained for the two anti-TNF drugs. Search of biomarkers of response to adalimumab included depletion of the most abundant serum proteins, 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) labeling, two-dimensional liquid chromatography fractionation and relative quantification with a hybrid Orbitrap mass spectrometer. With this approach, 264 proteins were identified in all the samples with at least 2 peptides and 95% confidence. Nine proteins showed differences between non-responders and responders (P < 0.05), representing putative biomarkers of response to adalimumab. These results were compared with the previous study of infliximab. Surprisingly, the non-responder/responder differences in the two studies were not correlated (rs = 0.07; P = 0.40). This overall independence with all the proteins showed two identifiable components. On one side, the putative biomarkers of response to either adalimumab or infliximab, which were not shared and showed an inverse correlation (rs = -0.69; P = 0.0023). On the other, eight proteins showing significant non-responder/responder differences in the analysis combining data of response to the two drugs. These results identify new putative biomarkers of response to treatment of rheumatoid arthritis and indicate that they

  6. Effects of a 6-month infliximab treatment on plasma levels of leptin and adiponectin in patients with rheumatoid arthritis.

    PubMed

    Derdemezis, Christos S; Filippatos, Theodosios D; Voulgari, Paraskevi V; Tselepis, Alexandros D; Drosos, Alexandros A; Kiortsis, Dimitrios N

    2009-10-01

    Patients with rheumatoid arthritis (RA) appear to have increased plasma levels of leptin and adiponectin. These adipokines may be implicated in the pathophysiology of RA. Tumour necrosis factor alpha (TNF-alpha) is a potential modulator of adipokines. The effects of long-term anti-TNF treatment on plasma levels of leptin and adiponectin are not clear. The aim of this study was to assess the effects of 6-month anti-TNF treatment (infliximab) on leptin and adiponectin plasma levels in RA patients. Thirty women with RA were included in the study. Patients with diabetes mellitus, any endocrine disorder or receiving any hypolipidemic or antidiabetic medication were not included. Thirty healthy age- and body mass index-matched women served as controls. Plasma levels of leptin and adiponectin were measured with enzyme immunoassay methods prior to and after the 6-month treatment with infliximab. Mean age and disease duration of patients were 51.8 +/- 14.4 and 12.2 +/- 6.7 years, respectively. Body weight did not change significantly over the 6-month period. Plasma levels of leptin and adiponectin were higher in patients than controls and did not change significantly after 6-month treatment. Interestingly, in the tertile of patients with the highest baseline adiponectin concentrations, adiponectin levels were significantly reduced (P < 0.05). Infliximab treatment did not change plasma levels of leptin and adiponectin after 6-month treatment in the whole study population. However, a reduction of adiponectin levels was observed in patients with higher baseline adiponectin levels. PMID:19563510

  7. 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

  8. Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile.

    PubMed

    Medrano, Luz María; Taxonera, Carlos; González-Artacho, Cristina; Pascual, Virginia; Gómez-García, María; Barreiro-de Acosta, Manuel; Pérez-Calle, José L; Bermejo, Fernando; López-Sanromán, Antonio; Martín Arranz, Dolores; Gisbert, Javier P; Mendoza, Juan Luis; Martín, Javier; Núñez, Concepción; Urcelay, Elena

    2015-01-01

    Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276* G/rs3014866* C/rs724781* C/rs3006488* A; P = 0.05); G0S2 (rs4844486* A/rs1473683* T; P = 0.15); TNFAIP6 (rs11677200* C/rs2342910* A/rs3755480* G/rs10432475* A; P = 0.10); and IL11 (rs1126760* C/rs1042506* G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway. PMID:26339133

  9. Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile

    PubMed Central

    Medrano, Luz María; Taxonera, Carlos; González-Artacho, Cristina; Pascual, Virginia; Gómez-García, María; Barreiro-de Acosta, Manuel; Pérez-Calle, José L.; Bermejo, Fernando; López-Sanromán, Antonio; Martín Arranz, Dolores; Gisbert, Javier P.; Mendoza, Juan Luis; Martín, Javier; Núñez, Concepción; Urcelay, Elena

    2015-01-01

    Substantial proportion of Crohn's disease (CD) patients shows no response or a limited response to treatment with infliximab (IFX) and to identify biomarkers of response would be of great clinical and economic benefit. The expression profile of five genes (S100A8-S100A9, G0S2, TNFAIP6, and IL11) reportedly predicted response to IFX and we aimed at investigating their etiologic role through genetic association analysis. Patients with active CD (350) who received at least three induction doses of IFX were included and classified according to IFX response. A tagging strategy was used to select genetic polymorphisms that cover the variability present in the chromosomal regions encoding the identified genes with altered expression. Following genotyping, differences between responders and nonresponders to IFX were observed in haplotypes of the studied regions: S100A8-S100A9 (rs11205276*G/rs3014866*C/rs724781*C/rs3006488*A; P = 0.05); G0S2 (rs4844486*A/rs1473683*T; P = 0.15); TNFAIP6 (rs11677200*C/rs2342910*A/rs3755480*G/rs10432475*A; P = 0.10); and IL11 (rs1126760*C/rs1042506*G; P = 0.07). These differences were amplified in patients with colonic and ileocolonic location for all but the TNFAIP6 haplotype, which evidenced significant difference in ileal CD patients. Our results support the role of the reported expression signature as predictive of anti-TNF outcome in CD patients and suggest an etiological role of those top-five genes in the IFX response pathway. PMID:26339133

  10. 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.

  11. Comparison of in-office magnetic resonance imaging versus conventional radiography in detecting changes in erosions after one year of infliximab therapy in patients with rheumatoid arthritis.

    PubMed

    Gaylis, Norman B; Needell, Steven D; Rudensky, Daniel

    2007-01-01

    The objective of this study was to compare standard hand radiographs with in-office 0.2 T magnetic resonance imaging (MRI) in monitoring response to therapy in patients with rheumatoid arthritis (RA) who were receiving infliximab, to evaluate the frequency and location of erosions, and to determine if there were differences in outcome based on disease duration at baseline. Patients who satisfied the American College of Rheumatology criteria for RA and were receiving infliximab therapy were evaluated with a baseline and 1-year follow-up MRI. Magnetic resonance images were interpreted by two blinded, board-certified radiologists. Bone erosions were identified as well-defined defects extending through the cortical margin. The mean age of the 48 patients was 58.5 years. The median infliximab dosage was 4 mg/kg. Baseline data showed that 41 patients had abnormal MRIs. The mean time between the baseline and follow-up MRI examinations was 10.5 months. Follow-up MRI revealed regression in 11 patients. Thirty-one patients had both MRIs and radiographs. Magnetic resonance imaging was approximately twice as sensitive as radiography in detecting erosions at baseline. In-office MRI was useful in monitoring disease response after the initiation of infliximab treatment. Magnetic resonance imaging is potentially a very valuable diagnostic tool and prognostic indicator for use in patients with RA. PMID:17694258

  12. [Treatment of rheumatoid arthritis in the Brazilian Unified National Health System: expenditures on infliximab compared to synthetic disease-modifying anti-rheumatic drugs, 2003-2006].

    PubMed

    Costa, Juliana de Oliveira; Almeida, Alessandra Maciel; Guerra Jr, Augusto Afonso; Cherchiglia, Mariangela Leal; Andrade, Eli Iola Gurgel; Acurcio, Francisco de Assis

    2014-02-01

    This study aimed to characterize the profile of users and related expenses with infliximab and synthetic disease-modifying anti-rheumatic drugs (DMARD) for rheumatoid arthritis treatment in the Brazilian Unified National Health System (SUS). We constructed a cohort from 2003 to 2006 drawing on databases of the SUS Outpatient Information System. Analyses were stratified by clinical and socio-demographic characteristics. We calculated average monthly expenditure per individual follow-up year and the factors that influenced it. The cohort consisted of 26,228 patients, mostly female, between 40 and 59 years of age, living in the Southeast of Brazil, and diagnosed with Felty's syndrome. Medicines for rheumatoid arthritis totalized BRL 74,306,087.18, of which infliximab accounted for 70%. Median monthly per capita expenditure was BRL 3,466.03 for patients receiving infliximab compared to BRL 143.85 for patients treated with synthetic DMARD. Drug treatment for rheumatoid arthritis was the main expense in SUS, with high economic impact from infliximab. Sex, diagnosis, age, and region of residence were factors that influenced expenditures.

  13. An unusual complication in ulcerative colitis during treatment with azathioprine and infliximab: Isospora belli as 'Casus belli'.

    PubMed

    Stein, Juergen; Tannich, Egbert; Hartmann, Franz

    2013-01-01

    The treatment of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and TNF-α antagonists. Patients undergoing such immunosuppressive treatment are more susceptible for infectious pathogens. Here, we report the case of a patient with a 13-year history of ulcerative colitis, treated initially with systemic corticosteroids in combination with immunomodulators, and subsequently with infliximab. The patient presented with severe watery diarrhoea, abdominal cramps, weight loss and low-grade fever. Stool examinations for cytomegalovirus, bacteria and parasites were negative. Following detection of numerous oocytes of Isospora belli (IB) in direct smear preparations of the diarrhoeic stool samples, the patient was successfully treated with trimethoprim-sulfamethoxazole (co-trimoxazole). PMID:23709557

  14. [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.

  15. 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

  16. 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. PMID:26386109

  17. 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.

  18. [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.

  19. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma.

    PubMed

    Scheinfeld, Noah

    2014-03-01

    Although rare, severe hidradenitis suppurativa (HS) of the anal, perianal, gluteal, thigh, and groin regions can evolve into squamous cell carcinoma (SCC). This usually does not occur until the HS has been present for more than 20 years. Malignant degeneration of HS in the axilla has not been reported. SCC has developed in dissecting cellulitis, acne conglobata, and pilonidal cysts (other members of the follicular tetrad). Whereas the male to female ratio of HS is 1:3, SCC in HS has a male to female ration of 5:1. The reasons behind malignant degeneration in HS are complex and might differ from the malignant degeneration causing Marjolin ulcers. It likely involves the presence of human papilloma virus (HPV) in affected areas (a rarity in the axilla), and impaired defensins, which combat HPV, in the skin of Hurley Stage III HS. In familial HS, the odds of developing SCC are likely greater because of independent loss-of-function mutations in the γ-secretase multiprotein complex, which regulates the Notch signaling pathway. Compromise of the Notch signaling pathway can undermine immune function and increase the risk of neoplastic development. Coincident SCC with use of tumor necrosis factor α blockers has been reported. I report a patient with long standing Hurley Stage III, familial HS, wwho developed metastatic SCC after 3 courses of infliximab and expired 11 months after the infliximab was started. A 47-year-old male presented with progressive HS since early adulthood. His stage III hidradenitis suppurativa (HS) involved his groin, legs buttocks, and perineal areas. Interestingly, his HS was familial; one daughter also suffered from HS. A pilonidal cyst had been excised in the past. He suffered from hypertension for which he took ramipril, 2.5 mg per day. He did not admit to smoking. He had undergone numerous surgeries and courses of clindamycin with rifampin and clindamycin with minocycline. He used pregablin among other stronger medications for pain control. He

  20. Infliximab, a TNF-α antagonist treatment in patients with ankylosing spondylitis: the impact on depression, anxiety and quality of life level.

    PubMed

    Ertenli, I; Ozer, S; Kiraz, S; Apras, S B; Akdogan, A; Karadag, O; Calguneri, M; Kalyoncu, U

    2012-02-01

    The objective of this study was to assess the effect of infliximab on depression, anxiety and quality of life in patients with active ankylosing spondylitis (AS). In this 6-week longitudinal study, 16 patients with AS were assessed. Active disease as defined by BASDAI ≥4.0 was sought for inclusion. Infliximab was administered 5 mg/kg at 0, 2 weeks and 6 weeks. Collected data included age, sex and date of onset of rheumatologic disease. Activity of disease was measured using Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Biological activity was evaluated with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). ESR and CRP were assessed at baseline and day 42. The Hospital Anxiety and Depression scale (HADS), Beck Depression Inventory (BDI) and 36-item Short Form Health Survey (SF-36) were used to evaluate anxiety, depression and quality of life. BASDAI, SF-36, HADS and BDE were assessed prior to the initial infliximab dose and at 2nd, 14th and 42nd day. Seven (43.8%) AS patients had depression scores above the cut off value for both the HADS depression (HADS-D) and BDI and 4 (25 %) had high HADS anxiety scores at baseline. Significant time effect for BDI and HADS-D scores were observed. Although significantly lower BDI scores were found after first, second and third infusions of infliximab, compared to initial score, the significant decrease in HADS-D appeared after second and third infusions. A significant time effect for HADS-anxiety scores were found as well. All of the subscales of SF-36 improved significantly during the course, with an exception of role emotional, for which the difference approached to the significance. The change in BASDAI scores and CRP and ESR, in the treatment process, were not correlated with the change in depression and anxiety scores. Infliximab which is an anti-TNF-α drug, may be effective in the treatment of depression accompanying AS. Possible implications for the treatment of major depressive

  1. Infliximab, methotrexate and their combination for the treatment of rheumatoid arthritis: a systematic review and meta-analysis.

    PubMed

    Costa, Juliana de Oliveira; Lemos, Lívia Lovato Pires de; Machado, Marina Amaral de Ávila; Almeida, Alessandra Maciel; Kakehasi, Adriana Maria; Araújo, Vânia de Eloísa; Cherchiglia, Mariângela Leal; Andrade, Eli Iola Gurgel; Acurcio, Francisco de Assis

    2015-01-01

    We performed a systematic review to evaluate the efficacy and safety of infliximab + methotrexate (IFX + MTX) regimens versus MTX alone or in combination with other disease-modifying anti-rheumatic drugs (DMARDs). We searched through major databases, the grey literature and did a manual search. Two independent reviewers conducted the selection, data extraction and analysis of the quality of the studies. Meta-analysis was conducted using Review Manager(®) 5.1 software. Nine trials were included. The mean modified Jadad score was 4.4, but only one study showed low risk of bias. IFX + MTX regimen presented better responses in clinical outcomes of ACR and DAS28 by up to 54 weeks, and of radiographic progression by up to 104 weeks. Withdrawals due to lack of efficacy was lower in the IFX + MTX group. No significant difference in adverse events was observed. The IFX + MTX combination is more effective than treatment with MTX alone or DMARDs combination. This regimen presented good tolerability in patients previously treated with DMARDs, not treated with MTX or with insufficient responses to MTX. The efficacy of IFX + MTX is noted primarily during initial periods of treatment. High doses of IFX were as effective as the standard dose, but with possible higher risk of serious infections. Therefore, we advise clinicians to use the standard dose of IFX 3 mg/kg every 8 weeks.

  2. A false occult hepatitis B virus infection developed in a patient with psoriatic arthritis under infliximab and methotrexate therapy.

    PubMed

    Notarnicola, A; Iannone, F; Lopalco, G; Covelli, M; Lapadula, G

    2013-01-01

    Despite lacking of international guidelines about the management of patients with occult hepatitis B virus infection (OBI) starting TNF-α blockers, there is some evidence from real life settings that these drugs are safe in OBI patients with rheumatic diseases. On the contrary, the management of the so-called false OBI patients appears still undefined. We describe a case of acute hepatitis B virus (HBV) infection occurred in an anti-HBs and anti- HBc positive patient affected by psoriatic arthritis, who had been treated for five years with infliximab. Baseline HBV-DNA analysis had not been performed. Although HBs Ag was still negative and the transaminases in the normal range, HBV-DNA serum analysis surprisingly showed high replication rate. Entecavir was added, and three months later HBV-DNA was no longer detectable. Even if HBs Ag is persistently negative, the assessment of HBV-DNA should be recommended at least at baseline in order to rule out hidden active necro-inflammatory liver disease.

  3. 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. PMID:25713985

  4. Disseminated tuberculosis infection and paradoxical reaction during antimycobacterial treatment related to TNF-alpha blocker agent Infliximab.

    PubMed

    Unlu, Mehmet; Cimen, Pınar; Ayranci, Aysu; Akarca, Tulay; Karaman, Onur; Dereli, Mustafa Sevket

    2014-01-01

    Tumor necrosis factor (TNF)-alpha inhibitors play an important role in the treatment of immun-mediated diseases such as Crohn's disease. But they also have been related to increased risk for disseminated Mycobacterium tuberculosis infections and paradoxical response to antimycobacterial treatment. Here we report a disseminated tuberculosis case and a paradoxical response to treatment after receiving TNF-inhibitor agent Infliximab for Crohn's disease. The patient had a severe clinical condition before the antimycobacterial treatment and although proper treatment was initiated his radiological findings were worsened one month after initiation of the treatment. All control microbologic tests for secondary infections were negative and this situation was accepted as a paradoxical response to antimycobacterial treatment and treatment was continued with the same regimen. At the end of the second month of the treatment, most of the symptoms disappeared and chest radiograph findings were better than the previous one. In conclusion, TNF-alpha inhibitor therapy increases risk of mycobacterial infections and patients should be examined carefully about tuberculosis before starting this therapy. Also, it is important for physicians to recognize and know how to manage paradoxical response related to TNF-alpha inhibitors during anti-tuberculosis treatment. PMID:26029559

  5. Disseminated tuberculosis infection and paradoxical reaction during antimycobacterial treatment related to TNF-alpha blocker agent Infliximab

    PubMed Central

    Unlu, Mehmet; Cimen, Pınar; Ayranci, Aysu; Akarca, Tulay; Karaman, Onur; Dereli, Mustafa Sevket

    2014-01-01

    Tumor necrosis factor (TNF)-alpha inhibitors play an important role in the treatment of immun-mediated diseases such as Crohn's disease. But they also have been related to increased risk for disseminated Mycobacterium tuberculosis infections and paradoxical response to antimycobacterial treatment. Here we report a disseminated tuberculosis case and a paradoxical response to treatment after receiving TNF-inhibitor agent Infliximab for Crohn's disease. The patient had a severe clinical condition before the antimycobacterial treatment and although proper treatment was initiated his radiological findings were worsened one month after initiation of the treatment. All control microbologic tests for secondary infections were negative and this situation was accepted as a paradoxical response to antimycobacterial treatment and treatment was continued with the same regimen. At the end of the second month of the treatment, most of the symptoms disappeared and chest radiograph findings were better than the previous one. In conclusion, TNF-alpha inhibitor therapy increases risk of mycobacterial infections and patients should be examined carefully about tuberculosis before starting this therapy. Also, it is important for physicians to recognize and know how to manage paradoxical response related to TNF-alpha inhibitors during anti-tuberculosis treatment. PMID:26029559

  6. 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

  7. The role of ABO blood groups in Crohn’s disease and in monitoring response to infliximab treatment

    PubMed Central

    Yu, Qiao; Wang, Lingyun; Zhang, Shenghong; Feng, Ting; Li, Li; Chen, Baili; Chen, Minhu

    2016-01-01

    Background The variation in ABO blood groups is reported to be associated with multiple diseases. Infliximab (IFX) has been widely used in the treatment of Crohn’s disease (CD). We aim to investigate the distribution of ABO blood groups in Chinese patients with CD and to explore its impact on response to IFX. Materials and methods Patients with CD were consecutively recruited to the study between 2007 and 2014. CD patients receiving IFX therapy were followed for at least two years. Results In 293 patients with CD, most patients (40.6%) had blood type O (119/293). The odds ratio (OR) of CD in blood type O patients was 1.06 (95%CI: 0.6–1.86; p=0.84) compared to all other blood types. Among those CD patients, 107 patients received IFX treatment. One year after the first course of IFX, a significant association was found between the overall ABO system and outcomes of IFX treatment (p<0.001). CD patients with blood type AB (OR=4.42, 95% CI: 1.04–18.76; p=0.044) were more likely to achieve mucosal healing, while CD patients with blood type A had a high risk of losing response (OR=0.38, 95% CI: 0.15–0.96; p=0.040). Discussion ABO blood groups are not associated with prevalence of CD. Patients with blood type AB had a better response to IFX while those with blood type A appeared to have a risk of losing response to IFX. PMID:27136434

  8. Comparative Study of Infliximab Therapy and Methotrexate Monotherapy to Improve the Clinical Effect in Rheumatoid Arthritis Patients.

    PubMed

    Miwa, Yusuke; Isojima, Sakiko; Saito, Mayu; Ikari, Yuzo; Kobuna, Mika; Hayashi, Tomoki; Takahashi, Ryo; Kasama, Tsuyoshi; Hosaka, Michio; Sanada, Kenji

    2016-01-01

    Objective We examined whether infliximab (IFX) therapy was more effective than methotrexate (MTX) monotherapy to achieve an improvement in depressive states in Rheumatoid Arthritis (RA) patients. Methods We examined 152 RA patients (72 IFX patients and 80 MTX patients). We conducted an open-label cohort study to evaluate the disease activity of RA (Simplified Disease Activity Index; SDAI), depressive states (Hamilton Rating Scale for Depression; HAM-D), Activity of Daily Living (ADL) (modified Health Assessment Questionnaire; mHAQ) and Quality of Life (QOL) [Short Form (SF)-36] in patients before and 6 months after receiving therapy. The HAM-D, SDAI, mHAQ and SF-36 scores after 6 months of therapy were measured as the outcomes. Results We analyzed 60 IFX patients and 53 MTX patients. The HAM-D scores significantly improved in both groups (p<0.001), but there was no significant difference in the effectiveness between the IFX and MTX therapies (p=0.792). The SDAI scores significantly improved in both groups after therapy (p<0.001), and IFX therapy was more effective than MTX therapy (p=0.004). The mHAQ and HAM-D scores also improved significantly in both groups after therapy (p<0.001), but no significant difference in the effectiveness between the IFX and MTX therapies was observed (p=0.272, 0.792). The scores of all 8 items of the SF-36 improved in both groups after therapy, but IFX therapy was more effective than MTX therapy in only 4 of the 8 items (p<0.05). Conclusion Both IFX and MTX therapy improved the clinical efficacy, ADL, QOL and depressive states. However, no significant differences regarding an improvement in the depressive states and ADL were observed between IFX therapy and MTX monotherapy. PMID:27629950

  9. Fiber optic-SPR platform for fast and sensitive infliximab detection in serum of inflammatory bowel disease patients.

    PubMed

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

    2016-05-15

    Infliximab (IFX) is a therapeutic monoclonal antibody used for treating patients with inflammatory bowel disease (IBD). In order to improve therapeutic outcomes it is recommended to monitor IFX trough concentrations. Although ELISA is currently widely used for this purpose, this method is not suitable for single patient testing. In this paper we describe the development of a fast bioassay for determining IFX concentration in serum using an in-house developed fiber-optic surface plasmon resonance (FO-SPR) biosensor. Studies were first conducted to optimize covalent immobilization of the IFX-specific antibody on the sensor surface as well as to select an optimal blocking buffer for restraining the non-specific binding. In order to reach clinically relevant sensitivity for detecting IFX in patients' serum, the SPR signal was amplified by employing gold nanoparticles functionalized with another set of IFX specific antibodies. Using the optimized sandwich bioassay, calibration curves were made with series of IFX concentrations spiked in buffer and 100-fold diluted serum, reaching the limit of detection of 0.3 and 2.2ng/ml, respectively. The established bioassay was finally validated using five IFX treated IBD patients samples. Results from the FO-SPR platform were compared with an in-house developed, clinically validated ELISA resulting in excellent Pearson and intraclass correlation coefficient of 0.998 and 0.983, respectively. Furthermore, the assay time of the FO-SPR platform was significantly reduced compared to ELISA, demonstrating the potential of this platform to be used as a point-of-care diagnostic tool for improving therapeutic outcomes of IBD patients.

  10. Interleukin-15 receptor α expression in inflammatory bowel disease patients before and after normalization of inflammation with infliximab

    PubMed Central

    Perrier, Clémentine; Arijs, Ingrid; Staelens, Dominiek; Breynaert, Christine; Cleynen, Isabelle; Covens, Kris; Ferrante, Marc; Assche, Gert; Vermeire, Séverine; Hertogh, Gert; Schuit, Frans; Rutgeerts, Paul; Ceuppens, Jan L

    2013-01-01

    Interleukin-15 (IL-15) is a pro-inflammatory cytokine thought to contribute to the inflammation in inflammatory bowel diseases (IBD). The specific receptor chain IL-15Rα can be expressed as a transmembranous signalling receptor, or can be cleaved by a disintegrin and metalloprotease domain 17 (ADAM17) into a neutralizing, soluble receptor (sIL-15Rα). The aim of this study is to evaluate the expression of IL-15Rα in ulcerative colitis (UC) and Crohn's disease (CD) patients before and after infliximab (IFX) therapy. Gene expression of IL-15Rα, IL-15 and ADAM17 was measured at the mRNA level by quantitative reverse transcription-PCR in mucosal biopsies harvested before and after first IFX therapy. Concentrations of sIL-15Rα were measured in sera of patients by ELISA and IL-15Rα protein was localized in the gut by immunohistochemistry and immunofluorescence. Mucosal expression of IL-15Rα is increased in UC and CD patients compared with controls and it remains elevated after IFX therapy in both responder and non-responder patients. The concentration of sIL-15Rα in serum is also increased in UC patients when compared with controls and does not differ between responders and non-responders either before or after IFX. CD patients have levels of sIL-15Rα comparable to healthy controls before and after therapy. In mucosal tissues, IL-15Rα+ cells closely resemble activated memory B cells with a pre-plasmablastic phenotype. To conclude, IBD patients have an increased expression of IL-15Rα mRNA in the mucosa. Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX. PMID:23039249

  11. Fiber optic-SPR platform for fast and sensitive infliximab detection in serum of inflammatory bowel disease patients.

    PubMed

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

    2016-05-15

    Infliximab (IFX) is a therapeutic monoclonal antibody used for treating patients with inflammatory bowel disease (IBD). In order to improve therapeutic outcomes it is recommended to monitor IFX trough concentrations. Although ELISA is currently widely used for this purpose, this method is not suitable for single patient testing. In this paper we describe the development of a fast bioassay for determining IFX concentration in serum using an in-house developed fiber-optic surface plasmon resonance (FO-SPR) biosensor. Studies were first conducted to optimize covalent immobilization of the IFX-specific antibody on the sensor surface as well as to select an optimal blocking buffer for restraining the non-specific binding. In order to reach clinically relevant sensitivity for detecting IFX in patients' serum, the SPR signal was amplified by employing gold nanoparticles functionalized with another set of IFX specific antibodies. Using the optimized sandwich bioassay, calibration curves were made with series of IFX concentrations spiked in buffer and 100-fold diluted serum, reaching the limit of detection of 0.3 and 2.2ng/ml, respectively. The established bioassay was finally validated using five IFX treated IBD patients samples. Results from the FO-SPR platform were compared with an in-house developed, clinically validated ELISA resulting in excellent Pearson and intraclass correlation coefficient of 0.998 and 0.983, respectively. Furthermore, the assay time of the FO-SPR platform was significantly reduced compared to ELISA, demonstrating the potential of this platform to be used as a point-of-care diagnostic tool for improving therapeutic outcomes of IBD patients. PMID:26706938

  12. 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

    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

  13. 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

  14. Systematic safety follow up in a cohort of 107 patients with spondyloarthropathy treated with infliximab: a new perspective on the role of host defence in the pathogenesis of the disease?

    PubMed Central

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

    2003-01-01

    Background: Recent studies with infliximab indicate the therapeutic potential of tumour necrosis factor α blockade in spondyloarthropathy (SpA). Because defective host defence is implicated in the pathogenesis of SpA, the potential side effects of this treatment due to impact on the antimicrobial defence are a major concern. Objective: To report systematically the adverse events seen in a large cohort of patients with SpA treated with infliximab, with special attention to bacterial infections. Patients and methods: 107 patients with SpA were treated with infliximab for a total of 191.5 patient years. All serious and/or treatment related adverse events were reported. Results: Eight severe infections occurred, including two reactivations of tuberculosis and three retropharyngeal abscesses, and six minor infections with clear bacterial focus. One patient developed a spinocellular carcinoma of the skin. No cases of demyelinating disease or lupus-like syndrome were seen. Two patients had an infusion reaction, which, however, did not relapse during the next infusion. Finally, three patients with ankylosing spondylitis developed palmoplantar pustulosis. All patients recovered completely with adequate treatment, and infliximab treatment had to be stopped in only five patients with severe infections. Conclusions: Although the global safety of infliximab in SpA is good compared with previous reports in rheumatoid arthritis and Crohn's disease, the occurrence of infections such as tuberculosis and retropharyngeal abscesses highlights the importance of careful screening and follow up. Focal nasopharyngeal infections and infection related symptoms, possibly induced by streptococci, occurred frequently, suggesting an impairment of specific host defence mechanisms in SpA. PMID:12922954

  15. Pre-Treatment Whole Blood Gene Expression Is Associated with 14-Week Response Assessed by Dynamic Contrast Enhanced Magnetic Resonance Imaging in Infliximab-Treated Rheumatoid Arthritis Patients

    PubMed Central

    MacIsaac, Kenzie D.; Baumgartner, Richard; Kang, Jia; Loboda, Andrey; Peterfy, Charles; DiCarlo, Julie; Riek, Jonathan; Beals, Chan

    2014-01-01

    Approximately 30% of rheumatoid arthritis patients achieve inadequate response to anti-TNF biologics. Attempts to identify molecular biomarkers predicting response have met with mixed success. This may be attributable, in part, to the variable and subjective disease assessment endpoints with large placebo effects typically used to classify patient response. Sixty-one patients with active RA despite methotrexate treatment, and with MRI-documented synovitis, were randomized to receive infliximab or placebo. Blood was collected at baseline and genome-wide transcription in whole blood was measured using microarrays. The primary endpoint in this study was determined by measuring the transfer rate constant (Ktrans) of a gadolinium-based contrast agent from plasma to synovium using MRI. Secondary endpoints included repeated clinical assessments with DAS28(CRP), and assessments of osteitis and synovitis by the RAMRIS method. Infliximab showed greater decrease from baseline in DCE-MRI Ktrans of wrist and MCP at all visits compared with placebo (P<0.001). Statistical analysis was performed to identify genes associated with treatment-specific 14-week change in Ktrans. The 256 genes identified were used to derive a gene signature score by averaging their log expression within each patient. The resulting score correlated with improvement of Ktrans in infliximab-treated patients and with deterioration of Ktrans in placebo-treated subjects. Poor responders showed high expression of activated B-cell genes whereas good responders exhibited a gene expression pattern consistent with mobilization of neutrophils and monocytes and high levels of reticulated platelets. This gene signature was significantly associated with clinical response in two previously published whole blood gene expression studies using anti-TNF therapies. These data provide support for the hypothesis that anti-TNF inadequate responders comprise a distinct molecular subtype of RA characterized by differences in pre

  16. 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

    2014-01-01

    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

  17. Short treatment with the tumour necrosis factor-α blocker infliximab diminishes chronic chagasic myocarditis in rats without evidence of Trypanosoma cruzi reactivation

    PubMed Central

    Pérez, A R; Fontanella, G H; Nocito, A L; Revelli, S; Bottasso, O A

    2009-01-01

    Tumour necrosis factor (TNF)-α is crucial for resistance to Trypanosoma cruzi acute infection, but there is scant information on its role during the chronic phase. To address this issue, we analysed whether a short treatment with a TNF-α blocker affected the course and characteristics of chronic disease in a rat experimental model of T. cruzi infection. An anti-TNF-α agent (infliximab) was administered during the chronic phase for a period of 4 weeks (3 mg/kg/week), while control infected rats were inoculated with saline physiological solution. Search for parasites yielded non-successful results in all infected groups, irrespective of treatment. Nevertheless, the presence of T. cruzi kDNA in heart tissue was detected in infected and infected plus treated animals. Because infliximab might induce changes in the anti-parasite cytokine response, circulating levels of interleukin (IL)-10, interferon-gamma and nitric oxide were evaluated. An increase in IL-10 levels was observed only in the infected group treated with the anti-TNF-α blocker compared to the remaining groups (P < 0·05). A clear attenuation of histological damage associated with a diminution of cardiac TNF-α mRNA expression was observed in the infected and treated animals compared to the infected and non-treated group. Blocking of TNF-α during a relatively short period in chronically infected rats did not lead to evident parasite reactivation but reduced myocarditis severity significantly, indicating a role of this cytokine in the pathogenesis of chronic myocardial damage. PMID:19604269

  18. Evaluation of the pharmacokinetic equivalence and 54-week efficacy and safety of CT-P13 and innovator infliximab in Japanese patients with rheumatoid arthritis

    PubMed Central

    Takeuchi, Tsutomu; Yamanaka, Hisashi; Tanaka, Yoshiya; Sakurai, Takeo; Saito, Kazuyoshi; Ohtsubo, Hideo; Lee, Sang Joon; Nambu, Yoshihiro

    2015-01-01

    Objectives. To demonstrate the pharmacokinetic equivalence of CT-P13 and its innovator infliximab (IFX) in Japanese patients with rheumatoid arthritis (RA), and to compare the efficacy and safety of these drugs, administered for 54 weeks. Methods. In a randomized, double-blind, parallel-group, multicenter study, 3 mg/kg of CT-P13 or IFX, in combination with methotrexate (MTX) (6–16 mg/week), was administered for 54 weeks to Japanese active RA patients with an inadequate response to MTX, to demonstrate the pharmacokinetic equivalence, based on the area under the curve (AUCτ) (weeks 6–14) and Cmax (week 6) of these drugs, and to compare their efficacy and safety. Results. The CT-P13-to-IFX ratios (90% confidence intervals) of the geometric mean AUCτ and Cmax values in patients negative for antibodies to infliximab at week 14 were 111.62% (100.24–124.29%) and 104.09% (92.12–117.61%), respectively, demonstrating the pharmacokinetic equivalence of these drugs. In the full analysis set, CT-P13 and IFX showed comparable therapeutic effectiveness, as measured by the American College of Rheumatology, Disease Activity Score in 28 joints, the European League Against Rheumatism, and other efficacy criteria, at weeks 14 and 30. The incidence of adverse events was similar for these drugs. Conclusion. CT-P13 and IFX, administered at a dose of 3 mg/kg in combination with MTX to active RA patients, were pharmacokinetically equivalent and comparable in efficacy and safety. PMID:25736355

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

    PubMed Central

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

    2016-01-01

    Abstract 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

  20. 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

  1. 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.

  2. The impact of induction therapy with three doses of infliximab on deep histological healing in paediatric patients with active Crohn’s disease

    PubMed Central

    Dadalski, Maciej; Szymanska, Sylwia; Grajkowska, Wieslawa; Pronicki, Maciej; Kierkus, Jaroslaw

    2016-01-01

    Introduction The clinical efficacy of infliximab (IFX) for induction of remission in both adults and children with active Crohn’s disease (CD) has been well documented. Recently, so-called “deep remission” defined as mucosal healing has become the ultimate endpoint of the most recent therapeutic advances for CD. However, endoscopic evidence of mucosal healing is not necessarily associated with histological evidence of suppression of inflammation. Aim Since data on that issue are limited, especially in the paediatric population, the aim of this study was to assess the impact of induction therapy with IFX on deep microscopic remission in paediatric patients with CD. Material and methods Fifty-six children (32 boys and 24 girls) aged 13.0 ±9.3 years with moderate to severely active CD diagnosed at the mean age of 5.5 ±0.83 years were included into the study. Colonoscopy and gastroscopy with sample collection were performed in all patients before and after three injections of IFX. Clinical activity of the disease was assessed using the Paediatric Crohn’s Disease Activity Index (PCDAI), and the endoscopic activity was scored using the Simple Endoscopic Score (SES-CD). Histological changes were evaluated by a previously described numerical scoring system. Results Thirty-nine (69.6%) patients reached clinical remission (PCDAI ≤ 10). When comparing data at baseline and at week 10, a significant decrease was observed in median PCDAI, and in SES-CD score between the initial and control colonoscopies. We also reported a decrease in histological scale. However, the difference was not statistically significant (p = 0.63). Three (5.4%) patients had a score of zero in the control histological examination. The correlation was found only between histological score and SES-CD score. Clinical remission correlated better with mucosal healing expressed by a decrease in SES-CD score than with microscopic changes. Conclusions Biological therapy with infliximab enables mucosal

  3. Long-Term Clinical Remission in Biologically Naïve Crohn's Disease Patients with Adalimumab Therapy, Including Analyses of Switch from Adalimumab to Infliximab.

    PubMed

    Mizoshita, Tsutomu; Tanida, Satoshi; Ozeki, Keiji; Katano, Takahito; Shimura, Takaya; Mori, Yoshinori; Kubota, Eiji; Kataoka, Hiromi; Kamiya, Takeshi; Joh, Takashi

    2016-01-01

    There is little evidence regarding the maintenance of long-term clinical remission by adalimumab (ADA) therapy in Crohn's disease (CD) patients naïve to anti-tumor necrosis factor treatment (naïve CD patients), since most CD patients are treated with ADA after infliximab (IFX) therapy. The long-term clinical response to ADA was retrospectively analyzed in 17 naïve CD patients for at least 24 months, and the serum trough IFX levels were evaluated in patients switching from ADA to IFX. Of the 17 naïve CD patients, 14 (82.4%) maintained long-term clinical remission with ADA therapy for at least 24 months, without serious adverse events. The clinical condition of 7 patients was observed for more than 36 months, and 3, 1, 1, and 2 cases maintained remission at months 42, 48, 54, and 60 after ADA therapy, respectively. Three patients (17.6%) switched from ADA to IFX less than 24 months after the start of ADA therapy, and they had remission, retaining trough levels of IFX higher than 1 μg/ml, occasionally by dose escalation. In conclusion, maintenance ADA therapy achieves long-term clinical remission in naïve CD patients. Switching from ADA to IFX is an important therapeutic option in CD patients showing loss of response to ADA, occasionally with dose escalation, based on the analysis of serum IFX trough levels. PMID:27462198

  4. 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

  5. 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

  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. PMID:27559045

  7. 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.

  8. Anti-Drug Antibodies, Drug Levels, Interleukin-6 and Soluble TNF Receptors in Rheumatoid Arthritis Patients during the First 6 Months of Treatment with Adalimumab or Infliximab: A Descriptive Cohort Study

    PubMed Central

    Bouchelouche, Pierre; Bartels, Else Marie; Bliddal, Henning; Bendtzen, Klaus; Stoltenberg, Michael

    2016-01-01

    Objectives With the present study we wanted to explore the impact of treatment with a tumor necrosis factor-α -inhibitor (TNFi) on levels of soluble biomarkers in rheumatoid arthritis (RA) patients and to identify predictors of impaired drug levels and development of anti-TNFi antibodies (anti-TNFi Abs). Methods Blood samples from 26 patients with established RA were taken at baseline and following 6 months of treatment with adalimumab or infliximab. Samples were analyzed for levels of TNFi, interleukin (IL)-6, and soluble TNF-receptors 1 and -2 (sTNF-R1 and -2) and for presence of anti-TNFi Abs. Clinical and demographic data were recorded as well. Results During the initial 6 months treatment, DAS28(CRP) (Disease activity score in 28 joints using C-reactive protein) and levels of IL-6 and sTNF-R2 decreased significantly in patients without anti-TNFi Abs and in patients retaining detectable drug levels. The levels of other tested cytokines (TNF-α, TNF-β, IL-1ra, IL-1b, IL-8, IL-10, IL-12(p70), IL-13, IL-17A, IL-17F, and IL-33) were generally below detection limits. Higher baseline levels of IL-6 associated with undetectable levels of TNFi at follow-up. Anti-TNFi Abs were associated with decreased drug levels, but no predictors for anti-TNFi Ab development could be found. Conclusion The effect of treatment with TNFi on RA disease activity depends on levels of active drug, and by presence of anti-TNFi Abs. In patients who retain detectable drug levels, and in the absence of anti-TNFi Abs, clinical outcome is improved during treatment, and circulating levels of IL-6 and sTNF-R2 decrease. Baseline levels of IL-6 may predict depletion of TNFi and may identify patients at risk of treatment failure. PMID:27606615

  9. 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.

  10. 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…

  11. 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

  12. 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. PMID:20232594

  13. 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.

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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...

  20. Infliximab, adalimumab and golimumab for treating moderately to severely active ulcerative colitis after the failure of conventional therapy (including a review of TA140 and TA262): clinical effectiveness systematic review and economic model.

    PubMed Central

    Archer, Rachel; Tappenden, Paul; Ren, Shijie; Martyn-St James, Marrissa; Harvey, Rebecca; Basarir, Hasan; Stevens, John; Carroll, Christopher; Cantrell, Anna; Lobo, Alan; Hoque, Sami

    2016-01-01

    BACKGROUND Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the UK. UC can have a considerable impact on patients' quality of life. The burden for the NHS is substantial. OBJECTIVES To evaluate the clinical effectiveness and safety of interventions, to evaluate the incremental cost-effectiveness of all interventions and comparators (including medical and surgical options), to estimate the expected net budget impact of each intervention, and to identify key research priorities. DATA SOURCES Peer-reviewed publications, European Public Assessment Reports and manufacturers' submissions. The following databases were searched from inception to December 2013 for clinical effectiveness searches and from inception to January 2014 for cost-effectiveness searches for published and unpublished research evidence: MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, The Cochrane Library including the Cochrane Systematic Reviews Database, Cochrane Controlled Trials Register, Database of Abstracts of Reviews of Effects, the Health Technology Assessment database and NHS Economic Evaluation Database; ISI Web of Science, including Science Citation Index, and the Conference Proceedings Citation Index-Science and Bioscience Information Service Previews. The US Food and Drug Administration website and the European Medicines Agency website were also searched, as were research registers, conference proceedings and key journals. REVIEW METHODS A systematic review [including network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of named interventions. The health economic analysis included a review of published economic evaluations and the development of a de novo model. RESULTS Ten randomised controlled trials were included in the systematic review. The trials suggest that adult patients receiving infliximab (IFX) [Remicade(®), Merck Sharp & Dohme Ltd (MSD)], adalimumab (ADA) (Humira(®), Abb

  1. 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.

  2. 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.

  3. 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...

  4. 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

  5. Combinación de radioterapia con quimioterapia mejora la supervivencia con raro cáncer cerebral

    Cancer.gov

    Los resultados de dos estudios clínicos de seguimiento a largo plazo confirman que ciertos pacientes viven substancialmente más si se les trata con una combinación de quimioterapia y radioterapia en comparación con radioterapia solamente.

  6. View forward of interior of conning tower and steering station; ...

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

    View forward of interior of conning tower and steering station; helmsman or observer viewed action through narrow opening at top of photo. (p57) - USS Olympia, Penn's Landing, 211 South Columbus Boulevard, Philadelphia, Philadelphia County, PA

  7. [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. PMID:27514827

  8. 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

  9. "CON-CON" assignment strategy for highly flexible intrinsically disordered proteins.

    PubMed

    Piai, Alessandro; Hošek, Tomáš; Gonnelli, Leonardo; Zawadzka-Kazimierczuk, Anna; Koźmiński, Wiktor; Brutscher, Bernhard; Bermel, Wolfgang; Pierattelli, Roberta; Felli, Isabella C

    2014-12-01

    Intrinsically disordered proteins (IDPs) are a class of highly flexible proteins whose characterization by NMR spectroscopy is complicated by severe spectral overlaps. The development of experiments designed to facilitate the sequence-specific assignment procedure is thus very important to improve the tools for the characterization of IDPs and thus to be able to focus on IDPs of increasing size and complexity. Here, we present and describe the implementation of a set of novel ¹H-detected 5D experiments, (HACA)CON(CACO)NCO(CA)HA, BT-(H)NCO(CAN)CONNH and BT-HN(COCAN)CONNH, optimized for the study of highly flexible IDPs that exploit the best resolved correlations, those involving the carbonyl and nitrogen nuclei of neighboring amino acids, to achieve sequence-specific resonance assignment. Together with the analogous recently proposed pulse schemes based on ¹³C detection, they form a complete set of experiments for sequence-specific assignment of highly flexible IDPs. Depending on the particular sample conditions (concentration, lifetime, pH, temperature, etc.), these experiments present certain advantages and disadvantages that will be discussed. Needless to say, that the availability of a variety of complementary experiments will be important for accurate determination of resonance frequencies in complex IDPs.

  10. [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.

  11. [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. PMID:27571559

  12. Paramagnetic-to-Ferromagnetic Transition in Con Under Pressure

    NASA Astrophysics Data System (ADS)

    Kasinathan, Deepa; Pickett, Warren

    2004-03-01

    Motivated by reports of synthesis of zincblende (ZB) structure CrAs in thin film form, strong interest has developed in understanding transition metal pnictides and their tendencies toward magnetic order.Literature on the experimental analysis of the structure of CoN is varied, with reports of both magnetically ordered NaCl structure CoN and non-magnetic ZB CoN. We present results of first principles analysis of electronic structure, magnetism and Murnaghan equation of state for both structures. The non-magnetic ZB structure, stable at ambient pressure transforms to a collapsed ferromagnetic NaCl phase at 10GPa (ΔV = -15%). These results will be compared to data and similarities/differences with other transition metal nitrides will be discussed.

  13. ProbCons: Probabilistic consistency-based multiple sequence alignment.

    PubMed

    Do, Chuong B; Mahabhashyam, Mahathi S P; Brudno, Michael; Batzoglou, Serafim

    2005-02-01

    To study gene evolution across a wide range of organisms, biologists need accurate tools for multiple sequence alignment of protein families. Obtaining accurate alignments, however, is a difficult computational problem because of not only the high computational cost but also the lack of proper objective functions for measuring alignment quality. In this paper, we introduce probabilistic consistency, a novel scoring function for multiple sequence comparisons. We present ProbCons, a practical tool for progressive protein multiple sequence alignment based on probabilistic consistency, and evaluate its performance on several standard alignment benchmark data sets. On the BAliBASE, SABmark, and PREFAB benchmark alignment databases, ProbCons achieves statistically significant improvement over other leading methods while maintaining practical speed. ProbCons is publicly available as a Web resource.

  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. 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…

  16. 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.

  17. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 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...

  18. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 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...

  19. 9 CFR 319.300 - Chili con carne.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... CERTIFICATION DEFINITIONS AND STANDARDS OF IDENTITY OR COMPOSITION Canned, Frozen, or Dehydrated Meat Food... 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...

  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. 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.

  2. ConStrains identifies microbial strains in metagenomic datasets

    PubMed Central

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-01-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived data sets provides insights into microbial community dynamics. PMID:26344404

  3. ConStrains identifies microbial strains in metagenomic datasets.

    PubMed

    Luo, Chengwei; Knight, Rob; Siljander, Heli; Knip, Mikael; Xavier, Ramnik J; Gevers, Dirk

    2015-10-01

    An important fraction of microbial diversity is harbored in strain individuality, so identification of conspecific bacterial strains is imperative for improved understanding of microbial community functions. Limitations in bioinformatics and sequencing technologies have to date precluded strain identification owing to difficulties in phasing short reads to faithfully recover the original strain-level genotypes, which have highly similar sequences. We present ConStrains, an open-source algorithm that identifies conspecific strains from metagenomic sequence data and reconstructs the phylogeny of these strains in microbial communities. The algorithm uses single-nucleotide polymorphism (SNP) patterns in a set of universal genes to infer within-species structures that represent strains. Applying ConStrains to simulated and host-derived datasets provides insights into microbial community dynamics.

  4. [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.

  5. 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.

  6. 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

  7. Topical Oxygen for Chronic Wounds: A PRO/CON Debate

    PubMed Central

    Mutluoglu, Mesut; Cakkalkurt, Aslican; Uzun, Gunalp; Aktas, Samil

    2014-01-01

    The role of oxygen in wound healing is universally accepted and does not require any further evidence; however the controversy as to whether oxygen delivery systems have the potential to improve wound healing remains to be concluded. Topical oxygen treatment (TOT) involves the delivery of 100% oxygen for a mean of 90 min, once a day at an atmospheric pressure slightly above 1 atm abs. The use of TOT gained increasing interest recently. The current manuscript will summarize the pros and cons of TOT in the view of the available literature. PMID:26199891

  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. 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.

  10. 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

  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. [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. PMID:26021098

  13. RoboCon: Operator interface for robotic applications

    SciTech Connect

    Schempf, H.; Warwick, J.; Fung, M.; Chemel, B.; Blackwell, M.

    1996-12-31

    Carnegie Mellon U. and ORNL`s Robotics and Process Systems Division are developing a state-of-the-art robot operator control station (RoboCon) with standardized hardware and software control interfaces to be adaptable to a variety of remote and robotic equipment currently funded by DOE`s Office of Science & Technology Robotics Technology Development Program. The human operation and telerobotic and supervisory control of sophisticated and remote and robotic systems is a complex, tiring, and non-intuitive activity. Since decontamination & decommissioning, selective equipment removal, mixed waste operations, and in-tank cleanup are going to be a major future activity in DOE environmental restoration and waste management cleanup agenda, it seems necessary to utilize an operator control station and interface which maximizes operator comfort and productivity.

  14. 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.

  15. 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.

  16. 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.

  17. Con A conjugated to Europium(III) cryptate as a new histological tool for prostate cancer investigation using confocal microscopy.

    PubMed

    Rêgo, M J B M; Silva, L P B G; Medeiros, J K G; Figueiredo, R C B Q; Alves-Júnior, S; Beltrão, E I C

    2014-07-01

    Lectins are carbohydrate recognition proteins that can be used as probes to reveal the glycosylation state of cells. They frequently have been used for diagnostic and prognostic cancer studies. For fluorescence based analysis, lectins commonly are conjugated to fluorescein isothiocyanate (Con A-FITC); however, this molecule loses its fluorescence quickly. We conjugated Europium cryptate to Con A (Con A-cryp-Eu) for use as a histochemical luminescent probe to recognize glucose/mannose residues in benign prostatic hyperplasia and prostatic carcinoma tissues, and used confocal microscopy instead of commercial Con A-FITC. Tissues were treated with Evans blue to suppress intrinsic tissue fluorescence before incubation with Con A-cryp-Eu or Con A-FITC. Con A-cryp-Eu exhibited hemagglutinating activity. Con A-cryp-Eu showed the same binding pattern as Con A-FITC in prostate stroma and gland cells. Staining was strong in benign prostate hyperplasia and prostate carcinoma tissues. Con A-cryp-Eu probe stained glucose/mannose residues in prostatic carcinoma more intensely than Con A-FITC. Furthermore, staining with Con A-cryp-Eu showed greater fluorescence intensity than Con A-FITC and the emission of Con A-cryp-Eu was more stable than the Con A-FITC for seven days under the same storage conditions. Maintenance of the luminescent properties and the binding pattern of Con A-cryp-Eu favor its use as an auxiliary histochemistry probe for prostatic tissue studies. PMID:24160413

  18. Con A conjugated to Europium(III) cryptate as a new histological tool for prostate cancer investigation using confocal microscopy.

    PubMed

    Rêgo, M J B M; Silva, L P B G; Medeiros, J K G; Figueiredo, R C B Q; Alves-Júnior, S; Beltrão, E I C

    2014-07-01

    Lectins are carbohydrate recognition proteins that can be used as probes to reveal the glycosylation state of cells. They frequently have been used for diagnostic and prognostic cancer studies. For fluorescence based analysis, lectins commonly are conjugated to fluorescein isothiocyanate (Con A-FITC); however, this molecule loses its fluorescence quickly. We conjugated Europium cryptate to Con A (Con A-cryp-Eu) for use as a histochemical luminescent probe to recognize glucose/mannose residues in benign prostatic hyperplasia and prostatic carcinoma tissues, and used confocal microscopy instead of commercial Con A-FITC. Tissues were treated with Evans blue to suppress intrinsic tissue fluorescence before incubation with Con A-cryp-Eu or Con A-FITC. Con A-cryp-Eu exhibited hemagglutinating activity. Con A-cryp-Eu showed the same binding pattern as Con A-FITC in prostate stroma and gland cells. Staining was strong in benign prostate hyperplasia and prostate carcinoma tissues. Con A-cryp-Eu probe stained glucose/mannose residues in prostatic carcinoma more intensely than Con A-FITC. Furthermore, staining with Con A-cryp-Eu showed greater fluorescence intensity than Con A-FITC and the emission of Con A-cryp-Eu was more stable than the Con A-FITC for seven days under the same storage conditions. Maintenance of the luminescent properties and the binding pattern of Con A-cryp-Eu favor its use as an auxiliary histochemistry probe for prostatic tissue studies.

  19. Opciones de cirugía para mujeres con CDIS o con cáncer de seno- página de publicaciones

    Cancer.gov

    Contiene información sobre los tipos de cirugía de seno, como la operación para conservar el seno y la mastectomía, y ayuda a las mujeres diagnosticadas con CDIS o con cáncer de seno a decidir cuál cirugía es la más conveniente para ellas.

  20. 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.

  1. Pruebas de BRCA en pacientes jóvenes con cáncer

    Cancer.gov

    Pruebas de mutaciones genéticas fuertemente asociadas con un mayor riesgo de cáncer de seno han aumentado dramáticamente entre mujeres menores de 40 años diagnosticadas con la enfermedad, según un nuevo estudio.

  2. Control del dolor: Apoyo para las personas con cáncer

    Cancer.gov

    Contiene información sobre las medicinas contra el dolor para pacientes con cáncer, los planes para controlarlo, cómo hablar con su equipo de atención médica sobre el dolor que usted siente y qué hacer para controlar los efectos físicos y emocionales del

  3. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate.

    PubMed

    Anande, Nalini M; Jain, Sunil K; Jain, Narendra K

    2008-07-01

    The aim of the research work was to develop cyst-targeted novel concanavalin-A (Con-A) conjugated mucoadhesive microspheres of diloxanide furoate (DF) for the effective treatment of amoebiasis. Eudragit microspheres of DF were prepared using emulsification-solvent evaporation method. Formulations were characterized for particle size and size distribution, % drug entrapment, surface morphology and in vitro drug release in simulated gastrointestinal (GI) fluids. Eudragit microspheres of DF were conjugated with Con-A. IR spectroscopy and DSC were used to confirm successful conjugation of Con-A to Eudragit microspheres while Con-A conjugated microspheres were further characterized using the parameters of zeta potential, mucoadhesiveness to colonic mucosa and Con-A conjugation efficiency with microspheres. IR studies confirmed the attachment of Con-A with Eudragit microspheres. All the microsphere formulations showed good % drug entrapment (78+/-5%). Zeta potential of Eudragit microspheres and Con-A conjugated Eudragit microspheres were found to be 3.12+/-0.7mV and 16.12+/-0.5mV, respectively. Attachment of lectin to the Eudragit microspheres significantly increases the mucoadhesiveness and also controls the release of DF in simulated GI fluids. Gamma scintigraphy study suggested that Eudragit S100 coated gelatin capsule retarded the release of Con-A conjugated microspheres at low pH and released microspheres slowly at pH 7.4 in the colon.

  4. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Definitions § 227.27 Limiting permissible con-cen-tra-tion (LPC). (a) The limiting permissible...

  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. Differential effect of low molecular weight alcohols on the Con A stimulation of mouse spleen cells.

    PubMed

    Raile, A; Hammann, K P; Scheiner, O; Schulz, T; Erdei, A; Dierich, M P

    1982-06-01

    Incorporation of [3h]thymidine ([3H]TdR) into concanavalin A (Con A)-stimulated murine splenocytes was found to be enhanced by addition of certain concentrations of ethanol, 2-propanol and acetone. The alcohol/acetone-induced enhancement of the Con A response was found to be accompanied by an increase of the percentage of living cells as assessed by trypan blue exclusion. Concentrations of ethanol and 2-propanol which caused maximum [3H]TdR uptake in Con A cultures were also found to lead to higher percentages of aggregated cells than in comparison to Con A cultures without alcohol. The data suggest that alcohols in certain concentrations are capable to achieve optimum Con A stimulation.

  7. [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.

  8. Glycogen synthase kinase-3 facilitates con a-induced IFN-γ-- mediated immune hepatic injury.

    PubMed

    Tsai, Cheng-Chieh; Huang, Wei-Ching; Chen, Chia-Ling; Hsieh, Chia-Yuan; Lin, Yee-Shin; Chen, Shun-Hua; Yang, Kao-Chi; Lin, Chiou-Feng

    2011-10-01

    Immune hepatic injury induced by Con A results primarily from IFN-γ-mediated inflammation, followed by hepatic cell death. Glycogen synthase kinase (GSK)-3, which acts proapoptotically and is proinflammatory, is also important for facilitating IFN-γ signaling. We hypothesized a pathogenic role for GSK-3 in Con A hepatic injury. Con A stimulation caused GSK-3 activation in the livers of C57BL/6 mice. Inhibiting GSK-3 reduced Con A hepatic injury, including hepatic necrosis and apoptosis, inflammation, infiltration of T cells and granulocytes, and deregulated expression of adhesion molecule CD54. Con A induced hepatic injury in an IFN-γ receptor 1-dependent manner. Con A/IFN-γ induced activation and expression of STAT1 in a GSK-3-dependent manner. GSK-3 facilitated IFN-γ-induced inducible NO synthase, but had limited effects on CD95 upregulation and CD95-mediated hepatocyte apoptosis in vitro. Notably, inhibiting GSK-3 decreased Con A-induced IFN-γ production in both wild-type and IFN-γ receptor 1-deficient C57BL/6 mice. In Con A-activated NKT cells, GSK-3 was also activated and was required for nuclear translocation of T-box transcription factor Tbx21, a transcription factor of IFN-γ, but it was not required for CD95 ligand expression or activation-induced cell death. These results demonstrate the dual and indispensable role of GSK-3 in Con A hepatic injury by facilitating IFN-γ-induced hepatopathy.

  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. 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.

  11. 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.

  12. ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids.

    PubMed

    Ashkenazy, Haim; Erez, Elana; Martz, Eric; Pupko, Tal; Ben-Tal, Nir

    2010-07-01

    It is informative to detect highly conserved positions in proteins and nucleic acid sequence/structure since they are often indicative of structural and/or functional importance. ConSurf (http://consurf.tau.ac.il) and ConSeq (http://conseq.tau.ac.il) are two well-established web servers for calculating the evolutionary conservation of amino acid positions in proteins using an empirical Bayesian inference, starting from protein structure and sequence, respectively. Here, we present the new version of the ConSurf web server that combines the two independent servers, providing an easier and more intuitive step-by-step interface, while offering the user more flexibility during the process. In addition, the new version of ConSurf calculates the evolutionary rates for nucleic acid sequences. The new version is freely available at: http://consurf.tau.ac.il/.

  13. ConSite: web-based prediction of regulatory elements using cross-species comparison.

    PubMed

    Sandelin, Albin; Wasserman, Wyeth W; Lenhard, Boris

    2004-07-01

    ConSite is a user-friendly, web-based tool for finding cis-regulatory elements in genomic sequences. Predictions are based on the integration of binding site prediction generated with high-quality transcription factor models and cross-species comparison filtering (phylogenetic footprinting). By incorporating evolutionary constraints, selectivity is increased by an order of magnitude as compared to single-sequence analysis. ConSite offers several unique features, including an interactive expert system for retrieving orthologous regulatory sequences. Programming modules and biological databases that form the foundation of the ConSite service are freely available to the research community. ConSite is available at http:/www.phylofoot.org/consite.

  14. Critical role of interleukin-17/interleukin-17 receptor axis in mediating Con A-induced hepatitis.

    PubMed

    Yan, Shu; Wang, Luman; Liu, Nan; Wang, Ying; Chu, Yiwei

    2012-04-01

    Concanavalin A (Con A)-induced hepatitis is thought to be a T-cell-mediated disease with active destruction of liver cells. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells. However, whether IL-17/IL-17 receptor (IL-17/IL-17R)-mediated responses are involved in T-cell-mediated Con A-induced liver injury remains unclear. In this study, we found that IL-17 expression was highly elevated in liver tissues during Con A-induced hepatitis. The increased levels of IL-17 were paralleled with the severity of liver injury reflected by Alanine aminotransaminase and histological assay as well as the secretion of tumor necrosis factor (TNF)-α and IL-6. Blockage of IL-17 significantly ameliorated Con A-induced hepatitis, while overexpression of IL-17 systemically resulted in massive hepatocyte necrosis in mice. Furthermore, overexpression of an IL-17R immunoglobulin G1 fusion protein significantly attenuated liver inflammation after acute Con A treatment. High expression of IL-17R on Kupffer cells was also observed along with the production of cytokines including TNF-α and IL-6. Inhibition of Kupffer cells by gadolinium chloride completely prevented Con A-induced liver injury and cytokine release. Finally, IL-17-expressing CD4(+) T and natural killer T cells were greatly increased in Con A-injected mice compared with that in controls. Overall, our results indicate that IL-17R signaling is critically involved in the pathogenesis in Con A-induced hepatitis, and blockade of IL-17/IL-17R signaling pathway may represent a novel therapeutic intervention in human autoimmune-related hepatitis.

  15. 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.

  16. Recognition of glycoprotein peroxidase via Con A-carrying self-assembly layer on gold.

    PubMed

    Liu, Songqin; Wang, Kewei; Du, Dan; Sun, Yueming; He, Lin

    2007-07-01

    We have successfully fabricated a self-assembled layer of concanavalin A (Con A) on a gold surface for recognition of glycoproteins. The type IV Con A is covalently bound to 11-mercaptoundecanoic acid (MUA) on gold with a 2-(5-norbornene-2,3-dicarboximido)-1,1,3,3-tetramethyluronium tetrafluoroborate (TNTU) linkage. The binding interaction between glycoproteins and self-assembled Con A is studied using horseradish peroxidase (HRP) as a model glycoprotein. Voltammetric, electrochemical impedance studies, and photometric activity measurements show the presence of both specific and nonspecific bindings of HRP to the Con A interface. The specific binding is attributed to the Con A-sugar interaction where Con A selectively recognizes the glycosylation sites of HRP. The catalytic current of the HRP-loaded electrode, because of catalytic oxidation of thionine in the presence of hydrogen peroxide (H2O2), is found to be proportional to the HRP concentrations in the incubation solution. A linear correlation coefficient of 0.993 was obtained over a wide HRP concentration range of 12.5 microg/mL to 1 mg/mL. The approach described in this study provides a simple yet selective means to immobilize glycoproteins on a solid support. The specific binding achieved is desirable in biosensor fabrication, glycoprotein separation, recognition, and purification as well as in drug-releasing systems.

  17. [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.

  18. Con-specific neighbours may enhance compensation capacity in an invasive plant.

    PubMed

    Lu, X; Dai, H; Ding, J

    2010-05-01

    Facilitation, both by inter- and intra-specific neighbours, is known to be an important process in structuring plant communities. However, only a small number of experiments have been reported on facilitation in plant invasions, especially between invasive con-specific individuals. Here, we focus on how con-specific neighbours of the invasive alien plant alligator weed affect the tolerance of alligator weed to herbivory by the introduced biological control agent, Agasicles hygrophila. We conducted greenhouse and garden experiments in which invasive plant density and herbivory intensity (artificial clipping and real herbivory) were manipulated. In the greenhouse experiment, artificial clipping significantly reduced plant biomass when plants were grown individually, but when con-specific neighbours were present in the same pot, biomass was not significantly different from control plants. Similarly, when compared to control plants, plants that were subjected to herbivory by A. hygrophila produced more biomass when grown with two con-specific neighbours than when grown alone. Real herbivory also resulted in an increased number of vegetative buds, and again when two con-specific neighbours were present this effect was increased (a 55.3% increase in buds when there was no neighbour, but a 111.6% increase in buds when two con-specific neighbours were present). In the garden experiment, in which plants were grown at high density (6 plants per pot), alligator weed fully recovered from defoliation caused by insects at levels from 20-30% to 100%. Our results indicate that the con-specific association may increase the compensatory ability to cope with intense damage in this invasive plant.

  19. Virulence, Speciation and Antibiotic Susceptibility of Ocular Coagualase Negative Staphylococci (CoNS)

    PubMed Central

    Priya, Ravindran; Mythili, Arumugam; Singh, Yendremban Randhir Babu; Sreekumar, Haridas; Manikandan, Palanisamy; Panneerselvam, Kanesan

    2014-01-01

    Background: Coagulase negative Staphylococci (CoNS) are common inhabitants of human skin and mucous membranes. With the emergence of these organisms as prominent pathogens in patients with ocular infections, investigation has intensified in an effort to identify important virulence factors and to inform new approaches to treatment and prevention. Aim: To isolate CoNS from ocular specimens; to study the possible virulence factors; speciation of coagulase negative staphylococci (CoNS) which were isolated from ocular complications; antibiotic susceptibility testing of ocular CoNS. Materials and Methods: The specimens were collected from the target patients who attended the Microbiology Laboratory of a tertiary care eye hospital in Coimbatore, Tamilnadu state, India. The isolates were subjected to tube and slide coagulase tests for the identification of CoNS. All the isolates were subjected to screening for lipase and protease activities. Screening for other virulence factors viz., slime production on Congo red agar medium and haemagglutination assay with use of 96-well microtitre plates. These isolates were identified upto species level by performing biochemical tests such as phosphatase test, arginine test, maltose and trehalose fermentation tests and novobiocin sensitivity test. The isolates were subjected to antibiotic susceptibility studies, based on the revised standards of Clinical and Laboratory Standards Institutes (CLSI). Results: During the one year of study, among the total 260 individuals who were screened, 100 isolates of CoNS were obtained. Lipolytic activity was seen in all the isolates, whereas 38 isolates showed a positive result for protease. A total of 63 isolates showed slime production. Of 100 isolates, 30 isolates were analyzed for haemagglutination, where 4 isolates showed the capacity to agglutinate the erythrocytes. The results of the biochemical analysis revealed that of the 100 isolates of CoNS, 43% were Staphylococcus epidermidis. The other

  20. 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.

  1. Structural basis of ConM binding with resveratrol, an anti-inflammatory and antioxidant polyphenol.

    PubMed

    Rocha, Bruno A M; Teixeira, Claudener S; Silva-Filho, José C; Nóbrega, Raphael B; Alencar, Daniel B; Nascimento, Kyria S; Freire, Valder N; Gottfried, Carmem J S; Nagano, Celso S; Sampaio, Alexandre H; Saker-Sampaio, Silvana; Cavada, Benildo S; Delatorre, Plínio

    2015-01-01

    Resveratrol can also inhibit the activation of proinflammatory mediators and cytokines at the early gene expression stage. It is well known that lectins are sugar-binding proteins that act as both pro- and anti-inflammatory molecules. Thus, the objective of this work was to verify the binding of a polyphenol compound with a lectin of Canavalia maritima (ConM) based on their ability to inhibit pro-inflammatory processes. To accomplish this, ConM was purified and crystallized, and resveratrol was soaked at 5mM for 2h of incubation. The crystal belongs to the monoclinic space group C2, the final refinement resulted in an Rfactor of 16.0% and an Rfree of 25.5%. Resveratrol binds in the rigid β-sheet through H-bonds and hydrophobic interaction with amino acids that compose the fifth and sixth β-strands of the rigid β-sheet of ConM. The ConM and resveratrol inhibited DPPH oxidation, showing synergic activity with the most effective ratio of 2:3 and carbohydrate binding site is not directly related to antioxidant activity. It is the interaction between ConM and resveratrol that indicates the synergism of these two molecules in acting as free radicals scavengers and in reducing the inflammatory process through the inhibition of many pro-inflammatory events. PMID:25192853

  2. Endothelial cells are damaged by autophagic induction before hepatocytes in Con A-induced acute hepatitis.

    PubMed

    Yang, Ming-Chen; Chang, Chih-Peng; Lei, Huan-Yao

    2010-08-01

    We have reported both T-cell-dependent and -independent hepatitis in immunocompetent and immunodeficiency mice, respectively, after intravenous injection of Con A in mice. The mode of hepatocyte cell death is different: autophagy for T-cell-independent hepatitis in contrast to apoptosis for T-cell-dependent one. In this study, we further demonstrate that liver blood vessels are the first target in both modes. The infused Con A bond to the hepatic vascular endothelial cells and cause its damage with autophagy. Before the elevation of the serum alanine aminotransferase at 6 h post-injection, the plasma leakage and hemorrhage occur at 1-3 h without inflammation. Con A induces autophagy of endothelial cells and hemorrhage that is enhanced by IFN-gamma. Using the endothelial cell line HMEC-1, a dose- and time-dependent cell death with autophagic LC3-II (microtubule-associated protein light chain 3) conversion was induced by Con A and was enhanced by IFN-gamma. In conclusion, Con A induced autophagy on hepatic endothelial cells; the damage of liver blood vessel occurs before the induction of T-cell-dependent hepatitis via apoptosis or T-cell-independent hepatitis via autophagy.

  3. Influence of protic ionic liquids on the structure and stability of succinylated Con A.

    PubMed

    Attri, Pankaj; Venkatesu, Pannuru

    2012-01-01

    We report the synthesis of a series of ionic liquids (ILs) from various ions having different kosmotropicity including dihydrogen phosphate (H(2)PO(4)(-)), hydrogen sulfate (HSO(4)(-)) and acetate (CH(3)COO(-)) as anions and chaotropic cation such as trialkylammonium cation. To characterize the biomolecular interactions of ILs with protein, we have explored the stability of succinylated Con A (S Con A) in the presence of these aqueous ILs, which are varied combinations of kosmotropic anion with chaotropic cation such as triethylammonium dihydrogen phosphate [(CH(3)CH(2))(3)NH][H(2)PO(4)] (TEAP), trimethylammonium acetate [(CH(3))(3)NH][CH(3)COO] (TMAA), trimethylammonium dihydrogen phosphate [(CH(3))(3)NH][H(2)PO(4)] (TMAP) and trimethylammonium hydrogen sulfate [(CH(3))(3)NH][HSO(4)] (TMAS). Circular dichroism (CD) and fluorescence experiments have been used to characterize the stability of S Con A by ILs. Our data distinctly demonstrate that the long alkyl chain IL TEAP is a strong stabilizer for S Con A. Further, our experimental results reveal that TEAP is an effective refolding enhancer for S Con A from a thermally denatured protein structure.

  4. ConPlex: a server for the evolutionary conservation analysis of protein complex structures.

    PubMed

    Choi, Yoon Sup; Han, Seong Kyu; Kim, Jinho; Yang, Jae-Seong; Jeon, Jouhyun; Ryu, Sung Ho; Kim, Sanguk

    2010-07-01

    Evolutionary conservation analyses are important for the identification of protein-protein interactions. For protein complex structures, sequence conservation has been applied to determine protein oligomerization states, to characterize native interfaces from non-specific crystal contacts, and to discriminate near-native structures from docking artifacts. However, a user-friendly web-based service for evolutionary conservation analysis of protein complexes has not been available. Therefore, we developed ConPlex (http://sbi.postech.ac.kr/ConPlex/) a web application that enables evolutionary conservation analyses of protein interactions within protein quaternary structures. Users provide protein complex structures; ConPlex automatically identifies protein interfaces and carries out evolutionary conservation analyses for the interface regions. Moreover, ConPlex allows the results of the residue-specific conservation analysis to be displayed on the protein complex structure and provides several options to customize the display output to fit each user's needs. We believe that ConPlex offers a convenient platform to analyze protein complex structures based on evolutionary conservation of protein-protein interface residues.

  5. The effects of CON repeal on Medicaid nursing home and long-term care expenditures.

    PubMed

    Grabowski, David C; Ohsfeldt, Robert L; Morrisey, Michael A

    2003-01-01

    Certificate-of-need (CON) and construction moratorium laws are used widely by states as a potential mechanism for constraining Medicaid nursing home expenditures. However, there is only limited empirical work examining whether these policies are effective at lowering Medicaid spending. Using aggregate state-level data from 1981 through 1998, this study found that states that repealed their CON and moratorium laws had no significant growth in either nursing home or long-term care Medicaid expenditures. In the context of declining occupancy rates within the nursing home market, this study provides strong evidence that states have little to fear in terms of increased expenditures with the repeal of CON and moratorium laws.

  6. 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.

  7. A Con A- purified hydatid glycoprotein fraction effectively diagnoses human hydatidosis.

    PubMed

    Kamel, Manal M; Maher, Kesmat M; Rabia, Ibrahim; Helmy, Ahmed H; El-Adawi, Azza I; Mousa, Mousa A; Mahgoub, Abeer M

    2006-12-01

    Diagnosis and quantification of Echinococcus granulosus infection in man and animal hosts are centralized to feasible control. This study included 93 serum samples, 25 sure positive hydatid cases confirmed surgically, 7 suspected cases diagnosed by indirect haemagglutination IHA and 41 cases other parasitic infections (15 S. mansoni, 8 Fasciola, 7 Ascaris, 5 H. nana & 6 Ancylostoma) diagnosed by microscopic examination and were negative by ELISA and/or IHA for anti-hydatid antibody. Twenty negative serum samples served as healthy controls. Six types of hydatid fluid antigens (crude, host-free & Con-A purified) of human and camel origin were subjected to electrophoretic separation (SDS-PAGE) and immunoblotting (EITB). The anti-hydatid IgG was detected in sera of the different groups for evaluation of sensitivity, specificity and diagnostic efficacy of each type of antigens. Detection of circulating hydatid antigen (CAg) was performed using anti rabbit hyperimmune sera raised against Con-A purified either human or camel hydatid antigen. SDS-PAGE revealed several bands ranging from 55-185 kDa with 10 kDa band shared by all antigens. The specific bands revealed by EITB for Con-A purified camel and human antigens were at 80, 110 & 55, 110 kDa respectively. ELISA highest sensitivity (96.9%) was by using host-free Con-A purified glycoprotein fraction of human hydatid antigen. Highest specificity (98.4%) was recorded upon use of either Con-A purified camel or human antigen with 94.5% & 97.7% diagnostic efficacy respectively. Detection of circulating antigen by polyclonal antibodies against Con-A purified human hydatid antigen revealed 91.8% specificity.

  8. 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.

  9. NCPP treatment alleviates ConA-induced hepatitis via reducing CD4+T activation and NO production.

    PubMed

    Liu, Chenghu; Gao, Shangxian; Qu, Zhonghua; Wang, Qun; Zhu, Faliang; Guo, Chun; Hou, Li; Wu, Ping; Shi, Yanping; Zhang, Lining

    2012-12-01

    Corynebacterium parvum (CP), a kind of immunomodulator, has been well documented in many diseases. Non-cell C. parvum product (NCPP) is a newly-found nano-preparation. To investigate the effect of NCPP on Con A-induced murine severe hepatitis, we pretreated mice with NCPP intraperitoneally. After 12 h, ConA (25 μg/g body wt) was injected intravenously to provoke severe hepatitis and the degree of liver injury was evaluated by serum transaminase analysis and heptatic tissue pathology. Results have shown that levels of serum transaminase and degree of liver injury in ConA/NCPP groups had significantly declined than those in ConA/PBS groups. Notably, results of flow cytometry have demonstrated that activation of CD4+T cells in ConA/NCPP groups has been down-regulated, compared with ConA/PBS groups. Further, levels of serum and KC-related nitric oxide (NO) was displayed significantly lower in ConA/NCPP groups than those in ConA/PBS groups. The results indicate that NCPP may alleviate ConA-induced hepatitis by reducing CD4+T activation and NO production. PMID:22537148

  10. Jóvenes con cáncer y supervivientes participan en estudio de oncofertilidad

    Cancer.gov

    Artículo sobre los esfuerzos que se realizan para conectar con pacientes jóvenes y lograr su participación en estudios clínicos para evaluar y remediar la esterilidad causada por el cáncer y su tratamiento.

  11. 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. PMID:26351131

  12. Algunas mujeres con cáncer de seno pueden abstenerse de quimioterapia

    Cancer.gov

    Resumen de resultados del estudio TAILORx indica que mujeres con cáncer de seno receptor de hormonas en estadio inicial tienen un riesgo bajo de recurrencia según una prueba de expresión de 21 genes.

  13. 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…

  14. Asociación de XMRV con enfermedades humanas se debe a contaminación

    Cancer.gov

    Nuevas investigaciones muestran que una asociación, mencionada en numerosos estudios, entre el retrovirus conocido como XMRV y el cáncer de próstata así como el síndrome de fatiga crónica, se debe a contaminación de laboratorio con un virus que se originó en ratones.

  15. 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…

  16. 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…

  17. Faculty Study of Pros and Cons of Clusters and Divisions. Final Report.

    ERIC Educational Resources Information Center

    Jaffe, Phil; And Others

    As part of a reorganization study underway at Oakton Community College, this report presents the pros and cons of retaining the college's interdisciplinary learning clusters or moving to discipline-based divisions. Following introductory material, the report explains the methodology by which two representatives from each campus cluster, one…

  18. 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…

  19. CHILES Con Pol: An ultra-deep JVLA survey probing galaxy evolution and cosmic magnetism

    NASA Astrophysics Data System (ADS)

    Hales, Christopher A.; Momjian, Emmanuel; van Gorkom, Jacqueline; Rupen, Michael P.; Greiner, Maksim; Ensslin, Torsten A.; Bonzini, Margherita; Padovani, Paolo; Harrison, Ian; Brown, Michael L.; Gim, Hansung; Yun, Min S.; Maddox, Natasha; Stewart, Adam; Fender, Rob P.; Tremou, Evangelia; Chomiuk, Laura; Peters, Charee; Wilcots, Eric M.; Lazio, Joseph

    2015-08-01

    We are undertaking a 1000 hour campaign with the Karl G. Jansky VLA to survey 0.2 square degrees of the COSMOS field in full polarization continuum at 1.4 GHz. Our observations are part of a joint program with the spectral line COSMOS HI Large Extragalactic Survey (CHILES). When complete, we expect our CHILES Continuum Polarization (CHILES Con Pol) survey to reach an SKA-era sensitivity of 500 nJy per 4 arcsecond resolving beam, the deepest view of the radio sky yet. CHILES Con Pol will open new and fertile parameter space, with sensitivity to star formation rates of 10 Msun per year out to an unprecedented redshift of z=2, and ultra-luminous infrared galaxies and sub-millimeter galaxies out to redshifts of z=8 and beyond. This rich resource will extend the utility of radio band studies beyond the usual radio quasar and radio galaxy populations, opening sensitivity to the starforming and radio-quiet AGN populations that form the bulk of extragalactic sources detected in the optical, X-ray, and infrared bands. In this talk I will outline the key science of CHILES Con Pol, including galaxy evolution and novel measurements of intergalactic magnetic fields. I will present initial results from the first 180 hours of the survey and describe our forthcoming Data Release 1. I invite the astronomical community to consider unique science that can be pursued with CHILES Con Pol radio data.

  20. 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...

  1. 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

  2. The crystal structures of the calcium-bound con-G and con-T[K7gamma] dimeric peptides demonstrate a metal-dependent helix-forming motif.

    PubMed

    Cnudde, Sara E; Prorok, Mary; Dai, Qiuyun; Castellino, Francis J; Geiger, James H

    2007-02-14

    Short peptides that have the ability to form stable alpha-helices in solution are rare, and a number of strategies have been used to produce them, including the use of metal chelation to stabilize folding of the backbone. However, no example exists of a structurally well-defined helix stabilized exclusively through metal ion chelation. Conantokins (con)-G and -T are short peptides that are potent antagonists of N-methyl-D-aspartate receptor channels. While con-G exhibits no helicity alone, it undergoes a structural transition to a helical conformation in the presence of a variety of multivalent cations, especially Mg2+ and Ca2+. This complexation also results in antiparallel dimerization of two peptide helices in the presence of Ca2+, but not Mg2+. A con-T variant, con-T[K7gamma], displays very similar behavior. We have solved the crystal structures of both Ca2+/con-G and Ca2+/con-T [K7gamma] at atomic resolution. These structures clearly show the nature of the metal-dependent dimerization and helix formation and surprisingly also show that the con-G dimer interface is completely different from the con-T[K7gamma] interface, even though the metal chelation is similar in the two peptides. This represents a new paradigm in helix stabilization completely independent of the hydrophobic effect, which we define as the "metallo-zipper."

  3. Papás que tienen a un niño con cáncer

    Cancer.gov

    Información práctica para los padres, cuando un hijo tiene cáncer. Sugerencias para ayudar a los niños y a los padres a salir adelante y mantenerse fuertes; junto con respuestas a preguntas que padres e hijos hacen con frecuencia.

  4. 76 FR 54533 - Pipeline Safety: Issuance of Draft Decision on GexCon US, Inc. Petition for Approval of Flame...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-01

    ... Statement in the Federal Register published on April 11, 2000 (65 FR 19477) or visit http://www.regulations...Con US, Inc. Petition for Approval of Flame Acceleration Simulator AGENCY: Pipeline and Hazardous... a Draft Decision on GexCon US, Inc.'s petition for approval of Flame Acceleration Simulator...

  5. 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.

  6. Confirmatory analysis of opinions regarding the pros and cons of mammography.

    PubMed

    Rakowski, W; Andersen, M R; Stoddard, A M; Urban, N; Rimer, B K; Lane, D S; Fox, S A; Costanza, M E

    1997-09-01

    This investigation extends prior research to apply decision-making constructs from the transtheoretical model (TTM) of behavior change to mammography screening. Study subjects were 8,914 women ages 50-80, recruited from 40 primarily rural communities in Washington State. Structural equation modeling showed that favorable and unfavorable opinions about mammography (i.e., pros and cons) fit the observed data. Analysis of variance supported the associations between readiness to obtain screening (i.e., stage of adoption) and opinions about mammography (i.e., decisional balance) previously found in research using smaller samples from another geographic region. This report extends these earlier studies by using structural equation modeling, opinion scales based both on principal component analyses and on a priori definitions, a developmental sample and a confirmatory sample, and by sampling from a different geographic region. It is recommended that future research examine whether opinions regarding the cons of mammography are more individually specific than the pros. PMID:9302540

  7. 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.

  8. 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.

  9. Cómo hacer las gestiones con su plan de salud

    Cancer.gov

    Hay formas de saber si su plan de salud cubre los costos de atención médica de rutina durante un estudio clínico. Esta información puede servirle para saber con quién comunicarse para solicitar ayuda, preguntas que puede hacer y la información que debe recoger y guardar si decide participar en un estudio clínico.

  10. 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

    2016-07-01

    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.

  11. Online measurement of motivational processes: introducing the Continuous Delay Aversion Test (ConDAT).

    PubMed

    Müller, Ueli C; Sonuga-Barke, Edmund J S; Brandeis, Daniel; Steinhausen, Hans-Christoph

    2006-02-15

    The Continuous Delay Aversion Test (ConDAT), a new computer task for online monitoring and continuously measuring delay aversion (DA), is introduced. DA is a motivational style related to a shortened delay gradient which is proposed as a major endophenotype of attention deficit hyperactivity disorder (ADHD). It is characterised by avoiding or escaping from delay-rich situations despite the prospects of a reward. In each ConDAT trial the rapidly diminishing reward/delay ratio, which tends asymptotically towards zero, is visually presented on the computer screen. The test subject is permanently confronted with the question whether to quit or to continue the trial in the face of the deteriorating reward/time ratio. An elaborated control of stimuli and responses, including the sending of trigger codes to external recording devices, makes the task useful for neurophysiological or brain imaging experiments. Compared to existing tasks, the ConDAT is more flexible and sensitive due to its asymptotic open-ended trials and the interval-scaled output measure. Pilot data give evidence for satisfactory reliability and external validity of the task. PMID:16376991

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27166375

  17. 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.

  18. 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. PMID:25724751

  19. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures.

    PubMed

    Landau, Meytal; Mayrose, Itay; Rosenberg, Yossi; Glaser, Fabian; Martz, Eric; Pupko, Tal; Ben-Tal, Nir

    2005-07-01

    Key amino acid positions that are important for maintaining the 3D structure of a protein and/or its function(s), e.g. catalytic activity, binding to ligand, DNA or other proteins, are often under strong evolutionary constraints. Thus, the biological importance of a residue often correlates with its level of evolutionary conservation within the protein family. ConSurf (http://consurf.tau.ac.il/) is a web-based tool that automatically calculates evolutionary conservation scores and maps them on protein structures via a user-friendly interface. Structurally and functionally important regions in the protein typically appear as patches of evolutionarily conserved residues that are spatially close to each other. We present here version 3.0 of ConSurf. This new version includes an empirical Bayesian method for scoring conservation, which is more accurate than the maximum-likelihood method that was used in the earlier release. Various additional steps in the calculation can now be controlled by a number of advanced options, thus further improving the accuracy of the calculation. Moreover, ConSurf version 3.0 also includes a measure of confidence for the inferred amino acid conservation scores.

  20. The ConSurf-DB: pre-calculated evolutionary conservation profiles of protein structures.

    PubMed

    Goldenberg, Ofir; Erez, Elana; Nimrod, Guy; Ben-Tal, Nir

    2009-01-01

    ConSurf-DB is a repository for evolutionary conservation analysis of the proteins of known structures in the Protein Data Bank (PDB). Sequence homologues of each of the PDB entries were collected and aligned using standard methods. The evolutionary conservation of each amino acid position in the alignment was calculated using the Rate4Site algorithm, implemented in the ConSurf web server. The algorithm takes into account the phylogenetic relations between the aligned proteins and the stochastic nature of the evolutionary process explicitly. Rate4Site assigns a conservation level for each position in the multiple sequence alignment using an empirical Bayesian inference. Visual inspection of the conservation patterns on the 3D structure often enables the identification of key residues that comprise the functionally important regions of the protein. The repository is updated with the latest PDB entries on a monthly basis and will be rebuilt annually. ConSurf-DB is available online at http://consurfdb.tau.ac.il/

  1. Con-T[M8Q] potently attenuates the expression and development of morphine tolerance in mice.

    PubMed

    Ren, Baolan; Zhou, Zhijie; Liu, Zhuguo; Li, Bailin; Ou, Jie; Dai, Qiuyun

    2015-06-15

    As a variant of peptide conantokin-T (con-T), con-T[M8Q] is derived from the venom of Conus tulipa. Our previous study has demonstrated that con-T[M8Q] selectively targets N-methyl-d-aspartate receptor (NMDAR) NR2B subunit. In the present study, we determined the effects of con-T[M8Q] on the expression and development of morphine tolerance using hot plate test and acetic acid writhing test. Our results demonstrated that con-T[M8Q] could efficiently attenuate the expression and development of morphine analgesic tolerance in mice at low doses (5-20nmol/kg), and it exhibited more potent effects compared with ifenprodil, a typical small-molecule antagonist of NMDAR. In addition, low doses of con-T[M8Q] (5-20nmol/kg) did not cause drug resistance and apparent analgesic activity compared with morphine. Taken together, con-T[M8Q] could be a promising new candidate in attenuating morphine tolerance. PMID:25896730

  2. Con-T[M8Q] potently attenuates the expression and development of morphine tolerance in mice.

    PubMed

    Ren, Baolan; Zhou, Zhijie; Liu, Zhuguo; Li, Bailin; Ou, Jie; Dai, Qiuyun

    2015-06-15

    As a variant of peptide conantokin-T (con-T), con-T[M8Q] is derived from the venom of Conus tulipa. Our previous study has demonstrated that con-T[M8Q] selectively targets N-methyl-d-aspartate receptor (NMDAR) NR2B subunit. In the present study, we determined the effects of con-T[M8Q] on the expression and development of morphine tolerance using hot plate test and acetic acid writhing test. Our results demonstrated that con-T[M8Q] could efficiently attenuate the expression and development of morphine analgesic tolerance in mice at low doses (5-20nmol/kg), and it exhibited more potent effects compared with ifenprodil, a typical small-molecule antagonist of NMDAR. In addition, low doses of con-T[M8Q] (5-20nmol/kg) did not cause drug resistance and apparent analgesic activity compared with morphine. Taken together, con-T[M8Q] could be a promising new candidate in attenuating morphine tolerance.

  3. 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.

  4. Estudio muestra reducción de mortalidad en hombres con cáncer de próstata de grado intermedio

    Cancer.gov

    Terapia hormonal por corto tiempo administrada en combinación con radioterapia a hombres con cáncer de próstata en estadio inicial aumentó sus posibilidades de vivir más en comparación con tratamiento de radioterapia sola, según un estudio clínico patroci

  5. ConMap: Investigating new computer-based approaches to assessing conceptual knowledge structure in physics

    NASA Astrophysics Data System (ADS)

    Beatty, Ian D.

    2000-06-01

    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 in this dissertation, proposed and investigated some novel methods for assessing the conceptual knowledge structure of physics students. A set of brief computer-administered tasks for eliciting students' conceptual associations was designed. The basic approach of the tasks was to elicit spontaneous term associations from subjects by presenting them with a prompt term, or problem, or topic area, and having them type a set of response terms. Each response was recorded along with the time spent thinking of and typing it. Several studies were conducted in which data was collected on introductory physics students' performance on the tasks. A detailed statistical description of the data was compiled. Phenomenological characterization of the data (description and statistical summary of observed patterns) provided insight into the way students respond to the tasks, and discovered some notable features to guide modeling efforts. Possible correlations were investigated, some among different aspects of the ConMap data, others between aspects of the data and students' in-course exam scores. Several correlations were found which suggest that the ConMap tasks can successfully reveal information about students' knowledge structuring and level of expertise. Similarity was observed between data from one of the tasks and results from a traditional concept map task. Two rudimentary quantitative models for the temporal aspects of student performance on one of the tasks were constructed, one based on random probability distributions and the other on a detailed deterministic representation of conceptual knowledge structure. Both models were

  6. Nitrogen-detected CAN and CON experiments as alternative experiments for main chain NMR resonance assignments

    PubMed Central

    Takeuchi, Koh; Heffron, Gregory; Sun, Zhen-Yu J.; Frueh, Dominique P.

    2010-01-01

    Heteronuclear direct-detection experiments, which utilize the slower relaxation properties of low γ nuclei, such as 13C have recently been proposed for sequence-specific assignment and structural analyses of large, unstructured, and/or paramagnetic proteins. Here we present two novel 15N direct-detection experiments. The CAN experiment sequentially connects amide 15N resonances using 13Cα chemical shift matching, and the CON experiment connects the preceding 13C′ nuclei. When starting from the same carbon polarization, the intensities of nitrogen signals detected in the CAN or CON experiments would be expected four times lower than those of carbon resonances observed in the corresponding 13C-detecting experiment, NCA-DIPAP or NCO-IPAP (Bermel et al. 2006b; Takeuchi et al. 2008). However, the disadvantage due to the lower γ is counteracted by the slower 15N transverse relaxation during detection, the possibility for more efficient decoupling in both dimensions, and relaxation optimized properties of the pulse sequences. As a result, the median S/N in the 15N observe CAN experiment is 16% higher than in the 13C observe NCA-DIPAP experiment. In addition, significantly higher sensitivity was observed for those residues that are hard to detect in the NCA-DIPAP experiment, such as Gly, Ser and residues with high-field Cα resonances. Both CAN and CON experiments are able to detect Pro resonances that would not be observed in conventional proton-detected experiments. In addition, those experiments are free from problems of incomplete deuterium-to-proton back exchange in amide positions of perdeuterated proteins expressed in D2O. Thus, these features and the superior resolution of 15N-detected experiments provide an attractive alternative for main chain assignments. The experiments are demonstrated with the small model protein GB1 at conditions simulating a 150 kDa protein, and the 52 kDa glutathione S-transferase dimer, GST. PMID:20556482

  7. 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.

  8. Nitrogen-detected CAN and CON experiments as alternative experiments for main chain NMR resonance assignments.

    PubMed

    Takeuchi, Koh; Heffron, Gregory; Sun, Zhen-Yu J; Frueh, Dominique P; Wagner, Gerhard

    2010-08-01

    Heteronuclear direct-detection experiments, which utilize the slower relaxation properties of low gamma nuclei, such as (13)C have recently been proposed for sequence-specific assignment and structural analyses of large, unstructured, and/or paramagnetic proteins. Here we present two novel (15)N direct-detection experiments. The CAN experiment sequentially connects amide (15)N resonances using (13)C(alpha) chemical shift matching, and the CON experiment connects the preceding (13)C' nuclei. When starting from the same carbon polarization, the intensities of nitrogen signals detected in the CAN or CON experiments would be expected four times lower than those of carbon resonances observed in the corresponding (13)C-detecting experiment, NCA-DIPAP or NCO-IPAP (Bermel et al. 2006b; Takeuchi et al. 2008). However, the disadvantage due to the lower gamma is counteracted by the slower (15)N transverse relaxation during detection, the possibility for more efficient decoupling in both dimensions, and relaxation optimized properties of the pulse sequences. As a result, the median S/N in the (15)N observe CAN experiment is 16% higher than in the (13)C observe NCA-DIPAP experiment. In addition, significantly higher sensitivity was observed for those residues that are hard to detect in the NCA-DIPAP experiment, such as Gly, Ser and residues with high-field C(alpha) resonances. Both CAN and CON experiments are able to detect Pro resonances that would not be observed in conventional proton-detected experiments. In addition, those experiments are free from problems of incomplete deuterium-to-proton back exchange in amide positions of perdeuterated proteins expressed in D(2)O. Thus, these features and the superior resolution of (15)N-detected experiments provide an attractive alternative for main chain assignments. The experiments are demonstrated with the small model protein GB1 at conditions simulating a 150 kDa protein, and the 52 kDa glutathione S-transferase dimer, GST.

  9. Zebrafish con/disp1 reveals multiple spatiotemporal requirements for Hedgehog-signaling in craniofacial development

    PubMed Central

    2009-01-01

    Background The vertebrate head skeleton is derived largely from cranial neural crest cells (CNCC). Genetic studies in zebrafish and mice have established that the Hedgehog (Hh)-signaling pathway plays a critical role in craniofacial development, partly due to the pathway's role in CNCC development. Disruption of the Hh-signaling pathway in humans can lead to the spectral disorder of Holoprosencephaly (HPE), which is often characterized by a variety of craniofacial defects including midline facial clefting and cyclopia [1,2]. Previous work has uncovered a role for Hh-signaling in zebrafish dorsal neurocranium patterning and chondrogenesis, however Hh-signaling mutants have not been described with respect to the ventral pharyngeal arch (PA) skeleton. Lipid-modified Hh-ligands require the transmembrane-spanning receptor Dispatched 1 (Disp1) for proper secretion from Hh-synthesizing cells to the extracellular field where they act on target cells. Here we study chameleon mutants, lacking a functional disp1(con/disp1). Results con/disp1 mutants display reduced and dysmorphic mandibular and hyoid arch cartilages and lack all ceratobranchial cartilage elements. CNCC specification and migration into the PA primorida occurs normally in con/disp1 mutants, however disp1 is necessary for post-migratory CNCC patterning and differentiation. We show that disp1 is required for post-migratory CNCC to become properly patterned within the first arch, while the gene is dispensable for CNCC condensation and patterning in more posterior arches. Upon residing in well-formed pharyngeal epithelium, neural crest condensations in the posterior PA fail to maintain expression of two transcription factors essential for chondrogenesis, sox9a and dlx2a, yet continue to robustly express other neural crest markers. Histology reveals that posterior arch residing-CNCC differentiate into fibrous-connective tissue, rather than becoming chondrocytes. Treatments with Cyclopamine, to inhibit Hh

  10. 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.

  11. 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.

  12. Hable con Ella (Talk to Her) through the lens of gender.

    PubMed

    Yanof, Judith A

    2008-04-01

    In the 2002 film Hable con Ella (Talk to Her), Spanish writer-director Pedro Almodóvar plays with the ambiguity of gender, transcending conventional assumptions about "masculinity" and "femininity." Each of the four main characters holds complex, varied, and, in some cases, gender-bending gender identifications. The theme of gender plasticity is a prominent motif in this film. However, underlying the narrative, there is also a perverse subtext that relies on rigidly binary gender stereotypes to define relationships between men and women. Both these views of gender which operate dialectically, create a complex tapestry through which Almodóvar explores his characters' problems in attaining intimacy.

  13. 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.

  14. Avoided costs associated with cogeneration: a case study of Con Ed

    SciTech Connect

    Bright, R.; Davitian, H.; Martorella, J.

    1980-08-01

    The potential impact of cogeneration in office and apartment buildings in New York City on the Consolidated Edison Company (Con Ed) has been investigated using a method of utility cost and fuel use analysis developed at Brookhaven National Laboratory. This method computes a utility's long run marginal costs and long run marginal fuel consumption associated with load modifications due to the introduction of on-site energy producing technologies. The principal findings of this study show that Con Ed's long run average cost is more likely to go down than up due to cogeneration in office and apartment building; the utility's avoided costs (i.e., its long run marginal savings) associated with the gross power output of the cogeneration systems are 10.5 cents/KWh for the office building and 6.4 cents/KWh for the apartment buildings; the utility's marginal savings include a component for avoided capacity costs; and there are net savings in the use of oil due to cogeneration (assuming the building used oil for its boilers before it switched and diesel fuel in its cogenerators afterwards).

  15. Co-N Decorated Hierarchically Porous Graphene Aerogel for Efficient Oxygen Reduction Reaction in Acid.

    PubMed

    Fu, Xiaogang; Choi, Ja-Yeon; Zamani, Pouyan; Jiang, Gaopeng; Hoque, Md Ariful; Hassan, Fathy Mohamed; Chen, Zhongwei

    2016-03-01

    Nitrogen-functionalized graphene materials have been demonstrated as promising electrocatalyst for the oxygen reduction reaction (ORR), owning to their respectable activity and excellent stability in alkaline electrolyte. However, they exhibit unacceptable catalytic activity in acid medium. Here, a hierarchically porous Co-N functionalized graphene aerogel is prepared as an efficient catalyst for the ORR in acid electrolyte. In the preparation process, polyaniline (PANI) is introduced as a pore-forming agent to aid in the self-assembly of graphene species into a porous aerogel networks, and a nitrogen precursor to induce in situ nitrogen doping. Therefore, a Co-N decorated graphene aerogel framework with a large surface area (485 m(2) g(-1)) and an abundance of meso/macropores is effectively formed after heat treatment. Such highly desired structures can not only expose sufficient active sites for the ORR but also guarantee the fast mass transfer in the catalytic process, which provides significant catalytic activity with positive onset and half wave potentials, low hydrogen peroxide yield, high resistance to methanol crossover, and remarkable stability that is comparable to commercial Pt/C in acid medium. PMID:26937737

  16. 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

  17. 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

  18. Retinoic acid alleviates Con A-induced hepatitis and differentially regulates effector production in NKT cells.

    PubMed

    Lee, Kyoo-A; Song, You Chan; Kim, Ga-Young; Choi, Gyeyoung; Lee, Yoon-Sook; Lee, Jung-Mi; Kang, Chang-Yuil

    2012-07-01

    Retinoic acid (RA) is a diverse regulator of immune responses. Although RA promotes natural killer T (NKT) cell activation in vitro by increasing CD1d expression on antigen-presenting cells (APCs), the direct effects of RA on NKT-cell responses in vivo are not known. In the present study, we demonstrated the effect of RA on the severity of Con A-induced hepatitis and molecular changes of NKT cells. First, we demonstrated that Con A-induced liver damage was ameliorated by RA. In correlation with cytokine levels in serum, RA regulated the production of IFN-γ and IL-4 but not TNF-α by NKT cells without influencing the NKT-cell activation status. However, RA did not alleviate α-GalCer-induced liver injury, even though it reduced IFN-γ and IL-4 but not TNF-α levels in serum. This regulation was also detected when liver mononuclear cells (MNCs) or NKT hybridoma cells were treated with RA in vitro. The regulatory effect of RA on NKT cells was mediated by RAR-α, and RA reduced the phosphorylation of MAPK. These results suggest that RA differentially modulates the production of effector cytokines by NKT cells in hepatitis, and the suppressive effect of RA on hepatitis varies with the pathogenic mechanism of liver injury.

  19. PDP-CON: prediction of domain/linker residues in protein sequences using a consensus approach.

    PubMed

    Chatterjee, Piyali; Basu, Subhadip; Zubek, Julian; Kundu, Mahantapas; Nasipuri, Mita; Plewczynski, Dariusz

    2016-04-01

    The prediction of domain/linker residues in protein sequences is a crucial task in the functional classification of proteins, homology-based protein structure prediction, and high-throughput structural genomics. In this work, a novel consensus-based machine-learning technique was applied for residue-level prediction of the domain/linker annotations in protein sequences using ordered/disordered regions along protein chains and a set of physicochemical properties. Six different classifiers-decision tree, Gaussian naïve Bayes, linear discriminant analysis, support vector machine, random forest, and multilayer perceptron-were exhaustively explored for the residue-level prediction of domain/linker regions. The protein sequences from the curated CATH database were used for training and cross-validation experiments. Test results obtained by applying the developed PDP-CON tool to the mutually exclusive, independent proteins of the CASP-8, CASP-9, and CASP-10 databases are reported. An n-star quality consensus approach was used to combine the results yielded by different classifiers. The average PDP-CON accuracy and F-measure values for the CASP targets were found to be 0.86 and 0.91, respectively. The dataset, source code, and all supplementary materials for this work are available at https://cmaterju.org/cmaterbioinfo/ for noncommercial use.

  20. Aggregation analysis of Con A binding proteins of human seminal plasma: a dynamic light scattering study.

    PubMed

    Tomar, Anil Kumar; Sooch, Balwinder Singh; Singh, Sarman; Yadav, Savita

    2013-02-01

    Concanavalin A (Con A) binding fraction of human seminal plasma is vital as it shows decapacitating activity and contains proteins which have critical roles in fertility related processes. Con A binding proteins were isolated by lectin affinity chromatography. These proteins form high molecular weight aggregates at near physiological pH (7.0) as inferred by gel filtration. Aggregation analysis was performed by dynamic light scattering (DLS). DLS analysis was also performed at different pH values and in presence of various additives including NaCl, EDTA, cholesterol and sugars, such as d-glucose, d-fructose and d-mannose to identify their effect on aggregation size. The results indicate that degree of aggregation was highly reduced in presence of d-fructose, EDTA and at lower and higher pH values as depicted by lowering of hydrodynamic radii. This aggregation behaviour might be decisive for fertility related events with a suggestive role towards inhibition of premature capacitation.

  1. Co-N Decorated Hierarchically Porous Graphene Aerogel for Efficient Oxygen Reduction Reaction in Acid.

    PubMed

    Fu, Xiaogang; Choi, Ja-Yeon; Zamani, Pouyan; Jiang, Gaopeng; Hoque, Md Ariful; Hassan, Fathy Mohamed; Chen, Zhongwei

    2016-03-01

    Nitrogen-functionalized graphene materials have been demonstrated as promising electrocatalyst for the oxygen reduction reaction (ORR), owning to their respectable activity and excellent stability in alkaline electrolyte. However, they exhibit unacceptable catalytic activity in acid medium. Here, a hierarchically porous Co-N functionalized graphene aerogel is prepared as an efficient catalyst for the ORR in acid electrolyte. In the preparation process, polyaniline (PANI) is introduced as a pore-forming agent to aid in the self-assembly of graphene species into a porous aerogel networks, and a nitrogen precursor to induce in situ nitrogen doping. Therefore, a Co-N decorated graphene aerogel framework with a large surface area (485 m(2) g(-1)) and an abundance of meso/macropores is effectively formed after heat treatment. Such highly desired structures can not only expose sufficient active sites for the ORR but also guarantee the fast mass transfer in the catalytic process, which provides significant catalytic activity with positive onset and half wave potentials, low hydrogen peroxide yield, high resistance to methanol crossover, and remarkable stability that is comparable to commercial Pt/C in acid medium.

  2. Effect of endogenous catecholamines on apoptosis of Con A-activated lymphocytes of rats.

    PubMed

    Jiang, Jian-Lan; Peng, Yu-Ping; Qiu, Yi-Hua; Wang, Jian-Jun

    2007-12-01

    Our previous studies show that lymphocytes express tyrosine hydroxylase (TH) and synthesize catecholamines (CAs) including dopamine, epinephrine and norepinephrine, and that the lymphocytes-derived endogenous CAs affect function of lymphocytes via autocrine/paracrine pathways. Over recent years, induction of apoptosis has been suggested to be a possible mechanism underlying the endogenous CAs-mediated lymphocyte proliferation, differentiation and activation. However, direct effect of the lymphocytes-synthesized CAs on lymphocyte apoptosis is less known. In the present study, TH inhibitor alpha-methyl-p-tyrosine (alpha-MT) and monoamine oxydase inhibitor pargyline were employed to block the synthesis and degradation of CAs in lymphocytes activated by concanavalin A (Con A). Apoptotic cells and apoptosis-related genes and proteins, Bax, Bcl-2, Fas, Fas-Ligand (FasL) and caspase-3, were examined in the lymphocytes treated with alpha-MT or pargyline by means of Annexin V/propidium iodide (PI) staining, real-time PCR and Western blot analyses, respectively. The treatment with alpha-MT of 10(-6) M and 10(-5) M (not 10(-7) M) notably reduced intracellular and supernatant DA, E and NE of the Con A-activated lymphocytes in a dose-dependent manner, and correspondingly, the treatment induced a remarkable decrease of apoptotic lymphocytes but not necrotic cells. The expression of Bax, Fas, FasL and caspase-3 mRNAs and proteins was significantly inhibited in the Con A-activated lymphocytes after the cells were treated with alpha-MT of 10(-6) M and 10(-5) M; but the expression of Bcl-2 mRNA and protein was dramatically increased by the alpha-MT treatment. Contrarily, the treatment with pargyline of 10(-6) M and 10(-5) M (not 10(-7) M) evidently increased the intracellular and supernatant DA, E and NE contents of the Con A-activated lymphocytes in a dose-dependent manner, and meanwhile, it caused a striking increase of apoptotic lymphocytes but not necrotic cells. The expression

  3. 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.

  4. 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. PMID:27020875

  5. Perceived pros and cons of smoking and quitting in hard-core smokers: a focus group study

    PubMed Central

    2014-01-01

    Background In the last decade, so-called hard-core smokers have received increasing interest in research literature. For smokers in general, the study of perceived costs and benefits (or ‘pros and cons’) of smoking and quitting is of particular importance in predicting motivation to quit and actual quitting attempts. Therefore, this study aims to gain insight into the perceived pros and cons of smoking and quitting in hard-core smokers. Methods We conducted 11 focus group interviews among current hard-core smokers (n = 32) and former hard-core smokers (n = 31) in the Netherlands. Subsequently, each participant listed his or her main pros and cons in a questionnaire. We used a structural procedure to analyse the data obtained from the group interviews and from the questionnaires. Results Using the qualitative data of both the questionnaires and the transcripts, the perceived pros and cons of smoking and smoking cessation were grouped into 6 main categories: Finance, Health, Intrapersonal Processes, Social Environment, Physical Environment and Food and Weight. Conclusions Although the perceived pros and cons of smoking in hard-core smokers largely mirror the perceived pros and cons of quitting, there are some major differences with respect to weight, social integration, health of children and stress reduction, that should be taken into account in clinical settings and when developing interventions. Based on these findings we propose the ‘Distorted Mirror Hypothesis’. PMID:24548463

  6. Highly sensitive gold nanoparticles biosensor chips modified with a self-assembled bilayer for detection of Con A.

    PubMed

    Guo, Caixin; Boullanger, Paul; Jiang, Long; Liu, Tao

    2007-03-15

    In this paper, an improved method for detection of Concanavalin A (Con A) with label-free optical biosensors is reported. 1-Dodecanethiol (DDT) was self-assembled onto gold nanoparticles which were deposited on glass slides, and then glycolipid molecules were inserted into dodecanethiol by physical interactions only. The recognition between Con A and carbohydrate was observed by UV-vis spectrophotometry. The absorption spectrum shifted when Con A was bound to the sugar residues of glycolipids immobilized onto nanogold slides, while almost no spectrum change was observed when another nonspecific protein molecule met the nanogold slides. The self-assembled bilayer on nanogold substrates had very high sensitivity for Con A, the minimum detection concentration of Con A can be down to 0.1 nM. In addition to the ultra sensitivity for investigating carbohydrate-lectin interaction, the self-assembled bilayer structure, is expected to replace many receptors which require time-consuming organic syntheses for the fixation to the transducer. The simplicity and sensitivity of this biosensor architecture once again show the prospect of nanogold application in biosensor.

  7. Multi-wall carbon nanotube-polyaniline biosensor based on lectin-carbohydrate affinity for ultrasensitive detection of Con A.

    PubMed

    Hu, Fangxin; Chen, Shihong; Wang, Chengyan; Yuan, Ruo; Xiang, Yun; Wang, Cun

    2012-04-15

    In this paper, a novel method for detecting concanavalin A (Con A) was developed based on lectin-carbohydrate biospecific interactions. Multi-wall carbon nanotube-polyaniline (MWNT-PANI) nanocomposites, synthesized by in situ polymerization, were chosen to immobilize d-glucose through the Schiff-base reaction. The immobilized D-glucose showed high binding sensitivity and excellent selectivity to its target lectin, Con A. Cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), transmission electron microscopy (TEM) and atomic force microscopy (AFM) were applied to characterize the assembly process of the modified electrode. Due to the high affinity of Con A for D-glucose and high stability of the propounded sensing platform, the fabricated biosensor achieved ultrasensitive detection of Con A with good sensitivity, acceptable reproducibility and stability. The changes of response current were proportional to the Con A concentrations from 3.3 pM to 9.3 nM, with a detection limit of 1.0 pM. Therefore, the combination of MWNT-PANI nanocomposites and the special binding force between lectin and carbohydrate provides an efficient and promising platform for the fabrication of bioelectrochemical devices.

  8. [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. PMID:27362821

  9. Methane activation by cobalt cluster cations, Con+ (n=2-16): Reaction mechanisms and thermochemistry of cluster-CHx (x=0-3) complexes

    NASA Astrophysics Data System (ADS)

    Citir, Murat; Liu, Fuyi; Armentrout, P. B.

    2009-02-01

    The kinetic energy dependences of the reactions of Con+ (n =2-16) with CD4 are studied in a guided ion beam tandem mass spectrometer over the energy range of 0-10 eV. The main products are hydride formation, ConD+, dehydrogenation to form ConCD2+, and double dehydrogenation yielding ConC+. These primary products decompose to form secondary and higher order products, ConCD+, Con-1D+, Con-1C+, Con-1CD+, and Con-1CD2+ at higher energies. Adduct formation of ConCD4+ is also observed for the largest cluster cations, n ≥10. In general, the efficiencies of the single and double dehydrogenation processes increase with cluster size, although the hexamer cation shows a reduced reactivity compared to its neighbors. All reactions exhibit thresholds, and cross sections for the various primary and secondary reactions are analyzed to yield reaction thresholds from which bond energies for cobalt cluster cations to D, C, CD, CD2, and CD3 are determined. The relative magnitudes of these bond energies are consistent with simple bond order considerations. Bond energies for larger clusters rapidly reach relatively constant values, which are used to estimate the chemisorption energies of the C, CD, CD2, and CD3 molecular fragments to cobalt surfaces.

  10. [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.

  11. Vibrational relaxation of CO(n = 1) in collisions with He

    NASA Astrophysics Data System (ADS)

    Schinke, R.; Diercksen, G. H. F.

    1985-11-01

    A ful ab inition study of vibrational relaxation of CO(n = 1) in collisions with the normal and lightweight isotopes of helium is presented. The vibrational coordinate dependence of the interaction potential is calculated directly. Dynamical calculations are performed within the infinite-order-sudden (IOS) and centrifugal-sudden (CS) approximations. The IOS cross sections agree very well with the corresponding CS results for both He isotopes, but the IOS/CS ratio shows a different energy behavior for each isotope. It is explicitly demonstrated that the often used procedure to extract the vibrational coordinate dependence of the interaction potential from a dumbbell fit of the rigid-rotor surface is wrong for He-CO.

  12. Cogenerator to quit Con Ed by selling kWh to neighbor

    SciTech Connect

    Springer, N.

    1986-02-10

    Selling 125 kilowatts of electricity around the clock to a nearby supermarket will make cogeneration feasible for the Flagship Restaurant in White Plains, NY, allowing it to drop off Consolidated Edison's grid and pay for a necessary backup generator, according to John Prayias, the restaurant's owner. The ambitious $536,000 project, which will be financed conventionally with a commercial bank loan, will eliminate the Flagship's $70,000 electricity costs and the $7240 spent of heating and domestic hot water, Prayias said. By selling the power to the supermarket at 9 cents per kilowatt hour - 3 cents less than Con Ed's rate of 12 cents per kWh - the restaurant will collect $120,000 a year in revenues - just about enough to cover the cost of diesel fuel for the 350-kW system and pay for monitoring and maintenance.

  13. Nest destruction elicits indiscriminate con- versus heterospecific brood parasitism in a captive bird.

    PubMed

    Shaw, Rachael C; Feeney, William E; Hauber, Mark E

    2014-12-01

    Following nest destruction, the laying of physiologically committed eggs (eggs that are ovulated, yolked, and making their way through the oviduct) in the nests of other birds is considered a viable pathway for the evolution of obligate interspecific brood parasitism. While intraspecific brood parasitism in response to nest predation has been experimentally demonstrated, this pathway has yet to be evaluated in an interspecific context. We studied patterns of egg laying following experimental nest destruction in captive zebra finches, Taeniopygia guttata, a frequent intraspecific brood parasite. We found that zebra finches laid physiologically committed eggs indiscriminately between nests containing conspecific eggs and nests containing heterospecific eggs (of Bengalese finches, Lonchura striata vars. domestica), despite the con- and heterospecific eggs differing in both size and coloration. This is the first experimental evidence that nest destruction may provide a pathway for the evolution of interspecific brood parasitism in birds.

  14. Protective Effects of Dracocephalum heterophyllum in ConA-Induced Acute Hepatitis

    PubMed Central

    Wang, Qilan; Lu, Xiaohua; Shi, Qiangqiang; Zou, Junhui

    2016-01-01

    Dracocephalum heterophyllum (DH) is a Chinese herbal medicine used in treating hepatitis. However, the protective effects and pharmacological mechanisms of DH in hepatitis are unknown. In this study, we found that pretreatment with DH extract significantly ameliorated liver injury and suppressed the production of inflammatory cytokines, including tumor necrosis factor (TNF-α) and interferon-γ (IFN-γ) in Concanavalin A- (ConA-) induced hepatitis (CIH). DH recruited more CD11b+ Gr1+ myeloid-derived suppressor cells (MDSCs) to the liver and suppressed infiltration of macrophages (Kupffer cells) in the liver. The present work explores DH as an effective hepatoprotective medicine to inhibit inflammation and liver injury caused by hepatitis. PMID:27524863

  15. 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.

  16. A new look at the infrared spectrum of the weakly bound CO-N2 complex.

    PubMed

    Rezaei, Mojtaba; Michaelian, K H; Moazzen-Ahmadi, N; McKellar, A R W

    2013-12-19

    A broad-band (2135-2165 cm(-1)) infrared spectrum of the CO-N2 van der Waals complex is obtained, using a tunable quantum cascade laser to probe a pulsed supersonic expansion from a slit jet source. Analysis of the spectrum results in the characterization of four new 'stacks' of rotational levels for CO-orthoN2 (all in the v(CO) = 1 upper state) and five new stacks for CO-paraN2 (three in the upper state and two in the vCO = 0 lower state). This considerably expands our knowledge of a rather fundamental weakly bound complex and should lead to improved determinations of the intermolecular forces governing interactions between the carbon monoxide and nitrogen molecules.

  17. 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

  18. Comparison of three distinct ELLA protocols for determination of apparent affinity constants between Con A and glycoproteins.

    PubMed

    Mislovičová, D; Katrlík, J; Paulovičová, E; Gemeiner, P; Tkac, J

    2012-06-01

    A procedure for determination of apparent affinity constants K(D)(app) between Concanavalin A (Con A) and naturally d-mannose containing glycoproteins using enzyme-linked lectin assay (ELLA) is reported. Three distinct ELLA protocols are compared to each other with 3 different fitting models used (Liliom, Hill with and without a cooperativity factor). The glycoproteins were physisorbed on a highly charged polystyrene solid surface of immunoassay plates and the amount of lectin bound to the glycoproteins was determined by photometry. The interactions of Con A with five mannose-containing glycoproteins, invertase (INV), glucoamylase (GA), glucose oxidase (GOx), ovalbumin (OVA), and transferrin (TRF) were quantified with apparent affinity constant being in the range 2×10(-7) to 9×10(-6)M. The strength of interaction between Con A and glycoproteins is discussed on the basis of glycan structure/exposure on the protein backbone for each glycoprotein.

  19. [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.

  20. 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

  1. [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.

  2. Metal ion determinants of conantokin dimerization as revealed in the X-ray crystallographic structure of the Cd(2+)/Mg (2+)-con-T[K7gamma] complex.

    PubMed

    Cnudde, Sara E; Prorok, Mary; Castellino, Francis J; Geiger, James H

    2010-06-01

    Predatory sea snails from the Conus family produce a variety of venomous small helical peptides called conantokins that are rich in gamma-carboxyglutamic acid (Gla) residues. As potent and selective antagonists of the N-methyl-D: -aspartate receptor, these peptides are potential therapeutic agents for a variety of neurological conditions. The two most studied members of this family of peptides are con-G and con-T. Con-G has Gla residues at sequence positions 3, 4, 7, 10, and 14, and requires divalent cation binding to adopt a helical conformation. Although both Ca(2+) and Mg(2+) can fulfill this role, Ca(2+) induces dimerization of con-G, whereas the Mg(2+)-complexed peptide remains monomeric. A variant of con-T, con-T[K7gamma] (gamma is Gla), contains Gla residues at the same five positions as in con-G and behaves very similarly with respect to metal ion binding and dimerization; each peptide binds two Ca(2+) ions and two Mg(2+) ions per helix. To understand the difference in metal ion selectivity, affinity, and the dependence on Ca(2+) for dimer formation, we report here the structure of the monomeric Cd(2+)/Mg(2+)-con-T[K7gamma] complex, and, by comparison with the previously published con-T[K7gamma]/Ca(2+) dimer structure, we suggest explanations for both metal ion binding site specificity and metal-ion-dependent dimerization.

  3. 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

  4. 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

  5. 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].

  6. 78 FR 70396 - Parts and Accessories Necessary for Safe Operation; Renewal of Exemption for Con-Way Freight, TK...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ..., 2010 (73 FR 82132) or you may visit http://edocket/ access.gpo.gov/2008/pdf/E8-785.pdf . FOR FURTHER... asked for public comment (75 FR 33666). Section 393.60(e)(1) of the FMCSRs prohibits the obstruction of.... Con-way, Takata, and Iteris provided diagrams and photos showing the dimensions of their...

  7. Comparative immunoprophylactic efficacy of Haemonchus contortus recombinant enolase (rHcENO) and Con A purified native glycoproteins in sheep.

    PubMed

    Kalyanasundaram, Aravindan; Jawahar, Shabnam; Ilangopathy, Manikkavasagan; Palavesam, Azahahianambi; Raman, Muthusamy

    2015-07-01

    Haemonchus contortus is the most economically important blood feeding nematode parasite of sheep and goats all over the world. Enolase in helminth parasites is a multi-functional enzyme which involves in glycolysis and host tissue invasion. In this study, the recombinant H. contortus enolase (rHcENO) was evaluated for its immunoprophylactic efficacy in sheep along with Con A purified native glycoproteins in a vaccine challenge trial. Group I and Group II experimental sheep were immunized thrice with rHcENO and Con A purified native glycoproteins along with Montanide ISA 61 VG adjuvant. The animals were challenged with 5000 L3 stage active H. contortus larvae after 21 days of third immunization. A significant increase in the IgG titre was observed in rHcENO and Con A purified native glycoproteins immunized animals as compared to the control animals. Immunoprotective efficacy of Con A purified native glycoproteins was comparatively higher than rHcENO antigen.

  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. Un programa innovador busca ayudar a las personas que cuidan a pacientes con cáncer

    Cancer.gov

    Artículo sobre un programa educativo del City of Hope Cancer Center que ofrece a los profesionales de salud la información y las herramientas necesarias para ayudar a los familiares a saber cómo cuidarse a si mismos y a sus seres queridos con cáncer.

  10. iPathCons and iPathDB: an improved insect pathway construction tool and the database.

    PubMed

    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/

  11. 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

  12. Pro/con ethics debate: is nonheart-beating organ donation ethically acceptable?

    PubMed

    Whetstine, Leslie; Bowman, Kerry; Hawryluck, Laura

    2002-06-01

    This pro/con debate explores the ethical issues surrounding nonheart-beating organ donation (NHBD), a source of considerable controversy. It is estimated that NHBD can increase the number of organs available for transplant by 25% at a time of great need. However, should NHBD be ethically acceptable? In support of NHBD, it may be acceptable practice if there is a separation of the rationale to withdraw life support/to withhold cardiopulmonary resuscitation from the decision to recover organs, if no conflicts of interest exist, if a waiting time precluding spontaneous return of circulation is included, and if NHBD conforms to a standardized protocol. Against NHBD, there are questions regarding the ambiguity and cultural perspectives of death, regarding whether a separation of rationale between withdrawal and donation is sufficient to preclude conflicts of interest, and regarding whether variable protocols arise that subordinate the patient to the goal of donation. Such concerns suggest NHBD may damage the trust in patient-physician relationships and may adversely affect organ donation rates.

  13. Weighing the cons and pros: women's reasons for discontinuing hormone replacement therapy.

    PubMed

    Reece, Susan McClennan

    2002-01-01

    As a greater proportion of U.S. women move into midlife, there has been increased interest in meeting their preventive health needs. Although hormone replacement therapy (HRT) may not be an option for all postmenopausal women, it has been documented as prolonging life expectancy and protecting against osteoporosis. Despite its advantages for many women, often those who initiate HRT discontinue its use within a short time. The purpose of this qualitative study is to gain insights into women's reasons for discontinuing HRT. We collected data by semistructured interview from three diverse samples: 10 women who had been on HRT for two years or less, 11 health care providers of women, and 34 women who had gone off HRT. Reasons for discontinuing fell into seven broad categories: general Gestalt, somatic complaints, mind (knowledge, emotion), not being heard, hassles, indecisive medical community, and cons outweighed pros. Results indicate that women who discontinue HRT do so for a variety of reasons, many of which are connected to the health care system and its providers. Outcomes also suggest that sharing in decision making along with increased education, support, and individualized care are necessary to better address the preventive health care needs of postmenopausal women. PMID:11822557

  14. [Emission spectrum of liquid CO-N2 mixture at shock compression].

    PubMed

    Sun, Yue; Yi, Peng-Fei; Chen, Xian-Meng; Liu, Fu-Sheng; Zhang, Ming-Jian; Zheng, Xue-Ping; Xue, Xue-Dong

    2009-04-01

    Driving a copper projectile to impact a cryo-target made of aluminous alloy at the speed of 2.21 km x s(-1) with a two stage light gas gun, a proper one dimensional shockwave with a speed of 18.76 km x s(-1) was generated and directly acted on a uniform liquid in target, which was condensed by proportional gaseous carbon monoxide and nitrogen. At the measurement of Hugoniots, the full linear spectrum entirely dissociated with the plasma under the shock pressure of 33.5 GPa was caught by the use of intensified charge coupled device and accurate spectrographic technology. From the analysis of the spectrum, the authors know that the transient spectrograph with six channels can be used to measure and record the course of shock compression-irradiancy reliably, and the emitted spectral lines of shock compressed products indicated that the thermal dissociation and phase transition had occurred in homogeneous liquid of CO-N2. Furthermore, comparing the spectral intensity of lower central wavelength with that of higher, the fact of stronger intensity of 488 nm also validates that changes from "optic thin" to "optic thick" exist indeed in dense hydrocarbon liquid acted on by shock pressure.

  15. 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.

  16. Apoptotic cells actively inhibit the expression of CD69 on Con A activated T lymphocytes.

    PubMed

    Sun, E; Zhang, L; Zeng, Y; Ge, Q; Zhao, M; Gao, W

    2000-03-01

    Although apoptosis is commonly viewed as a silent cell death without damage to adjacent tissues, the effect of apoptosis on immunity has been unclear. We have investigated the influence of apoptotic cells on T-cell activation. The K562 or HL-60 human leukemia cell lines that had been induced apoptosis by FTY720 or cycloheximide (CHX) were added into the culture of mouse spleen cells stimulated with Con A. Six to 20 h later, the expression of CD69, an early T-cell activation antigen, was detected using flowcytometry. Living cells and necrotic cells served as control groups. Apoptotic K562 or HL-60 cells induced by either FTY720 or CHX unanimously inhibited CD69 expression on the CD3+ mouse T cells while living and necrotic cells did not. The inhibition was proportional to the number of apoptotic cells and was different in the T-cell subsets, showing a rapid and transient inhibition on the CD3+CD8+ T-cell activation but with a slow and continuous inhibition on CD3+CD8- T-cell activation. In conclusion, the apoptotic cells actively inhibit a T-cell activation that is independent of the cell lines or the apoptotic inducers, indicating that the apoptotic cells dominantly regulate T-cell immunity. PMID:10736091

  17. 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.

  18. Pro-Con Debate: Protracted Bacterial Bronchitis as a Cause of Chronic Cough in Children.

    PubMed

    Bidiwala, Aneela; Krilov, Leonard R; Pirzada, Melodi; Patel, Sameer J

    2015-08-01

    Pro: Children with chronic cough present a diagnostic challenge. Protracted bacterial bronchitis (PBB) is a chronic, persistent bacterial infection of conducting airways defined by the presence of cough for longer than 4 weeks that resolves with antimicrobial therapy and without an alternative diagnosis. The diagnosis is made by the findings of increased bronchial secretions and edema of the lower airways on flexible bronchoscopy and positive cultures on bronchoalveolar lavage. It is speculated that an initial respiratory insult such as viral infection disrupts normal surface morphology and ciliary function, which leads to chronic self-perpetuating inflammation with the formation of bacterial biofilms, leading to PBB. PBB is often misdiagnosed as asthma, leading to inappropriate and excessive use of steroids. The importance of timely diagnosis should be emphasized due to the potential that PBB may be a precursor to chronic suppurative lung disease or bronchiectasis if left untreated; however, every patient should be adequately assessed to exclude other causes of chronic cough. Con: Clinical criteria for the diagnosis of PBB are nonspecific and may not distinguish it from other known causes of chronic cough, including viral infections. Benefits from antibiotic therapy (particularly prolonged therapy) have not been demonstrated. Respiratory conditions are the most common reason for antibiotic prescriptions during ambulatory visits in the United States, and many of these prescriptions are inappropriate and/or unnecessary. The proposed diagnostic criteria and recommendations for the treatment of PBB will lead to unnecessary overuse of antibiotics.

  19. [Caesarean sections under regional anesthesia: pros and cons of supplementary oxygen].

    PubMed

    Aust, H; Zemlin, M; Woernle, F; Wulf, H; Rüsch, D

    2013-03-01

    The routine administration of supplemental oxygen to women undergoing elective caesarean section under regional anesthesia in order to optimize oxygen supply to the fetus is common anesthetic practice in many German hospitals. However, this practice has been controversially discussed in the non-German literature for many years. This review presents and discusses the pros and cons of routinely providing supplemental oxygen to a parturient during caesarean section on the basis of the literature published over the last 30 years. Proponents of routine oxygen administration point to potential and unforeseeable risks of caesarean sections and consider the prophylactic administration of oxygen based on physiological considerations to be advantageous in terms of patient safety. Interestingly, data regarding the effects of an increased maternal FIO2 on improvement of fetal oxygenation are inconsistent, therefore, no unambiguous recommendation concerning which FIO2 to choose can be given. Opponents of routine oxygen supplementation allude above all to an increase in free radical activity in both mother and fetus; however, data in this respect are not consistent either. As supplemental oxygen to patients undergoing elective caesarean section without any risk factors under regional anesthesia is associated with potential risks while no advantage has so far been demonstrated, routine administration of oxygen has to be challenged and is no longer considered to be indicated by many. On the contrary, in cases of emergency with a concomitant risk of hypoxia for mother and fetus, administration of oxygen is indispensable in the light of present data. PMID:23392217

  20. 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. PMID:12925313

  1. 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...

  2. Añadir quimioterapia después de la radioterapia mejora la supervivencia de adultos con un tipo de tu

    Cancer.gov

    Adultos con gliomas de grado bajo, una forma de tumor cerebral, que recibieron tratamiento con quimioterapia después de la radioterapia vivieron más tiempo que pacientes que recibieron solo radioterapia, según los resultados de seguimiento a largo plazo d

  3. 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.

  4. [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

    2016-01-01

    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.

  5. (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.

  6. 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.

  7. (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

  8. 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

  9. 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.

  10. 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.

  11. 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

  12. Quantum analytical modeling and simulation of CNT on insulator (COI) and CNT on nothing (CON) FET: a comparative analysis

    NASA Astrophysics Data System (ADS)

    Mukherjee, Sudipta; Bandyopadhyay, Dipan; Dutta, Pranab Kishore; Sarkar, Subir Kumar

    2016-06-01

    A comprehensive performance analysis by quantum analytical modeling of CNT on insulator (COI) and CNT on nothing (CON) FET having channel length 20 nm has been proposed and investigated on the basis of 2D Poisson's Equation and solution of 1-D Schrodinger's Equation and validated using ATLAS 2D simulator. As classical approximations fail to describe carrier quantization, charge inversion and potential profile of a device at sub-100 nm regime, here for the first time an analytical model in quantum mechanical aspect for COI/CON devices has been derived. Effects of high-k dielectrics in place of conventional SiO2 over the device characteristics have been thoroughly discussed. Moreover, all noticeable benefits of our device to the so called SOI/SON architecture have also been vividly justified.

  13. A new species of kukri snake (Squamata: Colubridae: Oligodon Fitzinger, 1826) from Con Dao Islands, southern Vietnam.

    PubMed

    Nguyen, Sang Ngoc; Nguyen, Vu Dang Hoang; Le, Son Hong; Murphy, Robert W

    2016-07-20

    We describe a new kukri snake, Oligodon condaoensis sp. nov., from Con Dao Islands, southern Vietnam based on the morphological characters of four specimens. It differs from other congeners by a combination of the following characters: medium size in adults (total length up to 552 mm); 17-17-15 dorsal scale rows; deeply forked hemipenes without spines and papillae, extending to subcaudal 13 or 14; 11-13 maxillary teeth, the posterior three being enlarged; cloacal plate undivided; head scalation complete; nasal divided; presubocular absent; 168-176 ventrals; 33-37 subcaudals; overall dorsal coloration dark gray, faint body stripes present or absent; and ventral coloration cream to dark gray without rectangular blotches. We also provide a list of 43 species of amphibians and terrestrial reptiles recorded from Con Dao Islands.

  14. A new species of kukri snake (Squamata: Colubridae: Oligodon Fitzinger, 1826) from Con Dao Islands, southern Vietnam.

    PubMed

    Nguyen, Sang Ngoc; Nguyen, Vu Dang Hoang; Le, Son Hong; Murphy, Robert W

    2016-01-01

    We describe a new kukri snake, Oligodon condaoensis sp. nov., from Con Dao Islands, southern Vietnam based on the morphological characters of four specimens. It differs from other congeners by a combination of the following characters: medium size in adults (total length up to 552 mm); 17-17-15 dorsal scale rows; deeply forked hemipenes without spines and papillae, extending to subcaudal 13 or 14; 11-13 maxillary teeth, the posterior three being enlarged; cloacal plate undivided; head scalation complete; nasal divided; presubocular absent; 168-176 ventrals; 33-37 subcaudals; overall dorsal coloration dark gray, faint body stripes present or absent; and ventral coloration cream to dark gray without rectangular blotches. We also provide a list of 43 species of amphibians and terrestrial reptiles recorded from Con Dao Islands. PMID:27470803

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. ConTra v2: a tool to identify transcription factor binding sites across species, update 2011.

    PubMed

    Broos, Stefan; Hulpiau, Paco; Galle, Jeroen; Hooghe, Bart; Van Roy, Frans; De Bleser, Pieter

    2011-07-01

    Transcription factors are important gene regulators with distinctive roles in development, cell signaling and cell cycling, and they have been associated with many diseases. The ConTra v2 web server allows easy visualization and exploration of predicted transcription factor binding sites in any genomic region surrounding coding or non-coding genes. In this new version, users can choose from nine reference organisms ranging from human to yeast. ConTra v2 can analyze promoter regions, 5'-UTRs, 3'-UTRs and introns or any other genomic region of interest. Hundreds of position weight matrices are available to choose from, but the user can also upload any other matrices for detecting specific binding sites. A typical analysis is run in four simple steps of choosing the gene, the transcript, the region of interest and then selecting one or more transcription factor binding sites. The ConTra v2 web server is freely available at http://bioit.dmbr.ugent.be/contrav2/index.php.

  20. CHILES Con Pol: Probing galaxy evolution, the dark Universe, and cosmic magnetism with a deep 1000 hour Jansky VLA survey

    NASA Astrophysics Data System (ADS)

    Hales, Christopher A.; Chiles Con Pol Collaboration

    2014-04-01

    We recently started a 1000 hour campaign to observe 0.2 square degrees of the COSMOS field in full polarization continuum at 1.4 GHz with the Jansky VLA, as part of a joint program with the spectral line COSMOS HI Large Extragalactic Survey (CHILES). When complete, we expect our CHILES Continuum Polarization (CHILES Con Pol) survey to reach an unprecedented SKA-era sensitivity of 0.7 uJy per 4 arcsecond FWHM beam. Here we present the key goals of CHILES Con Pol, which are to (i) produce a source catalog of legacy value to the astronomical community, (ii) measure differential source counts in total intensity, linear polarization, and circular polarization in order to constrain the redshift and luminosity distributions of source populations, (iii) perform a novel weak lensing study using radio polarization as an indicator of intrinsic alignment to better study dark energy and dark matter, and (iv) probe the unknown origin of cosmic magnetism by measuring the strength and structure of intergalactic magnetic fields in the filaments of large scale structure. The CHILES Con Pol source catalog will be a useful resource for upcoming wide-field surveys by acting as a training set for machine learning algorithms, which can then be used to identify and classify radio sources in regions lacking deep multiwavelength coverage.

  1. Integrated Concentration in Science (iCons): Undergraduate Education Through Interdisciplinary, Team-Based, Real-World Problem Solving

    NASA Astrophysics Data System (ADS)

    Tuominen, Mark

    2013-03-01

    Attitude, Skills, Knowledge (ASK) - In this order, these are fundamental characteristics of scientific innovators. Through first-hand practice in using science to unpack and solve complex real-world problems, students can become self-motivated scientific leaders. This presentation describes the pedagogy of a recently developed interdisciplinary undergraduate science education program at the University of Massachusetts Amherst focused on addressing global challenges with scientific solutions. Integrated Concentration in Science (iCons) is an overarching concentration program that supplements the curricula provided within each student's chosen major. iCons is a platform for students to perform student-led research in interdisciplinary collaborative teams. With a schedule of one course per year over four years, the cohort of students move through case studies, analysis of real-world problems, development of potential solutions, integrative communication, laboratory practice, and capstone research projects. In this presentation, a track emphasizing renewable energy science is used to illustrate the iCons pedagogical methods. This includes discussion of a third-year laboratory course in renewable energy that is educationally scaffolded: beginning with a boot camp in laboratory techniques and culminating with student-designed research projects. Among other objectives, this course emphasizes the practice of using reflection and redesign, as a means of generating better solutions and embedding learning for the long term. This work is supported in part by NSF grant DUE-1140805.

  2. A novel biclustering algorithm of binary microarray data: BiBinCons and BiBinAlter.

    PubMed

    Saber, Haifa Ben; Elloumi, Mourad

    2015-01-01

    The biclustering of microarray data has been the subject of a large research. No one of the existing biclustering algorithms is perfect. The construction of biologically significant groups of biclusters for large microarray data is still a problem that requires a continuous work. Biological validation of biclusters of microarray data is one of the most important open issues. So far, there are no general guidelines in the literature on how to validate biologically extracted biclusters. In this paper, we develop two biclustering algorithms of binary microarray data, adopting the Iterative Row and Column Clustering Combination (IRCCC) approach, called BiBinCons and BiBinAlter. However, the BiBinAlter algorithm is an improvement of BiBinCons. On the other hand, BiBinAlter differs from BiBinCons by the use of the EvalStab and IndHomog evaluation functions in addition to the CroBin one (Bioinformatics 20:1993-2003, 2004). BiBinAlter can extracts biclusters of good quality with better p-values.

  3. [Food Addiction: definizione, misurazione e prevalenza in soggetti sani e in pazienti con disturbi del comportamento alimentare].

    PubMed

    Imperatori, Claudio; Fabbricatore, Mariantonietta; Vumbaca, Viviana; Innamorati, Marco; Contardi, Anna; Farina, Benedetto

    2016-01-01

    RIASSUNTO. Il costrutto della "Food Addiction" (FA) è stato introdotto negli ultimi anni per meglio comprendere i pattern alimentari disfunzionali osservati nei pazienti obesi e in sovrappeso e nei pazienti con disturbi del comportamento alimentare (DCA). Nonostante i numerosi parallelismi tra la dipendenza da sostanze e la FA, non c'è ancora accordo nel considerare la FA come un indipendente DCA né un concetto utile. L'obiettivo della presente rassegna è stato quello di riassumere i dati disponibili al fine di aumentare le conoscenze su: 1) definizione, misurazione e caratteristiche generali della FA; 2) prevalenza della FA in campioni clinici e non clinici. I dati disponibili suggeriscono che la FA sia un costrutto transnosografico presente in tutti i DCA, con una prevalenza più elevata nella bulimia nervosa. Nonostante il dibattito sull'autonomia della FA come DCA rimanga aperto, gli studi riportati suggeriscono che la comorbilità tra FA e DCA sia associata con peggiori outcome clinici, giustificando di conseguenza l'assessment e il trattamento della FA. PMID:27183510

  4. 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. PMID:20355346

  5. [Food Addiction: definizione, misurazione e prevalenza in soggetti sani e in pazienti con disturbi del comportamento alimentare].

    PubMed

    Imperatori, Claudio; Fabbricatore, Mariantonietta; Vumbaca, Viviana; Innamorati, Marco; Contardi, Anna; Farina, Benedetto

    2016-01-01

    RIASSUNTO. Il costrutto della "Food Addiction" (FA) è stato introdotto negli ultimi anni per meglio comprendere i pattern alimentari disfunzionali osservati nei pazienti obesi e in sovrappeso e nei pazienti con disturbi del comportamento alimentare (DCA). Nonostante i numerosi parallelismi tra la dipendenza da sostanze e la FA, non c'è ancora accordo nel considerare la FA come un indipendente DCA né un concetto utile. L'obiettivo della presente rassegna è stato quello di riassumere i dati disponibili al fine di aumentare le conoscenze su: 1) definizione, misurazione e caratteristiche generali della FA; 2) prevalenza della FA in campioni clinici e non clinici. I dati disponibili suggeriscono che la FA sia un costrutto transnosografico presente in tutti i DCA, con una prevalenza più elevata nella bulimia nervosa. Nonostante il dibattito sull'autonomia della FA come DCA rimanga aperto, gli studi riportati suggeriscono che la comorbilità tra FA e DCA sia associata con peggiori outcome clinici, giustificando di conseguenza l'assessment e il trattamento della FA.

  6. [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.

  7. Mitochondria-dependent apoptosis of con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis.

    PubMed

    Guo, Wenjie; Liu, Wen; Hong, Shaocheng; Liu, Hailiang; Qian, Cheng; Shen, Yan; Wu, Xuefeng; Sun, Yang; Xu, Qiang

    2012-01-01

    Selectively facilitating apoptosis of activated T cells is essential for the clearance of pathogenic injurious cells and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. In the present study, we found that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner indicated by the disruption of the mitochondrial transmembrane potential, release of cytochrome c from mitochondria to cytosol, caspases activation, and cleavage of PARP. In addition, asiatic acid also induced the cleavage of caspase 8 and Bid and augmented Fas expression in Con A-activated T cells. However, following activation of T cells from MRL(lpr/lpr) mice with mutation of Fas demonstrated a similar susceptibility to asiatic acid-induced apoptosis compared with normal T cells, suggesting that Fas-mediated death-receptor apoptotic pathway does not mainly contribute to asiatic acid-induced cell death. Furthermore, asiatic acid significantly alleviated Con A-induced T cell-dependent fulminant hepatitis in mice, as assessed by reduced serum transaminases, pro-inflammatory cytokines, and pathologic parameters. Consistent with the in vitro results, asiatic acid also induced apoptosis of activated CD4(+) T cells in vivo. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.

  8. 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

  9. ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites.

    PubMed

    Lelieveld, Stefan H; Schütte, Judith; Dijkstra, Maurits J J; Bawono, Punto; Kinston, Sarah J; Göttgens, Berthold; Heringa, Jaap; Bonzanni, Nicola

    2016-05-01

    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.

  10. The Con-A-peroxidase method for tissue localization of glucosyl and mannosyl groups applied to mouse hepatocytes and chicken erythrocytes.

    PubMed

    Moraes, Alberto S; Mello, Maria Luiza S

    2006-01-01

    A variation of the Concanavalin A (Con-A)-peroxidase labelling method originally described by Kiernan [Localization of alpha-D-glucosyl and alpha-D-mannosyl groups of mucosubstances with Concanavalin A and horseradish peroxidase. Histochemistry 1975;44:39-45] was applied to unsectioned cell preparations, with an emphasis on the nuclear localization of glycoproteins. Mouse liver imprints and chicken blood smears fixed in acetic acid-ethanol solution were studied. Modifications of the method included using increased Con-A concentration, and a range of pH values for the Con-A solutions. The strongest Con-A labelling of both erythrocytes and hepatocytes was obtained after incubation with Con-A at pH 6.5 and with Con-A concentrations at least two-fold greater than those used for tissue sections. These conditions may alter the Con-A conformation, enabling the lectin molecule to enter the cell nucleus and bind to nuclear glycoproteins, thus allowing their localization and quantification.

  11. Prevalence and antimicrobial susceptibility pattern of coagulase-negative staphylococci (CoNS) isolated from clinical specimens in Northern of Jordan

    PubMed Central

    Al Tayyar, Ibrahim Ali; AL-Zoubi, Mazhar Salim; Hussein, Emad; Khudairat, Salih; Sarosiekf, Konrad

    2015-01-01

    Background: Coagulase negative Staphylococci (CoNS) are one of the most common bacteria found on human skin and on mucous membranes as a component of normal flora. The presence of CoNS in clinical specimens is frequently associated with an infectious aetiology or contamination. Objectives: We aimed to evaluate CoNS species distribution and susceptibility patterns in specimens obtained from clinics and hospitals in the Northern area of Jordan. Methods: Standard identification methods showed the presence of CoNS in 223 specimens at different local hospitals. Susceptibility testing was performed using 18 antibiotics in accordance with the Clinical and Laboratory Standards Institute (CLSI) recommendations. Results: Staphylococcus epidermidis and S. haemolyticus were found to be the most common species isolated from all specimens representing 122 (54.7%) and 52 (23.4%) of all CoNS species, respectively. Antibiotic susceptibility testing of CoNS species revealed their sensitivity to vancomycin, linozolid, rifampin and nitrofurantin, while showing a highly resistant pattern to ampicillin, penicillin, ceftriaxone, cefazolin, amoxicillin-clavulanic acid and erythromycin. Some variation of the susceptibility pattern of CoNS species were identified in specimens isolated from the ICU and paediatric hospital wards as well as from clinical specimens of urine, blood and catheter tips. Conclusion: The most common CoNS isolates were found to be S. epidermidis and S. haemolyticus with variable percentages according to the specimen source. Moreover, a high susceptibility CoNS to vancomycin, rifampin, and linezolid showed resistance to amoxicillin and penicillin. PMID:26885328

  12. 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

  13. 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.

  14. [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.

  15. "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.

  16. 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

  17. 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

  18. 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

  19. 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).

  20. 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).

  1. EPA site demonstration of the international waste technologies/Geo-Con in-situ stabilization/solidification process

    SciTech Connect

    Stinson, M.K.

    1990-11-01

    The paper presents an EPA evaluation of the first field demonstration of an in situ stabilization/solidification process for contaminated soil under the EPA Superfund Innovative Technology Evaluation (SITE) program. Demonstration of the process was a joint effort of two vendors: International Waste Technologies' (IWT) of Wichita, Kansas, who provided the treatment process, specifically the proprietary additive called HWT-20, and Geo-Con, Inc., of Pittsburgh, Pennsylvania, who provided both engineering and hardware for the in situ soil treatment. The field demonstration took place in April, 1988 at a site contaminated mainly with polychlorinated biphenyls (PCBs). EPA tested the soil before and after treatment and the EPA evaluation of the process is based on results from the testing. A year later, in April 1989, EPA tested again the treated soil and results of that testing were compared to those of the demonstration. Results of the EPA evaluation of the IWT process, the Geo-Con performance, and treatment costs are discussed separately.

  2. 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.]. PMID:27648873

  3. 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

  4. 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

  5. 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

  6. Fluoroalcohols induced unfolding of Succinylated Con A: native like beta-structure in partially folded intermediate and alpha-helix in molten globule like state.

    PubMed

    Fatima, Sadaf; Ahmad, Basir; Khan, Rizwan Hasan

    2006-10-15

    Concanavalin A (Con A) exists in dimeric state at pH 5. In concentration range 20-60% (v/v) 2,2,2-trifluoroethanol (TFE) and 2-40% (v/v) 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), Con A at pH 5.0 shows visible aggregation. However, when succinyl Con A was used, no aggregation was observed in the entire concentration range of fluoroalcohols (0-90% v/v TFE and HFIP) and resulted in stable alpha-helix formation. Temperature-induced concentration-dependent aggregation in Con A was also found to be prevented/reduced in succinylated form. Possible role of electrostatic repulsion among residues in the prevention of hydrophobically driven aggregation has been discussed. Results indicate that succinylation of a protein resulted in greater stability (in both beta-sheet and alpha-helical forms) against alcohol-induced and temperature-induced concentration-dependent aggregation and this observation may play significant role in amyloid-forming proteins. Effect of TFE and HFIP on the conformation of a dimeric protein, Succinylated Con A, has been investigated by circular dichroism (CD), fluorescence emission spectroscopy, binding of hydrophobic dye ANS (8-anilinonaphthalene-1-sulfonic acid). Far UV-CD, a probe for secondary structure shows loss of native secondary structure in the presence of low concentration of both the alcohols, TFE (10% v/v) and HFIP (4% v/v). Upon addition of higher concentration of these alcohols, Succinylated Con A exhibited transformation from beta-sheet to alpha-helical structure. Intrinsic tryptophan fluorescence studies, ANS binding and near UV-CD experiments indicate the protein is more expanded, have more exposed hydrophobic surfaces and highly disrupted tertiary structure at 60% (v/v) TFE and 30% (v/v) HFIP concentrations. Taken together, these results it might be concluded that TFE and HFIP induce two intermediate states at their low and high concentrations in Succinyl Con A.

  7. 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.

  8. 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

  9. 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. PMID:25264397

  10. 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

  11. 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. PMID:26840219

  12. Accurate macromolecular crystallographic refinement: incorporation of the linear scaling, semiempirical quantum-mechanics program DivCon into the PHENIX refinement package

    SciTech Connect

    Borbulevych, Oleg Y.; Plumley, Joshua A.; Martin, Roger I.; Merz, Kenneth M. Jr; Westerhoff, Lance M.

    2014-05-01

    Semiempirical quantum-chemical X-ray macromolecular refinement using the program DivCon integrated with PHENIX is described. 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.

  13. 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.

  14. Blockade of IL-33 ameliorates Con A-induced hepatic injury by reducing NKT cell activation and IFN-γ production in mice.

    PubMed

    Chen, Jie; Duan, Lihua; Xiong, Ali; Zhang, Hongwei; Zheng, Fang; Tan, Zheng; Gong, Feili; Fang, Min

    2012-12-01

    IL-33, a recently described member of the IL-1 family, has been identified as a cytokine endowed with pro-Th2 type functions. To date, there are only limited data on its role in physiological and pathological hepatic immune responses. In this study, we examined the role of IL-33 in immune-mediated liver injury by exploring the model of concanavalin A (Con A)-induced hepatitis. We observed that the level of IL-33 expression in the liver was dramatically increased at 12 h after Con A injection. Meanwhile, ST2L, the receptor of IL-33, was significantly up-regulated in lymphocytes including T and natural killer T (NKT) cells, especially in NKT cells. Moreover, administration of recombinant IL-33 exacerbated Con A-induced hepatitis, while pretreatment of IL-33-blocking antibody or psST2-Fc plasmids showed a protective effect probably by inhibiting the activation of late stage of T cells and NKT cells and also decreasing the production of the cytokine IFN-γ. Furthermore, depletion of NKT cells abolished the protective effect of IL-33-blocking antibody, and IL-33 failed to exacerbate Con A-induced hepatitis in IFN-γ(-/-) mice. These data suggested the critical roles of NKT cells and IFN-γ in the involvement of IL-33 in Con A-induced hepatitis. Blockade of IL-33 may represent a novel therapeutic strategy through IL-33/ST2L signal to prevent immune-mediated liver injury.

  15. Effect of concanavalin A (Con-A) on the hormone production of the unicellular Tetrahymena and the immune cells of the rat. A comparative study.

    PubMed

    Csaba, György; Pállinger, Eva

    2008-01-01

    Tetrahymena populations were treated with 10(-15) g ml(-1) or 10(-6) g ml(-1) concanavalin-A (Con-A) in tryptone-yeast medium for 1 h. Rat peritoneal immune cells (mast cells, lymphocytes, monocyte-granulocyte group) were also treated with 10(-6) g ml(-1) Con-A, for 1 h. The cells' hormone (ACTH, histamine, serotonin, endorphin, triiodothyronine (T(3))) content was measured by using immunocytochemistry and flow cytometry. The extremely low dose of Con-A universally and significantly elevated the hormone contents, while the result of higher dose was uncertain. In the immune cells, Con-A significantly decreased the ACTH level in each cell type and histamine level in mast cells. The results demonstrate the very high sensitivity of Tetrahymena receptors for a non-hormone (lectin) molecule, which can bind to the insulin receptors and mimics the effect of insulin. The results also show that Tetrahymena receptors are more sensitive to lower concentrations of molecules than to higher ones. The universal hormone-production stimulating effect of Con-A-which is observed in Tetrahymena-is specified in rat.

  16. Proteomic profiling of N-linked glycoproteins identifies ConA-binding procathepsin D as a novel serum biomarker for hepatocellular carcinoma.

    PubMed

    Qi, Yi-Jun; Ward, Douglas G; Pang, Chun; Wang, Qi-Ming; Wei, Wenbin; Ma, Jin; Zhang, Juan; Lou, Qiang; Shimwell, Neil J; Martin, Ashley; Wong, Nathalie; Chao, Wei-Xia; Wang, Ming; Ma, Yuan-Fang; Johnson, Philip J

    2014-02-01

    The aim of this study was to identify novel biomarkers for the diagnosis of, and potential therapeutic targets for, hepatocellular carcinoma (HCC). Multilectin affinity chromatography was used to enrich N-linked glycoproteins from nontumorous liver and HCC tissues followed by 2DE and protein identification by MS. Twenty-eight differentially expressed proteins were identified. Western blotting validated consistently lower concentrations of human liver carboxylesterase 1 and haptoglobin, and higher concentration of procathepsin D (pCD) in HCC tissues. Knockdown of cathepsin D (CD) expression mediated by siRNA significantly inhibited the in vitro invasion of two HCC cell lines, SNU449 and SNU473, which normally secrete high-levels of CD. Prefractionation using individual lectins demonstrated an elevation in ConA-binding glycoforms of proCD and CD in HCC tissues. In the serum of HCC patients, "ConA-binding proCD" (ConA-pCD) is significantly increased in concentration and this increase is comprised of several distinct upregulated acidic isoforms (pI 4.5-5.5). Receiver operating characteristic analysis showed that the sensitivity and specificity of serum ConA-pCD for HCC diagnosis were 85% and 80%, respectively. This is the first report that serum ConA-pCD is increased significantly in HCC and is potentially useful as a serological biomarker for diagnosis of HCC.

  17. Uptake of antioxidants by natural nutrition and supplementation: pros and cons from the dermatological point of view.

    PubMed

    Lademann, J; Patzelt, A; Schanzer, S; Richter, H; Meinke, M C; Sterry, W; Zastrow, L; Doucet, O; Vergou, T; Darvin, M E

    2011-01-01

    The pros and cons of the systemic and topical application of antioxidant substances are a subject of intense discussion among experts, with resulting confusion for consumers and producers. The objective of the present article is to clarify the various uncertainties relating to the use of antioxidant substances in dermatology. Whereas inappropriate application of antioxidant substances (concerning their concentration and composition) might induce harmful effects, the consumer will definitively benefit from physiological concentrations and compositions of antioxidants. The most suitable method is the consumption of natural antioxidants in the form of fruit and vegetables, for example. In addition, the skin, which also accumulates antioxidant substances, may profit from a sufficient antioxidative level, as damage induced by sun radiation in addition to skin aging is reduced.

  18. 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

  19. 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.

  20. Effect of the carboxylate salt on the C--ON bond homolysis of SG1-based alkoxyamines.

    PubMed

    Bertin, Denis; Gigmes, Didier; Marque, Sylvain R A; Siri, Didier; Tordo, Paul; Trappo, Gregory

    2008-02-01

    Alkoxyamines and persistent nitroxides are important regulators of the nitroxide mediated radical polymerization (NMP). Since the polymerization time decreases with increasing values of the homolysis rate constant (kd) for the C--ON bond between the polymer chain and the nitroxide moiety, the factors influencing kd are of considerable interest. Environmentally friendly polymerization methods, such as NMP in emulsion medium, have now been developed. The success of the polymerization depends not only on the strength of the C--ON bond but also on the solubility of the initiator/controller alkoxyamines, which control the nucleation. Various salts of SG1-based alkoxyamines (S+-OOCCMeH-SG1) labelled 1 a-f, where S+=Li+ (a), Na+ (b), K+ (c), nBu3HN+ (d), NH4+ (e), and nBu4N+ (f) are prepared, all of which are soluble in most organic solvents (e.g. pentane, dichlomethane, benzene, ethanol, etc.) as well as in water. Their kd values, which are measured in tert-butylbenzene, reveal unexpected behaviors depending on the diastereoisomers. For the RR/SS diatereoisomers (i.e. slowly homolyzing isomers), kd was not found to be sensitive to any of the salts, whereas for the RS/SR diastereoisomers (i.e. quickly homolyzing isomers), kd is observed to decrease to a greater or lesser extent depending on the type of salt. The conformations of the diastereoisomers of several salts are determined by means of DFT calculations, and the orbital interactions are studied by natural bond orbital (NBO) analysis. PMID:18200479

  1. Neuropeptide S reduces fear and avoidance of con-specifics induced by social fear conditioning and social defeat, respectively.

    PubMed

    Zoicas, Iulia; Menon, Rohit; Neumann, Inga D

    2016-09-01

    Neuropeptide S (NPS) has anxiolytic effects and facilitates extinction of cued fear in rodents. Here, we investigated whether NPS reverses social fear and social avoidance induced by social fear conditioning (SFC) and acute social defeat (SD), respectively, in male CD1 mice. Our results revealed that intracerebroventricular NPS (icv; 10 and 50 nmol/2 μl) reversed fear of unknown con-specifics induced by SFC and dose-dependently reduced avoidance of known aggressive con-specifics induced by SD. While 50 nmol of NPS completely reversed social avoidance and reinstated social preference, 10 nmol of NPS reduced social avoidance, but did not completely reinstate social preference in socially-defeated mice. Further, a lower dose (1 nmol/2 μl) of NPS facilitated the within-session extinction of cued fear, while a higher dose (10 nmol/2 μl) reduced the expression of cued fear. We could also confirm the anxiolytic effects of NPS (1, 10 and 50 nmol/2 μl) on the elevated plus-maze (EPM), which were not accompanied by alterations in locomotor activity either on the EPM or in the home cage. Finally, we could show that icv infusion of the NPS receptor 1 antagonist D-Cys((t)Bu)(5)-NPS (10 nmol/2 μl) did not alter SFC-induced social fear, general anxiety and locomotor activity. Taken together, our study extends the potent anxiolytic profile of NPS to a social context by demonstrating the reduction of social fear and social avoidance, thus providing the framework for studies investigating the involvement of the NPS system in the regulation of different types of social behaviour.

  2. Preliminary laboratory study of plutonium-238 dissolution from Mound soil by means of the ACT*DE*CON sup SM process

    SciTech Connect

    Brown, K.A.; Heinrich, R.R.; Johnson, D.O.; Edgar, D.E. )

    1992-04-01

    The treatment of contaminated soil presents a significant technical problem. Soil-washing and chemical-extraction methods have proven to be effective for specific applications, but a process with more comprehensive treatment properties that is both cost-effective and environmentally propitious is needed. Bradtec, Inc., has developed a process, the ACT*DE*CON{sup SM} process, that has been tested on soil contaminated with plutonium. The process effectively extracted Pu-238 after three washes, reducing the contamination levels from approximately 20 Bq/g to 1.6--1.9 Bq/g and yielding a decontamination factor ranging from 11 to 13. By using four or more ACT*DE*CON{sup SM} washes or a continuous-flow process with ACT*DE*CON{sup SM} solvents on a pilot-scale test, a target decontamination level of 0.93 Bq/g might be achievable.

  3. Preliminary laboratory study of plutonium-238 dissolution from Mound soil by means of the ACT*DE*CON{sup SM} process

    SciTech Connect

    Brown, K.A.; Heinrich, R.R.; Johnson, D.O.; Edgar, D.E.

    1992-04-01

    The treatment of contaminated soil presents a significant technical problem. Soil-washing and chemical-extraction methods have proven to be effective for specific applications, but a process with more comprehensive treatment properties that is both cost-effective and environmentally propitious is needed. Bradtec, Inc., has developed a process, the ACT*DE*CON{sup SM} process, that has been tested on soil contaminated with plutonium. The process effectively extracted Pu-238 after three washes, reducing the contamination levels from approximately 20 Bq/g to 1.6--1.9 Bq/g and yielding a decontamination factor ranging from 11 to 13. By using four or more ACT*DE*CON{sup SM} washes or a continuous-flow process with ACT*DE*CON{sup SM} solvents on a pilot-scale test, a target decontamination level of 0.93 Bq/g might be achievable.

  4. The anti-inflammatory effect of the SOCC blocker SK&F 96365 on mouse lymphocytes after stimulation by Con A or PMA/ionomycin.

    PubMed

    Ye, Yanxia; Zhang, Yaxing; Lu, Xiaoyu; Huang, Xiuyan; Zeng, Xiangfeng; Lai, Xinqiang; Zeng, Yaoying

    2011-09-01

    SK&F 96365, 51-(beta-[3-(p-methoxyphenyl)-propyloxy]-p-methoxyphenethyl)-1H-imidazole hydrochloride, has emerged as a useful pharmacological tool in the study of store-operated Ca²⁺ entry (SOCE). But the precise molecular mechanism and effect of SK&F 96365 on mouse lymphocytes are still not well determined. This study investigated the pharmacological profile of SK&F 96365 on mouse lymphocytes stimulated by mitogen concanavalin A (Con A) or by a combination of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate (PMA) and a calcium ionophore, ionomycin in vitro. Our results showed that SK&F 96365 pre-treatment diminished the cytosolic calcium rise on lymphocytes induced by ionomycin, PMA/ionomycin, and thapsigargin (TG), respectively. CFDA-SE staining results showed that SK&F 96365 (5-20 μM) inhibited both Con A- and PMA/ionomycin-induced lymphocytes proliferation in a time- and dose-dependent manner. Upon the same stimulation, SK&F 96365 inhibited the expression of CD69 and CD25 on CD3⁺ T lymphocytes in a dose-dependent manner. The cell cycle analyzing results showed that SK&F 96365 caused a G0/G1 phase cell cycle arrest on both Con A- and PMA/ionomycin-activated lymphocytes in a dose-dependent manner. In addition, SK&F 96365 induced a decrease in mitochondrial membrane potential (ΔΨm) and promoted mitochondrial permeability transition (MPT) in both Con A- and PMA/ionomycin-activated lymphocytes. Furthermore, SK&F 96365 significantly inhibited the production of proinflammatory cytokines (interferon (IFN)-γ and tumor necrosis factor (TNF)), and the anti-inflammatory cytokine (IL-10) on both Con A- and PMA/ionomycin-activated lymphocytes. SK&F 96365 did not induce a statistically significant increase in levels of proinflammatory IL-6 and monocyte chemoattractant protein-1 (MCP-1) but of IL-12p70 upon the stimulation of Con A, whereas these three cytokines were markedly inhibited by it upon the stimulation of PMA/ionomycin. This finding

  5. 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

  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. 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.

  8. Synthesis of water-soluble Ag₂Se QDs as a novel resonance Rayleigh scattering sensor for highly sensitive and selective ConA detection.

    PubMed

    Yan, Shuguang; Zhang, Lichun; Tang, Yurong; Lv, Yi

    2014-09-01

    Ag2Se quantum dots (QDs) have attracted a lot of interest due to their potential applications in biosensing and bioimaging. A strategy is presented that involves coupling of selenium powder reduction with the binding of silver ions, and thioglycollic acid (TGA) and glycine as stabilizers to obtain ultrasmall Ag2Se QDs at 85 °C in aqueous solution. This strategy avoids high temperatures, high pressures and organic solvents so that water-soluble 3 nm Ag2Se QDs can be directly obtained. The conjugation of ConA to TGA stabilized Ag2Se QDs by hydrogen bonds leads to the adsorption of ConA to Ag2Se QDs and forms the aggregation and leads to the generation of resonance Rayleigh scattering (RRS) as a readout signal for the sensing events. The reaction mechanism of Ag2Se QD RRS enhancement is studied in this work. The resulting RRS sensor enables the detection of ConA with limit of detection reaching 0.08 μg mL(-1) concentration in a wide linear range from 0.27 μg mL(-1) to 35 μg mL(-1). The recovery of spiked ConA in human serum samples ranges from 94% to 106%. The relative standard deviation (RSD) for eleven replicate detections is 3.6%. Our results correlate many important experimental observations and will fuel the further growth of this field.

  9. Media-Based Interactive Visual Image-Controlled (Vis-I-Con) Instruction Delivery System for Instruction of Deaf and Hearing-Impaired.

    ERIC Educational Resources Information Center

    Fox, Raymond

    1979-01-01

    Originally part of a symposium on educational media for the deaf, the paper describes a programmable media-based microprocessor-controlled interactive instruction delivery system using super 8 film and addressable audiotape messages, the Vis-I-Con system. (Author/PHR)

  10. 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.

  11. Tensión postraumática relacionada con el cáncer (PDQ®)—Versión para profesionales de salud

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y tratamiento de estos síntomas.

  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

    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).

  13. Oxacilin-resistant Coagulase-negative staphylococci (CoNS) bacteremia in a general hospital at São Paulo city, Brasil

    PubMed Central

    d’Azevedo, P.A.; Secchi, C.; Antunes, A.L.S.; Sales, T.; Silva, F.M.; Tranchesi, R.; Pignatari, A.C.C.

    2008-01-01

    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. PMID:24031279

  14. Galectin-9 Ameliorates Con A-Induced Hepatitis by Inducing CD4+CD25low/int Effector T-Cell Apoptosis and Increasing Regulatory T Cell Number

    PubMed Central

    Zhang, Mengying; Zhong, Min; Suo, Qifeng

    2012-01-01

    Background T cell-mediated liver damage is a key event in the pathogenesis of many chronic human liver diseases, such as liver transplant rejection, primary biliary cirrhosis, and sclerosing cholangitis. We and other groups have previously reported that galectin-9, one of the β-galactoside binding animal lectins, might be potentially useful in the treatment of T cell-mediated diseases. To evaluate the direct effect of galectin-9 on hepatitis induced by concanavalin A (Con A) administration in mice and to clarify the mechanisms involved, we administered galectin-9 into mice, and evaluated its therapeutic effect on Con A-induced hepatitis. Methodology/Principal Findings Galectin-9 was administrated i.v. to Balb/c mice 30 min before Con A injection. Compared with no treatment, galectin-9 pretreatment significantly reduced serum ALT and AST levels and improved liver histopathology, suggesting an ameliorated hepatitis. This therapeutic effect was not only attributable to a blunted Th1 immune response, but also to an increased number in regulatory T cells, as reflected in a significantly increased apoptosis of CD4+CD25low/int effector T cells and in reduced proinflammatory cytokine levels. Conclusion/Significance Our findings constitute the first preclinical data indicating that interfering with TIM-3/galectin-9 signaling in vivo could ameliorate Con A-induced hepatitis. This strategy may represent a new therapeutic approach in treating human diseases involving T cell activation. PMID:23118999

  15. Aumento de la supervivencia en hombres con cáncer de próstata metastásico que reciben quimioterapia

    Cancer.gov

    Los hombres con cáncer de próstata metastásico sensible a las hormonas que recibieron el fármaco quimioterapéutico docetaxel al inicio de la terapia hormonal convencional vivieron más tiempo que los pacientes que recibieron solo terapia hormonal, de acuer

  16. Toward Lower Overpotential through Improved Electron Transport Property: Hierarchically Porous CoN Nanorods Prepared by Nitridation for Lithium-Oxygen Batteries.

    PubMed

    Xu, Shu-Mao; Zhu, Qian-Cheng; Harris, Michelle; Chen, Tong-Heng; Ma, Chao; Wei, Xiao; Xu, Hua-Sheng; Zhou, Yong-Xian; Cao, Yu-Cai; Wang, Kai-Xue; Chen, Jie-Sheng

    2016-09-14

    To lower the overpotential of a lithium-oxygen battery, electron transport at the solid-to-solid interface between the discharge product Li2O2 and the cathode catalyst is of great significance. Here we propose a strategy to enhance electron transport property of the cathode catalyst by the replace of oxygen atoms in the generally used metal oxide-based catalysts with nitrogen atoms to improve electron density at Fermi energy after nitridation. Hierarchically porous CoN nanorods were obtained by thermal treatment of Co3O4 nanorods under ammonia atmosphere at 350 °C. Compared with that of the pristine Co3O4 precursor before nitridation, the overpotential of the obtained CoN cathode was significantly decreased. Moreover, specific capacity and cycling stability of the CoN nanorods were enhanced. It is assumed that the discharged products with different morphologies for Co3O4 and CoN cathodes might be closely associated with the variation in the electronic density induced by occupancy of nitrogen atoms into interstitial sites of metal lattice after nitridation. The nitridation strategy for improved electron density proposed in this work is proved to be a simple but efficient way to improve the electrochemical performance of metal oxide based cathodes for lithium-oxygen batteries. PMID:27504675

  17. 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

  18. Beneficios y riesgos de la terapia estrogénica en la menopausia varían por edad, de acuerdo con el e

    Cancer.gov

    Los datos de seguimiento a largo plazo del estudio Iniciativa para la Salud de la Mujer (WHI) proporcionan información nueva e importante sobre los posibles riesgos y beneficios de la terapia hormonal para tratar síntomas relacionadas con la menopausia.

  19. Tensión postraumática relacionada con el cáncer (PDQ®)—Versión para pacientes

    Cancer.gov

    Resumen de información revisada por expertos acerca de la tensión postraumática y los síntomas relacionados en los pacientes con cáncer, sobrevivientes del cáncer y miembros de la familia. Se discuten la evaluación y el tratamiento de estos síntomas.

  20. Toward Lower Overpotential through Improved Electron Transport Property: Hierarchically Porous CoN Nanorods Prepared by Nitridation for Lithium-Oxygen Batteries.

    PubMed

    Xu, Shu-Mao; Zhu, Qian-Cheng; Harris, Michelle; Chen, Tong-Heng; Ma, Chao; Wei, Xiao; Xu, Hua-Sheng; Zhou, Yong-Xian; Cao, Yu-Cai; Wang, Kai-Xue; Chen, Jie-Sheng

    2016-09-14

    To lower the overpotential of a lithium-oxygen battery, electron transport at the solid-to-solid interface between the discharge product Li2O2 and the cathode catalyst is of great significance. Here we propose a strategy to enhance electron transport property of the cathode catalyst by the replace of oxygen atoms in the generally used metal oxide-based catalysts with nitrogen atoms to improve electron density at Fermi energy after nitridation. Hierarchically porous CoN nanorods were obtained by thermal treatment of Co3O4 nanorods under ammonia atmosphere at 350 °C. Compared with that of the pristine Co3O4 precursor before nitridation, the overpotential of the obtained CoN cathode was significantly decreased. Moreover, specific capacity and cycling stability of the CoN nanorods were enhanced. It is assumed that the discharged products with different morphologies for Co3O4 and CoN cathodes might be closely associated with the variation in the electronic density induced by occupancy of nitrogen atoms into interstitial sites of metal lattice after nitridation. The nitridation strategy for improved electron density proposed in this work is proved to be a simple but efficient way to improve the electrochemical performance of metal oxide based cathodes for lithium-oxygen batteries.

  1. MicroRNA let-7a ameliorates con A-induced hepatitis by inhibiting IL-6-dependent Th17 cell differentiation.

    PubMed

    Zhang, Yingying; Wang, Xiangmin; Zhong, Min; Zhang, Mengying; Suo, Qifeng; Lv, Kun

    2013-04-01

    In this study we explored the effects of microRNA let-7a on Con A-induced hepatitis and its possible mechanisms involved. We demonstrated that IL-6 and IL-17 expression were significantly upregulated in the liver following Con A treatment and IL-6 level was correlated with the IL-17 expression. To explore whether let-7a may have therapeutic effect on Con A-induced hepatitis, mice was infected with a lentiviral vector containing the let-7a sequence 7 days before Con A treatment. Significantly reduced Th17 cells and remarkably increased regulatory T cells frequency in the liver tissue were found as compared to control mice. It was accompanied by a significant decreased level of inflammatory cytokines as TNF-α, IL-6 and IFN-γ in the serum, and an decreased level of Th17 lineage-specific genes such as Il17a, Il17f, Il21 and Il23r. let-7a was further found to inhibit Th17 differentiation by downregulating IL-6 secretion. It may represent as a novel therapeutic strategy in treating immune-mediated inflammatory hepatitis.

  2. 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. PMID:26847412

  3. [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.

  4. 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

  5. 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

  6. [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.

  7. Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

    PubMed

    Miller, Lowell A; Fagerstone, Kathleen A; Wagner, Robert A; Finkler, Mark

    2013-09-23

    Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets. PMID

  8. Vγ4 γδ T cell-derived IL-17A negatively regulates NKT cell function in Con A-induced fulminant hepatitis.

    PubMed

    Zhao, Na; Hao, Jianlei; Ni, Yuanyuan; Luo, Wei; Liang, Ruifang; Cao, Guangchao; Zhao, Yapu; Wang, Puyue; Zhao, Liqing; Tian, Zhigang; Flavell, Richard; Hong, Zhangyong; Han, Jihong; Yao, Zhi; Wu, Zhenzhou; Yin, Zhinan

    2011-11-15

    Con A-induced fulminant hepatitis is a well-known animal model for acute liver failure. However, the role of γδ T cells in this model is undefined. In this report, using TCR δ(-/-) mice, we demonstrated a protective role of γδ T cells in Con A-induced hepatitis model. TCR δ(-/-) mice showed significantly decreased levels of IL-17A and IL-17F in the Con A-treated liver tissue, and reconstitution of TCR δ(-/-) mice with wild-type (Wt), but not IL-17A(-/-), γδ T cells significantly reduced hepatitis, strongly suggesting a critical role of IL-17A in mediating the protective effect of γδ T cells. Interestingly, only Vγ4, but not Vγ1, γδ T cells exerted such a protective effect. Furthermore, depletion of NKT cells in TCR δ(-/-) mice completely abolished hepatitis, and NKT cells from Con A-challenged liver tissues of TCR δ(-/-) mice expressed significantly higher amounts of proinflammatory cytokine IFN-γ than those from Wt mice, indicating that γδ T cells protected hepatitis through targeting NKT cells. Finally, abnormal capacity of IFN-γ production by NKT cells of TCR δ(-/-) mice could only be downregulated by transferring Wt, but not IL-17(-/-), Vγ4 γδ T cells, confirming an essential role of Vγ4-derived IL-17A in regulating the function of NKT cells. In summary, our report thus demonstrated a novel function of Vγ4 γδ T cells in mediating a protective effect against Con A-induced fulminant hepatitis through negatively regulating function of NKT cells in an IL-17A-dependent manner, and transferring Vγ4 γδ T cells may provide a novel therapeutic approach for this devastating liver disease.

  9. Deletion of gp130 in myeloid cells modulates IL-6-release and is associated with more severe liver injury of Con A hepatitis.

    PubMed

    Lutz, H H; Sackett, S D; Kroy, D C; Gassler, N; Trautwein, C

    2012-01-01

    IL-6/gp130 dependent signaling plays an important role in modulating inflammation in acute and chronic diseases. The course of Concanavalin A- (Con A) induced hepatitis can be modulated by different immune-mediated mechanisms. IL-6/gp130-dependent signaling has been shown to be protective in hepatocytes. However, the role of this pathway in myeloid cells has not yet been studied. In our present study we used macrophage/neutrophil-specific gp130 knockout (gp130(ΔLys), KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130(ΔLys)-macrophages. We demonstrate that gp130(ΔLys) animals are more susceptible to Con A-induced hepatitis. This is reflected by higher transaminases, higher lethality and more severe liver injury as shown by histological staining. Using flow cytometry analysis we further could show that increased liver injury of gp130(ΔLys) animals is associated with a stronger infiltration of CD11b/F4/80 double-positive cells compared to wild-type (gp130(flox/flox), WT) controls. To further characterize our observations we studied thioglycolate-elicited peritoneal macrophages from gp130(ΔLys) animals. Interestingly, the LPS-dependent IL-6 release in gp130(ΔLys) macrophages is significantly reduced (p<0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130(ΔLys) animals compared to WT animals (p<0.05). In summary, our results suggest that gp130-deletion in macrophages and granulocytes leads to diminished IL-6 release from these cells, which is associated with more severe Con A-induced hepatitis.

  10. Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments.

    PubMed

    Rudnicki, Marek; Armstrong, John H; Clark, Clancy; Marcus, Stuart G; Sacks, Lee; Moser, A James; Reid-Lombardo, K Marie

    2016-02-01

    The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "ObamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons. PMID:26589524

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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. PMID:26596682

  17. 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

  18. [Sedation concepts with volatile anaesthetics in intensive care: practical use and current experiences with the AnaConDa system].

    PubMed

    Kompardt, J; Schärff, K; Kubosch, K; Pohl, C; Bomplitz, M; Soukup, J

    2008-12-01

    The use of volatile anaesthetics in intensive care medicine has so far been limited by the lack of equipment suitable for daily routine use and the need for an anaesthetic machine. The new Anaesthetic Conserving Device (AnaConDa) enables the routine use of volatile anaesthetics for long-term sedation via intensive care ventilators. The Anaesthetic Conserving Device replaces the common heat and moisture exchanger in the ventilation circuit. The volatile anaesthetic is continuously applied in liquid status via a syringe pump to a form of mini-vaporiser where the anaesthetic agent is vaporised. The expired anaesthetic gas is stored in the carbon filter and approximately 90% of the gas is resupplied into the breathing cycle. The current experiences suggest that volatile anaesthetics present an alternative for long-term sedation in intensive care units, providing optimised pathways, from a medical as well as from an economical point of view. It must, however, be emphasized that the use of volatile anaesthetics for longer periods of time is an off-label use and should only undertaken by medical professionals at their own risk. PMID:18839123

  19. Tissue-Specific Regulation of p38α-Mediated Inflammation in Con A-Induced Acute Liver Damage.

    PubMed

    Kang, Young Jun; Bang, Bo-Ram; Otsuka, Motoyuki; Otsu, Kinya

    2015-05-15

    Because p38α plays a critical role in inflammation, it has been an attractive target for the development of anti-inflammation therapeutics. However, p38α inhibitors showed side effects, including severe liver toxicity, that often prevailed over the benefits in clinical studies, and the mechanism of toxicity is not clear. In this study, we demonstrate that p38α regulates the inflammatory responses in acute liver inflammation in a tissue-specific manner, and liver toxicity by p38α inhibitors may be a result of the inhibition of protective activity of p38α in the liver. Genetic ablation of p38α in T and NKT cells protected mice from liver injury in Con A-induced liver inflammation, whereas liver-specific deletion of p38α aggravated liver pathology. We found that p38α deficiency in the liver increased the expression of chemokines to recruit more inflammatory cells, indicating that p38α in the liver plays a protective anti-inflammatory role during acute liver inflammation. Therefore, our results suggest that p38α regulates the inflammatory responses in a tissue-specific manner, and that the tissue-specific p38α targeting strategies can be used for the development of an effective anti-inflammation treatment with an improved side-effect profile.

  20. Expected and Unexpected Consequences of the Affordable Care Act: The Impact on Patients and Surgeons-Pro and Con Arguments.

    PubMed

    Rudnicki, Marek; Armstrong, John H; Clark, Clancy; Marcus, Stuart G; Sacks, Lee; Moser, A James; Reid-Lombardo, K Marie

    2016-02-01

    The Patient Protection and Affordable Care Act (PPACA), called the Affordable Care Act (ACA) or "ObamaCare" for short, was enacted in 2010. The Public Policy and Advocacy Committee of the Society for Surgery of the Alimentary Tract (SSAT) hosted a debate with an expert panel to discuss the ACA and its impact on surgical care after the first year of patient enrollment. The purpose of this debate was to focus on the impact of ACA on the public and surgeons. At the core of the ACA are insurance industry reforms and expanded coverage, with a goal of improved clinical outcomes and reduced costs of care. We have observed supportive and opposing views on ACA. Nonetheless, we will witness major shifts in health care delivery as well as restructuring of our relationship with payers, institutions, and patients. With the rapidly changing health care landscape, surgeons will become key members of health systems and will likely need to lead transition from solo-practice to integrated care systems. The full effects of the ACA remain unrealized, but its implementation has begun to change the map of the American health care system and will surely impact the practice of surgery. Herein, we provide a synopsis of the "pro" and "con" arguments for the expected and unexpected consequences of the ACA on society and surgeons.

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:21459155

  5. 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.

  6. Circumcision: pros and cons.

    PubMed

    Burgu, Berk; Aydogdu, Ozgu; Tangal, Semih; Soygur, Tarkan

    2010-01-01

    Circumcision is possibly the most frequently performed elective surgical procedure in men. It can simply be described as the excision of the preputium. There have been several studies about the association between circumcision and urinary tract infections (UTI). Many studies have demonstrated that the frequency of UTI increase in uncircumcised males, especially in the first year of life. This review discusses the embryology of the preputium, epidemiology, indications, complications and benefits of circumcision, as well as operation and anesthesiology techniques. It especially examines the association between UTI and circumcision and the importance of circumcision in congenital urinary system anomalies. In addition, this review examines the associations between circumcision and sexually transmitted diseases, including HIV, and the protective role of circumcision on penile cancer.

  7. Circumcision: Pros and cons

    PubMed Central

    Burgu, Berk; Aydogdu, Ozgu; Tangal, Semih; Soygur, Tarkan

    2010-01-01

    Circumcision is possibly the most frequently performed elective surgical procedure in men. It can simply be described as the excision of the preputium. There have been several studies about the association between circumcision and urinary tract infections (UTI). Many studies have demonstrated that the frequency of UTI increase in uncircumcised males, especially in the first year of life. This review discusses the embryology of the preputium, epidemiology, indications, complications and benefits of circumcision, as well as operation and anesthesiology techniques. It especially examines the association between UTI and circumcision and the importance of circumcision in congenital urinary system anomalies. In addition, this review examines the associations between circumcision and sexually transmitted diseases, including HIV, and the protective role of circumcision on penile cancer. PMID:20535279

  8. 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.

  9. 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,…

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Li storage and impedance spectroscopy studies on Co3O4, CoO, and CoN for Li-ion batteries.

    PubMed

    Reddy, M V; Prithvi, Gundlapalli; Loh, Kian Ping; Chowdari, B V R

    2014-01-01

    The compounds, CoN, CoO, and Co3O4 were prepared in the form of nano-rod/particles and we investigated the Li-cycling properties, and their use as an anode material. The urea combustion method, nitridation, and carbothermal reduction methods were adopted to prepare Co3O4, CoN, and CoO, respectively. X-ray diffraction (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), and the Brunauer-Emmett-Teller (BET) surface and density methods were used to characterise the materials. Cyclic voltammetry (CV) was performed and galvanostatic cycling tests were also conducted up to 60-70 cycles. The observed reversible capacity of all compounds is of the increasing order CoO, Co3O4, CoN and all compounds showed negligible capacity fading. CoO allows for Li2O and Co metal to form during the discharge cycle, allowing for a high theoretical capacity of 715 mA h g(-1). Co3O4 allows for 4 Li2O and 3Co to form, and has a theoretical capacity of 890 mAhg(-1). CoN is the best anode material of the three because the nitrogen allows for Li3N and Co to form, resulting in an even higher theoretical capacity of 1100 mAhg(-1) due to the Li3N and Co metal formation. Irrespective of morphology the charge profiles of all three compounds showed a major plateaux ~2.0 V vs. Li and potential values are almost unchanged irrespective of crystal structure. Electrochemical impedance spectroscopy (EIS) was performed to understand variation resistance and capacitance values.

  17. 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.

  18. Modulation of Salmonella infection by the lectins of Canavalia ensiformis (Con A) and Galanthus nivalis (GNA) in a rat model in vivo.

    PubMed

    Naughton, P J; Grant, G; Bardocz, S; Pusztai, A

    2000-04-01

    The plant lectins, Concanavalin A (Con A) and Galanthus nivalis agglutinin (GNA) have been prefed to rats for 3 d pre- and 6 d postinfection with Salmonella typhimurium S986 or Salm. enteritidis 857. Con A significantly increased numbers of Salm. typhimurium S986 in the large intestine and in faeces, and severely impaired growth of the rats, more severely than is the case of infection with Salmonella typhimurium alone. Con A had much less effect on rats infected with Salm. enteritidis 857 only showing a significant increase in numbers in the colon, accompanied by intermittent increases of Salmonella in the faeces during the study. GNA significantly reduced pathogen numbers in the lower part of the small bowel and the large intestine of rats infected with Salm. typhimurium S986 and significantly improved rat growth. GNA had little effect on infection by Salm. enteritidis 857 with slight decreases in Salmonella numbers in the small intestine and large intestine and transient increases in the faeces.

  19. A review of the practice of sedation with inhalational anaesthetics in the intensive care unit with the AnaConDa® device

    PubMed Central

    Misra, Satyajeet; Koshy, Thomas

    2012-01-01

    The intensive care unit (ICU) environment is often perceived to be hostile and frightening by patients due to unfamiliar surroundings coupled with presence of numerous personnel, monitors and other equipments as well as a loss of perception of time. Mechanical ventilation and multiple painful procedures that often need to be carried out in these critically ill patients add to their overall anxiety. Sedation is therefore required not only to allay the stress and anxiety, but also to allow for mechanical ventilation and other invasive therapeutic and diagnostic procedures to be performed. The conventional intravenous sedative agents used in ICUs suffer from problems of over sedation, tachyphylaxis, drug accumulation, organ specific elimination and often lead to patient agitation on withdrawal. All this tend to prolong the ventilatory as well as ICU and hospital discharge time, which increase the risk for infection and add to the overall increase in morbidity, mortality and hospital costs. In 2005, the anaesthetic conserving device (AnaConDa®) was marketed for ICU sedation with volatile anaesthetic agents. A number of trials have shown the effectiveness of using volatile anaesthetic agents for ICU sedation with the AnaConDa device. Compared with intravenous sedatives, use of volatile anaesthetic agents have resulted in shorter wake up and extubation time, lesser duration of mechanical ventilation and faster discharge from hospitals. This review shall focus on the benefits, technical pre-requisites and status of sedation with volatile anaesthetic agents in ICUs with the AnaConDa® device. PMID:23325934

  20. 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.

  1. 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

  2. TNF-α Promoter Polymorphisms Predict the Response to Etanercept More Powerfully than that to Infliximab/Adalimumab in Spondyloarthritis.

    PubMed

    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. In vitro and in vivo binding of snowdrop (Galanthus nivalis agglutinin; GNA) and jackbean (Canavalia ensiformis; Con A) lectins within tomato moth (Lacanobia oleracea) larvae; mechanisms of insecticidal action.

    PubMed

    Fitches, E; Woodhouse, S D.; Edwards, J P.; Gatehouse, J A.

    2001-07-01

    When fed in semi-artificial diet the lectins from snowdrop (Galanthus nivalis: GNA: mannose-specific) and jackbean (Canavalia ensiformis: Con A: specific for glucose and mannose) were shown to accumulate in vivo in the guts, malpighian tubules and haemolymph of Lacanobia oleracea (tomato moth) larvae. Con A, but not GNA, also accumulated in the fat bodies of lectin-fed larvae. The presence of glycoproteins which bind to both lectins in vitro was confirmed using labelled lectins to probe blots of polypeptides extracted from larval tissues. Immunolocalisation studies revealed a similar pattern of GNA and Con A binding along the digestive tract with binding concentrated in midgut sections. Binding of lectins to microvilli appeared to lead to transport of the proteins into cells of the gut and malpighian tubules. These results suggested that both lectins are able to exert systemic effects via transport from the gut contents to the haemolymph across the gut epithelium. The delivery of GNA and Con A to the haemolymph was shown to be dependent on their functional integrity by feeding larvae diets containing denatured lectins. Con A, but not GNA, was shown to persist in gut and fat body tissue of lectin-fed larvae chased with control diet for three days. Con A also shows more extensive binding to larval tissues in vitro than GNA, and these two factors are suggested to contribute to the higher levels of toxicity shown by Con A, relative to GNA, in previous long term bioassays.

  4. 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

  5. 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

  6. 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.

  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. 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

  9. 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.

  10. The beliefs about pros and cons of drinking and intention to change among hazardous and moderate alcohol users: a population-based cross-sectional study

    PubMed Central

    Helgason, Asgeir R.; Ahacic, Kozma

    2014-01-01

    Background: Fundamental to supporting hazardous alcohol users are the rationales for reducing alcohol intake highlighted by the users themselves. This study analyses the relative importance of beliefs about pros and cons of drinking in relation to having an intention to reduce intake among both hazardous and moderate alcohol users. Methods: Intention to change was assessed in a representative sample of Stockholm’s population (n = 4278, response rate 56.5%). Alcohol use was assessed using the Alcohol Use Disorders Identification Test measure. A decisional balance inventory was used to examine various beliefs about the pros and cons of drinking, which covered affect changes, social gains and losses, and possible adverse effects. Independent correlations were determined by logistic regression using a backward exclusion procedure (P > 0.05). Results: Higher ratings of importance were generally related to intent, whether or not the contrast was with having no intent or already having made a reduction. This was especially true for hazardous users. Only two beliefs were independently correlated with change among hazardous users: ‘Drinking could get me addicted’ and ‘Drinking makes me more relaxed/less tense’ (pseudo-R2 < 0.1). Among moderate users, there was no uniform pattern in the relationships. Conclusions: Unexpectedly, hazardous users with an intent to change rated pro arguments as more important than those with no intent to change. Of the investigated pros and cons, only a few were independently related to intention to change drinking behaviour. These arguments provide interesting topics in consultations. Little support was found for any rational decision making behind the intention to reduce alcohol intake. PMID:24567291

  11. [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

  12. 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.

  13. 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

  14. 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

  15. Early and repeated IgG1Fc-pCons chimera vaccinations (GX101) improve the outcome in SLE-prone mice.

    PubMed

    Ferrera, Francesca; Fenoglio, Daniela; Cutolo, Maurizio; Balbi, Giuseppe; Parodi, Alessia; Battaglia, Florinda; Kalli, Francesca; Barone, Domenico; Indiveri, Francesco; Criscuolo, Domenico; Filaci, Gilberto

    2015-08-01

    A previous study showed that a tolerogenic gene vaccine based on a IgG1Fc-pCons chimera (here named GX101) protects NZB/NZW mice from SLE development. The present study was aimed at identifying the most effective schedule of immunization and the possible involvement of CD4(+) Foxp3(+) Treg in the mechanism of action, in view of its eventual translation to the human studies. NZB/NZW mice were vaccinated with B lymphocytes made transgenic by spontaneous transgenesis with a gene coding for a chimeric IgG1Fc-pCons construct. Different schedules of vaccination were set in relation to the timing and number of administrations. Survival, proteinuria levels, and CD4(+) Foxp3(+) Treg frequency were monitored during the full experiments. GX101-treated mice showed delayed disease onset and delayed mortality than controls. GX101 effects were implemented by early as well as repeated vaccine administrations. GX101 vaccination was associated with increased frequencies of CD4(+) CD25(+) Foxp3(+) Treg with respect to controls. This study demonstrates that early and repeated immunizations with GX101 vaccine provide a better outcome than late or single vaccine administration regarding onset/development in SLE-prone mice, acting as a possible disease-modifying approach. Vaccine effects are likely related to CD4(+) Foxp3(+) Treg cell expansion.

  16. 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. PMID:23820156

  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. 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).

  19. 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

  20. The soil-water balance simulations of a grassland in response to CO2, rainfall, and biodiversity manipulations at BioCON

    NASA Astrophysics Data System (ADS)

    Flinker, R. H.; Cardenas, M.; Caldwell, T. G.; Rich, R.; Reich, P.

    2013-12-01

    The BioCON (Biodiversity, CO2 and N) experiment has been continuously running since 1997. Operated by the University of Minnesota and located within the Cedar Creek Ecosystem Science Reserve in Minnesota, USA, BioCON is a Free-Air CO2 Enrichment (FACE) experiment that investigates plant community response to three key environmental variables: nitrogen, atmospheric CO2 and biodiversity. More recently rainfall exclusion and temperature manipulation were added to the experiment which amounts to 371 plots. The site attempts to replicate predicted average temperature increases and a northern shift of plant species and any associated consequences. FACE experiments have been conducted for a number of years in different countries, but the focus has generally been on how plant communities, soil respiration and microbes respond. Minimal work has been focused on the hydrologic aspects of these experiments which are potentially valuable for investigating global warming effects on local and plot-scale ecohydrology. Thus, the objective of this work is to characterize and model unsaturated flow for different CO2 and rainfall treatments in order to see how they affect soil moisture dynamics and groundwater recharge on grasslands of central Minnesota. Our study focuses on simulating soil moisture dynamics in eighteen of the BioCON plots: six bare plots with regular rainfall regimes (zero plant species, three plots with elevated atmospheric CO2 levels), six regular rainfall regimes (nine plant species, three plots with elevated atmospheric CO2 levels) and six reduced rainfall regimes (nine plant species, three plots with elevated atmospheric CO2 levels). The Simultaneous Heat and Water (SHAW) model, which solves the Richards equation for unsaturated zone water flow coupled to a comprehensive energy balance model, was parameterized with a combination of field and lab estimates of soil properties. Field estimates of saturated hydraulic conductivity using tension infiltrometers ranged

  1. 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.

  2. 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.

  3. The role of intracellular high-mobility group box 1 in the early activation of Kupffer cells and the development of Con A-induced acute liver failure.

    PubMed

    Yang, Qiao; Liu, Yanning; Shi, Yu; Zheng, Min; He, Jiliang; Chen, Zhi

    2013-10-01

    Acute liver failure (ALF) is a highly complex syndrome characterized by devastating activation of early activation of Kupffer cells (KCs) has been implicated in the pathogenesis of ALF. However, the factors regulating KC early activation are virtually unexplored. The aim of present study was to determine the role of the intracellular high-mobility group box 1 (HMGB1) in modulating the early activation of KCs during ALF. The intravenous injection of Concanavalin A (Con A) was used to establish a mouse model of ALF. The dynamic pro-inflammatory properties and MHC II expression of KCs were measured by qRT-PCR and flow cytometry. HMGB1 expression in KCs was measured by qRT-PCR and Western blotting. The immunofluorescence was implemented to determine the relocation of HMGB1 in KCs, and the siRNA against HMGB1 was utilized to assess the impact of HMGB1 on KC pro-inflammatory properties. The peak of pro-inflammatory cytokines production and MHC II expression in KCs appeared at the early stage of ALF. The up-regulation of HMGB1 expression and the translocation of HMGB1 in KCs were in parallel with the early activation of KCs. The blockade of intracellular HMGB1 expression caused by siRNA significantly inhibited the production of KC-derived pro-inflammatory cytokines, and led to a down-regulation of MAP kinase activation in KCs. The self-derived HMGB1 is an "early alarmin" of KC activation during Con A-induced ALF. HMGB1 might be a potential target for cell-specific strategy in ALF.

  4. 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

  5. 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

  6. Estudio de NIH señala relación de la TC en la infancia con leucemia y cáncer de cerebro más tarde

    Cancer.gov

    Niños y adultos jóvenes a quienes se les hicieron exploraciones muchas veces con tomografía computarizada (TC), una herramienta de diagnóstico de uso frecuente, tienen un riesgo ligeramente mayor de padecer leucemia y tumores cerebrales en la década poste

  7. 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.

  8. Development of Fluorescence Label and Con-focal Laser Scanning Microscopy Method for Non-Destructive Local Impurity Distribution Analysis in Protein Crystals

    NASA Astrophysics Data System (ADS)

    Iimura, Yoshikazu; Yoshizaki, Izumi; Nakamura, Hirohiko; Yoda, Shinichi; Komatsu, Hiroshi

    2003-09-01

    A new method for quantitative analysis of the impurity concentration in protein crystals and solutions was developed. This technique utilizes fluorescence label (FL) with con-focal laser scanning microscopy (CLSM), which is more effective than SDS-PAGE analysis currently used for this purpose. The advantages of CLSM are that, it is non-destructive so that the impurity incorporation and local distribution could be observed in situ, and also that only a micro-quantity of protein solution is needed. The impurity protein is labeled with fluorescence material, and mixed with the crystallization solution. The solution and the crystal are observed by CLSM, and the fluorescence intensity from the labeled impurity is then converted to the impurity concentration by using calibration curves. A case study using Hen Egg White Lysozyme as a sample is reported. Calibration curves were obtained by comparing the fluorescence intensity and the actual impurity concentration determined by the absorbance at 280 nm and SDS-PAGE. A few factors such as the numerical aperture of the objective lens or the pinhole size were fixed. The utilization of this technique leads to the understanding of the effect of impurities on protein crystal growth.

  9. 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.

  10. Biochar Usage: Pros and Cons

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil fertility benefits of charcoal application have been reported as early as 1847 indicating that plant nutrients are sorbed within charcoal pores. The use of biomass-derived black carbon or biochar, the solid byproduct from the pyrolysis processing of any organic feedstock, has garnered recent a...

  11. [Induced abortion: pro and con].

    PubMed

    Balić, Adem; Balić, Devleta; Habibović, A; Adzajlić, A

    2003-01-01

    Induced abortion like a method of birth control is the most unpopular method but it is a choice of great deal women especially in our environment. In connection with very loud demands for sharpened the low of pregnancy interrupting, many authors analyse methods, complications and risk groups of women, its acceptability like a method of family planning. At the end they give conclusion with some concrete suggestions and the aim to reduce the number of induced abortions. PMID:14528715

  12. Temperature optimization of high con

    NASA Astrophysics Data System (ADS)

    Sabry, M.

    2016-06-01

    Active cooling is essential for solar cells operating under high optical concentration ratios. A system comprises four solar cells that are in thermal contact on top of a copper tube is proposed. Water is flowing inside the tube in order to reduce solar cells temperature for increasing their performance. Computational Fluid Dynamics (CFD) simulation of such system has been performed in order to investigate the effect of water flow rate, tube internal diameter, and convective heat transfer coefficient on the temperature of the solar cells. It is found that increasing convective heat transfer coefficient has a significant effect on reducing solar cells temperatures operating at low flow rates and high optical concentration ratios. Also, a further increase of water flow rate has no effect on reducing cells temperatures.

  13. 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…

  14. Venus lightning: PROS and cons

    NASA Astrophysics Data System (ADS)

    Hunten, D. M.

    1995-04-01

    The evidence concerning the presence of lightning on Venus is summarized. There are several observations of electromagnetic pulses, but the only claimed optical detection is ambiguous. Another optical search, making use of an unusual mode of the Pioneer Venus star sensor, set an upper limit on the flash rate, 1.6% of the corresponding Earth rate. Given these difficulties and the unfavorable environment for charge separation, it is concluded that the presence of lightning at anything like the Earth rate is doubtful.

  15. 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...

  16. [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.

  17. 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

  18. HP and UHT metamorphic associations in the Day Nui Con Voi,northwestern Vietnam: The consequence of convergence between the Indian and the Eurasian plates

    NASA Astrophysics Data System (ADS)

    Zhang, J.; Liu, J.; Tran, M. D.; Nguyen, Q. L.

    2014-12-01

    The Red River shear zone (RRSZ) is the most significant geologic discontinuity in Southeast Asia. The Day Nui Con Voi (DNCV) massif at the southernmost part of the shear zone bears records of Cenozoic RRSZ activity. The DNCV in northwestern Vietnam predominantly consists of HP granulite facies metapelites, and lenticular enclaves of HP mafic granulites, calc-silicate granulites and UHT aluminum-rich rocks in the metapelites. HP granulites are characterized by the key associations of garnet-kyanite-ternary feldspar (in metapelites) and garnet-clinopyroxene-plagioclase-quartz (in mafic granulites). In the latter case, rocks are typically orthopyroxene-free. The peak assemblage of the HP metapelites includes garnet + kyanite + ternary feldspar + quartz + rutile. The peak assemblage of the HP mafic granulites is garnet + clinopyroxene + plagioclase + quartz. Meanwhile, the peak assemblage of the calc-silicate granulites is high-Ca garnet (Grs>50) + diopside + scapolite + quartz. On the other hand, characteristic UHT metamorphic assemblage occur as the coexistence of spinel and quartz which indicates the metamorphic temperature is higher than 900℃. The peak assemblage of the UHT rocks in DNCV is corundum + spinel + garnet + sillimanite + quartz. P-T conditions of peak metamorphism within HP granulite facies are: T = 750~850℃, P = 12.5~14kbar. The temperature of UHT metamorphism is higher than 900℃, the pressure is higher than 9~9.4 kbar. SHRIMP U-Pb dating of zircons from the HP mafic granulites and UHT rocks gave minimum ages of ca. 59 Ma and 40 Ma, respectively. HP metapelites gave ca. 60~50Ma and 30Ma. The above facts suggest the DNCV massif experienced HP granulite facies at its peak metamorphism at ˜59 Ma. Thermal disturbance on the local scale to UHT metamorphism occurred at ˜40 Ma. Then isothermal decompression to medium-pressure granulite facies occurred at ˜30Ma, which may reflect a rapid exhumation. The HP rocks are interpreted to be resulted

  19. 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, related regulations and assessment indicators of soil and water conservation. 5. Maintain the biodiversity of the slopeland and reduce the ecological footprint

  20. [Prognosis of non-symptomatic epilepsy in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years].

    PubMed

    Ochoa-Gómez, Laura; López-Pisón, Javier; Fuertes-Rodrigo, Cristina; Fernando-Martínez, Ruth; Samper-Villagrasa, Pilar; Monge-Galindo, Lorena; Peña-Segura, José Luis

    2016-02-16

    Objetivo. Analizar los factores implicados en el pronostico de las epilepsias no sintomaticas (idiopaticas y criptogenicas) en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante un periodo de tres años. Pacientes y metodos. Analisis de los pacientes con diagnostico de epilepsia no sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos, examenes complementarios y datos evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 156 (25,79%) fueron epilepsias idiopaticas, y 172 (28,43%), criptogenicas. El 15,7% de las epilepsias criptogenicas y el 14,1% de las idiopaticas son refractarias al tratamiento. Algunos sindromes epilepticos, como las epilepsias reflejas, el sindrome de Dravet, el sindrome de Ohtahara o el sindrome de Lennox-Gastaut, tienen mayores tasas de farmacorresistencia. No presentan otra alteracion neurologica asociada el 84,62% de las epilepsias idiopaticas y el 79,77% de las epilepsias criptogenicas. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz sea el inicio y en etiologias concretas.

  1. [Prognosis of symptomatic epilepsies in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years].

    PubMed

    Ochoa-Gomez, Laura; Lopez-Pison, Javier; Fernando-Martinez, Ruth; Fuertes-Rodrigo, Cristina; Samper-Villagrasa, Pilar; Monge-Galindo, Lorena; Peña-Segura, José Luis; García-Jiménez, M Concepción

    2016-03-16

    Objetivo. Analizar los factores implicados en el pronostico de las epilepsias sintomaticas en relacion con su edad de inicio, controladas en una unidad de neuropediatria de referencia regional durante tres años. Pacientes y metodos. Revision de los pacientes con diagnostico de epilepsia sintomatica, controlados desde el 1 de enero de 2008 hasta el 31 de diciembre de 2010, recogiendo datos epidemiologicos, clinicos y evolutivos. Resultados. Del total de 4.595 niños atendidos en el periodo, se establecio el diagnostico de epilepsia en 605 (13,17%), de las cuales 277 (45,79%) son epilepsias sintomaticas. En los pacientes que iniciaron la epilepsia por debajo del año de vida predominan las de etiologia sintomatica (67,72%), y tambien entre 1-3 años (61,39%). El 37,54% de las epilepsias sintomaticas son refractarias, el 72,92% asocian un deficit cognitivo, el 55,23%, alguna afectacion motora, y el 17,32%, algun trastorno del espectro autista. A menor edad, mayor porcentaje de refractariedad y de presentar alguna repercusion neurologica o del desarrollo asociada. Algunas etiologias tienen mayores tasas de refractariedad. Conclusiones. Una clasificacion util de la epilepsia es la etiologica, con dos grupos: un gran grupo con las etiologias establecidas o sindromes geneticos muy probables, y otro de casos sin causa establecida. La edad de inicio de la epilepsia en cada grupo etiologico añade orientacion pronostica. El pronostico lo ensombrecen la refractariedad y las alteraciones asociadas del neurodesarrollo, y es peor, en general, cuanto mas precoz es el inicio y en etiologias concretas.

  2. Comparación de resultados del método de clasificación de órbitas por análisis de frecuencias con el método de exponentes de Lyapunov

    NASA Astrophysics Data System (ADS)

    Carpintero, D. D.; Muzzio, J. C.; Wachlin, F. C.

    Hemos realizado extensas comparaciones del método de análisis de frecuencias con el de exponentes de Lyapunov. El primero resulta claramente superior por las siguientes razones: 1) permite distinguir distintos tipos de órbitas y no sólo si son regulares o caóticas 2) es mucho más veloz requiriendo mucho menos tiempo de cómputo. La concordancia de resultados es, en general, buena y se discuten algunas discrepancias.

  3. Maintenance Therapy in IBD

    MedlinePlus

    ... Infliximab is given as a single-dose intravenous infusion, and many patients may be able to wait ... is recommended to wait at least for two infusions to see infliximab's effectiveness. Adalimumab Adalimumab (Humira®) is ...

  4. Aceptabilidad del diagnóstico rápido casero para HIV entre hombres gay y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires.

    PubMed

    Balán, Iván C; Carballo-Diéguez, Alex; Marone, Rubén O; Pando, María A; Barreda, Victoria; Avila, María M

    2011-03-01

    El uso del diagnóstico rápido para HIV en Argentina, así como otros países de Latinoamérica, ha sido limitado hasta el momento. Este trabajo reporta los resultados provenientes de un estudio cualitativo realizado entre hombres gays y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires, Argentina. El objetivo principal del mismo fue conocer las ventajas y desventajas que los hombres G&HSH perciben en relación al diagnóstico rápido casero para HIV. Se realizaron ocho grupos focales con 73 participantes en los cuales se discutió acerca de las ventajas y desventajas del uso de los diagnósticos rápidos. Las respuestas fueron codificadas utilizando un programa para análisis de datos cualitativos (NVivo) y analizadas temáticamente. Los participantes describieron numerosas ventajas sobre el uso del diagnóstico rápido casero, aunque algunos reportaron importantes preocupaciones dentro de las cuales se destaca la posibilidad de impulsos suicidas si alguien recibe un resultado positivo estando solo. En términos generales se observó una gran aceptabilidad para el uso del diagnóstico rápido si el mismo es realizado por personal de salud en lugares acondicionados para este fin.

  5. Do not disturb the animals! or, how Con Edison saved $300,000 using a trenchless technology to renew 3,000 feet of leaking gas main at the Bronx Zoo

    SciTech Connect

    Bufe, M.

    1995-07-01

    Every leaking gas main presents a challenge. But when that leaking main follows a series of sweeping bends on its route through North America`s largest urban wildlife park, it presents a special challenge. That was the situation Consolidated Edison Company of New York Inc. recently faced when numerous leaks were discovered along 3,000 feet of a 95-year-old, 12-inch cast-iron main that winds through New York City`s Bronx Zoo. Con Edison knew it needed a long-term solution to this increasingly common problem. Thanks to the cooperative efforts of the utility`s operations and research departments and the Gas Research Institute (GRI), Con Edison also knew about a trenchless technology that could renew the pipe with minimal impact to the environment--while saving the utility a substantial sum of money in the process. In the Paltem system, a woven polyester hose is injected with an epoxy resin and then inverted (turned inside out) into a pipe at an access pit. The liner then bonds to the inside wall of the pipe, forming a smooth, flexible and pressure-resistant lining. The process is environmentally safe, requires very little excavation and can be installed in days, rather than the weeks or months it can take to dig up and replace existing pipe.

  6. Aceptabilidad del diagnóstico rápido casero para HIV entre hombres gay y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires

    PubMed Central

    Balán, Iván C.; Carballo-Diéguez, Alex; Marone, Rubén O.; Pando, María A.; Barreda, Victoria; Ávila, María M.

    2011-01-01

    Resumen El uso del diagnóstico rápido para HIV en Argentina, así como otros países de Latinoamérica, ha sido limitado hasta el momento. Este trabajo reporta los resultados provenientes de un estudio cualitativo realizado entre hombres gays y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires, Argentina. El objetivo principal del mismo fue conocer las ventajas y desventajas que los hombres G&HSH perciben en relación al diagnóstico rápido casero para HIV. Se realizaron ocho grupos focales con 73 participantes en los cuales se discutió acerca de las ventajas y desventajas del uso de los diagnósticos rápidos. Las respuestas fueron codificadas utilizando un programa para análisis de datos cualitativos (NVivo) y analizadas temáticamente. Los participantes describieron numerosas ventajas sobre el uso del diagnóstico rápido casero, aunque algunos reportaron importantes preocupaciones dentro de las cuales se destaca la posibilidad de impulsos suicidas si alguien recibe un resultado positivo estando solo. En términos generales se observó una gran aceptabilidad para el uso del diagnóstico rápido si el mismo es realizado por personal de salud en lugares acondicionados para este fin. PMID:25284951

  7. Aceptabilidad del diagnóstico rápido casero para HIV entre hombres gay y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires.

    PubMed

    Balán, Iván C; Carballo-Diéguez, Alex; Marone, Rubén O; Pando, María A; Barreda, Victoria; Avila, María M

    2011-03-01

    El uso del diagnóstico rápido para HIV en Argentina, así como otros países de Latinoamérica, ha sido limitado hasta el momento. Este trabajo reporta los resultados provenientes de un estudio cualitativo realizado entre hombres gays y otros hombres que tienen sexo con hombres (G&HSH) de la Ciudad de Buenos Aires, Argentina. El objetivo principal del mismo fue conocer las ventajas y desventajas que los hombres G&HSH perciben en relación al diagnóstico rápido casero para HIV. Se realizaron ocho grupos focales con 73 participantes en los cuales se discutió acerca de las ventajas y desventajas del uso de los diagnósticos rápidos. Las respuestas fueron codificadas utilizando un programa para análisis de datos cualitativos (NVivo) y analizadas temáticamente. Los participantes describieron numerosas ventajas sobre el uso del diagnóstico rápido casero, aunque algunos reportaron importantes preocupaciones dentro de las cuales se destaca la posibilidad de impulsos suicidas si alguien recibe un resultado positivo estando solo. En términos generales se observó una gran aceptabilidad para el uso del diagnóstico rápido si el mismo es realizado por personal de salud en lugares acondicionados para este fin. PMID:25284951

  8. Revision curricular a partir de un analisis comparativo de las discrepancias en los curriculos de una escuela de optometria en Puerto Rico con las competencias requeridas para las agencias de revalida y acreditacion 2004

    NASA Astrophysics Data System (ADS)

    Rivera Pacheco, Andres

    El proposito de esta investigacion, un estudio cualitativo de caso, fue comparar y contrastar el curriculo vigente de la Escuela de Optometria de la UIAPR con las competencias y estandares requeridos por las agencias de acreditacion y de revalida. Con este proposito, decidimos realizar una revision y un analisis de documentos: el prontuario de cada uno de los cursos de los curriculos implantados en el 1993 y en el 2001; las competencias y estandares establecidos por las agencias de revalida y de acreditacion; y las estadisticas en las que se analiza el porcentaje de estudiantes que aprueban cada una de las partes de los examenes de revalida entre el 1998 al 2003. Se realizaron entrevistas dirigidas para dar apoyo y complementar la revision y el analisis de estos documentos. Los participantes de las entrevistas fueron tres estudiantes de la clase de optometria del 2004 (ultima clase del curriculo del 1993); tres estudiantes de la clase de optometria del 2005 (primera clase graduanda del curriculo vigente) y tres profesores y/o directores de los Departamentos de Ciencias Basicas, Ciencias Clinicas y Cuidado al Paciente. Esta investigacion se enmarco en el modelo de evaluacion curricular de discrepancia de Malcolm Provus y en el modelo de desarrollo basado en competencias. Uno de los hallazgos mas importantes del estudio es que los cambios que se implantaron al curriculo del 2001 no han logrado que los estudiantes mejoren su ejecucion en los examenes de revalida. Por otro lado, se encontro que el curriculo vigente atiende completamente los estandares de la practica de Optometria, pero no las competencias. Esta informacion fue validada mediante el uso de una tabla de cotejo para el analisis de los cursos y de la informacion obtenida de las entrevistas. El estudio determina y concluye que existen discrepancias entre los prontuarios de los cursos del curriculo y las competencias requeridas por la agencia de revalida. Segundo, que el Departamento de Ciencias Basicas es el

  9. El rol de Ia colaboracion y el Modelo de Aprendizaje Basado en Proyectos (ABPr) mediante el lente de la Teoria de Actividad (CHAT): un estudio de caso con estudiantes de 9no grado

    NASA Astrophysics Data System (ADS)

    Delgado, Isabel C.

    Los modelos de eensenanza y aprendizaje constructivistas conceptualizan el aprendizaje como un proceso activo. El modelo de Aprendizaje Basado en Proyectos (ABPr) se distingue por una serie de componentes, entre los cuales se destaca el aspecto colaborativo y cooperativo como un reto al momento de su implantacion. Son pocas las investigaciones que se concentran en este aspecto del modelo. En este estudio, se analizaron las diversas interacciones que surgen durante la implantacion de una unidad curricular sobre el tema de Geologia de Puerto Rico, la cual se diseno con el modelo ABPr cuyo enfoque es orientacion a proyectos. Particularmente, se examinaron las interacciones sociales que surgen entre los pares y entre pares y docente durante el proceso de planificacion y desarrollo de los productos finales, al igual que las interacciones entre los estudiantes y el material didactico en estas etapas del modelo. La investigacion es de tipo cualitativo e incorpora como diseno el estudio de caso. Las diversas interacciones constituyen la unidad de analisis. En el estudio participaron 19 estudiantes de 9no grado, a quienes se organizaron en 5 grupos colaborativos por temas de interes (Pangea, Placas tectonicas, Volcanes, Tsunamis y Terremotos). Las tecnicas que se utilizaron para recopilar los datos fueron: observaciones participativas, grupos focales y analisis de documentos (cuadernos reflexivos y respuestas de los estudiantes a la pregunta central del proyecto). Para el analisis de los datos se aplico la teoria de actividad (CHAT) que concentra la unidad de analisis en la actividad humana en un contexto particular. Los resultados del estudio senalan que las interacciones entre pares, entre pares y docente, asi como entre estudiantes y material didactico son fundamentales en el proceso de aprendizaje. Una mayor interaccion entre pares durante las etapas de planificar y desarrollar los productos finales de la unidad, promueve una mejor comprension de los conceptos de la

  10. [Retrospective analysis of the effect of a vagus nerve stimulator implanted in paediatric patients with refractory epilepsy].

    PubMed

    Fuentes-Pita, P; Gomez-Lado, C; Dacruz, D; Eiris-Punal, J; Prieto-Gonzalez, A; Castro-Gago, M

    2016-07-01

    Introduccion. El estimulador vagal es una alternativa terapeutica en los pacientes con epilepsia refractaria al tratamiento con farmacos antiepilepticos que no son candidatos a cirugia de reseccion. Objetivo. Analizar la eficacia del estimulador vagal en los pacientes pediatricos de nuestro centro. Pacientes y metodos. Conjunto de 13 pacientes implantados entre los años 2008 y 2013. Se registro la frecuencia de crisis previa a la implantacion, al año, a los dos años y al final del seguimiento. Asimismo, se recogio el numero de farmacos antiepilepticos utilizados, de forma cualitativa la mejoria conductual y el cambio en la intensidad de las crisis, asi como la aparicion de efectos secundarios y la retirada o no del dispositivo. Resultados. Al año, a los dos años y al final del seguimiento se habia producido una reduccion en el numero de crisis del 61%, 66,7% y 69%, respectivamente, y uno de los pacientes se encontro libre de crisis a los dos años. Al final del seguimiento, un 23% de los que habian disminuido sus crisis habia experimentado una reduccion superior al 90%. De forma independiente al efecto sobre el numero de crisis, el 77% de los pacientes presento una mejoria en la intensidad y duracion de las crisis, y ese mismo porcentaje mostro una mejoria conductual. Los efectos secundarios aparecieron en un 30,7% de los pacientes y fueron de intensidad leve. Conclusiones. A pesar del pequeño tamaño de la muestra, nuestros resultados indican que el estimulador vagal tiene una eficacia relevante en la poblacion pediatrica farmacorresistente, tanto sobre la frecuencia e intensidad de las crisis como sobre la conducta.

  11. [Economic evaluation of Thrombopoietin Receptor Agonists in the treatment of chronic primary immune thrombocytopenia].

    PubMed

    Parrondo, J; Grande, C; Ibáñez, J; Palau, J; Páramo, J A; Villa, G

    2013-01-01

    Objetivo: Desarrollar una herramienta de apoyo a la decisión en la selección de agonistas del receptor de trombopoyetina en el tratamiento de pacientes adultos con trombocitopenia inmune primaria crónica (PTI) refractaria. Métodos: Análisis coste-efectividad estocástico con un modelo de Markov de seis estados: estable, sangrado tipo 2, 3 ó 4, post-sangrado 4 y muerte. Cada simulación analiza un escenario aleatoriamente generado que describe las características del paciente, los resultados medidos en años de vida ajustados a calidad (AVACs) y los costes (en ?2011). Se obtuvieron distribuciones a partir de los datos para España de la Encuesta Europea de Salud de 2009, de la estimación de población para 2011 del INE, de los estudios a 6 meses de Eltrombopag y Romiplostim, de las utilidades obtenidas de la bibliografía y de las tarifas oficiales en España para procesos y actividad. Se generaron 10.000 escenarios aleatorios y se simuló la evolución de los pacientes de cada escenario durante un horizonte temporal de cinco años (ciclos de dos semanas). Perspectiva del Sistema Nacional de Salud (SNS). Tasa de descuento anual del 3% para costes y efectos. Resultados: En 9.983 escenarios Eltrombopag mostró mayor efectividad y en 17 no hubo diferencias. Eltombopag fue la alternativa dominante en 7.048 escenarios y la más coste efectiva en otros 19 (umbral 30.000 ?/AVAC). Conclusiones: Eltrombopag es la alternativa más coste-efectiva en el 70,67% de los escenarios simulados, por lo que su uso podría producir menores costes al SNS.

  12. Multi-analytical approach applied to the provenance study of marbles used as covering slabs in the archaeological submerged site of Baia (Naples, Italy): The case of the "Villa con ingresso a protiro"

    NASA Astrophysics Data System (ADS)

    Ricca, Michela; Belfiore, Cristina Maria; Ruffolo, Silvestro Antonio; Barca, Donatella; De Buergo, Monica Alvarez; Crisci, Gino Mirocle; La Russa, Mauro Francesco

    2015-12-01

    This paper is focused on archaeometric investigations of white marbles taken from the submerged archaeological site of Baia (Naples). The marine area includes the ruins of this ancient Roman city, whose structures range from luxurious maritime villas and imperial buildings with private thermae and tabernae, to more simple and modest houses. Analyses were carried out on fifty marble fragments of covering slabs, belonging to several pavements of the monumental villa, called the Villa con ingresso a protiro, in order to ascertain their provenance. The most distinctive properties of marbles are their variety of textural property especially regarding grain size (MGS), associated with the Mn content and the variation of stable isotopes. These features, supported by the contribution of other variables and studies, establish the basis for the correct identification of the marbles. For this purpose, minero-petrographic and geochemical techniques were used. Results were compared with literature data of white marbles commonly used in antiquity, especially in the Mediterranean basin and showed that a variety of precious marbles from Carrara, Docimium (Afyon), Thasos-D, Aphrodisias, Proconnesos (Marmara), Paros and Pentelicon were used in the ancient roman city of Baia, confirming the importance of the submerged archaeological site and also allowing researchers to broaden the existing database.

  13. Bridge over troubled proline: assignment of intrinsically disordered proteins using (HCA)CON(CAN)H and (HCA)N(CA)CO(N)H experiments concomitantly with HNCO and i(HCA)CO(CA)NH.

    PubMed

    Hellman, Maarit; Piirainen, Henni; Jaakola, Veli-Pekka; Permi, Perttu

    2014-01-01

    NMR spectroscopy is by far the most versatile and information rich technique to study intrinsically disordered proteins (IDPs). While NMR is able to offer residue level information on structure and dynamics, assignment of chemical shift resonances in IDPs is not a straightforward process. Consequently, numerous pulse sequences and assignment protocols have been developed during past several years, targeted especially for the assignment of IDPs, including experiments that employ H(N), H(α) or (13)C detection combined with two to six indirectly detected dimensions. Here we propose two new HN-detection based pulse sequences, (HCA)CON(CAN)H and (HCA)N(CA)CO(N)H, that provide correlations with (1)H(N)(i - 1), (13)C'(i - 1) and (15)N(i), and (1)H(N)(i + 1), (13)C'(i) and (15)N(i) frequencies, respectively. Most importantly, they offer sequential links across the proline bridges and enable filling the single proline gaps during the assignment. We show that the novel experiments can efficiently complement the information available from existing HNCO and intraresidual i(HCA)CO(CA)NH pulse sequences and their concomitant usage enabled >95 % assignment of backbone resonances in cytoplasmic tail of adenosine receptor A2A in comparison to 73 % complete assignment using the HNCO/i(HCA)CO(CA)NH data alone. PMID:24346685

  14. Implantation des sites de soins communautaires en République Démocratique du Congo: consécration d'un double standard dans l'accès aux soins

    PubMed Central

    Dunia, Gisèle Mawazo Binti

    2013-01-01

    Depuis 2005, la République Démocratique du Congo a amorcé l'implantation des sites de soins communautaires. Cette stratégie a pour objectif de rapprocher les services de santé des populations éloignées. Bien que cela parte d'une bonne intention, elle résulte, à notre sens, en une consécration d'un système de santé à deux vitesses. En effet, les populations vivant en ville ont accès à des soins prestés par des agents de santé formés alors que celles vivant en milieu rural reculé ont pour prestataires de soins des relais communautaires. Cette situation marginalise encore plus des populations dont la situation géographique est déjà préoccupante. Pourtant, la population est prête à parcourir des kilomètres en échange d'un service qu'elle estime de qualité. PMID:23785563

  15. Pros and cons of apartment complex submetering

    SciTech Connect

    Reichelt, G.; Jones, J.

    1982-08-09

    Mastermetering was popular when energy costs were low, but landlords can no longer raise rents fast enough to keep up with rising utility costs. Individual metering and submetering are a growing trend in Texas in order to regulate cash flow and keep rents competitive. Individual metering encourages conservation, but reduces the owner's incentives to improve building efficiency. Owners may not have the capital to cover submetering costs. A variety of heating and cooling monitors, volumetric meters, time meters, temperature monitors, and contract submetering are among the available options. The Residential Utility Billing System, which charges tenants a fixed rent plus an energy bill, retains mastermetering, but allows a square foot surcharge for energy use. Two studies show less energy is used with submetering. (DCK)

  16. Nanoparticles: Health Effects—Pros and Cons

    PubMed Central

    Gwinn, Maureen R.; Vallyathan, Val

    2006-01-01

    With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown. Many fine particles generally considered “nuisance dusts” are likely to acquire unique surface properties when engineered to nanosize and may exhibit toxic biological effects. Consequently, the nuisance dust may be transported to distant sites and could induce adverse health effects. In addition the beneficial uses of NPs in drug delivery, cancer treatment, and gene therapy may cause unintentional human exposure. Because of our lack of knowledge about the health effects associated with NP exposure, we have an ethical duty to take precautionary measures regarding their use. In this review we highlight the possible toxic human health effects that can result from exposure to ultrafine particles (UFPs) generated by anthropogenic activities and their cardiopulmonary outcomes. The comparability of engineered NPs to UFPs suggests that the human health effects are likely to be similar. Therefore, it is prudent to elucidate their toxicologic effect to minimize occupational and environmental exposure. Highlighting the human health outcomes caused by UFPs is not intended to give a lesser importance to either the unprecedented technologic and industrial rewards of the nanotechnology or their beneficial human uses. PMID:17185269

  17. Proceedings of noise-con 91

    SciTech Connect

    Quinlan, D.A.; Prasad, M.G.

    1991-01-01

    This volume covers the following topics related to noise control: control of mine ventilation fans; physical phenomena; gas turbine exhaust system silencing; computer models for estimating electric utility environmental noise; noise from rotary coal car unloading; noise analysis.

  18. Pros and cons of hydraulic drilling

    SciTech Connect

    Not Available

    1984-06-01

    The advantages and disadvantages of using hydraulic drilling are discussed. The low maintenance, energy efficiency, drilling speeds, and operating costs are the main advantages of the hydraulic drills. The economics and maintenance of air drills are also compared.

  19. The pros and cons of code validation

    NASA Technical Reports Server (NTRS)

    Bobbitt, Percy J.

    1988-01-01

    Computational and wind tunnel error sources are examined and quantified using specific calculations of experimental data, and a substantial comparison of theoretical and experimental results, or a code validation, is discussed. Wind tunnel error sources considered include wall interference, sting effects, Reynolds number effects, flow quality and transition, and instrumentation such as strain gage balances, electronically scanned pressure systems, hot film gages, hot wire anemometers, and laser velocimeters. Computational error sources include math model equation sets, the solution algorithm, artificial viscosity/dissipation, boundary conditions, the uniqueness of solutions, grid resolution, turbulence modeling, and Reynolds number effects. It is concluded that, although improvements in theory are being made more quickly than in experiments, wind tunnel research has the advantage of the more realistic transition process of a right turbulence model in a free-transition test.

  20. Conning Our Kids into Military Combat

    ERIC Educational Resources Information Center

    Ashford, Ellie

    2005-01-01

    There are some school leaders who believe that the military offers just one more option for students to consider. Others, however, think that military recruiters are too aggressive and that the privacy of students should be better protected. The No Child Left Behind Act (NCLB) gives the armed services unprecedented access to potential recruits at…